Clinical Update on Marijuana/Cannabis/THC - Dale Mortimer, M.D.

Clinical Update on Marijuana/Cannabis/THC

INTRODUCTION

Below is Dr. Mortimer's synthesis of what he believes to be credible, non–biased, recently published studies and other articles on marijuana/ cannabinoids – plus his clinical experience over the past 35+ years as: a child and adolescent psychiatrist; a general adult psychiatrist; a former addiction psychiatrist; an ex–prison psychiatrist (who “paroled” in 1997); and as a parent who in June 2016 while on vacation in Canada was inadvertently poisoned by an innocent–looking but THC–laced peanut butter and jelly sandwich. Dr. Mortimer has excerpted liberally from the articles and books cited at the conclusion of this summary. Lastly, for an example of how high–dose and frequent cannabis abuse can masquerade as chronic schizophrenia, see Dr. Mortimer's companion piece: “Clinical Lessons Learned About Cannabis Over the Past Thirty–Five Years – Starting with James.”

The most common varieties of marijuana are Cannabis sativa and Cannabis indica. Marijuana is composed of more than 400 chemical compounds, including over 60 cannabinoids that contribute to its psychopharmacological effects. The primary psychoactive constituent of cannabis is delta–9–tetrahydrocannabinol (THC). Other plant cannabinoids include delta–8–tetrahydrocannabinol; cannabinol; and cannabidiol (CBD). CBD is the second major psychoactive constituent of cannabis. The ratios of THC and CBD and other cannabinoids vary widely in the various preparations of cannabis. In the 1960s, the THC content of marijuana plants was thought to be somewhere in the range of 1–3%; today the THC content can reach up to 20%. Furthermore, those who “dab” are smoking up to 96% pure THC. The potency of today’s marijuana preparations is so great today compared to what the hippies and others were smoking in the 1960s that we might as well be discussing two different drugs.

According to the National Survey of Drug Use and Health, more than 47% of American age 12 or older have used marijuana  during their lifetime. About 45% of 12th graders and more than 50% of 18– to 25–year–olds have tried cannabis, and cannabis use is steadily increasing. A 2012 study by Salomonsen–Sautel et al found that 74% of 164 adolescents (age 14 to 18 years old) surveyed in a Denver area chemical dependence treatment program had used someone else’s medical [sic] marijuana; most of these chemically dependent adolescents started using marijuana at 12 years of age, and they reported having used diverted medical marijuana (i.e., they personally used someone else’s medical marijuana) a median of 50 times (with a range of 1 to 1,000 times).

Any cannabis product found in the blood increases the risk of a fatal car crash by 280%; and the psychomotor impairment (e.g., slower reaction time and problems with coordination) resulting from cannabis can continue for three weeks after the last cannabis use. Since over 19,000,000 American have used marijuana within the past month, and since marijuana/ cannabinoids are metabolized much more slowly than is alcohol, then at any one time, there are a lot of cannabis–impaired drivers on our public roads.

THC is a fat–soluble molecule which crosses both the blood–brain barrier and the placenta, and accumulates in adipose tissue (e.g., in the lipids found in our neurons’ cell membranes), where its half–life ranges from several days to a week. THC acts on natural cannabinoid receptors (e.g., anandamide), which are located throughout the brain. Discovered in 1988, anandamide and the endocannabinoid system help regulate a variety of neuron functions and how much neurotransmitter is released when the neuron is stimulated. The neurotransmitters that are affected by THC include dopamine, glutamate, endorphins, and serotonin. These neurotransmitters affect perception of pleasure, mood, pain, and appetite; motivation, memory, and muscle activity. The endocannabinoid system helps keep brain cell activity in a homeostatic balance. When THC artificially stimulates cannabinoid receptors, the function of the natural cannabinoid system is disrupted.  The endocannabinoid system is also important in regulating brain development in immature brains (i.e., children and adolescents). Because the natural cannabinoid system modulates neuronal activity, it plays a major role in neuroplasticity (i.e., how brain cells develop new synapses and how they connect to other neurons in response to a novel stimulus). However, exogenous THC has much stronger, longer–lasting effects and interferes with normal neuronal cell function and growth (including the normal neuronal pruning of the developing child and adolescent brain). Thus, use of cannabis in children and adolescents increase the likelihood of causing a psychotic episode.

