CANNABIS CULTURE – I was reading an article from the Calgary Herald entitled, “AHS [Alberta Health Service] doctor worries more kids will self-medicate with pot once it’s legalized”.

On first reading, I essentially thought, “There’s a lot of claims being made here – claims that are not necessarily backed by the science”. I also remembered that this is an article that quotes Dr. Wilkes, and that sometimes things can be taken out of context. I prefer to try and read things as charitably and fairly as possible, with as objective a mind as it is possible for a subjective being to take. The article seems to be a mish-mash of scaremongering and some concerns that are understandable and genuine. Also, for the sake of this article, I will make a differentiation between “recreational” and “medical” use, even if i don’t personally agree with this arbitrary line. So, with that in mind, let’s take a look at some of the major claims Dr. Chris Wilkes (as well as Dr. Eddy Lang) makes.

The article seems to touch on two main areas of concern. One is the impact of cannabis legalization on young people, particularly on their mental health and development. The other is the uptick in hospitalizations related to cannabis due to Cannabinoid Hyperemesis Syndrome (CHS – sometimes called “Cannabis Hyperemesis Syndrome). Related to both of these points is also the idea of “self-medicating”, and how people may turn to cannabis use in order to relieve themselves of stress and anxiety. The concern also seems to be mostly related to the “recreational” side of cannabis.

Let’s look at the first claim:

““The perception now with legalization is that marijuana is safe, and it’s less toxic than alcohol. But that is not that case at all,” said Wilkes, estimating about 37 per cent of Grade 12 students in Alberta have used marijuana, and of that 10 per cent are believed to be using daily or are dependent.”

Now, I don’t wish to completely dismiss Dr. Wilkes’ remarks out-of-hand. There is a point to be made, even if it’s not being expressed in the article. Cannabis contains a huge number of compounds. We cannot say for certain whether or not all of these compounds are “toxic”, and at what dosage and what segment/s of the population. The endocannabinoid system (ECS) is complex, and what may be helpful to one person may be harmful or neutral to another.

The ECS is also a very powerful system, and modulating it can have all sorts effects, especially as it seems to be so intimately linked to homeostasis and other receptors in the body. There may also be a huge number of interactions with other drugs and medications, and even diet and levels of physical activity. The fact is, we don’t know a huge amount about the ECS, and treading carefully when we’re faced with a complex mountain that requires a surefooted approach is a wise move.

Yet (and this is a big yet), the idea that the cannabis plant is necessarily more toxic than alcohol seems alien to me. The more accurate answer at the moment seems to be “We don’t know how toxic long-term or short-term cannabis use is. However, it does seem that there has not been a death attributable to cannabis use alone (negative interactions with other drugs and medications is a possibility), and the chances of facing a deadly overdose on cannabis are theoretical.” Most comparative risk assessments I have read tend to come to the conclusion that “Cannabis is less toxic, although not necessarily completely non-toxic, than most other illicit drugs, and even many licit ones. However, more study is needed in this area, and we must also take into account the environmental conditions in which the drug was taken.” Alcohol often comes somewhere near the top when it comes to how toxic a substance is, but exposure to alcohol in many populations is also quite high, which may push it up a little.

This also brings us to the difference between moderate and compulsive use. Yes, compulsive use of cannabis may potentially be bad, but so is alcohol use; and, unlike with cannabis, compulsive use of alcohol can cause death. The 10% figure given is a little confusing – is it 10% of all Grade 12 students who become dependent on cannabis, or 10% of the 37% of grade 12 students are said to be using cannabis? The latter figure is more inline with the percentage of those who develop cannabis/marijuana use disorder, and it must be stated that, for many people at least, cannabis withdrawal is not a hugely difficult or life-threatening problem.

Remember also that the cannabis plant is a living organism, meaning that it has “checks and balances” (a feedback system) of its own. Should the plant start producing one set of cannabinoids to a dangerous level, it may well start producing other cannabinoids to counteract this. This is one theoretical reason why so many people may respond better to a broader profile of cannabinoids, although it must also be said that some people and some conditions may well need a very specific cannabinoid or set of cannabinoids for any health issues they suffer from.

