A new study finds that a synthetic form of THC, the active ingredient in marijuana, is an effective antidepressant at low doses. But, at higher doses, the effect reverses itself and can actually worsen depression.
This study offers the first evidence that cannabis can -- at least at lower doses - increase serotonin, an important neurotransmitter that regulates mood.
The study, published in The Journal of Neuroscience, was led by Dr. Gabriella Gobbi of McGill University and Le Centre de Recherche Fernand Seguin. She says she was prompted to explore marijuana's potential as an antidepressant through her work as a psychiatrist, where she noticed that several of her patients suffering from depression smoked pot.
"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," Gobbi said in a statement. "But there were no laboratory studies demonstrating the antidepressant mechanism of action of cannabis."
To conduct their study, Gobbi's team injected the synthetic cannabinoid WIN55,212-2 into laboratory rats and then had them perform a test to measure their "depression."
The rats were placed in a water tank that was impossible to escape. Typically, the animals will swim hard for 10 minutes, trying to find a way out, then give up and float until researchers remove them. The next day, the rats are put back in the water, whereupon they give up much faster, usually after two minutes. This, researchers say, illustrates the "learned helplessness" model of depression.
Gobbi's team observed that when the rats were given small doses of the synthetic canniboid, the rats showed no depression and once again swam hard, nearly as fast on the second day as they did on the first.
The research team also used electrodes to monitor brain activity and noticed a parallel effect of an increased activity in the neurons that produce serotonin.
Gobbi believes that the antidepressant 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 stress or pain.
However, increasing the cannabinoid dose beyond a set point completely undid the benefits, with the serotonin in the rats' brains actually dropping below the level of those rats in the control group, who were simply typically "depressed."
"So we actually demonstrated a double effect: At low doses it increases serotonin, but at higher doses the effect is devastating, completely reversed," says Gobbi.
For this reason, Gobbi's team calls cannabis "a double-edged sword."
Gobbi's team concludes that there are risks associated with using cannabis directly as an anti-depressant, since it could worsen depression - especially since controlling the dosage of natural cannabis is difficult when it is smoked in the form of marijuana joints.
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.
