I had the opportunity to recently attend a “Psychedelics and Psychiatry” conference and was struck by so many new developments over the past year. Some lingering questions from recent years now have some answers but there are always new questions since the research into psychedelics is still in its infancy. In this article, I will share the top 5 take home messages about psychedelics that are relevant to the practice of psychiatry.
The horserace to see which psychedelic will be FDA approved first appears to have a winner. MDMA will likely receive FDA approval for Post Traumatic Stress Disorder (PTSD) in late 2023-early 2024 based upon 2 clinical trials which showed very impressive results in patients who received just 3 doses of MDMA; there was a 32% remission in patients who just received therapy compared to 67% remission in patients after 2 months who received MDMA and therapy combined. The effects are durable over time with continued 67% remission at 1 year and 74% at nearly 4 years. The number one side effect was muscle tightness (30%), decreased appetite and sweating. This will not be a take home drug and the FDA will give guidelines for its use after its approval.
There are no safety concerns mixing an SSRI antidepressant with a psychedelic such as MDMA or psilocybin but there’s a good chance based upon preliminary studies that being on an SSRI does interfere with the full antidepressant effect of a psychedelic. The potential issue would be that patients might have to be off antidepressants for 6-8 weeks to have a better response to the psychedelic but would patients be able to wait during that time period they are off medication? There are some anecdotal reports that doubling the dose of the psychedelic might rectify the issue. Another option is to consider ketamine; one advantage of ketamine which is not technically a psychedelic but has very similar psychedelic effects would be not having to taper off antidepressants to get the full benefit from the ketamine treatment.
Specific mental health problems are more responsive to psychedelics than more chronic conditions like Major Depression. That might explain why treating PTSD would be easier to treat as it is often based upon a specific traumatic event such as military combat or abuse and the psychedelic helps fix the acute problem. In contrast, treatment resistant depression would require more frequent treatment with the psychedelic as the benefits seem short-lived. Thus, the idea of getting continued psychedelic treatment over time based upon a certain frequency (such as 2-3 doses per year) may lose its appeal for someone who was hoping to be off all external agents over time whether it be an antidepressant or a psychedelic. However, while a study that compared psilocybin to an SSRI as equal in the treatment of depression, the following measures favored psilocybin: wellbeing, flourishing, ability to take pleasure in life, improved work and social function, and increased connectedness with self, others, and the wider world. Thus, the increased effort to have maintenance treatment with a psychedelic could be worth it.
All the data so far on microdosing psychedelics suggests it’s not about the drug. Microdosing involves taking very small doses of the psychedelic in order to benefit from its physiological action while minimizing undesirable side effects. People microdose to alleviate anxiety/depression, enhance performance, improve creativity, improve energy and facilitate social interactions. There were 3 different studies comparing placebo with a microdose of psychedelic. What drove the beneficial result was not what was actually taken but what the person thought they took. For example, if a person thought they took the drug but actually took the placebo, the results suggested that the placebo worked just as well. Placebo responses can be very powerful and there are changes in the brain with placebo but it’s due to the person’s heart and soul and not the drug. This will be further clarified in bigger randomized trials.
There is going to be new subspecialty in psychiatry called Psychedelic Medicine and three universities (Harvard, Yale, and Johns Hopkins) so far will offer fellowship training. While some psychiatrists may get extra training to offer psychedelics, what will likely happen is there will be a Psychedelic Medicine Specialist who a psychiatrist will refer appropriate patients for psychedelic interventions. Don’t be surprised to see Psychedelic Therapy Centers in the coming years where there will be therapists cross-trained in different modalities based upon what psychedelics are approved and appropriate for any given patient.
Research continues to explode with psilocybin and many psychiatric and medical conditions. The list includes: Parkinson’s Disease, Bipolar II Depression, chronic suicidality, Anorexia Nervosa, Body Dysmorphic Disorder, Binge Eating Disorder, Fibromyalgia, chronic pain, Obsessive Compulsive Disorder, Alzheimer’s Disease, and palliative care. There has never been a study comparing psychedelic alone versus psychedelic plus therapy; that is now occurring in which subjects will receive a psychedelic while under general anesthesia to see if the biological changes alone account for some or all of the benefit. There still have been no studies comparing psychedelics against each other or what happens when psychedelics are combined at the same time. While there is a lot of hope about the potential of psychedelics, time will tell with more comprehensive research and clinical experience what it’s true role will be in psychiatry and perhaps in the culture at large.