Each marijuana joint contains about 0.5 grams of active ingredient; therefore, one ounce [28.35 grams] of today’s marijuana is enough to roll about 56 joints. Thus, those persons who posses one ounce of marijuana are not using marijuana for “personal use” are execrable drug dealers until proven otherwise.

POLITICS

As everyone knows, there is a growing movement across the United States legalizing the medical and recreational use of marijuana.The District of Columbia and well over half of the country’s 50 states have passed legislation removing state–level penalties for the use of marijuana by patients who have obtained medical certification that their medical condition would most likely benefit from the use of marijuana (which in almost all cases, in retrospect, is almost complete flapdoodle). There is, however, one medical condition the clinical data for which is so strong that it justifies the title of “medical marijuana” and that is, the use of marijuana or cannabinol for the treatment of nausea and vomiting caused by cancer chemotherapy. Thus, dronabinol [purified oral Delta9–tetrahydrocannabinol (THC)] and nabilone (an oral THC analog) have been approved in the United States for the treatment of nausea and vomiting associated with cancer chemotherapy.

Do note: there are no studies looking at medical marijuana use in children. This becomes relevant in the discussion of cannabis diversion to children and adolescents below.

Other than for the treatment of nausea and vomiting associated with cancer chemotherapy, the various states’ list of medical conditions for which medical marijuana is claimed to be effective is complete bullshit. It appears that at least once, the Feds got it right, and marijuana rightly continues to be a Schedule I substance under United States Federal Law (– examples of other Schedule I substances include such popular substances as: heroin and LSD). While varying from state to state, here is the list of conditions (in at least one state) which qualify for a medical marijuana card:

More people use marijuana than any other illicit drug, and more people meet criteria for marijuana addiction than to any other illicit drug. And I argue here that the vast majority of people who hold a state medical marijuana card ("medical card") are not in the midst of receiving cancer chemotherapy.

In its Public Policy Statement on Medical Marijuana, the American Society of Addiction Medicine clearly rejects smoking marijuana as a means of drug delivery. ASAM further recommends that “…cannabis, cannabis–based products, and cannabis delivery devices should be subject to the same standards that are applicable to other prescription medications and medical devices and…should not be distributed or otherwise provided to patients until such products or devices have received marketing approval from the Food and Drug Administration.” ASAM also “discourages state interference in the federal medication approval process.” ASAM has also stated that ASAM “does not support the legalization of marijuana.”

Policies for “medical marijuana” seems to be based primarily on profit and addiction. State–approved “medical marijuana” is largely a political decision not based on solid medical data. In addition, while the public may want to expand availability of marijuana to recreational users, it is doubtful that the public understands that many marijuana users are heavy users, not recreational users. ‍

RISKS ASSOCIATED WITH ACUTE MARIJUANA/CANNABIS/THC USE

The data demonstrating the potential harms of marijuana/cannabinoids are clear and convincing. The most commonly reported side effects in clinical trials of cannabinoids include:

In trials of smoked marijuana, probably everyone by now knows the common side effects of acute marijuana intoxication, which may include:


Other side effects of acute marijuana intoxication may include:

More worrisome, potential adverse effects as a consequence of marijuana/ cannabinoids may include:

CANNABIS/THC/MARIJUANA TOLERANCE, DEPENDENCE AND WITHDRAWAL

There is a distinction between experimental use, abuse and substance dependence. Regular cannabis use is defined as smoking cannabis at least four times per week. Heavy use is defined as smoking a half–ounce of marijuana per week. While most people who use cannabis do not become dependent [i.e., chemically addicted] to marijuana/cannabis, some will develop an addiction. For daily marijuana users, it is estimated that 25% to 50% will become addicted to marijuana. Cannabis use typically crosses the line into cannabis dependence/addiction when a person uses marijuana daily or nearly every day. Marijuana/cannabis addiction means: repeated and compulsive use of cannabis despite harm; a predictable chemical withdrawal syndrome; difficulty quitting cannabis; loss of control over cannabis consumption; loss of interest in activities not involving cannabis; recurrent use resulting in failure to fulfill major obligations; and high relapse rate.  Adults who seek cannabis dependence treatment average more than 10 years of daily or almost daily cannabis use, and average about 6 attempts to reduce or stop cannabis consumption. About 9% of adults and 17% of adolescents who use cannabis develop an addiction to cannabis (– and 9% or 17% of 18 million cannabis users is a substantial number of cannabis addicts). Most people with any sort of addiction problems do not seek treatment, and in this way, those people with cannabis addiction are no different than other addicts. In fact, those with cannabis addiction are even less likely to seek treatment since they are bombarded with inaccurate messages in the mass media that cannabis is not addictive.

