Timothy Leary really screwed things up for science. By abandoning the scientific method for a mystical embrace of hallucinogenic drugs, the Harvard-professor-turned-LSD-evangelist became a symbol of ’60s-era drug-fueled degeneracy. Worse, the ensuing backlash pushed these drugs underground and caused an enormously promising field of research to go dormant for nearly half a century.

Or so say some scientists who met in Oakland, California last weekend for a conference on the science and therapeutic potential of psychedelic drugs. “The antics of Timothy Leary really undermined the scientific approach to studying these compounds,” psychopharmacologist Roland Griffiths of Johns Hopkins University told the audience.

But the times they are a-changin’. In recent years, a small cadre of scientists has cautiously rekindled the scientific study of psychedelics. At the conference, they reported new findings on how these drugs scramble brain activity in ways that might help explain their mind-bending effects. They’re also slowly building a case that these drugs might help people with depression, anxiety and other disorders.

Roughly a dozen small clinical trials are now underway worldwide. But the idea isn’t “take two tabs of acid and call me in the morning.” Instead, these trials are testing the idea that psychedelics taken in a therapist’s office as part of a series of psychotherapy sessions can make talk therapy more effective.

'The illegality of these drugs ... is one of the greatest scandals in modern research'

“Now that we’ve been able to start getting some evidence on the benefits, it changes people’s calculus,” said Rick Doblin, the founder and executive director of the Multidisciplinary Association for Psychedelic Studies (MAPS), one of the meeting’s sponsors.

Doblin and MAPS have been battling regulators since the mid-80s to allow research and clinical trials with psychedelics. The recent revival of psychedelic science may be one sign their efforts are finally paying off.

Public attitudes towards illegal drugs in general may be shifting. A recent Pew Research Center survey, for example, found for the first time that more than half of Americans think marijuana should be legal. Baby boomers in particular, who may have hidden their stash while raising kids, seem to be loosening up in their old age, the survey found.

The interest in psychedelics may also have something to do with a growing sense of frustration over the lack of promising new psychiatric drugs in the pipeline. Many of the current drugs are based on compounds discovered serendipitously in the 1950s, and true innovation has been so hard to come by that many companies are giving up.

Meanwhile, people have been using hallucinogens for centuries, often in religious healing ceremonies, and yes, sometimes just for the hell of it. But just because they’re party drugs for some doesn’t mean they can’t be the subject of serious scientific inquiry. Or does it? After all, it didn’t end so well the first time around.

From its inception in 2010, the Psychedelic Science meeting has brought together an interesting mix of people. A record 1,800 of them attended this year. The prevalence of ponytails, nose rings and hemp accessories is predictably higher than at a typical science conference. There was also a tea lounge, a psychedelic art gallery, and a quiet room for anyone in need of riding out a rough trip.

“Absolutely some scientists would see the rainbow colors on the logo and the psychedelic art exhibits and say ‘that’s not real science,'” said Brad Burge, the communication director for MAPS. At the same time, some of the more mystically inclined devotees of psychedelics are averse to the scientific dissection of what they see as a sacred experience, Burge says. The conference isn’t for the folks at those ends of the spectrum.

Burge acknowledges there’s a tricky balancing act involved in hosting a forum for scientists who want their work to be taken seriously without excluding those who use psychedelic drugs recreationally. Even so, “we’re trying to get around the idea that there has to be a separation,” he said.

After all, this latter group helps fund much of the research through their donations to MAPS and other private organizations like the Heffter Research Institute and Beckley Foundation. Government funders like the National Institutes of Health are still skittish about psychedelic research.

This year’s conference showcased one area of research that’s exploded recently. It involves ayahuasca, a potent hallucinogenic brew of vines and leaves used in healing ceremonies by Amazonian shamans (as well as tourists — a pamphlet included in the conference swag bag advertised one center offering ayahuasca retreats).

Dráulio Barros de Araújo, a neuroscientist at the Brain Institute at the Universidade Federal do Rio Grande do Norte in Brazil, presented new findings from an fMRI brain scan study with 10 experienced ayahuasca users, followers of Santo Daime, a spiritual practice that uses the brew.

Araújo’s team found that ayahuasca reduces neural activity in something called the default mode network, an web of interconnected brain regions that fire up whenever people aren’t focused on any specific task. It’s active when people daydream or let their minds wander, for example.

The default mode network has been a hot topic in neuroscience in recent years. Scientists don’t really know what it does, but they love to speculate. One interpretation is that activity in this network may represent what we experience as our internal monologue and may help generate our sense of self.

Last year, British scientists reported that psilocybin, the active ingredient in magic mushrooms, like ayahuasca, reduces activity in the brain’s default mode network.

The researchers proposed that interfering with the default network could be how psychedelic drugs cause what users often describe as a disintegration of the self, or even a sense of oneness with the universe.

Robin Carhart-Harris, the neuroscientist who led the psilocybin study, reported new findings at the conference from a study that used a method called magnetoencephalography, which tracks brain activity with better time resolution than fMRI does. The results suggest psilocybin affects not only the default mode network, but also disrupts a certain type of rhythmic brain activity.

