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And then on Aug. 9, the F.D.A.\u2019s decision came through: rejection. It was the capstone to months of increasingly loud concerns being voiced over the quality of Lykos\u2019s clinical trials. And in the wake of the F.D.A. decision, the journal Psychopharmacology\u00a0<\/em>retracted three papers<\/a>\u00a0related to research on MDMA, citing \u201cunethical conduct<\/a>,\u201d an apparent reference to\u00a0allegations<\/a>\u00a0of sexual abuse on the part of an unlicensed therapist at one of the trial sites. Several of the authors of the retracted papers were affiliated with Lykos.<\/p>\n\n\n\n It is a shocking decrescendo for a drug that had been promoted for years as best positioned to lead a psychedelic mental health revolution. The F.D.A.\u2019s rejection signals greater uncertainty for the future of psychedelic medicine. And it will take more than just additional clinical trials for advocates to get back on track \u2014 it might require changing the culture of the research community from within.<\/p>\n\n\n\n First synthesized<\/a>\u00a0by the drug company Merck in 1912, MDMA, also known as the party drug Ecstasy or molly, has both stimulant and hallucinogenic properties. It also has the ability to foster feelings of\u00a0connectedness<\/a>\u00a0and to seemingly dissolve a person\u2019s mental boundaries, which advocates say can help patients\u00a0revisit their trauma<\/a>\u00a0more comfortably during psychotherapy sessions in order to heal from it. Lykos has spent years conducting clinical trials testing whether MDMA-assisted psychotherapy could alleviate the symptoms of PTSD. Its most\u00a0recent drug trial<\/a>\u00a0showed that more than 86 percent of people treated had a\u00a0measurable reduction<\/a>\u00a0in symptom severity. Even more impressive, the effect seemed to be lasting. Had the therapy been approved, it would have become\u00a0the first new treatment<\/a>\u00a0for PTSD in decades and would have handed over administration and control of prescription MDMA to Lykos for at least five years.<\/p>\n\n\n\n More broadly, proponents hoped a green light from the F.D.A. would open the door to regulatory approval for other psychedelics in mental health treatment, an area of medicine that has been desperate for innovation. Mental health disorders are surging<\/a>, with rates of depression, anxiety and PTSD all on the rise, and current drugs don\u2019t work terribly well. The majority of patients diagnosed with depression do not benefit<\/a> from the first medications they are given. Conditions like PTSD are challenging to treat, and veterans\u2019 groups<\/a> have been especially supportive of the potential for psychedelics to address the mental trauma suffered during combat. Amid growing enthusiasm, drug companies, clinicians and patients had enormous hope that psychedelics could relieve the symptoms of millions.<\/p>\n\n\n\n But that hope began to fray in June, when an advisory panel to the F.D.A. voted almost unanimously against recommending Lykos\u2019s MDMA treatment. With what seemed to be audible irritation, the chair of the F.D.A. review panel, Dr. Rajesh Narendran, called Lykos\u2019s study so poorly conducted as to be \u201cmeaningless,\u201d adding that he was \u201cnot convinced at all\u201d that MDMA could effectively treat PTSD.<\/p>\n\n\n\n Asked about the reasoning behind the formal rejection of Lykos\u2019s application delivered on Aug. 9, an F.D.A. spokeswoman told me that significant limitations to the data \u201cprevent the agency from concluding that this drug is safe and effective.\u201d (The spokeswoman noted that the F.D.A. couldn\u2019t legally share more details since Lykos has so far declined to make public the letter that contained the agency\u2019s reasoning.)<\/p>\n\n\n\n If you had asked me some years ago whether the F.D.A. would and should approve this much-anticipated new drug, I would have given an enthusiastic yes. I was for a long time a psychedelic proponent, bullish on the idea that a once-illicit treatment could have widespread benefits for the many who are suffering. But through my own experience in the psychedelic community and proximity to the science of psychedelic therapy, I\u2019ve come to realize that the field is plagued with poor clinical trial design and questionable practices that have led researchers and clinicians to premature confidence in what psychedelics can do. The recent F.D.A. decision has added to my concern that Western medicine\u2019s promotion of psychedelics might have oversold hope to the most vulnerable among us while fueling an industry that was once projected to be worth over $7 billion<\/a> by 2029.