In a 2007 study, genetic factors accounted for 35% of the heritability of marijuana/cannabis/THC addiction; and environmental factors accounted for 47%.

The basis for marijuana’s chemical addictive action is located in various portions of the brain, and its addiction potential is subserved in the mesolimbic system, similar to how other addicting drugs work. Cannabinoid receptors and endogenous cannabinoids have been isolated, and marijuana is believed to act at the cannabis receptors, similar to endogenous opioids.

While marijuana is considered a “soft drug” by many, marijuana is, in fact, more similar to “hard drugs” like heroin and cocaine than it is different from them. Specifically, marijuana leads to a dramatic increase in the release of of dopamine in the brain – dopamine is a neurotransmitter involved in the brain’s pleasure, reinforcement, and reward centers. In humans, marijuana tolerance develops to its effects on mood, memory and cognition, heart rate, blood pressure and hormones. The magnitude of marijuana tolerance is proportional to the dose and duration of marijuana exposure.

While very few people are aware that stopping cannabis use can cause a cannabis withdrawal syndrome, stopping cannabis, in fact, can and does cause a cannabis withdrawal syndrome – with cannabis  withdrawal especially causing anxiety, irritability and insomnia – similar to tobacco/nicotine withdrawal. Most symptoms of cannabis withdrawal appear within one day of abstinence, peak within 10 days, and resolve within 1–3 weeks, although some studies reported withdrawal symptoms persisting longer than 4 weeks.

Clinical studies suggest that smoked marijuana is associated with poor social outcomes and employment, lower income, lower levels of life satisfaction, and lower levels of relationship satisfaction.

The Cannabis/THC/marijuana withdrawal syndrome is characterized by some or all of the following:

➛ Aggression

➛ Anger and increased irritability

➛ Anxiety

➛ Appetite changes

➛ Depressed mood

➛ Marijuana craving

➛ Physical discomfort

➛ Restlessness

➛ Difficulty falling asleep, difficulty staying asleep, and/or strange dreams

➛ Stomach pain

➛ Sweating

➛ Weight loss

ACUTE ADVERSE COGNITIVE DEFICITS ASSOCIATED WITH CANNABIS/THC/MARIJUANA

Marijuana/cannabis impairs mental and physical coordination, alters perceptions of time and surroundings, distorts comprehension of information and cognition, and interferes with insight and judgment. While these changes are usually transient, they may be persistent in certain cases. Cannabis causes users to become “stoned,” which includes a perceptual distortion of time, and can induce psychotic symptoms consisting of hallucinations, paranoia, and delusions. In persons with pre–existing schizophrenia, marijuana can worsen the course of illness, and in bipolar disorder, marijuana can precipitate a manic episode with or without pre–existing identified bipolar disease. Cannabis can cause anxiety and depression in its users, which might include brief panic reactions, but in other persons, long–lasting psychotic symptoms have been described. Cannabis impairs the capacity for users to properly operate machinery and vehicles, and under the influence of cannabis, high rates of traffic accidents and deaths have been reported.

Acute effects of marijuana/cannabis and other cannabinoids can acutely impair several domains of cognitive functioning. Among other things, cannabis disrupts the function of the hippocampus, which is the brain structure crucial to memory. Cognitive impairment from cannabis includes:

➛ Impaired allocation of attention and divided attention;

➛ Impaired associative learning;

➛ Impaired danger perception;

➛ Impaired distance estimation;

➛ Impaired information processing speed;

➛ Impaired motor coordination;

➛ Impaired procedural memory;

➛ Impaired reaction time;

➛ Impaired set shifting;

➛ Impaired signal detection;

➛ Impaired spatial working memory and spatial maze accuracy;

➛ Impaired time estimation;

