Imhigh85
Well-Known Member
Sweetsue I am stopping by in your Journal to see how everything is going maybe learn a few new things along the way but I'm here to say that I will be subscribing and you will see me from time to time
SweetSue's Class Notes
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Imhigh85, this is one of my many threads, and not one I usually get traffic on. I pull together notes for future threads in this space.
My regular journal is my grow journal, the link to which you'll find in my signature. I'm happy to have you stop and engage in any of the threads. 
Imhigh85
Well-Known Member
Yeah I'm not very good with technology I suck eventually I will wander around and find your thread like I found this one but I appreciate it I tried
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- #44
And I appreciate your trying.
Here, this is a link to the current page of the grow journal. No one expects you to read through or try to keep up with the manic pace, but we sure have fun together, and you're more than welcome to join in. 
SweetSue's Perpetual 2.0 - The Transition To Doc Bud's HBB Kit
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- #45
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- #46
I watched a webinar by Mary Morrissery tonight. Brilliant marketing! 
There's a two to three-day build up with enticing promises in a slick video presentation that left me in awe of the woman's ability to transmit authenticity. I have no doubt she's an effective mentor, but I feel about this the way I feel about Christianity, or for that matter any religious message.
At their core the belief is that what they have to share is meant to be shared openly and honestly. This marketing of the "secret" that we live in a vibrational universe and the vibration we chose to express determines the reality we live in kind of turns my stomach. Even knowing the flawed human side of Esther Hicks, I have to give the girl my respect for giving it away. She understands that she's going to make the money anyway. You can't turn around without running into someone else spouting the same message with more effort.
Effort on your part. With a sizable financial "investment." Hmmmm...... trying not to be judgemental.
I smell a future thread. These are the notes I took while watching. I have to be honest, she lost me to dreams of what it was I really wanted in my life, so I went on to making a list and firming up the vision a little more. The assumption is always that I'll still be active here. That calls for cosmic support to fuel the necessary expansion to include all of that fun.
I love a good seminar.
There's a two to three-day build up with enticing promises in a slick video presentation that left me in awe of the woman's ability to transmit authenticity. I have no doubt she's an effective mentor, but I feel about this the way I feel about Christianity, or for that matter any religious message. At their core the belief is that what they have to share is meant to be shared openly and honestly. This marketing of the "secret" that we live in a vibrational universe and the vibration we chose to express determines the reality we live in kind of turns my stomach. Even knowing the flawed human side of Esther Hicks, I have to give the girl my respect for giving it away. She understands that she's going to make the money anyway. You can't turn around without running into someone else spouting the same message with more effort.
Effort on your part. With a sizable financial "investment." Hmmmm...... trying not to be judgemental.
I smell a future thread. These are the notes I took while watching. I have to be honest, she lost me to dreams of what it was I really wanted in my life, so I went on to making a list and firming up the vision a little more. The assumption is always that I'll still be active here. That calls for cosmic support to fuel the necessary expansion to include all of that fun.
I love a good seminar.
- Thread starter
- #47
Marx's 4 points of alienation
1. From nature
2. From our true self
3. From others
4. From work (what you do doesn't represent the true you)
Society reinforces alienation. It's all driven by the egocentric mind.
The solution is to be still and reconnect with the greater part of you, but as societies we get to be very good at escaping stillness.
At 17:45 he hints at the ECS, although I don't believe that's what he was talking about.
19:45 - the duality of perspective (it's all in the perspective you choose)
20:15 The importance of acceptance. The e ego mind can only view the world through the lense of loss (if you have it I don't) and limitation.
31:00 The four qualities necessary to get beyond the ego-controlled mind and overcome addiction:
1. Compassion for the self (something else is possible and I deserve it)
2. Courage to see the situation as it really is, not like you want it to be.
3. Disidentify with the experience. You are not the experience, no matter how long you experienced it.
4. Ask yourself what experiences you're practicing that keep you in the loop of addiction.
It's all about not letting the addicted ego is mind control you. You control the addicted mind.
48:00 The nature of society and the negative effects on human expression.
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- #48
In a nutshell, chronic stress changes the plasticity of the receptors that regulate mood, causing depression. This process appears to be triggered by the downregulation of CB1 receptors in certain areas of the brain closely associated with the adrenal system. This downregulation may be caused by the increase in stress hormones floating in the internal sea of the brain.
It's CB1 receptors we want to activate for the mood regulation, and I believe CBD may fascilitate this by working on the receptors in subtle ways. It's been shown that injury to the brain causes an uptick in the number of CB2 receptors, but this is for purposes of reducing inflammatory response, as far as I can understand.
My experience has been that a balanced ratio, or one slightly tilted in favor of CBD, works effectively in the treatment of depression, at least with my patients. Every individual body will have an individual experience. This is why we start low and work up slowly.
Work for another day.
Chronic Stress Impairs α1-Adrenoceptor-Induced Endocannabinoid-Dependent Synaptic Plasticity in the Dorsal Raphe Nucleus
Samir Haj-Dahmane and Roh-Yu Shen
Journal of Neuroscience 29 October 2014, 34 (44) 14560-14570; DOI: https://doi.org/10.1523/JNEUROSCI.1310-14.2014
Serotonin (5-hydroxytryptamine [5-HT]) neurons in the dorsal raphe nucleus (DRn) (Dahlström and Fuxe, 1964) provide major serotonergic projections to brain areas controlling the behavioral and neuroendocrine responses to stress (Petrov et al., 1994). By modulating the stress-associated neuronal circuits, DRn 5-HT neurons control stress homeostasis and mood (Joëls and Baram, 2009). Indeed, animal studies have shown that the behavioral responses to various stressors are mediated, at least in part, by the activation of 5-HT system. For instance, exposure to uncontrollable stressors (e.g., tail shock) activates DRn 5-HT neurons and enhances 5-HT transmission (Amat et al., 1998; Maswood et al., 1998; Grahn et al., 1999). Activation of DRn 5-HT neurons also regulates uncontrollable stress-induced learned helplessness (Grahn et al., 1999), characterized by a set of behaviors, including reduced escape to aversive stimuli, increased fear conditioning, and anxiety (Maier et al., 1994, 1995). Conversely, inhibition of DRn 5-HT neurons reduces the behavioral responses to uncontrollable stressors (Maier et al., 1994, 1995), indicating that DRn 5-HT neurons play a key role in modulating the behavioral responses to uncontrollable stress (Maier and Watkins, 2005). Furthermore, results from clinical studies have established that stress-induced dysregulation of the 5-HT system is a major contributing factor for the development of mood disorders, such as depression and anxiety (Southwick et al., 2005; Lupien et al., 2009).
The DRn receives a major noradrenergic input from the locus ceruleus (Baraban and Aghajanian, 1981), which activates DRn 5-HT neurons (Baraban and Aghajanian, 1981) and regulates arousal and stress homeostasis (Morilak et al., 2005; Stone et al., 2007). Previous studies have shown that exposure to various stressors increases noradrenaline release in the DRn (Tanaka et al., 1983; Shimizu et al., 1994) and induces anxiety-like behaviors (Chiba et al., 2012; Kim et al., 2012), at least in part, via the activation of α1-ARs located on DRn 5-HT neurons (Stone et al., 2007). α1-AR signaling in the DRn also regulates fear conditioning, as blockade of these receptors prevents conditioned fear and impairs escape performance (Grahn et al., 2002). Furthermore, disruption of DRn α1-AR signaling alters the behavioral effects of antidepressant and antianxiety drugs (O'Leary et al., 2007; Doze et al., 2009). Collectively, these studies indicate that α1-AR-mediated control of DRn 5-HT neurons plays an important role in the regulation of stress homoeostasis and that the alteration of α1-AR signaling in the DRn might contribute to stress-related mood disorders.
Remarkably, despite the crucial role of α1-AR signaling in the DRn in controlling the behavioral responses to stress, the effects of chronic stress on α1-AR-mediated control of the excitability of 5-HT neurons and synaptic transmission in the DRn remain unknown. In this study, we show that exposure to chronic restraint stress (CRS) impairs α1-AR LTD of glutamate synapses in the DRn but has no effects on α1-AR-induced membrane depolarization/inward current in DRn 5-HT neurons. The CRS-induced impairment of α1-AR LTD is mediated by a downregulation of eCB signaling. Such results unravel a novel cellular mechanism by which chronic stress could induce long-lasting changes in the function of the 5-HT system.
Discussion
The present study shows that activation of α1-ARs elicits LTD of glutamate synapses onto DRn 5-HT neurons. This form of synaptic plasticity is initiated by the activation of postsynaptic α1-ARs but expressed presynaptically by a decrease in glutamate release. The α1-AR LTD is signaled by retrograde eCB messengers acting on presynaptic CB1 receptors. More importantly, we report that exposure to CRS profoundly reduces of the magnitude of α1-AR LTD. The CRS-induced impairment of α1-AR LTD is essentially mediated by a downregulation of presynaptic CB1 receptors. As such, our study reveals a novel cellular mechanism by which noradrenaline controls the function of DRn 5-HT. It also provides the first direct evidence that chronic stress reduces eCB signaling at glutamate synapses of DRn 5-HT neurons, which could have important functional implications for stress-induced maladaptation of the 5-HT system.
Previous studies have examined the regulation of glutamate synapses by α1-ARs in various brain areas (Scanziani et al., 1993; Scheiderer et al., 2004; Choi et al., 2005; McElligott and Winder, 2008; Marzo et al., 2010; McElligot et al., 2010). Generally, these studies have reported that activation of α1-ARs elicits a transient inhibition of glutamatergic transmission. However, in some brain areas, such as the cerebral cortex (e.g., visual cortex and prefrontal cortex), hippocampus, and the bed nucleus of striata terminalis, activation of α1-ARs induces LTD of glutamate synapses (Scheiderer et al., 2004; Choi et al., 2005; McElligott and Winder, 2008; Marzo et al., 2010; McElligot et al., 2010). Depending on the brain area studied, the α1-AR LTD seems to be mediated by different cellular mechanisms. In the hippocampus and cerebral cortex, the α1-AR LTD is mediated by a postsynaptic mechanism that involves α1-AR-induced activation of the extracellular signal regulating kinase (ERK1/2) pathways (Scheiderer et al., 2008; Marzo et al., 2010). Activation of ERK 1/2 induces LTD by reducing the function and/or number of AMPARs. At glutamate synapses of the bed nucleus of striata terminalis, the α1-AR LTD is mediated by a switch of the subunit composition of AMPARs from GluA2-lacking, which exhibit higher unitary conductance and calcium permeability (Kamboj et al., 1995; Dingledine et al., 1999), to GluA2 containing AMPARs (McElligott et al., 2010). In the DRn, the present study shows that the α1-AR LTD is initiated by the activation of postsynaptic α1-ARs but mediated by a decrease in glutamate release induced by retrograde eCB messengers. This cellular mechanism is supported by multiple lines of evidence. First, inhibition of postsynaptic α1-AR signaling with G-protein inhibitors abolishes the LTD. Second, α1-AR LTD is associated with a persistent decrease in glutamate release as indicated by the increase in PPR and CV. Finally, blockade of presynaptic CB1 receptors or inhibition of 2-AG synthesis abolishes the α1-AR LTD. The conclusion that the α1-AR LTD of glutamate synapses onto DRn 5-HT neurons is mediated by 2-AG acting at presynaptic CB1 receptors is consistent with numerous studies showing that activation of Gq/11-coupled receptors, such as Group I metabotropic glutamate receptors (mGluR1/5), M1/M5 muscarinic receptors, and orexin receptors, increase the synthesis/release of 2-AG in various brain areas (Maejima et al., 2001; Kim et al., 2002; Ohno-Shosaku et al., 2003), including the DRn (Haj-Dahmane and Shen, 2005). Generally, Gq/11 coupled receptor-driven 2-AG synthesis and release mediate transient inhibition of excitatory and inhibitory synaptic transmission (Maejima et al., 2001; Kim et al., 2002; Haj-Dahmane and Shen, 2005). However, growing evidence indicates that this mode of 2-AG synthesis/release also mediates the presynaptic form of LTD at glutamate and GABA synapses and, hence, plays an ubiquitous role in regulating synaptic plasticity in the brain (Castillo et al., 2012).
Results from previous studies have reported that chronic exposure to various stressors increases the expression in the DRn of various synaptic proteins, such as synaptosomal-associated protein 25 and synaptic vesicle glycoprotein 2B (Abumaria et al., 2006, 2007), suggesting that chronic stress can induce a long-lasting alteration of synaptic function and plasticity in the DRn. Consistent with this idea, we report that CRS impairs the α1-AR LTD of glutamate synapses onto DRn 5-HT neurons. The alteration of α1-AR-mediated synaptic plasticity in the DRn may represent an important cellular mechanism by which chronic stress can induce a long-lasting alteration of the 5-HT system. The effects of restraint stress on the α1-AR-mediated control of synaptic transmission have also been examined in several other brain areas. In the amygdala, exposure to acute restraint stress combined with tail shock blocks the α1-AR-mediated facilitation of GABA-ergic transmission (Braga et al., 2004). The mechanisms underlying this effect remain unknown. Here, we find that acute exposure to restraint stress has no effect on the ability of α1-ARs to control the function of glutamate synapses. In contrast, exposure to CRS profoundly impairs the α1-AR LTD of glutamate synapses in the DRn by blocking the induction and maintenance of the LTD. Such finding is in agreement with a previous study showing that exposure to CRS, but not to acute restraint stress, also impairs the LTD of glutamate synapses induced by α1-ARs (McElligott et al., 2010) in the basal nucleus of striata terminalis. Collectively, these studies suggest that the impairment of the α1-AR-mediated control of the strength and plasticity of glutamate synapses may represent a common response to chronic stress exposure. Importantly, such alterations of synaptic plasticity may mediate the maladaptive behavioral responses to chronic stress, including depression and anxiety.
An interesting finding of the present study is that exposure to CRS has no significant effect on the amplitude of the α1-AR-induced inward current but reduces the effect of presynaptic CB1 receptors on glutamate release. These results strongly indicate that the CRS-induced impairment of the α1-AR LTD is not mediated by a downregulation of α1-ARs but by a profound reduction of presynaptic CB1 receptor function. However, it remains possible that CRS could also reduce eCB synthesis/release, which may contribute to the impairment of the α1-AR LTD. The conclusion that CRS reduces the function of presynaptic CB1 receptors is consistent with previous studies showing that chronic exposure to various stressors, including CRS, downregulates CB1 receptors and impairs eCB-mediated control of glutamatergic (Rossi et al., 2008; Wang et al., 2010; Reich et al., 2013) and GABAergic synaptic transmission in other brain areas (Wamsteeker et al., 2010; Hu et al., 2011). Importantly, in the nucleus accumbens, exposure to chronic stress has also been shown to block the eCB-mediated LTD induced by mGluR1 at glutamate synapses onto medium spiny neurons (Wang et al., 2010). As in the DRn, the blockade of the mGluR1 LTD is mainly attributed to a reduction of presynaptic CB1 receptor function (Wang et al., 2010). Together, the results of these studies indicate that reduced retrograde eCB signaling (e.g., downregulation of CB1 receptors) may represent a common mechanism by which chronic stress impairs Gq/11-coupled receptor-mediated control of synaptic function and plasticity in the brain.
Although exposure to chronic stress has been shown to impair the function of presynaptic CB1 receptors in various brain areas (Hill et al., 2005; Wang et al., 2010), the precise molecular mechanisms underlying this effect remain unknown. It is well established that exposure to chronic stress increases the circulating levels of corticosterone and noradrenaline (Krugers et al., 2012). Because both of these stress mediators stimulate eCB synthesis and release in the DRn (Wang et al., 2012; present study) and other brain areas (Di et al., 2003), it is tempting to speculate that the high circulating levels of noradrenaline and corticosterone during daily stress lead to chronic increase in eCB release and activation of CB1 receptors, which could induce downregulation of these receptors. Consistent with this idea, results from previous studies have shown that chronic exposure to stress enhances the release of 2-AG in various brain regions (Patel and Hillard, 2008; Patel et al., 2009). More importantly, chronic activation of CB1 receptors with eCBs or exogenous cannabinoids has been shown to reduce the function of presynaptic CB1 receptors (Sim et al., 1996; Breivogel et al., 1999). Thus, it is possible that the CRS-induced functional downregulation of presynaptic CB1 receptors reported in this study could be attributed to an agonist-induced downregulation. However, future studies are required to further test this notion and determine the precise cellular mechanisms underlying the downregulation of presynaptic CB1 receptors.
Extensive work has established that noradrenergic inputs from the locus ceruleus provide a major excitatory drive to the DRn, which is mediated by α1-ARs. Activation of these receptors increases the excitability of DRn 5-HT neurons by inducing membrane depolarization (Aghajanian, 1985; Pan et al., 1994) and reducing the amplitude of after hyperpolarizing potential (Pan et al., 1994). In addition to these excitatory effects, the present study shows that activation of postsynaptic α1-ARs enhances 2-AG release, which in turn reduces the strength of glutamate synapses onto DRn 5-HT neurons (Fig. 8). Combined, these studies indicate that the noradrenergic modulation of 5-HT neurons is more complex than initially thought and that α1-AR signaling in the DRn exerts a bidirectional control on the excitability of 5-HT neurons. The bidirectional control exerted by α1-AR could play an important role in maintaining the activity of 5-HT neurons within desirable range and prevent excessive excitation of DRn 5-HT neurons, especially during heightened arousal (e.g., stress), which is characterized by increased noradrenergic tone (Krugers et al., 2012). As such, the reduction of eCB signaling and the impairment of α1-AR LTD induced by chronic stress may lead to an abnormal increase in the excitability of DRn 5-HT neurons and persistent alteration of central 5-HT transmission. Furthermore, the impairment of eCB signaling in the DRn could mediate, at least in part, some of the behavioral consequences of chronic stress exposure, such as depression-like behaviors. It is noteworthy that pharmacological manipulation that increases eCB signaling has been shown to block chronic stress-induced depression-like behaviors (Zhong et al., 2014).
A model of α1-ARs mediated regulation of glutamate synapses onto DRn 5-HT neurons. Activation of α1-ARs elicits an increase in the synthesis/release of the eCB messenger 2-AG. The release of 2-AG reduces the strength of glutamate synapses by the activation of presynaptic CB1 receptors. Exposure to CRS impairs α1-AR-mediated depression of glutamate synapses by reducing the function of presynaptic CB1 receptors.
It's CB1 receptors we want to activate for the mood regulation, and I believe CBD may fascilitate this by working on the receptors in subtle ways. It's been shown that injury to the brain causes an uptick in the number of CB2 receptors, but this is for purposes of reducing inflammatory response, as far as I can understand.
My experience has been that a balanced ratio, or one slightly tilted in favor of CBD, works effectively in the treatment of depression, at least with my patients. Every individual body will have an individual experience. This is why we start low and work up slowly.
Work for another day.
Chronic Stress Impairs α1-Adrenoceptor-Induced Endocannabinoid-Dependent Synaptic Plasticity in the Dorsal Raphe Nucleus
Samir Haj-Dahmane and Roh-Yu Shen
Journal of Neuroscience 29 October 2014, 34 (44) 14560-14570; DOI: https://doi.org/10.1523/JNEUROSCI.1310-14.2014
Serotonin (5-hydroxytryptamine [5-HT]) neurons in the dorsal raphe nucleus (DRn) (Dahlström and Fuxe, 1964) provide major serotonergic projections to brain areas controlling the behavioral and neuroendocrine responses to stress (Petrov et al., 1994). By modulating the stress-associated neuronal circuits, DRn 5-HT neurons control stress homeostasis and mood (Joëls and Baram, 2009). Indeed, animal studies have shown that the behavioral responses to various stressors are mediated, at least in part, by the activation of 5-HT system. For instance, exposure to uncontrollable stressors (e.g., tail shock) activates DRn 5-HT neurons and enhances 5-HT transmission (Amat et al., 1998; Maswood et al., 1998; Grahn et al., 1999). Activation of DRn 5-HT neurons also regulates uncontrollable stress-induced learned helplessness (Grahn et al., 1999), characterized by a set of behaviors, including reduced escape to aversive stimuli, increased fear conditioning, and anxiety (Maier et al., 1994, 1995). Conversely, inhibition of DRn 5-HT neurons reduces the behavioral responses to uncontrollable stressors (Maier et al., 1994, 1995), indicating that DRn 5-HT neurons play a key role in modulating the behavioral responses to uncontrollable stress (Maier and Watkins, 2005). Furthermore, results from clinical studies have established that stress-induced dysregulation of the 5-HT system is a major contributing factor for the development of mood disorders, such as depression and anxiety (Southwick et al., 2005; Lupien et al., 2009).
The DRn receives a major noradrenergic input from the locus ceruleus (Baraban and Aghajanian, 1981), which activates DRn 5-HT neurons (Baraban and Aghajanian, 1981) and regulates arousal and stress homeostasis (Morilak et al., 2005; Stone et al., 2007). Previous studies have shown that exposure to various stressors increases noradrenaline release in the DRn (Tanaka et al., 1983; Shimizu et al., 1994) and induces anxiety-like behaviors (Chiba et al., 2012; Kim et al., 2012), at least in part, via the activation of α1-ARs located on DRn 5-HT neurons (Stone et al., 2007). α1-AR signaling in the DRn also regulates fear conditioning, as blockade of these receptors prevents conditioned fear and impairs escape performance (Grahn et al., 2002). Furthermore, disruption of DRn α1-AR signaling alters the behavioral effects of antidepressant and antianxiety drugs (O'Leary et al., 2007; Doze et al., 2009). Collectively, these studies indicate that α1-AR-mediated control of DRn 5-HT neurons plays an important role in the regulation of stress homoeostasis and that the alteration of α1-AR signaling in the DRn might contribute to stress-related mood disorders.
Remarkably, despite the crucial role of α1-AR signaling in the DRn in controlling the behavioral responses to stress, the effects of chronic stress on α1-AR-mediated control of the excitability of 5-HT neurons and synaptic transmission in the DRn remain unknown. In this study, we show that exposure to chronic restraint stress (CRS) impairs α1-AR LTD of glutamate synapses in the DRn but has no effects on α1-AR-induced membrane depolarization/inward current in DRn 5-HT neurons. The CRS-induced impairment of α1-AR LTD is mediated by a downregulation of eCB signaling. Such results unravel a novel cellular mechanism by which chronic stress could induce long-lasting changes in the function of the 5-HT system.
Discussion
The present study shows that activation of α1-ARs elicits LTD of glutamate synapses onto DRn 5-HT neurons. This form of synaptic plasticity is initiated by the activation of postsynaptic α1-ARs but expressed presynaptically by a decrease in glutamate release. The α1-AR LTD is signaled by retrograde eCB messengers acting on presynaptic CB1 receptors. More importantly, we report that exposure to CRS profoundly reduces of the magnitude of α1-AR LTD. The CRS-induced impairment of α1-AR LTD is essentially mediated by a downregulation of presynaptic CB1 receptors. As such, our study reveals a novel cellular mechanism by which noradrenaline controls the function of DRn 5-HT. It also provides the first direct evidence that chronic stress reduces eCB signaling at glutamate synapses of DRn 5-HT neurons, which could have important functional implications for stress-induced maladaptation of the 5-HT system.
Previous studies have examined the regulation of glutamate synapses by α1-ARs in various brain areas (Scanziani et al., 1993; Scheiderer et al., 2004; Choi et al., 2005; McElligott and Winder, 2008; Marzo et al., 2010; McElligot et al., 2010). Generally, these studies have reported that activation of α1-ARs elicits a transient inhibition of glutamatergic transmission. However, in some brain areas, such as the cerebral cortex (e.g., visual cortex and prefrontal cortex), hippocampus, and the bed nucleus of striata terminalis, activation of α1-ARs induces LTD of glutamate synapses (Scheiderer et al., 2004; Choi et al., 2005; McElligott and Winder, 2008; Marzo et al., 2010; McElligot et al., 2010). Depending on the brain area studied, the α1-AR LTD seems to be mediated by different cellular mechanisms. In the hippocampus and cerebral cortex, the α1-AR LTD is mediated by a postsynaptic mechanism that involves α1-AR-induced activation of the extracellular signal regulating kinase (ERK1/2) pathways (Scheiderer et al., 2008; Marzo et al., 2010). Activation of ERK 1/2 induces LTD by reducing the function and/or number of AMPARs. At glutamate synapses of the bed nucleus of striata terminalis, the α1-AR LTD is mediated by a switch of the subunit composition of AMPARs from GluA2-lacking, which exhibit higher unitary conductance and calcium permeability (Kamboj et al., 1995; Dingledine et al., 1999), to GluA2 containing AMPARs (McElligott et al., 2010). In the DRn, the present study shows that the α1-AR LTD is initiated by the activation of postsynaptic α1-ARs but mediated by a decrease in glutamate release induced by retrograde eCB messengers. This cellular mechanism is supported by multiple lines of evidence. First, inhibition of postsynaptic α1-AR signaling with G-protein inhibitors abolishes the LTD. Second, α1-AR LTD is associated with a persistent decrease in glutamate release as indicated by the increase in PPR and CV. Finally, blockade of presynaptic CB1 receptors or inhibition of 2-AG synthesis abolishes the α1-AR LTD. The conclusion that the α1-AR LTD of glutamate synapses onto DRn 5-HT neurons is mediated by 2-AG acting at presynaptic CB1 receptors is consistent with numerous studies showing that activation of Gq/11-coupled receptors, such as Group I metabotropic glutamate receptors (mGluR1/5), M1/M5 muscarinic receptors, and orexin receptors, increase the synthesis/release of 2-AG in various brain areas (Maejima et al., 2001; Kim et al., 2002; Ohno-Shosaku et al., 2003), including the DRn (Haj-Dahmane and Shen, 2005). Generally, Gq/11 coupled receptor-driven 2-AG synthesis and release mediate transient inhibition of excitatory and inhibitory synaptic transmission (Maejima et al., 2001; Kim et al., 2002; Haj-Dahmane and Shen, 2005). However, growing evidence indicates that this mode of 2-AG synthesis/release also mediates the presynaptic form of LTD at glutamate and GABA synapses and, hence, plays an ubiquitous role in regulating synaptic plasticity in the brain (Castillo et al., 2012).