'This opens a door to the scientific study of mystical experience'

Individual subjects who experienced more of this desychronization while on the drug tended to report a greater subjective sense of disintegration. “For me this is the most interesting observation of the lot,” Carhart-Harris said. “Our sense of self, the sense of being someone, really is a kind of an illusion. All we are is a product of our brain activation.”

Eroding the sense of self may be one way hallucinogens produce what many users experience as profound spiritual insights. In 2008 Griffiths and his team at Johns Hopkins reported that the majority of 36 ordinary people who took psilocybin for the first time in an 8-hour session in his lab still regarded the experience as one of the five most personally meaningful events of their lives more than a year later. Two-thirds of them rated it among their top five spiritual experiences.

“It seemed so improbable to me when we started that they’d compare this to birth of a child or death of a parent,” he said at the conference.

More recently, Griffiths surveyed 1,600 recreational psilocybin and found that 40 percent ranked the experience in their top five most personally meaningful. The somewhat lower percentage isn’t surprising, Griffith says, because in the lab he and his colleagues went out of their way to make the environment as positive and comfortable as possible. But he’s encouraged that the results seem to generalize.

“This opens a door to the scientific study of mystical experiences,” Griffiths said. In future work, he hopes to investigate how the psilocybin experience may differ in people with different personality types, religious backgrounds, and genetics.

Clearly, drugs like psilocybin have powerful effects on the mind, but the rationale for using them in psychiatry requires a fair amount of hand waving. The same could be said of virtually all psychiatric treatments already on the market, however: Nobody really knows how they work.

The classic psychedelics, including psilocybin and LSD, stimulate receptors for serotonin, a neurotransmitter that’s also targeted, albeit in different ways, by approved antidepressant and anti-anxiety drugs like Prozac and Zoloft.

Several scientists at the conference pointed to findings that activity in the brain’s default mode network is elevated in people with depression. Because psilocybin and ayahuasca seem to dampen activity in this network, perhaps they could help.

It’s hard to connect those dots without a strong dose of speculation, but one idea is that the elevated activity in the default mode network reflects too much attention directed inward. People in the grips of depression, the thinking goes, are trapped in an endless cycle of critical self-examination, and a little neural desynchronization might help them reboot.

Araújo presented promising preliminary findings on using ayahausca to reduce symptoms of depression, and he’s recently gotten approval for a larger clinical trial in Brazil. The British group has approval to begin a trial with psilocybin.

Recent clinical trials Ayahuasca Depression: Brazil (upcoming)

Depression: Brazil (upcoming) Psilocybin Depression: UK (pending), Smoking cessation: US (ongoing)

Depression: UK (pending), Smoking cessation: US (ongoing) MDMA PTSD: Switzerland (completed), Spain (completed), Israel (ongoing), US (ongoing), Canada (upcoming)

PTSD: Switzerland (completed), Spain (completed), Israel (ongoing), US (ongoing), Canada (upcoming) LSD End of life anxiety: Switzerland (completed)

End of life anxiety: Switzerland (completed) Ibogaine Addiction: Mexico, New Zealand (ongoing) Source: MAPS/Psychedelic Science conference

Meanwhile, researchers in Switzerland, Israel, and elsewhere have been investigating MDMA (more commonly known as Ecstasy) to treat post-traumatic stress disorder (PTSD) and other anxiety disorders. Ravers love the drug for the sense of euphoria and comfort and closeness with others it engenders. Some therapists think its anti-anxiety and pro-social effects might help put anxious patients at ease and make them more receptive to psychotherapy.

MAPS is sponsoring several studies to test this idea. The first, begun in 2004 and led by psychiatrist Michael Mithoefer in South Carolina, treated 19 people with PTSD, mostly women who’d survived sexual abuse or assault. Although these patients had had little success with conventional treatments, 14 of 19 still had significant reductions in their symptoms one to six years after undergoing MDMA-assisted psychotherapy, the researchers reported in the Journal of Psychopharmacology in November.

Another trial underway in South Carolina is testing the therapy in military veterans, police and firefighters, and Doblin says MAPS has been talking with the Pentagon about a study involving active duty soldiers with PTSD. MAPS is willing to pay for it if the Pentagon will allow the soldiers to participate. “We were there about a month ago, and we got a very good reception,” he said. “Now we’re working our way up the chain of command.”

The fact that the US military would even consider such a thing is a sign of how much things have changed. But that’s not to say there’s no resistance left.

Psychedelic scientists still face obstacles at every step of the process, from getting research funding, to getting the compounds themselves, to publishing the findings, says psychiatrist David Nutt of Imperial College London. Nutt recently won a large grant from the British government to conduct a clinical trial of psilocybin for depression. But red tape is holding it up.

To comply with the law, Nutt has to find a manufacturer who’s capable of making medical-grade psilocybin and has all the proper permits to make controlled substances. So far, he hasn’t found one. The study is on hold.

“The illegality of these drugs has profoundly distorted research and continues to do so,” Nutt said at the conference. “It’s one of the greatest scandals in modern research.”