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Psychedelic medicine: Hallucination or reality?

Psychedelics: On a medical trip?

Almost half a century after psychedelic prince Timothy Leary enjoined a generation to "turn on, tune in and drop out," and then followed his own prescription to the letter, medical and psychological researchers are again dabbling in hallucinogens. The few studies that have been published show that psychedelics produce a powerful mystical experience that can

lessen the depression and anxiety of terminal cancer;

alleviate the symptoms of obsessive-compulsive disorder; and

mitigate hard-to-treat cases of post-traumatic stress disorder.

The psychedelic experience, aided by LSD, psilocybin and mescaline, was both cause and effect of the '60s counterculture. But to some people, the hippie pharmacology was a siren that corrupted the young and vulnerable, and the psychedelics came under increasing restriction. In 1970, the U.S. government lumped LSD, psilocybin and mescaline with heroin, cocaine and marijuana into Schedule 1.

Framed poster with rock band image, colorful lettering advertising band names and concert info
Photo of poster: Cliff1066
1967, the "summer of love," made a lot of people familiar with hallucinogens, but it also retarded serious psychedelic research for decades.

That's the category for drugs that have high potential for abuse, but no potential for medicine.

As other nations followed suit, legal restrictions brought a juddering halt to research on the awesome mental effects of natural and artificial chemicals that could cause religious, mystical and out-of-body experiences - and also fear, anxiety and, once in a while, symptoms of psychosis.

Although LSD (lysergic acid diethylamide, likely the most powerful hallucinogen) was at the center of the psychedelic spasm of the 1960s, current studies of the therapeutic potential of psychedelics focus on psilocybin, the active compound in psilocybe mushrooms.

Psilocybin "is gentler, less intense, and produces a shorter duration experience," says Charles Grob, director of the division of child and adolescent psychiatry at the University of California at Los Angeles. "There is more euphoria, less anxiety, less likelihood of paranoia, and most important, there is far less cultural baggage." Grob, who is studying how psilocybin may reduce the anguish of terminal illness, adds that, "LSD was too strongly associated with the counterculture," and that scares off potential research subjects.

Although psychedelics have extremely limited risks in highly selected populations who "trip" in highly controlled circumstances, nobody is claiming that psychedelics have cured anything just yet, and those severe federal Schedule 1 restrictions have not gone away.

Turning the corner

In the past few years, with little fanfare, a few researchers have begun to apply rigorous clinical-trials techniques to the psychedelics. To ensure solid results, they tightly restrict entry to their studies: subjects must not have a psychiatric diagnosis and must discontinue drugs for pain or mood. In some cases, past use of hallucinogens is a disqualifier.

Instead of "let's drop some acid, get groovy and see what happens!" the modern studies are "double-blind" experiments where neither subject nor experimenter knows exactly what is being tested at the moment. By using placebos with noticeable mental effects, the researchers partly excised the excited expectation that "I'm taking magic mushrooms!" that can skew results.

Psychedelics have helped explore the mystical world, says Dennis McKenna, senior lecturer at the Center for Spirituality and Healing at the University of Minnesota. "For the first time, this transcendent experience that was hard to describe could be approached quantitatively, through controlled experiments. Neural imaging revealed a similarity in brain activity between mystical states, meditation and the psychedelic experience." The Ninth Annual International Bioethics Forum,1 discussed how these altered states, and brain scanning, psychiatry, neurochemistry and ethnology, could support a "science of consciousness."

The scientists who have begun to study the psychedelics, using the techniques of legitimate psychology and medicine, are benefiting from a creeping relaxation of federal restrictions, yet the few studies that have been permitted are small and arduous, and "It's very difficult to get funding," says David Nichols, chair of the department of medicinal chemistry and molecular pharmacology at Purdue University. "Most funding comes from NIDA [the National Institute on Drug Abuse], and they are concerned about stopping drug use, showing how drugs are bad. I had grants for ecstasy in 1982, before it was called ecstasy. I thought it had some therapeutic benefits ... but I quit sending in grants. All NIDA wanted to know was why it was neurotoxic; I wasn't interested in that. The funding situation today is the same: 'Why is it toxic? How do you stop people from taking it?'"

hree old men sitting together, man on left with glasses and camera, man in center smiling
Psychedelic pioneer Timothy Leary (center), during his later years, with poet Allen Ginsberg (left) and John Lilly, a doctor who explored consciousness in dolphins and humans, and took LSD in a sensory-deprivation tank.

Some background

Psychedelics are drugs that create "sensory distortion, synesthesia [hearing colors or seeing sounds], closed-eye imagery, a distorted body image, dream-like ideas, hypersensitivity to sensory stimuli and unusual thought processes," says McKenna, an expert in mind-altering natural substances. "Psychedelic" means "making the mind manifest."

McKenna says archeological evidence suggests that psychedelics have been used for at least 10,000 years, particularly by shamans. "Shamanism is a range of traditional beliefs and practices concerned with communicating with the spirit world. The shaman has techniques for accessing the supernatural world, often through the use of psychedelic plants, or drumming or dancing, that induce altered states where the shaman can download information from the supernatural world that is important for the current world: when to plant crops, understanding the cause of illness, healing."

Sealed clear plastic baggie with brown and greenish mushrooms inside
Magic mushrooms contain psilocybin, a major focus of modern psychedelic research.

The suppression of hallucinogens dates back at least to 1500, where the Spanish conquistadors tried to subjugate shamanistic use of psilocybe ("magic") mushrooms in Mexico. People called the mushrooms "god's flesh, and the [Catholic] church felt that only one religious institution could have that franchise," McKenna says.

