Altered Perceptions: Good Outcomes from Club Drugs

Altering perceptions: Good outcomes from “club drugs”?

Researchers are investigating whether the illicit drugs that keep some revelers on the dance floor for hours have legitimate medical uses.

By Victoria Stagg Elliott

Published in the AMNews
on Oct. 1, 2007.

John H. Halpern, MD, associate director of substance abuse research at McLean Hospital in Belmont, Mass., was researching the long-term consequences of hallucinogen use among American Indians when he noticed something. Many of his subjects’ experiences were positive, and he became part of a select group of researchers who chose to investigate whether certain controlled substances — drugs bought and sold on the sly at nightclubs and parties or on the street — could, under the right circumstances and in the hands of trained medical professionals, benefit patients.

Much of this work has regulatory approval. Some has government funding.

“If you’re interested in studying the potential harms from these substances, you come face to face with people describing beneficial uses from [them]. That [finding] merits good, careful research to follow up, too,” said Dr. Halpern, who is also an assistant professor of psychiatry at Harvard Medical School in Boston.

His work includes a Food and Drug Administration-approved study into whether ecstasy (methylenedioxymethamphetamine, or MDMA) can reduce the anxiety of terminal cancer patients. Other current projects on so-called “club drugs” include research funded by the National Institute of Mental Health into ketamine as a treatment for major depression and a FDA-approved study regarding the use of MDMA for posttraumatic stress disorder. Researchers at the University of Arizona are investigating psilocybin, the active ingredient in “magic mushrooms,” as an option for obsessive-compulsive disorder. In addition, the first study in decades into lysergic acid diethylamide, LSD, in a medical setting is expected to launch this fall in Switzerland.

“These drugs have tremendous potential,” said Rick Doblin, PhD, president and founder of the Multidisciplinary Assn. for Psychedelic Studies, which funds several of these projects and has been working to establish trials that meet regulatory standards. “We have to start with one drug for one clinical indication, but 20 years from now, we hope to have a field of psychedelic psychotherapy where people can administer multiple different drugs in the course of a therapeutic relationship.”

The idea that these substances may have a medical purpose is not a new one, although it has lain dormant for quite some time. MDMA was originally developed in the early part of the 20th century in hopes of discovering an improved blood-clotting drug. In the latter part of the century, some mental health professionals used it as an adjunct to therapy, until it became a schedule I drug in 1985. Ketamine has long been an FDA-approved anesthetic. And most notoriously, Timothy Leary, PhD, experimented in the 1960s with the therapeutic possibilities of psilocybin and LSD.

“It was really the cutting edge of psychiatric research,” said Charles Grob, MD, professor of psychiatry and pediatrics at Harbor-UCLA Medical Center in Los Angeles. Dr. Grob is in the process of completing a study using psilocybin for easing the anxiety of terminal cancer patients. “By the mid to late ’60s, the psychedelics had escaped the lab. Young people were using them, and it became a public health crisis. Everything was shut down for decades, but enough time has elapsed. We have a whole new generation of investigators, and there’s a willingness to take another look.”

The results from this more recent wave of psychedelic research have been intriguing. A study published in the November 2006 Journal of Clinical Psychiatry, from the University of Arizona team, documented the experiences of nine patients with severe obsessive compulsive disorder treated with psilocybin. The researchers found that the drug was safe and led to a reduction in symptoms. Another paper published in the August 2006 Archives of General Psychiatry found that ketamine relieved the symptoms of major depression within hours rather than the weeks or months antidepressants usually require.

But those researching these drugs say the barriers are significant. The scrutiny of working with controversial substances can overwhelm the research. For example, Dr. Grob led the first FDA-approved studies of ecstasy in healthy volunteers in the mid-1990s, but a later project involving treatment for cancer patient anxiety focused on psilocybin, in part because it’s less controversial.

“Because of sensationalism around [MDMA] I decided not to go for permission to use it with the cancer study,” he said. “I thought psilocybin was somewhat safer physiologically, and it didn’t have the level of press sensationalist coverage that MDMA had.”

Limping toward mainstream

Although some government funding is available for these efforts, the majority comes from private nonprofits, such as the Heffter Research Institute and the psychedelic studies association. The regulatory issues related to researching schedule I drugs are tough, and the studies that are ongoing remain small.

“I can count on one hand the number of credible researchers in the United States who are doing this,” said Dr. Halpern. “And if you tell me who has federal funding to do work with hallucinogens — take a couple fingers away.”

Researchers also need to address widespread concerns about misuse and possible adverse effects of these drugs. Those organizing these projects say they are set up to screen out people seeking the substances for non-medicinal reasons. And if these drugs do receive FDA approval, the researchers add, they will be used quite differently from the majority of other drugs on the market.

For starters, these drugs would be administered under close medical supervision. Subjects who took psilocybin for obsessive-compulsive disorder in the University of Arizona trial, for instance, received the drug in an outpatient clinic and stayed for at least eight hours before being transferred to a psychiatric inpatient unit for overnight observation.

Patients participating in the research into MDMA for PTSD resulting from being victimized by violent crime or childhood sexual abuse have dozens or more psychotherapy sessions before and after the three drug-assisted ones. In addition, the drug-assisted sessions are eight hours long and followed by an overnight stay in the clinic. Few subjects consider it a pleasant experience.

“Several people have said, ‘I don’t know why they call this ecstasy,’ ” said Michael Mithoefer, MD, a Mt. Pleasant, S.C., psychiatrist in private practice and principal investigator of that study. “It’s intensive, and we’re talking about a session where we’re processing really traumatic experiences. It’s hard work.”

