Photo: Mikael Svensson/Getty Images/Johner RF

For most of the 1950s and 1960s, researchers enthusiastically studied the psychological properties — and potential — of hallucinogens like LSD and psilocybin, the active ingredient in “magic” mushrooms. “Psychedelics were tested on alcoholics, people struggling with obsessive-compulsive disorder, depressives, autistic children, schizophrenics, terminal cancer patients, and convicts, as well as on perfectly healthy artists and scientists (to study creativity) and divinity students (to study spirituality),” Michael Pollan wrote in The New Yorker in 2015. “The results reported were frequently positive,” even if many of the studies were methodologically shaky by modern standards. The mystical experiences elicited by the substances seemed to open up in patients new ways of understanding themselves, their problems, and the world.

Then, in 1970, with the nation in the midst of a moral panic about the recreational use of hallucinogens, Richard Nixon signed the Controlled Substances Act. This effectively shut down all academic research into psychedelics, putting a potentially groundbreaking area of study on hold for decades.

In recent years, the government has finally gotten a bit more willing to let researchers experiment with psilocybin, which, as Pollan noted, has less of the cultural baggage and a likely lower potential for harming experimental subjects than LSD. As a result, a new generation of small studies, many of them conducted on seriously ill or dying ill patients — ethics boards have less of a problem administering substances that are mostly untested in clinical settings to such populations — have begun popping up. The early returns have been exciting: It appears that in a surprising number of cases, a single dose of psilocybin can lead to lasting improvements to mental health and the abatement of serious psychological issues. As Pollan explains in his important article, for example, a single psilocybin trip conducted under clinical supervision appeared to significantly ameliorate some terminally ill patients’ fear of death, reducing their anxiety and depression as a result, making the end of their lives easier (relatively speaking) for them and their families and caretakers.

And now we have some more evidence that psilocybin could be the real deal. The entire December issue of the Journal of Psychopharmacology is given over to two new studies that examined the substance’s psychiatric effects on cancer patients dealing with depression and anxiety, as well as a pile of commentaries explaining these studies’ ramifications. The results are very, very exciting.

In one of the studies, led by Roland Griffiths of the Johns Hopkins University School of Medicine, 51 cancer patients with “life-threatening diagnoses and symptoms of depression and/or anxiety” were given two doses of psilocybin. Half were first given a very small “placebo-like” dose during one session, then a full dose 5 weeks later; for the other half, the sequence was reversed.

The sessions themselves were simple: Participants took a capsule with the psilocybin and were encouraged to lay on a couch, put on an eye mask, and listen to preselected music through headphones. They were asked to simply “focus their attention on their inner experiences throughout the session,” write the researchers. “Thus, there was no explicit instruction for participants to focus on their attitudes, ideas, or emotions related to their cancer.” That allowed the researchers to rule out, to a certain extent, the so-called “expectancy effects,” in which placebo-ish mechanisms, rather than the psilocybin itself, might cause improvements. (The participants weren’t just dropped cold into these psilocybin experiences, by the way; rather, they had what were effectively orientation sessions with the “session monitors,” who would later supervise their psilocybin experiences.)

At multiple points throughout the study, and six months later, “[p]articipants, staff, and community observers rated participant moods, attitudes, and behaviors,” focusing on their depression and anxiety. Overall:

High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with [more than] 80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.

These are pretty phenomenal numbers, and they were similar to what researchers found in the other study. For that one, led by Stephen Ross of NYU School Medicine and Bellevue Hospital, “29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy.” (Niacin doesn’t do much of anything, psychiatrically speaking.) Half the group was administered psilocybin during the first session, and then, seven weeks later, niacin during the second; for the other half, the order was reversed. One of the primary differences between this study and the other one is the psychotherapy — some of that aforementioned past research on hallucinogens has suggested that when therapists help guide patients through their trips, it can lead to lasting benefits.

The results:

[P]silocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month followup, psilocybin was associated with enduring [anti-anxiety] and anti-depressant effects (approximately 60–80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death.

Both studies have limitations that are worth highlighting. For one thing, so-called crossover studies like these, in which all patients effectively spend time in both the control and active conditions, are viewed as a bit weaker than randomized-controlled trials with full-blown control groups whose members are never exposed to the treatment being tested. For another, the authors of both studies noted that the participants were disproportionately white and not poor, which limits the ability to generalize from the results. And as one of the commentaries in the journal points out, by dint of the experiments’ design, it can’t be ruled out that some of the improvements may be explained by demand effects — that is, patients and those close to them sensing that they were expected to say things have gotten better.

That said, it is extremely unusual to see credible published research that suggests that administering a substance once can offer such lasting benefits to such a large percentage of subjects in an experiment. Those effects seem to be connected, as one might expect, to the mystical experiences sometimes elicited by psilocybin — patients who reported such experiences were more likely to see improvement. And both studies, like the rest of the small but growing body of research on the effects of psilocybin, showed that the substance is safe. The most serious adverse effects, other than migraines, were fleeting episodes of anxiety. This fits into a broader body of evidence suggesting the psychological risks of psilocybin and some other hallucinogens has been seriously overblown. (Now, none of this should be taken as license to go gobble a bunch of ’shrooms recreationally with the expectation that there would be absolutely no risks to doing so — in all clinical experiments involving hallucinogens, factors like dose, setting, and supervision are tightly controlled.)

Psilocybin is still a Schedule I substance, which means it still isn’t easy to study. But if results like those reported in the Journal of Psychopharmacology keep piling up, the case will grow only stronger to accelerate the pace of research. In one of the commentaries accompanying the two articles, Craig D. Blinderman, director of the adult-palliative-care service at Columbia University Medical Center/New York-Presbyterian Hospital and an associate professor there, explains the stakes:

If these findings are confirmed, or other therapeutic effects are demonstrated, in large, powered, randomized controlled studies in a diverse population of patients, then the classification of psilocybin as a Schedule 1 drug should be challenged, for this would represent a treatment modality unlike anything in psychiatry: a rapid and sustained reduction in depression and anxiety with a single dose of a psychoactive compound (combined with guided psychotherapy). The closest example is the immediate effect ketamine has been shown to have in the treatment of [treatment-resistant] depression[.] However, even in the case of ketamine, the enduring effect last[s] for days to perhaps weeks, not weeks or months.

As a general rule, med-school professors do not throw around terms like “treatment modality unlike anything in psychiatry.” Again: This isn’t normal! There is something potentially groundbreaking going on in this research; there’s a reason the journal packed so many commentaries around those two studies.

It’s always important to maintain one’s sense of skepticism and critical thinking in light of an exciting set of findings, of course, but between these latest results and all the research summed up in Michael Pollan’s piece, the only rational stance here is one of optimism: It will be extremely exciting to see where psilocybin research goes from here, and it could change a lot of people’s lives. Assuming, of course, the government doesn’t again butt its head in.