Results from previous studies have reported that chronic exposure to various stressors increases the expression in the DRn of various synaptic proteins, such as synaptosomal-associated protein 25 and synaptic vesicle glycoprotein 2B (Abumaria et al., 2006, 2007), suggesting that chronic stress can induce a long-lasting alteration of synaptic function and plasticity in the DRn. Consistent with this idea, we report that CRS impairs the α1-AR LTD of glutamate synapses onto DRn 5-HT neurons. The alteration of α1-AR-mediated synaptic plasticity in the DRn may represent an important cellular mechanism by which chronic stress can induce a long-lasting alteration of the 5-HT system. The effects of restraint stress on the α1-AR-mediated control of synaptic transmission have also been examined in several other brain areas. In the amygdala, exposure to acute restraint stress combined with tail shock blocks the α1-AR-mediated facilitation of GABA-ergic transmission (Braga et al., 2004). The mechanisms underlying this effect remain unknown. Here, we find that acute exposure to restraint stress has no effect on the ability of α1-ARs to control the function of glutamate synapses. In contrast, exposure to CRS profoundly impairs the α1-AR LTD of glutamate synapses in the DRn by blocking the induction and maintenance of the LTD. Such finding is in agreement with a previous study showing that exposure to CRS, but not to acute restraint stress, also impairs the LTD of glutamate synapses induced by α1-ARs (McElligott et al., 2010) in the basal nucleus of striata terminalis. Collectively, these studies suggest that the impairment of the α1-AR-mediated control of the strength and plasticity of glutamate synapses may represent a common response to chronic stress exposure. Importantly, such alterations of synaptic plasticity may mediate the maladaptive behavioral responses to chronic stress, including depression and anxiety.
An interesting finding of the present study is that exposure to CRS has no significant effect on the amplitude of the α1-AR-induced inward current but reduces the effect of presynaptic CB1 receptors on glutamate release. These results strongly indicate that the CRS-induced impairment of the α1-AR LTD is not mediated by a downregulation of α1-ARs but by a profound reduction of presynaptic CB1 receptor function. However, it remains possible that CRS could also reduce eCB synthesis/release, which may contribute to the impairment of the α1-AR LTD. The conclusion that CRS reduces the function of presynaptic CB1 receptors is consistent with previous studies showing that chronic exposure to various stressors, including CRS, downregulates CB1 receptors and impairs eCB-mediated control of glutamatergic (Rossi et al., 2008; Wang et al., 2010; Reich et al., 2013) and GABAergic synaptic transmission in other brain areas (Wamsteeker et al., 2010; Hu et al., 2011). Importantly, in the nucleus accumbens, exposure to chronic stress has also been shown to block the eCB-mediated LTD induced by mGluR1 at glutamate synapses onto medium spiny neurons (Wang et al., 2010). As in the DRn, the blockade of the mGluR1 LTD is mainly attributed to a reduction of presynaptic CB1 receptor function (Wang et al., 2010). Together, the results of these studies indicate that reduced retrograde eCB signaling (e.g., downregulation of CB1 receptors) may represent a common mechanism by which chronic stress impairs Gq/11-coupled receptor-mediated control of synaptic function and plasticity in the brain.
Although exposure to chronic stress has been shown to impair the function of presynaptic CB1 receptors in various brain areas (Hill et al., 2005; Wang et al., 2010), the precise molecular mechanisms underlying this effect remain unknown. It is well established that exposure to chronic stress increases the circulating levels of corticosterone and noradrenaline (Krugers et al., 2012). Because both of these stress mediators stimulate eCB synthesis and release in the DRn (Wang et al., 2012; present study) and other brain areas (Di et al., 2003), it is tempting to speculate that the high circulating levels of noradrenaline and corticosterone during daily stress lead to chronic increase in eCB release and activation of CB1 receptors, which could induce downregulation of these receptors. Consistent with this idea, results from previous studies have shown that chronic exposure to stress enhances the release of 2-AG in various brain regions (Patel and Hillard, 2008; Patel et al., 2009). More importantly, chronic activation of CB1 receptors with eCBs or exogenous cannabinoids has been shown to reduce the function of presynaptic CB1 receptors (Sim et al., 1996; Breivogel et al., 1999). Thus, it is possible that the CRS-induced functional downregulation of presynaptic CB1 receptors reported in this study could be attributed to an agonist-induced downregulation. However, future studies are required to further test this notion and determine the precise cellular mechanisms underlying the downregulation of presynaptic CB1 receptors.
Extensive work has established that noradrenergic inputs from the locus ceruleus provide a major excitatory drive to the DRn, which is mediated by α1-ARs. Activation of these receptors increases the excitability of DRn 5-HT neurons by inducing membrane depolarization (Aghajanian, 1985; Pan et al., 1994) and reducing the amplitude of after hyperpolarizing potential (Pan et al., 1994). In addition to these excitatory effects, the present study shows that activation of postsynaptic α1-ARs enhances 2-AG release, which in turn reduces the strength of glutamate synapses onto DRn 5-HT neurons (Fig. 8). Combined, these studies indicate that the noradrenergic modulation of 5-HT neurons is more complex than initially thought and that α1-AR signaling in the DRn exerts a bidirectional control on the excitability of 5-HT neurons. The bidirectional control exerted by α1-AR could play an important role in maintaining the activity of 5-HT neurons within desirable range and prevent excessive excitation of DRn 5-HT neurons, especially during heightened arousal (e.g., stress), which is characterized by increased noradrenergic tone (Krugers et al., 2012). As such, the reduction of eCB signaling and the impairment of α1-AR LTD induced by chronic stress may lead to an abnormal increase in the excitability of DRn 5-HT neurons and persistent alteration of central 5-HT transmission. Furthermore, the impairment of eCB signaling in the DRn could mediate, at least in part, some of the behavioral consequences of chronic stress exposure, such as depression-like behaviors. It is noteworthy that pharmacological manipulation that increases eCB signaling has been shown to block chronic stress-induced depression-like behaviors (Zhong et al., 2014).
A model of α1-ARs mediated regulation of glutamate synapses onto DRn 5-HT neurons. Activation of α1-ARs elicits an increase in the synthesis/release of the eCB messenger 2-AG. The release of 2-AG reduces the strength of glutamate synapses by the activation of presynaptic CB1 receptors. Exposure to CRS impairs α1-AR-mediated depression of glutamate synapses by reducing the function of presynaptic CB1 receptors.
- Thread starter
- #49
Glad I grabbed this when I did. It's been pulled from YouTube, and this was very insightful information. Learned that lesson. If it catches my eye, grab the pertinent stuff NOW!
Anandamide and anxiety with particular attention to PTSD - Nancy Minyanou in fulfillment for a class requirement.
"This video plans to give evidence that modulation of anandamide Cann be a powerful treatment for anxiety disorders, such as PTSD, for its effects on anxiety behavior and memory consolidation.
Amandine is an endogenous endocannabinoid, also known as AEA. It is an L-peptide linking polymer of amino acids, according to the Protein Data Base's ligand entry.
Cannabinoid agonists have a bi-physic reaction such that higher doses are associated with having an anxiety-inducing effect, where lower doses have an anti-anxiety effect.
Receptor type 1 activation reduces GABA release from pre-synaptic terminals, increasing cell excitability.
Type 1 is most densely found in the amygdala, hippocampus, anterior cingulate cortex, and prefrontal cortex, all important regions for anxiety regulation.
Type 2 is found periferally.
Experiments suggest that endogenous cannabinoids have a hand in regulating emotional behavior. There appears to be a functional relationship between cannabinoid CB1 and 5HT1A receptors in modulation of adrenal cortical activity.
AM 404, an anandamide transport inhibitor, inhibits the breakdown and uptake of AEA. AM251 is a CB1 receptor antagonist.
AEA-injected rats spent more time on the elevated arms with lower doses, and after they were first injected with AM404.
Using ACEA alone or with AM404 resulted in a bell-shaped response curve.
Neither AM251 or AM404 were effective alone in modifying animal behavior.
Peripheral levels of AEA and other compounds were assessed in healthy individuals, those who had experienced trauma, and those with PTSD, which is more pronounced in women.
the elevated +/0 mazes were used to test for anxiety via time spent on open sections of the platform. The acetic acid test performed had mice injected with acetic acid and the number of reads was counted to measure nose inception(??????)
Fear, conditioned to object and context recognition was used to test the effects of URB597 on memory consolidation. Graph C's middle bar shows a lowered freezing after given URB597. Graph D shows the increased level of AEA after administration of URB597. It inhibits the AEA degradation enzyme, fatty acid amide hydrolase. It produced anxiolytics effects in both mazes through the activation of different cannabinoid receptors, suggesting CB2 being a good target for future treatment of anxiety disorders and modified brain content of AEA.
They found that URB597 mediated modulation of ARA promotes memory deficits through similar mechanisms as that for THC, the psychoactive component of cannabis.
- Thread starter
- #50
Ethan Russo MD - The Endocannabinoid System in Health and Disease
speaking in Sydney, Australia on June 8, 2016 * United in Compassion Medicinal Cannabis Symposium (United in Compassion)
ethanrusso@comcast.net
Basics:
- Cannabis sativa makes trichomes, which are filled with the essential oil of the plant. This oil includes cannabinoids and terpenoids.
- Cannabinoids bind to the CB receptors found in the body. Most are CB1, and are found in the brain.
- The receptors are like the locks, and cannabinoids are the keys that unlock the receptors.
- Endogenous cannabinoids (anandamide and 2-AG, surely among others, yet to be identified) are those produced by your own body.
- They're created on site and on demand, and bind to the CB1 receptor.
- There are 3 kinds of cannabinoids,
1) phytocannabinoids: basically, 21-carbon items from cannabis, with exception of plants that have Beta-Caryophyllene, which activates the CB2 receptors
2) endocannabinoids: produced by the body
- The ECS has been described as having functions regulating Relaxation Appetite, Sleep, Memory (I always forget this one), and Protection. Rest, Eat, Sleep, Forget, Protect
3) synthetic cannabinoids: some developed before we knew about receptors, some after
- In the brain endogenous cannabinoids act in a retrograde fashion, downregulating the neurotransmitters, originating in the post-synaptic neuron and traveling upstream to attach to CB1 receptors on the other side of the gap. The primary reason for their attachment is to reduce the release of neurotransmitters.
- They're damping down whatever particular function and response that neuron is set for.
- Found throughout the animal kingdom in cordates, animals with a spinal cord Makes sense. The function of the ECS is to balance the immune and nervous systems, creating homeostasis.
The ECS has three components
1. endocannabinoids
2. cannabinoid receptors: CB1, CB2, and ionitropic cannabinoid receptor (TRPV 1)
From Medical Jane (highlights are mine): Specialized receptors are located throughout the human body, including but not limited to, in the hippocampus, (memory and learning), the cerebral cortex ( decision making, emotional behavior), the cerebellum (motor control, coordination), putamen (movement, learning), the hypothalamus (appetite, body temperature), and the amygdala (emotions).
When a specific cannabinoid or a combination of cannabinoids bind to a specialized receptor, an event or a series of events, is triggered in the cell, resulting in a change in
- the cell's activity
- its gene regulation and/or the signals that it sends to neighboring cells through the process we call "signal transduction."
3. enzymes that make cannabinoids and break them down; these can be be manipulated pharmacologically and serve as medicines as well Interesting. This is the first time I caught this.
Entourage Effect
- You have anandamide and 2-AG, but there're also other compounds within the body that, on their own, don't have much power, but working synergistically can deliver a powerful therapeutic punch.
- Soloists and supporting cast. Hmmm.... Our thinking may be skewered on this point. Those "supporting cast" members may turn out to be equal partners.
CB1 receptors in the brain are located heavily in areas that're nociceptive, places having to do with mediating pain
- Additionally found the cerebellum, the limbic system, (emotion), the basal ganglia (movement)
- Receptors are also in reward pathways (addiction and its many effects on the system)
- Receptors aren't found in the areas of the brain having to do with respiration, so cannabinoids can't kill you like all the wonder drugs can. This is how opioids kill.
They suppress the respiratory center of the brain and your body forgets to breath. Dammit!!
Gosh, that hurt to write, and just as much to read. So many people in such needless pain, it all came crashing in. Moments like this leave me shaking, but I've created enough equanimity that it doesn't have me crying anymore. Almost, but I caught it and deflected the momentum. Whew! Stopping at 6:56. I'll pick up tomorrow. I'm seeing double. Lol!
This was what was playing when I finished for the night. Lol! God, I love the way she does this song.
[video=youtube;oTbObag1r0I]https:/www.youtube.com/watch?v=oTbObag1r0I[/video]
Sweet way to end the night.
speaking in Sydney, Australia on June 8, 2016 * United in Compassion Medicinal Cannabis Symposium (United in Compassion)
ethanrusso@comcast.net
Basics:
- Cannabis sativa makes trichomes, which are filled with the essential oil of the plant. This oil includes cannabinoids and terpenoids.
- Cannabinoids bind to the CB receptors found in the body. Most are CB1, and are found in the brain.
- The receptors are like the locks, and cannabinoids are the keys that unlock the receptors.
- Endogenous cannabinoids (anandamide and 2-AG, surely among others, yet to be identified) are those produced by your own body.
- They're created on site and on demand, and bind to the CB1 receptor.
- There are 3 kinds of cannabinoids,
1) phytocannabinoids: basically, 21-carbon items from cannabis, with exception of plants that have Beta-Caryophyllene, which activates the CB2 receptors
2) endocannabinoids: produced by the body
- The ECS has been described as having functions regulating Relaxation Appetite, Sleep, Memory (I always forget this one
), and Protection. Rest, Eat, Sleep, Forget, Protect3) synthetic cannabinoids: some developed before we knew about receptors, some after
- In the brain endogenous cannabinoids act in a retrograde fashion, downregulating the neurotransmitters, originating in the post-synaptic neuron and traveling upstream to attach to CB1 receptors on the other side of the gap. The primary reason for their attachment is to reduce the release of neurotransmitters.
- They're damping down whatever particular function and response that neuron is set for.
- Found throughout the animal kingdom in cordates, animals with a spinal cord Makes sense. The function of the ECS is to balance the immune and nervous systems, creating homeostasis.
The ECS has three components
1. endocannabinoids
2. cannabinoid receptors: CB1, CB2, and ionitropic cannabinoid receptor (TRPV 1)
From Medical Jane (highlights are mine): Specialized receptors are located throughout the human body, including but not limited to, in the hippocampus, (memory and learning), the cerebral cortex ( decision making, emotional behavior), the cerebellum (motor control, coordination), putamen (movement, learning), the hypothalamus (appetite, body temperature), and the amygdala (emotions).
When a specific cannabinoid or a combination of cannabinoids bind to a specialized receptor, an event or a series of events, is triggered in the cell, resulting in a change in
- the cell's activity
- its gene regulation and/or the signals that it sends to neighboring cells through the process we call "signal transduction."
3. enzymes that make cannabinoids and break them down; these can be be manipulated pharmacologically and serve as medicines as well Interesting. This is the first time I caught this.
Entourage Effect
- You have anandamide and 2-AG, but there're also other compounds within the body that, on their own, don't have much power, but working synergistically can deliver a powerful therapeutic punch.
- Soloists and supporting cast. Hmmm.... Our thinking may be skewered on this point. Those "supporting cast" members may turn out to be equal partners.
CB1 receptors in the brain are located heavily in areas that're nociceptive, places having to do with mediating pain
- Additionally found the cerebellum, the limbic system, (emotion), the basal ganglia (movement)
- Receptors are also in reward pathways (addiction and its many effects on the system)
- Receptors aren't found in the areas of the brain having to do with respiration, so cannabinoids can't kill you like all the wonder drugs can. This is how opioids kill.
They suppress the respiratory center of the brain and your body forgets to breath. Dammit!!Gosh, that hurt to write, and just as much to read. So many people in such needless pain, it all came crashing in. Moments like this leave me shaking, but I've created enough equanimity that it doesn't have me crying anymore. Almost, but I caught it and deflected the momentum. Whew!
Stopping at 6:56. I'll pick up tomorrow. I'm seeing double. Lol!
This was what was playing when I finished for the night. Lol! God, I love the way she does this song.
[video=youtube;oTbObag1r0I]https:/www.youtube.com/watch?v=oTbObag1r0I[/video]
Sweet way to end the night.
- Thread starter
- #51
Picking up where I left off.
Ethan Russo MD - The Endocannabinoid System in Health and Disease
speaking in Sydney, Australia on June 8, 2016 * United in Compassion Medicinal Cannabis Symposium (United in Compassion)
ethanrusso@comcast.net
Basics:
- Cannabis sativa makes trichomes, which are filled with the essential oil of the plant. This oil includes cannabinoids and terpenoids.
- Cannabinoids bind to the CB receptors found in the body. Most are CB1, and are found in the brain.
- The receptors are like the locks, and cannabinoids are the keys that unlock the receptors.
- Endogenous cannabinoids (anandamide and 2-AG, surely among others, yet to be identified) are those produced by your own body.
- They're created on site and on demand, and bind to the CB1 receptor.
- There are 3 kinds of cannabinoids,
1) phytocannabinoids: basically, 21-carbon items from cannabis, with exception of plants that have Beta-Caryophyllene, which activates the CB2 receptors
2) endocannabinoids: produced by the body
- The ECS has been described as having functions regulating Relaxation Appetite, Sleep, Memory (I always forget this one), and Protection. Rest, Eat, Sleep, Forget, Protect
3) synthetic cannabinoids: some developed before we knew about receptors, some after
- In the brain endogenous cannabinoids act in a retrograde fashion, downregulating the neurotransmitters, originating in the post-synaptic neuron and traveling upstream to attach to CB1 receptors on the other side of the gap. The primary reason for their attachment is to reduce the release of neurotransmitters.
- They're damping down whatever particular function and response that neuron is set for.
- Found throughout the animal kingdom in cordates, animals with a spinal cord
The ECS has three components
1. endocannabinoids
2. cannabinoid receptors: CB1, CB2, and ionitropic cannabinoid receptor (TRPV 1)
From Medical Jane (highlights are mine): Specialized receptors are located throughout the human body, including but not limited to, in the hippocampus, (memory and learning), the cerebral cortex ( decision making, emotional behavior), the cerebellum (motor control, coordination), putamen (movement, learning), the hypothalamus (appetite, body temperature), and the amygdala (emotions).
When a specific cannabinoid or a combination of cannabinoids bind to a specialized receptor, an event or a series of events, is triggered in the cell, resulting in a change in
- the cell's activity
- its gene regulation and/or the signals that it sends to neighboring cells through the process we call "signal transduction."
3. enzymes that make cannabinoids and break them down; these can be be manipulated pharmacologically and serve as medicines as well
Entourage Effect
- You have anandamide and 2-AG, but there're also other compounds within the body that, on their own, don't have much power, but working synergistically can deliver a powerful therapeutic punch.
- Soloists and supporting cast.
CB1 receptors in the brain are located heavily in areas that're nociceptive, places having to do with mediating pain
- Additionally found the cerebellum, the limbic system, (emotion), the basal ganglia (movement)
- Receptors are also in reward pathways (addiction and its many effects on the system)
- Receptors aren't found in the areas of the brain having to do with respiration, so cannabinoids can't kill you like all the wonder drugs can. This is how opioids kill. They depress the respiratory center of the brain and your body forgets to breathe.
The cannabinoids also work in the spinal cord, in the periphery, and in the gut.
- CB1 is the most prolific CB G-protein receptor in the brain, where it modulates the release of neurotransmitters.
- Glutamate is typically overactive in neuropathic pain. If cannabinoids damp down glutamate response, that would effect pain over time.
- Modulates pain, memory, movement, whether someone will vomit or not, their seizure threshold.
- Also modulate many other body systems, incl. the gut.
The brain and the gut speak for themselves same language.
- Cannabinoids mo
- propulsion: the speed with which things move through the gut
- secretion: how much liquid or lack of liquid is brought into play during digestion and elimination
- One of the first successful treatments for cholera (major symptom is deadly diarrhea) in the 19th century was cannabis.
If we think of CB1 as the psychoactive receptor we then look at CB2 receptors, found mainly in the periphery, as pain and inflammation.
- Drugs that could effect only CB2 receptors wouldn't have any euphoric effect.
- Such drugs could be promising in treating fibrotic diseases like scarring in the liver or other organs.
Both kinds of receptors are found in the skin.
- Exciting therapeutically due to accessibility (don't need to go through a lot of layers to be active)
- Currently an area of intense research.
CBD, which doesn't attach to either receptor with any real affinity seems to be a valuable cannabinoid for the skin.
- A full-spectrum cannabis extract with CBD would show antibacterial effects (as in acne).
- CBD works on TRPV-4 receptors, which reduces the release of fat (sebum), which contribute to acne.
se·bum
ˈsēbəm/
noun
an oily secretion of the sebaceous glands.
Sebum Definition - Verywell
Apr 15, 2017 - Sebum is a light yellow, oily substance that is secreted by the sebaceous glands that help keep the skin and hair moisturized. Sebum is made up of triglycerides, free fatty acids, wax esters, squalene, cholesterol esters, and cholesterol. ... It also includes lipids from skin cells, sweat, and environmental matter
CBD was recently shown to stimulate bone fracture healing.
- Right now cannabinoids are banned from professional and amateur sports. It might be time to rethink that. Cannabidiol will speed the healing, without side effects.
Cannabis will accelerate the heart rate.
- Interestingly, at a higher dose it will slow the heart rate down, far enough to make it difficult to regulate blood pressure.
- You can pass out from orthostatic hypertension.
Concerns:
- There was a rise in concern that cannabis might contribute to heart attack, but the thinking is the signalling isn't strong enough to make this drastic an effect. It may be a concern for individual patients, but not as a population concern.
- For a time there was concern that there might be an arthritic response to cannabis. Upon closer inspection it was discovered that the patients were all tobacco smokers, and tobacco is known to constrict blood vessels in the hands (Berger's Disease).
The most common use of cannabis is for the treatment of chronic pain conditions. Cannabis offers relief through various pathways
- Through neurotransmitters
- through interaction with opioids, whether by pill form or the endogenous opioid system
- direct effects in the brain
- other components in cannabis beyond the major cannabinoids, CBD and THC
The brain has a base-line level of cannabinoid function (the endocannabinoid tone)
- Under certain conditions activity can be either depressed or enhanced.
- the periaqueductal gray is a mind brain generator (???)
The periaqueductal gray, or PAG, is an area of gray matter found in the midbrain. The PAG surrounds the cerebral aqueduct (hence the name periaqueductal) and occupies a column of brainstem that stretches about 14 mm long. There are no obvious visible anatomical divisions within the PAG, but researchers have divided the PAG into four columns based on differences in connectivity and function: the dorsomedial, dorsolateral, lateral, and ventrolateral columns.
What is the periaqueductal gray and what does it do?
Although the functions of the PAG are complex and not fully understood, since the 1970s it has best been known for its role in the inhibition of pain. Indeed, some have argued that its identification as an "analgesia center" has hindered a more complete understanding of the functions of the PAG. An increasingly intricate appreciation of PAG function, however, has been emerging over the past few decades
When the PAG was first found to have an association with pain, it was observed as playing a role in pain transmission---or the sending of pain signals to the cortex---and not the mitigation of those signals. Eventually, the PAG would come to be much better recognized as an area important to pain inhibition. In the late 1960s, the first indication of the role of the PAG in pain suppression emerged from a study that found that stimulation of the PAG in rats allowed researchers to perform surgery on the rats without the use of anesthetics (and without the animals exhibiting signs of severe pain). Further studies found that PAG activation was associated with the inhibition of spinal cord neurons involved in pain signaling. By the mid-1970s, stimulation of the PAG was already being used as an experimental approach to treating chronic pain in human patients. The fact that some of these experiments reported success in the treatment of chronic pain supported the role of the PAG in analgesia. The patients involved in these experiments also often complained of a wide range of side effects linked to PAG stimulation, however, suggesting that many more functions than analgesia were connected to the PAG.
