“To be shaken out of the ruts of ordinary perception, to be shown for a few timeless hours, the outer and inner world, not as they appear to an animal obsessed with survival or to a human being obsessed with words and notions, but as they are apprehended directly and unconditionally by Mind at Large—this is an experience of inestimable value to everyone and especially to the intellectual.”

—Aldous Huxley, The Doors of Perception (1954)

“Chemically induced hallucinations, delusions and raptures may be frightening or wonderfully gratifying; in either case they are in the nature of confidence tricks played on one’s own nervous system.”

—Arthur Koestler, “Return Trip to Nirvana,” from The Sunday Telegraph (1967)

“If it [a psychedelic]…helps people to die peacefully with their friends and their family at their side, I don’t care if it’s real or an illusion.”

—David Nichols, Purdue University chemist and pharmacologist

Introduction

Mention the term “psychedelic” to a Baby Boomer, and you will trigger memories (and in some cases flashbacks) of hippies, tie-dyed T-shirts, rock-and-roll, cannabis, civil rights demonstrations, Vietnam War protests, and Woodstock.REF The term would also bring to mind 1960s countercultural icons like Ken Kesey, Aldous Huxley, Hunter Thompson, and especially Timothy Leary.REF

Leary, at one time a Harvard University psychology professor, aggressively touted the use of psychedelics as a means of “expanding” one’s mind by altering a person’s sensory perceptions and thoughts.REF He had quite an effect on popular culture, which rebroadcasted his utopian, messianic visions to people in their 20s and applauded his psychedelic use.REF (Think of the Beatles’ songs Lucy in the Sky with Diamonds,REF Tomorrow Never Knows,REF and I Am the Walrus;REF Jefferson Airplane’s White Rabbit;REF The Doors’ Break on Through (To the Other Side);REF and the Grateful Dead’s Black PeterREF or movies like Easy RiderREF and Yellow Submarine.REF) Leary became the “pied piper” of one particular hallucinogenic drug: lysergic acid diethylamide, better known by its acronym LSD or nickname “acid.” He also became famous (or infamous; take your pick) for the line “Tune in, turn on, drop out.”REF Indeed, the use of psychedelics was the common denominator to every item mentioned above. “Although the matter was often obscured for tactical reasons, there is no doubt that the initiating element, the sacrament, the symbolic center, the source of group identity in hippie lives was the psychedelic drug trip.”REF

For thousands of years, Native American tribes in the lower 48 states, people in the Amazonian Region, and others elsewhere used psychedelics for their psychoactive effect in religious ceremonies.REF Beginning in the 1950s, the medical profession became interested in psychedelics as a treatment for refractory mental disorders as different as alcoholism, depression, and schizophrenia.REF Psychedelic use was legal throughout the United States until 1966, and researchers published more than one thousand articles on their clinical results.REF Psychedelic use did not become a recreational activity until it “escaped” from labs onto college campuses in the 1960s,REF and the trip ended in the 1970s. The drugs did not altogether disappear, but cannabis and cocaine became the principal drugs of choice because they had “reliably euphoric effects” and did “not alter consciousness too much.”REF

Recently, there has been a renewed interest in the therapeutic uses of psychedelics. Researchers hope that they can enhance nervous system neuroplasticity (the ability to jettison old interneuronal connections and form new onesREF) and enhance a person’s ability to engage in blame-free introspection, potentially enabling individuals suffering from disorders such as depression,REF addiction,REF and post-traumatic stress disorder (PTSD)REF to “unlearn” their self-destructive attitudes. If that were to occur, the benefits would be enormous.

The purpose of this Special Report is to summarize the arguments pro and con in the current debate about whether to legalize this category of drugs. The parts below will discuss the history of psychedelic use, the early scientific interest in their potential therapeutic uses, their decline and fall as legitimate treatment tools, the rebirth of research into psychedelics over the past two decades, and the arguments supporting and questioning the use of psychedelics as an adjunct to psychotherapy. The last part will offer some additional factors for consideration.

The bottom line is this: Psychedelic-assisted therapy (PAT)REF has the potential to offer patients relief from otherwise debilitating and unrelievable conditions, but legalizing psychedelic use poses a goodly number of issues about the treatment’s potential benefits, harms, and the likelihood of their occurrence—issues that should be resolved before the drugs become mainstreamed. We might see answers to those questions in 2024 or soon thereafter. The reason is that pending before the U.S. Food and Drug Administration (FDA) is an application for approval of the psychedelic drug 3,4-methylenedioxymethamphetamine (MDMA, also known as “ecstasy” or “molly”)REF for use in conjunction with psychotherapy as a treatment for PTSD.REF

One of the questions that the agency officials will ask themselves is: What are the proven and potential beneficial and adverse effects of psychedelics on patients in the short and long runs? Although the short-term results appear promising, one question is whether psychedelics can alleviate disorders such as PTSD, which afflicts a large number of Americans on a long-term basis, without also causing them long-term harm. Caution might militate in favor of awaiting the results of studies of the long-term use of psychedelics for treatment of chronic disorders—treatment that, following the strategy of the tortoise, not the hare, while potentially beneficial for some patients, could prove costly for others. Then there is the risk of unsupervised recreational use, a problem aggravated by the lack of a Narcan-like medication that can immediately “turn off” a psychedelic.REF Science might not provide a clear and easy answer in this case or in the ones that are likely to follow as different sponsors submit new applications to the agency for other psychedelics.

At the end of the day, the question is how to proceed in the face of uncertainty. For 80-plus years, America has entrusted the FDA to make that call, and it appears that the agency will make it again in the near future.

The Rise and Fall of Psychedelics

The term “psychedelic,” coined in 1956 by the psychiatrist Humphrey Osmond, comes from the melding of two Greek words: psyche, which means mind, spirit, or soul, and delos, which means manifest or clear.REF Some psychedelics are organically based—such as psilocybin (a compound extracted from the Psilocybe genus of mushrooms that places the “magic” in those fungi);REF mescaline (a substance found in the peyote cactus);REF ayahuasca (a tea produced from boiling certain Amazon-basin plants);REF N,N-dimethyltryptamine (DMT, a plant compound); and ibogaine (a plant compound grown in Africa).REF Others are synthetic—such as LSD, ketamine (or “Special K”);REF MDMA; and phencyclidine (PCP or “angel dust”).REF Though similar, they are not identical; psychedelic drugs “have a vague family resemblance rather than an easily described set of features.”REF

Psychoactive drugs work on the brain in different ways. As Drs. Lester Grinspoon and James Bakalar put it, “[t]his topic has supplied volumes of eloquence.”REF Their effect is far greater than what is experienced from cannabis. “Marijuana has been compared to walking a foot off the ground as opposed to the intergalactic voyage produced by LSD.”REF Alternatively, cannabis has been “likened to a pony in contrast with the locomotive of mescaline.”REF And if mescaline is a locomotive, what is LSD, given that it is “several thousand times as powerful as mescaline”?REF

Psychedelics distort our visual, auditory, and tactile interactions with the world or how we process them.REF Psychedelics reshape “sensory, self, time and space perception” in a manner “alien to everyday experience.”REF Leary wrote that “[a] psychedelic experience is a journey to new realms of consciousness,”REF a journey also known by the slang term “tripping.” In his words, “[t]he scope and content of the experience is limitless, but its characteristic features are the transcendence of verbal concepts, of space and time dimensions, and of the ego or vanity.”REF They “reset” or “reboot” the brain or help it form new interneuronal connections.REF Psychedelics also enable us to access unconscious or repressed memories.REF In Jungian terms, psychedelics help to make “the unconscious conscious”REF or elicit “a confrontation with the unconscious.”REF

