Cannabis & Mental Illness: What Does the Research Say?

Cannabis—it’s a plant that’s well known for getting people high, but it’s also become increasingly accepted for medicinal purposes, particularly for pain and nausea. But what do we know about the interaction between cannabis and mental illness?

There’s been a clearly established link between cannabis use and triggering the onset of psychotic illness in people who are susceptible. When it comes to mood and anxiety disorders, there isn’t as much research.

Cannabis is now legal in Canada and a number of American states, and I suspect that one of the benefits of this is that there will likely be increased funding available for cannabis research.

The Canadian Institutes of Health Research, a government agency, currently has a competition open for grants to conduct cannabis research. The amount earmarked for mental health research is $4.5 million. Doing a quick search I wasn’t able to find an estimate of research dollars in the U.S.

Hopefully, in a few more years we’ll have a much better understanding of the science of cannabis. But here’s a brief look at what science can tell us now.

What’s in cannabis?

While Cannabis sativa plants contain more than 100 different types of cannabinoid elements, two in particular appear to be key in mediating the health effects of cannabis.

Delta-9-tetrahydrocannabinol (THC) is responsible for the psychoactive effect, or “high”, that cannabis produces. It also has analgesic and anti-nauseant effects.

Cannabidiol (CBD) is non-psychotomimetic, meaning it does not cause a “high”; in fact, it may even counteract that effect of THC. It’s being researched for potential use in a number of different health conditions, including epilepsy.

Both THC and CBD act on cannabinoid receptors in the brain, much like the body’s own natural endocannabinoids do. This is along the same lines of how opioids act on the body’s endogenous opioid receptors. As with opioids, the fact that these molecules act on endogenous receptors is not inherently a good or bad thing.

Endocannabinoid receptors

The endocannabinoid system involves two key receptors, CB1 and CB2, and influences a variety of cognitive processes including learning, memory, mood, sleep, and motivation.

The anti-obesity drug rimonabant acts as an antagonist at CB1 endocannabinoid receptors, and it can produce symptoms of depression and anxiety in individuals without mental illness. This suggests that decreased natural activity at endocannabinoid receptors can negatively impact serotonin signalling in the brain. One study found lower than normal concentrations of CB1 receptors in autopsies of the brains of depressed people.

THC is a CB1 and CB2 agonist. CBD boosts the activity of one of the body’s natural endocannabinoids and antagonizes the effects of THC.

Cannabis use and mental health

A statement by the National Academies of Science, Engineering, & Medicine found evidence of a number of mental health effects associated with cannabis:

• increased symptoms of mania and hypomania in people with bipolar disorder with regular cannabis use (moderate evidence)
• small increase in the risk of developing depression (moderate evidence)
• increased suicidal ideation, attempts, and completion (moderate evidence)
• increased social anxiety disorder among regular users (moderate evidence)
• There is no evidence indicating for or against an effect of cannabis on changes in symptoms or course of illness in people with depression
• There is moderate evidence that depression is a major risk factor for developing cannabis abuse

According to Lev-Ran and colleagues., multiple large cross-sectional studies have demonstrated high rates of co-occurring cannabis use and depression, although that level of evidence is insufficient to make inferences around causation.

They found that cannabis use moderately increased the risk of developing depression, with a somewhat larger increase in risk associated with heavy cannabis use. Similar results were found in both adult and adolescent populations. The mechanism for this was unclear, and the authors suggested that it could be related to direct effects on cannabinoid receptors, or it could be mediated indirectly by psychosocial consequences of cannabis use.

A study by Agrawal et al. found that heavy cannabis use was associated with an increased incidence of depression and suicidal ideation. However, a study by Blanco and colleagues did not find a significant association between cannabis use and the development of depression. A study by Schoeler et al. concluded that onset of cannabis use before age 18 was associated with an increased risk of developing MDD, but late-onset use (after age 27) was not.

Feingold et al. found that people with depression were more likely to start using cannabis, and the authors suggested this might e a form of self-medication.

What does this mean?

One of the benefits often ascribed to cannabis is that it’s a natural alternative to pharmaceuticals. However, the fact that a substance is plant-based rather than synthetic does not necessarily mean that the substance is either a) therapeutically effective, b) safe, or c) free of unwanted effects (i.e. side effects). If cannabis has therapeutic benefits, that’s great, but for me, the “natural” argument in and of itself doesn’t hold water. And with these findings, the biggest take-away message that I’m getting is that more research is needed.

Hopefully, with government research funding agencies offering more grant money for research into the effects of cannabis, we’ll have a clearer picture of how components the various components of cannabis affect mental health and mental illness. It would be particularly interesting to see what potential role CBD might play. Until the science is there to back it up, though, it’s probably not something that I’m going to be putting into my body.

References

• Agrawal, A. et al. (2017). Major depressive disorder, suicidal thoughts and behaviours, and cannabis involvement in discordant twins: A retrospective cohort study Lancet Psychiatry, 4(9), 706-714.
• Ashton, C.H., & Moore, P.B. (2011). Endocannabinoid system dysfunction in mood and related disorders. Acta Psychiatrica Scandinavica, 124(4), 250-261.
• Blanco, C. et al. (2016). Cannabis use and risk of psychiatric disorders: Prospective from a U.S. National Longitudinal Study. JAMA Psychiatry, 73(4), 388-395.
• Feingold, D., et al. (2017). Cannabis use and the course and outcome of major depressive disorder: A population-based longitudinal study. Psychiatry Research, 251(2017), 225-234.
• Feingold, D., et al. (2015). The association between cannabis use and mood disorders: A longitudinal study. Journal of Affective Disorders, 172(2015), 211-218.
• Lev-Ran, S., et al. (2014). The association between cannabis use and depression: A systematic review and meta-analysis of longitudinal studies. Psychological Medicine, 44(4), 797-810.
• Schoeler, T., et al. (2017). Developmental sensitivity to cannabis use patterns and risk for major depressive disorder in mid-life: Findings from 40 years of follow-up. Psychological Medicine, 48(13), 2169-2176.
• The Alcohol and Drug Foundation. (2018). Medical cannabis.
• The National Academy of Sciences, Engineering & Medicine. (2017). The health effects of cannabis and cannabinoids: Committee’s conclusions.