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July 29, 2020

The Current Status of Psychedelics in Psychiatry

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  • 1Imperial College London, London, United Kingdom
JAMA Psychiatry. 2021;78(2):121-122. doi:10.1001/jamapsychiatry.2020.2171
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    3 Comments for this article
    Psilocybin in Psychiatry: An Additional Dose of History
    Brian Anderson, MD, MSc | UCSF / Zuckerberg San Francisco General Hospital
    We thank Drs. Nutt and Carhart-Harris for their Viewpoint on the Current Status of Psychedelics in Psychiatry. Their text provides a helpful overview of our field’s recent history, appropriately emphasizes that these are drug-assisted psychotherapies (vs purely pharmacotherapies), and correctly underscores the importance of clinical training for the future of these promising but complex interventions. We offer the following comments.

    Although infrequently-cited, Moreno et al.’s 2006 pilot study of psilocybin therapy for treatment-resistant obsessive-compulsive disorder (OCD)(1) was the first 21st-Century psilocybin trial conducted in a clinical population. Not only did this study jumpstart the current era of treatment studies
    with classic psychedelics, it also produced the first modern data in support of psilocybin’s ability to disrupt maladaptive, ruminative thoughts in a treatment-resistant psychiatric population. Shortly thereafter, Grob et al.’s pilot study of psilocybin therapy for anxiety in patients with advanced cancer,(2) which began in 2004, provided important safety and feasibility data that supported subsequent Phase 2 trials for anxiety and depression in cancer patients.(3) These pilot trials established with modern methodologies the proof-of-concept necessary for the use of moderate-to-high doses of oral psilocybin in psychiatric patients.

    It remains unclear what the optimum dose of psilocybin is for different patient populations. It is true that several recent trials in mood disorders have used a 25mg po fixed dose, but the majority of modern experience with psilocybin has been with weight-based dosing, with ‘high dose’ meaning 0.3-0.6mg/kg po, which often translates to doses much higher than 25mg. To date, no head-to-head comparisons have been made between psilocybin doses in the same patient population to assess comparative safety, efficacy, and durability of effect. And even though high-dose regimens have produced many of the impressive clinical outcomes cited in the literature,(3) they also likely carry greater safety risks than moderate doses, thus the need for careful attention to adequate screening and psychological support.

    There is as yet no standard dose of psychotherapy in psilocybin therapy trials. Some studies may limit preparation to a single visit the day before medication administration, but most recent trials have provided this behavioral support over several sessions spread out over days-to-weeks prior to the first medication session. To avoid some of the adverse reactions seen in the early days of psychedelic psychiatry,(4) we encourage investigators to offer robust preparation and trust-building prior to high-dose psilocybin treatments for clinical populations.

    Brian Anderson, MD, UCSF/ZSFG
    Alicia Danforth, PhD, Lundquist Institute
    Charles Grob, MD, Harbor-UCLA/Lundquist Institute

    1. Moreno FA, Wiegand CB, Taitano EK, Delgado PL. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J Clin Psychiatry. 2006;67(11):1735-1740.
    2. Grob CS, Danforth AL, Chopra GS, et al. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry. 2011;68(1):71-78.
    3. Reiff CM, Richman EE, Nemeroff CB, et al. Psychedelics and psychedelic-assisted psychotherapy. Am J Psychiatry. 2020;177(5):391-410. doi:10.1176/appi.ajp.2019.19010035
    4. Johnson MW, Richards WA, Griffiths RR. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008;22(6):603-620. doi:10.1177/0269881108093587
    Psychedlic therapy is an healing ceremony
    Andrew Ferber, MD | Assoc Prof. of Psychiatry AECOM(ret) .Director Osho Inst. for the Art of Living and Dying
    All healing ceremonies, from the beginning of time can be conceptualized as having three factors: the intent of the patient/seeker to be healed; the being/presence of the healer; the techniques/medicines of the therapy . This excellent review shows the current,pathetic state of Western medicine and thought.It acts as if the intentions of the patients were uniform,and the beings of the healers were irrelevant. Psychedelics facilitate the healing ceremony by showing the patient the movies in his/her own mind while allowing the witness,the self,the watcher , to helplessly become aware of old movies it can let go of and new possibilities it can embrace. The intent of the patient to be healed is primary.