Psychedelics attracted the interest of the American psychiatric profession in the 1950s.REF One reason was that LSD’s hallucinogenic effects resembled symptoms of acute psychosis, such as visual misperceptions, thought disorders, and ego-dissolution, leading psychiatrists to hope that LSD could help treat psychosis or at least enhance their understanding of its origins.REF A second reason was that after using a psychedelic, some test subjects felt “less depressed, anxious, guilty, and angry, and more self-accepting, tolerant, deeply religious, and sensually alert.”REF Another interest was “using the powerful experiences of regression, abreaction, intense transference, and symbolic drama in psychodynamic psychotherapy.”REF Because the Swiss company Sandoz was willing to supply LSD to legitimate researchers and psychedelics could be lawfully distributed throughout the United States until the mid-1960s, research flourished.REF

Some of the hoped-for prospects, however, did not pan out. Initial tests revealed that LSD exacerbated the symptoms of schizophrenics.REF Nonetheless, LSD research continued because the drug seemed to enable users to access repressed memories. For that reason, researchers thought that it might become a useful adjunct to psychotherapy for people suffering from otherwise untreatable disorders such as depression and addiction.REF Unlike the schizophrenia-focused trials, those initial clinical trials seemed promising.REF Some researchers believed that they might serve as valuable therapeutics that did not pose the risk of physical harm, dependence, or addiction; others were far less sanguine.REF Although psychedelics were always controversial, their potential therapeutic uses were the subject of concentrated scientific examination during the 1950s and early 1960s.REF

Those hoped-for treatments ended in the 1970s. Contrary to popular belief, the end was not due primarily to the “war on drugs.”REF Following the thalidomide tragedies in Europe, Congress tightened the pharmaceutical regulatory approval process early in the 1960s, making the application and clinical processes more rigorous and laborious than the practices governing the early trials.REF Atop that, the European drug company Sandoz stopped providing LSD, the best-known psychedelic, to laboratories for research in 1965 because the firm concluded that Leary’s endorsement of recreational LSD use, along with reports of adverse effects such as psychosis and suicide, was damaging Sandoz’s reputation.REF The result was to limit the amount of research being conducted.REF

A handful of social factors also coalesced to turn society against those psychedelics.REF After becoming known and available to college students,REF psychedelics led some novice users to experience “bad trips”REF and appear in considerable numbers in hospital emergency rooms.REF Also, the unsavory association of psychedelic use with the horrific crimes of the Charles Manson Family,REF as well as the Central Intelligence Agency’s administration of psychedelics to servicemembers and civilians without their consent or knowledge as part of a research program into their effectiveness, stained this category of drugs without leaving any room for their short-term rehabilitation.REF Finally, a massive increase in drug use in the 1960s led Congress to outlaw a host of drugs, including psychedelics, in the Controlled Substances Act of 1970 (CSA) by placing them in Schedule I, the category of drugs seen as dangerous, subject to abuse, and lacking any legitimate medical use.REF The effect of that law has been to prohibit any physician from prescribing LSD for any purpose.REF Psychedelics can still be approved for use in carefully supervised clinical trials, but obtaining approval for trial is a daunting affair, so federally funded clinical trials gradually disappeared.REF

The Resurrection of Psychedelics Research

In this century, psychedelics have become the subject of renewed interest. The hope is that they can serve as an adjunct to psychotherapy for certain intractable or “treatment resistant” disorders, such as PTSD, as well as for Substance Use Disorders (SUDs), whether due to nicotine, alcohol, or illicit drugs,REF or other purposes, such as improved psychological well-being or enhanced spiritual awareness.REF

The principal cause of psychological disability today is depression, particularly the worst form of that disorder, major depressive disorder (MDD).REF Always sizeable,REF the number of people afflicted by MDD has increased since 1990 due to population growth and enhanced longevity.REF The U.S. Centers for Disease Control and Prevention estimates that 14 percent of American adults suffer from mood disorders, including depression, and that an estimated 300 million people worldwide are afflicted with that disorder.REF Untreated depression can ruin a person’s mental health as well as adversely affect a person’s physical health in several ways: It can increase the rate of heart disease and diabetes, greatly reduce one’s daily functioning ability and quality of life, and—even worse—lead to suicide.REF The cost of depressive disorders in this nation alone is also considerable with one rough calculation exceeding $210 billion.REF

The FDA has approved more than 30 drugs for the treatment of depression,REF but none provides a guaranteed cure. Those drugs provide no relief in 20 percent–40 percent of cases and have their own adverse side effects.REF Research for new MDD treatments appears to have entered a “dark age” with no new major advance since Dwight Eisenhower was President.REF MDD therefore remains a relentless affliction.REF

Over the past few decades, researchers have re-examined psychedelicsREF to learn whether they can provide relief for treatment-resistant mental disorders.REF The effect of plant-based psychedelics such as psilocybin—which have been used for millennia for their psychoactive effect in religious ceremoniesREF and were the subject of “intense scientific inquiry”REF in the 1950s and early 1960s—has been known (anecdotally at least) for decades but is now under serious scientific investigation.REF Synthetically produced hallucinogens—such as LSD—came along in the 20th century.REF They also are being studied.REF There have been a goodly number of clinical studies and meta-analyses of those studies investigating and discussing the potential therapeutic effects of psychedelics for various disorders, including addictive behavior.REF More than 200 additional studies are underway.REF

Some nongovernmental organizations devoted to the study of psychedelic medicine have come into being since this renaissance began.REF Several highly respected academic institutions in other countries—Imperial College London and Queens University in CanadaREF—along with Johns Hopkins University; Mount Sinai Icahn School of Medicine; New York University Grossman School of Medicine; Stanford University; the University of California (Berkeley and Davis); University of Michigan; University of Texas at Austin; Washington State University; University of Wisconsin–Madison; and Yale—have created centers or programs for the study of psychedelic research.REF Recognizing that this large number of investigations is underway, in June 2023, the FDA issued guidance to the scientific community regarding the conduct of psychedelic investigations.REF

Those drug trials have shown promise.REF In 2019, the FDA approved the drug Spravato, a derivative of ketamine, as a Schedule III drug for use as a nasal spray for treatment-resistant MDD at a certified physician’s workplace.REF FDA-approved clinical trials for medical use with counseling of other psychedelics are also currently underway.REF For example, Johns Hopkins is researching the effects of psilocybin (a compound that creates a hallucinogenic effect) on depression, anxiety, PTSD, opioid-use and alcohol-use disorders, smoking cessation, anorexia nervosa, and obsessive-compulsive disorder, among other research projects.REF That research seems promising. According to Bertha Madras, Professor of Psychobiology at the Harvard Medical School, “[c]linical trials in the past several years have shown that one or two doses of psilocybin rapidly alleviated depressive symptoms, with therapeutic benefit lasting from 4 weeks to as long as 12 months.”REF Australia has already approved the therapeutic use of two psychedelics—MDMA and psilocybin.REF