- Cannabinoids also active in the thalamus (ventral postural lateral nucleus). Tested in this area cannabinoids are 10 times more powerful than morphine. It becomes obvious that using the two drugs together would be a beneficial approach for pain management.
- There are additional functions in the spinal cord by which cannabinoids effect pain levels and perception.
Cannabinoids can be effective against contact dermatitis (poison ivy or plain old itching)
There are numerous randomized trials on cannabis and pain. The problem is that the company that holds the rights to market isn't choosing to do so in many markets. Just exactly what we anticipated. Give Big Pharma control and they won't market something they can't make the big money on. Keep this plant out of their hands and in the control of the people.
An interesting thing occurred when they tested cannabis with cancer pain in hospice settings. The patients got relief and the tolerance levels didn't rise in the same way they see with opioids. There wasn't the standard increase in pain levels with cannabis or Sativex.
- The gold standard in pain is the group that has a 30% reduction in pain over time.
- In the study 43% of patients using Sativex got relief, as opposed to 21% with the placebo.
- The study contrasted placebo, Sativex and a full THC isolate extraction. The isolate didn't work any better than the placebo. The Sativex, with its inclusion of CBD, did work, and in dramatic fashion.
- This was the first concrete evidence of th entourage effect in pain control.
Placebos work Faith is a powerful tool, and I'm convinced the ECS can heal a disease-wracked body instantaneously, so the placebo effect doesn't surprise me in the slightest.
- Have a placebo that works so well and you'll end up with your effective drug looking ineffective next to the placebo, making your drug look statistically insignificant.
In a randomized withdrawal study of Nabixinol,Sativex, and MS patients were unknowingly started on Sativex at either a level to control spacisity or to keep them from having too many side effects.
- The 20% who improved were brought back and then randomly half were refilled with placebos.
- All patients who stayed on Sativex improved spacisity, and all patients on the placebo went into decline.
- These results were the impetus for gaining approval for Sativex administration in 27 countries. Are we one of those lucky countries?
- They had patients with twisted limbs that had the muscles relax after administration of Sativex I believe Sayivex is a balanced ratio medication.
Clinical Endocannabinoid Deficiency
- Your endocannabinoid tone is an indicator of the number of cannabinoids available, how their produced and degraded, and how many receptors you have available.
- A change to any of those areas can effect the endocannabinoid tone, resulting in pain, stiffness in the muscles, the seizure threshold, etc.
- The theory was that in certain conditions if the tone is depressed too low it'll produce disease and symptoms in the system.
- In original 2004 paper he focused on migraine, fibromyalgia and IBS. All three are hyper analgesic responses, where the system has a heightened pain response.
- All three are difficult, if not impossible to track or determine by lab testing, so they're diagnosed based on clinical determination of the patient's described patterns.
- They're all also comorbid, meaning if you have one, you likely have the other two. Primary headache turned up in 97% of the cases with fibromyalgia. 33% of patients with chronic daily headaches (a type of migraine) also had fibromyalgia. 32% of patients with IBS had fibromyalgia and 32% of fibromyalgia patients also had IBS.
Unfortunately, these conditions show up in large numbers of women who get misdiagnosed as being psychosomatic by their male doctors.
- Russo maintains that this is a biochemical disorder, possibly due to a drop in endocannabinoid expression, and there's no mind game these women are playing with themselves.
IBS: Sometimes thought of as a life-long condition, but people clearly acquire this at some point.
- It's the most frequent diagnosis among gastroenterologist in the states.
- There are no particular regular signs, but there is a pattern of irregular bowel movements, often diarrhea, although this could be constipation. They can alternate too.
- It's being described as a disorder of unknown origin and treated by agents of an unknown mechanism of action.
- There are many ineffective drugs. The target should be the ECS instead.
- IBS brings the joy of visceral hypersensitivity. Things hurt, and hurt bad. Again, an over abundance of pain.
- It's known that anandamide works with colonergic neurons, the primary movers of the gut. It performs a modulatory role on the speed of digestion and elimination.
- The ECS appears to be unregulated in diseases of the gut with inflammation. This would be true in the case of IBS as well.
The Mayo clinic, looking at genetic markers of IBS, found CNRI (has to do with cannabinoid function)
- Patients with IBS responded positively to THC.
- CB1 receptors seem to modify the speed through the gut.
Relationships to diet
- If you eat the right things you might not have to use cannabis so much.
- Replenishing the gut flora with probiotics enhanced pain management. They positively effect the RNA expression of the gene associated with CB receptors when taken as a supplement.
- This enhanced the pain control function of morphine.
- It was proposed that taking a CB2 antagonist would enhance that function.
- 32 out of 45 studies on the addition of probiotics showed an improvement in gut performance and health for patients with IBS, incl. less pain, less bloating, etc...
- 5-6 months of continuious supplementation created a stable environment in the gut.
A recent study found that THC alters the bacterial presence in the gut.
- In these mice that had a predisposition to being obese, the THC prevented weight gain through the action of changing the balance of the gut bacteria.
Prebiotics, vegetable matter that feed the good gut flora. (FOS) They don't get broken down in the stomach and they're fermented by the gut flora.
- There are over a thousand different species of bacteria being brewed.
- Prebiotocs help the healthy, beneficial gut flora grow and prosper.
- It's estimated that ancient man ate a lot more of these valuable vegetables. Modern humans may only get a few grams a day.
- Best sources acacia fiber, gum arabic, chicory, burdock, sunchokes (Jerusalem artichoke), onions, leek, garlic, dandelion greens,
- They reduce infectious diarrhea, alleviate inflammatory bowel diseases, reduce cancer risk in the gut, increase mineral absorbtion, lower cardiac risk, and decrease obesity.
- 10 grams a day - a heaping tablespoon of acacia fiber that could be added to any number of foods, increased lactobacillus sixfold and increased balance of the gut flora. It also appears to decrease the bug that causes c-diff.
Begin at 36:50
Ethan Russo MD - The Endocannabinoid System in Health and Disease
speaking in Sydney, Australia on June 8, 2016 * United in Compassion Medicinal Cannabis Symposium (United in Compassion)
ethanrusso@comcast.net
Basics:
- Cannabis sativa makes trichomes, which are filled with the essential oil of the plant. This oil includes cannabinoids and terpenoids.
- Cannabinoids bind to the CB receptors found in the body. Most are CB1, and are found in the brain.
- The receptors are like the locks, and cannabinoids are the keys that unlock the receptors.
- Endogenous cannabinoids (anandamide and 2-AG, surely among others, yet to be identified) are those produced by your own body.
- They're created on site and on demand, and bind to the CB1 receptor.
- There are 3 kinds of cannabinoids,
1) phytocannabinoids: basically, 21-carbon items from cannabis, with exception of plants that have Beta-Caryophyllene, which activates the CB2 receptors
2) endocannabinoids: produced by the body
- The ECS has been described as having functions regulating Relaxation Appetite, Sleep, Memory (I always forget this one
), and Protection. Rest, Eat, Sleep, Forget, Protect3) synthetic cannabinoids: some developed before we knew about receptors, some after
- In the brain endogenous cannabinoids act in a retrograde fashion, downregulating the neurotransmitters, originating in the post-synaptic neuron and traveling upstream to attach to CB1 receptors on the other side of the gap. The primary reason for their attachment is to reduce the release of neurotransmitters.
- They're damping down whatever particular function and response that neuron is set for.
- Found throughout the animal kingdom in cordates, animals with a spinal cord
The ECS has three components
1. endocannabinoids
2. cannabinoid receptors: CB1, CB2, and ionitropic cannabinoid receptor (TRPV 1)
From Medical Jane (highlights are mine): Specialized receptors are located throughout the human body, including but not limited to, in the hippocampus, (memory and learning), the cerebral cortex ( decision making, emotional behavior), the cerebellum (motor control, coordination), putamen (movement, learning), the hypothalamus (appetite, body temperature), and the amygdala (emotions).
When a specific cannabinoid or a combination of cannabinoids bind to a specialized receptor, an event or a series of events, is triggered in the cell, resulting in a change in
- the cell's activity
- its gene regulation and/or the signals that it sends to neighboring cells through the process we call "signal transduction."
3. enzymes that make cannabinoids and break them down; these can be be manipulated pharmacologically and serve as medicines as well
Entourage Effect
- You have anandamide and 2-AG, but there're also other compounds within the body that, on their own, don't have much power, but working synergistically can deliver a powerful therapeutic punch.
- Soloists and supporting cast.
CB1 receptors in the brain are located heavily in areas that're nociceptive, places having to do with mediating pain
- Additionally found the cerebellum, the limbic system, (emotion), the basal ganglia (movement)
- Receptors are also in reward pathways (addiction and its many effects on the system)
- Receptors aren't found in the areas of the brain having to do with respiration, so cannabinoids can't kill you like all the wonder drugs can. This is how opioids kill.
They depress the respiratory center of the brain and your body forgets to breathe.The cannabinoids also work in the spinal cord, in the periphery, and in the gut.
- CB1 is the most prolific CB G-protein receptor in the brain, where it modulates the release of neurotransmitters.
- Glutamate is typically overactive in neuropathic pain. If cannabinoids damp down glutamate response, that would effect pain over time.
- Modulates pain, memory, movement, whether someone will vomit or not, their seizure threshold.
- Also modulate many other body systems, incl. the gut.
The brain and the gut speak for themselves same language.
- Cannabinoids mo
- propulsion: the speed with which things move through the gut
- secretion: how much liquid or lack of liquid is brought into play during digestion and elimination
- One of the first successful treatments for cholera (major symptom is deadly diarrhea) in the 19th century was cannabis.
If we think of CB1 as the psychoactive receptor we then look at CB2 receptors, found mainly in the periphery, as pain and inflammation.
- Drugs that could effect only CB2 receptors wouldn't have any euphoric effect.
- Such drugs could be promising in treating fibrotic diseases like scarring in the liver or other organs.
Both kinds of receptors are found in the skin.
- Exciting therapeutically due to accessibility (don't need to go through a lot of layers to be active)
- Currently an area of intense research.
CBD, which doesn't attach to either receptor with any real affinity seems to be a valuable cannabinoid for the skin.
- A full-spectrum cannabis extract with CBD would show antibacterial effects (as in acne).
- CBD works on TRPV-4 receptors, which reduces the release of fat (sebum), which contribute to acne.
se·bum
ˈsēbəm/
noun
an oily secretion of the sebaceous glands.
Sebum Definition - Verywell
Apr 15, 2017 - Sebum is a light yellow, oily substance that is secreted by the sebaceous glands that help keep the skin and hair moisturized. Sebum is made up of triglycerides, free fatty acids, wax esters, squalene, cholesterol esters, and cholesterol. ... It also includes lipids from skin cells, sweat, and environmental matter
CBD was recently shown to stimulate bone fracture healing.
- Right now cannabinoids are banned from professional and amateur sports. It might be time to rethink that. Cannabidiol will speed the healing, without side effects.
Cannabis will accelerate the heart rate.
- Interestingly, at a higher dose it will slow the heart rate down, far enough to make it difficult to regulate blood pressure.
- You can pass out from orthostatic hypertension.
Concerns:
- There was a rise in concern that cannabis might contribute to heart attack, but the thinking is the signalling isn't strong enough to make this drastic an effect. It may be a concern for individual patients, but not as a population concern.
- For a time there was concern that there might be an arthritic response to cannabis. Upon closer inspection it was discovered that the patients were all tobacco smokers, and tobacco is known to constrict blood vessels in the hands (Berger's Disease).
The most common use of cannabis is for the treatment of chronic pain conditions. Cannabis offers relief through various pathways
- Through neurotransmitters
- through interaction with opioids, whether by pill form or the endogenous opioid system
- direct effects in the brain
- other components in cannabis beyond the major cannabinoids, CBD and THC
The brain has a base-line level of cannabinoid function (the endocannabinoid tone)
- Under certain conditions activity can be either depressed or enhanced.
- the periaqueductal gray is a mind brain generator (???)
The periaqueductal gray, or PAG, is an area of gray matter found in the midbrain. The PAG surrounds the cerebral aqueduct (hence the name periaqueductal) and occupies a column of brainstem that stretches about 14 mm long. There are no obvious visible anatomical divisions within the PAG, but researchers have divided the PAG into four columns based on differences in connectivity and function: the dorsomedial, dorsolateral, lateral, and ventrolateral columns.
What is the periaqueductal gray and what does it do?
Although the functions of the PAG are complex and not fully understood, since the 1970s it has best been known for its role in the inhibition of pain. Indeed, some have argued that its identification as an "analgesia center" has hindered a more complete understanding of the functions of the PAG. An increasingly intricate appreciation of PAG function, however, has been emerging over the past few decades
When the PAG was first found to have an association with pain, it was observed as playing a role in pain transmission---or the sending of pain signals to the cortex---and not the mitigation of those signals. Eventually, the PAG would come to be much better recognized as an area important to pain inhibition. In the late 1960s, the first indication of the role of the PAG in pain suppression emerged from a study that found that stimulation of the PAG in rats allowed researchers to perform surgery on the rats without the use of anesthetics (and without the animals exhibiting signs of severe pain). Further studies found that PAG activation was associated with the inhibition of spinal cord neurons involved in pain signaling. By the mid-1970s, stimulation of the PAG was already being used as an experimental approach to treating chronic pain in human patients. The fact that some of these experiments reported success in the treatment of chronic pain supported the role of the PAG in analgesia. The patients involved in these experiments also often complained of a wide range of side effects linked to PAG stimulation, however, suggesting that many more functions than analgesia were connected to the PAG.
- Cannabinoids also active in the thalamus (ventral postural lateral nucleus). Tested in this area cannabinoids are 10 times more powerful than morphine. It becomes obvious that using the two drugs together would be a beneficial approach for pain management.
- There are additional functions in the spinal cord by which cannabinoids effect pain levels and perception.
Cannabinoids can be effective against contact dermatitis (poison ivy or plain old itching)
There are numerous randomized trials on cannabis and pain. The problem is that the company that holds the rights to market isn't choosing to do so in many markets. Just exactly what we anticipated. Give Big Pharma control and they won't market something they can't make the big money on. Keep this plant out of their hands and in the control of the people.
An interesting thing occurred when they tested cannabis with cancer pain in hospice settings. The patients got relief and the tolerance levels didn't rise in the same way they see with opioids. There wasn't the standard increase in pain levels with cannabis or Sativex.
- The gold standard in pain is the group that has a 30% reduction in pain over time.
- In the study 43% of patients using Sativex got relief, as opposed to 21% with the placebo.
- The study contrasted placebo, Sativex and a full THC isolate extraction. The isolate didn't work any better than the placebo. The Sativex, with its inclusion of CBD, did work, and in dramatic fashion.
- This was the first concrete evidence of th entourage effect in pain control.
Placebos work Faith is a powerful tool, and I'm convinced the ECS can heal a disease-wracked body instantaneously, so the placebo effect doesn't surprise me in the slightest.
- Have a placebo that works so well and you'll end up with your effective drug looking ineffective next to the placebo, making your drug look statistically insignificant.
In a randomized withdrawal study of Nabixinol,Sativex, and MS patients were unknowingly started on Sativex at either a level to control spacisity or to keep them from having too many side effects.
- The 20% who improved were brought back and then randomly half were refilled with placebos.
- All patients who stayed on Sativex improved spacisity, and all patients on the placebo went into decline.
- These results were the impetus for gaining approval for Sativex administration in 27 countries. Are we one of those lucky countries?
- They had patients with twisted limbs that had the muscles relax after administration of Sativex I believe Sayivex is a balanced ratio medication.
Clinical Endocannabinoid Deficiency
- Your endocannabinoid tone is an indicator of the number of cannabinoids available, how their produced and degraded, and how many receptors you have available.
- A change to any of those areas can effect the endocannabinoid tone, resulting in pain, stiffness in the muscles, the seizure threshold, etc.
- The theory was that in certain conditions if the tone is depressed too low it'll produce disease and symptoms in the system.
- In original 2004 paper he focused on migraine, fibromyalgia and IBS. All three are hyper analgesic responses, where the system has a heightened pain response.
- All three are difficult, if not impossible to track or determine by lab testing, so they're diagnosed based on clinical determination of the patient's described patterns.
- They're all also comorbid, meaning if you have one, you likely have the other two. Primary headache turned up in 97% of the cases with fibromyalgia. 33% of patients with chronic daily headaches (a type of migraine) also had fibromyalgia. 32% of patients with IBS had fibromyalgia and 32% of fibromyalgia patients also had IBS.
Unfortunately, these conditions show up in large numbers of women who get misdiagnosed as being psychosomatic by their male doctors.
- Russo maintains that this is a biochemical disorder, possibly due to a drop in endocannabinoid expression, and there's no mind game these women are playing with themselves.
IBS: Sometimes thought of as a life-long condition, but people clearly acquire this at some point.
- It's the most frequent diagnosis among gastroenterologist in the states.
- There are no particular regular signs, but there is a pattern of irregular bowel movements, often diarrhea, although this could be constipation. They can alternate too.
- It's being described as a disorder of unknown origin and treated by agents of an unknown mechanism of action.
- There are many ineffective drugs. The target should be the ECS instead.
- IBS brings the joy of visceral hypersensitivity. Things hurt, and hurt bad. Again, an over abundance of pain.
- It's known that anandamide works with colonergic neurons, the primary movers of the gut. It performs a modulatory role on the speed of digestion and elimination.
- The ECS appears to be unregulated in diseases of the gut with inflammation. This would be true in the case of IBS as well.
The Mayo clinic, looking at genetic markers of IBS, found CNRI (has to do with cannabinoid function)
- Patients with IBS responded positively to THC.
- CB1 receptors seem to modify the speed through the gut.
Relationships to diet
- If you eat the right things you might not have to use cannabis so much.
- Replenishing the gut flora with probiotics enhanced pain management. They positively effect the RNA expression of the gene associated with CB receptors when taken as a supplement.
- This enhanced the pain control function of morphine.
- It was proposed that taking a CB2 antagonist would enhance that function.
- 32 out of 45 studies on the addition of probiotics showed an improvement in gut performance and health for patients with IBS, incl. less pain, less bloating, etc...
- 5-6 months of continuious supplementation created a stable environment in the gut.
A recent study found that THC alters the bacterial presence in the gut.
- In these mice that had a predisposition to being obese, the THC prevented weight gain through the action of changing the balance of the gut bacteria.
Prebiotics, vegetable matter that feed the good gut flora. (FOS) They don't get broken down in the stomach and they're fermented by the gut flora.
- There are over a thousand different species of bacteria being brewed.
- Prebiotocs help the healthy, beneficial gut flora grow and prosper.
- It's estimated that ancient man ate a lot more of these valuable vegetables. Modern humans may only get a few grams a day.
- Best sources acacia fiber, gum arabic, chicory, burdock, sunchokes (Jerusalem artichoke), onions, leek, garlic, dandelion greens,
- They reduce infectious diarrhea, alleviate inflammatory bowel diseases, reduce cancer risk in the gut, increase mineral absorbtion, lower cardiac risk, and decrease obesity.
- 10 grams a day - a heaping tablespoon of acacia fiber that could be added to any number of foods, increased lactobacillus sixfold and increased balance of the gut flora. It also appears to decrease the bug that causes c-diff.
Begin at 36:50
- Thread starter
- #52
The new study presents evidence that chemotherapy can switch on a repair mechanism in the body which ultimately allows tumours to grow back stronger. It also increases the number of ‘doorways’ on blood vessels which allow cancer to spread throughout the body
Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism
Closing the door to cancer cells
Breast cancer is one of the most common tumor types, and metastasis greatly increases the risk of death from this disease. By studying the process of intravasation or entry of cells into the vasculature, Karagiannis et al. discovered that, in addition to killing tumor cells, chemotherapy treatment can also increase intravasation. Groups of cells collectively known as tumor microenvironment of metastasis (TMEM) can serve as gateways for tumor cells entering the vasculature, and the authors discovered that several types of chemotherapy can increase the amounts of TMEM complexes and circulating tumor cells in the bloodstream. The researchers also determined that a drug called rebastinib can interfere with TMEM activity and help overcome the increased risk of cancer cell dissemination.
Abstract
Breast cancer cells disseminate through TIE2/MENACalc/MENAINV-dependent cancer cell intravasation sites, called tumor microenvironment of metastasis (TMEM), which are clinically validated as prognostic markers of metastasis in breast cancer patients. Using fixed tissue and intravital imaging of a PyMT murine model and patient-derived xenografts, we show that chemotherapy increases the density and activity of TMEM sites and Mena expression and promotes distant metastasis. Moreover, in the residual breast cancers of patients treated with neoadjuvant paclitaxel after doxorubicin plus cyclophosphamide, TMEM score and its mechanistically connected MENAINV isoform expression pattern were both increased, suggesting that chemotherapy, despite decreasing tumor size, increases the risk of metastatic dissemination. Chemotherapy-induced TMEM activity and cancer cell dissemination were reversed by either administration of the TIE2 inhibitor rebastinib or knockdown of the MENA gene. Our results indicate that TMEM score increases and MENA isoform expression pattern changes with chemotherapy and can be used in predicting prometastatic changes in response to chemotherapy. Furthermore, inhibitors of TMEM function may improve clinical benefits of chemotherapy in the neoadjuvant setting or in metastatic disease.
Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism
Closing the door to cancer cells
Breast cancer is one of the most common tumor types, and metastasis greatly increases the risk of death from this disease. By studying the process of intravasation or entry of cells into the vasculature, Karagiannis et al. discovered that, in addition to killing tumor cells, chemotherapy treatment can also increase intravasation. Groups of cells collectively known as tumor microenvironment of metastasis (TMEM) can serve as gateways for tumor cells entering the vasculature, and the authors discovered that several types of chemotherapy can increase the amounts of TMEM complexes and circulating tumor cells in the bloodstream. The researchers also determined that a drug called rebastinib can interfere with TMEM activity and help overcome the increased risk of cancer cell dissemination.
Abstract
Breast cancer cells disseminate through TIE2/MENACalc/MENAINV-dependent cancer cell intravasation sites, called tumor microenvironment of metastasis (TMEM), which are clinically validated as prognostic markers of metastasis in breast cancer patients. Using fixed tissue and intravital imaging of a PyMT murine model and patient-derived xenografts, we show that chemotherapy increases the density and activity of TMEM sites and Mena expression and promotes distant metastasis. Moreover, in the residual breast cancers of patients treated with neoadjuvant paclitaxel after doxorubicin plus cyclophosphamide, TMEM score and its mechanistically connected MENAINV isoform expression pattern were both increased, suggesting that chemotherapy, despite decreasing tumor size, increases the risk of metastatic dissemination. Chemotherapy-induced TMEM activity and cancer cell dissemination were reversed by either administration of the TIE2 inhibitor rebastinib or knockdown of the MENA gene. Our results indicate that TMEM score increases and MENA isoform expression pattern changes with chemotherapy and can be used in predicting prometastatic changes in response to chemotherapy. Furthermore, inhibitors of TMEM function may improve clinical benefits of chemotherapy in the neoadjuvant setting or in metastatic disease.
- Thread starter
- #53
Finished notes
Ethan Russo MD - The Endocannabinoid System in Health and Disease
speaking in Sydney, Australia on June 8, 2016 * United in Compassion Medicinal Cannabis Symposium (United in Compassion)
ethanrusso@comcast.net
Basics:
- Cannabis sativa makes trichomes, which are filled with the essential oil of the plant. This oil includes cannabinoids and terpenoids.
- Cannabinoids bind to the CB receptors found in the body. Most are CB1, and are found in the brain.
- The receptors are like the locks, and cannabinoids are the keys that unlock the receptors.
- Endogenous cannabinoids (anandamide and 2-AG, surely among others, yet to be identified) are those produced by your own body.
- They're created on site and on demand, and bind to the CB1 receptor.
- There are 3 kinds of cannabinoids,
1) phytocannabinoids: basically, 21-carbon items from cannabis, with exception of plants that have Beta-Caryophyllene, which activates the CB2 receptors
2) endocannabinoids: produced by the body
- The ECS has been described as having functions regulating Relaxation Appetite, Sleep, Memory (I always forget this one), and Protection. Rest, Eat, Sleep, Forget, Protect
3) synthetic cannabinoids: some developed before we knew about receptors, some after
- In the brain endogenous cannabinoids act in a retrograde fashion, downregulating the neurotransmitters, originating in the post-synaptic neuron and traveling upstream to attach to CB1 receptors on the other side of the gap. The primary reason for their attachment is to reduce the release of neurotransmitters.
