In 1966, psychedelic drug advocate and former Harvard professor Timothy Leary appeared on the Merv Griffin Show.

"I'm in the unfortunate situation of being about 20 years ahead of my time," Leary said. When asked how many times he'd taken LSD, he answered 311. The audience gasped.

Leary was fired for experimenting with psychedelics on undergraduates, and before long, LSD was classified as a Schedule I drug, meaning it had "no known medical use." Research on the medical uses of LSD and other psychedelics came to a halt.

Today, psychedelic drug research is coming back, and scientists are picking up where Leary and other researchers left off, conducting experiments on therapeutic uses of these drugs. But the research still faces stigma, and funding is hard to get.

Renewing The Research

Stanislav Grof was one of the leading researchers on the therapeutic applications of LSD in the 1950s and '60s. He studied the effect of hallucinogens on mental disorders, including addiction.

Grof says LSD seemed to accelerate treatment of mental illness exponentially.

"It was quite extraordinary," Grof tells NPR's Arun Rath. "This was a tremendous deepening and acceleration of the psychotherapeutic process, and compared with the therapy in general, which mostly focuses on suppression of symptoms, here we had something that could actually get to the core of the problems."

But the pervasive image of LSD was that it was not an acceptable treatment.

The Schedule 1 classification of LSD and other hallucinogenic substances in 1970 was a huge blow to research. Grof abandoned his experiments on alcoholism.

Through the "Just Say No" campaigns of the 1980s, no researchers were willing to jump through all the hoops necessary to study stigmatized drugs.

But by the '90s, attitudes had begun to change, and there was a flurry of studies on psychedelic drugs.

By the 2000s, a small but growing research community was picking up where Grof and others had left off. One area that showed promise was using hallucinogens to ease anxiety and depression in patients with cancer, like Erica Rex.

"I was diagnosed with breast cancer, stage 2, in 2009," Rex says. "Even if people are happy to spout statistics at you about your chances of survival, that's not what happens in emotional or human terms. I went through the treatment, and then there are some drugs that have terrible side effects."

Those side effects can include depression, which Rex experienced. She says she became obsessed with the possibility of her death, and it was crippling. Then Rex found out she might qualify for a study on the experimental drug psilocybin, an active compound in psychedelic mushrooms.

To be determined eligible for the study, she took a series of lab tests, spent days at the hospital and then went through a very intense psychological workup with some probing questions.

"It's like having five years of therapy or psychoanalysis stuffed into three days. It was exhausting," she says.

But at the end of it all, she was approved for the study. She was given two doses of the hallucinogen in two separate sessions, with trained guides sitting with her as the drugs — taken in the form of a small, purple pill — took effect.

The session began in a windowless room, with Rex wearing an eye shade and headphones to listen to music. She experienced moments of laughter, memories of the past and emotional highs and lows. But it was not, Rex says, like a dream.

"People want it to be described as a dream, but it's not — it is actual," she says. "It is all entirely real."

Once the session was over, Rex says, she spent time writing up everything that she remembered. And in the end, she says, it helped her depression.

"I'm much better," she says. "I am able to plan; I don't sit around obsessing about what the future may hold nearly as much."

A Word Of Caution

As much as Rex says the psychedelic experience helped her, some authorities say there are significant questions about the safety and efficacy of such treatment. Glen Hanson, a senior adviser for the National Institute on Drug Abuse, says there "still needs to be an asterisk next to it."

"I don't think it's a brand new antidepressant," Hanson says. He says the main problem with hallucinogens is the lack of predictability and that they affect people in wildly different ways. Hanson says hallucinogens scramble the brain's chemistry, so if someone's brain chemistry is "already abnormal, where are you going to end up with this person?"

All of the questions Rex answered before her experiment were intended to address that concern, weeding out people who might have issues. But Hanson says questions like that aren't foolproof.

Even Charles Grob of the University of California, Los Angeles — one of the few researchers actually studying medical uses of psychedelic drugs — agrees there are reasons to be cautious. He says researchers have demonstrated safety in the lab, but the real risks are in the outside world, in recreational settings.

Outside laboratory settings, he says, "naive individuals who really don't know what they're getting into take it under adverse conditions [and] often mix it with alcohol or other drugs. That's where you have the serious potential for adverse outcome."

Finding Support

Along with facing a tougher approval process, psychedelic drug research doesn't attract much funding, Grob says. He says national funding sources, like the National Institutes of Health, are not receptive at all. All of his support up to this point has come from private sources, which he says is difficult in a tough economy.

"Hopefully that will change and hopefully in the near future there may be some opportunity to see some progress in that arena," he says.