There are developments in the United States. In 2017, the FDA granted breakthrough therapy designationsREF for MDMA for the treatment of PTSD, and in 2018 and 2019, the FDA granted breakthrough therapy designations for psilocybin for use with treatment-resistant depression and MDD, respectively.REF On December 12, 2023, a drug sponsor filed a New Drug Application (NDA) with the FDA seeking approval of MDMA as a treatment in combination with psychotherapy for PTSD.REF The ongoing research into psychedelic medications and their subsequent approval could have value beyond the usefulness of these medications as a treatment for MDD, PTSD, and the like. The NDA tees up for the FDA the issue of whether MDMA, like ketamine, should be approved for treatment purposes.REF

Will New Zealand, Canada, Great Britain, the European Union, or the United States follow Australia’s lead? One or more of those nations might witness a groundswell of support for the proposition that the drug laws should be re-examined and revised to permit physicians to prescribe and supervise the administration of psychedelics for various psychiatric disabilities that currently approved pharmaceuticals cannot remedy. In this country, two states—Oregon and Colorado—have already revised their state criminal codes to permit the use of psilocybin for treatment purposes; others are considering the same option.REF At the same time, a Congress that has proved itself unwilling to address our incoherent national cannabis policyREF—one where states can issue licenses to violate the federal controlled substances laws—is not likely to take up the legalization of psychedelics today, tomorrow, or even the days or months afterwards. But that day might come soon.REF

The medical and scientific communities are debating the therapeutic value of psychedelics. So far, the participants have migrated to one of two camps.REF One believes that, under proper medical supervision and with necessary pre-treatment and in-treatment counseling, psychedelics can offer relief for select patients suffering from treatment-resistant disorders such as depression, PTSD, or addiction. The other camp is skeptical as to whether, because of shortcomings in early trials along with the lack of long-term studies of the effect of psychedelics on patients suffering from chronic disorders, the evidence known to date justifies administering psychedelics to patients.

The Arguments in Favor of Psychedelic Therapy

Several justifications, supported by a still-growing body of clinical studies, have been offered for psychedelic use. One is that psychedelics, in conjunction with psychoanalysis or some other form of “talk therapy,”REF can provide relief at minimal riskREF for patients suffering from treatment-resistant psychological disorders, such as depression and PTSD,REF or physiological ones, such as migraines and cluster headaches.REF A second justification is that psychedelics can help people—as they helped Bill Wilson, founder of Alcoholics AnonymousREF—who suffer from substance abuse disorders to transition off drugs such as nicotine, alcohol, or heroin in multiple ways: by pruning neuronal connections that reinforce damaging learned behaviors, by retraining a user’s mind so that he or she can understand the self-destructive patterns of a life ruled by drugs,REF or by enhancing a user’s brain’s ability to develop new interconnectionsREF that enable the learning (or relearning) of healthy lifestyles.REF A third argument is that psychedelics help terminal patients overcome a sometimes suffocating “fear of death” and accept their mortality.REF A fourth justification is that psychedelics enhance users’ performance by enabling “more creative thinking,” which enables them to find “unconventional solutions.”REF A fifth justification is that psychedelics can enhance the lives of people who use them responsibly and that such an opportunity should not be deemed irrelevant or discounted to near zero.REF

It also appears that, when dispensed by physicians to patients under appropriate medical supervision during treatment, psychedelics appear to pose little harm to a user. Said in a more technical way, psychedelics have “a wide therapeutic index and favorable safety profile when administered in doses within the therapeutic range under controlled and comfortable settings.”REF Adverse effects have generally been mild or moderate in severity and were treatable.REF Effects such as dissociation (from ketamine) were not debilitating under proper supervision.REF

Advocates for the use of psychedelics realize that they have an uphill battle because drugs like LSD are currently in CSA Schedule I, which means that they cannot be prescribed for any non-research medical purpose. Two developments, however, have convinced advocates that they might be able to persuade the federal and state governments to change the law. One is the FDA’s 2019 approval of ketamine, a drug often abused as a “club drug” because of its dissociative effect.REF The other development is the series of revisions that numerous state legislatures have made in their own laws to allow cannabis to be used for medical purposes.REF Those facts have likely persuaded supporters of psychedelics that pursuing the liberalization of the laws governing psychedelics is not a quixotic goal.

The Concerns About Psychedelic Therapy

On the other hand, some commentators have various concerns about psychedelic use.REF Skeptics have identified several features of past studies that limit their usefulness as a basis for drawing broad conclusions.REF For example, critics have pointed out that initial clinical studies lacked a control group receiving a placebo, sample populations were too small and too uniform in their composition, and studies were too short and too recent to uncover potential long-term problems.REF Those are legitimate points, and later trials addressed many of them. Nonetheless, certain issues are unresolved and require attention.REF

The Value of Double-Blind Studies. The first issue involves a problem with the nature of clinical tests of psychedelics. Double-blind drug clinical trials—studies in which neither the clinicians nor the subjects know who is receiving the test substance or a placebo—are the gold standard for measuring a pharmaceutical’s safety and effectiveness, yet it is difficult to conduct a truly blind study of the effects of psychedelics. Unlike antibiotics, psychedelics have an inherent ability to distort perception and cognition, which lets test subjects know whether they have received such a drug.REF To obtain a subject’s informed consent to treatment, the physicians responsible for managing any clinical test would need to inform the subjects that they might receive a psychedelic drug. As a result, any group experiencing perceptual and cognitive distortion would know that they received one, while subjects not undergoing those experiences would realize that they did not.REF

That difference creates a quandary. On the one hand, an inactive placebo “allows for better contextualization of any safety findings.”REF On the other hand, subjects receiving a placebo might experience a nocebo effect—that is, “a worsening [of] symptoms as a result of knowing that they did not get active treatment.”REF The FDA suggests that sponsors might be able either to substitute “subperceptual doses of a psychedelic drug” or “other psychoactive drugs that mimic some aspects of the psychedelic experience”REF for an inert placebo or use non-treating psychologists unaware of who received a psychedelic in a post-treatment analysis of its effects.REF Those options, however, still might not do the trick over the long haul. The upshot is that there might be no realistic way to conduct a double-blind clinical study of psychedelics in the same manner that we would use for other drugs.

The Long-Term Effect of Psychedelics on Patients. Another issue is whether we need long-term studies of the effects of psychedelics on patients.REF We do not yet know all of the potential problems that can result from their long-term use.REF Drugs like psilocybin and ketamine increase a person’s heart rate and blood pressure, and the long-term physical effect of those drugs on a long-term user’s cardiovascular system, for example, is unknown.REF For some patients, psychedelics can replace one debilitating condition—depression—with another—acute or chronic psychosisREF (although the incidence of those disorders appears to be quite rare).REF

Disorders such as MDD are chronic problems and, at least under our current knowledge, cannot be solved by a single dose of any approved treatment.REF Psychedelics also are not a silver bullet. They take effect quickly, but their effect fades over time, requiring repeated dosing on a regular basis to afford patients continued relief, as the FDA noted in its 2023 psychedelic guidance.REF Two scholars have written that MDMA, while valuable in the short run, might not be “suitable” for long-term use if users are also taking other illicit drugs and perhaps even if they are not.REF Even a recent study finding that the drug MDMA showed value in treating PTSD recognized that long-term investigation is necessary “to assess durability of treatment.”REF

Some scholars have concluded that there is little physiological or psychological risk from long-term psychedelic use.REF Nonetheless, reasonable people could also believe that long-term studies are necessary to learn the dose level that is safe and necessary for repeated treatments to be successful, for determining the appropriate intervals before redosing should be undertaken, and for learning whether such repeated dosing has adverse chronic physical or psychological effects on patients.REF For example, the FDA has expressed concern that long-term psychedelic drug use could lead to a potentially serious condition involving thickening of the heart valves.REF There also is the question of who, if anyone, should be excluded from psychedelic treatment, particularly on a long-term basis, because of, for example, a risk of suffering an adverse physical or psychological reaction.REF The FDA will need to decide whether such long-term studies are necessary before it decides whether to approve psychedelics for therapeutic use.

