SweetSue's Class Notes

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SweetSue

Member of the Year: 2015 & 2016 - Member of the Month: Mar 2015, Sept 2016 - Nug of the Month: Oct 2017 - Creme de la Creme Photos: Dec 2016

Ah Warner has insight into terpenes for topicals. She's the woman who got it written into Washington State law that topicals could be sold in any store that wanted to sell them, and where I learned that b-caryophyllene and linalool will improve the skin absorption of cannabis topicals by creating a transdermal effect. In her opinion it's not worth dealing with DMSO when terpenes already available in canna is will do the job for targeted relief with topicals.

I'll pick up the comments later. This is a panel I've been meaning to dissect for quite some time. She also mentioned high mrycene and high limonene, but my notes were sketchy.
 
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Thread starter #322

SweetSue

Member of the Year: 2015 & 2016 - Member of the Month: Mar 2015, Sept 2016 - Nug of the Month: Oct 2017 - Creme de la Creme Photos: Dec 2016
From Prof of Pot. I brought it here so I wouldn’t have to go looking for it again.

Thank you m’lord. This is a crash course on eCBs. :yahoo:



7 Things You Never Knew About Cannabinoid CB1 Receptors

The cannabinoid CB1 receptor is more complex than the “lock and key” model lets on. Here are 7 facts that everyone should learn.

The “lock and key” model is often used to explain interactions between receptors and their ligands. The CB1 receptor is like the “lock” which is activated by a single “key” such as THC.

While this analogy may be useful for someone new to pharmacology, it is incredibly oversimplified. After reading the 7 facts below, you will be able to appreciate how complex CB1 receptors really are.
And just for fun, let’s see how long we can keep the lock and key analogy going…

1. The CB1 Receptor is Found in Unexpected Places
You expect to find locks on a car door, but not necessarily under the hood inside the engine.

Mitochondria in green [NICHD]The classical view of the CB1 receptor is that it is expressed on the cell surface and its function is to bind a ligand on the outside of the cell and generate a signal on the inside of the cell.

If this were true, then what the *#%! is the CB1receptor doing inside the cell on the mitochondria? This is still being worked out, but by regulating cellular energetics, mitochondrial CB1 receptors may influence memory, and a variety of other brain and bodily functions.


2. The CB1 Receptor Is Always Turned On
It is one of those chain locks that allow the door to be like 10% open, but still secure.
Another outdated model is that the CB1receptor is completely “off” until an endocannabinoid or THC turns it on. Wrong again! The CB1 receptor has what is called constitutive activity. It has a basal level of signaling even in the absence of any ligand that regulates release of neurotransmitters such as GABA.
Drugs called inverse agonists are capable of blocking constitutive activity. They tested a CB1inverse agonist called rimonabant and it produced serious psychiatric issues such as anxiety and depression in some people. It turns out that constitutive activity is important!

3. THC Is A Partial Agonist of the CB1Receptor…Until It’s Not
THC can open a locked door part way, but sometimes it just gets stuck so that better keys can’t open it.

You may have read that THC is a partial agonist at the CB1 receptor. This means that it activates the CB1 receptor, but not all the way. Although this is true in isolated cells, it does not always work that way in real life.
The effects of THC depend on the CB1 receptor density, coupling efficiency, and presence of endocannabinoids that are even stronger CB1receptor agonists. In the right context, THC can actually act like an antagonist and reduce activation of the CB1 receptor.

4. The CB1 Receptor Can Generate Multiple Signals
Sometimes the CB1 receptor opens a door to one hallway, but sometimes the same door leads to a different hallway. We are all in the Twilight Zone.
The old model of the CB1 receptors was that it could activate a single signaling pathway within a cell. Whether it was being activated by THC, an endocannabinoid, or a synthetic cannabinoid didn’t really matter.
Now we know better… not only can the CB1receptor activate different signaling pathways, but different ligands can selectively activate one pathway over the other. This phenomenon is called biased agonism, and opens the possibility of activating the pathways most beneficial for certain conditions while reducing side effects.

5. The CB1 Receptor Gets Around With Other Receptors
Two locks come together and you have to turn multiple keys at the same time as if you were launching nuclear missiles.

Another limitation of the lock and key model is that it shows each lock working independently. Nothing could be further from the truth! The CB1 receptor is floating in a lipid membrane where it can directly interact with many other receptors. In fact, the CB1 receptor can interact with at least 10 other receptor types.
The receptors in each heterodimer pair can modulate each others function in various ways. This is one mechanism of how the cannabinoid system interacts with the opioid system, the serotonin system, the dopamine system, and various others. Let’s not even get into the issue that CB1 may get down with multiple other receptor types at the same time (insert polyamorous joke here).

6. The CB1 Receptor Can Quickly Be Downregulated
If you unlock the door too many times, the keyhole disappears.
Consuming THC multiple times can cause tolerance to its effects. One of the way this happens is through receptor endocytosis – cells literally swallowing the receptor into itself so that there is less of it at the cell surface.
But here’s an interesting twist – CB1 receptor downregulation does not happen equally in all brain areas. This may explain why you can develop tolerance to some effects of THC more than others.

7. Not All CB1Receptors Are the Same
There are many different brands of locks.

Finally, your CB1 “lock” is not mass produced. The CB1 receptor is highly polymorphic, meaning that there is a lot of genetic variation in its DNA sequence. The CB1 receptor that you have is not necessarily the same as that of your neighbors.
Although not all CB1 genetic polymorphisms have functional consequences, several CB1polymorphisms affect expression or signaling. Pharmacogenetic studies have linked these to psychiatric, cardiovascular, and inflammatory conditions and how you respond to THC.
 
Thread starter #324

SweetSue

Member of the Year: 2015 & 2016 - Member of the Month: Mar 2015, Sept 2016 - Nug of the Month: Oct 2017 - Creme de la Creme Photos: Dec 2016
Oh........ that deserves another hug. :5::5::5::5::5: