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When David Nichols earned a Ph.D in medicinal chemistry from the University of Iowa in 1973 by studying psychedelics, he thought he would continue studying hallucinogens indefinitely. “I thought I would work on it for the rest of my life,” he says.

His timing was less than fortuitous. In 1970, the year after Nichols started grad school, Richard Nixon signed into law the Controlled Substances Act, designed to clamp down on the manufacture and distribution of drugs in the U.S. The act classified hallucinogenic substances like LSD, DMT, psilocybin (the psychedelic alkaloid in mushrooms) and mescaline as Schedule I substances–the most restrictive use category, reserved for drugs with high potential for abuse and no accepted medical use. Marijuana was also placed in this category, and 15 years later when ecstasy came onto the scene, MDMA was emergency-classified as a Schedule I substance as well. By contrast, cocaine, opium and morphine are Schedule II substances, meaning they can be prescribed by a doctor.

Despite some promising results from trials of psychedelics in treating alcoholism, psychiatric conditions and modeling mental illness, by the early ’70s, the government had tightened control of Schedule I substances, even for research. It’s only now that we’re starting to return to the notion that these drugs could be medicine.

If you wanted to kill your career, you did research on psychedelics.
Starting in the early ’90s, and as more scientists prove it’s feasible, increasingly in the last decade, researchers have been approved to conduct clinical trials with human subjects, and there are promising results showing that substances like MDMA could be useful in treating depression and curing PTSD, and that classical psychedelics like psilocybin and LSD could be a way to soothe anxiety in the terminally ill, treat alcoholism and more. But it’s still far from an easy field to break into.

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In 1938, a Swiss chemist named Albert Hofmann synthesized LSD for the first time while studying ergots, a type of fungus. Though the pharmaceutical company that he worked for, Sandoz, didn’t have any interest in the compound, Hofmann found himself inexplicably drawn to it. Five years later, in the spring of 1943, he synthesized it again, noticing that it seemed to have unusual properties: After accidentally absorbing small amounts through his fingertips one day in the lab, Hofmann had to leave work early, under the effects of what he called “a not unpleasant intoxicated-like condition.” A few days later, he experimented with taking what he thought was a small dose of LSD, about 250 micrograms (a common dose now is more on the order of 100 micrograms), and proceeded to trip out of his mind, an experience he describes in his book LSD: My Problem Child.

Thinking that it could have medical uses, Hofmann and fellow researchers at Sandoz research laboratories began testing LSD in animals, and in 1947, the first paper looking at psychiatric LSD use in was published. Researchers saw in acid the potential to model psychotic disorders in healthy brains–a way for psychiatrists to induce in themselves the kinds of sensations their patients experienced as a result of mental illness. It could also be a way to break down boundaries, freeing the mind so patients could open up in psychotherapy.

Despite its current reputation, LSD wasn’t just for the Beatles and California hippies, it was seen as “an invaluable weapon to psychiatrists,” as Time magazine called it in 1955. Research varied widely in legitimacy, but LSD was tested on an estimated 40,000 people around the world between 1950 and 1963.

The CIA saw insidious potential in LSD: They thought it could be a route to mind control.
In 1953, a pair of Canadian researchers tried to use high doses of LSD to scare alcoholics into sobriety, but discovered it instead produced a kind of mystical, near-religious experience for them that convinced them to stop drinking. They were onto something: A 2012 meta-analysis of LSD-alcoholism trials found though many of the trials from the late 1960s were too small to produce statistically-viable results on their own, in conjunction, they showed consistent, positive results.

At the same time, the government was also dipping its toes in an acid-filled pool. The CIA saw a more insidious potential in LSD: They thought it could be a truth serum or a route to mind control. Josef Mengele and other Nazi doctors had experimented on concentration camp prisoners with mescaline and other psychotropic drugs.In the midst of Cold War paranoia, the U.S. Navy thought mescaline could be used to get people to reveal information against their will. When the experiments ultimately proved unsuccessful, the government turned to Albert Hofmann’s new wonder drug, already beginning to emerge as a psychiatric juggernaut.

