Cannabis Good and Bad News for Depression Treatment

First the good news: recent neurobiological research from McGill University has found that THC, one of marijuanas active ingredients, is a helpful anti-depressant at low doses. Now the bad news- at higher doses, the effect is nullified and can even worsen depression, along with other psychiatric conditions such as psychosis.

This is the first study to offer evidence that cannabis can increase brain levels of the neurotransmitter serotonin, at least at lower doses. It is known that depletion of serotonin in the brain leads to depression, which is why SSRI-class anti-depressants such as Paxil and Prozac work via enhancement of serotonin levels in the brain.

In the study, published in the October 24 issue of The Journal of Neuroscience, lab animals were injected with synthetic cannabinoid (WIN55,212-2) and then tested with the Forced Swim test. This is a test that measures “depression” in animals. Researchers saw an antidepressant effect, as well as increased activity in the neurons that produce serotonin. Increasing the cannabinoid dose beyond a set point completely undid the benefits, said Dr. Gabriella Gobbi of of McGill University, who led the study.

“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.” said Dr. Gobbi.

The Endo-cannabinoid System

The anti-depressant and intoxicating effects of cannabis are owed to its similar chemical structure 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.

The endocannabinoid system regulates the probability of neurotransmitter release in many neuronal tissues including the hippocampus, amygdala, basal ganglia, and cerebellum. The endocannabinoid system is believed to be important in memory, motor learning , and synaptic plasticity.

Dr. Gobbi and her colleagues were inspired to look at 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.

Adapted from a McGill University Press Release authored by Mark Shainblum

Cannabis Leaf Image- Wellcome Images Creative Commons.