<\/p>\n\n\n\n My personal Summer of Love kicked off in 2018, when I first dropped acid and slipped into a community of medical professionals and researchers who both promoted and used psychedelics. The excitement for these drugs seemed to be in the very air of Cambridge, Mass., where I had moved for a science journalism fellowship, auditing classes at M.I.T. and Harvard. I attended a seminar taught by Michael Pollan before he released his 2018 book on the resurgent popularity and potential of psychedelics, \u201cHow to Change Your Mind.<\/em>\u201d Society seemed to be slowly opening up to these drugs, and it felt as though we were at the center of things. Taking MDMA also felt like a doorway to the purest form of love and truth I had ever experienced; it seemed obvious to me that MDMA had benefits.<\/p>\n\n\n\n In hindsight, the confidence we had in these substances before the clinical trials were finished should have been a warning sign that hype was outstripping the science. In November of 2018, I was invited to a dinner where the host rang up Rick Doblin, the founder and president of the nonprofit Multidisciplinary Association for Psychedelic Studies, which launched Lykos as its for-profit arm 10 years ago and is arguably the most prominent face of the current renaissance in psychedelics. Dr. Doblin gave an impromptu speech over speakerphone about the promise of MDMA for trauma. Barring an unforeseen derailment, he expected the F.D.A. to approve his company\u2019s new drug application for MDMA-assisted psychotherapy in just a few years. (The F.D.A. does not regulate psychotherapy; its purview is solely whether to allow clinical use of these drugs.)<\/p>\n\n\n\n I had assumed, based on the enthusiasm of researchers and clinicians in Cambridge also taking psychedelics at the time and on my own experiences, that the evidence this treatment worked was overwhelmingly positive.<\/p>\n\n\n\n Sign up for the Opinion Today newsletter <\/strong>Get expert analysis of the news and a guide to the big ideas shaping the world every weekday morning. Get it sent to your inbox.<\/p>\n\n\n\n But the potential for researchers to bias the outcomes of these trials has become a common criticism of the psychedelic research field. It is unusual for a drug under F.D.A. consideration to also be used personally and recreationally by the researchers studying it or even for clinical trial researchers and clinicians to be encouraged <\/em>to test the drug themselves. But that\u2019s exactly what Lykos has done with MDMA. In a phone conversation after the F.D.A. decision, Dr. Doblin told me that therapists should be \u201cstrongly encouraged\u201d to have their own psychedelic experiences, as it \u201creally helps therapists to better understand their patients.\u201d He says almost all of the researchers in the Lykos Phase 3 clinical trials underwent MDMA experiences themselves, and many studying the drug are open about their own recreational use.<\/p>\n\n\n\n It\u2019s difficult to disentangle the personal enthusiasm for psychedelics with the study of these drugs as therapeutic interventions. And the extraordinary claims of some of its leading researchers \u2014 Dr. Doblin has professed a belief that psychedelics will usher in world peace \u2014 as well as criticisms of the quality of the clinical trials only accentuate how much the enthusiasm has gotten ahead of the science.<\/p>\n\n\n\n After years of\u00a0growing hype<\/a>\u00a0around psychedelics and their therapeutic potential, the F.D.A.\u2019s rejection of Lykos\u2019s application was sobering. But the decision draws from\u00a0new studies<\/a>\u00a0and\u00a0independent reviews<\/a>\u00a0calling into question the quality of research and data around MDMA, as well as the safety and efficacy of psychedelics as a treatment for mental disorders more broadly. Fundamental questions about risk factors, side effects and potential for abuse are still unanswered. Among the\u00a0concerns<\/a>raised by official reviews of the MDMA trials: skewed results caused by the fact that around 40 percent of all participants had prior experience with MDMA, participants\u2019 propensity to guess correctly whether they\u2019d received the drug or a placebo, small sample sizes, organizers\u2019 failure to respond to allegations of abuse of patients and a lack of monitoring for adverse events and the likelihood that abuse of the drug will occur. Growing evidence elsewhere\u00a0indicates that the placebo effect<\/a>\u00a0and the\u00a0biasing of study participants<\/a>, as well as the bias of the researchers themselves, might actually be what accounts for much of the improvements seen in psychedelic trial participants.<\/p>\n\n\n\n The psychedelic renaissance is now at a point of reckoning, and the extraordinary promise of these drugs to quickly and easily transform lives for the better is starting to look more like a fever dream.