Psychedelics Back in the Spotlight

But will it be any different this time?

Two papers on the use of psychedelics for the treatment of mood disorders surfaced last week in the prestigious journals Science and Nature. The articles have garnered a great deal of publicity, especially the results having to do with the effect of ketamine on depression. I cannot pretend to offer more insightful coverage than the posts and articles listed below have already done, but I do think it’s profitable to take a closer look at the Nature piece by Franz X. Vollenweider and Michael Kometer. This paper looked at both dissociative anesthetics, like PCP and ketamine, AND “classical hallucinogens,” like psilocybin and LSD.

Traditionally, LSD has been thought of as a relentlessly serotonin-active drug, while ketamine was more actively involved with NMDA and other glutamate receptors. There is accumulating evidence, the researchers believe, that a common mechanism undergirds the operations of both kinds of psychedelics. “Despite their different primary modes of action,” they write, “classical hallucinogens and dissociative anesthetics both modulate glutamatergic neurotransmission in the prefrontal-limbic circuitry that is implicated in the pathophysiology of mood disorders.”

It’s worth noting that Vollenweider and Kometer maintain that almost all depressed patients relapse within two weeks after a single dose of ketamine. In studies of patients with advanced cancer, say the authors, psilocybin improves mood just as effectively, and lasts longer, than ketamine.

While there are significant differences between the subjective effects of ketamine and LSD, there is also “a set of overlapping psychological experiences.” The two trips are different, but not completely different—they share effects such as distortion of perception, visual and auditory hallucinations, a sense that the boundaries of self have softened, and often an ecstatic experience or sense of profound unity. The serotonin-glutamate connection leads the authors to assert that “classical hallucinogens are potent modulators of prefrontal network activity that involves a complex interaction between the serotonin and glutamate systems in prefrontal circuits.”

Alternately, these drugs can trigger a classic “bad trip” in certain users--time, place, circumstance, and innate biology depending.  As the authors put it: “The same hallucinogen might produce a pleasurable loss of ego boundaries combined with feelings of oneness or might lead to a more psychotic ego dissolution that involves fear and paranoid ideation.”

And there you have it: In the case of psychedelics, there are certain extenuating factors which may forever limit the use of these substances for therapeutic purposes. The primary problem is that the drugs are clinically unreliable. With psychedelics, it is always, in a sense, the Lady or the Tiger.  “The strongly dissociative effects of ketamine may limit clinical use despite its reported efficacy,” the researchers conclude. Which is, I think, putting it mildly--and which brings the authors to suggest that pharmacology-assisted psychotherapy might require some tweaks.

Specifically, the hunt is now on for psychedelics that are, well, less psychedelic. In the same way that pharmacologists seek to dial down the euphoric effects of pain medication to lessen the chances for black market abuse, researchers are now looking for ways to tone down the mental fireworks often associated with the use of ketamine, LSD, or psilocybin, on the assumption that these represent nothing but unwanted side effects, rather than the core of the experience that alleviates depression, OCD, and addiction—at least for awhile. These drugs are among the most powerful mind-altering compounds on the planet. So good luck with that project. Studying the behavioral effects of these drugs in the first place is a bit like trying to pin down a writhing fire hose with a pair of tweezers.

Curing or successfully treating chronic ailments like depression and addiction with a power psychoactive medication is both an old and an exciting idea. The Nature opinion piece also documents studies, beginning in the 1960s, which showed that psilocybin and LSD were effective treatments for Obsessive-Compulsive Disorder (OCD).  Other studies have shown alleged successes using low-dose ketamine for heroin addiction. And some of the earliest LSD studies of all showed impressive results when LSD and psychotherapy were combined as a treatment for alcoholism.

 By 1965, the authors claim, there were more than 1,000 published clinical studies on the therapeutic effects of psychedelics.  But many, if not most, of the early studies were marred by procedural problems, lack of control groups, and the fact that researchers from a dozen different disciplines, representing a dozen different experimental methods, predictably emphasized different kinds of experiential results.  The authors suggest that novel neuroimaging techniques combined with an increased understanding of molecular mechanisms of action mean that it will be different this time. If the only real result of the ketamine studies is increased funding for research on psychedelic drugs after a long hiatus, that is still progress, and it’s long overdue.

Resources

David Biello, Scientific American

Maia Szalavitz, New Scientist

and MSN Health and Fitness

Scicurious at Neurotic Physiology

Neuroskeptic at Neuroskeptic

Eugene Rubin, Psychology Today

Jonah Lehrer at Frontal Cortex

Photo Credit: http://cherished79.wordpress.com/

Clinical LSD

“Psychedelic psychotherapy” makes a comeback.



“Take a tab of Sunshine and call me in the morning.”

No, we haven’t reached that point yet. But there is a growing movement among research scientists to take another look at powerfully psychoactive drugs like LSD, psilocybin, MDMA and ibogaine as treatments for a variety of illnesses.

In June, the first clinical trial of LSD since the 1970s began in Switzerland, according to the U.K. Guardian. While LSD has sparked renewed interest as a potential treatment for everything from depression to cluster headaches to post-traumatic stress disorder, the Swiss trial will focus on administering LSD in varying doses to eight terminally ill subjects. “During the course of therapy,” the Guardian reported, “researchers will assess the patients’ anxiety levels, quality of life and pain levels.”

“The working hypothesis is that if psilocybin or LSD can occasion these experiences of great personal meaning and spiritual significance,” said Professor Roland Griffiths of the Johns Hopkins School of Medicine in Baltimore, “then it would allow [terminal patients] hopefully to face their own demise completely differently—to restructure some of the psychological angst that so often occurs concurrently with severe disease.”

Griffiths recently conducted a study of the effects of psilocybin on 36 health adult volunteers, the results of which were published in the British Journal of Psychopharmacology. “When administered under supportive conditions,” Griffiths concluded, “psilocybin occasioned experiences similar to spontaneously occurring mystical experiences that, at 14-month follow-up, were considered by volunteers to be among the most personally meaningful and spiritually significant of their lives.”

Griffiths told the Guardian that drugs classed as hallucinogenic had become thoroughly demonized after the excesses of the 1960s. “As a culture we just decided clinical research shouldn’t be done with this class of compounds,” he commented. “This was partly the federal regulatory authorities, it was partly the funding agencies and it was partly the academics themselves—Leary had so discredited a scientific approach to studying these compounds that anyone who expressed an interest in doing so was automatically discredited.”

The Journal of Psychopharmacology recently published a training manual for the use of investigators who are currently studying the effects of such drugs. According to the manual, psychedelic drugs are relatively safe when administered at the proper dose by a trained medical professional. The drugs are non-toxic, non-addictive, and, except in rare cases, do not cause long-lasting psychoses.

A paper in the same journal by B. Sessa of the Psychopharmacology Unit, Bristol University, concluded:

“There are similarities between the typical traits of creative people and the subjective psychological characteristics of the psychedelic (hallucinogenic) drug experience. This phenomenon was studied in a number of small trials and case studies in the 1960s. Results were inconclusive, and the quality of these studies – by modern research standards – was merely anecdotal. Nevertheless, with today’s current renaissance in psychedelic drug research and the growing interest in cognitive enhancing drugs, now may be the time to re-visit these studies with contemporary research methods.”

In the U.S., psychology professor Charles Grob of the Harbor-UCLA Medical Centre also recently completed a clinical trial using psilocybin to treat terminally ill cancer patients.

Graphics Credit: www.rsc.org