“No amount of sleep in the world could cure the tiredness I feel.” - Anonymous
Depression has long been a major public health issue. According to the National Institute of Mental Health, 15.7 million adults (6.7% of all U.S. adults) aged 18 or older in the United States experienced a major depressive episode in 2014. For those who suffer, depression can be a hell that has been described as “living in a body that fights to survive while your mind tries to die.”
To treat depression, doctors generally prescribe a pharmaceutical like Prozac or Zoloft. Often, they’ll also prescribe an antianxiety medication like Valium or Xanax. However, antidepressants don’t work for everyone. Worse, benzodiazepines such as Valium or Xanax can be highly addictive. Of course, we’ve all seen the commercials for these drugs. The part of the commercial devoted to listing the potential adverse side effects is usually longer than the part of the commercial describing the benefits. And, what are one of the potential side effects? Thoughts of suicide!
Clearly, the limited number of effective options to treat depression are, in fact, depressing! No wonder many people choose to self-medicate with cannabis to treat depression. However, how does cannabis play into the equation? There has long been an association between depression and cannabis consumption. But, it’s been a chicken and the egg thing. Does cannabis consumption cause depression, or do people with depression use cannabis to to alleviate their depression?
While all important considerations, first, let’s start by defining “depression.”
While everyone experiences periods where they “feel depressed,” at what point is it depression? Feeling sad or blue after experiencing a common life event — such as a job loss or the break up of a relationship — is a normal human response. But, what actually constitutes clinically diagnosable depression?
According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) — the “bible” used by mental health professionals in the U.S. to diagnose mental health conditions — major depressive disorder is defined as experiencing either depressed mood or loss of interest or pleasure over a period of two weeks or longer, and at least five out of nine identified symptoms that reflect a change in functioning, such as problems with sleep, diet, energy, feelings of self-worth, and concentration.
It’s important differentiate between “risk factors,” “triggers,” and “causes.” They’re all closely related and often used interchangeably, but there are subtle, notable, distinctions.
Risk factors - Natural or environmental factors that increase one’s likelihood of developing depression. For example, heredity can be a natural risk factor, as mental illness is known to run in the family. Substance abuse, on the other hand, is an example of an environmental risk factor. For example, it’s well established that alcoholism is a major risk factor in developing depression.
Trigger - A causal event that triggers the onset of a depressive episode. For example, a death in the family, job loss, emotional abuse, disease, or even taking a medication, as some medications are known to trigger depression.
Causes - In this context, what is the physiological explanation for depression? For example, a chemical imbalance (i.e. a serotonin deficiency).
Contrary to popular belief, we can’t point to a single factor — like serotonin deficiency — that causes depression. It’s likely the interaction of several factors, such as stressful life events, medical issues, genetic vulnerability and physiological functions that work together to elicit the onset of a depressive episode.
Further, evidence suggests there are multiple pathways that could be factors in causing major depression, including faulty mood regulation by the brain, chronic inflammatory response and alterations of the endocannabinoid system. Of course, ingestion of cannabinoids affect endocannabinoid system (ECS), and the ECS plays an important role in modulating the body’s inflammatory response. Which, of course, makes the study of cannabis and depression even more interesting. Could cannabis provide the key to unlocking a class of new therapeutic options to treat depression? Quite possibly.
Australian psychiatry researchers from the University of Newcastle upon Tyne write: “Anandamide, tetrahydrocannabinol (THC) and cannabidiol (CBD) variously combine antidepressant, antipsychotic, anxiolytic, analgesic, anticonvulsant actions, suggesting a therapeutic potential [for cannabinoids] in mood and related disorders.”
Our body’s own cannabinoid system — the endocannabinoid system (ECS) — is one of the most important physiological systems in our bodies, as it plays an indispensible role in helping us maintain physical and emotional health. The ECS does far more than just modulate the psychoactive effects of cannabis — it plays a major role in appetite, pain sensitivity, memory, and of course, mood and well-being.
There are numerous paths to manipulate the endocannabinoid system. When you ingest cannabis, you’re also ingesting THC and CBD (along with dozens of other plant cannabinoids). These cannabinoids then bind to receptors in the ECS to elicit pharmacological effects beyond just getting you “high,” or creating euphoria. (This is why cannabis can be medicine or an inebriant.)
Interestingly, exercise can stimulate production of the body’s naturally occurring version of THC, the “bliss molecule,” anandamide. You’ve no doubt heard about the “runner’s high.” Well, it’s likely anandamide molecules (not endorphins) cause this high. Chocolate lovers take note — dark chocolate also stimulates anandamide production.
As researchers have noted, the endocannabinoid system is involved in mood and related disorders. Clearly, modifying the ECS through activities like exercise is beneficial in regulating mood. Likewise, consuming synthetic and plant-based cannabinoids modify the ECS. Obviously, many people use cannabis because it makes them “feel good.” What’s less clear is to what degree the short-term benefits translate into potential long-term benefits or adverse effects.