Essential to the resolution of that issue are various subissues. What are the relative risks of short-term and long-term harm to patients from delaying the approval of psychedelics until we have studies of their long-term effects versus the risk of creating new problems by approving those drugs before we know the results of long-term studies? What is the relative importance of relieving disorders today versus that of avoiding chronic problems by waiting for proof as to the effects and side effects of long-term use of this category of drugs?REF What is the likelihood of psychedelic users developing a tolerance to the drug with long-term use? Will it be necessary for those who do use psychedelics to escalate the amount they consume? What risks does that pose?REF Do we need a Narcan-like “rescue” treatment for adverse effects before we legalize psychedelics?REF Those issues should be identified, investigated, debated, and resolved.REF

In that regard, the FDA’s decision to approve Spravato (esketamine) is not necessarily a “precedent” for the approval of all other psychedelic drugs or ones that have psychedelic-like effects. Each such drug should be examined independently.REF

The Relationship, If Any, Between the Sensory and Cognitive Disruptions Caused by Psychedelics and Their Therapeutic Effect. A third important but unanswered question is whether—and, if so, to what extent—the sensory and cognitive distortions produced by drugs like psilocybin are unavoidably tied to their potential therapeutic effect.REF Some researchers have suggested that nonpsychedelic drugs might be able to activate the neural receptors necessary to provide relief, as an example, for depression without generating the psychedelic experience of drugs like psilocybin.REF According to Dr. Nora Volkow, Director of the National Institute on Drug Abuse (NIDA), there is no firm conclusion either way: “There is evidence to suggest that psilocybin’s therapeutic efficacy is tied to the mystical-type experiences it commonly precipitates,” although that connection is “controversial.”REF In addition, psilocybin is but one of the potential psychedelics being considered, and what is true in the case of one might not be true for the entire class of potential treatments.

As the FDA has noted, some psychedelic drugs have been the subject of “numerous investigations, as documented in the published scientific literature,” but not all of them have been as rigorously examined.REF Those drugs should be subjected to “a full abuse potential assessment.”REF Decoupling “depression-ameliorating neuroplastic effects” from “the cognitive and sensory distortions” might eliminate or reduce safety concerns with respect to psychedelic drugs,REF but that would not be possible if the latter are essential to achieve the former.REF We might have to accept the bitter with the sweet, but we should find out whether that is true before we commit to this course. We also should find out whether nonpsychedelic receptor agonists might prove to be safe and rapidly acting antidepressants.REF

The Combination of Psychedelics and Psychotherapy. Another issue is how psychedelic pharmacology and psychotherapy should be combined. Some believe that psychedelics do not themselves resolve a patient’s mental disorder but enable psychotherapy to do that work.REF Rick Doblin, founder and president of the Multidisciplinary Association for Psychedelic Studies, has said that “[c]ritically, MDMA taken in isolation, without therapy, does not automatically produce a beneficial effect,” adding that “‘[i]t’s not the drug—it’s the therapy enhanced by the drug’” that addresses a patient’s underlying problem.REF

Commentators have recognized, however, that psychedelics pose special risks that other drugs do not pose. There might be serious adverse effects from improper use. As Dr. Ben Sessa, a psychiatrist and psychedelics advocate, has acknowledged:

There is no doubting that the misuse of psychedelic drugs can cause harm (by definition). The psychedelic experience can certainly be frightening and disorienting for ill-prepared users. Feelings of panic and losing control can become overwhelming. For some people with pre-existing mental illness, especially those with psychosis, psychedelic use can trigger severe reactions. The concept of a “bad trip” is well documented by both users and non-users of psychedelics.REF

Doctors Lester Grinspoon and James Bakalar have made the same point:

The worst kind of psychological reaction is a fixed intense emotion or distorted thought that can seem like an eternity of hell; for example, remorse, suspicion, delusions of persecution or of being irreversibly insane. The metaphysical bad trip is a devastating extension of this in which everything is implicated in the drug taker’s misery, his wretched feelings are seen as revelations of the ultimate nature of the universe, and he experiences some version of what mystics have called the dark night of the soul.REF

Psychotherapy accompanying psychedelic use is offered as the solution to those problems.REF As Dr. Sessa has explained, psychedelics are “non-specific amplifiers,” meaning that “any emotion, good or bad, benign or destructive, can be magnified to dramatic proportions.”REF Qualified psychotherapists can help a patient address and understand those emotions or any perceptual distortions that arise during treatment.REF

If so, it is important to consider how psychedelic treatments should be carried out. Both the patient’s “set” (expectations) and the treatment’s “setting” (environment) are important to the success of psychedelic-assisted therapy.REF “Twenty years of research has standardized the dosage of the drugs used in clinical trials, but the therapy component has not received similar scrutiny.”REF Counseling is “‘often based on tradition rather than empirical evidence.’”REF

The treatment afforded clinical trial participants has involved far more than simply hooking a patient up to an IV drip and handing him or her a magazine. Participants are carefully chosen and receive exhaustive physical and psychological testing before any trial begins, in part to exclude anyone suffering from a severe mental illness such as psychosis.REF Studies have made extensive use of psychiatrists and other mental health professionals to educate participants about the effects (for example) of psilocybin before receiving treatment and to have those professionals (or trained psychologists or other personnel) present or available during its course.REF The testing or treatment has taken place in a comfortable, almost spa-like setting, sometimes with participants wearing sunglasses and listening to background music while undergoing treatment—all of which is designed to keep a psychedelic experience from going south.REF “The general consensus of clinicians and scientists in the field,” two scholars have found, “is that it is important to have one or two trained persons present during a psychedelic session in order to keep patients’ attention focused inward, and to provide physical and emotional support during the session.”REF

There is a powerful need to decide precisely what the quantity and quality of that counseling should entail.REF To start, skepticism is justified in concluding that psychedelic therapy will be provided only in spa-type settings rather than play out the same way that medical cannabis programs handed out that drug: in businesses with in-house physicians writing a recommendation for medical cannabis use to anyone with $40 and enough time for a coffee-break-long interview with nothing more than a fast-food version of a physical or psychological exam.REF That could spell serious trouble for some people. Psychedelics are not for everyone,REF which is why serious clinical studies carefully screen potential participants to exclude any for whom psychedelics might be harmful.REF In-treatment medical monitoring of a patient is also necessary to prevent adverse outcomes.REF

There is widespread agreement that pretreatment, in-treatment, and post-treatment counseling is valuable, if not necessary,REF but there are numerous questions that need answers. For example, it is unclear how the psychoanalysis accompanying psychedelics should proceed because we lack a consensus on its proper role, content, and importance. Is it necessary or merely valuable? If merely valuable, how valuable is it—that is, what is its marginal contribution to the overall treatment package? What counseling should psychotherapists offer patients? How should that counseling be conducted—that is, should therapists be present throughout a treatment in the same room? Or should they be in the same office or clinic, nearby but immediately available? Or can they be on-call? Can the appropriate psychotherapy be “protocolized” because the FDA might have difficulty giving blanket approval to a medication requiring psychotherapy that lacks a consensus-driven protocol? Is it possible to have a “placebo cohort” because, as a practical matter, the protocol would be different if someone is or is not hallucinating? Should there be a 1-to-1 ratio between therapists and patients or should therapists be permitted to treat a larger number of patients at any one time? If so, what is the maximum reasonable ratio? What are the risks of illicit psychedelic use, with or without medical involvement, and the resulting harms? What risk should patients be allowed to bear? What are the risks and social costs that society should be forced to bear if we underestimate the potential adverse results?