➛ Impaired tracking accuracy; and

➛ Impaired verbal accuracy, verbal learning and recall

PERSONAL EXPERIENCE WITH ACUTE CANNABIS POISONING. On July 23, 2016, while driving to a photographers’ workshop and waiting for my son and wife to return from walk before we completed the last leg to our destination, I looked around our Vancouver, British Columbia apartment for something to eat. I found two baggies, each containing identical–looking peanut butter and jelly sandwiches, with the only difference being a fading inked cryptic “X” on the  outside of one of the plastic baggies. Opening up the X–marked baggie, I nibbled on perhaps a an eighth of the sandwich before my son and wife returned from their outing. After being unjustly accused of eating the wrong peanut butter and jelly sandwich (– heck, they looked the same to me!), I put the remainder of the purloined sandwich back in the baggie and packed it away in a cooler. We then packed the car, and began traveling the last leg to our final destination, with my wife offering to take the wheel so that I got a reprieve from driving. I rested in the back seat of our car. About an hour into the drive, I experienced the sudden onset of a distinct and disturbing change in my sensorium and thinking. Was I having a heart attack? I then checked my pulse: it was strong and regular. Was I having a migraine? No, I’ve never had a migraine and, besides, I wasn’t experiencing any pain. Was I having a stroke? I then checked my motor function, including hand coordination – it also was normal. But I found myself too befuddled to even speak. Was I car sick? Well, I was mildly nauseous, but this wasn’t really that, either. Some acute infection? No - no fever, chills. Had I been poisoned? But by what ?– a peanut butter and jelly sandwich? No, impossible! Should I say something to my wife? Well, maybe – but I couldn’t concentrate intently enough to utter anything resembling human speech. Should we divert the car to an emergency department at hospital? In a foreign country? No. As we drove along, I sunk deeper into a cognitive abyss, becoming increasingly unable to think logically, and sensing a growing foreboding that my worsening cognitive difficulties – including my inability to even speak one word – was most certainly permanent. I became resigned to the idea that I would be completely and utterly disabled – a veritable vegetable – forever after. Concluding that I was simply car–sick as we arrived at our destination, my wife suggested that she drop me off at a bench on the side of a  manicured park area while she and our son registered for the scheduled three–day event, and then unpacked the car. I was barely able to stumble out of the car and then to the bench. I sat on the bench with my head between my knees, unable to move, realizing that I was completely defenseless against an attack from any nefarious miscreant who might wander by. It was about an hour later that I learned the appalling truth about the cannabis–laced peanut butter and jelly sandwich! I was too cognitively compromised to verbally express my great displeasure. My son held me upright as I stumbled to the cottage, and with his help, I was able to collapse into my bunk bed by 6:30PM. I then slept 12+ hours. Still a bit “zonked” the next morning, I was at least reassured by the information that I had merely been inadvertently acutely poisoned by highly potent cannabis concealed in peanut butter and jelly 20 hours earlier, I slowly regained my ability to speak, walk and – eventually – think clearly again, feeling almost back to normal by the end of the next day. Consider this: I had only consumed an eighth of the intended cannabis dose that fateful day. Good thing I wasn’t driving when the cannabis dose hit my brain!

LONG–TERM ADVERSE EFFECTS ASSOCIATED WITH MARIJUANA/ THC/CANNABIS

Long–term effects of marijuana/cannabis and other cannabinoids can acutely impair several domains of cognitive functions, resulting in:

➛ Poor academic performance;

➛ Impaired motivation probably due to a marijuana–induced depressive disorder;

➛ Cognitive decline as measured by decreased attention; decreased frontal lobe executive functioning [– the ability to perform tasks that require complex thinking]; decreased memory; and decreased IQ [–the IQ decline is greatest in those who begin using marijuana before age 16 years of age (8 point IQ decline) versus     adulthood (6 point  IQ decline). This statistical trend of lowered IQ may not reverse after stopping cannabis. If the lowered IQ is reversed, it may take up to two years of abstinence before cognitive  improvement is identified.

ADVERSE EFFECTS OF MARIJUANA/THC/CANNABINOIDS ON DRIVING

Cannabis is the most common illicit drug implicated in motor vehicle fatalities. Epidemiological data suggests that recent cannabis use doubles the risk of a motor vehicle accident. Occasional users of cannabis are more sensitive to the driving impairing effects of cannabis and THC than heavy users. Marijuana/cannabis and cannabinoids are well–known to impair a number of driving–related conditions including:

➛ Attention

➛ Distance estimation

➛ Procedural memory

➛ Processing speed

➛ Reaction time [It takes a longer period of time for a marijuana–impaired driver to

   react after seeing a child runs into the street in front of him or her.]

➛ Time estimation

➛ Tracking accuracy

➛ Working memory

➛ Marijuana and THC significantly impair on–road driving to levels equivalent to

    driving with blood alcohol levels of 0.05% to 0.1% (legal intoxication in

   Oregon and Washington is 0.08%).

