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Psychiatrist, internist, and addiction medicine specialist Muhamad Aly Rifai discusses his article “Psychedelic-assisted therapy: science, safety, and regulation.” Muhamad explores the complex landscape of psychedelic medicine, balancing the growing public interest with the necessity of rigorous FDA oversight and safety protocols. The conversation examines the distinction between classic psychedelics like psilocybin and dissociatives like ketamine while highlighting why “set and setting” are critical for therapeutic success in treating depression and trauma. Muhamad emphasizes that these powerful agents are not simple pill swaps but require structured psychological support to translate peak experiences into lasting behavioral change. Discover why the path to effective treatment relies on transparent regulation and clinician humility rather than unsupervised experimentation.

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Transcript

Kevin Pho: Hi, and welcome to the show. Subscribe at KevinMD.com/podcast. Today we welcome back Muhamad Aly Rifai, psychiatrist, internist, and addiction medicine specialist. Today’s KevinMD article is “Psychedelic-assisted therapy: science, safety, and regulation.” Muhamad, welcome back to the show.

Muhamad Aly Rifai: Thank you very much for having me to talk about this timely topic about psychedelic-assisted therapy in psychiatry and talk a little bit about the science, the safety, as well as the regulation.

Kevin Pho: All right, so tell us what your article is about.

Muhamad Aly Rifai: My article talks about psychedelics. We hear a lot in the news about mushrooms. We hear about other substances such as MDMA, LSD, and psilocybin. We hear about some people who go off to Mexico or other South American countries and have these spiritual resets and spiritual retreats. Your blog has talked a little bit about this psychedelic revolution as well. This is partially because in American psychiatry we are running low on new pharmaceutical targets that can help people with depression, anxiety, mood issues, and psychosis. So we have basically turned to newer potential alternative medications that are derived from natural products as well as man-made products.

Psychedelics are one of them. Psychedelics in general affect a multitude of neurotransmitters. Some of them will affect serotonin in the brain. Some of them will affect norepinephrine. Some of them will affect dopamine. We have also talked in the past about ketamine as an anesthetic, which is also something that causes dissociation. But for legal purposes, the Food and Drug Administration and the Drug Enforcement Agency designate psychedelics as Schedule I. By Schedule I, I mean these are substances and medications that have no medical utility at this time, similar to heroin and cocaine. Basically, they have not approved any of these medications except for ketamine, which already has utility as an anesthetic and has been approved for depression.

But to recognize that there is a new wave coming, the American Journal of Psychiatry from the American Psychiatric Association actually devoted a whole issue to psychedelics. About a year and a half ago, we were on the precipice of the Food and Drug Administration approving MDMA to treat post-traumatic stress disorder. However, it declined to approve it. There was a protocol submitted for MDMA-assisted psychotherapy to treat post-traumatic stress disorder, which a lot of people were hopeful was going to be approved, but the FDA declined to approve it. There are more studies and research ongoing. Up until today, we do not have any FDA-approved psychedelic medication, though there are many in the pipeline. I think this really necessitates physicians having discussions about what is coming for the future.

Kevin Pho: So in terms of the data, you mentioned PTSD potentially. What are some of the more recent numbers showing potential efficacy and utility for psychedelics in any psychiatric disorder?

Muhamad Aly Rifai: The one that really has been studied a lot, and there are some specific states that approve that substance, is psilocybin. Psilocybin is a derivative of a natural mushroom. Basically, it is given in a one- or two-time dose. Most research suggests that it is actually very effective in terms of treating depression even on a one- or two-dose level. It creates a significant change in the brain that actually resolves an episode of depression that a person is going through.

There are a couple of states that actually have approved it. Oregon has a regulated psilocybin service. It opened that in 2023. It requires specific licensure. Colorado also has a natural medicine program and a licensure pathway that actually allows people to utilize psilocybin specifically. It is a natural mushroom product that helps with depression. There are multiple pharmaceutical companies that have psilocybin-type products in the pipeline. Psilocybin mostly affects serotonin in the brain. These companies are seeking approval for the treatment of depression, anxiety, and post-traumatic stress disorder. This is very exciting because we are going to have different products than the SSRIs, antipsychotics, and mood stabilizers that will treat psychiatric disorders. Specifically, the treatment modality is associated with psychotherapy. The treatment is not a pill that you take on a regular basis. You get one or two or three treatments and your depression is resolved.

Kevin Pho: So in Oregon and Colorado, you mentioned that there is a special pathway for prescribers to prescribe psilocybin. Are they psychiatrists and do you have to take some type of course or CME in order to be certified? Is that the case?

Muhamad Aly Rifai: Similar to other medications, psychiatrists and some naturopaths have to take specialized courses to be able to prescribe that, and it is in a protected environment. Specifically, the worry is that, like cannabis, it is still not FDA and DEA approved. It is still a Schedule I medication. So we are still in that gray zone similar to cannabis, though there has been movement with cannabis getting closer to being approved. But that is what we are dealing with in the psychedelic movement. A lot of these medications are not approved. There are some clinical trials ongoing. The hope is that in the next year or two we are going to see some agents approved for depression, anxiety, and post-traumatic stress disorder.

