PTSD And Cannabis: A Clinician Ponders Mechanism Of Action


One often intractable problem for which cannabis provides relief is post-traumatic stress disorder (PTSD). I have more than 100 patients with PTSD.
Among those reporting that cannabis alleviates their PTSD symptoms are veterans of the war in Vietnam, the first Gulf War, and the current occupation of Iraq. Similar benefit is reported by victims of family violence, rape and other traumatic events, and children raised in dysfunctional families.
Post-Traumatic Stress Disorder
Post-Traumatic Stress Disorder —once referred to as “shell shock” or “battle fatigue” — is a debilitating condition that follows exposure to ongoing emotional trauma or in some instances a single terrifying event. Many of those exposed to such experiences suffer from PTSD. The symptoms of PTSD include persistent frightening thoughts with memories of the ordeal. PTSD patients have frightening nightmares and often feel anger and an emotional isolation.
Sadly, PTSD is a common problem. Each year millions of people around the world are affected by serious emotional trauma. In more than 100 countries there is recurring violence based on ethnicity, culture, religion or political orientation.
Men, women and children suffer from hidden sexual and physical abuse. The trauma of molestation can cause PTSD. So can rape, kidnapping, serious accidents such as car or train wrecks, natural disasters such as floods or earthquakes, violent attacks such as mugging, torture, or being held captive.
The event that triggers PTSD may be something that threatened the person’s life or jeopardized someone close to him or her. Or it could simply be witnessing acts of violence, such as a mass destruction or massacre. PTSD can affect survivors, witnesses and relief workers.
Whatever the source of the problem, PTSD patients continually relive the traumatic experience in the form of nightmares and disturbing recollections. They are hyper-alert. They may experience sleep problems, depression, feelings of emotional detachment or numbness, and may be be easily aroused or startled. They may lose interest in things they used to enjoy and have trouble feeling affectionate. They may feel irritable, be violent, or be more aggressive than before the traumatic exposure.
Seeing things that remind them of the incident(s) may be very distressing, which could lead them to avoid certain places or situations that bring back those memories. Anniversaries of a traumatic event are often difficult.
Ordinary events can serve as reminders of the trauma and trigger flashbacks or intrusive images. Movies about war or TV footage of the Iraqi war can be triggers. People with PTSD may respond disproportionately to more or less normal stimuli —a car backfiring, a person walking behind them. A flashback may make the person lose touch with reality and re-enact the event for a period of seconds, hours or, very rarely, days. A person having a flashback in the form of images, sounds, smells, or feelings experiences the emotions of the traumatic event. They relive it, in a sense.
Symptoms may be mild or severe — people may become easily irritated or have violent outbursts. In severe cases victims may have trouble working or socializing. Symptoms can include:
• Problems in affect regulation —for instance persistent depressive symptoms, explosion of suppressed anger and aggression alternating with blockade and loss of sexual potency;
• Disturbance of conscious experience, such as amnesia, dissociation of experience, emotions, and feelings;
• Depersonalization (feeling strange about oneself), rumination;
• Distorted self-perception —for instance, feeling of helplessness, shame, guilt, blaming oneself, self-punishment, stigmatization, and loneliness;
• Alterations in perception of the perpetrator —for instance, adopting distorted beliefs, paradoxical thankfulness, idealization of perpetrator and adoption of his system of values and beliefs;
• Distorted relationship to others, for instance, isolation, retreat, inability to trust, destruction of relations with family members, inability to protect oneself against becoming a victim again;
• Alterations in systems of meaning, for instance, loss of hope, trust and previously sustaining beliefs, feelings of hopelessness;
• Despair, suicidal thoughts and preoccupation;
• Somatization —for instance persistent problems in the digestive system, chronic pain, cardiopulmonary symptoms (shortness of breath, chest pain, dizziness, palpitations).
• Cannabis
Ample anecdotal evidence suggests that cannabis enhances ability to cope with PTSD. Many combat veterans suffering from PTSD rely on cannabis to control their anger, nightmares and even violent rage. Recent research sheds light on how cannabis may work in this regard.
Neuronal and molecular mechanisms underlying fearful memories are often studied in animals by using “fear conditioning.” A neutral or conditioned stimulus, which is typically a tone or a light, is paired with an aversive (unconditioned) stimulus, typically a small electric shock to the foot. After the two stimuli are paired a few times, the conditioned stimulus alone evokes the stereotypical features of the fearful response to the unconditioned stimulus, including changes in heart rate and blood pressure and freezing of ongoing movements. Repeated presentation of the conditioned stimulus alone leads to extinction of the fearful response as the animal learns that it need no longer fear a shock from the tone or light.