Now turn to questions about the therapists. Who is qualified to serve as a treatment counselor? What is the risk that an inadequately educated and trained psychoanalyst will torpedo the value of psychedelic therapy? How do we guarantee that only qualified individual therapists are involved?REF How do we ensure that an adequate supply of qualified personnel is available?REF The FDA’s guidance on psychedelic drugs offers recommendations—such as using two observers during a treatment session with the lead monitor possessing “graduate-level training and clinical experience in psychotherapy” as well as being “licensed to practice independently”REF—and researchers would be wise to consider them. But the FDA also notes that variability in the answers to the questions above presents a “challenge” for product labeling, which the FDA regulates.REF Remember: The FDA regulates the interstate distribution of drugs; it does not license psychotherapists. That is in the states’ bailiwick.REF How, therefore, can the FDA ensure that dangerous drugs are not distributed to people who use unqualified therapists? And who should answer those questions—states, which regulate the practice of medicine,REF or the FDA, which regulates the interstate distribution of pharmaceuticals?REF

Further complicating the issue is the development of telemedicine: the use of modern communication technology to obtain over the Internet a diagnosis and prescribed medication from a physician without any face-to-face meeting, let alone a physical examination.REF Telemedicine would allow a physician in Maine to diagnose and treat a patient in Hawaii over a platform like Skype that he doesn’t know and will never treat again.REF Even if Hawaii finds that practice hunky-dory, the federal government might disagree. It could refuse to reimburse the prescription of psychedelics by telemedicine whenever Medicare or Medicaid is responsible for payment. The federal government also might be able to regulate that practice even when Medicare or Medicaid does not foot the bill by invoking its authority over interstate commerce,REF which includes the use of the facilities of interstate telecommunications to complete credit card transactions.REF The federal government might be able to stop a patient from receiving psychedelics even if he is treated in-person by a local physician and pays for the treatment in cash if the drug has traveled in interstate commerce.REF Those issues, however, are yet to be decided.

Regardless of how those issues are resolved, there is yet another one: the risk that patients will seek treatment from multiple physicians to obtain multiple prescriptions for psychedelics. That was one of the problems we saw during the opioid epidemic: Patients obtained multiple prescriptions for narcotics from different physicians because there was no way for each doctor to know what others had prescribed.REF Telemedicine means that we could see the same outcome here. The result is that, absent a federal law or nationwide practice of collecting and sharing psychedelic prescriptions, perhaps one that is similar to the system now in effect for opioids—the Prescription Drug Monitoring ProgramREF—some patients might obtain and use more of those drugs than is safe or might use them at home without any direct medical oversight.REF

At the end of the day, it is likely that the states might be responsible for answering many, if not most, of those questions. Historically, the states have the responsibility for regulating the practice of medicine, while the federal government has the authority to decide what drugs may be shipped in interstate commerce. Once the FDA approves that shipment, the states regulate how a physician may use it as part of his or her professional judgment when treating a specific patient. That is why the co-called “off-label” use of a medication—viz., the use of a medication for a purpose not identified on its FDA-approved label—is generally permissible. Private insurers also have a say in how a drug should be administered because they decide what treatments are covered and reimbursable.REF The FDA might not be able to address those problems on its own, but it might solicit the assistance of the states and private insurers, who might not all agree on what is the best resolution. Regardless of how those issues are resolved, the appropriate safety and ethical rules for psychedelic treatment should be defined and in place before the treatment is rolled out.REF

In this regard, discussions about that regulation must involve some consideration of how treatment protocols can and will be enforced. Standards without penalties for noncompliance are just advice, not rules. We could, of course, rely on the tort system to provide governing rules in the standard after-the-fact fashion that malpractice damages actions have traditionally served. It would be preferable, however, for patients, physicians, therapists, and pharmaceutical companies to have the guidelines resolved ex ante rather than ex post. Here, too, the federal and state government might need to work with the private parties just mentioned to hammer out reasonable conventions in the pre–FDA approval period.REF

One tool that the FDA can use as part of the drug approval process is to require a drug distributor to adopt a Risk Evaluation and Mitigation Strategy (REMS)—“a drug safety program…for certain medications with serious safety concerns” that is designed “to help ensure the benefits of the medication outweigh its risks.”REF For example, one long-lasting antipsychotic drug carries a risk of “serious” post-injection reactions called “post-injection delirium sedation syndrome.”REF The symptoms include “feeling sleepier than usual (sedation), coma, and feeling confused or disoriented (delirium).”REF The rationale for requiring a REMS is “to ensure that the drug is administered only in certified health care facilities that can observe patients for at least three hours and provide the medical care necessary in case of an adverse event.”REF Here, the FDA could require a psychedelic drug distributor to have a REMS that the agency finds is sufficient to address all of the issues discussed above regarding the need for an appropriate setting for administration of the drug. In particular, the FDA could limit pharmaceutical companies’ distribution of psychedelics to those physicians with REMS that the FDA finds satisfactory.REF

The failure to comply with a REMS potentially exposes a physician to more than civil liability. The U.S. Department of Justice recently persuaded a grand jury to indict two physicians for allegedly illegally administering ketamine to patients and billing Medicare for that treatment because the physician licensed to distribute ketamine was not an active participant in the treatment.REF The result is that the federal government might have some valuable tools that it can use to police the actual practice of medicine, at least where the federal government is billed for it.

Additional Considerations

There are a few additional considerations worth noting.

Federal vs. State Regulatory Authority. With only two statewide exceptions—Oregon and ColoradoREF—the United States has addressed the issue of whether to approve psychedelic therapy by following the approach that the nation has used for 85 years to measure the safety and effectiveness of a new drug: Leave the responsibility to answer those questions with the FDA. Congress made that decision in 1938, and since then, that approach has become the traditional, settled, and legally and socially accepted model for recognition of new drugs.REF

That process is underway. In 2019, the FDA approved the drug Spravato, an isomer (esketamine) of the dissociative drug ketamine, for use in treating MDD.REF The FDA also approved clinical trials for psilocybin and MDMA. What is more, as noted above, the FDA has a pending application seeking approval of MDMA as an adjunct to psychotherapy.REF The agency will review the studies submitted by the sponsor, along with the other materials in the sponsor’s application, and make its decision in due course. Whatever the FDA’s decision on that application might be, one promising result of current events to which the nation appears willing to adhere is the traditional practice that the country has long used for the evaluation of the safety and usefulness of a new drug. That allocation of responsibilities is an important one because there are numerous factors that the FDA should consider in making its determination; it has the medical and scientific experts qualified to make drug safety judgments, while the states do not; and the judgments the FDA makes have important public health consequences.

