Psychedelics Have a Shaky-Science Problem

No psychiatric treatment has attracted quite as much cash and hype as psychedelics have in the past decade. Articles about the drugs’ surprising results—including large improvements on depression scores and inducing smokers to quit after just a few doses—earned positive coverage from countless journalists (present company included). Organizations researching psychedelics raised millions of dollars, and clinicians promoted their potential to be a “new paradigm” in mental-health care. Michael Pollan’s 2018 psychedelics book, How to Change Your Mind, became a best seller and a Netflix documentary. Psychedelics were made out to be a safe solution for society’s most challenging mental-health problems.

But the bubble has started to burst: It’s been a bad year for fans of psychedelics.

A few months ago, two articles appeared, one in The New York Times and another in Business Insider, that portrayed major figures in psychedelics research as evangelists whose enthusiasm for the drugs compromised the integrity of their findings. In August, the FDA rejected the first application for therapy assisted by MDMA, the drug commonly known as ecstasy, saying that it “could not be approved based on data submitted to date,” according to the company that brought the application, Lykos. And five people, including two doctors, were recently charged in the death of the Friends actor Matthew Perry, who was found unconscious in his pool after he took large doses of the psychedelic ketamine. (Three of the five have reached plea agreements; the other two pleaded not guilty.)

These incidents, though unrelated, point to a problem for psychedelic research: Many of the studies underpinning these substances’ healing powers are weak, marred by a true-believer mentality among its researchers and an underreporting of adverse side effects, which threatens to undermine an otherwise bright frontier in mental-health treatment.

[Read: Psychedelics open your brain. You might not like what falls in.]

Psychedelics are by nature challenging to research because most of them are illegal, and because blinding subjects as to whether they’ve taken the drug itself or a placebo is difficult. (Sugar pills generally do not make you hallucinate.) For years, scientific funding in the space was minimal, and many foundational psychedelic studies have sample sizes of just a few dozen participants.

The field also draws eccentric types who, rather than conducting research with clinical disinterest, tend to want psychedelics to be accepted by society. “There’s been really this cultlike utopian vision that’s been driving things,” Matthew W. Johnson, himself a prominent psychedelic researcher at Sheppard Pratt, a mental-health hospital in Baltimore, told me.

Johnson, who has published many studies on psilocybin, the active compound in magic mushrooms, recently left his lab at Johns Hopkins after a dispute with Roland Griffiths, a senior researcher with whom he worked closely. Griffiths, who died last year, said in talks that psychedelics might be “critical to the survival of the human species.” He also behaved like a “spiritual leader,” according to a complaint by Johnson obtained by The New York Times, ran “his psychedelic studies more like a ‘new-age’ retreat center,” and recommended spiritual literature and meditation classes to study participants. Johnson argued that Griffiths’s emphasis on the metaphysical risked steering study participants toward his desired outcomes.

Albert Garcia-Romeu, the current associate director of the Hopkins psychedelics lab, disputes this description of Griffiths and the lab in general. “I never saw him behave like a ‘spiritual leader,’ or running the lab like a ‘new-age retreat center,’ whatever that means,” Garcia-Romeu told me. He noted that researchers have long used psychedelics to explore spiritual experiences but that “there was no imposition of any particular beliefs going on.”

Still, Griffiths isn’t the only one who zealously promoted psychedelics. Take Rick Doblin, the founder of an organization called the Multidisciplinary Association for Psychedelic Studies, or MAPS. He, too, is prone to grandiose thinking, saying he believed psychedelics could be “an antidote to evil” or might lead to a more “spiritualized humanity.” Doblin also encouraged marijuana use at work, arguing that there are “smokable tasks,” which some people “do better while under the influence of marijuana, such as working on complicated spreadsheets.” (Betty Aldworth, the director of education at MAPS, told me that Doblin was “adamant about the science being valid and proving out the answers to these questions through clinical trials.” Doblin did not reply to a request for comment.)

Neşe Devenot, a Johns Hopkins writing instructor and a former MAPS volunteer, told me that many people in the psychedelics field let their political and spiritual beliefs “influenc[e] the type of data that is being collected. The researchers should have more clinical equipoise and not be so assured of what works.”