- They're damping down whatever particular function and response that neuron is set for.
- Found throughout the animal kingdom in cordates, animals with a spinal cord
The ECS has three components
1. endocannabinoids
2. cannabinoid receptors: CB1, CB2, and ionitropic cannabinoid receptor (TRPV 1)
From Medical Jane (highlights are mine): Specialized receptors are located throughout the human body, including but not limited to, in the hippocampus, (memory and learning), the cerebral cortex ( decision making, emotional behavior), the cerebellum (motor control, coordination), putamen (movement, learning), the hypothalamus (appetite, body temperature), and the amygdala (emotions).
When a specific cannabinoid or a combination of cannabinoids bind to a specialized receptor, an event or a series of events, is triggered in the cell, resulting in a change in
- the cell's activity
- its gene regulation and/or the signals that it sends to neighboring cells through the process we call "signal transduction."
3. enzymes that make cannabinoids and break them down; these can be be manipulated pharmacologically and serve as medicines as well
Entourage Effect
- You have anandamide and 2-AG, but there're also other compounds within the body that, on their own, don't have much power, but working synergistically can deliver a powerful therapeutic punch.
- Soloists and supporting cast.
CB1 receptors in the brain are located heavily in areas that're nociceptive, places having to do with mediating pain
- Additionally found the cerebellum, the limbic system, (emotion), the basal ganglia (movement)
- Receptors are also in reward pathways (addiction and its many effects on the system)
- Receptors aren't found in the areas of the brain having to do with respiration, so cannabinoids can't kill you like all the wonder drugs can. This is how opioids kill. They depress the respiratory center of the brain and your body forgets to breathe.
The cannabinoids also work in the spinal cord, in the periphery, and in the gut.
- CB1 is the most prolific CB G-protein receptor in the brain, where it modulates the release of neurotransmitters.
- Glutamate is typically overactive in neuropathic pain. If cannabinoids damp down glutamate response, that would effect pain over time.
- Modulates pain, memory, movement, whether someone will vomit or not, their seizure threshold.
- Also modulate many other body systems, incl. the gut.
The brain and the gut speak for themselves same language.
- Cannabinoids mo
- propulsion: the speed with which things move through the gut
- secretion: how much liquid or lack of liquid is brought into play during digestion and elimination
- One of the first successful treatments for cholera (major symptom is deadly diarrhea) in the 19th century was cannabis.
If we think of CB1 as the psychoactive receptor we then look at CB2 receptors, found mainly in the periphery, as pain and inflammation.
- Drugs that could effect only CB2 receptors wouldn't have any euphoric effect.
- Such drugs could be promising in treating fibrotic diseases like scarring in the liver or other organs.
Both kinds of receptors are found in the skin.
- Exciting therapeutically due to accessibility (don't need to go through a lot of layers to be active)
- Currently an area of intense research.
CBD, which doesn't attach to either receptor with any real affinity seems to be a valuable cannabinoid for the skin.
- A full-spectrum cannabis extract with CBD would show antibacterial effects (as in acne).
- CBD works on TRPV-4 receptors, which reduces the release of fat (sebum), which contribute to acne.
se·bum
ˈsēbəm/
noun
an oily secretion of the sebaceous glands.
Sebum Definition - Verywell
Apr 15, 2017 - Sebum is a light yellow, oily substance that is secreted by the sebaceous glands that help keep the skin and hair moisturized. Sebum is made up of triglycerides, free fatty acids, wax esters, squalene, cholesterol esters, and cholesterol. ... It also includes lipids from skin cells, sweat, and environmental matter
CBD was recently shown to stimulate bone fracture healing.
- Right now cannabinoids are banned from professional and amateur sports. It might be time to rethink that. Cannabidiol will speed the healing, without side effects.
Cannabis will accelerate the heart rate.
- Interestingly, at a higher dose it will slow the heart rate down, far enough to make it difficult to regulate blood pressure.
- You can pass out from orthostatic hypertension.
Concerns:
- There was a rise in concern that cannabis might contribute to heart attack, but the thinking is the signalling isn't strong enough to make this drastic an effect. It may be a concern for individual patients, but not as a population concern.
- For a time there was concern that there might be an arthritic response to cannabis. Upon closer inspection it was discovered that the patients were all tobacco smokers, and tobacco is known to constrict blood vessels in the hands (Berger's Disease).
The most common use of cannabis is for the treatment of chronic pain conditions. Cannabis offers relief through various pathways
- Through neurotransmitters
- through interaction with opioids, whether by pill form or the endogenous opioid system
- direct effects in the brain
- other components in cannabis beyond the major cannabinoids, CBD and THC
The brain has a base-line level of cannabinoid function (the endocannabinoid tone)
- Under certain conditions activity can be either depressed or enhanced.
- the periaqueductal gray is a mind brain generator (???)
The periaqueductal gray, or PAG, is an area of gray matter found in the midbrain. The PAG surrounds the cerebral aqueduct (hence the name periaqueductal) and occupies a column of brainstem that stretches about 14 mm long. There are no obvious visible anatomical divisions within the PAG, but researchers have divided the PAG into four columns based on differences in connectivity and function: the dorsomedial, dorsolateral, lateral, and ventrolateral columns.
What is the periaqueductal gray and what does it do?
Although the functions of the PAG are complex and not fully understood, since the 1970s it has best been known for its role in the inhibition of pain. Indeed, some have argued that its identification as an "analgesia center" has hindered a more complete understanding of the functions of the PAG. An increasingly intricate appreciation of PAG function, however, has been emerging over the past few decades
When the PAG was first found to have an association with pain, it was observed as playing a role in pain transmission---or the sending of pain signals to the cortex---and not the mitigation of those signals. Eventually, the PAG would come to be much better recognized as an area important to pain inhibition. In the late 1960s, the first indication of the role of the PAG in pain suppression emerged from a study that found that stimulation of the PAG in rats allowed researchers to perform surgery on the rats without the use of anesthetics (and without the animals exhibiting signs of severe pain). Further studies found that PAG activation was associated with the inhibition of spinal cord neurons involved in pain signaling. By the mid-1970s, stimulation of the PAG was already being used as an experimental approach to treating chronic pain in human patients. The fact that some of these experiments reported success in the treatment of chronic pain supported the role of the PAG in analgesia. The patients involved in these experiments also often complained of a wide range of side effects linked to PAG stimulation, however, suggesting that many more functions than analgesia were connected to the PAG.
- Cannabinoids also active in the thalamus (ventral postural lateral nucleus). Tested in this area cannabinoids are 10 times more powerful than morphine. It becomes obvious that using the two drugs together would be a beneficial approach for pain management.
- There are additional functions in the spinal cord by which cannabinoids effect pain levels and perception.
Cannabinoids can be effective against contact dermatitis (poison ivy or plain old itching)
There are numerous randomized trials on cannabis and pain. The problem is that the company that holds the rights to market isn't choosing to do so in many markets. Just exactly what we anticipated. Give Big Pharma control and they won't market something they can't make the big money on. Keep this plant out of their hands and in the control of the people.
An interesting thing occurred when they tested cannabis with cancer pain in hospice settings. The patients got relief and the tolerance levels didn't rise in the same way they see with opioids. There wasn't the standard increase in pain levels with cannabis or Sativex.
- The gold standard in pain is the group that has a 30% reduction in pain over time.
- In the study 43% of patients using Sativex got relief, as opposed to 21% with the placebo.
- The study contrasted placebo, Sativex and a full THC isolate extraction. The isolate didn't work any better than the placebo. The Sativex, with its inclusion of CBD, did work, and in dramatic fashion.
- This was the first concrete evidence of th entourage effect in pain control.
Placebos work Faith is a powerful tool, and I'm convinced the ECS can heal a disease-wracked body instantaneously, so the placebo effect doesn't surprise me in the slightest.
- Have a placebo that works so well and you'll end up with your effective drug looking ineffective next to the placebo, making your drug look statistically insignificant.
In a randomized withdrawal study of Nabixinol,Sativex, and MS patients were unknowingly started on Sativex at either a level to control spacisity or to keep them from having too many side effects.
- The 20% who improved were brought back and then randomly half were refilled with placebos.
- All patients who stayed on Sativex improved spacisity, and all patients on the placebo went into decline.
- These results were the impetus for gaining approval for Sativex administration in 27 countries. Are we one of those lucky countries?
- They had patients with twisted limbs that had the muscles relax after administration of Sativex I believe Sayivex is a balanced ratio medication.
Clinical Endocannabinoid Deficiency
- Your endocannabinoid tone is an indicator of the number of cannabinoids available, how their produced and degraded, and how many receptors you have available.
- A change to any of those areas can effect the endocannabinoid tone, resulting in pain, stiffness in the muscles, the seizure threshold, etc.
- The theory was that in certain conditions if the tone is depressed too low it'll produce disease and symptoms in the system.
- In original 2004 paper he focused on migraine, fibromyalgia and IBS. All three are hyper analgesic responses, where the system has a heightened pain response.
- All three are difficult, if not impossible to track or determine by lab testing, so they're diagnosed based on clinical determination of the patient's described patterns.
- They're all also comorbid, meaning if you have one, you likely have the other two. Primary headache turned up in 97% of the cases with fibromyalgia. 33% of patients with chronic daily headaches (a type of migraine) also had fibromyalgia. 32% of patients with IBS had fibromyalgia and 32% of fibromyalgia patients also had IBS.
Unfortunately, these conditions show up in large numbers of women who get misdiagnosed as being psychosomatic by their male doctors.
- Russo maintains that this is a biochemical disorder, possibly due to a drop in endocannabinoid expression, and there's no mind game these women are playing with themselves.
IBS: Sometimes thought of as a life-long condition, but people clearly acquire this at some point.
- It's the most frequent diagnosis among gastroenterologist in the states.
- There are no particular regular signs, but there is a pattern of irregular bowel movements, often diarrhea, although this could be constipation. They can alternate too.
- It's being described as a disorder of unknown origin and treated by agents of an unknown mechanism of action.
- There are many ineffective drugs. The target should be the ECS instead.
- IBS brings the joy of visceral hypersensitivity. Things hurt, and hurt bad. Again, an over abundance of pain.
- It's known that anandamide works with colonergic neurons, the primary movers of the gut. It performs a modulatory role on the speed of digestion and elimination.
- The ECS appears to be unregulated in diseases of the gut with inflammation. This would be true in the case of IBS as well.
The Mayo clinic, looking at genetic markers of IBS, found CNRI (has to do with cannabinoid function)
- Patients with IBS responded positively to THC.
- CB1 receptors seem to modify the speed through the gut.
Relationships to diet
- If you eat the right things you might not have to use cannabis so much.
- Replenishing the gut flora with probiotics enhanced pain management. They positively effect the RNA expression of the gene associated with CB receptors when taken as a supplement.
- This enhanced the pain control function of morphine.
- It was proposed that taking a CB2 antagonist would enhance that function.
- 32 out of 45 studies on the addition of probiotics showed an improvement in gut performance and health for patients with IBS, incl. less pain, less bloating, etc...
- 5-6 months of continuious supplementation created a stable environment in the gut.
A recent study found that THC alters the bacterial presence in the gut.
- In these mice that had a predisposition to being obese, the THC prevented weight gain through the action of changing the balance of the gut bacteria.
Prebiotics, vegetable matter that feed the good gut flora. (FOS) They don't get broken down in the stomach and they're fermented by the gut flora.
- There are over a thousand different species of bacteria being brewed.
- Prebiotocs help the healthy, beneficial gut flora grow and prosper.
- It's estimated that ancient man ate a lot more of these valuable vegetables. Modern humans may only get a few grams a day.
- Best sources acacia fiber, gum arabic, chicory, burdock, sunchokes (Jerusalem artichoke), onions, leek, garlic, dandelion greens,
- They reduce infectious diarrhea, alleviate inflammatory bowel diseases, reduce cancer risk in the gut, increase mineral absorbtion, lower cardiac risk, and decrease obesity.
- 10 grams a day - a heaping tablespoon of acacia fiber that could be added to any number of foods, increased lactobacillus sixfold and increased balance of the gut flora. It also appears to decrease the bug that causes c-diff.
All of this information on the gut is in a recently published article (published last May or June).
Fibromyalgia
- German study looked at nine patients of fibromyalgia, taking up to 15 mg of THC daily.
- It was a THC isolate, and too strong an experience for 5 of the 9, who dropped out of the study.
- The remaining 4 patients saw relief, a decrease in Allodynia (extremely painful touch), or Hyperalgesia (hyper sensitivity to pain).
- Also saw a sipratistically significant reduction in pain overall. Statistically, this should only happen in 1 out of 100 patients, and yet all four saw this improvement.
Nabilone is a THC semi-synthetic marketed in some countries.
- It's about 10x the potency of THC. Not really therapeutically useful except in the most extreme cases, and even then.....
- Study tracked 40 patients that got one dose a day equivalent to 20 mg of THC, a fairly high dose.
- After four weeks a review of a visual analog scale (where patient judges their pain on a numeric scale), the Fibromyalgia Impact Questionaire, and anxiety levels.
- Improvement was statistically significant across the board.
- Regardless, not a drug that patients can take over the long run with any success.
Mark Ware in Canadian study contrasted Nabilone compared to Amotriptoline (?), a commonly prescribe bed drug for fibromyalgia, looking at sleep.
- 100% of fibromyalgia patients suffer from sleep disturbance. Patients won't improve until sleep is restored.
- In this study sleep was improved, but there was no significant reduction in pain.
A Spanish study of smoked cannabis was only done acutely, looking at pain, stiffness, relaxation, sleepiness, and wellbeing.
- 28 patients with cannabis, 28 controls.
- Within 2 hours, many parameters were statistically improved.
- Mental health component was also higher in the group that recieved cannabis, meaning they had psychoactive side effects.
- It's almost a given that it was a high THC variety used in this study, with no Cannabidiol because that was what was available at the time of the study.
National Pain Report looked at 1300 patients with fibromyalgia and asked for their benefits from taking 3 FDA-approved drugs commonly prescribed for fibromyalgia, contrasted with cannabis.
- The Pharma drugs were basically ineffective.
- Over 60% of cannabis-using patients claimed a really good result and found cannabis effective. Only 5% had no benefit with cannabis.
- Which is the best choice? Hands down cannabis.
Migraine
- For a common affliction migraine is probably the most biochemically complex malady people suffer.
Study of women with migraine looked at the anandamide membrane transporter and the activity of FAAH (enzyme that degrades anandamide).
- Looking at platelets in the blood (brain tissue isn't ethical in living patients).
- Compared patients with chronic headaches vs controls.
- Levels of CB1 receptors were equivalent in the two groups, but women with migraine had an increased degradation rate of anandamide, and decreased platelet levels that could indicate an ECS deficiency that was contributing to the migraine.
Airman et al did a series of studies looking at ECS function in migraine.
- One of the things that migraine does is make blood vessels too big or too small. Not the cause of the disease, just an epiphenomonen, a secondary effect.
- Anandamide reduced blood vessel diameter in the dura ( the protective cover of the brain) by 30%, through a complex biochemical mechanism.
- It was felt that anandamide maintains a base level in the brain (a tonic level of activity).
- Anandamide modifies the trigeminalvascular system, the path of physiological mechanism in migraines.
Another study of the vascular system showed the involvement of TRRP-V1 set of eCB receptors.
- Used a synthetic cannabinoid, looking at synaptic activity.
- Study suggested that CB1 antagonists like THC have therapeutic promise in migraine and cluster headaches.
- Authors were fearful of the psychoactive side effects.
- Overlooks the fact that a very low dose, that isn't psychoactive is sufficient to treat these disorders, or that you can temper the euphoria with the inclusion of Cannabidiol or terpenoids.
Probable the best evidence of clinical eCB deficiency is a study proposed in 2004 but carried out later by the Italians.
- He suggested that looking at cerebral spinal fluid for levels of eCB in patients with migraines.
- It requires a spinal tap, something the ethics committees in the US would be adverse to allow.
- The Italian researchers looked at normal levels (it's unknown how they convinced the patients to do a spinal tap - maybe ethics weren't the big concern in Italy) in control group, contrasted by patients with migraines.
- Only a 1 in 10,000 possibility that the results were by chance.
- Author said "Reduced eCB levels in the cerebral spinal fluid of chronic migraine sufferers support the hypothesis of the failure of the ECS in chronic migraine.
- This proves the existence of clinical eCB deficiency.
In another Italian study, both anandamide and 2-AG markers were dramatically reduced in the platelets of chronic migraine patients as compared to controls.
- Very highly statistically significant.
In another Italian study an animal model of migraine is explored.
-Migraine creates some bizarre symptoms, like the loss of vision on one side with bursts of light (sparkles), caused by a depression on the surface of the brain.
- The study showed the involvement of the ECS. Theoretically, THC could prevent or stop the progression of this effect.
- Many patients report that cannabis is used at the onset of the array it will prevent the symptom from becoming full-blown.
There's a genetic predisposition to migraine.
- It's been mapped to CNR1, an eCB gene, on chromosome 6.
- Patients with the strongest evidence for this gene also had the highest likelihood of having symptoms like sensitivity to light, nausea, and significant disability with their headaches.
- Patients with strongest evidence of CNR1 also showed neuroticism, depression, and a tendency towards drug dependence. (Someone with mirgraines will obviously be trying to treat it with one substance or another.)
Study out of Colorado in mid 2016 looked at 120 patients with migraine using cannabis to prevent or control migraine.
- Patients were treated prophylactically to prevent migraine.
- 60% of patients had used cannabis previously.
- Of those who went on to use cannabis regularly dropped the occurance rate from 10.4 a month to 4.6 a month, very statistically significant.
- Also reduced headache frequency and were able to abort, or stop their headaches when cannabis was used acutely.
- It's a selective population. The same thing needs to be done in randomized, controlled trials. Russo has been unsuccessfully trying to get those trials to happen for over 20 years.
John McPartland wrote "The Care and Feeding of the ECS."
Care and Feeding of the Endocannabinoid System: A Systematic Review of Potential Clinical Interventions that Upregulate the Endocannabinoid System
- Looked at issue of the eCB deficiency
Where do we go from here?
- We need better studies of IBS, Fibromyalgia, and migraine, looking for levels in the blood, levels in the cerebral spinal fluid.
- It'd be better to do this with scans of the brain, but for right now we don't have great tools this way.
- There's active research, but it'd be nice to be able to assess the eCB function or eCB density in the brain without having a needle stuck into your back.
- We need better work genetically. There are companies looking for markers of these diseases and trying to coordinate them with eCB function.
- Controlled clinical trials of cannabis-based medicines in these clinical conditions are what will convince physicians and politicians.
"Only time and the scientific method will ascertain whether a new paradigm is applicable to human physiology and the treatment of its derangements. Our insight into these possibilities is dependent on the contribution of one unique healing plant. For clinical cannabis has become a therapeutic compass to what modern medicine fails to cure."
Cannabis modulates the ECS, which is, in itself, an innate homeostatic regulator of human physiology. If there's too much of something, it brings it back down into balance. It there's too little of something, it brings it up into balance.
- Cannabidiol is a particularly interesting cannabinoid system modulator.
- In future we may see more CBD with only a little THC.
- The ECS is influenced by lifestyle and dietary factors.
- Primary beneficial approaches would be low-impact exercises, an antioxidant, anti-inflammatory diet, probiotics and probiotics. Of of these will improve the conditions discussed.
Ethan Russo MD - The Endocannabinoid System in Health and Disease
speaking in Sydney, Australia on June 8, 2016 * United in Compassion Medicinal Cannabis Symposium (United in Compassion)
ethanrusso@comcast.net
Basics:
- Cannabis sativa makes trichomes, which are filled with the essential oil of the plant. This oil includes cannabinoids and terpenoids.
- Cannabinoids bind to the CB receptors found in the body. Most are CB1, and are found in the brain.
- The receptors are like the locks, and cannabinoids are the keys that unlock the receptors.
- Endogenous cannabinoids (anandamide and 2-AG, surely among others, yet to be identified) are those produced by your own body.
- They're created on site and on demand, and bind to the CB1 receptor.
- There are 3 kinds of cannabinoids,
1) phytocannabinoids: basically, 21-carbon items from cannabis, with exception of plants that have Beta-Caryophyllene, which activates the CB2 receptors
2) endocannabinoids: produced by the body
- The ECS has been described as having functions regulating Relaxation Appetite, Sleep, Memory (I always forget this one
), and Protection. Rest, Eat, Sleep, Forget, Protect3) synthetic cannabinoids: some developed before we knew about receptors, some after
- In the brain endogenous cannabinoids act in a retrograde fashion, downregulating the neurotransmitters, originating in the post-synaptic neuron and traveling upstream to attach to CB1 receptors on the other side of the gap. The primary reason for their attachment is to reduce the release of neurotransmitters.
- They're damping down whatever particular function and response that neuron is set for.
- Found throughout the animal kingdom in cordates, animals with a spinal cord
The ECS has three components
1. endocannabinoids
2. cannabinoid receptors: CB1, CB2, and ionitropic cannabinoid receptor (TRPV 1)
From Medical Jane (highlights are mine): Specialized receptors are located throughout the human body, including but not limited to, in the hippocampus, (memory and learning), the cerebral cortex ( decision making, emotional behavior), the cerebellum (motor control, coordination), putamen (movement, learning), the hypothalamus (appetite, body temperature), and the amygdala (emotions).
When a specific cannabinoid or a combination of cannabinoids bind to a specialized receptor, an event or a series of events, is triggered in the cell, resulting in a change in
- the cell's activity
- its gene regulation and/or the signals that it sends to neighboring cells through the process we call "signal transduction."
3. enzymes that make cannabinoids and break them down; these can be be manipulated pharmacologically and serve as medicines as well
Entourage Effect
- You have anandamide and 2-AG, but there're also other compounds within the body that, on their own, don't have much power, but working synergistically can deliver a powerful therapeutic punch.
- Soloists and supporting cast.
CB1 receptors in the brain are located heavily in areas that're nociceptive, places having to do with mediating pain
- Additionally found the cerebellum, the limbic system, (emotion), the basal ganglia (movement)
- Receptors are also in reward pathways (addiction and its many effects on the system)
- Receptors aren't found in the areas of the brain having to do with respiration, so cannabinoids can't kill you like all the wonder drugs can. This is how opioids kill.
They depress the respiratory center of the brain and your body forgets to breathe.The cannabinoids also work in the spinal cord, in the periphery, and in the gut.
- CB1 is the most prolific CB G-protein receptor in the brain, where it modulates the release of neurotransmitters.
- Glutamate is typically overactive in neuropathic pain. If cannabinoids damp down glutamate response, that would effect pain over time.
- Modulates pain, memory, movement, whether someone will vomit or not, their seizure threshold.
- Also modulate many other body systems, incl. the gut.
The brain and the gut speak for themselves same language.
- Cannabinoids mo
- propulsion: the speed with which things move through the gut
- secretion: how much liquid or lack of liquid is brought into play during digestion and elimination
- One of the first successful treatments for cholera (major symptom is deadly diarrhea) in the 19th century was cannabis.
If we think of CB1 as the psychoactive receptor we then look at CB2 receptors, found mainly in the periphery, as pain and inflammation.
- Drugs that could effect only CB2 receptors wouldn't have any euphoric effect.
- Such drugs could be promising in treating fibrotic diseases like scarring in the liver or other organs.
Both kinds of receptors are found in the skin.
- Exciting therapeutically due to accessibility (don't need to go through a lot of layers to be active)
- Currently an area of intense research.
CBD, which doesn't attach to either receptor with any real affinity seems to be a valuable cannabinoid for the skin.
- A full-spectrum cannabis extract with CBD would show antibacterial effects (as in acne).
- CBD works on TRPV-4 receptors, which reduces the release of fat (sebum), which contribute to acne.
se·bum
ˈsēbəm/
noun
an oily secretion of the sebaceous glands.
Sebum Definition - Verywell
Apr 15, 2017 - Sebum is a light yellow, oily substance that is secreted by the sebaceous glands that help keep the skin and hair moisturized. Sebum is made up of triglycerides, free fatty acids, wax esters, squalene, cholesterol esters, and cholesterol. ... It also includes lipids from skin cells, sweat, and environmental matter
CBD was recently shown to stimulate bone fracture healing.
- Right now cannabinoids are banned from professional and amateur sports. It might be time to rethink that. Cannabidiol will speed the healing, without side effects.
Cannabis will accelerate the heart rate.
- Interestingly, at a higher dose it will slow the heart rate down, far enough to make it difficult to regulate blood pressure.
- You can pass out from orthostatic hypertension.