That regulatory model is far preferable to the approach that society has witnessed playing out over the past three decades with respect to the legalization of cannabis.REF Since 1996, numerous states, with California in the lead, legalized cannabis for medical use without waiting for the FDA to find that the botanical cannabis is safe, effective, and uniform and without independently performing (or requiring sellers to complete) any of the rigorous studies that the FDA would demand before legalizing a new drug for interstate distribution.REF A result has been the large-scale distribution of botanical cannabis that the FDA could not find qualifies for interstate distribution for a host of reasons, such as the possibility that it could be adulterated with multiple dangerous contaminants and the likelihood that it would vary greatly both in its ingredients and in the amount of its psychoactive content.REF The public is therefore exposed to a variety of cannabis products, in various forms, that have not been found to be safe, effective, and uniform as federal law requires.

The decision by Oregon and Colorado to authorize the use of psychedelics for medical treatment raises serious questions about whether the law is outpacing the science.REF Those decisions also run headlong into the governing federal law: the Controlled Substances Act. Federal law deems psychedelics like LSD to be Schedule I drugs, which no physician may prescribe,REF so administering psychedelics to a patient outside of federally approved clinical studies would be a federal offense regardless of what state law provides.REF Accordingly, unless and until the FDA approves the use of psychedelics (and the Drug Enforcement Administration reclassifies those drugs out of Schedule I), Oregon and Colorado are just daring the federal government to stop their programs in the hope that their state congressional delegations will raise such a ruckus that the U.S. Department of Justice will back off prosecuting physicians for what appears to be federal crimes. The federal government’s investigation of medical-use cannabis led Congress, beginning in 2015, to intervene through appropriations riders barring the federal government from “prevent[ing]” states from “implementing” state medical cannabis programs.REF Oregon and Colorado might well be taunting the federal government to knock the chips off their shoulders in the hope that the public will have the same adverse reaction here as it did in the case of cannabis and persuade Congress to say no mas.

But even if Congress were not to follow that path—if only because there is no groundswell of public support for legalizing psychedelics, and certainly nothing that compares with the public attitude toward cannabis—the law as it stands now still gives rise to a problem. Consider the regulatory status of the dissociative drug ketamine. As noted above, in the 1970s, the FDA approved one isomer of that drug (esketamine) for use as an anesthetic, and in 2019, the agency approved that isomer as a nasal spray for treatment-resistant depression.REF Physicians therefore can prescribe it for other purposes—the “off-label” use of that drug—without always or automatically violating federal law.REF

Yet, in 2022 and 2023, the FDA issued separate warnings about the misuse of the FDA-approved ketamine, isomer Spravato.REF The agency noted that the drug had been “compounded” and distributed for the unsupervised, at-home use contrary to the warning that the FDA requires be placed on the drug.REF The FDA noted that it had approved ketamine for use in limited circumstances and that use otherwise, as seems to have occurred,REF could lead to potentially serious physical and psychological problems.REF Nonetheless, because the FDA approved ketamine in the 1970s for use as an anesthetic, physicians can prescribe it for other purposes.REF In 2023, the FDA issued its second noticeREF warning about the misuse of ketamine, noting that the drug had been “compounded” and distributed for the unsupervised, at-home use contrary to what the FDA had authorized.REF

In one recent case, ketamine was designated as the cause of the death of the actor Matthew Perry, a cast member of the well-known television show Friends.REF His death was initially reported as “an apparent drowning,” but “according to an autopsy released by the County of Los Angeles Department of Medical Examiner,” Perry died of “‘[a]cute effects of ketamine.’”REF He “reportedly received ‘ketamine infusion therapy for depression and anxiety,’” but “[h]is last known treatment was more than one week prior to death.”REF The medical examiner determined that although “[t]he exact method of intake in Mr. Perry’s case is unknown,”REF the amount of ketamine in his system at death could not have resulted from that therapy because ketamine’s half-life is three to four hours (or less),REF and Perry’s blood contained an amount of ketamine equivalent to what would be found during general anesthesia.REF Accordingly, the FDA might decide that it is important to continue our investigation into the long-term effects of therapeutic psychedelic use and consider whether there should be reasonable but enforceable limitations on how much of a psychedelic drug a person should be allowed to use within a defined period.

Safety Considerations. Although researchers have attested to the safety of psychedelics when properly administered and supervised, psychedelics are potentially dangerous drugs even when used in a treatment setting, let alone recreationally.REF Not everyone should use them, and the proper dosages must be identified.REF Even FDA-approved drugs like ketamine can have adverse effects,REF and people can endanger themselves or others by engaging in risky conduct while under their influence.REF The safeguards that accompany therapeutic administration of psychedelics will not protect someone who uses a psychedelic without medical supervision or recreationally. That is particularly true because we lack a Narcan-like “rescue” treatment for a psychedelic’s adverse effects.REF

Aside from the risk of improper psychedelic use for medical purposes, ketamine has been used recreationally because of its short-term dissociative and hallucinogenic effects.REF Some individuals will be highly motivated to find a physician willing to prescribe psychedelics for that purpose, and, though we might wish it were not so, there is no rule of law or life guaranteeing that every physician will “do no harm.” On the contrary, the case lawREF proves that not every physician has the scruples of ER’s Mark Greene.REF Moreover, legalizing psychedelic use, even under responsible, close medical supervision, removes whatever stigma is associated with its current Schedule I status, thereby weakening a potential deterrent to illicit use.REF

Justified Skepticism. We should be wary of claims that psychedelics (or any other drugs, for that matter) are “wonder drugs.” Consider methamphetamine.REF Meth was originally hyped as a “wonder drug.” It was useful to the military for fending off fatigue and sleepiness while also generating strong feelings of alertness, vigilance, stamina, peripheral vision, and self-confidence. For civilians, meth was initially seen as valuable for working, studying, or weight loss.REF Now we realize that methamphetamine, like heroin—which was also initially hyped but later crashed and burned—is a drug that, like Icarus, flew too close to the sun. The long-term use of meth leads to physical and mental deterioration, rendering “speed freaks” akin to the hungry ghosts in Buddhist cosmology: creatures always searching for satisfaction but never finding it. We do not want to make a mistake today that ruins the lives of numerous others.REF To be sure, that concern does not require us to abandon research into psychedelics’ safety, effectiveness, and uniformity; not at all. But it does militate caution lest our eagerness to find a new treatment lead us into mistakenly concluding that psychedelics work when they don’t or that there are no long-term risks from their frequent, if not daily, use.