<\/p>\n\n\n\n S<\/strong>ome of the criticisms of the current research and the ethics of its leaders have been present from the start. As part of a postwar pharmacological boom, psychiatrists in the 1950s explored psychedelics<\/a> enthusiastically. About a thousand research papers were produced; tens of thousands of patients were prescribed LSD. But as the lines between scientific, clinical and recreational drug experimentation among researchers blurred, experts who once saw potential in psychedelics warned against their potential dangers.<\/p>\n\n\n\n \u201cThe trouble is, LSD attracts unstable therapists as much as it does the neurotic patient,\u201d said Sidney Cohen, a leading psychedelic researcher and psychiatrist, in 1963. \u201cIt gives them an intoxicating sense of power to bestow such a fabulous experience on others.\u201d<\/p>\n\n\n\n The Controlled Substances Act of 1970 turned many psychedelics, including psilocybin and LSD, into Schedule I drugs, meaning the government believed they had no accepted medical use and a high potential for abuse. (MDMA was classified as a Schedule I drug in 1985.) This hobbled research and sent much of the experimenting underground for more than a quarter century.<\/p>\n\n\n\n In the 1990s, researchers were able to gain\u00a0limited government permission<\/a>\u00a0to study the psychedelics DMT and psilocybin, opening the door to renewed study of psychedelics for mental health disorders. One of the leaders to emerge from the underground was\u00a0Dr. Doblin<\/a>, who founded MAPS in\u00a01986<\/a>. MAPS and its corporate spinoff Lykos have emerged as leaders in psychedelic medicine, collecting hundreds of millions in donations and investment in psychedelic research and advocacy. That money has enabled and accelerated MDMA clinical trials through Lykos.\u00a0Since he was 18,<\/a>Dr. Doblin says, he has been committed to \u201cbringing back psychedelics,\u201d drawing on his ties to the LSD evangelist Timothy Leary and the New Age Human Potential Movement.<\/p>\n\n\n\n Despite spearheading the clinical trials for MDMA, Dr. Doblin is not a scientist. He holds a Ph.D. in public policy from Harvard\u2019s Kennedy School of Government, where he did his dissertation on how to get psychedelics<\/a> and marijuana adopted by Western medicine, and has openly said that he sees his role as finding a strategic route to popularize psychedelics. \u201cWe don\u2019t actually do science; we do political science,\u201d Dr. Doblin said of his work with MAPS in a 2021 podcast with the activist Marianne Williamson<\/a>. He described his organization\u2019s focus on veterans as a calculated public relations move. \u201cIn this country, there\u2019s kind of a veneration of veterans,\u201d he said. \u201cThat\u2019s how I chose MDMA for PTSD.\u201d<\/p>\n\n\n\n Critics have often cited Dr. Doblin\u2019s public comments as overzealous and beyond the scope of treating mental health conditions. He has encouraged personal use of psychedelics, claiming they have the potential to change the world for the better. \u201cI continue to be a drug user or a medicine user or whatever you want to call it,\u201d Dr. Doblin said<\/a> in a June podcast. This summer he repeated his hopes<\/a> that MDMA could help achieve \u201ca world of net zero trauma<\/a>,\u201d as well as \u201cmass mental health and a spiritualized humanity.\u201d<\/p>\n\n\n\n Ne\u015fe Devenot was once a believer. A psychedelic humanities researcher at Johns Hopkins University and a researcher at the Project on Psychedelics Law and Regulation at Harvard, Dr. Devenot, who uses they\/them pronouns, used to volunteer for MAPS. But they began to have doubts about the organization\u2019s work, in part because they argue that the therapeutic practices MAPS promotes increase the likelihood of boundary violations.<\/p>\n\n\n\n Lykos has maintained the importance of using MDMA in conjunction with its peculiar form of psychotherapy. The treatment manual for MAPS therapists<\/a> includes several recommendations, such as using \u201cnurturing touch\u201d and the power of suggestion. The manual also instructs therapists to utilize \u201cinner healing intelligence.\u201d The idea, roughly, is that patients can heal themselves, provided they can connect with this personal spiritual force.<\/p>\n\n\n\n Dr. Devenot helped organize\u00a0a formal petition<\/a>\u00a0to the F.D.A., released in April, calling for a slowdown in F.D.A. approval of MDMA-assisted psychotherapy for PTSD, signed by several dozen psychedelic scientists and clinicians from major research institutions. A co-author of the petition was Brian Pace, who teaches psychedelic studies at the Ohio State University and testified to the F.D.A. advisory committee that \u201cLykos is a therapy cult that uses the application under review to further mystical and utopian goals. This lens explains the mounting allegations against them regarding research misconduct and clinical trial participant harms.