Despite these challenges, Grob is pressing on and has been approved to begin a new study next month on social anxiety in adults on the autism spectrum and the drug MDMA. He says the country needs to recognize that the '60s are over and that Timothy Leary is gone and no longer on the stage.

"I believe we are on the threshold of some very exciting discoveries," he says, "that the health field can only benefit from."

Copyright 2015 NPR. To see more, visit http://www.npr.org/.

Transcript

ARUN RATH, HOST:

If you're just joining us, this is ALL THINGS CONSIDERED from NPR West. I'm Arun Rath.

In 1966, psychedelic drug advocate and former Harvard professor Timothy Leary appeared on "The Merv Griffin Show."

(SOUNDBITE OF TV SHOW, "THE MERV GRIFFIN SHOW")

MERV GRIFFIN: Dr. Timothy Leary has been described as being either a prophet or a fiend. He is the dominant figure in the current uproar on the use of LSD. In 1963, he was fired from the Harvard faculty for involving undergraduates in his experiments with drugs. A man very much in the news, here is Dr. Timothy Leary.

DR. TIMOTHY LEARY: I'm in the unfortunate position of being about 20 years ahead of my time. You know, when the airplane came along 20, 30 years ago, the older generation (unintelligible) said they'll never get me up there. I don't want to get high. The next generation, everyone's flying around in airplanes.

GRIFFIN: How many times have you taken LSD, Doctor?

LEARY: I've taken LSD 311 times.

GRIFFIN: We'll be right back.

RATH: You can tell that sounded completely insane to the studio audience. It was the late 1960s, the summer of love, the massive anti-war protests and experimentation with psychedelic drugs. The authorities cracked down on hallucinogens, reclassifying them as Schedule I drugs, meaning they had no known medical use. Research on the medical uses of LSD and other psychedelics was effectively shut down. Today, scientists are picking up where Timothy Leary and others left off. Psychedelic research is back, and that's our cover story today.

(SOUNDBITE OF SONG, "LEGEND OF A MIND")

MOODY BLUES: (Singing) Timothy Leary's dead. No, no, no, no.

RATH: Back in the '50s and '60s, Stanislav Grof was one of the leading researchers on the therapeutic applications of LSD and other hallucinogens. He studied their effects on mental disorders, including addiction. Grof says LSD seemed to accelerate treatment of mental illness exponentially. Some alcoholics even appeared to be cured, never touching a drink again after their LSD session.

DR. STANISLAV GROF: It was quite extraordinary. This was a tremendous deepening and acceleration of the psychotherapeutic process. And compared with the therapy in general, which mostly focuses on suppression of symptoms, here, we had something that could actually get to the core of the problems.

RATH: But the pervasive image of LSD was as a recreational drug and not a medicine. By the 1970s, research had been stigmatized. But in the 1990s, attitudes began to change. There was a flurry of studies on psychedelic drugs. By the 2000s, there was a small but growing research community picking up where Grof and others had left off. One area that showed promise was using hallucinogens to ease anxiety and depression in patients with cancer. Patients like Erica Rex.

ERICA REX: I was diagnosed with breast cancer stage 2 in 2009, on April Fools' Day, great day to be diagnosed with breast cancer. Even if people are happy to spout statistics at you about your chances for survival, that's not exactly what happens in emotional or human terms. I went through the treatment, and there's a group of drugs called aromatase inhibitors. They have extreme side effects, and that can also include depression, which, for me, it did.

RATH: Erica told me she became obsessed with the possibility of her death. It was crippling. And then Rex found out she might qualify for a depression study using an experimental drug: psilocybin. It's an active compound in psychedelic mushrooms. Just to get into the study was an ordeal - tons of lab tests, days at the hospital and then a very intense psychological workup with some probing questions.

REX: One that stuck out was, do you think that people on the television or the radio are saying things specifically to you or that there are coded messages in advertising, stuff like that. It's like having five years of therapy or psychoanalysis stuffed into three days. It was exhausting.

RATH: But at the end of it all, she was approved for the study. She would be given two doses of the hallucinogen in two separate sessions, with trained guides sitting with her as the drugs took effect. Now, what she's about to describe is an intense drug experience, a trip. It's also a science experiment. Her experience began in a windowless room.

REX: The setting is basically a room, an office or a hospital room, and it's been decorated with sort of lots of hangings, and it looks like a sitting room. It's comfortable enough. They have a blood pressure machine because they take your blood pressure every 15 minutes or half an hour during the whole experience.

RATH: So then you take the hallucinogen psilocybin. What does a psilocybin pill look like?

REX: It was a little purple capsule. You take the capsule, you drink a whole cup of water, and you have an eyeshade on and you have earphones on through which there's music. They have a very elaborately, thought-out music track that they play throughout the day that doesn't - essentially doesn't repeat. It started out being very ecclesiastical.