We should be skeptical of media stories about high-profile individuals who claim to have benefitted from psychedelics,REF sometimes by “microdosing”—that is, the use of minute quantities of psychedelics below the threshold that would generate hallucinationsREF (as opposed to “minidosing”—that is, the use of quantities just above that threshold, which generates some perceptible effectREF). Psychedelics, they say, enhance their creativity and “get the juices flowing” in fields where competition is fierce.REF Whether or not those stories are true—they might just be attempts (by the individuals themselves or their publicists) to make someone look like an outlaw or “edgy”—they are not the stuff that proves a drug is safe and effective. “From a scientific perspective it makes no difference how many people make such claims.”REF Such reports are only “anecdotal evidence, which is much like gossip; it spreads quickly, but it often unreliable.”REF Increasing the number of celebrities who endorse psychedelics or the amount of media attention they receive does not increase the value of what they say. Whatever their number might be, celebrity endorsements are not remotely the type of proof that the FDA demands.REF

It should go without saying that we should be wary of claims made by people who are not treating patients but who can benefit financially from the government’s approval. Cannabis advocates had considerable success persuading states to change their laws to allow cannabis to be sold for medical or recreational purposes. Private investors are attempting to repeat that outcome in the case of psychedelics.REF Yet people who have their own financial interests in mind rather than the health of their employees or the public might not be the most impartial experts to look to for advice.REF

The effort to legalize therapeutic psychedelic use is uncomfortably familiar to the one that we saw in the 1990s (and have seen since then) for legalizing medical-use cannabis.REF That opinion is not mine alone. As Professor Madras noted in 2022, “The momentum to also legalize hallucinogens shares strategies in common with movements that were calculated to increase legal access to prescription opioids and marijuana in the United States.”REF NIDA Director Volkow made the same point in 2023, writing in the Journal of the American Medical Association Psychiatry that “[d]espite the promising early results, it is clear that psychedelics are not wonder drugs, but the hype has gotten ahead of the science.”REF She also directly drew a parallel to the efforts to legalize cannabis for medical use: “This is reminiscent of what happened with medical cannabis: regulations pertaining to its medical use were approved, promoting a booming cannabis industry, despite lack of scientific evidence for its therapeutic efficacy.”REF

The cannabis-legalization movement began in 1996 when California passed the Compassionate Use Act by voter referendum, ostensibly for the limited purpose of alleviating the suffering of people who were dying and in chronic pain.REF Yet the available evidence—some of which came from the mouths of the act’s own supportersREF—justifies the inference that the 1996 California law was a sham to allow for recreational use.REF The same can be said of the medical-use programs in other states.REF The states that legalized cannabis did not await an FDA determination that botanical cannabis is safe, effective, and uniformly made, nor did the states conduct their own investigations and make those findings themselves. Perhaps acting out of the mistaken belief that compassion for the suffering or dying can substitute for sound medical judgment, perhaps to find a new resource stream to fund existing or new projects, perhaps to satisfy constituents who wanted to use cannabis for medical or recreational purposes, perhaps to trade off (“log-roll”) a vote for legalization in return for a vote in favor of a different bill—whatever the reason might have been, state legislators presumed to enjoy the medical knowledge or wisdom to reject the federal government’s long-standing decision that agricultural cannabis has not been proved to be a safe, effective, and uniform drug.REF

We face the same risk. The same strategies that were used effectively to legalize cannabis for medical use are now being retooled for psychedelics.REF “One such strategy is to minimize potential adverse consequences and dismiss evidence-based safety concerns for general use.”REF Another strategy is to “recruit mainstream media to enthusiastically endorse a class of drugs and shape restricted access as a political ‘war on drugs’ (rather than acknowledge the need to exercise caution),” as well as to “develop industry-led campaigns to increase demand, and advocate legalization as a source of tax revenue.”REF Then there is the always popular strategy of using celebrities to tout a product, including psychedelics.REF One way or another, parties who hope to make millions from the sale of psychedelics will attempt to find a way to persuade legislatures to permit their retail sale.REF

The Problem of Drug-Impaired Driving. At the risk of being tedious,REF it behooves me to note that legalizing psychedelics, even just for therapeutic use, will aggravate the problem that we already face from drug-impaired drivers. As the FDA explained in its 2023 guidance document, “[p]sychedelic drugs can cause intense perceptual disturbances and alterations in consciousness that can last for several hours.”REF While undergoing a psychedelic treatment, users can mistakenly judge physical dimensions and time, and some psychedelics can impair a person’s motor coordination and working memory.REF That might be a manageable issue when treatment is administered in a controlled, comfortable setting with a qualified professional available to remind a patient that his or her perceptions are not real,REF but it is not exactly a state of mind conducive to safe vehicle handling on the nation’s roadways.REF Consider the words of Timothy Leary: “For the unprepared, the heavy game players, those who anxiously cling to their egos, and for those who take the drug in a non-supporting setting, the struggle to regain reality begins early and usually lasts to the end of their session.”REF Well, he would know. A person undergoing such an experience has no business driving a motor vehicle.

The FDA has recognized that psychedelics use can impair one’s driving skills, explaining when it announced the approval of the ketamine isomer called Spravato that it “may impair attention, judgment, thinking, reaction speed and motor skills,” so “[p]atients should not drive or operate machinery until the next day after a restful sleep.”REF The U.S. National Highway Traffic Safety Administration (NHTSA) agrees. In a 2014 report, the NHTSA wrote that while LSD can have person-specific effects and while “the incidence of LSD in driving under the influence cases is extremely rare”—it likely occurs far less often than alcohol-impaired or cannabis-impaired drivingREF—the psychological effects of LSD include “[h]allucinations, increased color perception, altered mental state, thought disorders, temporary psychosis, delusions, body image changes, and impaired depth, time and space perceptions.”REF Users can feel several different emotions simultaneously or rapidly swing back and forth from one to another.REF And that’s when a user is enjoying his or her experience. “‘Bad trips’ may consist of severe, terrifying thoughts and feelings, fear of losing control, and despair.”REF No one driving on a freeway wants to be mistaken for a White Rabbit by someone behind the wheel who’s tripping. In sum, legalizing psychedelic use will increase the number of drivers who should not be behind the wheel, which in turn will increase the number of roadway crashes, serious injuries, and fatalities.

Yet few people who have discussed this research development—including the physicians and researchers who have published many of the articles supporting psychedelic therapy—have addressed the problem of driving under the influence of those drugs.REF That is disappointing and distressing. It is not as if this concern is brand new. After all, physicians advise patients not to drive for 24 hours (or more) after general anesthesia because it impairs cognitive and psychomotor functions necessary for safe vehicle handling.REF That is why physicians want their patients to be driven home by a responsible third party after receiving general anesthesia.

The commentators who have addressed the highway safety problems posed by psychedelic use have recognized that no one should drive a motor vehicle while under the influence of any psychoactive drug, including psychedelics.REF As several researchers have explained, “[t]he perceptual and psychomotor distortions associated with hallucinogen use have alarming implications for driving safety,” such as “impairment in attention, focus, memory, response time, motor abilities, and the interpretation of visual and auditory stimuli.”REF Atop that, “[d]riving under the influence of hallucinogens is also associated with risk-taking and impulsive behaviors such as speeding or disregarding traffic signals,” as seen in “increased collisions” in “experimental groups.”REF What is more, police officers can use Breathalyzers to measure a driver’s blood-alcohol content to learn whether he or she is over the legal limit of grams per deciliter (g/dL),REF but there is no similar roadside test yet available that an officer can use to determine whether someone is under the influence of a psychedelic. Legalizing psychedelics atop the legalization of cannabis is likely to offset the remarkable success that society has had over the past four decades in reducing the number of alcohol-induced traffic crashes, injuries, and fatalities. The result could be a step backwards in public safety.REF

There is a response to that argument, and it would go like this: “Fine. Driving under the influence of psychedelics is unlawful and risks injury or death to others. And, yes, that is why ambulatory patients are told not to drive for a full day after receiving general anesthesia. But that analogy needs to be played out in full. An estimated 21 million people receive general anesthesia each year for surgery,REF and ambulatory patients are released to the care of a third party with the injunction not to drive for 24 hours. Society should be free to rely on the same admonition for patients who have received not a general anesthetic, but a psychedelic. After all, there is no good reason to deny people safe, effective, and available relief from afflictions like depression just because a small number of users will violate the rule against driving after use.”