• Fear Extinction
Emotions and memory formation are regulated by the limbic system, which includes the hypothalamus, the hippocampus, the amygdala, and several other structures in the brain that are particularly rich in CB1 receptors.
The amygdala, a small, almond-shaped region lying below the cerebrum, is crucial in acquiring and, possibly, storing the memory of conditioned fear. It is thought that at the cellular and molecular level, learned behavior —including fear— involves neurons in the baso-lateral part of the amygdala, and changes in the strength of their connection with other neurons (“synaptic plasticity”).
CB1 receptors are among the most abundant neuroreceptors in the central nervous system. They are found in high levels in the cerebellum and basal ganglia, as well as the limbic system. The classical behavioral effects of exogenous cannabinoids such as sedation and memory changes have been correlated with the presence of CB1 receptors in the limbic system and striatum.
In 2003 Giovanni Marsicano of the Max Planck Institute of Psychiatry in Munich and his co-workers showed that mice lacking normal CB1 readily learn to fear the shock-related sound, but in contrast to animals with intact CB1, they fail to lose their fear of the sound when it stops being coupled with the shock.
The results indicate that endocan-nabinoids are important in extinguishing the bad feelings and pain triggered by reminders of past experiences. The discoveries raise the possibility that abnormally low levels of cannabinoid receptors or the faulty release of endogenous cannabinoids are involved in post-traumatic stress syndrome, phobias, and certain forms of chronic pain.
This suggestion is supported by our observation that many people smoke marijuana to decrease their anxiety and many veterans use marijuana to decrease their PTSD symptoms. It is also conceivable, though far from proved, that chemical mimics of these natural substances could allow us to put the past behind us when signals that we have learned to associate with certain dangers no longer have meaning in the real world.
What is the Mechanism of Action?
Many medical marijuana users are aware of a signaling system within the body that their doctors learned nothing about in medical school: the endocan-nabinoid system. As Nicoll and Alger wrote in “The Brain’s Own Marijuana” (Scientific American, December 2004):
“ Researchers have exposed an entirely new signaling system in the brain: a way that nerve cells communicate that no one anticipated even 15 years ago. Fully understanding this signaling system could have far-reaching implications. The details appear to hold a key to devising treatments for anxiety, pain, nausea, obesity, brain injury and many other medical problems.”
As a clinician, I find the concept of retrograde signaling extremely useful. It helps me explain to myself and my patients why so many people with PTSD get relief from cannabis.
We are taught in medical school that 70% of the brain is there to turn off the other 30%. Basically our brain is designed to modulate and limit both internal and external sensory input.
The neurotransmitter dopamine is one of the brain’s off switches.The endocannabinoid system is known to play a role in increasing the availability of dopamine. I hypothesize that it does this by freeing up dopamine that has been bound to a transporter, thus leaving dopamine free to act by retrograde inhibition.
By release of dopamine from dopamine transporter, cannabis can decrease the sensory input stimulation to the limbic system and it can decrease the impact of over-stimulation of the amygdala.
I postulate that exposure to the PTSD-inducing trauma causes an increase in production of dopamine transporter. The dopamine transporter ties up much of the free dopamine. With the brain having lower-than-normal free dopamine levels, there are too many neural channels open, the mid-brain is overwhelmed with stimuli and so too is the cerebral cortex. Hard-pressed to react to this stimuli overload in a rational manner, a person responds with anger, rage, sadness and/or fear.
With the use of cannabis or an increase in the natural cannabinoids (anandamide and 2-AG), there is competition with dopamine for binding with the dopamine transporter and the cannabinoids win, making a more normal level of free dopamine available to act as a retrograde inhibitor.
This leads to increased inhibition of neural input and decreased negative stimuli to the midbrain and the cerebral cortex. Since the cerebral cortex is no longer overrun with stimuli from the midbrain, the cerebral cortex can assign a more rational meaning and context to the fearful memories.
I have numerous patients with PTSD who say “marijuana saved my life,” or “marijuana allows me to interact with people,” or “it controls my anger,” or “when I smoke cannabis I almost never have nightmares.” Some say that without marijuana they would kill or maim themselves or others. I have no doubt that cannabis is a uniquely useful treatment. What remains is for the chemists to determine the precise mechanism of action.