Portentous discoveries

The more recent history of psychedelics offers some precedent for the prospect of using these mind-bending drugs in medicine: The discovery of LSD by Swiss chemist Albert Hoffman in 1943 helped jump-start a quarter-century of psychedelic research related to brain chemistry, psychotherapy and the nature of consciousness.

LSD played a key role in discovering how nerve cells communicate, says Nichols, the medicinal chemist. "The fascination with LSD, and the effort to understand it, led to the discovery of serotonin, and increased understanding of neurotransmission [signaling among neurons]."

LSD activates at least two types of serotonin receptor in the brain's cortex, site of higher functioning and decision-making, among many other regions.

Serotonin pathway for MDMA ("ecstasy")

Illustrated image of the head and brain, pink line with arrows directed throughout the brain
Neurotransmitters transmit signals between neurons. Serotonin is involved in the regulation of many brain processes, including mood, emotions, aggression, sleep, appetite, anxiety, memory and perception. MDMA, LSD and psilocybin are structurally similar to serotonin and trigger specific serotonin pathways.

Serotonin seems a patriarch among neurotransmitters, Nichols contends. "Serotonin has the most types of receptors in the brain, so from an evolutionary standpoint, it's one of the most ancient neurotransmitters." One of the serotonin receptors that LSD activates, he adds, is "very old, and is even found in the paramecium and mollusks."

What, we had to wonder, would make for an awesome acid trip in a quahog clam?

Tripped-out human figure with bee head, black spots, head dress, mushrooms protruding from body
Drawn by Kat Harrison McKenna from a photograph by Lajoux (1961) (?) zenarchy
People on the Tassilli plateau of Algeria made this cave drawing about 5,000 BC. It's evidence, some say, of a magic-mushroom culture. Notice the mushroom shapes?

"The discovery that psychoactive drugs could powerfully affect behavior, and had a similar structure to serotonin, sparked a tremendous amount of research in the '50s and '60s," says Nichols. "This was the first recognition that neurochemistry could affect behavior. If you were schizophrenic in 1940, the doctor would say your mother had not nurtured you properly; that seems bizarre in modern time." Research with serotonin produced some significant medicines, Nichols adds. "Prozac [and similar selective serotonin reuptake inhibitors], and the triptans for migraine headache would not have been discovered as quickly without LSD."

Weapon or medicine?

During the 1950s and '60s, according to one count, more than 1,000 approved studies tested hallucinogen-assisted psychotherapy on more that 40,000 people. "The clinical indications were for alcohol and drug addiction, psychosomatic disease, [what we now call] post-traumatic stress disorder, obsessive-compulsive disorder, anti-social behavior, autism and existential anxiety in terminal cancer," says Grob of UCLA. "Many of these conditions are among the most difficult to treat, even to the present day."

The British doctor Humphrey Osmond "found a surprising rate of recovery" after a single psychedelic treatment session for alcoholism, says Grob: "one-third of the subjects were sober over the entire follow-up period." The strongest predictor of success, he adds, was a "powerful esthetic experience, a powerful spiritual experience." Psilocybin is one of the psychedelics that can reliably send people into the mystical realm. In the 1962 "Good Friday experiment," for example, Harvard theology student Walter Pahnke used psilocybin to induce a mystical experience among people attending church services.

Some of the most intriguing psychedelic studies showed that they could alleviate fear of death.

But as psychedelics moved into the streets, the legal experiments were doomed. "By the 1970s, human research was completely suppressed, due to a virtual worldwide consensus that the risk-benefit ratio was just too high," says Roland Griffiths, a professor of behavioral biology at Johns Hopkins School of Medicine.

Open book to inside cover, text and STASH logo printed on page
STASH Press, Beloit, Wis
In the late 1960s and early '70s, the Student Association for the Study of Hallucinogens (STASH) operated a medical library devoted to psychoactive drugs. STASH, which issued reports like this one, dissolved about 1979. (Mouse-over to see title page.)

LSD and psilocybin accounted for less than 0.1 percent of drug-related emergency visits in 2002, Griffiths says. "That's a tiny figure, but despite the low risk of addiction and toxicity, there remains concern about adverse effects, including panic reactions" and psychiatric difficulties among people with a family history of psychosis.

Don't try this at home!

Although rates of problems are "incredibly low," Griffiths says the U.S. government long considered psychedelics "too dangerous to study. In spite of the fact that they produce very unique effects, we decided nothing further should be done. I was really puzzled; it may be unprecedented in science to have a whole class of research that we deem too dangerous."

Yet the psychedelic parade persisted; laws failed to stop devotees, and ethnobotanists continued to find cultures where the use of hallucinogens was accepted, normal or even necessary. Over the past decade or so, as memories of the 1960s faded, U.S. regulators gradually loosened their death-grip on psychedelic research and started to permit a scant few trials.

To avoid negative outcomes, modern researchers play enormous attention to the subject's frame of mind and the experimental situation ("set and setting," in psycho-lingo). Therapists prepare their subjects for the strong, and occasionally fearful, psychedelic experience. Familiar "guides" are available during the entire "trip" (both terms, holdovers from the 1960s, are uniformly eschewed by today's researchers).

And as a result, serious side effects are essentially absent in the modern studies.

So what have we learned from the latest studies of psychedelics?

Terry Devitt, editor; Steve Furay, project assistant; S.V. Medaris, designer/illustrator; David Tenenbaum, feature writer; Amy Toburen, content development executive

©2018, University of Wisconsin, Board of Regents.