Could ‘magic mushrooms’ work magic for certain mental disorders?

New research in Proceedings of the National Academy of Sciences sheds light on why one of the mushrooms' hallucinogenic chemical compounds, psilocybin, may hold promise for the treatment of depression.

Scientists explored the effect of psilocybin on the brain, documenting the neural basis behind the altered state of consciousness that people have reported after using magic mushrooms.

"We have found that these drugs turn off the parts of the brain that integrate sensations – seeing, hearing, feeling – with thinking," said David Nutt, co-author of the study and researcher at Imperial College London in Britain.

Nutt is also Britain's former chief drug adviser, who has published controversial papers about the relative harms of various drugs. He was asked to leave his government position in 2009 because "he cannot be both a government adviser and a campaigner against government policy," according to a letter in the Guardian from a member of the British Parliament.

Psilocybin is illegal in the United States and considered a Schedule 1 drug, along with heroin and LSD. Schedule 1 drugs "have a high potential for abuse and serve no legitimate medical purpose in the United States," according to the Department of Justice.

But in the early stages of research on psilocybin, there's been a bunch of good news for its medicinal potential: psilocybin has shown to be helpful for terminally ill cancer patients dealing with anxiety, and preliminary studies on depression are also promising.

Nutt's study is also preliminary and small, with only 30 participants. His group used magnetic resonance imaging (MRI) to look at how the brain responds to psilocybin, from normal waking consciousness to a psychedelic state.

The study found that the more psilocybin shuts off the brain, the greater the feeling of being in an altered state of consciousness, he said. It's not the same as dreaming, because you're fully conscious and aware, he said.

The medial prefrontal cortex, the front part of the brain in the middle, appears to be crucial - it determines how you think, feel and behave. Damage to it produces profound changes in personality, and so if you switch it off, your sense of self becomes fragmented, Nutt said. That's what happens when psilocybin decreases activity in it.

"Some people say they become one with the universe," he said. "It's that sort of transcendental experience."

Another brain region that psilocybin affects is the anterior cingulate cortex, which is over-active in depression, Nutt said. Some patients with severe depression that cannot be treated with pharmaceuticals receive deep brain stimulation, a technique of surgically implanting a device that delivers electrical impulses directed at decreasing activity in that brain region. Psilocybin could be a cheaper option, Nutt said.

It's counterintuitive that a hallucinogenic drug would de-activate rather than stimulate key brain regions, although other studies have shown a mix of results regarding psilocybin turning brain areas on and off, said Roland Griffiths, a professor of psychiatry and neuroscience at the Johns Hopkins University School of Medicine. Griffiths was not involved in Nutt's study, but has also researched the effects of psilocybin.

Even if this drug gets approved someday, don't expect to be able to pick up a prescription for psilocybin at your local pharmacy, Griffiths cautioned. There's too much potential for abuse, he said.

Although scientists have found many positive effects of psilocybin in experimental trials, there are, of course, potential dangers. Some people have frightening experiences while on psilocybin. The fear and anxiety responses of magic mushrooms can be so great that, when taken casually in a non-medical setting, people can cause harm to themselves or others. They may jump out a window or run into traffic because of a panic reaction.

The drug would have to be administered in a controlled setting in a hospital, if found in further research to be an effective and safe therapy for certain mental illnesses, Griffiths said. It would not be appropriate for people who already have psychotic disorders such as schizophrenia, since psilocybin can exacerbate those symptoms.

But among healthy volunteers, Griffiths and others have found that people may have long-lasting positive effects from the vivid memories of being on psilocybin (in a controlled, experimental setting). People report mystical experiences of feeling the "interconnectedness of all things," which can be life-changing.

"People claim to have an enhanced sense of self, more emotional balance, they're more compassionate, they're more sensitive to the needs of others," he said. "They have more well-being and less depression, but they're not 'high' in any conventional sense. They feel like their perceptual set has shifted."

The memories of the psilocybin experience, and positive outcomes that users attribute toward them, can last as much as 25 years, research has shown.

Still, there's just not enough known yet about the long-term safety of psilocybin to say whether it could also do damage to the brain, Griffiths said.

"There’d have to be changes in the brain for these long-lasting memories and attributions to occur," Griffiths said. "We don’t know how those changes occur, and why."