Here’s what we know so far...
Dr. Ethan Russo, one of the most important figures in cannabis medicine, notes that in India, cannabis was credited for helping alleviate anxiety and depression as far back as 1500 B.C.E. In recent history, the Ohio State Medical Committee on Cannabis stated in 1860: "As a calmative and hypnotic, in all forms of nervous inquietude and cerebral excitement, it will be found an invaluable agent, as it produces none of those functional derangement or sequences that render many of the more customary remedies objectionable.”
It’s a truism, to proclaim that a great many people use cannabis because it makes them “feel good.” Because it makes them “happy,” and it elevates their mood. There’s nothing particularly controversial about those statements. However, what has been a source of controversy during recent years is what the relationship is between cannabis and depression. It’s only been quite recently that among mainstream scientific community has there been an interest in studying cannabis and cannabinoids for its potential therapeutic value in treating psychiatric conditions such as depression.
As part of the perpetual, seemingly unending, “War on Drugs,” research funding has been allocated disproportionately to prove cannabis is a dangerous drug that warrants residency in perpetuity on the DEA’s infamous Schedule I — reserved for the world’s most dangerous and addictive drugs. Consequently, despite the fact throughout recorded history cannabis has been credited for its antidepressive powers, there are very few high-quality, scientifically rigorous studies that exist demonstrating cannabis’s potential as an antidepressant. As the public’s perception of cannabis continues to rapidly evolve over recent years, and the scientific community follows, more research is now being done. But, we’re still in our infancy.
Irrespective, of federal policy that has impeded serious scientific study of whole-plant cannabis for decades, we’ve managed to accumulate some notable research no less.
Here’s what the research tells us so far:
One thing that is well-established is that THC produces dose-dependent biphasic effects. What the heck does that mean? Low to moderate effects elicit desirable effects; too high of doses, produce the exact opposite effects. This should be pretty obvious to anyone who has ingested too much of an edible, or smoked too much. You can get paranoid or anxious. Quite simply: moderate doses of THC tend to produce pleasant effects like euphoria and relaxation, while too high of doses could exacerbate anxiety or depression — at least acutely. The science is still out on the long-term effects of chronic consumption.
Again, we don’t have much “gold standard” research studies on humans, but preclinical research — on lab rats and mice — tend to support this hypothesis. Anecdotal reports from her patients inspired Dr. Gabriella Gobbi — and her team at McGill University — to embark on a study to evaluate the potential of cannabis to act as an antidepressant.
"As a psychiatrist, I noticed that several of my patients suffering from depression used to smoke cannabis. And in the scientific literature, we had some evidence that people treated with cannabis for multiple sclerosis or AIDS showed a big improvement in mood disorders. But there were no laboratory studies demonstrating the antidepressant mechanism of action of cannabis."
Gobbi and her team conducted their research on experimental animal models by injecting the mice with a synthetic version of THC. What they found is that in low doses, the synthetic version of THC had a potent antidepressant effect, significantly increasing serotonin in the rats' brains. However, at higher doses the exact opposite occurred: serotonin levels dropped significantly. She noted, also, that “excessive cannabis use in people with depression poses high risk of psychosis.” However, since this study, research has emerged to suggest THC only increases the risk of psychosis in individuals who are predisposed to it.
Notably, Gobbi’s research only tested synthetic isolated THC. We now know that CBD — the (largely) non-psychoactive sibling of THC — is a potent force of temperance against THC. CBD — proportional to its concentration — offsets most potential adverse effects of THC.
Remarkably, our appreciation for CBD’s huge therapeutic potential is a recent phenomenon — it’s only really taken off over the last five years. Within psychiatric research, preclinical studies in humans and animals have found that not only could CBD potentially treat depression and anxiety, it alleviates withdrawal effects from drugs like opioids. (In fact, it can even reduce cue-driven drug-seeking behaviors and cravings.)
CBD is the most popular (largely) non-psychoactive cannabinoid found in cannabis. Researchers (and others) frequently point to CBD as having tremendous potential to treat psychiatric conditions, noting, also, that among its antidepressant and antianxiety potential, it can counteract potential adverse effects of THC. (In fact, it could quite possibly also be a powerful antipsychotic agent.)
Other studies, too, suggest CBD has powerful antidepressant and antianxiety properties.
Spanish researchers, conducting (another) experimental study using animal models (e.g. mice), found that by enhancing serotonin and glutamate levels, CBD could be a fast-acting antidepressant drug.
Another study conducted by researchers in Israel and Brazil noted that in human trials, CBD doses producing the most impressive results were nominally high (well, not that high!), however, they identified three other CBD derivatives that could be incredibly potent antianxiety and antidepressant agents at very low doses.