Kevin Pho: What is some of the safety data in the studies that have looked at psilocybin? What are some of the short-term and potential long-term side effects of that medication?

Muhamad Aly Rifai: The safety data is very robust with psilocybin if it is in a protected environment where a patient is monitored. In the study submitted to the FDA utilizing MDMA for individuals with post-traumatic stress disorder, the patient received the treatment under the supervision of two treaters. Two therapists ensured the patient’s safety and monitored them over an extended period of time. After they receive the treatment, they receive psychotherapy or preparation treatment prior to the ingestion of the medication. While they are receiving the medication, they process that experience because it causes a dissociative episode. Then afterwards they also process it post-treatment. Those experiences are the ones where individuals actually receive the most benefit from the medication.

The safety has been significantly enhanced with supervision. As with every medication, there are significant side effects such as dissociation or the possibility of inducing psychotic experiences. But with appropriate monitoring and appropriate selection of patients, these are very minimal. What happened with the MDMA is that the FDA did not approve it because in MDMA-assisted psychotherapy, the psychotherapy was a significant part of the treatment while the medication was not the main part. The FDA wanted something that specifically focused on what the medication does as opposed to the psychotherapy. So the drug manufacturers are back to the drawing board. They are doing additional clinical trials to see if maybe MDMA or psilocybin could soon be quickly approved as medications to help depression, anxiety, and post-traumatic stress disorder.

Kevin Pho: Where do you see psychedelic medications in the treatment options when we talk about treating depression? Where do you see that as part of the armamentarium?

Muhamad Aly Rifai: We have reached a stage where a lot of patients who have depression, anxiety, or post-traumatic stress disorder have tried all of the treatment modalities that are available on the market. They have tried the SSRIs, the anti-anxiety agents, the mood stabilizers, and the antipsychotics. They have also tried ketamine, for example. They are trying transcranial magnetic stimulation. But these individuals are kind of at the end of their rope. This is a significant amount of people who are basically what we call treatment-resistant or refractory to treatment. This is around 30 or 40 percent of our patients. I think psychedelics do offer them a new pathway with a different mechanism of action, increased utility, and improved efficacy with not a lot of side effects. These are medications that will be given one, two, or three times, and then people see whether they work for them or not. So I think there is a significant percentage of our patients with psychiatric illness who will utilize psychedelics in the future once they are approved. I am very hopeful that there is a bright future for psychedelic use in psychiatry.

Kevin Pho: So it sounds like psychedelics are almost the last line of defense after they have tried every other modality for their depression.

Muhamad Aly Rifai: The hope is that once these modalities are approved, maybe people will try them sooner rather than waiting until they are suffering and not responding to other medications. I believe that is going to happen. These individuals are going to be utilizing these medications early because of their significant efficacy. For post-traumatic stress disorder, the efficacy of MDMA was as close as 80 or 90 percent from two or three doses for somebody who has severe refractory post-traumatic stress disorder. They do the therapy and they take one or two doses of MDMA, and their post-traumatic stress disorder goes into remission. So I feel that a lot of people may not wait until they have tried a lot of other treatments. They actually may prefer to try these treatments earlier.

Kevin Pho: What do you see as the path forward? Do you see other states joining Oregon and Colorado and having these special treatment programs? Do you see eventually the FDA removing psychedelics from being Schedule I? What do you anticipate the path forward to be?

Muhamad Aly Rifai: I think it is coming. We know of at least ten psychedelic-based medications that are in the pipeline in phase two and phase three trials. So there are serious trials being monitored by the FDA for approval. There are a variety of products for depression, anxiety, and post-traumatic stress disorder. The veteran population is really excited about psychedelics and they are really pushing for these medications to be approved to help with their symptoms of post-traumatic stress disorder. I see in the next year or so one or two agents being FDA-approved and moving off of Schedule I to a more appropriate category where they would be used to treat depression, anxiety, and post-traumatic stress disorder. I am hoping it is going to happen sooner rather than later.

Kevin Pho: We are talking to Muhamad Aly Rifai, psychiatrist, internist, and addiction medicine specialist. Today’s KevinMD article is “Psychedelic-assisted therapy: science, safety, and regulation.” Muhamad, as always, let’s end with take-home messages that you want to leave with the KevinMD audience.

Muhamad Aly Rifai: I believe that psychedelic-assisted therapy stands as a candidate for the treatment of depression, trauma, addiction, and post-traumatic stress disorder. It is going to be within disciplined science and accountable systems, and the path really runs through transparent regulations. Clinicians should be involved, and we should protect people who feel desperate to receive treatment. So I feel that hopefully in the next 12 to 18 months we are going to see products that will help patients who are suffering from refractory symptoms of depression, anxiety, and post-traumatic stress disorder.

Kevin Pho: Muhamad, thank you so much for sharing your perspective and insight. Thanks again for coming back on the show.

Muhamad Aly Rifai: My pleasure. Thank you.