Spring 2006
O'Shaughnessy's
Journal of the California Cannabis Research Medical
Group
|
Patients Out-of Time Perspectives
PTSD and Cannabis: A Clinician
Ponders Mechanism of Action
By David Bearman, MD
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.
Symptoms
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.
Triggers
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.