Monday, April 27, 2015


Here's another update of this post, to account for studies between 2009 and 2015.

Marijuana use is quite common in the university population I see in my clinic.

It is my opinion that sporadic recreational marijuana use is less dangerous than alcohol use, for many people.  For others, it is more problematic, and the risks may be underestimated. 

Cannabis is an acute intoxicant, which could make activities such as driving much more dangerous. Also, smoking marijuana undoubtedly causes harm to the lungs, though probably not quite to the same degree as smoking tobacco cigarettes (see references below).

There is strong evidence that marijuana use increases the risk of developing a psychotic disorder, probably by about 40%.

People who have a psychotic illness, or who have a family history of psychotic illnesses, are at higher risk for having new or continuing psychotic symptoms if they use marijuana.

Also, based on some of the evidence cited below,  children and adolescents are probably much more vulnerable to negative, long-term emotional and cognitive effects from marijuana use. 

Many regular consumers of cannabis have problems with motivation. This may be reflected in poor grades in school, lack of success in building a career, etc.  This is possibly a non-causal association, but if someone has low motivation to begin with, the addition of cannabis is not likely to help.

There may be some selected exceptions.  For example, some have claimed that a culture of cannabis use has had a catalytic role in helping reclusive technical geniuses relax their social and creative inhibitions, to permit some examples of very successful scientific and business innovation, such as in Silicon Valley.

There is strong evidence that marijuana use is associated with more severe psychiatric symptoms, of almost every type; but much of this association could be due to the fact that those with more severe symptoms are more likely to use marijuana, not the other way around. In any case, those who choose to use marijuana more regularly as a cultural pursuit may be surrounding themselves with others who have more severe symptoms.   This is similar to the case  of alcohol:  part of the harmful effect of drinking heavily is due to proximity to places (such as rough bars) where there are a lot of other heavy drinkers -- in this environment, there is likely to be more physical danger, and much less breadth of social or cultural opportunity.  Ironically, decriminalization should probably reduce this effect, and therefore reduce some of the potential social harms.

There is some evidence that marijuana or other cannabinoids could be helpful to treat a variety of medical ailments. This evidence needs to be taken seriously.

Here is a brief survey of the very large literature on this subject:

Evidence of Risk and Harm

     Psychiatric Risks

This 2007 review from Lancet shows convincing evidence that marijuana use increases the risk of developing a psychotic disorder, and that the risk is dose-dependent (i.e. the more marijuana one uses, the higher the risk is of developing a psychotic disorder):

It concluded that the evidence is less clear linking marijuana to other problems, such as depression and anxiety: many of the studies looking at this did not sufficiently address non-causal reasons for the association between marijuana and other problems. For example, people who are more depressed or anxious may have a higher likelihood of using marijuana to treat their symptoms. Or, people whose cultural style may lead them away from conventional treatments for depression, may be more likely to use marijuana regularly.    Use of psychotherapy and antidepressants are also more common among those with depression, but this does not prove that psychotherapy and antidepressants cause depression! 

In this 2008 review from the British Journal of Psychiatry, the authors conclude that marijuana use is associated with worse outcome in psychotic disorders--but they say that the existing studies show only an association, not causality. Once again, confounding variables may cause this association to exist:

A significant cannabis withdrawal syndrome is described in the literature, particularly for heavy, long-term users. The syndrome involves about 2 weeks of irritability, restlessness, and insomnia, which could be quite destabilizing for someone struggling with mood symptoms, therefore leading to continued marijuana/cannabis use. Here is a 2006 review of the subject:

A few recent prospective studies have demonstrated increased dysphoria, anxiety, tiredness, ideas of reference, and schizotypal symptoms as a result of marijuana intoxication. In particular, individuals with pre-existing schizotypal personality traits had a more substantial increase in schizotypal symptoms following THC exposure. This adds to an evidence base suggesting that marijuana use carries a significant risk of exacerbating a variety of psychiatric symptoms, particularly psychosis-spectrum symptoms, and particularly in those with risk factors for psychotic illness.
Here are the references, which are both from Psychological Medicine in 2009:

This interesting study involved administration of THC to healthy volunteers who did not use THC.  Some members of the cohort experienced transient psychotic phenomena, while others did not.  These differences were associated with differences in cognitive impairment and functional MRI results. This supports the common-sensical observation that some individuals may be more vulnerable than others, to having adverse neuropsychiatric effects from THC use.