These medications also are not for daily or even weekly use. They are meant to be taken only a few times, thereby avoiding possible adverse effects from long-term use. The composition of the drug from a pharmacy or other appropriate channel also will be far more reliable than what is available illicitly, which will reduce the risk of untoward events.

“If MDMA was approved for medical use, it would not be a drug where a doctor writes a prescription and the patient picks it up at a drugstore,” said George Greer, MD, medical director of Heffter. He researched MDMA in the early 1980s and published several papers on his findings in the Journal of Psychoactive Drugs. “It’s something that someone might repeat once or twice, and that’s probably it.”

In addition, some of this research is not intended to prove that the particular drug can treat a certain condition but rather aid in developing better treatments or understanding of the neurobiology of various illnesses.

tamine has been used in experiments on healthy volunteers to better understand alcoholism and schizophrenia. Those researching the drug in relation to major depression do not expect it will be used for that purpose because of side effects, such as hallucinations, and the fact that it needs to be administered intravenously. Researchers do, however, expect findings to lead to a new option for major depression that may have ketamine’s rapid onset without the undesirable effects.

“At this time, it’s a tool to better understand what will lead to a rapid antidepressant response,” said Carlos Zarate Jr., MD, lead author on the Archives of General Psychiatry paper and chief of experimental therapeutics for the mood and anxiety disorders program at the National Institute of Mental Health.

Experts also expect that any regulatory approval will come with attached restrictions. This circumstance, too, is not unheard of in the medical arena.

“There are a lot of fears and misconceptions about these compounds because of their recreational use,” said Dr. Mithoefer. “We use many things in medicine that can be really dangerous if they’re misused and can be really helpful if they’re used right. The fact that [a drug] can be really problematic in the wrong setting doesn’t mean it isn’t worth looking really carefully at it as a medicine.”

In some areas of the country, marijuana increasingly is used by patients with glaucoma, HIV and cancer, among other conditions. But whether and how patients obtain it varies from state to state. Researchers are investigating ways to deliver its beneficial effects without the harms of smoking, and American Medical Association policy calls for well-controlled studies of this substance.

Gamma-hydroxybutyric acid, another club drug, is also the FDA-approved medication sodium oxybate, used to treat narcolepsy with cataplexy. Researchers view it as a possible treatment for chronic insomnia, fibromyalgia, chronic fatigue syndrome and binge eating disorder, but the agency keeps a tight rein on its use. Distribution is limited to one pharmacy in the country, and patients and physicians are required to be part of a registry.


Club drugs: Tomorrow’s medicines?

Methylenedioxymethamphetamine (MDMA)

Nicknames: Ecstasy, XTC, E, X, essence, adam
History: Developed by a German pharmaceutical company in 1912 as part of work to create a better blood-clotting medication, then ignored for decades except for a handful of animal studies in the 1950s. By the 1970s, it was appearing as a recreational drug, and a few mental health professionals were using it in therapy. In 1985, it became a schedule I substance.
Possible future: Treatment for posttraumatic stress disorder; anxiety in terminal cancer patients.

Psilocybin, the active ingredient in “magic” mushrooms

Nicknames: Shrooms, caps
History: The fungi has been consumed in religious ceremonies around the world for thousands of years. The effects were researched by Timothy Leary, PhD, at Harvard University in the 1960s.
Possible future: Treatment of obsessive-compulsive disorder; cluster headaches; anxiety in cancer patients.


Nicknames: K, Special K, Ket, Kit Kat
History: Developed in 1962 as an anesthetic and still widely used in human and veterinary medicine. Used as a psychedelic throughout the 1960s and 1970s.
Possible future: Treatment of heroin addiction; major depression; alcoholism.


Nicknames: Mary Jane, weed, ganja, pot
History: Most likely used during the Neolithic age and introduced to the Americas in the mid-19th century. Medical use is growing but controversial. AMA policy calls for additional controlled studies into its use by seriously ill patients.
Possible future: Vaporization devices that deliver marijuana for pain, appetite, nausea and/or spasticity without the negative effects of smoke inhalation.

Lysergic acid diethylamide (LSD)

Nicknames: Acid, Alice, blotter, liquid
History: Synthesized in 1938, its psychoactive properties were discovered in 1943. The drug has been used in hundreds of trials as a psychotherapy adjunct and treatment for drug addiction, alcoholism and anxiety associated with terminal illness. It was banned in 1967.
Possible future: Treatment of anxiety associated with terminal illness; cluster headaches.

Gamma-hydroxybutyric acid (GHB)

Nicknames: Blue, cherry meth, goop
History: A naturally occurring substance in the central nervous system, it was synthesized in 1874. The drug’s first major human trials occurred in the 1960s. It was initially used as an anesthetic, sleep aid and muscle builder and has Food and Drug Administration approval for treating narcolepsy. Sales are strictly regulated in the medical setting because of the potential for misuse.
Possible future: Treatment of fibromyalgia; chronic insomnia; chronic fatigue syndrome; binge eating disorder.


Center for Medicinal Cannabis Research, University of California, San Diego (
American Medical Association, Council on Scientific Affairs on Medical Marijuana, 2001 (

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American Medical News published a feature article entitled “Altered Perceptions: Good Outcomes from ‘Club Drugs'”? MAPS President Rick Doblin, PhD, and researchers Michael Mithoefer, MD, John Halpern, MD, and Charles Grob, MD, are quoted. American Medical News is a weekly newspaper for physicians published by the American Medical Association that is ciculated to over 230,000 physicians and health policy regulators.