Clearly, our scientific understanding of cannabis and ongoing research are pointing to expanding therapeutic roles of cannabis (particularly CBD) to elevate mood and alleviate depression, but what about all the talk over the years that cannabis use can actually cause depression? Well, that research has been largely debunked.
Swedish researchers conducted a study of 8598 Swedish men and women between the ages of 20 and 64 over a three year period. After factoring in other risk factors such as alcohol and illicit drug use, adverse life events, family tension, they found no statistically significant data to suggest that cannabis use triggers depression.
In January 2015, researchers published a longitudinal study in Journal of Affective Disorders releasing findings from data they analyzed that was collected by the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and concluded that cannabis use was not significantly associated with an increase in major depressive episodes.
But, of course, all the news can’t be good. While cannabis may not cause depression — users generally perceive cannabis as helping them alleviate depressive symptoms — there is strong evidence that already depressed individuals are at an elevated risk to increase their cannabis consumption to potentially problematic levels. Moreover, there’s a risk that depression could increase anxiety levels and accelerate transition in vulnerable individuals from casual to problematic use.
Keep in mind, however, that in studies there were generally overlapping factors beyond depression that lead to problematic use — such as a parent who had a history of mental illness or drug use disorder.
A 2014 study showed that depression or “pre-existing anxiety was associated with higher average levels of cannabis intoxication, which in turn was linked to acute anxiety responses due to cannabis use." Further, researchers have found depressive episodes were “associated with increased speed of transition to dependence, which is consistent with emerging findings of an association between depression and cannabis use disorders.”
Interestingly, the perception of getting better or higher quality sleep may be one of the reasons people increase cannabis use. A study published in The American Journal of Drug and Alcohol Abuse suggests that “individuals with heightened depression may have higher rates of problematic cannabis use, in part, because of the beneficial effects of cannabis in terms of perceived sleep quality.” According to one of the study’s researchers, Marcel O. Bonn-Miller, “Sleep issues are often a problem in people who are depressed, and many individuals will use cannabis to help them sleep. Paradoxically, while the individual may solve one problem — in this case, sleep — they may creating a bigger long-term problem. Dependency.”
On another positive note, cannabis — or at least the enactment of medical marijuana laws — is saving lives! In the seminal paper, High on Life? Medical Marijuana Laws and Suicide, researchers reported that after states enact medical marijuana laws they experience a nearly 5 percent reduction in total suicide rate. And, it gets better! Among 20 to 29 year old males, the suicide rate declines by 11%, while 9% fewer 30 to 39 year old males commit suicide.
While this data provides compelling evidence for liberalizing cannabis laws, it doesn’t necessarily speak to the antidepressant powers of cannabis. There could be other factors contributing to the reduction in suicides:
First off, adverse life events which cause a shock in individuals who were otherwise happy can cause someone to commit suicide. Medical marijuana laws remove criminal penalties for qualified patients using, possessing or cultivating cannabis. While these penalties apply to medical marijuana patients, and few states allow patients to obtain a recommendation for mental health issues, most states allow patients to use marijuana to treat subjectively measured conditions like chronic pain and nausea.
Individuals often obtain a cannabis recommendation to treat chronic pain, when in fact, they are obtaining it for other reasons. By not having to risk arrest, they are no longer subjected to potential criminal penalties that could cause a whole host of issues that are known to cause significant stress. Beyond legal issues, following an arrest, individuals often face other stressors, such as the loss of employment, child custody, or a relationship.
Another interesting possible explanation is that because alcohol consumption goes down in medical marijuana states, so does suicide. There is a clear association between alcohol use and suicide. Alcoholism is associated with an increase in suicidal ideation and completed suicides.
While this research may not provide insights into the potential therapeutic benefits, it incontrovertibly demonstrates that liberalization of marijuana laws reduces suicides, and that is obviously a wonderful thing!
At the end of the day, depression is a complex condition, and cannabis is a highly complex plant with more than a hundred cannabinoids. We’re only just beginning to develop an understanding of how cannabis and cannabinoids could play a role in treating depression. Thus far, research is still in its infancy. Again, because most research has been confined to find negative associations between cannabis use and mood disorders, studies demonstrating how cannabis plays a role in psychiatric disorders are limited, but offer encouragement.
The data so far suggests cannabis research — from a sociopolitical and therapeutic perspective — should be a priority. However, as long as the federal government continues to consider cannabis a Schedule I drug — meaning they believe it’s highly addictive and there are no accepted medical uses — scientists have to navigate numerous bureaucratic obstacles to conduct much needed research. Nonetheless, the research is clear that there is a direct link between the enactment of medical marijuana laws and a reduction in suicides. The fact that suicide claims three times as many lives as homicides in the U.S. every year and cannabis could reduce this rate, provides a compelling argument to continue dismantling cannabis prohibition and ending the failed “War on Drugs.”