The effects were modest and waned over time but they occurred with a single experimental dose in people who previously had received little relief from standard antidepressants.

The study is part of a resurgence of research into potential medical uses of hallucinogenic drugs, and the results echo findings in smaller studies of the mushroom compound psilocybin.

The researchers say larger and longer studies are needed to determine the effectiveness and safety of using psilocybin for depression. Their results were published on Wednesday in the New England Journal of Medicine.

"The findings are both intriguing and sobering,'' said Bertha Madras, a psychobiology professor and researcher at Harvard Medical School.

Commenting in a journal editorial, Madras said the study was the most rigorous to date evaluating psilocybin for treating depression. She was not involved in the research.

Researchers tested the chemical in 233 adults in the US, Europe and Canada. Each swallowed capsules containing one of three doses of psilocybin during a six- to eight-hour session. Two mental health specialists guided them through hallucinatory experiences.

Results for the highest and medium-strength doses were compared with those in the very low-dose control group. There was no comparison with an inactive dummy drug or with conventional antidepressants.

Depression symptoms declined in all three groups, with the greatest initial improvement in the highest-dose group. At three weeks, 37 per cent of high-dose recipients had substantially improved. But those effects weren't as good as seen in studies of standard antidepressant drugs, and the results waned in the following weeks.

At three months, 20 per cent in the high-dose group still saw substantial improvement.

Compass Pathways, a London-based firm developing psilocybin for commercial use, paid for and helped conduct the study. It recently announced it is launching a larger, more rigorous study.

Side effects, including headaches and nausea, were common in all three study groups. Serious side effects were uncommon but they included suicidal thoughts and self-injury, mostly in participants with a history of suicidal thoughts.

Dr David Hellerstein, a co-author and Columbia University research psychiatrist, said those side effects were not surprising given the intensity of the psychedelic experience, and they underscored the importance of using psilocybin in a medical setting.

"This is not a home run, but it's very encouraging,'' Hellerstein said, noting that improvement was seen after just one dose.

However, he said it was likely that additional doses would be needed to achieve long-lasting results. That could make use costly, given the need for several hours of medically supervised treatment.

Australian Associated Press