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LSD Blotter

Between 1953 and 1964, in a project called MKULTRA, the CIA experimented with LSD on unwitting civilians, prisoners, government employees and even its own agents, in a manner that Senator Edward Kennedy later described to Congress as making “little scientific sense.” It came to the point where “surprise acid trips became something of an occupational hazard among CIA operatives,” as Martin Lee and Bruce Shlain describe in Acid Dreams.

The agents monitoring the experiments weren’t scientists, and at least one person died after jumping out of a window under the influence of LSD. By the time the Senate held hearings on MKULTRA in 1977, many documents related to the operation had been destroyed on the orders of then-CIA Director Richard Helms in 1973.

Disturbed by the CIA’s abuses, Congress restricted the use of hallucinogens like LSD to scientific research in 1965. By that point, the tide was already turning against psychedelics, in part due to unethical behavior (referred to by one contemporary researcher as “excessive enthusiasm”) by some of the scientists studying them. Timothy Leary, a psychologist and the psychedelic advocate of “Turn on, tune in, drop out” fame,” lost his appointment at Harvard University in 1963 due to the administration’s concerns that he and other Harvard Psilocybin Project researchers were sloppy in their scientific approach, even conducting investigations under the influence of psilocybin themselves, and after giving an undergraduate student psilocybin off-campus.

Political motives, too, added to the pressure to halt hallucinogenic research like Leary’s, even though it had been surprisingly successful in some aspects, like in reducing prisoner recidivism with psilocybin. LSD, psilocybin and other psychedelics were playing a vital role in a rising countercultural movement, as the forthcoming Albert Hofmann biography Mystic Chemist points out. They were agents of peace and love in a time when the government desperately needed soldiers for the Vietnam War, a war young people were increasingly refusing to serve in. In 1966 the U.S., soon followed by the rest of the world, made LSD illegal. Even the most promising psychedelic research slowed, and by the mid-70s, stopped.

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This was the world David Nichols faced when he emerged from his Ph.D. program brandishing a dissertation on psychedelic drugs. “If you wanted to kill your research career in academics, you did research on psychedelics,” Nichols remembers. To some extent, that’s still true, because psychedelic research remains difficult to fund. As a distinguished professor at Purdue University, Nichols received funding from the National Institute on Drug Abuse (NIDA) for 30 years to look into how exactly how these drugs work in the body. But since the organization concentrates specifically on stopping drug use, he couldn’t study their potential medical properties.

As psychiatrist Charles Grob wrote in a 1994 article in the Yearbook for Ethnomedicine and the Study of Consciousness:

Together with revelations of unethical activities of psychiatric researchers under contract to military intelligence and the CIA, the highly publicized and controversial behaviors of hallucinogen enthusiasts led to the repression of efforts to formally investigate these substances. For the next twenty-five years research with hallucinogens assumed pariah status within academic psychiatry, virtually putting an end to formal dialogue and debate.

In the early ’90s, Nichols was at a scientific meeting telling a story he had told a million times: It’s too bad there’s not any clinical research, research with human subjects, with psychedelics. “You could do it, but you need private money.” He decided he could find that private money, even though he didn’t have the medical degree necessary to do clinical research himself. Along with Grob and others, he founded the Heffter Research Institute in 1993 to do legitimate, rigorous scientific research on psychedelics.

For many years when the FDA got a protocol to study psychedelics in humans, they just put it on a shelf somewhere.
Grob, a professor at the UCLA Medical School, was one of the first researchers to get FDA approval to conduct a research study on the therapeutic effects of psychedelics since research had slowed to a halt 35 years earlier. He was interested in using psilocybin (a drug with less political baggage than LSD or even MDMA) to ease the anxieties and depression in cancer patients with limited life expectancy.