Concerns:
- There was a rise in concern that cannabis might contribute to heart attack, but the thinking is the signalling isn't strong enough to make this drastic an effect. It may be a concern for individual patients, but not as a population concern.
- For a time there was concern that there might be an arthritic response to cannabis. Upon closer inspection it was discovered that the patients were all tobacco smokers, and tobacco is known to constrict blood vessels in the hands (Berger's Disease).
The most common use of cannabis is for the treatment of chronic pain conditions. Cannabis offers relief through various pathways
- Through neurotransmitters
- through interaction with opioids, whether by pill form or the endogenous opioid system
- direct effects in the brain
- other components in cannabis beyond the major cannabinoids, CBD and THC
The brain has a base-line level of cannabinoid function (the endocannabinoid tone)
- Under certain conditions activity can be either depressed or enhanced.
- the periaqueductal gray is a mind brain generator (???)
The periaqueductal gray, or PAG, is an area of gray matter found in the midbrain. The PAG surrounds the cerebral aqueduct (hence the name periaqueductal) and occupies a column of brainstem that stretches about 14 mm long. There are no obvious visible anatomical divisions within the PAG, but researchers have divided the PAG into four columns based on differences in connectivity and function: the dorsomedial, dorsolateral, lateral, and ventrolateral columns.
What is the periaqueductal gray and what does it do?
Although the functions of the PAG are complex and not fully understood, since the 1970s it has best been known for its role in the inhibition of pain. Indeed, some have argued that its identification as an "analgesia center" has hindered a more complete understanding of the functions of the PAG. An increasingly intricate appreciation of PAG function, however, has been emerging over the past few decades
When the PAG was first found to have an association with pain, it was observed as playing a role in pain transmission---or the sending of pain signals to the cortex---and not the mitigation of those signals. Eventually, the PAG would come to be much better recognized as an area important to pain inhibition. In the late 1960s, the first indication of the role of the PAG in pain suppression emerged from a study that found that stimulation of the PAG in rats allowed researchers to perform surgery on the rats without the use of anesthetics (and without the animals exhibiting signs of severe pain). Further studies found that PAG activation was associated with the inhibition of spinal cord neurons involved in pain signaling. By the mid-1970s, stimulation of the PAG was already being used as an experimental approach to treating chronic pain in human patients. The fact that some of these experiments reported success in the treatment of chronic pain supported the role of the PAG in analgesia. The patients involved in these experiments also often complained of a wide range of side effects linked to PAG stimulation, however, suggesting that many more functions than analgesia were connected to the PAG.
- Cannabinoids also active in the thalamus (ventral postural lateral nucleus). Tested in this area cannabinoids are 10 times more powerful than morphine. It becomes obvious that using the two drugs together would be a beneficial approach for pain management.
- There are additional functions in the spinal cord by which cannabinoids effect pain levels and perception.
Cannabinoids can be effective against contact dermatitis (poison ivy or plain old itching)
There are numerous randomized trials on cannabis and pain. The problem is that the company that holds the rights to market isn't choosing to do so in many markets. Just exactly what we anticipated. Give Big Pharma control and they won't market something they can't make the big money on. Keep this plant out of their hands and in the control of the people.
An interesting thing occurred when they tested cannabis with cancer pain in hospice settings. The patients got relief and the tolerance levels didn't rise in the same way they see with opioids. There wasn't the standard increase in pain levels with cannabis or Sativex.
- The gold standard in pain is the group that has a 30% reduction in pain over time.
- In the study 43% of patients using Sativex got relief, as opposed to 21% with the placebo.
- The study contrasted placebo, Sativex and a full THC isolate extraction. The isolate didn't work any better than the placebo. The Sativex, with its inclusion of CBD, did work, and in dramatic fashion.
- This was the first concrete evidence of th entourage effect in pain control.
Placebos work Faith is a powerful tool, and I'm convinced the ECS can heal a disease-wracked body instantaneously, so the placebo effect doesn't surprise me in the slightest.
- Have a placebo that works so well and you'll end up with your effective drug looking ineffective next to the placebo, making your drug look statistically insignificant.
In a randomized withdrawal study of Nabixinol,Sativex, and MS patients were unknowingly started on Sativex at either a level to control spacisity or to keep them from having too many side effects.
- The 20% who improved were brought back and then randomly half were refilled with placebos.
- All patients who stayed on Sativex improved spacisity, and all patients on the placebo went into decline.
- These results were the impetus for gaining approval for Sativex administration in 27 countries. Are we one of those lucky countries?
- They had patients with twisted limbs that had the muscles relax after administration of Sativex I believe Sayivex is a balanced ratio medication.
Clinical Endocannabinoid Deficiency
- Your endocannabinoid tone is an indicator of the number of cannabinoids available, how their produced and degraded, and how many receptors you have available.
- A change to any of those areas can effect the endocannabinoid tone, resulting in pain, stiffness in the muscles, the seizure threshold, etc.
- The theory was that in certain conditions if the tone is depressed too low it'll produce disease and symptoms in the system.
- In original 2004 paper he focused on migraine, fibromyalgia and IBS. All three are hyper analgesic responses, where the system has a heightened pain response.
- All three are difficult, if not impossible to track or determine by lab testing, so they're diagnosed based on clinical determination of the patient's described patterns.
- They're all also comorbid, meaning if you have one, you likely have the other two. Primary headache turned up in 97% of the cases with fibromyalgia. 33% of patients with chronic daily headaches (a type of migraine) also had fibromyalgia. 32% of patients with IBS had fibromyalgia and 32% of fibromyalgia patients also had IBS.
Unfortunately, these conditions show up in large numbers of women who get misdiagnosed as being psychosomatic by their male doctors.
- Russo maintains that this is a biochemical disorder, possibly due to a drop in endocannabinoid expression, and there's no mind game these women are playing with themselves.
IBS: Sometimes thought of as a life-long condition, but people clearly acquire this at some point.
- It's the most frequent diagnosis among gastroenterologist in the states.
- There are no particular regular signs, but there is a pattern of irregular bowel movements, often diarrhea, although this could be constipation. They can alternate too.
- It's being described as a disorder of unknown origin and treated by agents of an unknown mechanism of action.
- There are many ineffective drugs. The target should be the ECS instead.
- IBS brings the joy of visceral hypersensitivity. Things hurt, and hurt bad. Again, an over abundance of pain.
- It's known that anandamide works with colonergic neurons, the primary movers of the gut. It performs a modulatory role on the speed of digestion and elimination.
- The ECS appears to be unregulated in diseases of the gut with inflammation. This would be true in the case of IBS as well.
The Mayo clinic, looking at genetic markers of IBS, found CNRI (has to do with cannabinoid function)
- Patients with IBS responded positively to THC.
- CB1 receptors seem to modify the speed through the gut.
Relationships to diet
- If you eat the right things you might not have to use cannabis so much.
- Replenishing the gut flora with probiotics enhanced pain management. They positively effect the RNA expression of the gene associated with CB receptors when taken as a supplement.
- This enhanced the pain control function of morphine.
- It was proposed that taking a CB2 antagonist would enhance that function.
- 32 out of 45 studies on the addition of probiotics showed an improvement in gut performance and health for patients with IBS, incl. less pain, less bloating, etc...
- 5-6 months of continuious supplementation created a stable environment in the gut.
A recent study found that THC alters the bacterial presence in the gut.
- In these mice that had a predisposition to being obese, the THC prevented weight gain through the action of changing the balance of the gut bacteria.
Prebiotics, vegetable matter that feed the good gut flora. (FOS) They don't get broken down in the stomach and they're fermented by the gut flora.
- There are over a thousand different species of bacteria being brewed.
- Prebiotocs help the healthy, beneficial gut flora grow and prosper.
- It's estimated that ancient man ate a lot more of these valuable vegetables. Modern humans may only get a few grams a day.
- Best sources acacia fiber, gum arabic, chicory, burdock, sunchokes (Jerusalem artichoke), onions, leek, garlic, dandelion greens,
- They reduce infectious diarrhea, alleviate inflammatory bowel diseases, reduce cancer risk in the gut, increase mineral absorbtion, lower cardiac risk, and decrease obesity.
- 10 grams a day - a heaping tablespoon of acacia fiber that could be added to any number of foods, increased lactobacillus sixfold and increased balance of the gut flora. It also appears to decrease the bug that causes c-diff.
All of this information on the gut is in a recently published article (published last May or June).
Fibromyalgia
- German study looked at nine patients of fibromyalgia, taking up to 15 mg of THC daily.
- It was a THC isolate, and too strong an experience for 5 of the 9, who dropped out of the study.
- The remaining 4 patients saw relief, a decrease in Allodynia (extremely painful touch), or Hyperalgesia (hyper sensitivity to pain).
- Also saw a sipratistically significant reduction in pain overall. Statistically, this should only happen in 1 out of 100 patients, and yet all four saw this improvement.
Nabilone is a THC semi-synthetic marketed in some countries.
- It's about 10x the potency of THC. Not really therapeutically useful except in the most extreme cases, and even then.....
- Study tracked 40 patients that got one dose a day equivalent to 20 mg of THC, a fairly high dose.
- After four weeks a review of a visual analog scale (where patient judges their pain on a numeric scale), the Fibromyalgia Impact Questionaire, and anxiety levels.
- Improvement was statistically significant across the board.
- Regardless, not a drug that patients can take over the long run with any success.
Mark Ware in Canadian study contrasted Nabilone compared to Amotriptoline (?), a commonly prescribe bed drug for fibromyalgia, looking at sleep.
- 100% of fibromyalgia patients suffer from sleep disturbance. Patients won't improve until sleep is restored.
- In this study sleep was improved, but there was no significant reduction in pain.
A Spanish study of smoked cannabis was only done acutely, looking at pain, stiffness, relaxation, sleepiness, and wellbeing.
- 28 patients with cannabis, 28 controls.
- Within 2 hours, many parameters were statistically improved.
- Mental health component was also higher in the group that recieved cannabis, meaning they had psychoactive side effects.
- It's almost a given that it was a high THC variety used in this study, with no Cannabidiol because that was what was available at the time of the study.
National Pain Report looked at 1300 patients with fibromyalgia and asked for their benefits from taking 3 FDA-approved drugs commonly prescribed for fibromyalgia, contrasted with cannabis.
- The Pharma drugs were basically ineffective.
- Over 60% of cannabis-using patients claimed a really good result and found cannabis effective. Only 5% had no benefit with cannabis.
- Which is the best choice? Hands down cannabis.
Migraine
- For a common affliction migraine is probably the most biochemically complex malady people suffer.
Study of women with migraine looked at the anandamide membrane transporter and the activity of FAAH (enzyme that degrades anandamide).
- Looking at platelets in the blood (brain tissue isn't ethical in living patients
).- Compared patients with chronic headaches vs controls.
- Levels of CB1 receptors were equivalent in the two groups, but women with migraine had an increased degradation rate of anandamide, and decreased platelet levels that could indicate an ECS deficiency that was contributing to the migraine.
Airman et al did a series of studies looking at ECS function in migraine.
- One of the things that migraine does is make blood vessels too big or too small. Not the cause of the disease, just an epiphenomonen, a secondary effect.
- Anandamide reduced blood vessel diameter in the dura ( the protective cover of the brain) by 30%, through a complex biochemical mechanism.
- It was felt that anandamide maintains a base level in the brain (a tonic level of activity).
- Anandamide modifies the trigeminalvascular system, the path of physiological mechanism in migraines.
Another study of the vascular system showed the involvement of TRRP-V1 set of eCB receptors.
- Used a synthetic cannabinoid, looking at synaptic activity.
- Study suggested that CB1 antagonists like THC have therapeutic promise in migraine and cluster headaches.
- Authors were fearful of the psychoactive side effects.
- Overlooks the fact that a very low dose, that isn't psychoactive is sufficient to treat these disorders, or that you can temper the euphoria with the inclusion of Cannabidiol or terpenoids.
Probable the best evidence of clinical eCB deficiency is a study proposed in 2004 but carried out later by the Italians.
- He suggested that looking at cerebral spinal fluid for levels of eCB in patients with migraines.
- It requires a spinal tap, something the ethics committees in the US would be adverse to allow.
- The Italian researchers looked at normal levels (it's unknown how they convinced the patients to do a spinal tap - maybe ethics weren't the big concern in Italy) in control group, contrasted by patients with migraines.
- Only a 1 in 10,000 possibility that the results were by chance.
- Author said "Reduced eCB levels in the cerebral spinal fluid of chronic migraine sufferers support the hypothesis of the failure of the ECS in chronic migraine.
- This proves the existence of clinical eCB deficiency.
In another Italian study, both anandamide and 2-AG markers were dramatically reduced in the platelets of chronic migraine patients as compared to controls.
- Very highly statistically significant.
In another Italian study an animal model of migraine is explored.
-Migraine creates some bizarre symptoms, like the loss of vision on one side with bursts of light (sparkles), caused by a depression on the surface of the brain.
- The study showed the involvement of the ECS. Theoretically, THC could prevent or stop the progression of this effect.
- Many patients report that cannabis is used at the onset of the array it will prevent the symptom from becoming full-blown.
There's a genetic predisposition to migraine.
- It's been mapped to CNR1, an eCB gene, on chromosome 6.
- Patients with the strongest evidence for this gene also had the highest likelihood of having symptoms like sensitivity to light, nausea, and significant disability with their headaches.
- Patients with strongest evidence of CNR1 also showed neuroticism, depression, and a tendency towards drug dependence. (Someone with mirgraines will obviously be trying to treat it with one substance or another.)
Study out of Colorado in mid 2016 looked at 120 patients with migraine using cannabis to prevent or control migraine.
- Patients were treated prophylactically to prevent migraine.
- 60% of patients had used cannabis previously.
- Of those who went on to use cannabis regularly dropped the occurance rate from 10.4 a month to 4.6 a month, very statistically significant.
- Also reduced headache frequency and were able to abort, or stop their headaches when cannabis was used acutely.
- It's a selective population. The same thing needs to be done in randomized, controlled trials. Russo has been unsuccessfully trying to get those trials to happen for over 20 years.
John McPartland wrote "The Care and Feeding of the ECS."
Care and Feeding of the Endocannabinoid System: A Systematic Review of Potential Clinical Interventions that Upregulate the Endocannabinoid System
- Looked at issue of the eCB deficiency
Where do we go from here?
- We need better studies of IBS, Fibromyalgia, and migraine, looking for levels in the blood, levels in the cerebral spinal fluid.
- It'd be better to do this with scans of the brain, but for right now we don't have great tools this way.
- There's active research, but it'd be nice to be able to assess the eCB function or eCB density in the brain without having a needle stuck into your back.
- We need better work genetically. There are companies looking for markers of these diseases and trying to coordinate them with eCB function.
- Controlled clinical trials of cannabis-based medicines in these clinical conditions are what will convince physicians and politicians.
"Only time and the scientific method will ascertain whether a new paradigm is applicable to human physiology and the treatment of its derangements. Our insight into these possibilities is dependent on the contribution of one unique healing plant. For clinical cannabis has become a therapeutic compass to what modern medicine fails to cure."
Cannabis modulates the ECS, which is, in itself, an innate homeostatic regulator of human physiology. If there's too much of something, it brings it back down into balance. It there's too little of something, it brings it up into balance.
- Cannabidiol is a particularly interesting cannabinoid system modulator.
- In future we may see more CBD with only a little THC.
- The ECS is influenced by lifestyle and dietary factors.
- Primary beneficial approaches would be low-impact exercises, an antioxidant, anti-inflammatory diet, probiotics and probiotics. Of of these will improve the conditions discussed.
- Thread starter
- #54
Cannabis Connection
Scientist Reveal What Cannabis Does to Your Bones…
Cannabis Information 2 months ago Cannabis, Diseases
A study was published by The Journal of Bone and Mineral Research, conducted by researchers from Tel Aviv University and Hebrew University. This study showed that a chemical in marijuana, known as cannabinoid cannabidiol (CBD), strengthens bones and accelerates the healing of fractures, without causing any psychotropic effects.
The researcher Yankel Gabet explained: “We found that CBD alone makes bones stronger during healing, enhancing the maturation of the collagenous matrix, which provides the basis for new mineralization of bone tissue. After being treated with CBD, the healed bone will be harder to break in the future.”
The team of experts inflicted mild femoral fractures on rats, and then gave an injection of CBD to some of them, while others received CBD plus tetrahydrocannabinol (THC, the ingredient that causes the marijuana high). They analyzed the healing between them and the rats that had not received any marijuana chemicals. Their conclusion was that rats injected with CBD experienced the same effects, regardless of the addition of THC.
Gabet added: “We found CBD alone to be sufficiently effective in enhancing fracture healing. Other studies have also shown CBD to be a safe agent, which leads us to believe we should continue this line of study in clinical trials to assess its usefulness in improving human fracture healing.”
The same team previously found that the body contains receptors which respond to cannabinoid compounds, and they are not confined to the brain. This study showed that the skeleton has cannabinoid receptors which trigger bone formation and prevent bone loss, and the second study just confirmed this.
Gabet said: “We only respond to cannabis because we are built with intrinsic compounds and receptors that can also be activated by compounds in the cannabis plant.”
This study is just a part of all research dedicated to the medical benefits of marijuana compounds, and new findings might stimulate researchers to analyze the positive effects of marijuana in the treatment of osteoporosis or other bone diseases.
Gabet added: “The clinical potential of cannabinoid-related compounds is simply undeniable at this point. While there is still a lot of work to be done to develop appropriate therapies, it is clear that it is possible to detach a clinical therapy objective from the psychoactivity of cannabis. CBD, the principal agent in our study, is primarily anti-inflammatory and has no psychoactivity.”
The medical properties of marijuana are numerous, and it is primarily used to boost appetite in the case of AIDS, to lower the side-effects of chemotherapy, and to soothe chronic pain. Numerous studies claim that it can regulate blood sugar, decelerate the HIV progression, and treat multiple sclerosis and Parkinson’s disease.
Researchers have shown that CBD suppresses seizures, inhibits the metastasis of many aggressive cancers, and destroys leukemia cells.
The journal Neuropsychopharmacology published a 2013 study which discovered that CBD is as effective as one antipsychotic drug, which is commonly used in the treatment of schizophrenia and paranoia but causes no side-effects. Other studies have also found that CBD can be used as a safe antipsychotic.
Marijuana is still technically illegal under U.S. federal law, but 17 U.S. states allow the use of CBD for research or for limited medical functions. Plus, the laws of 23 other countries permit the medical use of marijuana.
Marijuana is still classified as having “no currently accepted medical use” by the federal government. What might be a change in this approach is the recent decision of the FDA to approve the use of CBD extracts an experimental treatment for the Dravet syndrome, a rare form of childhood epilepsy.
Sources:
Science World Report
India News, Latest News Headlines, BSE live, NSE Live, Stock Markets Live, Financial News, Business News & Market Analysis on Indian Economy - Business Standard News
DNA India | Latest News, Live Breaking News on India, Politics, World, Business, Sports, Bollywood
Canadian News Stories, Breaking News, Opinion
The Times of Israel | News from Israel, the Middle East and the Jewish World
NORML Blog, Marijuana Law Reform | Working to reform marijuana laws
Credit: Natural Health News and Scientific Discoveries - NaturalNews.com
Image: Bernhard Ungerer/Flickr
Scientist Reveal What Cannabis Does to Your Bones…
Cannabis Information 2 months ago Cannabis, Diseases
A study was published by The Journal of Bone and Mineral Research, conducted by researchers from Tel Aviv University and Hebrew University. This study showed that a chemical in marijuana, known as cannabinoid cannabidiol (CBD), strengthens bones and accelerates the healing of fractures, without causing any psychotropic effects.
The researcher Yankel Gabet explained: “We found that CBD alone makes bones stronger during healing, enhancing the maturation of the collagenous matrix, which provides the basis for new mineralization of bone tissue. After being treated with CBD, the healed bone will be harder to break in the future.”
The team of experts inflicted mild femoral fractures on rats, and then gave an injection of CBD to some of them, while others received CBD plus tetrahydrocannabinol (THC, the ingredient that causes the marijuana high). They analyzed the healing between them and the rats that had not received any marijuana chemicals. Their conclusion was that rats injected with CBD experienced the same effects, regardless of the addition of THC.
Gabet added: “We found CBD alone to be sufficiently effective in enhancing fracture healing. Other studies have also shown CBD to be a safe agent, which leads us to believe we should continue this line of study in clinical trials to assess its usefulness in improving human fracture healing.”
The same team previously found that the body contains receptors which respond to cannabinoid compounds, and they are not confined to the brain. This study showed that the skeleton has cannabinoid receptors which trigger bone formation and prevent bone loss, and the second study just confirmed this.
Gabet said: “We only respond to cannabis because we are built with intrinsic compounds and receptors that can also be activated by compounds in the cannabis plant.”
This study is just a part of all research dedicated to the medical benefits of marijuana compounds, and new findings might stimulate researchers to analyze the positive effects of marijuana in the treatment of osteoporosis or other bone diseases.
Gabet added: “The clinical potential of cannabinoid-related compounds is simply undeniable at this point. While there is still a lot of work to be done to develop appropriate therapies, it is clear that it is possible to detach a clinical therapy objective from the psychoactivity of cannabis. CBD, the principal agent in our study, is primarily anti-inflammatory and has no psychoactivity.”
The medical properties of marijuana are numerous, and it is primarily used to boost appetite in the case of AIDS, to lower the side-effects of chemotherapy, and to soothe chronic pain. Numerous studies claim that it can regulate blood sugar, decelerate the HIV progression, and treat multiple sclerosis and Parkinson’s disease.
Researchers have shown that CBD suppresses seizures, inhibits the metastasis of many aggressive cancers, and destroys leukemia cells.
The journal Neuropsychopharmacology published a 2013 study which discovered that CBD is as effective as one antipsychotic drug, which is commonly used in the treatment of schizophrenia and paranoia but causes no side-effects. Other studies have also found that CBD can be used as a safe antipsychotic.
Marijuana is still technically illegal under U.S. federal law, but 17 U.S. states allow the use of CBD for research or for limited medical functions. Plus, the laws of 23 other countries permit the medical use of marijuana.
Marijuana is still classified as having “no currently accepted medical use” by the federal government. What might be a change in this approach is the recent decision of the FDA to approve the use of CBD extracts an experimental treatment for the Dravet syndrome, a rare form of childhood epilepsy.
Sources:
Science World Report
India News, Latest News Headlines, BSE live, NSE Live, Stock Markets Live, Financial News, Business News & Market Analysis on Indian Economy - Business Standard News
DNA India | Latest News, Live Breaking News on India, Politics, World, Business, Sports, Bollywood
Canadian News Stories, Breaking News, Opinion
The Times of Israel | News from Israel, the Middle East and the Jewish World
NORML Blog, Marijuana Law Reform | Working to reform marijuana laws
Credit: Natural Health News and Scientific Discoveries - NaturalNews.com
Image: Bernhard Ungerer/Flickr
- Thread starter
- #55
Using cannabis to treat asthma and COPD
From Medical Marajuana.EU
The New England Journal of Medicne published a study in 1973 that found:
“Marihuana smoke, unlike cigarette smoke, causes broncho-dilation rather than broncho-constriction [narrowing of the air passages] and, unlike opiates, does not cause central respiratory depression.”
A very well conducted study was published in 2006 again by Dr. Tashkin. This landmark study proved that cannabis smoke appears to have little in common with cigarette smoke as far as lung function goes. In fact, to their astonishment low to moderate cannabis smokers actually had better lung function and lung volumes both of which increased with each ‘joint year.
That certainly was an unexpected conclusion, especially since Dr. Tashkin receives his funding from the National Institute for Drug Abuse (NIDA) and related institutions. These governing bodies generally look for harms from illegal drug use, not benefits.
Another interesting finding is that orally ingested THC products produce better degrees of bronchodilation than smoking or aerosolized preparations. Both produce about 2-3 hours of bronchodilation, similar to a conventional inhaler.
Further investigations by the Respiratory Pharmacology Laboratory in Paris have shown that CB1 receptor stimulation (using THC) inhibits cholinergic (parasympathetic) bronchospasm in a concentration-dependent fashion.
What they found was that THC blocks the neurotransmitter acetylcholine at the muscarinic receptors located on smooth muscle lining the bronchioles of asthmatics. This end result is identical to the effects of the prescription drug ipratropium bromide which acts as an anticholinergic drug.
Looking around the best treatment approach appears to be a combination of edibles (think capsules, in particular either FHO or BioBombs) and vaping. Studies found that edibles work as effectively as inhaled and May last longer, which doesn't surprise me. My daughter's been on her capsules of infused oils for over a year now, and hasn't refilled her inhaler but once since she started.
I'd think a balanced ratio with as high a CBD value as possible. Both cannabinoids have shown promise as bronchiodilators. Expectation would be THC would relax muscle constriction while CBD would go to work eliminating inflammation. I'd go with 3-4 doses a day with the highest THC dose being the last one of the day. In this way you'd get more sleep and more benefit from the THC without having to deal with the euphoria.