Many other studies looked at populations who used different amounts of marijuana over time, and compared them in terms of various symptoms and intellectual functions, etc. Unfortunately, I find this type of retrospective analysis to be weak, and highly prone to confounding variables. In order to understand marijuana's long-term effects for sure, we would need to do a long-term, prospective, randomized, controlled study.

     Physical Risks

Here are some studies looking at risk to the lungs associated with marijuana smoking:

These studies show an increased risk of lung cancer in marijuana smokers:

These studies show a likely causal association between long-term marijuana smoking and obstructive lung disease:

     Prospective Animal Studies

Animal studies could add a little bit more information into the picture, since these have been done in a prospective, controlled fashion. Here is what I've found from the animal research literature:

This study showed that chronic marijuana exposure impairs spatial memory & learning in rats:

This study showed that chronic marijuana exposure impairs social and cognitive functions in rats, but especially when the period of exposure is during the pubertal ("adolescent") phase of development:

Another study showing that marijuana exposure may be particularly harmful to the "adolescent" brain in rats:

This study from UBC suggests that high-dose cannabinoids increase emotionality and "sensitize the stress axis" in rats:

Evidence of Benefits or Therapeutic Uses

This study shows that a synthetic cannabinoid promotes neurogenesis in the hippocampus, and may have antidepressant and anxiolytic effects:

Here is a reference to a good 2008 review of the pharmacology and potential therapeutic applications of cannabinoids such as marijuana:

     Neurological Diseases

Here's a 2012 study showing relief in muscle stiffness in multiple sclerosis patients, due to cannabis administration:

Another 2012 study from CMAJ showing relief of spasticity and pain in MS patients, following cannabis administration:

This study shows immediate relief of the symptoms of Parkinson's Disease following cannabis treatment:

     Bowel Disease

This study, from a major journal of gastroenterology, shows that cannabis dramatically improved symptoms  of Crohn's disease (a type of inflammatory bowel disease), in a prospective, placebo-controlled trial.

Another prospective study, showing that cannabis improves quality of life in inflammatory bowel disease:

     Pain Disorders

Here's a good 2013 study showing that cannabis compares favorably with other standard pharmacological treatments for neuropathic pain:

     Heart Disease

This 2005 study from the prestigious journal Nature suggests that cannabinoids could reduce the progression of atherosclerosis (the main cause of heart disease):

In conclusion, I think that marijuana use is dangerous, and harmful to your health in a variety of ways, due to acute intoxication, increased risk of psychosis, possible cognitive side-effects, and lung damage. It may be particularly harmful to adolescents. As a cultural pursuit, it may distract people from other life activities, or meaningful life roles, just as any habit or addictive behaviour can. But it may have beneficial effects for a variety of medical problems.

I have to admit, to be fair, that some people have psychological benefits from marijuana use -- certainly there are many testimonial accounts of this, but evidence beyond this is not clear on this point.  The few studies touting this application tend to be of short-duration, which leads to a similar criticism as that pertaining to mainstream pharmaceuticals:  short-term benefits for symptom relief do not always translate into long-term benefits, if the use continues for years.   More research is needed to gain a better understanding of the potential risks or benefits of cannabinoids, especially over longer-term use.

I have certainly seen people for whom cannabis appears to have a better benefit:risk profile than alternative treatments, for example to treat chronic pain symptoms and associated insomnia.    It may be preferable to use cannabis instead of a benzodiazepine, opiate, pregabalin, etc., particularly if these latter agents are causing a much higher load of side effects in a given person.

For some people, cannabis could be a relatively harmless entertainment, or even a catalyst for enjoying life more richly in various settings.  In this way, it could be analogous to having a glass of wine with meals, etc.

Another angle to the analysis is to consider relative risks of cannabis compared to other accepted intoxicants, such as alcohol.  With this type of risk analysis, one could often see greater risks with alcohol compared to cannabis, on a case-by-case basis, but we don't have good group data on this.  Suppose we had two adjacent similar countries, and prospectively allowed free access to alcohol in one country, and free access to cannabis in the other.  Then, suppose we were to assess health outcomes in these countries 20 years later.  I suspect we would have more examples of ruined families, criminal assaults or manslaughter, chronic diseases, and traffic fatalities, in the "alcohol" country compared to the "cannabis" country. 

The issue is complicated by the fact that those who are more apt to use cannabis are statistically also more apt to use alcohol and other street drugs.  It is possible that cannabis use could have "gateway" effects, leading people into a higher-probability zone of trying or using more dangerous drugs. But this is an open question. 

