"Magic mushrooms," the recreational hallucinogen long associated with music festivals and hippies, may also one day prove to have a powerful pharmaceutical effect for people with treatment-resistant depression.

In a small pilot study at the Center for Neuropsychopharmacology at Imperial College London, more than half of participants who took psilocybin, the active compound in psychedelic mushrooms, showed a marked improvement in their depression symptoms while also demonstrating the compound's safety in a supervised setting.

This is the first clinical trial to use the active chemical compound in so-called "magic mushrooms" to treat major depression. If the findings are confirmed in larger studies, it could mean a change in the way we treat depression symptoms in those who don't respond to therapy and traditional medications, like selective serotonin reuptake inhibitors.

What we knew before:

Mushrooms from the genus Psilocybe contain psilocybin, which the human body breaks down into a substance called psilocin. This psychedelic substance then crosses the blood-brain barrier and binds to a specific serotonin receptor known as 5-HT2A, creating a profound alteration of consciousness that has been described as a mystical event, a spiritual journey or simply a "trip." Psychedelic compounds in LSD, ayahuasca and mescaline bind to this same receptor.

Human beings have been consuming psychedelic mushrooms for thousands of years because of this effect, but it wasn't until the 1950s that scientists began examining psilocybin's therapeutic properties in earnest.

Previous pilot studies have shown that psilocybin could be a promising new way to treat mental health symptoms like anxiety, obsessive-compulsive behavior and addiction. Those worried about the compound's effects on mental health needn't worry: Research shows that lifetime use of psychedelics like psilocybin is not an independent risk factor for mental health problems.

Beyond binding with the 5-HT2A receptor, scientists don't really understand the chemical process that leads to this psychedelic experience. It's even less clear how having a mystical experience might produce long-term mental health benefits, but there are at least two theories, according to Dr. Stephen Ross, director of the Psychedelic Research Group at NYU Langone Medical Center. He was not involved in the study, but reviewed it.

In the first theory, the memory of the "trip" -- which can be a profound and extremely meaningful experience -- could have a strong psychological effect on people, lifting their moods for months at a time. Alternatively, there may be a biological explanation: It's possible the binding of psilocin to the serotonin receptor sets off a cascade of yet-unknown chemical reactions that persist for weeks or months.

The study details:

Six men and six women with chronic, treatment-resistant, moderate to severe major depression consented to take two different doses of psilocybin (10 mg and 25 mg), separated by one week. There was no control group, and the participants and in what's called an "open label trial," the investigators all knew that they were either taking or administering psilocybin.

During the dosing sessions, participants relaxed on a bed in a room with dim lighting and listened to music through earphones. Supervisors monitored their blood pressure, heart rate and the psychoactive effects of the compound intermittently for up to six hours after they took the pills, while psychiatrists offered support but mostly let patients have their own "inner journey," as the study put it, without interruptions.

None of the participants experienced serious or unexpected negative side effects that required medical intervention from the dosing, though some reported mild anxiety, confusion, nausea or headache. The psychedelic effects peaked about two to three hours after dosing and then became negligible after about six hours.

Most significantly, eight of the 12 patients responded extremely well to the psilocybin, meeting the criteria for remission from depression one week after the two treatments. After three months, five of them remained in remission, while another two continued to show improvement in their depression symptoms compared to baseline. Overall, all 12 patients showed at least some improvement in their symptoms for up to three weeks after the dose.

The results seem promising, but there are some caveats. The overall positive response to the dosing treatment could in part be chalked up to the fact that the participants actively sought out the psilocybin trial and were probably expecting the medicine to work on some level, creating a bias in favor of the intervention. Indeed, five of the participants had already tried psilocybin at least once -- one just six months before the experiment, others ranging from 14 to 48 years prior.

This past experience with a drug and its presumed positive effects could increase suggestibility and expectancy in people, which could affect the results. Double-blind trials in which neither patient nor therapist knows which intervention they received or administered, as well as the inclusion of a control group, could address these issues in