For moderate “recreational” cannabis users, using cannabis varietals with a mixed cannabinoid-terpenoid profile that doesn’t go overboard on one particular cannabinoid may well be no different from an occasional glass of wine in the evening. Furthermore, a person may still be getting the beneficial effects of cannabinoids, even if they are not using it for a specific medical purpose.

Let’s go into the next part …

“As a doctor who works directly with youth faced with mental health problems, Wilkes is concerned more youths will self-medicate with pot to deal with stress. That becomes particularly concerning at a time when marijuana can have a serious impact on young, developing brains, he added.

Wilkes explained that because the brain is still developing in young people well into their mid-twenties, cannabis use can impair the hippocampus, the part of the brain connected to attention and memory, as well as the pre-frontal cortex, which regulates emotions.

“If you’re a young adult, your brain is still developing, and cannabis impacts memory, attention skills, control of your impulses, prioritizing, and problem solving.”

I do have some sympathy with Dr. Wilkes’ statements here. Yes, cannabis could well be an issue for young, developing brains. Of course, this is also the case with alcohol and other drugs, so in this sense separating cannabis out seems a little unfair – we ought to give it a fair and proper overall assessment. However, it is definitely true that cannabis impacts the brain, and that it acts differently at different stages of life. The ECS is also involved in the development of the brain throughout one’s life, and foetal exposure to cannabis – in particular the cannabinoid THC – may well be harmful if the brain is still developing. However, using cannabis at a later age may prevent or mitigate hippocampal and other changes to the brain.

“So why is cannabis so often touted as a pediatric medicine?” You may ask. Well, as we’ve noted already, cannabis is a lot less toxic than many other drugs and medications, and as cannabinoids can be used as allosteric modulators, there is a decreased risk of toxic effects. This is because cannabinoids act on CB1 and CB2 receptors (as well as others), which are G-protein coupled receptors (GPCRs) and have therefore not faced the same pressure to produce a specific endogenous ligand. This means that the ECS has a very diverse set of compounds and neurotransmitters that can affect it. Furthermore, psychoactive amounts of THC or any other cannabinoid are not necessarily needed for therapeutic effects. This is a major reason why “medical marijuana” is a thing, and not just a figment of scientists’ collective imaginations.

“He added that pot users are also at increased risk of psychosis, an impaired perception of reality, including hallucinations and delusions.”

This is a very contentious issue. Yes, cannabis use, in particular the cannabinoid THC (CBD may be antipsychotic and anti-schizophrenic – another aspect of the “checks and balances” of the cannabis plant), may increase the likelihood of someone developing psychosis or psychotic symptoms, but this may be due to the fact that they have a family history of psychosis rather than cannabis use in and of itself. In other words, using cannabis may make latent psychosis blatant, but only in those who are already genetically predisposed to the condition – usually, those with polymorphisms in COMT or AKT1 genes. Correlation does not mean causation, and we must also take other factors into account. Amphetamine and alcohol misuse, for example, can also have a major impact on whether or not one develops psychotic symptoms. Cannabis is not unique in this regard, and we have to also take strain and cannabinoid type, dosage and age cannabis use first started into regard. To quote from “Gone to Pot – A Review of the Association between Cannabis and Psychosis” (2014):

“In individuals with an established psychotic disorder, cannabinoids can exacerbate symptoms, trigger relapse, and have negative consequences on the course of the illness. Several factors appear to moderate these associations, including family history, genetic factors, history of childhood abuse, and the age at onset of cannabis use. Exposure to cannabinoids in adolescence confers a higher risk for psychosis outcomes in later life and the risk is dose-related. Individuals with polymorphisms of COMT and AKT1 genes may be at increased risk for psychotic disorders in association with cannabinoids, as are individuals with a family history of psychotic disorders or a history of childhood trauma. The relationship between cannabis and schizophrenia fulfills many but not all of the standard criteria for causality, including temporality, biological gradient, biological plausibility, experimental evidence, consistency, and coherence. At the present time, the evidence indicates that cannabis may be a component cause in the emergence of psychosis, and this warrants serious consideration from the point of view of public health policy.”