Inside Lykos, a MAPS spinoff, many staffers were sold on the presumed benefits of MDMA, according to Stat News. One trial participant said her Lykos therapists told her she was “helping make history” and was “part of a movement.” The company failed to collect data on some of the side effects of MDMA, such as euphoria, that might have revealed the drug’s potential for abuse, Stat reported. (In a statement to Stat News, the company stood by its studies, saying that they were conducted with appropriate checks and balances and that the company did add data on positive side effects to some protocols.)

Last month, The Wall Street Journal reported that several participants in the Lykos studies said they felt pressured to report only good outcomes. Three of them said that their thoughts of suicide worsened after they took the MDMA, but that these deteriorations weren’t captured by the study results. (In response to the Journal, Lykos said it reported any significant increases in suicidality to the FDA.)

The FDA is reportedly now looking into Lykos’s data, and the journal Psychopharmacology retracted three papers stemming from MAPS’ early MDMA trials because of “protocol violations amounting to unethical conduct.” (MAPS’ Aldworth says the studies should have been revised instead of retracted. Lykos did not respond to a request for comment.)

The underreporting of adverse events and overhyping of tepid data appear to be widespread in psychedelic research. One review concluded that in many studies of psychedelics, adverse events “were not systematically assessed” and are therefore probably underreported.

And although esketamine (a ketamine-like nasal spray) was approved by the FDA in 2019, one 2021 review noted that there is “a paucity of data concerning long-term safety” of ketamine and esketamine, and a 2023 review found that esketamine’s negative side effects have been systematically underreported in journal articles. Some researchers overstate ketamine’s benefits and underplay its risks, according to a recent review article.

Many people taking ketamine for mental-health issues use the drug repeatedly for weeks or months, but little long-term safety data on the drug exist, says Boris Heifets, an anesthesiology and psychiatry professor at Stanford. For some, the drug’s dissociative effects can become addictive—Matthew Perry was injecting the drug six to eight times a day, prosecutors said, and he spent $55,000 on it in the month before he died. “You’re giving a drug that most definitely has abuse potential, and you’re giving it out online, without supervision, to anybody who can convince you they’re depressed,” Heifets told me. “It’s honestly a little fucked up.”

[Read: A new chapter in the science of psychedelic microdosing]

In a recent study conducted by Heifets, surgeons administered ketamine or a saline placebo to patients who were undergoing surgical anesthesia. Unlike patients in many psychedelic studies, these were truly blinded: They were unconscious, so those who got ketamine didn’t have a ketamine trip. It turned out that about half of both groups, ketamine and placebo, felt less depressed afterward. And those who felt less depressed assumed they had gotten ketamine.

In other words, ketamine did work, a little. But so did the placebo. Heifets attributes this effect to the extensive care and attention that all the study participants received before the procedure. The researchers told them that their mental health is important, and listened to them talk about their problems—in some cases, for hours. They told them that ketamine might make them feel better. To Heifets, this shows that rather than jumping to ketamine, doctors would do well to connect depressed people with caring, attentive therapists as a first step. (But “good luck finding one,” he acknowledged.)

These scientific shortcomings don’t seem to be dampening the enthusiasm about psychedelics. Hundreds of ketamine clinics across the country purport to treat conditions as varied as anxiety and chronic pain, and online services will send ketamine to people’s homes. An initiative to legalize psychedelics will be on the ballot in Massachusetts in November. Veterans’ groups and others are clamoring for the legalization of psychedelic therapies. This is understandable, because these drugs do show promise, especially for treating depression, PTSD, and certain types of addiction. The alternatives—bouncing between SSRIs or scrambling to find an in-network therapist—are bleak, and they fail plenty of desperate people. No new PTSD treatments have been approved in two decades. Some people truly have been cured of their ailments with short, monitored courses of psychedelics.

But the intense interest in psychedelics makes it only more important that the science behind them is as rigorous as possible, untainted by the personal views of researchers. Suggesting that people should get off proven medications in order to try MDMA or psilocybin is dangerous unless those drugs are backed by airtight evidence. And when dealing with psychologically vulnerable people, researchers would do well to align expectations with the reality of what psychedelics can actually accomplish.