\u201d<\/p>\n\n\n\n Dr. Doblin calls the allegations of cultlike behavior ridiculous. \u201cWhere are all my Rolls-Royces? Where\u2019s all my stock options? Where\u2019s everybody that agrees with me on everything?\u201d he asked rhetorically over the phone. \u201cThat\u2019s absurd. But it\u2019s part of this idea of just making whatever wild allegations you can.\u201d<\/p>\n\n\n\n He also dismissed criticisms of the clinical trials, telling me: \u201cIt\u2019s very well known that it\u2019s difficult to impossible to do double-blind studies with psychedelics.\u201d He defended the scientific rigor of the MDMA trials and emphasized that Lykos consulted with the F.D.A. on the design of the trials. He sees the agency\u2019s decision not as a scientific failure but as a failure by Lykos to communicate effectively to the public after submitting the new drug application.<\/p>\n\n\n\n Other extraordinary characters loom large over this scene. Another evangelist for the use of these drugs for therapeutic purposes is the psychiatrist Ben Sessa, who has trained with MAPS and helped lead training programs in Australia for new therapists after it became the first country<\/a> to classify psychedelics as medicine. He has boldly argued<\/a> that all psychedelics \u201cwork for everything\u201d and have universal efficacy for treating all kinds of mental disorders. Earlier this year, news broke that a medical tribunal had temporarily suspended Dr. Sessa\u2019s license for terminating his care of a female patient in 2021 so that he could have a sexual relationship with her.<\/p>\n\n\n\n Dr. Doblin credits the teachings of the psychiatrist Stanislav Grof, a New Age pioneer who\u2019s put forth many controversial ideas about psychology and consciousness, as helping to lay the foundation for much of the theory that underpins the MAPS approach to psychedelic therapy. The MAPS manual does not mention his belief that these drugs allow you to tap into \u201ccosmic consciousness\u201d and meet demons and deities<\/a> from other realms.<\/p>\n\n\n\n T<\/strong>he actual data on psychedelics for mental health tend to fall short of some of the staunchest advocates\u2019 most extraordinary claims.<\/p>\n\n\n\n Like many pharmaceuticals, it\u2019s not known yet how psychedelics work in the brain, but proponents talk excitedly about these drugs\u2019 ability to remove a patient\u2019s mental armor. Scholars suggest these drugs work by turning up the volume of individuals\u2019 surroundings, making them more suggestible and opening them up to ideas they might otherwise have shut out.<\/p>\n\n\n\n But how psychedelics \u2014 a loose term for a variety of different drugs with very different qualities<\/a> \u2014 affect the brain can differ from person to person. Some effects might lead to improvement in mental health in some people by reducing anxiety, fear and depression. Others may experience no effect or see an increased risk of negative outcomes<\/a>. Different drugs show different effects on memory<\/a> and brain connectivity<\/a>. Some might be desirable for some patients; others might not be. The recent death of the actor Matthew Perry from the acute effects of ketamine, a sedative anesthetic with psychedelic properties, highlights the risks of therapeutic use turning into harmful abuse<\/a>.<\/p>\n\n\n\n Research also increasingly indicates a large placebo effect in many psychedelic trials. Despite its blockbuster popularity<\/a>, the use of ketamine to treat depression has come under<\/a> new scrutiny<\/a>. A paper<\/a> released in Nature Mental Health last fall found that people with depression who were treated with ketamine experienced substantial improvement \u2014 but no more than when they were treated with a placebo. Participants in both the active and control patient groups were under anesthesia and couldn\u2019t tell which drugs they were receiving.<\/p>\n\n\n\n The senior author of the study, Boris Heifets, a longtime psychedelics researcher at Stanford, told me the results were a \u201cwake-up call\u201d for him. He expressed concern that the extraordinary hype around psychedelics as miracle cures could be responsible for positive clinical trial data.<\/p>\n\n\n\n \u201cThe placebo effect is still the strongest medicine we have,\u201d said Dr. Heifets. \u201cIf we want interpretable science on psychedelics, we have to design better clinical trials.