If it were me, and inn my dauter's case, it is me, I'd go with FHO at either full strength or double strength, possibly 3 capsule doses a day of the full strength and the last capsule of the day being double strength. Then, if it was a serious case, I'd supplement with one inhallation prior to each capsule. Not so critical cases might benefit from just one inhallation a day. That might do it, and it's worth a try to go with micro dosing first.
From Medical Marajuana.EU
The New England Journal of Medicne published a study in 1973 that found:
“Marihuana smoke, unlike cigarette smoke, causes broncho-dilation rather than broncho-constriction [narrowing of the air passages] and, unlike opiates, does not cause central respiratory depression.”
A very well conducted study was published in 2006 again by Dr. Tashkin. This landmark study proved that cannabis smoke appears to have little in common with cigarette smoke as far as lung function goes. In fact, to their astonishment low to moderate cannabis smokers actually had better lung function and lung volumes both of which increased with each ‘joint year.
That certainly was an unexpected conclusion, especially since Dr. Tashkin receives his funding from the National Institute for Drug Abuse (NIDA) and related institutions. These governing bodies generally look for harms from illegal drug use, not benefits.
Another interesting finding is that orally ingested THC products produce better degrees of bronchodilation than smoking or aerosolized preparations. Both produce about 2-3 hours of bronchodilation, similar to a conventional inhaler.
Further investigations by the Respiratory Pharmacology Laboratory in Paris have shown that CB1 receptor stimulation (using THC) inhibits cholinergic (parasympathetic) bronchospasm in a concentration-dependent fashion.
What they found was that THC blocks the neurotransmitter acetylcholine at the muscarinic receptors located on smooth muscle lining the bronchioles of asthmatics. This end result is identical to the effects of the prescription drug ipratropium bromide which acts as an anticholinergic drug.
Looking around the best treatment approach appears to be a combination of edibles (think capsules, in particular either FHO or BioBombs) and vaping. Studies found that edibles work as effectively as inhaled and May last longer, which doesn't surprise me. My daughter's been on her capsules of infused oils for over a year now, and hasn't refilled her inhaler but once since she started.
I'd think a balanced ratio with as high a CBD value as possible. Both cannabinoids have shown promise as bronchiodilators. Expectation would be THC would relax muscle constriction while CBD would go to work eliminating inflammation. I'd go with 3-4 doses a day with the highest THC dose being the last one of the day. In this way you'd get more sleep and more benefit from the THC without having to deal with the euphoria.
If it were me, and inn my dauter's case, it is me, I'd go with FHO at either full strength or double strength, possibly 3 capsule doses a day of the full strength and the last capsule of the day being double strength. Then, if it was a serious case, I'd supplement with one inhallation prior to each capsule. Not so critical cases might benefit from just one inhallation a day. That might do it, and it's worth a try to go with micro dosing first.
- Thread starter
- #56
CBD 101: What You Need To Know About Cannabidiol - a Green Flower Media class with Martin Lee of Project CBD
Cannabis has been a friend to humans since before recorded history
- fiber from the stalk
- nutrition from seeds
- as a medicine
- ritualistically
We've lost connection with the medicinal use of Cannabis because of prohibition
- an understanding of how to use it therapeutically
It's not as simple as lighting up a joint anymore
- potent oils in mixes of cannabinoids are now available
- consumers are confused and poorly educated on the therapeutic values and practices that make good use of cannabinoid therapies
CBD is a plant cannabinoid, a phytocannabinoid, with no psychoactive intoxicating effects.
- Discovered in 1940 by Roger Adams. Molecular structure wasn't mapped until 1963 by Dr. Raphael Mechoulam, who mapped THC the following year.
- CBD has astounding therapeutic potential.
- At the time, there wasn't any research that sprang up around CBD, since everyone was focused on that dangerous high, and all the money went to study THC.
- There was a scattering of clinical studies in Israel and Brazil.
- A 1980 study with a dozen epileptic youngsters that showed CBD would stop seizures.
- In 1988 NIH published a study identified THC and CBD as very potent antioxidants and neuroprotectors, protecting brain cells from damage.
- The Federal Government filed a patent in 2003 for the use of THC, CBD and other plant cannabinoids as neuroprotectors based on the 1988 study.
Both THC and CBD have been proven to support neurogenesis in adult mammals.
- As recently as 30 years ago accepted belief was that brain cells couldn't be regenerated or replaced. We now know that isn't true.
- We now have a new paradigm in brain science, because of the discovery of cannabinoids.
Properties of single molecule CBD
- antitumorial
- antispasmodic
- anticonvulsant
- antidepressant
- antipsychotic
- anti-addictive
- anti-anxiety
- antibiotic
- analgesic (pain relief)
CBD and THC work symbiotically. They should be used together to gain the maximum therapeutic value of the plant medicine.
- CBD can potentiate THC's pain-killing effects.
- CBD can enhance cannabis's efficacy for dealing with neuropathic pain, autoimmune diseases, cancer, and a whole slew of other known maladies that respond positively to cannabinoid therapies, because of this synergy.
Once CBD reappeared as part of the grass roots movement in 2009 in N. California and people began using CBD Rich Cannabis preparations it became obvious that CBD broadens the range of conditions treatable with cannabis-based medications.
- Conditions that don't respond as well to THC-rich formulations like liver conditions, cardiovascular conditions, and metabolic disorders.
A California Pacific Medical Center study in 2010 showed CBD enhances THC's inhibitory effects in the proliferation and survival of glioblastoma cells.
- Study showed that THC alone had antitumorial properties, as did CBD, with respect to this study of these brain cancers.
- When combined there was a stronger effect than either had alone.
CBD is not psychoactively intoxicating, like THC.
- Some people find that THC makes them anxious, parinoid. Not an enjoyable experience.
- CBD dampens the intoxicating effect of THC, depending on the ratio. More CBD = less high.
- Patients can now purchase products that allow you to balance your degree of psychoactivity.
There's no single ratio, dose, or cannabis product that's good for everyone.
- Today's options mean you can customize your high and your therapy to your individual level of comfort.
- Keep in mind that a low THC remedy may not be as therapeutically effective.
- A combination of the major cannabinoids will have a greater effect than either component can achieve alone.
Cannabis therapeutics are personalized medicines.
- The challenge is to find the ratios that work for you in the applications you're needing them to work. Where you're comfortable.
- A person's sensitivity to THC is the principle determinant in dosing ratios. How applicable is this to suppositories?
- All CBD-rich medications should have some THC in there to potentiate the CBD and make it more effective as medicine. The same principle applies to THC-rich meds.
- Patients can adjust the dose and ratio to control the psychoactive effects of THC.
- Cannabis naive patients can more easily enter the cannabis world through CBD-rich products.
The starting goal of a cannabis therapy is consistent, measurable doses of a CBD-rich medication with as much THC as the patient can tolerate comfortably.
- Dosing is everything.
The emphasis in personalized medicine should be on the person. Treat the person, not the disease or condition.
- It's not about lining the strains up and deciding what's best for the condition, but rather finding the remedy that the patient is comfortable with.
- Some will be comfortable with a balanced ratio with high values for each component. Others will find that too much, so they'll feel more comfortable with more CBD and less high.
- Where is the patient coming from? What's the history with cannabis? How comfortable are they with cannabis.
Gather information in a people-oriented way. The question shouldn't be "What should I take for my condition?" but rather turn the question around to the patient and ask
- Have you ever used cannabis?
- Describe your experience.
- What other drugs are you taking? We need to check for interactions.
- What's your goal with cannabinoid therapy?
Patients should ask about other options or complimentary modalities.
- People deserve a wide wide range of options when it comes to cannabis therapies.
When visiting a dispensary
- What other things can I do to augment or support my use of this products?
- If you're uncomfortable with getting high, you have to share that information with the person trying to line you up with an appropriate regimen.
- What other meds are you taking? Share this information so you can check for drug interactions.
- Ask lots and lots of questions. Share your qualms.
Cannabis naive patients can be handled gently.
- The goal isn't to heal the patient by offering the "perfect therapy", but to ease them into the cannabis landscape. Help them be comfortable with cannabis and offer or start with something that won't freak them out.
When introducing a new cannabis naive patient it's helpful to
- Help ease social qualms
- decipher the label (what's really in there and what does it mean?)
The starting ratio of a new patient is determined by
- the patient's history with cannabis
- the condition you're treating
The best approach in starting a new therapy is under the oversight of a qualified medical team.
- Unfortunately, there aren't many doctors who can do this type of work.
- What do they have access to?
- Ideally, start with a high CBD, low THC formulation and then incrementally increase the values of cannabinoids to reach the optimal therapeutic dose.
There's a of excitement developing around THCa.
- The precursor to THC is non-psychoactive, and shows promise for inflammation.
- In very small doses,THCa has incredible synergistic effects with other cannabis components, including CBD in particular.
- Children who didn't respond well to CBD oils did respond well to the addition of THC and THCa.
Where is the patient, physically, psychologically? What kind of support does the patient have? What community support exists?
With seizure disorders the key is what's the underlying concern. What's causing the seizures?
- It turns out with severe seizure disorders there're genes involved in the coding of the sodium channels.
- Apparently, if there's a genetic mutation in these genes you get seizures. These will respond to CBD.
- Other seizure disorders don't respond to CBD.
- In some cases the children will have adverse reactions to CBD.
Patterns have developed over the years, and they've noticed some at Project CBD.
- Anxiety patients tend to do well with a CBD-dominant medication with little THC.
- Depression, muscle spasm, and seizure disorders tend to respond well, at least initially, to the same - high CBD, low THC.
- Cancer, neurological disorders and diseases of the gut you'll be wanting a balanced ratio.
- Some gut issues may respond to CBD-dominant meds. It's really an individual choice, whatever works for you.
- GW Pharmaceuticals has done extensive testing that has shown that a balanced ratio is the best initial approach to chronic pain, and pain management.
- Sativex is accepted in over 2 dozen countries
Gioblastoma seems to respond best to high THC. Neuroblastoma, which usually hits young children, responds best to CBD-rich meds.
Many patients use different ratios at different times of the day.
- We see the symptoms, and they look alike, patient to patient, but in reality, the underlying problems that create those symptoms may be completely different, requiring totally different approaches to cannabinoid therapies.
- Find the cause of the symptoms and work from there to design the therapeutic path to homeostasis.
Your zip code determines your access.
Almost any cannabis will have a significant potential for treatment of autoimmune diseases.
- The immune system overreacts and inflammation abounds.
- Many modern diseases are autoimmune in nature.
- Cannabinoids attach to CB2 receptors in the peripheral nervous system, metabolic tissue, and in the immune system.
- Because cannabinoids, particularly THC, can come into play they can help the immune system dial back the erroneous response.
CBD-rich products available in today's market:
- flowers, oils, lozenges, edibles, beverages, gel caps, sublingual sprays and tinctures, suppositories, topicals, ointments, transdermal patches
- The CBD-rich products are available in the same way THC-rich products are.
Learn to to read the labels, and then read them.
- Ratio means nothing without values of cannabinoids. How many MG per dose, and how many doses in there?
- Insist that labels contain the pertinent information you need to know to make a good judgement on which product is best for you.
- Educate yourself on cannabis and cannabis products, so you can be informed.
If if you have the choice, choose a whole plant product over an isolate. Choose a Cannabis plant over a hemp plant in most cases.
What to look for
- Clear labeling specifying the quantity and ratio of THC and CBD, and the number of doses available in this product.
- Lab tested to identify the components and the presence of any pesticides, molds, fungi, etc.
- Pure ingredients, no artificial additives. No Trans fats, no propylene glycol (sometimes used as a thinning agent in the oils), or other artificial additives. This is a medicinal product.
- Look for products that are sustainably grown, from high-resin cannabis rather than from low-resin hemp.
- Avoid products made with toxic solvents like butane, hexane, or other hydrocarbons. You can do good extractions with these solvents, with the right training, equipment, and attention to detail and safety.
- There's too much bathtub chemistry going on in the modern cannabis world.
- Look for products made with supercritical CO2 or food-grade ethanol.
In the wild CBD and THC were close to a balance in volume in cannabis. The prohibition pushed cannabis as a medicine out of sight and the race was on to satisfy the recreational market where the money was. That meant breeding strains with higher and higher levels of THC, to the detriment of CBD, which was bred to less than 1% in most varieties. The growers in California's Golden Triangle were only too willing to participate.
- They were looking for the perfect high.
- When labs started testing in 2009 the occasional CBD-rich plant would appear.
Industrial hemp has 3.2% CBD, by weight. In comparison, cannabis rich in CBD can go as high as 20%.
- Hemp is described as a cannabis plant containing no more than 0.3% THC.
- There's good evidence that this designation exists only to perpetuate prohibition.
- If you have a plant that's very rich in CBD but it's slightly over the 0.3% threshold you're breaking federal law and dealing in a controlled substance.
You can get a decent CBD-rich product from well-grown industrial hemp BUT....
- you'll need huge amounts because there so little per plant
- cannabis is a bioaccumulator; polluted soil means polluted oils
Quality industrial hemp sources are becoming available.
- In Colorado the hemp farmers are growing high CBD, low THC strains and harvesting before the THC has developed above the 0.3% limit.
- It's legal, but it still limits the spectrum of what's available therapeutically. You get better medicine and better results when you include more THC. Patients deserve the full spectrum
CBD is NOT an FDA-approved nutritional supplement.
CBD is still federally illegal and that bars interstate commerce.
Quality control is lacking.
- CBD oil sold online often contains polypropylene glycol, which is safe for ingesting, but it's not safe to inhale.
- When overheated, polypropylene glycol breaks down into a carcinogen. People reaching for a CBD cartridge are likely sick and have no need for carcinogens to be introduced into their bodies.
- Many oils also come flavored, and no one has tested whether these flavors are safe to inhale. They ones that were tested were nasty.
- Avoid flavored oils unless they've been tested for inhalation.
Pharma CBD will soon be available, but researchers in Isreal discovered in 2015 that CBD as an isolate needs a high dose and the therape window is very narrow.
- With an isolate you have to be very precise. Going just a little bit over or under negates the therapeutic window.
- Full plant CBD allows for lower doses and offers a wider therapeutic window. The dose doesn't need to be so precise.
CBD Cautions: CBD will interact with at least 60% of pharma drugs.
- No problems have really surfaced with full plant extractions.
- Clinical trials with epileptic children saw problems with isolates.
- CBD makes other meds build up in the system and it also interfere with the metabolism of many pharma drugs.
- Ask if your meds caution grapefruit juice consumption. If so, this is a red flag for CBD. Proceed cautiously.
- Be particularly concerned with blood thinners. CBD interacts with the metabolism of blood thinners and they build up in the system. You need to have blood levels checked frequently to adjust the thinners.
Beneficial CBD drug interactions:
- Using THC can decrease the toxic effects of chemotherapy, allowing a lower dose of chemo drugs and a broader therapeutic window. We're discovering that CBD does the same thing.
- Epileptic meds can be decreased using CBD isolate.
- Opioids can be potentiated and decreased with any cannabis. It doesn't have to be CBD.
- Anxiety and depression are responding positively to CBD in balanced ratio formulations.
CBD matures earlier than THC
- harvest earlier for maximum CBD and lower THC.
A balanced ratio, or one with a 2:3 ratio are growing in popularity. Not everyone wants to be super stoned.
Certain terpenes improve transmembrane absorption (good for topicals).
- Some terpenes hit the same CB1 receptors in the brain that THC does.
Cannabinoids are dose specific, terpenes are more about the strain, the whole plant.
- They give the plant it's smell.
- They also effect the psychoactive component response, and the therapeutic values.
The cannabinoids and terpenes are in the resin, and most of the resin is in the buds.
- Since the entire plant is covered with trichomes, there's oil to be had in the stalks, but those trichomes are usually only one cell high, so you're not going to get very much pull.
Using CBD as a preventive medicine
- Use it in combination with a healthy lifestyle.
- If you're healthy already why not continue living healthy and avoid adding in another medicine, unless it's called for.
- Dr. Gregory Smith found a that high CBD tinctures at doses as low as 5mg a day correlated with a decrease in Alzheimer's cases.
Cannabis, used in any way, is benefitting the consumer. That's what cannabinoids do. If you take cannabis you're medicating.
- Using cannabis is a homeopathic way to augment the body's homeostatic system.
Studies in Brazil and Germany found that single molecule CBD was a potent antipsychotic, without the myriad of side effects found with mainline pharmaceuticals. Yale has an ongoing study in the works right now.
- The German study found CBD to be as effective as standard antipsychotic medications without the side effects.
Both depression and anxiety respond positively to a high CBD, low THC ratio in low doses.
CBD doesn't bind to the receptors the way THC does.
- So far they've identified about 70 different things CBD does in the body.
- It influences the expression of the eCB receptors, through a type of auxiliary receptor, a back door or side door, if you will. Think of it as THC gropes in through the front door, and CBD will find another way in to get the same results.
- CBD binds to many different receptors (remember the interference with the metabolism of the pharma meds?) but not to the eCB receptors.
- CBD works through different pathways to achieve similar results to THC.
- CBD also works through many receptor-independant channels.
CBD is a re-uptake inhibitor. Through interaction with the transporter molecules it blocks the uptake of eCBs.
- When you take cannabis reduces you're increasing the levels of your own endogenous cannabinoids.
- CBD always pushes to the front of the line for transportation through the cell membrane, so endogenous cannabinoids are forced to wait in line. In theory this makes them available for needy cells.
- Inside the cell they'd do their work and then be decommissioned by the enzymes.
This is highlights the importance of having healthy cell membranes.
- If the membrane is stiff, it'll be difficult to transport molecules through.
- Coconut oil, omega oils, olive oils, liquid sunflower lecithin, all assist cells in maintaining cell membrane flexibility.
The big takeaways:
- Cannabis is personalized medicine. You're treating the person, not the condition.
- There's no single ratio, dose, or cannabis product that's best for everyone.
- CBD and THC are the power couple of cannabinoid medicine. One shouldn't be used without the other.
- Whole plant CBD is safer and more effective than single molecule CBD.
Cannabis has been a friend to humans since before recorded history
- fiber from the stalk
- nutrition from seeds
- as a medicine
- ritualistically
We've lost connection with the medicinal use of Cannabis because of prohibition
- an understanding of how to use it therapeutically
It's not as simple as lighting up a joint anymore
- potent oils in mixes of cannabinoids are now available
- consumers are confused and poorly educated on the therapeutic values and practices that make good use of cannabinoid therapies
CBD is a plant cannabinoid, a phytocannabinoid, with no psychoactive intoxicating effects.
- Discovered in 1940 by Roger Adams. Molecular structure wasn't mapped until 1963 by Dr. Raphael Mechoulam, who mapped THC the following year.
- CBD has astounding therapeutic potential.
- At the time, there wasn't any research that sprang up around CBD, since everyone was focused on that dangerous high, and all the money went to study THC.
- There was a scattering of clinical studies in Israel and Brazil.
- A 1980 study with a dozen epileptic youngsters that showed CBD would stop seizures.
- In 1988 NIH published a study identified THC and CBD as very potent antioxidants and neuroprotectors, protecting brain cells from damage.
- The Federal Government filed a patent in 2003 for the use of THC, CBD and other plant cannabinoids as neuroprotectors based on the 1988 study.
Both THC and CBD have been proven to support neurogenesis in adult mammals.
- As recently as 30 years ago accepted belief was that brain cells couldn't be regenerated or replaced. We now know that isn't true.
- We now have a new paradigm in brain science, because of the discovery of cannabinoids.
Properties of single molecule CBD
- antitumorial
- antispasmodic
- anticonvulsant
- antidepressant
- antipsychotic
- anti-addictive
- anti-anxiety
- antibiotic
- analgesic (pain relief)
CBD and THC work symbiotically. They should be used together to gain the maximum therapeutic value of the plant medicine.
- CBD can potentiate THC's pain-killing effects.
- CBD can enhance cannabis's efficacy for dealing with neuropathic pain, autoimmune diseases, cancer, and a whole slew of other known maladies that respond positively to cannabinoid therapies, because of this synergy.
Once CBD reappeared as part of the grass roots movement in 2009 in N. California and people began using CBD Rich Cannabis preparations it became obvious that CBD broadens the range of conditions treatable with cannabis-based medications.
- Conditions that don't respond as well to THC-rich formulations like liver conditions, cardiovascular conditions, and metabolic disorders.
A California Pacific Medical Center study in 2010 showed CBD enhances THC's inhibitory effects in the proliferation and survival of glioblastoma cells.
- Study showed that THC alone had antitumorial properties, as did CBD, with respect to this study of these brain cancers.
- When combined there was a stronger effect than either had alone.
CBD is not psychoactively intoxicating, like THC.
- Some people find that THC makes them anxious, parinoid. Not an enjoyable experience.
- CBD dampens the intoxicating effect of THC, depending on the ratio. More CBD = less high.
- Patients can now purchase products that allow you to balance your degree of psychoactivity.
There's no single ratio, dose, or cannabis product that's good for everyone.
- Today's options mean you can customize your high and your therapy to your individual level of comfort.
- Keep in mind that a low THC remedy may not be as therapeutically effective.
- A combination of the major cannabinoids will have a greater effect than either component can achieve alone.
Cannabis therapeutics are personalized medicines.
- The challenge is to find the ratios that work for you in the applications you're needing them to work. Where you're comfortable.
- A person's sensitivity to THC is the principle determinant in dosing ratios. How applicable is this to suppositories?
- All CBD-rich medications should have some THC in there to potentiate the CBD and make it more effective as medicine. The same principle applies to THC-rich meds.
- Patients can adjust the dose and ratio to control the psychoactive effects of THC.
- Cannabis naive patients can more easily enter the cannabis world through CBD-rich products.
The starting goal of a cannabis therapy is consistent, measurable doses of a CBD-rich medication with as much THC as the patient can tolerate comfortably.
- Dosing is everything.
The emphasis in personalized medicine should be on the person. Treat the person, not the disease or condition.
- It's not about lining the strains up and deciding what's best for the condition, but rather finding the remedy that the patient is comfortable with.
- Some will be comfortable with a balanced ratio with high values for each component. Others will find that too much, so they'll feel more comfortable with more CBD and less high.
- Where is the patient coming from? What's the history with cannabis? How comfortable are they with cannabis.
Gather information in a people-oriented way. The question shouldn't be "What should I take for my condition?" but rather turn the question around to the patient and ask
- Have you ever used cannabis?
- Describe your experience.
- What other drugs are you taking? We need to check for interactions.
- What's your goal with cannabinoid therapy?
Patients should ask about other options or complimentary modalities.
- People deserve a wide wide range of options when it comes to cannabis therapies.
When visiting a dispensary
- What other things can I do to augment or support my use of this products?
- If you're uncomfortable with getting high, you have to share that information with the person trying to line you up with an appropriate regimen.
- What other meds are you taking? Share this information so you can check for drug interactions.
- Ask lots and lots of questions. Share your qualms.
Cannabis naive patients can be handled gently.
- The goal isn't to heal the patient by offering the "perfect therapy", but to ease them into the cannabis landscape. Help them be comfortable with cannabis and offer or start with something that won't freak them out.
When introducing a new cannabis naive patient it's helpful to
- Help ease social qualms
- decipher the label (what's really in there and what does it mean?)
The starting ratio of a new patient is determined by
- the patient's history with cannabis
- the condition you're treating
The best approach in starting a new therapy is under the oversight of a qualified medical team.
- Unfortunately, there aren't many doctors who can do this type of work.
- What do they have access to?
- Ideally, start with a high CBD, low THC formulation and then incrementally increase the values of cannabinoids to reach the optimal therapeutic dose.
There's a of excitement developing around THCa.
- The precursor to THC is non-psychoactive, and shows promise for inflammation.
- In very small doses,THCa has incredible synergistic effects with other cannabis components, including CBD in particular.
- Children who didn't respond well to CBD oils did respond well to the addition of THC and THCa.
Where is the patient, physically, psychologically? What kind of support does the patient have? What community support exists?
With seizure disorders the key is what's the underlying concern. What's causing the seizures?
- It turns out with severe seizure disorders there're genes involved in the coding of the sodium channels.
- Apparently, if there's a genetic mutation in these genes you get seizures. These will respond to CBD.
- Other seizure disorders don't respond to CBD.
- In some cases the children will have adverse reactions to CBD.
Patterns have developed over the years, and they've noticed some at Project CBD.
- Anxiety patients tend to do well with a CBD-dominant medication with little THC.
- Depression, muscle spasm, and seizure disorders tend to respond well, at least initially, to the same - high CBD, low THC.
- Cancer, neurological disorders and diseases of the gut you'll be wanting a balanced ratio.
- Some gut issues may respond to CBD-dominant meds. It's really an individual choice, whatever works for you.