Oregon in Denial Over Cannabis as an Antidepressant

By Ed Glick
I’ve been working as a nurse for 25 years, about half of that in acute care mental health nursing at Good Samaritan Regional Medical Center in Corvallis, Oregon. Eight years ago the Oregon Medical Marijuana Act pass-ed by the initiative process and a state program began registering patients.
It wasn’t long before I started meeting patients coming into the regional mental health unit who reported that they were using cannabis to self-medicate for a variety of mental-health symptoms. It wasn’t long after that that I started volunteering at the Compassion Center, a volunteer medical facility that helps assist patients with education, support and registration into the medical marijuana program.
Pretty soon I started seeing the same patients who were having psychiatric emergencies coming to the Compassion Center to see me for cannabis recommendations, which I can’t provide and which, actually, they couldn’t get because there is no allowance in Oregon for psychiatric treatments. All the “debilitating conditions” are physical with the exception of Alzheimer’s agitation.
In Corvallis, a very progressive community, there is virtually no doctor who will recommend cannabis for cancer pain or for severe nausea or AIDS. The whole medical system of Corvallis said “No, you’re locked out.” So then I go down to the Compassion Center and all these people from the medical system that I’m employed in say, “My doctor won’t do it, he’s afraid he’ll lose his license.”
So we assist these people by trying to find a physical correlation to their psychiatric symptom. For example, if they’re having PTSD symptoms they might be sick and have physical symptoms.
How high a percentage of these people were treating psychiatric symptoms? I put together a very simple survey to find out. I reviewed 172 charts. The average patient age was 43. All the patients were registered in OMMA; 95% were registered for pain. A very large percentage of Oregon registrants are pain patients.
Some 40% had multiple qualifying conditions (not including psychiatric) —physical pain and nausea, for example. Pain and with spasticity —they often go together.
The results: 64% of the patients in the survey showed some kind of significant psychiatric benefit; 39% reported insomnia relief; 5% reported PTSD symptom relief, many of them veterans who go to the VA hospital in Roseburg and are denied. The VA doctors tell them “No, I can’t. I’ll lose my DEA license.” They just don’t want to stand up to it —although they’re beginning to refer patients to us, which is kind of interesting.
Anxiety, 11%; depressive symptoms, 11%; 15% of the cohort reported that they were using cannabis to decrease the side effects of medications; 56% reported reduced use of medications.
What these patients report to me is that they’re sick and tired of Vioxx and they’re sick and tired of Flexeril, Vicodin —people are literally sick of these drugs. They can’t sleep, they can’t function, they’re drugged up, they don’t have any enjoyment of life.
When they start using cannabis they leave off the Vioxx and they leave off the Vicodin. Vicodin has a place, but for long-term pain management it is really poor.
Appetite stimulation —tremendously important for people who are in pain all the time— was 20%.
I put the survey together as a request to the Oregon Department of Human Services to reconvene the Debilitating Conditions Advisory Panel, which I was a member of in 2000. At that time nine patients had submitted requests to include psychiatric conditions to the list.
The state health officer did a fairly good job of bringing together the panel, but the whole thing was skewed from the outset by political manipulation by the governor’s office and by the head of the Department of Health Services. The information that they would allow us to consider had to be filtered through rules stating that if it’s not a double-blind, peer-reviewed clinical trial, it doesn’t get a lot of evidentiary weight.
We were not allowed to give much weight to patients’ reports. And of course there was no relevant double-blind, peer-reviewed clinical trial. So the panel was set up to fail.
A few patients came in and gave very compelling testimonials. And then out of nowhere came a whole bunch of medical experts —psychiatrists from Oregon Health Sciences University and the National Alliance for the Mentally Ill— and they just had fits. “This is quackery,” they said.
The only person who even differentiated between affective depressive-type disorders and schizophrenic thought disorders was one of the patients. None of the doctors even made any differentiation between these two completely different sets of medical problems.
After a long, protacted time we all wrote our comments out, and there was a vote, and we voted to add affective disorders —severe agitation and depressive symptoms. Didn’t happen. They finally did add Alzheimer’s agitation.
So, five years later I brought in the study I’d done with OMMP registrants and asked them to reconvene the Debilitating Conditions Panel based on this new evidence showing that indeed there is some psychiatric effect that people are getting from their cannabis use. And they rejected the request with a “summary denial.”
Then Lee Berger, an attorney in Portland, asked if I’d be willing to sue the Department of Human Services’ OMMP and I said yes. We filed our petition for judicial review in February —a formal request “to Add Clinical Depression, Depressive Symptoms, Post-Traumatic Stress Disorder (PTSD), Severe Anxiety, Agitation and Insomnia, to Those Diseases and Conditions Which Qualify as ‘Debilitating Medical Conditions’ under the Oregon Medical Marijuana Act.” And it worked! I can’t believe it!
We got word last week that, because the OMMP doesn’t really want to go to court, they’ve decided to kind of sue for peace. All we’re asking is that they reconvene a panel to evaluate these conditions. So, we’re in the process of negotiatng with them to get this thing back on track.
We want to close some of the loopholes that allow them to skew the evidence base. It’s pretty clear that there are a lot of patients who are using cannabis for insomnia, for mood stabilizing, and for peace. Just for a a very simple, elemental peace, especially with chronic diseases like severe chronic pain. Cannabis is actually a miracle drug for pain, in my opinion.
There’s no question the last thing the pharmacy industry wants is millions and millions of Americans growing and using their own medicine that covers such a wide array of diseases.