➛ Those under the influence of both alcohol and marijuana are even more

    impaired in their driving, and the effect is synergistic rather than merely

    additive.‍

OTHER PROBLEMS ASSOCIATED WITH MARIJUANA/ CANNABIS/CANNABINOID USE
Increasing research on the endocannabinoid system (which, in general terms, regulates the brain’s neurotransmitter systems) shows that the brain’s own natural cannabinoid system (endocannabinoid system) plays a crucial role in brain development and maturation (for example, neurogenesis, axon elongation, neural differentiation and migration, glia formation, and synaptic pruning), especially during adolescence and early adulthood. The endocannabinoid system also plays an important role in mediating hypothalamic–pituitary–adrenal axis stress responsiveness. Perturbing these brain systems with exogenous cannabinoids has have both immediate and long–term effects. Although occasional (– that is, neither regular nor heavy) marijuana use may be of little consequence to health adults, use among adolescents is a serious public health concern. Among other things, adolescents who regularly use cannabis are at a much greater risk for developing: impaired motivation, depressed mood, impairing anxiety, reduced academic performance, lower educational attainment/grades, and potentially even school dropout. MRI scans show that cannabis exposure during adolescence has significant effects on brain volume, the folding patterns of the cortex of the brain, neural connectivity, and white matter integrity.

Since reports on depression have failed to identify any trend wherein adolescent depression predicts cannabis use in adulthood, this provides evidence against the hypothesis that this cannabis–depression link is explained by adolescents at risk for depression using cannabis to self–medicate emerging symptoms. As is the case in alcohol dependence so it is the case in those with cannabis abuse: substance abuse starts first, with depressed mood in substance abusers occurring sometime after the onset of the substance abuse.

Another important association (especially identified in studies of monozygotic and dizygotic twins discordant for adolescent cannabis use) between heavy cannabis exposure and dysregulated mood sequelae in adolescence is the increased risk for suicide in early adulthood.

Although medical marijuana is currently approved only for those over the age of 18 years old, it has and will continue to make its way into the hands (and mouths) of children and adolescents – as shown by Salomonsen–Sautel’s 2012 study; and as shown by the increasing number of emergency department admissions for unintentional marijuana ingestion (e.g., including accidental ingestion of marijuana edibles by unsuspecting victims). This also means that medical marijuana will also be diverted to adolescents and adults who are at an increased vulnerability to addiction. Those with: brain injuries; fetal alcohol effects; and the mentally retarded are the three risk groups at greatest risk for the rapid development of seriously impairing marijuana addiction and worsening cognitive compromise.

SUMMARY AND CONCLUSIONS

After earning his medical degree (M.D.) from Oregon Health Sciences University in 1985, Dr. Mortimer continued at OHSU to complete general adult psychiatry training, and then a two–year child & adolescent psychiatry fellowship training program. After completing his training, Dr. Mortimer did a favor for a friend, and the next thing he knew, Dr. Mortimer was in prison, serving as the principle psychiatrist for the Oregon Department of Corrections from 1990 to 1997. While Dr. Mortimer’s son might try (unsuccessfully) to devalue and ignore his father’s extensive clinical expertise and wise counsel about cannabis, alcohol, and other substances of abuse, nevertheless, at last count, Dr. Mortimer has successfully served as psychiatric consultant to four separate out–patient, long–term residential, and hospital–based chemical dependence treatment programs. And over the past 31+ years, Dr. Mortimer has enjoyed seeing some of his many clinical writings published in peer–reviewed international medical journals.

Among Dr. Mortimer’s many professional medical accomplishments, Dr. Mortimer is a diplomate of (– that is, he has a diploma in general adult psychiatry from) the American Board of Psychiatry and Neurology (i.e., Dr. Mortimer is “Board Certified in Psychiatry”). Dr. Mortimer has also served as clinical teaching faculty for Oregon Health Science University’s Department of Psychiatry, and for the Family Practice Training Program at Eastmoreland Osteopathic Hospital in Milwaukie, Oregon. Dr. Mortimer has served as both a principle investigator and as a clinical investigator for an assortment of phase III clinical drug trials,

Dr. Mortimer is currently licensed to practice medicine only in the State of Washington, maintaining a full–time, solo private practice in child, adolescent, and general adult psychiatry in the non–incorporated Hazel Dell neighborhood of Vancouver, Washington.

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