So what changed? According to Nichols, now an adjunct professor at the University of North Carolina Chapel Hill, there wasn’t an abrupt change in regulations, but just a slow shift in attitudes. “For many years when [the FDA] got a protocol to study psychedelics in humans, they just put it on a shelf somewhere.”

Animal-based research went on, because the government was still interested in figuring out how these chemicals functioned, but “the presumption was that was impossible to do with humans,” according to Mark Geyer, another Heffter Research Institute founder who has been studying the basic neuroscience of psychedelics on animals for almost 30 years with funding from the National Institute on Drug Abuse. Even if the FDA had been willing to approve psychedelic trials with humans, there probably weren’t many applications being submitted, because researchers assumed it couldn’t be done.

“The goal wasn’t to stop scientists, the goal was to stop street use… but the side effect of that was that even legitimate research was curtailed,” Geyer explains. “It turns out, as I understand… there was no law on the books that forbade such research.”

According to Nichols, sometime in the early ’90s, a turnover in leadership loosened the agency’s attitude toward human-based trials with psychedelics. After years of lobbying the federal government for permission, psychiatrist Rick Strassman was able to do a study with human subjects of the psychedelic compound DMT.

“Legitimate human research with hallucinogenic drugs, although of great theoretical and practical interest, involves daunting regulatory hurdles that have discouraged investigators from attempting such work,” Strassman complained in a 1991 article for the Journal of Psychoactive Drugs. Nevertheless, his study, involving 60 volunteers and hundreds of doses of DMT, didn’t bring the world crashing around the FDA’s ears, opening up the possibility that the agency might approve more clinical trials with psychedelics.

With the Heffter Research Institute, Grob designed and received FDA approval for a small trial to administer psilocybin to 12 terminal cancer patients between 30 and 60 years old. The patients came in for two sessions a month apart — but everyone received a dose of psilocybin at one of the two sessions. “We didn’t feel it was ethical to deny anyone the active treatment because they had limited life expectancy,” Grob explains.

Because it was the first study to use psilocybin in decades, the FDA approved a very low dosage for the study. “People were not floridly hallucinating,” according to Grob, but the effect was instead more like a waking dream. After a six-month follow-up, the subjects showed a significant, lasting reduction in anxiety. The study paved the way for other research into using psilocybin to ease end-of-life anxieties at Johns Hopkins University and NYU.

A patient receives MDMA-assisted psychotherapy to treat PTSD during an ongoing study in South Carolina.

Psychedelic Medicine

A patient receives MDMA-assisted psychotherapy to treat PTSD during an ongoing study in South Carolina.

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Though Strassman proved clinical research to be both legal and possible, it’s still not an easy process for scientists. That’s part of the reason groups like the Heffter Research Institute and the Santa Cruz, Calif.-based Multidisciplinary Association for Psychedelic Studies (MAPS) exist: They have the resources and the motivation to wade through seemingly endless bureaucratic hurdles to move studies forward. The Heffter Research Institute can advise a researcher on what has worked in previous trials, and they provide a peer-review process for proposals. If their protocol is approved, the organization seeks private funding for it.

“It takes years to get all the approvals,” as Grob says. His first study took a particularly long time to receive approval, though now that multiple studies have established safety parameters and feasibility for these types of trials, the process is somewhat smoother.

You have to really want to work with hallucinogens.
For studies involving people, not only does the research have to be approved by the university’s institutional review board, as do most clinical trials, but it also has to be approved by the FDA and the researcher must be licensed to store and work with the drug by the DEA. The DEA requires intense security when it comes to storing the drugs, lest any resourceful college student try to relieve your lab of its drugs, and the licenses are specifically issued to one researcher in one lab–if you move rooms, you’ll have to get the DEA’s approval.

In clinical work, the drugs have to be manufactured in a specific pharmaceutical-grade manner to ensure quality. Though there aren’t the same manufacturing standards, you also need the same Schedule I license to work with animals as you do with humans, even though less than one human dose of MDMA, for example, could supply a study with hundreds of mice.