(SOUNDBITE OF MUSIC)

REX: The music became very absorbing and involved. I mean, it went to symphonic music, which I prefer and which was much better, and then kind of world music, you know, things that were more kind of indigenous-type music from foreign countries.

(SOUNDBITE OF MUSIC)

REX: It was a journey. There was a progression of things that happened. There was one that was very particular in which I was being confronted by a little boy with a slingshot who had his arm sort of braced in a tree and was ready to shoot a pebble at me.

(SOUNDBITE OF MUSIC)

REX: And then that was one image. And then something funny happened, and I started laughing. And my laughter was then jewels, like sparkling jewels or a starlight pouring out of a sky - an aperture in the sky. I can't verbalize it because people want it to be described as though it were a dream, and it's not. It is actual. So it is as real as my sitting on the bed clutching this microphone, and it's all entirely real.

(SOUNDBITE OF MUSIC)

RATH: But it wasn't all starlight and laughter.

REX: I became nauseated. There were parts of the struggle with nausea that brought back things, issues that were from my family, from my young life that were excruciating and upset me a whole lot. At the very end of the day, as I recall, the last song that is played at the end of whatever it is, six hours, is "Here Comes the Sun." And then you go spend an evening with a trusted person and write up everything that you can possibly remember.

RATH: Coming away from this now with some distance from it, how has it affected your depression?

REX: I'm much better. I am able to plan. I don't sit around obsessing about what the future may hold nearly as much.

RATH: Erica Rex tells me her depression lifted and her life is undoubtedly better. But as much as the psychedelic experience helped her, some authorities say there are significant questions about whether they are safe and effective for everyone. Glen Hanson is a senior adviser for the National Institute on Drug Abuse.

GLEN HANSON: I think there still needs to be an asterisk next to it. I don't think that it looks like a brand-new antidepressant. There are enough people who've gotten into trouble with these things. And we know that there's this lack of predictability.

RATH: Hanson says the main problem with hallucinogens is that they affect people in wildly different ways.

HANSON: There are people who get into trouble with these drugs. Usually, these are folks who have emotional disturbances already in place and you superimpose - like an LSD - on someone that's a schizophrenic, and you don't know what you're going to get. Because that's almost the definition of hallucinogens is you go in and you scramble the chemistry of the brain. And if it's already "scrambled" - again I put that in quotation marks - but if it's already abnormal, where are you going to end up with this person?

RATH: Remember all those questions Erica Rex had to answer before her session about voices in the TV and coded messages? Those were meant to screen out people who might have trouble. But Hanson says questions like that aren't foolproof. Charles Grob is at UCLA, and he's one of the few researchers actually studying medical uses of psychedelic drugs. Even he agrees there are reasons to be cautious but thinks federal regulations are still too strict.

CHARLES GROB: Our work, we feel we've demonstrated very good safety, as have the other researchers in the field. Where the risks come in are in a recreational setting where naive individuals who really don't know what they're getting into take it under adverse conditions, often mix it with alcohol or other drugs. That's where you have the serious potential for adverse outcome.

RATH: Can we talk about the current regulations with research on these drugs? What sort of restrictions are there? What sort of hoops do you have to jump through?

GROB: For starters, you have to go through FDA. You then have to go through the DEA. And then in California, we have our own kind of instate oversight body that looks at all research with Schedule 1 drugs, and that's the Research Advisory Panel of California. So many hoops to jump through. To work in this area, one has to be very patient.

RATH: You talked about how thanks to Timothy Leary and folks like that there have been kind of a stigma. Does that persist? Is it difficult to get funding?

GROB: Well, it's - funding is very challenging. It has not been possible to get funding from the National Institutes of Health, at least up to now, for funding these kinds of projects. Hopefully that will change and hopefully in the near future there may be some opportunity to see some progress in that arena. But up to now, all of our funding has come from private sources, which is, at times, particularly in a difficult economy, a difficult task.

RATH: Despite the difficulty finding funding, Charles Grob and others are pressing on.

GROB: I think we need to recognize the '60s are over. They're long gone. Timothy Leary is dead. Moody Blues sang that a long time ago when he wasn't dead but now he really is dead. He's off the stage. And I believe we're on the threshold of some very exciting discoveries that the health field can only benefit from.

RATH: Grob has been approved to begin a new study next month using the drug ecstasy to treat social anxiety in adults with autism. Timothy Leary may be dead, but a new debate over the use of psychedelics is just getting started.

(SOUNDBITE OF SONG, "LEGEND OF A MIND")

BLUES: (Singing) Timothy Leary, Timothy Leary. Timothy Leary is dead... Transcript provided by NPR, Copyright NPR.

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