To add to this, a quote from “Cannabis and psychosis/schizophrenia: human studies” (2009):

“Also clear is that in individuals with an established psychotic disorder, cannabinoids can exacerbate symptoms, trigger relapse, and have negative consequences on the course of the illness. The mechanisms by which cannabinoids produce transient psychotic symptoms, while unclear may involve dopamine, GABA, and glutamate neurotransmission. However, only a very small proportion of the general population exposed to cannabinoids develop a psychotic illness. It is likely that cannabis exposure is a “component cause” that interacts with other factors to “cause” schizophrenia or a psychotic disorder, but is neither necessary nor sufficient to do so alone.”

So, whilst cannabinoids can be a contributory factor to psychosis, it is not the only factor, and only a small proportion of the population are likely to be affected by it. I will cede, however, that care must be taken in this area, and any negatives that may arise – even if rare – be taken seriously. Whether or not young and adolescent minds are more likely to develop psychosis or any other mental health problem due to cannabis use alone depends on various factors is up in the air, but we must be careful of creating overbroad generalizations when there is still so much conflicting data out there.

Dosage matters. Which cannabinoids and terpenoids are used matter. Whether or not a young person is using cannabinoid-based medication for cancer, epilepsy, ADHD and more besides, matters. We cannot throw the baby out with the bathwater, and there are many potential uses for cannabis. Understanding various cannabinoids’ risk:benefit profiles over both short- and long- term usage, as well as regular and irregular usage and how they react with other cannabinoids, terpenoids and medications, is of utmost importance if we are to see the true medical potential of this plant, as well as their negatives. Clinical Endocannabinoid Deficiency (CECD) may well be behind the development of many conditions, including anxiety and depression in some cases, and in not learning how to modulate the ECS with cannabinoids we may in fact be missing a major trick by not utilizing cannabis.

Next is from Dr. Eddy Lang:

“Dr. Eddy Lang, professor and department head for emergency medicine at the University of Calgary’s Cumming School of Medicine, said Calgary is already seeing more emergency room visits related to marijuana use.

And he worries those most vulnerable to the drug’s effects, youth aged 18 to 24, are not educated enough around its potentially harmful impacts.

“On the eve of marijuana legalization, we have serious concerns,” Lang said.

“We’re very worried about a sharp uptick.”

As the country edges closer to legalizing the recreational use of pot, expected sometime this summer, Lang said Calgary emergency rooms have seen a marked increase in Cannabis Hyperemesis Syndrome, which results in prolonged attacks of severe vomiting and then dry-heaving every hour for up to two days.”

I do not wish to negate Dr. Lang’s experience here, but CHS tends to arise after long-term, regular exposure to cannabinoids, and its precise prevalence is not known. Until we have better clinical data, CHS could be seen as “rare” or “very rare”. Whether or not CHS is more likely to occur due to some of the high-THC strains and products we have available is debatable; but some of the increase he’s seeing might not be due to increase in usage per se, but people being more willing and honest about using cannabis and any problems that might be arising due to it. In some ways, this is may lead medical professionals to a more accurate diagnosis – something we might not have known about in the past. However, CHS definitely seems to be a condition we should be aware of, and learning about how cannabinoids affect the ECS may actually help us develop medications that could potentially prevent the occurrence of CHS.

The other issue that is bought up is the idea that cannabis legalization will lead to an increase in usage. I will let a quote from Elaine Hyshka, Assistant Professor at the School of Public Health, University of Alberta, answer this one, as it seems to slice through this quite well:

“It’s important to note that Canadian youth already report the highest rates of past year use, relative to other countries,” said Hyshka. “While there is evidence to suggest there may be an increase in use amongst young adults, cannabis will remain illegal for those under 18.”

Advertising regulations, strategic pricing and controlled distribution, are examples of policy levers that can discourage use. Hyshka points to the early experience of Washington state and Colorado, which legalized non-medical cannabis use. So far, they have found that use among young people has remained relatively stable.

To back this stance up, the study “The Effects of Marijuana Liberalizations: Evidence from Monitoring the Future”:

“By the end of 2016, 28 states had liberalized their marijuana laws: by decriminalizing possession, by legalizing for medical purposes, or by legalizing more broadly. More states are considering such policy changes even while supporters and opponents continue to debate their impacts. Yet evidence on these liberalizations remains scarce, in part due to data limitations.

