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Published On September 22, 2010

CLINICAL RESEARCH

A Trip to Therapy

Untouchable for decades, hallucinogenic drugs are back in the lab, with new research into how they work and what they might achieve.

THE EXAMINATION ROOMS IN THE BLUESTON CENTER FOR CLINICAL RESEARCH at the New York University College of Dentistry are exactly what you might expect of a facility that conducts trials of dental and medical therapies. There are reclining exam chairs, linoleum floors, fluorescent lights. The rooms are smartly professional and nondescript—with one exception.

If you were to walk through a certain door, you would find yourself standing on an Oriental carpet. You would also see a stereo system, abstract paintings, a Buddha head sculpture and a bookshelf whose titles include William James’s The Varieties of Religious Experience and Aldous Huxley’S The Doors of Perception. Replacing the exam chair is a well-cushioned sofa. This room is not for people with toothaches. It’s where participants in a certain clinical trial take psilocybin, the psychoactive compound in what are popularly known as magic mushrooms.

According to federal law, psilocybin has no medical uses, and in New York, possessing the substance may merit a year’s imprisonment. But researchers at NYU, along with teams at Johns Hopkins and the University of California, Los Angeles, have permission to study the drug. More than half a century earlier, psilocybin and lysergic acid diethylamide—LSD—had been the subject of intense clinical interest, until recreational abuses and their connection to antiestablishment sentiment made them taboo for serious research. A handful of researchers from the early studies remembered the drugs’ promise, while others—including psychiatrist Stephen Ross, head of the NYU study, who was born after the Summer of Love and unscarred by the culture wars that engulfed psychedelics—heard the old stories and found themselves fascinated.

Although the early studies were run too haphazardly to be conclusive by modern standards, the results were too intriguing to be dismissed out of hand. Some of the most promising findings involved using psychedelics with psychotherapy to ease anxiety and depression in people with terminal cancer—a group for whom modern medicine still has little to offer. “When you are diagnosed with terminal illness, it changes your construction of reality, your sense of place in the world,” says Ross. “Our hypothesis is that inducing a mystical experience leads to a shift in consciousness that creates a change in how you perceive yourself and your illness.”

While terminally ill patients are the main focus of the new psilocybin studies, the research is also targeting obsessive-compulsive disorder and cluster headaches. Other researchers, meanwhile, are investigating the neurobiology of psychedelics, hoping to explain the changes the drugs provoke in the brain and why some patients seem to benefit most from psychotherapy when it’s combined with the drugs.

During the heyday of formal psychedelic research—starting a decade after chemist Albert Hofmann’s 1938 synthesis of LSD and encompassing ethnomycologist R. Gordon Wasson’s ingestion in 1955 of Psilocybe mushrooms in rural Mexico—more than 1,000 scientific papers were published on psychedelics, and some 40,000 people took them in clinical settings. With compounds supplied in bulk to psychiatrists by drug manufacturer Sandoz, the field drew smart, ambitious researchers, not to mention celebrity test subjects, among them Huxley and composer André Previn. Bill Wilson, founder of Alcoholics Anonymous, took LSD with psychiatrist Sidney Cohen (later head of the National Institute of Mental Health’s drug abuse division) and compared the experience to those that catalyzed his sobriety; he tried unsuccessfully to make the drug a part of the AA program.

One prominent researcher was psychiatrist Walter Pahnke, whose interest was piqued in the early 1960s by Timothy Leary, his adviser at Harvard. Soon fired from his academic job, Leary became a countercultural icon who expounded on the potential of LSD at love-ins and light shows, and legitimate research into the drugs was overshadowed by stories of trippers staring at the sun or leaping out windows. In 1970 the Controlled Substances Act designated LSD and psilocybin as Schedule 1 drugs, posing extreme dangers and having no medical uses. Research on the drugs was still legal, but institutional support evaporated. The last bastion was the Maryland Psychiatric Research Center, where a team of researchers included Pahnke, until his death in a 1971 scuba accident, and Johns Hopkins clinical psychologist William Richards, among others. But there, too, research ground to a halt.

IN LATE 2002, WHEN PAMELA SAKUDA, AN EDUCATION SOFTWARE ENGINEER in her fifties, was diagnosed with colon cancer, her doctors told her she could expect to survive 6 to 14 months. Paralyzed by the news, Sakuda stopped making plans more than a few days ahead. Antidepressants didn’t help, and when she lived longer than her allotted time, she only felt more depressed, facing a death sentence that had become capricious.

Then, in spring 2005, Sakuda’s husband, Norbert Litzinger, saw a listing for a psilocybin trial run by Charles Grob, a UCLA psychiatrist. First learning of medical psychedelic research as a student in the early 1970s, Grob had become part of a loose group of researchers, activists and philanthropists who wanted the work to resume. The trial Sakuda’s husband spotted, along with other recent efforts at Hopkins and NYU, are the fruition of their efforts.

Sakuda, debilitated by the stress of terminal cancer, fit the profile for Grob’s study. Before her treatment, Grob and another therapist spent a day conducting a psychological examination, asking what she wanted to achieve and coaching her on what to expect. They would remain with her throughout the experience and counsel her afterward. Sakuda didn’t know whether she would receive psilocybin or a placebo. Yet within 45 minutes of taking the drug, according to her husband, Sakuda had no doubts. “She knew she wasn’t in Kansas anymore,” Litzinger says.

