The Government Exhibits Caution About Psychedelics
Publish Date: March 17, 2026
Author: Dr. Jeffrey A. Lieberman
Source: Shrink Speak substack
The FDA puts the brakes on psychedelics as treatments for mental illness.
Key Points:
- Slowing the approval of psychedelics for treatment of mental illness ensures stronger safety standards
- A more deliberate process helps avert harms from rushed quick-fix drugs
- Giving a drug additional time in the approval process allows clearer understanding of psychedelic science
- Greater caution reduces the risk of off-label misuse
In a blow to the psychedelic drug industry, the Trump administration has halted the Food and Drug Administration's plan to fast-track COMP360, a synthetic psilocybin treatment for treatment-resistant depression (TRD). Biotech company Compass Pathways had reported successful achievement of the primary endpoint in the first of two Phase-3 trials of COMP360 over the summer of 2025. They later reported “positive discussions with the FDA” and anticipation of an accelerated commercial launch timeline.
But of ten drugs that are up for accelerated review, the novel psychedelic agent was the only one vetoed by the U.S. Department of Health and Human Services and the White House. Critics of the move have suggested that political motives, rather than scientific objections, may be playing a role in the decision. But it is important to remember that the rejection of fast-track review is not an evaluation of the efficacy of the treatment itself—and as a practicing psychiatrist, I must admit that this move by the Trump administration is likely a judicious one.
Government Pitfalls
Americans have long been drawn to the idea of a “quick fix” solution, and even medicine has proven susceptible to its lure. Amphetamines and later fen-phen (fenfluoramine-phenteramine), for example, were circulated as weight-loss drugs without considering the effects of prolonged use in the real world. The eventual results were unmistakable: long-term amphetamine use led to dependency, stroke, and sudden death, while long-term use of fen-phen produced serious cardiac side effects.
In the twenty-first century, the U.S. government has bowed to public pressure in its willingness to consider legalization of previously illegal recreational drugs, as evidenced by the medicalization and then legalization of cannabis. Unrestricted use of commercially produced forms of cannabis at potency levels higher than the formerly used homegrown and black-market strains has led to increased risk of both psychotic disorders and heart attack. And while possible therapeutic value has been the apparent justification for legalization, public pressure, tax revenue for states, and profits for new industries have been important catalysts.
The Rise of Psychoactive Substances
We have now embarked on a similar course to gain FDA approval for psychoactive substances with dubious rationales. Following the path blazed by cannabis, an array of psychoactive pharmacologic agents is being explored ever more enthusiastically as therapy options for a variety of mental illnesses.
Source: Dr. Jeffrey Lieberman
The FDA greenlit an inhalant form of ketamine for treatment of depression in 2019 (Spravato by Johnson and Johnson), but this was a lyophilized formulation of a previously marketed parenteral formulation of the drug long used as a dissociative anesthetic. The first rehabilitated recreational drug was rejected by the FDA in June of 2025, when Lykos Therapeutics submitted a clearly flawed new-drug application (NDA) for MDMA as a treatment for PTSD.
With the success of the COMP360 trials, Compass Pathways’s synthetic formulation of psilocybin is expected to be the next rehabilitated recreational drug up for FDA review, although the rescission of Fast Track status will mean a longer timetable for review. The other psychoactive drug candidates in the queue will follow in due course.
While psychoactive drugs may show promise in the treatment of mental illnesses, we must not let enthusiasm and unsubstantiated expectations, let alone commercial opportunism, cause rush to judgement and sacrifice safety for expediency. Patience, dispassion, and rigorous research are required before we embrace these drugs as ready for prime time.
The Problems with the Process
Not only are the motives for legalizing these drugs questionable, but the current situation is fraught with problems and unanswered questions. The precise definition of pharmacologic classes, for example, is not being respected. Psychedelics have a unique clinical effect and specific pharmacology as a 5HT-2A receptor agonist. This class of drugs holds tremendous potential, but we don’t yet know their mechanism of action and therapeutic applications.
Moreover, other psychoactive agents with different clinical effects and pharmacological actions are being included as psychedelics even though they work by different mechanisms of action. As a result, we are developing drugs with unknown mechanisms of action for poorly rationalized indications.
Expanded Use and the Need for Caution
Should these drugs be approved for a given indication, then there is the problem of “application creep.” After a drug is approved by the FDA for a specific indication, it becomes fair game for physicians to prescribe it off-label for other purposes they feel are justified, even in the absence of evidence. The approval of psychoactive drugs will thus engender open season on their use – and will entice help-seeking patients into a wild west of improvised use, where they face the risk of currently unknown or unforeseen adverse effects.
Additionally, the non-clinical use of psychedelic drugs for recreational or self-medication purposes has risen in recent years, resulting in greater public pressure to legalize psychedelics, which warrants even greater caution. The approval of these drugs for ostensible therapeutic indications by prescription incurs one level of risk given the lack of a sufficient evidence-base, but it is also a transition point toward legalization and accessibility without a prescription.
When it comes to the adoption of psychedelics as therapeutics, therefore, it is imperative that U.S. legislators remember the dangers of the quick-fix solution and resist the pressure of public opinion and the temptation of additional tax revenues. Critically, we must ask two questions. First, are these drugs effective for the treatment of mental disorders? Early results appear hopeful, especially for psychedelics in the use of depression treatment.
But second – and here is where the danger lies – will these drugs be used appropriately when they are released to market? Psychedelic drugs will need to be prescribed correctly – for the right symptoms, at the right doses, and for precise durations. U.S. physicians have been sometimes overzealous in prescribing certain medications – psychostimulant drugs, antidepressant medications (SSRI), and ketamine (clinically proven for major depressive disorder, but also prescribed for mild depression and associated symptoms). And if the public succeeds in relaxing regulations around recreational use of psychedelics, the potential for abuse will increase exponentially.
We all desire a cure that is faster, better, and more permanent than traditional treatments. We celebrate scientific achievements in pharmacology, and we want the companies to succeed – if the treatments can be developed safely. As we determine the best path forward, we would do well to recall both wise words of caution against rushing to judgment (“trust, but verify”) and the Hippocratic oath (“first, do no harm”).
The FDA’s decision regarding COMP360 indicates a desirable return to caution in the development and approval process for psychedelic drugs. It remains to be seen how long the trend will last.