Rodney Dangerfield’s Lifelong Romance With Marijuana

By Joan Dangerfield
The comedian’s widow gave this talk at the Patients Out of Time conference on cannabis therapeutics in Santa Barbara April 7.
If Rodney were here today he would say something brilliant. He would probably open with a marijuana joke. He’d say, “I tell ya, that marijuana really has an effect on you. The other day I smoked a half a joint and I got so hungry, I ate the other half.”
Rodney had a fantastically unique mind. Few people knew he was a mathematical genius, but everyone knew he was hilarious. His humor was a razor thrust into social hypocrisy and the little injustices of life. He wrote “killers” and made the world laugh.
Another thing that was not widely known about Rodney is that he endured quite a bit of personal suffering in his life. He was heartbreakingly neglected as a child. We’ve all heard the expression “the tears of a clown,” and in many ways Rodney embodied that experience. Like most geniuses, the special chemistry that created his remarkable mind also created certain psychological challenges. Acute anxiety and manic depression were congenital issues that plagued Rodney’s life.
To give you an idea of how his anxiety would manifest itself, Rodney couldn’t sit still. In Caddyshack, his character, Al Cervic, is constantly fidgeting like he’s about to burst out of his skin. The truth is, this was no act. Rodney was under duress. He felt Chevy Chase was talking too slowly and it got on his nerves. Rodney’s impatience would come out through his body. The pace of the whole world was too slow for him until he found marijuana.
Rodney first lit up back in 1942 when he was 21. He was hanging out with a comic named Bobby Byron and his friend Joe E. Ross —some of you might remember Joe E. Ross from Car 54. They went to the Belvedere Hotel in New York where Bobby lived. The night would prove to have such an impact on Rodney’s life that he even remembered the room number they were in —1411.
Although he was supposed to be enjoying himself with friends, Rodney was characteristically agitated and anxiety ridden. It’s how he felt every day of his life to that point. But when Rodney got high, he couldn’t believe it.
For the first time in his life, he left relaxed and peaceful, and had a sense of well-being. That night marijuana became a new friend that would be in Rodney’s life for the next 62 years.
I met Rodney in 1983, and after a 10-year courtship, Rodney and I enjoyed 11 years of marriage. I must admit that when I became a part of Rodney’s life, I did not approve of his marijuana use. My Mormon background hadn’t given me experience with any illegal substances and I was always afraid Rodney would get arrested.
Rodney was concerned about my feelings and agreed to look for legal alternatives to treat his ailments. Over the years we consulted the best experts we could find in search of legal anti-anxiety and pain medications and even tried Marinol. But nothing worked for him the way real marijuana did.
A couple of years ago Rodney was in the process of writing his autobiography, in which he wanted to be very candid about everything in his life. He even wanted to title the book “My Lifelong Romance with Marijuana.”
I was sure then that Rodney would be arrested. So I looked for, and found, Dr. David Bearman here in Santa Barbara.
Dr. Bearman examined Rodney and obtained records from Rodney’s other doctors for review. In addition to his anxiety and depression, at the time Rodney’s medical conditions included constant pain from the congenital fusion of his spine, an inoperable dislocated shoulder and rotator-cuff tear and arthritis. Rodney wasn’t able to take traditional pain medications because of their interactions with his blood-thinning medication, Coumadin.

We were elated a few days after that initial visit with Dr. Bearman when Rodney’s medicinal use was approved. Rodney showed the approval letter to everyone and carried miniature versions in his pockets. Ever the worried wife, I included a copy of the letter in the memory box of his casket in case the feds were waiting for him at the Pearly Gates.
Even though Rodney endured numerous health challenges over the years, including aneurysms, heart surgeries and a brain bypass, he remained active and vital during his last incredible year. He swam regularly, went on a multi-city press tour to promote his best-selling book (the publisher made him change the title to “It’s Not Easy Bein’ Me”), recorded an album of love songs called “Romeo Rodney,” and wrote countless new jokes.
After all those years of pot smoking, his memory and his joke-writing ability did not suffer and his lungs were okay. He was as sharp as ever.
Even moments after brain surgery Rodney didn’t miss a beat. Rodney’s doctor came to his bedside after he was taken off the respirator. He said, “Rodney, are you coughing up much?” And Rodney said, “Last week, five-hundred for a hooker.”
Some of you may be aware that 4:20 is a symbolic time of day for many marijuana enthusiasts. About a year after Rodney’s brain surgery, he had heart surgery and due to complications his life ended… Coincidentally, or perhaps meaningfully, at 4:20 p.m. EST.

By David Bearman, MD