Marijuana Improves Depression in Low Doses, Worsens It in High Doses, Study Says

Marijuana is a potent antidepressant in low does, but worsens symptoms in high doses, according to a new study

THC, the active ingredient in marijuana, increases serotonin when smoked in low doses, similar to SSRI antidepressants, such as Prozac, according to researchers from McGill University and Le Centre de Recherche Fernand Seguin of Hôpital in Quebec and l'Université de Montréal in Montreal.

But at higher doses, the effect reverses itself and can actually worsen depression and other psychiatric conditions like psychosis.

During the study, published in the October 24 issue of The Journal of Neuroscience, laboratory rats 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 and 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 and Le Centre de Recherche Fernand Seguin of Hôpital Louis-H. Lafontaine.

"So we actually demonstrated a double effect: At low doses it increases serotonin, but at higher doses the effect is devastating, completely reversed," she said in a news release.

The antidepressant 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, said Gobbi. They interact with the brain through structures called cannabinoid CB1 receptors.

The study demonstrated that these receptors have a direct effect on the cells producing serotonin, which is a neurotransmitter that regulates the mood, she said.

Because controlling the dosage of natural cannabis is difficult — particularly when it is smoked in the form of marijuana joints — using it directly as an antidepressant would be difficult, said the researchers.

"Excessive cannabis use in people with depression poses high risk of psychosis," said Gobbi.

Gobbi and her colleagues are focusing their research on a new class of drugs which enhance the effects of the brain's natural endo-cannabinoids.