That response is a reasonable one, but it is not a slam dunk.

For many patients, surgery is the only route to enable them to save their lives or return them to a better state of health. Tumors do not remove themselves, and broken or damaged limbs and joints might need to be reset or replaced. Perhaps the same concern would justify psychedelic treatment for someone who is potentially suicidal or is so debilitated by a disorder that truly no other treatment can offer any relief from an utterly miserable existence. But a problem lies in distinguishing those patients from the ones who can fake their way to receive psychedelics or who find physicians willing to look the other way when a patient makes his or her case. Patients cannot fake x-rays or blood tests, but the average thespian might be able to portray someone claiming to be severely depressed via a telemedicine video-call with a physician.REF

We know that psychedelics have been used for medical purposes but without onsite medical supervision, as well as recreationally.REF Just as some people have used a host of other illicit drugs for recreational purposes, some individuals will be highly motivated to find someone willing to prescribe psychedelics for that use. Though we might wish it were not so, there is no rule of life or law guaranteeing that every physician will be noble.REF State legislatures are entirely justified in taking that fact into account and should not be condemned if they conclude that the risk of driving while tripping is too great to force upon potential innocent victims.REF

Some primitive cultures (and some contemporary ones as well) treat hallucinogens reverentially “as being sacred, put on the earth by the Supreme being(s) to allow communion between the spirit and the material worlds for the purposes of healing and divination.”REF Those cultures disallow the use of hallucinogens for “recreational or frivolous purposes” or beyond a “strict ritual context.”REF By contrast, there are no voluntarily followed or socially enforceable cultural guidelines that prevent tripping for fun and profit in the United States. “[C]ontemporary use of hallucinogens often distorts ancient traditions, compromises inherent safeguards, and sets the stage for dangerous abuse.”REF In some quarters, it takes little coaxing to generate widespread drug use. As a result, “[w]hat once was a sacred and reverent utilization of psychedelic substances among tribal peoples has devolved into the profaned and pathological phenomenon we now define as drug abuse.”REF

As far as the FDA’s responsibility goes, the risk that approval of psychedelics would increase the number of drug-impaired drivers is not a ground for disapproval of an otherwise beneficial drug. Opioids have that effect too. But the FDA could require a warning label about the risks of driving or operating other types of potentially dangerous machinery after consuming a psychedelic. The FDA or another branch of the federal government—such as the Department of Health and Human Services or the White House Office of National Drug Control Policy (ONDCP)—could issue an official advisory to drug manufacturers, physicians, and the public about the dangers of driving under the influence of a prescribed psychedelic. During the Obama Administration, ONDCP found that the problem of drug-impaired driving was as serious as the parallel problem of alcohol-impaired driving and demands an “equivalent” response.REF That response is particularly necessary given the number of states that now have medical-use or recreational-use cannabis programs.

Cannabis-impaired driving is becoming an even greater public health problem than it was in 2010. Sadly, neither the Obama, Trump, nor Biden Administration has followed through on ONDCP’s conclusion. None of those Presidents treated drug-impaired driving as a serious problem; none ordered federal officials to combat drug-impaired driving; and none used the bully pulpit to educate the public. Were the FDA to approve psychedelics for medical use, the agency would have the opportunity to address those shortfalls by confirming its importance, by urging ONDCP to coordinate a federal response, and by encouraging Congress to help the states and localities addressing this problem.REF

Conclusion

Depression causes its sufferers intense, all-encompassing, and unrelenting psychological misery, which is why MDD is strongly associated with suicide. PTSD forces some trauma victims, such as servicemembers, to relive a painful or frightening experience as if it were happening again and again. Substance abuse disorders shackle users to a life devoted to reliving a fleeting euphoria or avoiding a deep abyss. Psychedelics hold promise for people who suffer from those disorders, as well as others. Science certainly should continue its recently reinvigorated investigation of the potential benefits of this category of drugs.

But we must be sure not to let our desire to learn whether psychedelics truly are therapeutic, and at a cost that society is willing to bear, blind us to what the results of those inquiries reveal or don’t yet tell us. Wishing on a star might work in songs and movies, but it doesn’t make dreams come true in real life. Here, as elsewhere, we should remember that there might have been eminently sensible reasons why a particular category of drugs was outlawed. Perhaps the reason was that there was no proof (or only an inadequate amount) that those drugs, when used regularly on a long-term basis, would not cause long-term injury to patients. Perhaps it was a reluctance to force patients or innocent third parties to bear the cost of our mistaken judgment as to the safety and efficacy of drugs like psychedelics. Those reasons or others might still have currency today despite the hosannahs we hear from some advocates about psychedelics.

Author Michael Pollan expressed the opposing viewpoints in 2018 better than I can today:

We shouldn’t forget that irrational exuberance has afflicted psychedelic research since the beginning, and the belief that these molecules are a panacea for whatever ails us is at least as old as Timothy Leary. It could well be that the current enthusiasm will eventually give way to a more modest assessment of their potential. New treatments always look shiniest and most promising at the beginning. In early studies and with small samples, the researchers, who are usually biased in favor of finding an effect, have the luxury of selecting the volunteers most likely to respond. Because their number is so small, these volunteers benefit from the care and attention of exceptionally well-trained and dedicated therapists, who are also biased in favor of success. Also, the placebo effect is usually strongest in a new medication and tends to fade over time, as observed in the case of antidepressants; they don’t work nearly as well today as they did upon their introduction in the 1980s. None of these psychedelic therapies have yet proven themselves to work in large populations; what successes have been reported should be taken as promising signals standing out from the noise of data, rather than as definitive proofs of cure.

Yet the fact that psychedelics have produced such a signal across a range of indications can be interpreted in a more positive light. When a single remedy is prescribed for a great many illnesses, to paraphrase Chekhov, it could mean those illnesses are more alike than we’re accustomed to think. If a therapy contains an implicit theory of the disorder it purports to remedy, what might the fact that psychedelic therapy seems to address so many indications have to tell us about what those disorders might have in common? And about mental illness in general?REF

The FDA will now address those questions when it decides how to classify the drug MDMA in light of the new evidence of its utility. That is the approach we should have followed in the case of cannabis but didn’t. Well, better late than never. We can’t undo past mistakes, but we can refuse to treat them as binding precedents. Whatever the FDA’s decision might be, at least this time we have the right agency making the call.

Paul J. Larkin is the John, Barbara, and Victoria Rumpel Senior Legal Research Fellow in the Edwin J. Meese III Center for Legal and Judicial Studies at The Heritage Foundation. I would like to thank Robert L. DuPont, Keith Humphreys, Julia Jacobson, Bertha K. Madras, John G. Malcolm, Derrick Morgan, William Poole, Nina Owcharenko Schaefer (twice over), and Doug Simon for valuable comments on an earlier iteration of this Special Report. Any errors are mine alone.