For their part, neuroscientists want to understand in fine detail the neurological mechanisms active when someone takes a hallucinogenic drug. And their work, like the clinical experiments, has deep historical roots. Shortly after the 1948 discovery of serotonin and the recognition of its importance to mood, scientists linked the neurotransmitter to the effects of LSD. Another key discovery was mice whose heads would twitch in response to psychoactive drugs—a reaction that let researchers know whether a particular compound was neurologically active. From this work, they identified several types of serotonin receptors that seemed to fit the molecular shapes common to psilocybin and LSD, and that could modulate the drugs’ effects at the molecular level.

Using functional brain imaging techniques, which show brain activity, University of Zurich neuropsychopharmacologist Franz Vollenweider has scanned the brains of 82 people given psilocybin and charted the patterns of their responses. Most seem to experience a deactivation of the parietal lobes, which are linked to perception of and orientation in space. Altering those parts of the brain and certain prefrontal regions could be what leads to a sense of timelessness and oneness with the universe. In addition, activity is turned down in the amygdala, which is involved in the regulation of mood. That echoes what has been observed in people taking antidepressants and might be what allows emotions to surge.

Other research in rodents has found that psychedelics cause a momentary increase in the number of brain cell structures associated with enhanced plasticity—the capacity to add new information and subtract old. Vollenweider thinks the drugs briefly make crucial parts of the brain more open to psychotherapeutic insight. “The combination of acute therapeutic effects from the drugs and psychotherapy may facilitate learning and behavioral changes,” he says.

One goal of such research is to eliminate the psychedelic aspects of LSD and psilocybin. “Just because we give these drugs for their psychedelic effects, and we now see therapeutic benefits, doesn’t mean the effects cause the benefits,” says University of Arkansas pharmacologist William Fantegrossi. “Maybe you could design a molecule that isn’t psychedelic, but that leads to benefits without side effects.”

For Pamela Sakuda, however, the hallucinogenic aspects were front and center. “I felt this lump of emotions welling and firming, almost like an entity,” she says in a video taken months after her treatment. “I started to cry a little. I started to feel almost like everything came welling up, and then it started to dissipate. I started looking at my situation differently.”

Her description fits a framework, formalized by Pahnke in the 1960s, that’s composed of five types of psychedelic experience: The psychotic aspect, characterized by intense anxiety, paranoia and delusion; the psychodynamic, in which unconscious material becomes “vividly conscious”; the cognitive, which brings heightened lucidity and fresh perspective; the aesthetic, with its geometric eye candy and perceptual bliss; and, of most interest to therapists, the mystical—a sense of illumination, of transcending time and space, a deeply positive mood and a feeling of unity.

Earlier research had found the highest rates of long-term behavioral improvement in people who experienced that mystical state, and the methodology guiding the new cancer trials was expressly designed to facilitate it and then to help patients apply their insights. “They’re dealing with grief, guilt, anger—the stuff of ordinary psychotherapy—but with much more intensity and clarity,” says Richards.

Sakuda already knew she should focus on the moment and take each day as a gift. But with psilocybin, under Grob’s guidance, she felt the truth of those ideas. “I began to realize that all my negativity was a hindrance,” she says in the video. Her remaining time became “something so precious that it didn’t deserve to be clouded by fear and guilt.” And indeed, Litzinger recalls his wife enjoying a period of happiness, of making plans and living as before. He believes her change in mood, coupled with a return to exercise, also boosted her immune system. The therapy “allowed her to have another 23 months of very good life,” he says. Like the neuroscientists, Ross, Grob and Richards believe that mechanisms of brain plasticity are likely involved in experiences such as Sakuda’s, but they don’t think those can be separated from the mystical experience. And while talk of neurotransmitters and brain regions may sound authoritative, it’s still purely descriptive, not yet unified by a neurological model of consciousness.

Clearly the two sides need each other. Without biochemical work, the psychiatric researchers—who still don’t receive government funding—lose the plausible mechanism of action that is the currency of modern research. On the flip side, it’s the psychiatric researchers who are demonstrating psychedelics’ therapeutic potential.

In September, Grob published the results from his study of using psilocybin to treat anxiety inArchives of General Psychiatry. When the NYU and Hopkins arms are also complete, the research teams will have described the experiences of about 80 test subjects—perhaps enough to satisfy requirements for a large-scale clinical trial.

“We’re crawling out of the primeval mud when it comes to understanding the mysteries of human consciousness,” says Richards. “The psychedelics are to neuroscience as a telescope was to astronomy, or a microscope to biology. They’re incredibly powerful and effective tools in helping us explore what we are and how we function.”

 

DOSSIER

1. “Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer,” by Charles S. Grob et al., Archives of General Psychiatry, published online Sept. 6, 2010. The publication of Grob’s findings in such a high-profile journal is a milestone in the re-emergence of therapeutic hallucinogens as a research field.

2. “The Neurobiology of Psychedelic Drugs: Implications for the Treatment of Mood Disorders,” by Franz X. Vollenweider and Michael Kometer,Nature Reviews Neuroscience, September 2010. An exhaustively detailed summation of what”s known about the effects of psychedelic drugs on the brain.

3. “The Rebirth of Research With Entheogens: Lessons From the Past and Hypotheses for the Future,” by William A. Richards, The Journal of Transpersonal Psychology, July 1, 2009. One of the last great mid-century psychedelic researchers, Richards describes in passionate detail his field’s history.

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