We use data from Monitoring the Future’s annual surveys of high school seniors to evaluate the impact of marijuana liberalizations on marijuana use, other substance use, alcohol consumption, attitudes surrounding substance use, youth health outcomes, crime rates, and traffic accidents. These data have several advantages over those used in prior analyses.

We find that marijuana liberalizations have had minimal impact on the examined outcomes. Notably, many of the outcomes predicted by critics of liberalizations, such as increases in youth drug use and youth criminal behavior, have failed to materialize in the wake of marijuana liberalizations.”

Similar stories can be found in Europe as well, where cannabis legalization has not necessarily lead to more cannabis use. Cannabis use seems to stabilize over time, although there may be small increases in usage in the immediate aftermath of legalization. There are various statistical reasons for this, including people being more open about using cannabis, a change in survey methodology, and the fact that a small surge is obviously going to be seen as soon as something is legalized – it is, after all, very difficult to measure what you cannot see. Legalization merely allows us to measure usage more accurately, and does not necessarily always equal an increase in usage. Holland is an interesting case of this very phenomenon, where lifetime use may fall amongst the population but there may be a small increase followed by stabilization, with a trend to decreased use overall. Yes, younger people may occasionally use cannabis, but this does not necessarily translate to an increase in long-term and/or regular cannabis usage.

The “I was at college” phase may be a common experience in many places throughout the Western world, and cannabis use is not necessarily any better or worse than alcohol use. Indeed, some could very reasonably be argue that, for a person aged 21 or over and without a history of psychosis, having a small or moderate amount of cannabis at the weekend could be a far more sensible choice than using large or even moderate amounts of alcohol at the weekend.

Dr. Lang then goes on to say:

“Lang added that that he worries hospitals will also be presented with more mental health emergencies as youth experiment or self-medicate with marijuana during a time in their lives when they typically deal with high amounts of stress, from school deadlines and exams to new relationships or separating from parents.

“We have an epidemic of anxiety and kids are using cannabis to deal with all kinds of stress,” Lang said.

“Now they’ll also be faced with mental health emergencies.”

Lang agreed with Wilkes that educators need to step up efforts in helping youths understand marijuana, a complex issue that will become especially fluid with legalization.

“They have to be at the cutting edge of this stuff,” he said.”

We have already dealt with much of the relationship between cannabis use and mental health above, and there does seem to be a paradox when it comes to cannabis and anxiety, in that it can be potentially beat it and be a factor in causing it. Dosage seems to matter, with low doses of THC potentially alleviating anxiety and higher doses doing the opposite. Now, there does seem to be some association between anxiety disorders and cannabis use, but we could be getting the cart before the horse here. People may be using cannabis because they feel anxious, not necessarily anxious because they use cannabis; and, in some instances, they may be using cannabis to replace or use as an adjunct to antidepressants or harsher pharmaceuticals.

Finally, I would like to make a note on the concept of self-medication. As many of you know, I am a proponent of people being allowed to grow and consume their own cannabis, preferably without the use of chemical pesticides, herbicides and other nasty things that often end up on mass-produced cannabis. This means that, to some extent at least, I do not necessarily have a problem with people “self-medicating”. When a patients says, “this [cannabis]is helping me feel better”, it is worth listening to them. Should many patients start saying similarly, then it is worth asking, “What is going on here, and is there actually something to this beyond just placebo effect?” To which the answer is, “I know! Let’s research it and find out!”

Yes, there are of course huge problems with self-medicating as well, most notably the knowledge gap. We do not know a huge amount about the ECS as of yet, and we do not know what cannabinoid-terpenoid profiles work for which condition, and at what dosage. We also need to find out about any drug interactions. For example, we know that cannabidiol (CBD) desensitizes the liver enzyme cytochrome P450 (CYP450), and due to this may well have negative interactions with benzodiazepines.

However, doctors and patients can only learn about this if we are allowed to study it properly by allowing doctors and scientists to access it without having to jump through overzealous regulatory hoops. Doing so may help us in developing novel, intriguing classes of drugs and medications based on cannabinoids – ones with low toxicity and a wide safety margin. Not doing so could potentially be holding back a major treatment method for a huge number of health problems.