From Melancholia - Herbs: Cannabis

The Babylonians [Chapter 1] used cannabis as an analgesic and antidepressant. A 2010 study at the University of Mississippi suggests they were on to something. The trials used the "forced swim test," a common animal test for antidepressant activity. Rats are placed in a cylinder filled with water for 15 minutes. After 24-hours, a second 5-minute trial is performed. The time that the test animal spends without moving in the second trial is measured. This immobility time is decreased by antidepressants. Rats given Δ9-THC, the most well-known psychoactive cannabinoid, showed a significant decrease in immobility times. CBC and CBD, non-psychoactive compounds also found in cannabis, produced a similar effect. While the precise mechanisms by which each compound works are still unclear, it appears that several compounds within the cannabis plant have antidepressant effects and contribute to its mood-altering properties.

The FST showed a U-shaped curve on the response: after a certain point the antidepressant effect of these cannabinoid compounds appears to vanish. This is in keeping with the results of a 2007 study at McGill University using the synthetic cannabinoid WIN55,212-2. Says Dr. Gabriella Gobbi, who headed 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."

This suggests depressed people should use cannabis with caution. The levels of various cannabinoids can vary widely among different batches: a dose that lightens the mood one day might, with a different strain, plunge you deeper into depression. But it also suggests an untapped new field of exploration for pharmacology. Dr. Gobbi is also doing research has begun on compounds like URB597, a drug which produces noticeable antidepressant effects by raising the levels of endogenous cannabinoids in the brain.