marijuana effects on serotonin

Cannabis: Potent Anti-depressant In Low Doses, Worsens Depression At High Doses

A new neurobiological study has found that a synthetic form of THC, the active ingredient in cannabis, is an effective anti-depressant at low doses. However, at higher doses, the effect reverses itself and can actually worsen depression and other psychiatric conditions like psychosis.

It has been known for many years that depletion of the neurotransmitter serotonin in the brain leads to depression, so SSRI-class anti-depressants like Prozac and Celexa work by enhancing the available concentration of serotonin in the brain. However, this study offers the first evidence that cannabis can also increase serotonin, at least at lower doses.

Laboratory animals were injected with the synthetic cannabinoid WIN55,212-2 and then tested with the Forced Swim test — a test to measure “depression” in animals; the researchers observed an antidepressant effect of cannabinoids paralleled by an increased activity in the neurons that produce serotonin. However, increasing the cannabinoid dose beyond a set point completely undid the benefits, said Dr. Gabriella Gobbi of McGill University.

“Low doses had a potent anti-depressant effect, but when we increased the dose, the serotonin in the rats’ brains actually dropped below the level of those in the control group. So we actually demonstrated a double effect: At low doses it increases serotonin, but at higher doses the effect is devastating, completely reversed.”

The anti-depressant and intoxicating effects of cannabis are due to its chemical similarity to natural substances in the brain known as “endo-cannabinoids,” which are released under conditions of high stress or pain, explained Dr. Gobbi. They interact with the brain through structures called cannabinoid CB1 receptors. This study demonstrates for the first time that these receptors have a direct effect on the cells producing serotonin, which is a neurotransmitter that regulates the mood.

Dr. Gobbi and her colleagues were prompted to explore cannabis’ potential as an anti-depressant through anecdotal clinical evidence, she said. “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 anti-depressant mechanism of action of cannabis.”

Because controlling the dosage of natural cannabis is difficult — particularly when it is smoked in the form of marijuana joints — there are perils associated with using it directly as an anti-depressant.

“Excessive cannabis use in people with depression poses high risk of psychosis,” said Dr. Gobbi. Instead, she and her colleagues are focusing their research on a new class of drugs which enhance the effects of the brain’s natural endo-cannabinoids.

“We know that it’s entirely possible to produce drugs which will enhance endo-cannabinoids for the treatment of pain, depression and anxiety,” she said.

The study, published in the October 24 issue of The Journal of Neuroscience, was led by Dr. Gabriella Gobbi of McGill University and Le Centre de Recherche Fernand Seguin of Hôpital Louis-H. Lafontaine, affiliated with l’Université de Montréal. First author is Dr. Gobbi’s McGill PhD student Francis Bambico, along with Noam Katz and the late Dr. Guy Debonnel* of McGill’s Department of Psychiatry.

A new neurobiological study has found that a synthetic form of THC, the active ingredient in cannabis, is an effective anti-depressant at low doses. However, at higher doses, the effect reverses itself and can actually worsen depression and other psychiatric conditions like psychosis.

Cannabis And Serotonin: Can This Relationship Treat Anxiety?

As cannabis consumers, we’ve all experienced how it can improve our mood and help us relax. But nowadays, we’re starting to see how these qualities may truly help reduce symptoms of depression and anxiety – and it seems serotonin plays a major role.


The human body uses neurotransmitters to perform various functions. These “chemical messengers” communicate throughout the central nervous system. Serotonin is one such neurotransmitter made in the brain and intestines. It works to regulate mood, nausea, appetite, bone health, sleep, emotions, and even sexual function. The vast majority can be found in the gastrointestinal tract.

Serotonin is produced through a conversion process from essential amino acid tryptophan and tryptophan hydroxylase. Tryptophan can be found in common foodstuffs like cheese, red meat, and nuts. A lack of this amino acid in our diet will result in a serotonin level reduction. This, in turn, is linked to anxiety, depression, and other mood disorders. It’s because of factors like this that our diet is so closely linked to our mood and emotions.


The relationship between cannabis and serotonin is very interesting. Not only are cannabinoid receptors found [1] on serotonin neurons, they’re also apparent in the corresponding inhibitory receptors.

This leads to the conclusion that cannabinoids may increase serotonin levels in certain conditions, and reduce them in others. A migraine, for example, is a condition that correlates with increased serotonin levels in the brain. In this situation, the activation of inhibitory receptors would be the best solution to the problem. When one consumes THC in high doses, it triggers the inhibition of serotonin receptors. Just a few puffs of a jay will actually worsen your migraine. Once one recognises the importance of serotonin in mood disorders and the impact of cannabis on serotonin production, it’s easy to see how cannabis can really help patients suffering from certain mental illnesses.


In 2016, a study [2] was performed where mice were administered a chemical that mimics CBD. This led to the antidepressant effects one might expect from this calming cannabinoid. The interesting part was that when the researchers blocked the serotonin receptors, the effects were no longer noticeable. This further suggests that cannabinoids and the serotonergic system are in fact linked.

5 years before this, a paper [3] was published that showed how increasing endocannabinoid levels in the body made antidepressants more effective. The study also found that blocking CB1 receptors would completely stop the antidepressants from working.

This demonstrates how the endocannabinoid and the serotonergic systems work together in helping us achieve homeostasis. It also shows that if there is going to be a medicine developed, these two systems will have to be stimulated in a way that is balanced and supportive to the other. So is cannabis the future of antidepressants?


When comparing anxiety levels of 50 individuals who smoked cannabis regularly and 50 who didn’t smoke at all, a study [4] showed some interesting results. The patients who smoked marijuana experienced much lower levels of anxiety than those who didn’t. A 2012 paper [5] sought to assess multiple studies that looked into CBD as an anti-anxiety medication. Even though dosage and consumption mechanism are still factors that require more research, they concluded that CBD is an effective treatment for this psychological condition.

Before you embark on a healing journey with cannabis, it’s important you know what you’re doing. Not every strain will have the same effect on different people. It’s essential to keep track of how you feel in a “weed journal” of sorts. This will help you know which are your favourite strains as well as your ideal dosage and intake frequency. Another factor you need to pay attention to is THC. It isn’t always the best medicine to combat anxiety; CBD is what you really want. Look for strains that have a balanced THC:CBD profile or are CBD-dominant. Euphoria, Painkiller XL, and Stress Killer are three fantastic CBD strains from RQS to consider trying. The first two mentioned only have 9% THC, and Stress Killer has a manageable content of 11% THC.

As long as you stay informed and keep track of how you feel, you may very well feel a reduction in anxiety over time. Like many other scientific queries related to cannabis, so much more research is needed to confidently provide advice on the exact way to use cannabis as a treatment for various psychological disorders. What is encouraging, however, is that cannabis is a non-toxic substance that also seems to clearly interact with serotonin. In the future, we’re bound to see this relationship fleshed out further.

Find out how the relationship between cannabis and serotonin may help fight various psychological disorders like anxiety and depression.