A proliferation of cannabis dispensaries have appeared in Vancouver in the past year.  While I do think that legalization is a positive step, in terms of the various pros and cons for public health,  I am not happy with the idea being touted by some, that cannabis is some kind of health food, or panacea.   There is an issue of cultural freedom as well, which I support, though I think that many in this "4-20" movement have an exaggerated view of the benefits of cannabis, with an underestimation of risks.



Rach said...

I'm curious - is there any literature on the interactions (positive/negative) between psychotropic meds and marijuana?

GK said...

I don't find that there is a lot of literature out there on interactions.

Another reader inquired about marijuana use in treating anxiety, depression, and cocaine/heroin dependence.

I do not find that there is strong research evidence to support this practice. But there is support from some individuals' testimonial accounts.

Some of the publications released by overtly pro-marijuana groups appear to make strong positive claims with little evidence-based support (beyond testimonial accounts), and with minimal statements about risk, despite a fairly strong research literature about risk.

As I scan through the studies that have been done, I see some mixed results. Many of the studies suggest a negative influence of marijuana use on other addictive problems. But I found one study suggesting that marijuana use may improve cocaine abstinence in cocaine-dependent individuals who also have ADHD. Clearly, there are careful studies that need to be done to clarify this issue further.

So it may be that marijuana could have a useful role for some individuals, including those with a wide variety of different problems.

For other individuals they may continue to have quite serious problems while using marijuana regularly--and perhaps the marijuana is an exacerbating factor--yet they may insist that they are better off due to their marijuana use.

My reading of the evidence is mixed, and largely leads to a recommendation of being very cautious, as I have already described in my above post.

If more and better evidence comes my way, I would be interested in updating my post once again.

There are bound to be individuals who have strong opinions, on either side of this issue. And another angle of the issue is that it is a human rights matter: I think the civil liberties side of marijuana is very important, yet this may be quite a different matter than assessing the health impact of marijuana use. People trying to campaign for lenient marijuana laws, etc. or those advocating for people who believe strongly that marijuana helps them, may make strong positive health claims to bolster their case. Those campaigning for strict marijuana laws may exaggerate negative health claims. An unbiased reading of the evidence may be lost in the middle.

Anonymous said...

I came across a science news hour on TV and they were presenting information about psychotic symptoms and Cannabis. They covered a lot of things but one thing that stuck out was... depending on the cannabinoids in the cannabis (ie: CBD v.s. THC) the effects may be protective v.s deleterious (respectively).

I did some poking on OVID/Pubmed. And found some interesting results--- although not all of them are replicable.

And-- I selected the studies that DID show some beneficial results of CBD... because there are many that show no effect/little effect.

Search terms:
* cbd
* schizophrenia

Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug.|9|1

Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. [Review] [121 refs]|3|1

Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis.|5|1

On the TV show-- the narrators also pointed out that most street Cannabis is domesticated to possess high THC and low CBD. (This is because they seem to be mutually inclusive--ie: if the plant has high CBD it can't have equally high THC.)

Anyway I just thought to attend to the fact that as with almost anything, depending on what entity one picks to evaluate, the results will vary substantially.

And an overall cost/benefit analysis is needed in the end.


GK said...

Interesting. I'll have to check that out. Sometimes therapeutically beneficial effects can come from unexpected places. However, I would want to start this investigation from a position of skepticism. Also, unless there are long-term studies in humans (over 6 months), antipsychotic effects cannot be clearly assured, as immediate effects could be part of simple sedation, leading eventually to tolerance and a higher risk of psychosis later on, despite an apparently positive early effect (i.e. similar to benzodiazepine or alcohol effects on anxiety).

With regards to "with almost anything, depending on what entity one picks to evaluate, the results will vary substantially", I suppose that's true. Yet I believe that there is a preponderance of truth about things which a comprehensive view of evidence brings. And it should be our goal to seek, and expect, such a comprehensive view. Otherwise, we can become cynical, and start to believe any point of view can be supported just by selecting some part of the data, therefore we can't make a definitive statement about anything, etc.

A non-comprehensive understanding or presentation of evidence tends to cause biased persuasion or manipulation. For example, I have no doubt that many a cigarette manufacturer attempted to present data showing the health benefits of smoking in previous generations. Yet I think we can all realize today that such data was extremely manipulative (even if not dishonest, as there are certainly some positive psychopharmacological effects of nicotine despite the overwhelmingly deleterious long-term effects).

Anonymous said...

Exercise reduces Cannabis use

GK said...

Thanks for the comment. I wonder if the converse could be true also, i.e. that cannabis could reduce addictive/compulsive/harmful exercise use?