Psilocin vs. Psilocybin: Differences & Potential Clinical Uses with Josh Woolley, MD, PhD


In this episode of the Plant Medicine Podcast, Dr. Josh Woolley joins to discuss the differences between psilocin and psilocybin, and to share upcoming clinical research which will further clarify the safety profiles, subjective effects, and clinical uses of these psychedelic substances.

Dr. Woolley is an Associate Professor in Residence in the Department of Psychiatry and Behavioral Sciences at the University of California, San Francisco (UCSF) as well as a staff psychiatrist in Mental Health at the San Francisco Veterans Affairs Medical Center (SFVAMC). He is Board Certified in Psychiatry by the American Board of Psychiatry and Neurology. He is the Director of the Bonding and Attunement in Neuropsychiatric Disorders (BAND) lab at UCSF that focuses on understanding and treating social deficits in neuropsychiatric disorders including schizophrenia, substance use disorders, and mood disorders. He is also the Director of the Translational Psychedelic Research (TrPR) Program at UCSF, which brings together scientists and care providers across disciplines to understand how psilocybin, LSD, ketamine, MDMA, and related compounds impact the brain and other organ systems.

In this conversation, Dr. Woolley begins by sharing a bit about TrPR and the upcoming research they will be conducting on psychedelics as a treatment for depression in individuals living with Parkinson’s disease. Dr. Woolley then introduces the main topic of psilocin, psilocybin, and the differences between these two compounds. He explains that psilocybin is a prodrug for psilocin, meaning that the human body metabolizes psilocybin into psilocin, which is the compound responsible for the psychoactive effects produced by psilocybin-containing mushrooms.

Dr. Woolley’s upcoming research will provide more concrete data on the differences between these two compounds, as TrPR will be testing both psilocybin and psilocin in healthy volunteers, giving each participant both substances on different occasions so that effects can be studied both across the sample pool and within individuals. Dr. Woolley hypothesizes that psilocin could have certain clinical advantages over psilocybin: it could produce more consistent effects person-to-person at a given dose as individual differences in metabolism would be less relevant; it may more quickly induce a psychedelic experience, particularly when administering psilocin sublingually; and it is possible there may be fewer side effects related to the gastrointestinal tract.

Dr. Woolley closes out the discussion by sharing other upcoming research to be conducted by TrPR. In addition to the study investigating psilocin and the research into psychedelics for Parkinson’s disease, TrPR is also investigating the use of psychedelics to improve quality of life for individuals suffering from chronic pain and they will also be further investigating the interaction between psychedelics and bipolar disorder.

In This Episode

• The approach of the Translational Psychedelic Research (TrPR) Program and its upcoming research
• The pharmacological differences between psilocybin and psilocin and how the experience induced by the substances may differ
• In-subject study design and how it is used in Dr. Woolley’s psilocin trials
• The mechanisms for tolerance with using psychedelic drugs
• Data on the contraindication of psychedelic use for individuals with bipolar disorder


“For a long time, when you make [psilocin] synthetically—[…]—psilocin wasn’t stable. So, even if you made psilocin synthetically you would then turn it into psilocybin so it would be stable and then people would take it and it would get turned back into psilocin.” [8:39]

“You can’t do sublingual psilocybin because it won’t get broken down easily. But, sublingual psilocin doesn’t need to be metabolized and it can go across your buccal membrane, skipping the gut. That theoretically could be useful because then you might skip the first pass metabolism, it doesn’t have to go to the liver, and it might be faster that way and maybe again more consistent. And fewer side effects—maybe you won’t get any GI side effects if it doesn’t go to the GI tract.” [19:58]

“We think that psychedelics—psilocybin in particular—might be able to change people’s relationship to their [chronic] pain. It might be an analgesic too—it might make the pain go away, that would be great. But even if it doesn’t do that, we think that it should allow people to basically find the pain less impairing.” [41:22]


* The Psychedelic Medicine Podcast has allowed the Psychedelic Medicine Association to post episodes as an educational resource, and in return the PMA is hosting the podcast show notes.