- GW Pharmaceuticals has done extensive testing that has shown that a balanced ratio is the best initial approach to chronic pain, and pain management.
- Sativex is accepted in over 2 dozen countries
Gioblastoma seems to respond best to high THC. Neuroblastoma, which usually hits young children, responds best to CBD-rich meds.
Many patients use different ratios at different times of the day.
- We see the symptoms, and they look alike, patient to patient, but in reality, the underlying problems that create those symptoms may be completely different, requiring totally different approaches to cannabinoid therapies.
- Find the cause of the symptoms and work from there to design the therapeutic path to homeostasis.
Your zip code determines your access.
Almost any cannabis will have a significant potential for treatment of autoimmune diseases.
- The immune system overreacts and inflammation abounds.
- Many modern diseases are autoimmune in nature.
- Cannabinoids attach to CB2 receptors in the peripheral nervous system, metabolic tissue, and in the immune system.
- Because cannabinoids, particularly THC, can come into play they can help the immune system dial back the erroneous response.
CBD-rich products available in today's market:
- flowers, oils, lozenges, edibles, beverages, gel caps, sublingual sprays and tinctures, suppositories, topicals, ointments, transdermal patches
- The CBD-rich products are available in the same way THC-rich products are.
Learn to to read the labels, and then read them.
- Ratio means nothing without values of cannabinoids. How many MG per dose, and how many doses in there?
- Insist that labels contain the pertinent information you need to know to make a good judgement on which product is best for you.
- Educate yourself on cannabis and cannabis products, so you can be informed.
If if you have the choice, choose a whole plant product over an isolate. Choose a Cannabis plant over a hemp plant in most cases.
What to look for
- Clear labeling specifying the quantity and ratio of THC and CBD, and the number of doses available in this product.
- Lab tested to identify the components and the presence of any pesticides, molds, fungi, etc.
- Pure ingredients, no artificial additives. No Trans fats, no propylene glycol (sometimes used as a thinning agent in the oils), or other artificial additives. This is a medicinal product.
- Look for products that are sustainably grown, from high-resin cannabis rather than from low-resin hemp.
- Avoid products made with toxic solvents like butane, hexane, or other hydrocarbons. You can do good extractions with these solvents, with the right training, equipment, and attention to detail and safety.
- There's too much bathtub chemistry going on in the modern cannabis world.
- Look for products made with supercritical CO2 or food-grade ethanol.
In the wild CBD and THC were close to a balance in volume in cannabis. The prohibition pushed cannabis as a medicine out of sight and the race was on to satisfy the recreational market where the money was. That meant breeding strains with higher and higher levels of THC, to the detriment of CBD, which was bred to less than 1% in most varieties. The growers in California's Golden Triangle were only too willing to participate.
- They were looking for the perfect high.
- When labs started testing in 2009 the occasional CBD-rich plant would appear.
Industrial hemp has 3.2% CBD, by weight. In comparison, cannabis rich in CBD can go as high as 20%.
- Hemp is described as a cannabis plant containing no more than 0.3% THC.
- There's good evidence that this designation exists only to perpetuate prohibition.
- If you have a plant that's very rich in CBD but it's slightly over the 0.3% threshold you're breaking federal law and dealing in a controlled substance.
You can get a decent CBD-rich product from well-grown industrial hemp BUT....
- you'll need huge amounts because there so little per plant
- cannabis is a bioaccumulator; polluted soil means polluted oils
Quality industrial hemp sources are becoming available.
- In Colorado the hemp farmers are growing high CBD, low THC strains and harvesting before the THC has developed above the 0.3% limit.
- It's legal, but it still limits the spectrum of what's available therapeutically. You get better medicine and better results when you include more THC. Patients deserve the full spectrum
CBD is NOT an FDA-approved nutritional supplement.
CBD is still federally illegal and that bars interstate commerce.
Quality control is lacking.
- CBD oil sold online often contains polypropylene glycol, which is safe for ingesting, but it's not safe to inhale.
- When overheated, polypropylene glycol breaks down into a carcinogen. People reaching for a CBD cartridge are likely sick and have no need for carcinogens to be introduced into their bodies.
- Many oils also come flavored, and no one has tested whether these flavors are safe to inhale. They ones that were tested were nasty.
- Avoid flavored oils unless they've been tested for inhalation.
Pharma CBD will soon be available, but researchers in Isreal discovered in 2015 that CBD as an isolate needs a high dose and the therape window is very narrow.
- With an isolate you have to be very precise. Going just a little bit over or under negates the therapeutic window.
- Full plant CBD allows for lower doses and offers a wider therapeutic window. The dose doesn't need to be so precise.
CBD Cautions: CBD will interact with at least 60% of pharma drugs.
- No problems have really surfaced with full plant extractions.
- Clinical trials with epileptic children saw problems with isolates.
- CBD makes other meds build up in the system and it also interfere with the metabolism of many pharma drugs.
- Ask if your meds caution grapefruit juice consumption. If so, this is a red flag for CBD. Proceed cautiously.
- Be particularly concerned with blood thinners. CBD interacts with the metabolism of blood thinners and they build up in the system. You need to have blood levels checked frequently to adjust the thinners.
Beneficial CBD drug interactions:
- Using THC can decrease the toxic effects of chemotherapy, allowing a lower dose of chemo drugs and a broader therapeutic window. We're discovering that CBD does the same thing.
- Epileptic meds can be decreased using CBD isolate.
- Opioids can be potentiated and decreased with any cannabis. It doesn't have to be CBD.
- Anxiety and depression are responding positively to CBD in balanced ratio formulations.
CBD matures earlier than THC
- harvest earlier for maximum CBD and lower THC.
A balanced ratio, or one with a 2:3 ratio are growing in popularity. Not everyone wants to be super stoned.
Certain terpenes improve transmembrane absorption (good for topicals).
- Some terpenes hit the same CB1 receptors in the brain that THC does.
Cannabinoids are dose specific, terpenes are more about the strain, the whole plant.
- They give the plant it's smell.
- They also effect the psychoactive component response, and the therapeutic values.
The cannabinoids and terpenes are in the resin, and most of the resin is in the buds.
- Since the entire plant is covered with trichomes, there's oil to be had in the stalks, but those trichomes are usually only one cell high, so you're not going to get very much pull.
Using CBD as a preventive medicine
- Use it in combination with a healthy lifestyle.
- If you're healthy already why not continue living healthy and avoid adding in another medicine, unless it's called for.
- Dr. Gregory Smith found a that high CBD tinctures at doses as low as 5mg a day correlated with a decrease in Alzheimer's cases.
Cannabis, used in any way, is benefitting the consumer. That's what cannabinoids do. If you take cannabis you're medicating.
- Using cannabis is a homeopathic way to augment the body's homeostatic system.
Studies in Brazil and Germany found that single molecule CBD was a potent antipsychotic, without the myriad of side effects found with mainline pharmaceuticals. Yale has an ongoing study in the works right now.
- The German study found CBD to be as effective as standard antipsychotic medications without the side effects.
Both depression and anxiety respond positively to a high CBD, low THC ratio in low doses.
CBD doesn't bind to the receptors the way THC does.
- So far they've identified about 70 different things CBD does in the body.
- It influences the expression of the eCB receptors, through a type of auxiliary receptor, a back door or side door, if you will. Think of it as THC gropes in through the front door, and CBD will find another way in to get the same results.
- CBD binds to many different receptors (remember the interference with the metabolism of the pharma meds?) but not to the eCB receptors.
- CBD works through different pathways to achieve similar results to THC.
- CBD also works through many receptor-independant channels.
CBD is a re-uptake inhibitor. Through interaction with the transporter molecules it blocks the uptake of eCBs.
- When you take cannabis reduces you're increasing the levels of your own endogenous cannabinoids.
- CBD always pushes to the front of the line for transportation through the cell membrane, so endogenous cannabinoids are forced to wait in line. In theory this makes them available for needy cells.
- Inside the cell they'd do their work and then be decommissioned by the enzymes.
This is highlights the importance of having healthy cell membranes.
- If the membrane is stiff, it'll be difficult to transport molecules through.
- Coconut oil, omega oils, olive oils, liquid sunflower lecithin, all assist cells in maintaining cell membrane flexibility.
The big takeaways:
- Cannabis is personalized medicine. You're treating the person, not the condition.
- There's no single ratio, dose, or cannabis product that's best for everyone.
- CBD and THC are the power couple of cannabinoid medicine. One shouldn't be used without the other.
- Whole plant CBD is safer and more effective than single molecule CBD.
- Thread starter
- #57
Different types of cannabis (first described by Linnaeus)
- Type 1: high THC, the most common type found, due to the homogenization of the gene pool.
- Type 2: about equal ratio of THC and CBD, historically found in landraces in places like Morocco, Afganistan
- Type 3: CBD-dominant, more like industrial hemp
Cannabis sativa means "cultivated cannabis"
Cannabis indica, "from India"
The cannabis indica that Lemarck described was tall with narrow leaves, consistent with what had already been described as European hemp.
- Prof. Shultes of Harvard described a short, squat, broad leaflet plant in Afganistan as cannabis indica.
His classifications were:
1) Cannabis Sativa, tall, narrow-leaved
2) Cannabis Indica, short, squat, broad-leaved
3) Cannabis Ruderalis, an unbranched, one meter plant with low cannabinoid content.
Botanical taxonomists fight over names, making it difficult to keep it consistent.
- There hasn't been any consistency in the use of strain determination from the beginning.
In the last decade there's been a push to reclassify.
Terpenes provide the best determination between the chemovares - what most of us call strains.
To have a good classification system you need to determine
- the morphology, or shape of the plant. (broad-leaf, narrow-leaf, compact vs tall and spindly,
- it's chemical makeup
- it's intended use
- With cannabis it'd be good to include the cannabinoid profile, like Type 1 for high THC.
- It's be useful to include the specific cannabinoid content. This would be invaluable for the consumer.
- Since it's the terpene profile that distinguishes one plant from another that should also be included.
- It's be nice to have a description of the scent, the taste, if vaporized, and how the strain might be useful from a patient orientation.
PhytoFacts by Napro Research describes
- amount of cannabinoids
- a picture of the bud of an uncertified female flowering top
- scent and taste profile
- often pictures of a recognizable plant
- use of visual cues to describe predominant terpenes (lemon, peppercorns, etc)
- description of effects by consumers of this particular chemovare
Also contains an invaluable terpenoid profile:
- high yellow bar is limonene, making this a good strain to elevate the mood and have some immune potentiating effects
- high blue bar is Caryophyllene, an agonist at the CB2 receptor, an analgesic (pain killer), and an anti-inflammatory agent
- low myecene means no couch lock, more cerebral.
In the chemovare he's describing you have
- high THC, with all the benefits therein
- mood elevation from the limonene
- anti-inflammatory with the Beta-Caryophyllene
- low myrcene makes this a good agent for daytime use without sedation
pick up at 10:17
Goodnight moon.
- Thread starter
- #58
Just lost 12 minutes of transcription because I neglected to save it. Start again woman!
Medical Cannabis Treatment for Adults and Children - Dr. Bonnie Goldstein
United in Compassion Medical Cannabis Symposium, Sydney, Australia, June 14-15, 2016
We need to stop identifying cannabis as a drug of abuse. It's a medicine.
- In all her years working in pediatric ERs with over 60,000 patients she never saw a cannabis patient problem.
- No one has ever died from ingesting cannabis.
- Education is the only way to move the message forward. Educate ourselves and share that knowledge.
In her practice she sees both adult and pediatric patients.
- Pediatric patients are mostly confined to treatment-resistant epilepsy, autism, and advanced cancer, though she does have some psychiatric disorder patients.
- Beginning to see an increase in a newly-diagnosed and little understood PAD or PANDA, a type of Pediatric Autoimmune Disease.
- The most common thing they see adults for is chronic pain, followed by a long list of everything, including sleep disorders, psychiatric concerns, and so on.
- Because of where the receptors are located the ECS effects almost every physiological system in the body.
There are over 400 compunds in the typical cannabis plant, over 100 of which are cannabinoids, the most studied among them THC and CBD.
- It's going to work differently in the body than a single isolate med will.
- Breeders are beginning to develop designer strains with increased amounts of particular cannabinoids.
- The entourage effect: the sum is greater than its parts. Choose whole-plant medicines and full-plant extractions over isolates.
- Terpinoids are basically essential oils that have medicinal properties.
The choice of what strain to choose to treat a particular disease is entirely individual.
- Determine the patient's goals from the treatment and assess the general condition of the patient.
- How is the patient expressing the disease? What's the underlying cause and how is this disease expressing itself in this patient.
- You want to pursue an individualized approach. Cannabis will offer an individual response.
- Patients with identical diagnoses, using identical strains with th same cannabinoid and terpene profiles and at the same dose, and have completely different response and experiences.
Start low, go slow
- Begin sub-therapeutically and titrate up slowly and thoughtfully.
- Dr. Abrams of UCSF stated it as "Patient will determine self-titrating dose."
- Its a little different for epileptic and cancer patients, but generally the patient gets to choose the dose.
- You'll find the sweet spot by trial and error, titrating up until you feel "too much!!" and then backing off one increment. This is the optimal therapeutic dose.
I like the way Martin Lee expresses it: you want a CBD-rich medication with as much THC as the patient can tolerate.
Cannabis is not one size fits all.
Your endocannabinoid tone is of great importance. Fall below or above that baseline and disease comes calling.
- She explains it to her patients as you have a point of balance where your ECS is working well. Disease sets in if your tone becomes deficient. Over-excitability of the system leads to receptors being taken off line, which can complicate things too.
- She likens it to a thyroid condition. If the thyroid was deficient your doctor would prescribe thyroid medication. If the ECS is deficient you bring in more cannabinoids, terpenes, and flavonoids.
- If you or someone you love has disease you haven't found a pharmacological solution to its worth supporting the ECS.
- If you're not supporting the ECS you're shooting around the target when the ECS is the bullseye.
New patient intakes include
- history, what they've tried as treatment, whether or not they've used cannabis before
- A cannabis naïve patient or one who used slightly years ago need to be handled differently from experienced patients.
- If someone used years ago you want to know what they're experience was like to help you decide which strain to choose and what treatment path to take.
- For someone who remembers being stressed by the experience, this may suggest they have a sensitivity to high THC or sativas.
Delivery method needs to be properly matched to the patient.
- Ask the patient "What sounds good to you?" (Speaking of experience)
- A patient going through chemotherapy may not be able to process edibles in the way you need. Chemo destroys the gut flora, so things don't get absorbed. How frustrating would that be?
- There must be options for delivery methods so patients have a wide range to search through to find what works for them.
- A majority of patients us inhalation (smoking or vaping), sublingual tinctures, and a small percentage of patients find edibles help.
- Dosing through the liver can be trickier with metabolism.
Effects of THC and CBD
- With most patients a combination formulation works best.
Bonnie's 3-Tier approach, developed so that patients would be able to read labels and determine the anticipated effects of the different ratios.
1) THC-rich medications are strong in the THC effect.
- The thought that THC is only recreational is erroneous. THC is powerful medicine. Control it with dosing and delivery.
- Don't drive when you're intoxicated
- Patients use THC-rich meds to treat sleep, pain, nausea, mood and appetite.
2) High ratio CBD:THC will be mostly influenced by CBD.
- This offers meds for daytime that avoids euphoric effects that come with THC.
- It's not sedating
- choose this type if treating pain inflammation, mood, and seizure disorders.
- Patients usually see euphoria fall away at 10:1.
3) Low ratio CBD:THC will have some intoxication, depending on the CBD content and the terpene profile.
- May or may not be psychoactive, it's that individual response, determined by patient's condition, how experienced a cannabis consumer they are and how their brain responds to the cannabinoids.
- CBD will buffer some of the euphoria, depending on your system's response to the compounds.
- Patients find relief for pain, inflammation, mood, sleep, neuropathic pain, and nausea.
Case report: 54-yr old woman with diabetic neuropathy.
- Middle school counselor, so very private about her cannabis use.
- History of adult-onset Diabetes 2 with 6 years of nerve pain interfering with sleep.
- Used to be morbidly obese, and underwent gastric bypass. Glucose was controlled by the procedure, but neuropathic pain persisted.
- Tried numerous drugs, including Gabapentin and opiods, to no avail.
- A friend gave her a cannabis edible prior to her visit, probably a high THC product, and she had complete relief from pain and was able to sleep again. She visited Dr. G to become legal.
- Started her on high-CBD tincture (25:1) for pain and uses topicals for feet if bothering her.
- She only treats on days when she has pain. This seems counterproductive to me. Obviously a baseline of available cannabinoids would go a long way to promoting more healing.
- At bedtime she uses a 1:1 ratio edible. She takes it at about 8-9 PM and gets between 618 hours of uninterrupted sleep, and her feet don't hurt when she wakes up in the morning.
- Again, if no pain she passes on the dose. She says some weeks are good, some not so good.
- She's now off all pain and sleep medications. She is now controlling with diet and is pharmaceutical-free.
Case report: 26-yr old woman with juvenile rheumatoid arthritis, diagnosed at the age of 15.
- Dr. G saw her first at the age of 24.
- Patient had significant side effects with conventional medication. She'd had a life-threatening reaction to one medication that sent her to the ICU, and she sought out Dr. G following that event.
- She was wheelchair bound, severely depressed, with severe pain and swelling, unable to go to school and care for herself.
- She was the oldest of four sisters, and the other two were living normal lives. She was feeling left behind, which caused anxiety and depression.
- She started out anti-cannabis, but enough friends and family had suggested it that she wanted to at least try.
- Started on a high-dose CBD oil, at a ratio of 27:1, upwards to 200 MG of CBD per day in three doses, spaced 8 hours apart. Also uses high THC sublingual meds for breakthrough pain.
- She knew she was getting better can now clip her own fingernails. She started cooking and can now shower on her own.
- She isn't taking any other medications
Case report: 47-yr old man, a construction worker, father of two, who had a severe work injury to his spine that herniated lumbar disc.
- Went the typical pharma route of opioids, muscle relaxers, nonsteroidals, physical therapy and epidural injections, with no real relief from any of that.
- He was reluctant to have surgery. From a family of police officers, he was reluctant to enquirer about cannabis, but someone had started him on cannabis, it worked, and he wanted to be legal.
- CBD was ineffective for his pain. He uses THC-rich meds at night.
- He says if he's overexerted himself at work and feels inflammation flaring up he now uses CBD as well at night, and he found he doesn't get the full-blown episodes where he can't get out of bed.
- He uses acupuncture and exercise to assist healing and is now pharmaceutical-free.
Pediatric use
- Science is pointing to ECS deficiency with seizure disorders and autism. If it's the ECS that's failing, it's the ECS we need to treat.
- Cannabhas an excellent safety profile. She sees no negative side effects with any of her pediatric patients.
- Quality of life is everything for these families. It may not be the perfect solution, but ther usually will be some improvement and no negative side effects.
- Compassionate care for end-of-life patients.
- It took California nearly 22 years after passing the first MMJ law to finally get regulations up and running.
CBD use with epilepsy
There were some small trials with CBD and pediatric patients beginning in the 1960s. The last of the early trials with CBD and epilepsy was in 1985, and nothing else was done until 2005.
pick up at 30:43
Start again woman!Medical Cannabis Treatment for Adults and Children - Dr. Bonnie Goldstein
United in Compassion Medical Cannabis Symposium, Sydney, Australia, June 14-15, 2016
We need to stop identifying cannabis as a drug of abuse. It's a medicine.
- In all her years working in pediatric ERs with over 60,000 patients she never saw a cannabis patient problem.
- No one has ever died from ingesting cannabis.
- Education is the only way to move the message forward. Educate ourselves and share that knowledge.
In her practice she sees both adult and pediatric patients.
- Pediatric patients are mostly confined to treatment-resistant epilepsy, autism, and advanced cancer, though she does have some psychiatric disorder patients.
- Beginning to see an increase in a newly-diagnosed and little understood PAD or PANDA, a type of Pediatric Autoimmune Disease.
- The most common thing they see adults for is chronic pain, followed by a long list of everything, including sleep disorders, psychiatric concerns, and so on.
- Because of where the receptors are located the ECS effects almost every physiological system in the body.
There are over 400 compunds in the typical cannabis plant, over 100 of which are cannabinoids, the most studied among them THC and CBD.
- It's going to work differently in the body than a single isolate med will.
- Breeders are beginning to develop designer strains with increased amounts of particular cannabinoids.
- The entourage effect: the sum is greater than its parts. Choose whole-plant medicines and full-plant extractions over isolates.
- Terpinoids are basically essential oils that have medicinal properties.
The choice of what strain to choose to treat a particular disease is entirely individual.
- Determine the patient's goals from the treatment and assess the general condition of the patient.
- How is the patient expressing the disease? What's the underlying cause and how is this disease expressing itself in this patient.
- You want to pursue an individualized approach. Cannabis will offer an individual response.
- Patients with identical diagnoses, using identical strains with th same cannabinoid and terpene profiles and at the same dose, and have completely different response and experiences.
Start low, go slow
- Begin sub-therapeutically and titrate up slowly and thoughtfully.
- Dr. Abrams of UCSF stated it as "Patient will determine self-titrating dose."
- Its a little different for epileptic and cancer patients, but generally the patient gets to choose the dose.
- You'll find the sweet spot by trial and error, titrating up until you feel "too much!!" and then backing off one increment. This is the optimal therapeutic dose.
I like the way Martin Lee expresses it: you want a CBD-rich medication with as much THC as the patient can tolerate.
Cannabis is not one size fits all.
Your endocannabinoid tone is of great importance. Fall below or above that baseline and disease comes calling.
- She explains it to her patients as you have a point of balance where your ECS is working well. Disease sets in if your tone becomes deficient. Over-excitability of the system leads to receptors being taken off line, which can complicate things too.
- She likens it to a thyroid condition. If the thyroid was deficient your doctor would prescribe thyroid medication. If the ECS is deficient you bring in more cannabinoids, terpenes, and flavonoids.
- If you or someone you love has disease you haven't found a pharmacological solution to its worth supporting the ECS.
- If you're not supporting the ECS you're shooting around the target when the ECS is the bullseye.
New patient intakes include
- history, what they've tried as treatment, whether or not they've used cannabis before
- A cannabis naïve patient or one who used slightly years ago need to be handled differently from experienced patients.
- If someone used years ago you want to know what they're experience was like to help you decide which strain to choose and what treatment path to take.
- For someone who remembers being stressed by the experience, this may suggest they have a sensitivity to high THC or sativas.
Delivery method needs to be properly matched to the patient.
- Ask the patient "What sounds good to you?" (Speaking of experience)
- A patient going through chemotherapy may not be able to process edibles in the way you need. Chemo destroys the gut flora, so things don't get absorbed. How frustrating would that be?
- There must be options for delivery methods so patients have a wide range to search through to find what works for them.
- A majority of patients us inhalation (smoking or vaping), sublingual tinctures, and a small percentage of patients find edibles help.
- Dosing through the liver can be trickier with metabolism.
Effects of THC and CBD
- With most patients a combination formulation works best.
Bonnie's 3-Tier approach, developed so that patients would be able to read labels and determine the anticipated effects of the different ratios.
1) THC-rich medications are strong in the THC effect.
- The thought that THC is only recreational is erroneous. THC is powerful medicine. Control it with dosing and delivery.
- Don't drive when you're intoxicated
- Patients use THC-rich meds to treat sleep, pain, nausea, mood and appetite.
2) High ratio CBD:THC will be mostly influenced by CBD.
- This offers meds for daytime that avoids euphoric effects that come with THC.
- It's not sedating
- choose this type if treating pain inflammation, mood, and seizure disorders.
- Patients usually see euphoria fall away at 10:1.
3) Low ratio CBD:THC will have some intoxication, depending on the CBD content and the terpene profile.
- May or may not be psychoactive, it's that individual response, determined by patient's condition, how experienced a cannabis consumer they are and how their brain responds to the cannabinoids.
- CBD will buffer some of the euphoria, depending on your system's response to the compounds.
- Patients find relief for pain, inflammation, mood, sleep, neuropathic pain, and nausea.
Case report: 54-yr old woman with diabetic neuropathy.
- Middle school counselor, so very private about her cannabis use.
- History of adult-onset Diabetes 2 with 6 years of nerve pain interfering with sleep.
- Used to be morbidly obese, and underwent gastric bypass. Glucose was controlled by the procedure, but neuropathic pain persisted.
- Tried numerous drugs, including Gabapentin and opiods, to no avail.
- A friend gave her a cannabis edible prior to her visit, probably a high THC product, and she had complete relief from pain and was able to sleep again. She visited Dr. G to become legal.
- Started her on high-CBD tincture (25:1) for pain and uses topicals for feet if bothering her.
- She only treats on days when she has pain. This seems counterproductive to me. Obviously a baseline of available cannabinoids would go a long way to promoting more healing.
