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Suspended for decades after controversial results, research on the hallucinogen psilocybin is showing early promise in a new series of small studies.

In research presented at the annual meeting of the American College of Neuropsychopharmacology (ACNP), scientists highlighted the latest findings on the use of psilocybin, the synthetic version of the active compound in “magic mushrooms,” as a treatment for anxiety in terminal cancer patients, in smoking cessation and as a treatment for alcoholism.

Some of the studies are not complete and have not yet been reviewed by other experts, but they provide new information on psilocybin’s effects. Psilocybin is the active ingredient in over 100 species of mushrooms in the Psilocybe class, used for hundreds of years in shamanic ceremonies and other rituals in South America.

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Research conducted during the 1950s and early ’60s into possible therapeutic uses of drugs like LSD, another hallucinogen, and psilocybin suffered from their popularity in the counterculture of the time, which led to both the ban of recreational use of psilocybin and an end to virtually all the medical studies on its effects on people. Early studies suggested the compounds might help to fight addictions and ease end-of-life fears.

Pharmacologists continued to study the drugs, however, primarily in animal models, leading to the recognition in the 1950s that LSD was similar to the brain chemical serotonin (indeed, LSD was later found to act on certain serotonin receptors) and providing one of the first hints that drugs could affect behavior by affecting particular brain chemicals.

“[So] much of modern neurobiological chemistry results from studying psychedelics,” said Dr. Charles Grob, director of child psychiatry at Harbor-UCLA Medical Center, who is studying the effects of psilocybin on anxiety in terminal cancer patients.

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In Johns Hopkins’ ongoing program of psilocybin research, scientists have treated over 150 volunteers in 350 drug-trial sessions. Although many participants experienced at least some type of anxiety reaction while on the drug, none of them reported lasting harm, and 70% rated the experience as one of the top five most meaningful events of their lives, comparable to the birth of a first child or the loss of a parent.

Like previous psychedelic experimenters, today’s volunteers often report profoundly mystical experiences. But modern researchers are far more careful about documenting what the drugs actually do, avoiding the exaggerated claims of early pioneers in the field (including Harvard University’s Timothy Leary), which led to more skepticism and criticism than productive investigation.

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UCLA’s Grob studied 12 cancer patients with end-stage disease, ages 18 to 70, all of whom were highly anxious in facing death. They were given preparatory therapy sessions so that they would know what to expect while under the influence of psilocybin and then had two sessions a month apart, one with a placebo and one with psilocybin. The vitamin niacin was used in a high dose as the placebo because it produces a physiological sensation of burning or itching on the face that is harmless but produces some “drug” effect.

During their drug sessions, participants listened to music on headphones in a hospital room that had been upgraded with fresh flowers and more colorful furnishings than the typical sterile decor. They were asked to bring pictures of their loved ones and of important life occasions or experiences as well. During the sessions, therapists sat with them but did not direct them to reflect on anything in particular and only monitored the session and helped them to calm down if they became anxious.

“Nobody had a significant anxiety reaction or ‘bad trip,’” Grob reported, citing data he published in the Archives of General Psychiatry on the research in 2011. Six months later, participants showed significant reductions in depression symptoms. Curiously, however, although they didn’t report actually feeling anxious less of the time, they no longer considered themselves as being overly anxious or worried people.

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The studies on smoking cessation and on alcoholism have only just begun, but they show encouraging results in a small group of volunteers. Says Paul Kenny, associate professor of neuroscience at the Scripps Research Institute in Florida and a member of the program committee for the ACNP meeting: “The potential beneficial effects of psilocybin on addiction is an important question that should [be] thoroughly explored. Nevertheless, it is important to sound a note of caution. Psilocybin is unlikely to be used to treat addiction. As with other hallucinogenic drugs, it can have worrying side effects such as psychological distress or even psychosis.”

He adds, “Nevertheless, the renaissance in psilocybin research suggests that if we can understand the biological mechanisms underlying its therapeutic actions, then it may be possible to develop a new generation of drugs that lacks the notable hallucinogenic properties of psilocybin but that retains its beneficial effects. This assumes, of course, that the therapeutic and psychoactive properties of psilocybin can indeed be separated.”

It remains to be seen, however, whether that will be possible. Kenny thinks it could be, noting that the drug is relatively “promiscuous” and activates multiple brain receptors but only causes hallucinatory effects by one of those actions. But in psychedelic therapy, it could alternatively turn out that the psychological experience of the mind is what matters for the brain changes seen after taking the drug.

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