“You have to really want to work with these,” says Nichols, whose lab at Purdue made much of the clinical-grade hallucinogens for other researchers’ trials. “Anybody who’s a good chemist could probably do it, but there’s no money in it.”

Currently, according to the DEA, it takes about 9 months to get FDA and DEA approval for a license to research Schedule I substances, though researchers are a little more skeptical. “The DEA’s not in a hurry to grant these licenses,” according to Nichols.

Only 349 scientists have them, and that number is on the downswing: Three years ago, there were 550 licenses in the U.S. Nichols suggests that this could be a result of the DEA cracking down on researchers with extraneous licenses. In the past, Schedule I licenses had been renewed on a yearly basis without much fuss, but in recent years the agency has required Nichols to submit his current protocol and justify why he still needs the license.

***

Part of the problem with studying psychedelics–and other illicit drugs, such as marijuana–for medical use, is simply that they’re not high-tech, and no pharmaceutical company needs or wants to get involved. There’s no money in it for them. Though drugs like LSD and psilocybin are relatively easy to make in the lab, as MAPS founder Rick Doblin pointed out in a 2012 interview, “psychedelics are off-patent, can’t be monopolized, and compete with other psychiatric medications that people take daily.”

“My colleagues say to me, in these days of nanotechology and targeted therapy, what are you doing?” says Donald Abrams, a professor of medicine at the University of California, San Francisco who has done research on medical marijuana. “We live in the 21st century. Studying plants as medicine is not where most investigators are putting their money.”

And without the outside funding to continue researching, a scientist’s career goes nowhere, so even fewer scientists want to get involved.

Organizations like the Heffter Research Institute and MAPS are funded by private donors and don’t have the money to do the expensive, large-scale human trials that could show sound results one way or the other. Nichols hopes that federal funding will be available to do larger studies with psychedelics sometime in the next decade, if the ongoing smaller trials can show efficacy. “There’s movement toward accepting the possibility that these [psychedelic substances] are useful and not all that dangerous,” he says.

The stigma persists, though. “It’s still harder for somebody to get involved in psychedelic research, in terms of professionally and funding,” says MAPS communications director Brad Burge.

And although psychedelic research has made some headway in England and Switzerland, roadblocks against psychedelic research exist abroad, too. The first clinical trial using psilocybin to treat depression stalled in early April because U.K. regulations require drugs used in clinical trials to be made under strict Good Manufacturing Practice (GMP) standards, and the researchers, from Imperial College London, have been unable to find a company to manufacture psilocybin at that standard.

“The law for the control of drugs like psilocybin as a Schedule 1 Class A drug makes it almost impossible to use them for research,” Nutt said in a press statement. “The reason we haven’t started the study is because finding companies who could manufacture the drug and who are prepared to go through the regulatory hoops to get the license, which can take up to a year and triple the price, is proving very difficult. The whole situation is bedeviled by this primitive, old-fashioned attitude that Schedule 1 drugs could never have therapeutic potential, and so they have to be made impossible to access.”

There’s a growing generation of students and researchers who aren’t scared of studying the drugs.Yet despite the hurdles, for some researchers, the potential to cure some of our most troubling woes–like alcoholism, depression and PTSD–make the headaches of doing legitimate psychedelic science worthwhile. Later this week, around 1600 scientists from around the world devoted to this research will descend upon Oakland, Calif. to attend Psychedelic Science 2013, a three-day conference put on in part by MAPS and the Heffter Research Institute.

As Burge notes, the stigma that has haunted psychedelic science could be changing as a new generation of scientists arrive on the scene. “There’s a generation of researchers and therapists that worked in the 1960s and ’70s,” he says, “but also there’s this huge and growing generation of students and researchers who aren’t scared of studying the drugs…looking for treatments to our most debilitating epidemics.”