- At bedtime she uses a 1:1 ratio edible. She takes it at about 8-9 PM and gets between 618 hours of uninterrupted sleep, and her feet don't hurt when she wakes up in the morning.
- Again, if no pain she passes on the dose. She says some weeks are good, some not so good.
- She's now off all pain and sleep medications. She is now controlling with diet and is pharmaceutical-free.
Case report: 26-yr old woman with juvenile rheumatoid arthritis, diagnosed at the age of 15.
- Dr. G saw her first at the age of 24.
- Patient had significant side effects with conventional medication. She'd had a life-threatening reaction to one medication that sent her to the ICU, and she sought out Dr. G following that event.
- She was wheelchair bound, severely depressed, with severe pain and swelling, unable to go to school and care for herself.
- She was the oldest of four sisters, and the other two were living normal lives. She was feeling left behind, which caused anxiety and depression.
- She started out anti-cannabis, but enough friends and family had suggested it that she wanted to at least try.
- Started on a high-dose CBD oil, at a ratio of 27:1, upwards to 200 MG of CBD per day in three doses, spaced 8 hours apart. Also uses high THC sublingual meds for breakthrough pain.
- She knew she was getting better can now clip her own fingernails. She started cooking and can now shower on her own.
- She isn't taking any other medications
Case report: 47-yr old man, a construction worker, father of two, who had a severe work injury to his spine that herniated lumbar disc.
- Went the typical pharma route of opioids, muscle relaxers, nonsteroidals, physical therapy and epidural injections, with no real relief from any of that.
- He was reluctant to have surgery. From a family of police officers, he was reluctant to enquirer about cannabis, but someone had started him on cannabis, it worked, and he wanted to be legal.
- CBD was ineffective for his pain. He uses THC-rich meds at night.
- He says if he's overexerted himself at work and feels inflammation flaring up he now uses CBD as well at night, and he found he doesn't get the full-blown episodes where he can't get out of bed.
- He uses acupuncture and exercise to assist healing and is now pharmaceutical-free.
Pediatric use
- Science is pointing to ECS deficiency with seizure disorders and autism. If it's the ECS that's failing, it's the ECS we need to treat.
- Cannabhas an excellent safety profile. She sees no negative side effects with any of her pediatric patients.
- Quality of life is everything for these families. It may not be the perfect solution, but ther usually will be some improvement and no negative side effects.
- Compassionate care for end-of-life patients.
- It took California nearly 22 years after passing the first MMJ law to finally get regulations up and running.
CBD use with epilepsy
There were some small trials with CBD and pediatric patients beginning in the 1960s. The last of the early trials with CBD and epilepsy was in 1985, and nothing else was done until 2005.
pick up at 30:43
- Thread starter
- #59
Notes from The Sacred Plant Healing Secrets Explained Webinar #4: Proven Strategies: Not All Diseases Are Treated Equally with guest Dr. Bonnie Goldstein.
Cannabis is NOT a one size fits all medicine.
- Patients respond to cannabis in individual ways.
How to start
- Determine the goal of treatment. To have a better day? Get a better night's sleep? To treat pain, daytime and nighttime? Treating symptoms or trying for a cure?
- Sometimes people are in a desperate situation and only want results, but you work the protocol from that stated goal.
- Experiment with different types of cannabis, different methods of administration.
- There are hundreds of different compounds in the plant.
- Know enough about the different types of cannabis to be able to make an informed choice. This would come down to terpene profiles.
- One strain will make you sleepy, where another will make you energized. One will eleviate pain where another might aggravate it.
- Understand that the first attempt at cannabinoid therapy might not work. It's a matter of trial and error with a plant that really can't hurt you.
- Cannabis has more of an individual responses than many pharma drugs will.
Sativa and indica aren't helpful anymore. Too much cross breeding.
- Look for the cannabinoid and terpene profiles.
A patient in chemo with symptoms of nausea and bomiting might start with a medicine higher in THC to quell these unwanted symptoms.
- You have to be open to THC inclusion, because a CBD medicine low in THC wouldn't work in most cases.
- For a patient with an aversion to extreme euphoria a formulation can be worked out adding more CBD to the mix, that should tamp down the euphoric effects while still being therapeutically effective.
Someone with extreme inflammation who doesn't desire the intoxication of THC or sleepiness that comes with many high THC strains with particular terpene expressions can work out a formulation higher in CBD.
- You have to balance therapeutic goals with patient concerns. Education becomes a valuable tool.
- Determine if the patient will be using the medicine for daytime or nighttime. Nighttime you can get more THC in.
- An experienced cannabis patient will likely have a higher tolerance for THC, allowing higher doses.
Euphoria helps patients relax and step away from their pain. Her patients describe euphoria as the reset button. It allows them to distance themselves from pain and patterns of pain response and start anew.
Patient response is determined by the coding of your ECS, a genetic coding that you were born with.
- Endocannabinoid Deficiency is a condition that needs to be tended to first before we start treating everything around it, which is all monitored by the ECS anyway.
- The role of the ECS is to maintain cellular messages with the goal of homeostasis.
If you have a genetic disruption in your ECS you won't be able to keep up with demand and disease sets in.
- In such a case you can supplement the ECS with phytocannabinoids.
Dr. Goldstein has two patients with migraine and fibromyalgia; one responds well to THC, the e other hates the way it makes her feel and uses a CBD medicine. Both are doing well.
- Because of the genetic coding and the way cannabinoids interact with the body you're going to get individual effects.
Absorbtion is huge. Some patients absorb well, some not so. If the patient is a poor absorber edibles aren't going to be of much good.
- We don't absorb 100% of the medicine dosed.
- If you're in a very inflamed state you won't absorb well.
- Chemo patients have the gut inflamed from the mouth to the anus.
- Patients with inflamed guts don't get the effects.
- Poor absorbtion may explain most of the disparity in patient effects with the same meds for the same conditions, etc.
Could this be what it is with men who don't feel edibles the way most of us do? I've noticed more men with debilitating chronic back pain don't metabolize cannabis as efficiently through the gut as we'd like. Hmmmm...... They're probably big meat eaters too, which adds to the gut problems and supports imflammation.
Metabolization is broken down into four categories from very poor metabolic rate to ultra-metabolizes.
Allergic reactions to cannabis are few and far between, but we're humans, so that's to be expected.
- Safety regulations haven't gone into effect in California yet, so pesticides may be the culprit.
- Topical allergies might be the most common, but it's not something that shows up very often at all.
Cannabis can potentiate chemo drugs. Studies back this up. This allows the chemo drug to be reduced and have greater effect.
- She now asks for a list of chemo drugs and looks for literature about combinations.
- Cannabis works through receptors and other pathways to kill cancer cells.
- If you're using cannabis to simply counter the side effects of chemo you can get away with low doses, on demand.
- If you're treating cancer outright you're typically looking at lower numbers, although some clinicians are getting good results with lower numbers.
- She has a cancer patient who's 2-yrs old using a cannabis tincture. His low dose of THC and CBD has boosted his appetite, improved his mood, has him laughing and playing again, and healed the sloughing of the tissue inside of his mouth. In his mother's words, "the difference between night and day."
You don't talk cure with cancer. You talk about extension of life.
CBD improves the efficacy of radiation with some cancers.
- We already knew that CBD would protect you from the effects of radiation.
- Combination therapies can get you all of the benefits.
Lack of quality control means you never know for sure that what you buy is what you think you purchased.
- If the terpenoid profile changes from batch to batch - more common than you'd think - the effects can be drastically altered. You wouldn't know that, because the labels only tell you what cannabinoids are in there.
It's going to be up to us to educate our doctors.
Reach for the optimal therapeutic dose.
- Starting low and titrating slowly helps the patient avoid jumping right over that lower, effective dose.
- CBD has a wide therapeutic window.
- It takes longer, but it's worth the time to do it slowly. You won't know how your body will absorb this medication.
People who use cannabis have an obesity rate of around 17%. People who don't use have a rate around 25%.
- The ECS controls, energy metabolism, appetite, how we use calories.
- If you're sleeping well you're not stress-eating.
- Sleep is restorative.
- Rested patients improve their lifestyle choices.
The ECS sends messages that effect how we relax, eat, sleep, protect, and forget.
- Quality of life.
- Cannabis restores the balance. You feel better and you make better choices.
Anxiety can sometimes be dramatically reduced with restoration of sleep.
Administration choices
- Inhalation gives immediate effects. About a 4-hour window.
- Inhalation is often associated with drug behavior, but it works. Vaporization is commonly used for asthma.
- Edibles come in a myriad of choices. Anything that hits the gut is an edible.
- Can last 6-12 hours, dose dependant. The most common way to dose. Metabolization and absorbtion are primary concerns.
- THC is metabolized in the liver. More potent and sedating effect, and also cuts half-life.
- sublingual 15 min to 2.5 hr. onset, 6-8 hr window
- Topicals are as needed.
You can mix and match methods.
- Vaporize to fall asleep following an edible taken earlier to keep sleep going.
Suppositories don't have enough research to the explain disparate results
- Anecdotal evidence is strong.
Seniors: be careful that they don't overdose, thinking the dose must be too low.
Go over your med list to check with drug interactions
- Look for United Patient Group for link to research.
- Warfarin is one to be alert to.
- If you're taking a drug that offers an intoxicating effect and you want to take cannabis, don't take them at the same time. Leave a two hour break at least.
- There is no toxic overdose with THC. Use pinene and limonene to counteract an overdose. It can be psychologically uncomfortable for some patients.
Unless you do blood work to check serum levels you have no way of knowing what the Pharmacokenetics are with this medicine in this patient.
- Through the gut is between 4-25% absorption.
- You can take an edible one day and absorbtion is good, but tomorrow may be way different. Through the gut can be difficult to get consistent dosing with. It is possible but can be dramatically variable.
Have you used cannabis before?
How did you take it?
What was your experience like?
Someone who smoked or used years ago is to be considered a new cannabis patient.
Experiment. Find your strain, your ratio, your preferred terpene profile, your dose.
You can be dependent on cannabis, but it's not possible to get addicted to it.
When THC binds to the receptor it sends the message to the receptor to change the signal the cell is giving off.
When you flood the system with THC you'll lose access to receptors.
Whe you have a deficiency and you're successfully treat with phytocannabinoids the ECS will improve its tone and the need for supplements drops.
The therapeutic window is what works for you.
- Seizure patients use a wide range of doses and ratios
4:1 CBD:THC for arthritis (patient used once a day, in evening to help with sleep). After reducing dose by half he discovered he had therapeutic effect. He'd gone with the higher dose because he was concerned about losing sleep.
The brain has selective downregulation.
CBD saturation (seen in pediatric seizure patients taking high dose CBD meds 3-4 times daily)
- Sometimes a child will begin to have seizures or lose some benefits.
- Solution is to skip doses of CBD until seizures stop. Then you start lower and titrate up again.
- Maybe absorbtion has been compromised. It's all theory at this point.
- Cannabis in general is very safe and can be used with great comfort, but sometimes these things pop up.
THCa and CBDa are not psychoactive, but THCa is an unstable molecule and will quickly convert if not refrigerated.
- Left out for 10 days 25% of the THCa will convert.
- Both cannabinoids have cancer fighting properties and both treat inflammation.
- THCa meds are made cold-pressed or without heat.
- Some pediatric patients don't respond to CBD try THCa.
The findings that THC can proliferate ER+ breast cancers are questionably extrapolated to human patients. The mice in the study had no immune systems.
- She has a patient that followed a THC regimen with ER+ and it killed the tumor cells.
- Breast cancer has become a chronic condition.
- Lots of study points to CBD's ability to kill cancer cells through limiting blood vessel development.
THC is the cannabinoid that attaches to the receptor and gives the strongest benefit for most medical conditions.
- There is a medical dose and a recreational dose, with a little overlap.
- A red dose it to feel good, to get high. A med dose is to treat the condition. You can successfully treat a medical condition with THC if you pay attention to what you're doing.
- Take a small dose, pause and wait to see if you got the therapeutic result you were seeking.
- Most were introduced in the recreational realm, and that confuses the waters. Most med doses are much lower than therapeutic doses.
- THC is a medical compound. It all depends on your intention.
Chronic pain doesn't go away when it's inconvenient. THC allows respit and reset.
Single molecule CBD has a bell-shaped curve of therapeutic effect. the higher the dose the less effect. (Biphasic)
- A full plant med will have a wider therapeutic window. CBD has a dose-dependent effect, and you don't lose effect when you get too high.
- A med with will-spectrum, whole-plant components will be most effective over hemp CBD.
Chronic pain is where she sees the greatest improvement. You can wean off opioids with cannabis.
- It's not easy, but it is doable.
In CA there are basically four options that give patients a variety to find relief.
THC rich
CBD rich
- high ratio (i.e.,25:1, 20:1)
- low ratio (i.e. 4:1, 1:1)
THCa rich
CBDa rich
There is CBN rich showing up and THCV on the way.
Patients who do well in her practice: (not an inclusive list)
- IBS
- Crone's
- epilepsy
- Depression
- Anxiety
- sleep disorders
- phantom limb pain
- arthritis
- polypharmacology patients are able to reduce drug load
- psychological disorders
- PTSD
THC benefits
CBD benefits
Terpene overview:
Myrcene: sedating, anti cancer, will move cannabinoids through BBB more efficiently
Pinene: bronchodilator , focus
Linalool: relaxing, baby bath water with lavender, anticonvulsant
Limonene: antidepressant, acid reflux, anti anxiety
Flavonoids are antioxidants, anti inflammatory, anti aging
- green tea and berries are rich in flavonoids
There are companies adding food-grade terpenoids to the oils
- Not a bad thing if terps are coming from a natural source
- It can be a challenge to grow terpenoid-specific profiles for individual patients.
Dr. Goldstein has a book out - "Cannabis Revealed"
We need to change public perceptions. If you have a positive effect with cannabis share that and help to break down the bonds of prohibition and propaganda.
Cannabis is NOT a one size fits all medicine.
- Patients respond to cannabis in individual ways.
How to start
- Determine the goal of treatment. To have a better day? Get a better night's sleep? To treat pain, daytime and nighttime? Treating symptoms or trying for a cure?
- Sometimes people are in a desperate situation and only want results, but you work the protocol from that stated goal.
- Experiment with different types of cannabis, different methods of administration.
- There are hundreds of different compounds in the plant.
- Know enough about the different types of cannabis to be able to make an informed choice. This would come down to terpene profiles.
- One strain will make you sleepy, where another will make you energized. One will eleviate pain where another might aggravate it.
- Understand that the first attempt at cannabinoid therapy might not work. It's a matter of trial and error with a plant that really can't hurt you.
- Cannabis has more of an individual responses than many pharma drugs will.
Sativa and indica aren't helpful anymore. Too much cross breeding.
- Look for the cannabinoid and terpene profiles.
A patient in chemo with symptoms of nausea and bomiting might start with a medicine higher in THC to quell these unwanted symptoms.
- You have to be open to THC inclusion, because a CBD medicine low in THC wouldn't work in most cases.
- For a patient with an aversion to extreme euphoria a formulation can be worked out adding more CBD to the mix, that should tamp down the euphoric effects while still being therapeutically effective.
Someone with extreme inflammation who doesn't desire the intoxication of THC or sleepiness that comes with many high THC strains with particular terpene expressions can work out a formulation higher in CBD.
- You have to balance therapeutic goals with patient concerns. Education becomes a valuable tool.
- Determine if the patient will be using the medicine for daytime or nighttime. Nighttime you can get more THC in.
- An experienced cannabis patient will likely have a higher tolerance for THC, allowing higher doses.
Euphoria helps patients relax and step away from their pain. Her patients describe euphoria as the reset button. It allows them to distance themselves from pain and patterns of pain response and start anew.
Patient response is determined by the coding of your ECS, a genetic coding that you were born with.
- Endocannabinoid Deficiency is a condition that needs to be tended to first before we start treating everything around it, which is all monitored by the ECS anyway.
- The role of the ECS is to maintain cellular messages with the goal of homeostasis.
If you have a genetic disruption in your ECS you won't be able to keep up with demand and disease sets in.
- In such a case you can supplement the ECS with phytocannabinoids.
Dr. Goldstein has two patients with migraine and fibromyalgia; one responds well to THC, the e other hates the way it makes her feel and uses a CBD medicine. Both are doing well.
- Because of the genetic coding and the way cannabinoids interact with the body you're going to get individual effects.
Absorbtion is huge. Some patients absorb well, some not so. If the patient is a poor absorber edibles aren't going to be of much good.
- We don't absorb 100% of the medicine dosed.
- If you're in a very inflamed state you won't absorb well.
- Chemo patients have the gut inflamed from the mouth to the anus.
- Patients with inflamed guts don't get the effects.
- Poor absorbtion may explain most of the disparity in patient effects with the same meds for the same conditions, etc.
Could this be what it is with men who don't feel edibles the way most of us do? I've noticed more men with debilitating chronic back pain don't metabolize cannabis as efficiently through the gut as we'd like. Hmmmm...... They're probably big meat eaters too, which adds to the gut problems and supports imflammation.
Metabolization is broken down into four categories from very poor metabolic rate to ultra-metabolizes.
Allergic reactions to cannabis are few and far between, but we're humans, so that's to be expected.
- Safety regulations haven't gone into effect in California yet, so pesticides may be the culprit.
- Topical allergies might be the most common, but it's not something that shows up very often at all.
Cannabis can potentiate chemo drugs. Studies back this up. This allows the chemo drug to be reduced and have greater effect.
- She now asks for a list of chemo drugs and looks for literature about combinations.
- Cannabis works through receptors and other pathways to kill cancer cells.
- If you're using cannabis to simply counter the side effects of chemo you can get away with low doses, on demand.
- If you're treating cancer outright you're typically looking at lower numbers, although some clinicians are getting good results with lower numbers.
- She has a cancer patient who's 2-yrs old using a cannabis tincture. His low dose of THC and CBD has boosted his appetite, improved his mood, has him laughing and playing again, and healed the sloughing of the tissue inside of his mouth. In his mother's words, "the difference between night and day."
You don't talk cure with cancer. You talk about extension of life.
CBD improves the efficacy of radiation with some cancers.
- We already knew that CBD would protect you from the effects of radiation.
- Combination therapies can get you all of the benefits.
Lack of quality control means you never know for sure that what you buy is what you think you purchased.
- If the terpenoid profile changes from batch to batch - more common than you'd think - the effects can be drastically altered. You wouldn't know that, because the labels only tell you what cannabinoids are in there.
It's going to be up to us to educate our doctors.
Reach for the optimal therapeutic dose.
- Starting low and titrating slowly helps the patient avoid jumping right over that lower, effective dose.
- CBD has a wide therapeutic window.
- It takes longer, but it's worth the time to do it slowly. You won't know how your body will absorb this medication.
People who use cannabis have an obesity rate of around 17%. People who don't use have a rate around 25%.
- The ECS controls, energy metabolism, appetite, how we use calories.
- If you're sleeping well you're not stress-eating.
- Sleep is restorative.
- Rested patients improve their lifestyle choices.
The ECS sends messages that effect how we relax, eat, sleep, protect, and forget.
- Quality of life.
- Cannabis restores the balance. You feel better and you make better choices.
Anxiety can sometimes be dramatically reduced with restoration of sleep.
Administration choices
- Inhalation gives immediate effects. About a 4-hour window.
- Inhalation is often associated with drug behavior, but it works. Vaporization is commonly used for asthma.
- Edibles come in a myriad of choices. Anything that hits the gut is an edible.
- Can last 6-12 hours, dose dependant. The most common way to dose. Metabolization and absorbtion are primary concerns.
- THC is metabolized in the liver. More potent and sedating effect, and also cuts half-life.
- sublingual 15 min to 2.5 hr. onset, 6-8 hr window
- Topicals are as needed.
You can mix and match methods.
- Vaporize to fall asleep following an edible taken earlier to keep sleep going.
Suppositories don't have enough research to the explain disparate results
- Anecdotal evidence is strong.
Seniors: be careful that they don't overdose, thinking the dose must be too low.
Go over your med list to check with drug interactions
- Look for United Patient Group for link to research.
- Warfarin is one to be alert to.
- If you're taking a drug that offers an intoxicating effect and you want to take cannabis, don't take them at the same time. Leave a two hour break at least.
- There is no toxic overdose with THC. Use pinene and limonene to counteract an overdose. It can be psychologically uncomfortable for some patients.
Unless you do blood work to check serum levels you have no way of knowing what the Pharmacokenetics are with this medicine in this patient.
- Through the gut is between 4-25% absorption.
- You can take an edible one day and absorbtion is good, but tomorrow may be way different. Through the gut can be difficult to get consistent dosing with. It is possible but can be dramatically variable.
Have you used cannabis before?
How did you take it?
What was your experience like?
Someone who smoked or used years ago is to be considered a new cannabis patient.
Experiment. Find your strain, your ratio, your preferred terpene profile, your dose.
You can be dependent on cannabis, but it's not possible to get addicted to it.
When THC binds to the receptor it sends the message to the receptor to change the signal the cell is giving off.
When you flood the system with THC you'll lose access to receptors.
Whe you have a deficiency and you're successfully treat with phytocannabinoids the ECS will improve its tone and the need for supplements drops.
The therapeutic window is what works for you.
- Seizure patients use a wide range of doses and ratios
4:1 CBD:THC for arthritis (patient used once a day, in evening to help with sleep). After reducing dose by half he discovered he had therapeutic effect. He'd gone with the higher dose because he was concerned about losing sleep.
The brain has selective downregulation.
CBD saturation (seen in pediatric seizure patients taking high dose CBD meds 3-4 times daily)
- Sometimes a child will begin to have seizures or lose some benefits.
- Solution is to skip doses of CBD until seizures stop. Then you start lower and titrate up again.
- Maybe absorbtion has been compromised. It's all theory at this point.
- Cannabis in general is very safe and can be used with great comfort, but sometimes these things pop up.
THCa and CBDa are not psychoactive, but THCa is an unstable molecule and will quickly convert if not refrigerated.
- Left out for 10 days 25% of the THCa will convert.
- Both cannabinoids have cancer fighting properties and both treat inflammation.
- THCa meds are made cold-pressed or without heat.
- Some pediatric patients don't respond to CBD try THCa.
The findings that THC can proliferate ER+ breast cancers are questionably extrapolated to human patients. The mice in the study had no immune systems.
- She has a patient that followed a THC regimen with ER+ and it killed the tumor cells.
- Breast cancer has become a chronic condition.
- Lots of study points to CBD's ability to kill cancer cells through limiting blood vessel development.
THC is the cannabinoid that attaches to the receptor and gives the strongest benefit for most medical conditions.
- There is a medical dose and a recreational dose, with a little overlap.
- A red dose it to feel good, to get high. A med dose is to treat the condition. You can successfully treat a medical condition with THC if you pay attention to what you're doing.
- Take a small dose, pause and wait to see if you got the therapeutic result you were seeking.
- Most were introduced in the recreational realm, and that confuses the waters. Most med doses are much lower than therapeutic doses.
- THC is a medical compound. It all depends on your intention.
Chronic pain doesn't go away when it's inconvenient. THC allows respit and reset.
Single molecule CBD has a bell-shaped curve of therapeutic effect. the higher the dose the less effect. (Biphasic)
- A full plant med will have a wider therapeutic window. CBD has a dose-dependent effect, and you don't lose effect when you get too high.
- A med with will-spectrum, whole-plant components will be most effective over hemp CBD.
Chronic pain is where she sees the greatest improvement. You can wean off opioids with cannabis.
- It's not easy, but it is doable.
In CA there are basically four options that give patients a variety to find relief.
THC rich
CBD rich
- high ratio (i.e.,25:1, 20:1)
- low ratio (i.e. 4:1, 1:1)
THCa rich
CBDa rich
There is CBN rich showing up and THCV on the way.
Patients who do well in her practice: (not an inclusive list)
- IBS
- Crone's
- epilepsy
- Depression
- Anxiety
- sleep disorders
- phantom limb pain
- arthritis
- polypharmacology patients are able to reduce drug load
- psychological disorders
- PTSD
THC benefits
CBD benefits
Terpene overview:
Myrcene: sedating, anti cancer, will move cannabinoids through BBB more efficiently
Pinene: bronchodilator , focus
Linalool: relaxing, baby bath water with lavender, anticonvulsant
Limonene: antidepressant, acid reflux, anti anxiety
Flavonoids are antioxidants, anti inflammatory, anti aging
- green tea and berries are rich in flavonoids
There are companies adding food-grade terpenoids to the oils
- Not a bad thing if terps are coming from a natural source
- It can be a challenge to grow terpenoid-specific profiles for individual patients.
Dr. Goldstein has a book out - "Cannabis Revealed"
We need to change public perceptions. If you have a positive effect with cannabis share that and help to break down the bonds of prohibition and propaganda.
- Thread starter
- #60
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