\u201d<\/p>\n\n\n\n A systematic review published last year<\/a> in The Journal of Psychopharmacology scrutinized all clinical trials to date that tested whether classical psychedelics could be used to treat addiction, depression, obsessive-compulsive disorder and anxiety. It found numerous flaws in the design of these studies, including a high participant dropout rate, small sample sizes and difficulties keeping patients blinded to whether they received the drug or a placebo. And it also found a high risk of bias in all trials but one. The psychedelics researcher Matthew Johnson filed a complaint last year to Johns Hopkins University, his former employer, claiming that his former colleague Roland Griffiths biased the results<\/a> of his psilocybin trials by injecting personal beliefs and steering participants toward religious experiences. (Johns Hopkins did not respond to questions about the status of the investigation.)<\/p>\n\n\n\n Manoj Doss, a cognitive neuropsychopharmacologist at the University of Texas at Austin Dell Medical School, has found that psychedelics create a mix of novelty, familiarity and insight. This combination produces what he described as \u201cnoetic\u201d understanding, or the undeniable feeling that one has gained some insight or knowledge. Critically, notes Dr. Doss, this noetic feeling \u201cdoesn\u2019t have to be true.\u201d Those mystical, significant feelings you experience while on psychedelics, he and his co-authors wrote in a recent Communication Psychology<\/a> paper, aren\u2019t necessarily helpful from a therapeutic perspective and might even contribute to false beliefs and further mental health issues.<\/p>\n\n\n\n In other words, a beautiful trip may feel profound, but it doesn\u2019t necessarily translate into long-term mental health benefits.<\/p>\n\n\n\n If psychedelics make people more suggestible, they may also create feelings of possessing secret knowledge or insight \u2014 even for providers.<\/p>\n\n\n\n \u201cI ain\u2019t no snitch, but \u2026 most researchers I know have done these drugs themselves,\u201d said Dr. Doss in a talk in April. \u201cMy guess is that they felt like they\u2019re gaining insight into the mind. And yet when they come back, they\u2019re not doing anything \u2014 that I can tell \u2014 that has proved anything new.\u201d<\/p>\n\n\n\n Some of the most prominent figures from MAPS and Lykos have encouraged illicit, nonclinical use of psychedelics, by both clinicians and patients. Dr. Doblin himself has said that MDMA could be used by individuals with the help of a \u201ctrusted friend\u201d or alone, in order for people to be able to \u201cheal themselves<\/a>.\u201d<\/p>\n\n\n\n Dr. Sessa, who has trained countless practitioners in multiple countries in psychedelic therapy and guided clinical trials, speaks openly about his own recreational experiences and argues for normalizing unsupervised drug use to convince the broader public of psychedelic safety.<\/p>\n\n\n\n \u201cWe need everyday people to say, you know, \u2018I take acid a few times a year.\u2019 \u2018I\u2019ll take MDMA every now and then with my wife, and it brings us close together,\u2019 you know?\u201d Dr. Sessa said on a podcast in 2017<\/a>. \u201cI think the government will find that even harder to resist than data.\u201d<\/p>\n\n\n\n But encouraging people to break the law and tear down their own boundaries has obvious risks, particularly while chemically stripping away patients\u2019 fear responses. The F.D.A. review<\/a>\u201cidentified cases where MDMA was used to perpetrate sexual assault.\u201d Walter Dunn, a psychiatrist at U.C.L.A., wondered in an advisory panel meeting in June<\/a> how many such cases were going underreported and urged the F.D.A. to work closely with state medical boards to try to get a handle on the extent of therapists\u2019 abuses.<\/p>\n\n\n\n W<\/strong>hile I am now skeptical as to whether these drugs can be harnessed and used effectively in Western medical settings, I think it is worth continuing to research their effects. If breaking down boundaries is key to how these drugs might treat intractable mental illnesses, then medicine must be more vigilant about how they are studied and regulated. My own falling out with psychedelics took a long time, perhaps because of the strange faith people tend to have in these drugs and in those who provide them (a phenomenon Dr. Leary called \u201cimprinting\u201d). For many years, I accepted as normal the blurring of lines between clinical and research interests and recreational use. I failed to recognize the ways in which my own use made me more credulous and less clear about my own boundaries. Less like myself.<\/p>\n\n\n\n Lykos announced Dr. Doblin\u2019s resignation on Aug. 15, the same day it said that the company was laying off 75 percent of its staff<\/a>. He told me over the phone that what led him to step down were differences of opinion about how to handle communications with the public and whether therapists should be encouraged to take MDMA themselves. He still sees the path to \u201cspiritualized humanity\u201d as going through the F.D.A. and plans to use his position at MAPS to continue his mission of \u201cbringing MDMA to the world.\u201d Lykos did not respond to requests for comment.<\/p>\n\n\n\n