My last post talked about the depressing lack of progress in treatments for depression and other common psychological disorders. Talking cures and antidepressants alike are subject to the "dodo effect," which decrees that all therapies are roughly as effective—or ineffective—as one another. The dodo effect implies that treatments harness the placebo effect, the patient's expectation of improvement. Claims that one therapy beats all the others often reflect researchers' favoritism, called the "allegiance effect".

After reading the post one of my smart-ass students asked, "What about psychedelic therapies? Are those subject to the dodo and allegiance effects, too?" Good questions. He knew that, although bashing conventional psycho-treatments, I've written positively about psychedelics' therapeutic potential. Does my reporting reflect countercultural allegiance to psychedelics and distrust of clinical psychology, psychiatry and Big Pharma? Maybe a little. But I've also pointed out the risks of drugs such as DMT and LSD as well as the role of suggestion in shaping psychedelic trips.

Psychedelics clearly exploit the placebo effect, but in complicated ways. To make clinical trials of a drug more rigorous, researchers sometimes give subjects in the control group an "active placebo," which unlike a sugar pill has discernable physiological or mental effects, so subjects can't easily tell whether they are in the control group. If psychedelics are placebos, they should perhaps be called hyperactive placebos, because their psychotropic effects are so dramatic.

In the early 1960s Harvard University psychologist Timothy Leary, who later morphed into a counterculture guru, proposed that psychedelic trips are shaped by "set and setting." Set is mind-set, your overall psychic makeup as well as your expectations, hopes, fears. Setting is, well, setting—meaning the trip's locale as well as cultural context. If you think your trip will help you overcome alcoholism, obsessive-compulsive disorder, melancholy or fear of death, there is a chance it will, especially if you are tended by a caring therapist in a safe, clinical setting. Given the right set and setting, you might even have a religious experience.

The legendary Good Friday experiment, carried out in a Boston chapel on Good Friday 1962, shows the importance of set and setting—and the potential upside and downside of hyperactive placebos. Walter Pahnke, a psychiatrist studying under Leary, gave 10 divinity students psilocybin and 10 students an active placebo, nicotinic acid, which produces face-flushing and other effects. Most of those who received psilocybin had spiritual and even mystical experiences, which deepened their religious faith and improved their relations with others long after the trip ended, Pahnke reported in a 1966 write-up of the experiment.

What Pahnke neglected to mention was that most of the psilocybin-takers feared at times that they were "going crazy" or "dying," according to a follow-up study carried out by Rick Doblin, founder and head of the Multidisciplinary Association for Psychedelic Studies. Moreover, one extremely agitated participant, called L. R., veered between paranoia and mania. Suddenly convinced that he was the messiah, he burst out of the chapel and ran screaming through the streets of Boston. Only with difficulty did Pahnke and others chase L. R. down and persuade him to return to the church, where Pahnke injected him with Thorazine.

Pahnke's failure to report these tribulations reveals the allegiance effect at its worst; his omission resembles that of pharmaceutical companies that bury evidence when a drug doesn't work. Researchers at Johns Hopkins University carried out an experiment like Pahnke's in 2006 and reported in Psychopharmacology (pdf) that psilocybin "can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance." Subjects endured anxiety but no L. R.–scale freak-outs.

I witnessed the healing power of psychedelics firsthand in 2002 when I traveled to a Navajo reservation to participate in a peyote ceremony with 20 members of the Native American Church. My companion was John Halpern, a psychiatrist at Harvard Medical School studying peyote's effects. The focus of the all-night ceremony was a Navajo family—a husband and wife and their young son and daughter—afflicted, like many on the reservation, with medical and financial problems. The evening was in many respects agonizing, but the confessions, sobbing, moaning and vomiting seemed to have a cathartic effect. By morning, the husband and wife were beaming; their troubles seemed to have dissipated, at least temporarily.

Did this apparent therapeutic effect result from mescaline—the hyperactive ingredient of peyote? Or was it from the beautiful rituals of the ceremony that poetically evoked the Navajos' spiritual bond to nature? The outpouring of compassion from the family's friends and neighbors? The hypnotic chants of the medicine man who led the ceremony? The husband and wife's expectations? Who knows? Maybe peyote is just a hyperactive placebo, but there was no doubt in my mind that for that family on that night, it worked.

Photo of flowering peyote cactus courtesy of Wikimedia Commons