LSD to Cure Depression? Not So Fast

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Psychedelics, the fabled enlightenment drugs of the ’60s, are making a comeback — this time as medical treatment.

A recent study claimed that psilocybin, a mushroom-derived hallucinogenic, relieves anxiety and depression in people with life-threatening cancer. Anecdotal reports have said similar things about so-called microdoses of LSD.

The allure is understandable, given the limits of our treatments for depression and anxiety. About a third of patients with major depression don’t get better, even after several trials of different antidepressants. But I fear that in our desire to combat suffering, we will ignore the potential risks of these drugs, or be seduced by preliminary research that seems promising.

This appears to be the case with the new psilocybin study, which has some serious design flaws that cast doubt on the results (and which the authors mention briefly). The study, done at New York University School of Medicine, examined a very small number of people with cancer in a “crossover” design in which each subject served as her own control, sequentially receiving doses of psilocybin and the control drug niacin, in random order. (Another recent study of psilocybin, done at Johns Hopkins University, used a similar crossover design.)

Psilocybin, being a hallucinogen, has immediately recognizable mental effects, so subjects would almost certainly know when they were getting it compared with niacin, a vitamin that causes flushing but has no discernible effect on mood or thinking. This makes it hard to know if subjects got better because of the psilocybin, or because of a placebo effect.

The design also means that subjects who got psilocybin first could have had a “carry-over effect” from the drug when they received niacin. In other words, they might still have been under the influence, contaminating the control condition.

The fad of LSD microdosing — typified by Ayelet Waldman’s new memoir, “A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage and My Life” — is far more worrisome. LSD is an unregulated and superpotent drug; users cannot be sure what or how much they are actually taking.

Proponents point out that there is little evidence that these drugs are habit forming or harmful, especially not in low doses. This assertion seems to rest on short-term clinical studies that found no adverse effects (but which could miss problems that occur over longer periods) and on a study of data drawn from the National Survey on Drug Use and Health, which found no significant associations between hallucinogen use and mental illness (but it relied on retrospective self-reporting, which often involves memory lapses and underreporting).

There is little question from clinical experience that psychedelics can be behaviorally toxic, even if they are not addicting in the way cocaine or alcohol are. Bad trips and flashbacks occur with some frequency in recreational users — and sometimes hallucinogens can unleash a psychotic disorder in those who are genetically at risk. Microdoses are supposedly too small to cause those effects, but again, it could be easy to take more by accident.

The bottom line is that we don’t know how safe or effective psychedelics are because most of the data have been anecdotal or from small trials. Part of the reason is that hallucinogens have been classified as Schedule I drugs, the most restrictive category, reserved for drugs considered to have no legitimate medical use and to have a high abuse potential. This makes it somewhat difficult for researchers to conduct large studies, but it is by no means an absolute bar; there are many trials of Schedule I drugs like THC and cannabinol, active molecules in marijuana.

I am anxious that we do not repeat the mistake that we made with cocaine. Aside from Freud’s glowing 1884 monograph on cocaine, “Über Coca,” in which he described his research on cocaine — and his addiction to it — there was little modern research on the drug. In the ’70s and ’80s, people assumed that the absence of data that cocaine was addictive meant that it was safe and dismissed concerns as hysterical moralizing. An epidemic followed.

Psychedelic drugs don’t come close to the toxicity or abuse potential of cocaine. But we can’t assume they are perfectly safe just because we don’t yet have serious evidence of harm.

Psychedelics might turn out to have real promise, but that needs to be proven through large, rigorous, placebo-controlled trials. We’re not there yet.

In the end, I suspect they may prove more interesting as probes of brain function — perhaps illuminating the neural basis of extraordinary mental states, like our experiences of mysticism — than as therapeutic agents. What they tell us about our brain is probably more valuable than what they can do for us.