    In these uniquely uncertain times,people are eager to let go of pasts they no longer believe in with such certainty, and futures that are increasingly unpredictable. Psychedelic therapy allows a more rapid transformation than any talk therapy if combined with authentic ,ongoing practices to center a person and evolve each individual's consciousness. It is called therapy if the person is trying to readjust to the mass insanity called normal, and called spiritual growth if the patient realizes there must be something beyond what I was taught as being normal.

    In our current work as a ketamine facilitators at Myself Wellness in Bonita Springs Florida we find a tremendous range of responses,mostly positive to the experience. The healing presence of the guides/therapists is a neglected component of each healing journey. As a third generation physician I have always been aware that the best healers are those who are the most, not those who know the most or do the most.May all beings realize their intrinsic perfection.Love Andrew FerberMD aka Swami Anand Bodhicitta
    The Current Status of Psychedelics in Psychiatry: Only needs to use in the context of RCT
    Hunasikatti Mahadevappa, MD, FCCP | Fairfax Hospital, Private Practice , Fairfax, VA
    Dangerous: The authors state that “The current model is time and therapist intensive, and even though only a couple doses of medicine are required, this is currently costly because of the many regulatory challenges associated with psychedelics still being scheduled as very dangerous, illegal drugs under the UN Conventions and all Western governments’ drug laws. The authors lament on that fact that they are ‘still’ considered dangerous as there is some evidence on the short term and long-term adverse events. However, Vardy and Kay (1983) studied whether patients hospitalized for LSD psychosis are clinically separable from acute schizophrenics and analyzed for 52 LSD psychotics and 29 matched first-break schizophrenics. The LSD patients did not differ from schizophrenics in incidence of psychosis or suicide among the parents. In most respects the LSD psychotics were fundamentally similar to schizophrenics in genealogy, phenomenology, and course of illness. The findings supported a model of LSD psychosis as a drug-induced schizophreniform reaction in persons vulnerable to both substance abuse and psychosis. Until this risk of psychosis ,is evaluated and quantified, in larger clinical studies, the drug should remain under strict regulatory controls. The long-term potential for addiction, dependence , psychosis and suicidal risk needs to be well defined before the clinical use for use in psychiatric disorders. The small number of patients they have referenced are not supportive of the claim of long-term tolerability and long-term outcome is needed before embarking on regular use of these drugs in clinical care of patients.

    Legalization: Oregon made history on November 3, becoming not just the first U.S. state to legalize psilocybin, the psychoactive compound in “magic mushrooms,” but also the first jurisdiction in the world to lay out plans for regulating the drug’s therapeutic use( Cormier 2020). But the state-level ballot measure and positive study results broaden the legal circumstances should not be the way the psychedelics prescribed or used in US. This should be treated like any other drug with well-done Randomized , Double blind controlled, multicenter, clinical trial with long term clinical end points. As there are already available therapies for anxiety, depression and obsessive-compulsive disorders, instead of placebo standard of care drugs and interventions be used as comparators. Use of these in resistant depression, anxiety, OCD and other disorders may be involve careful enrollment of these patients in clinical trials. Swinging of the pendulum from extreme regulations to ‘make use of psychedelics’ legal and be available to the recreational users should be avoided.


    Vardy MM, Kay SR. LSD Psychosis or LSD-Induced Schizophrenia? A Multimethod Inquiry. Arch Gen Psychiatry. 1983;40(8):877–883. doi:10.1001/archpsyc.1983.01790070067008

    Cormier Z. Psilocybin Treatment for Mental Health Gets Legal Framework. Scientific American. Dec 2020.