Understanding Receptor Occupancy and Psilocybin Binding

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Video Episode  👈

Dr. Mikael Palner is an associate professor in the Department of Clinical Research at the University of Southern Denmark, studying the biological correlates of maladaptive neuropsychiatric diseases—such as anxiety, obsessive-compulsive disorder, post-traumatic stress syndrome.

He joins us to discuss his research on the positive effects of psilocybin microdosing on stress resiliency, compulsions, and neuroplasticity; as well as what microdosing IS NOT good for, and some important cautions to consider with respect to potential harms of microdosing.

We also discuss why studies in rats show clear biological effects of microdosing on behaviour, but human studies seem to suggest placebo; a neural level definition of psychedelic microdosing; why microdosing research is being polluted by a lack of specificity; the value of the “psychedelic” effect of psychedelics in their use as a medicine; and why what rats need higher doses of psychedelics than human by weight.

Enjoy!

🌀 Website and Episode Show Notes

FULL TOPICS BREAKDOWN BELOW

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Episode Breakdown

• (00:00) Opening
• (05:02) Interview begins
• (05:08) Psychedelic microdosing (vs low doses)
• (06:44) The scientific study of psychedelic microdosing
• (08:43) A neural level definition of psychedelic microdosing
• (10:36) An explanation of receptor site binder occupancy and how it relates to microdosing vs macrodosing
• (16:27) Why the whole mushroom is more potent than equivalent psilocybin in extracted form
• (17:22) Rats need more drugs by weight than humans to get high
• (19:40) The models Palner used to study low dose psilocybin's effect on stress
• (26:27) The results of their study on low dose psilocybin, anhedonia
• (28:53) The stress-buffering effects were on the day after the psilocybin
• (32:01) psilocybin microdosing increases stress resilience, lowering compulsion pressure
• (34:37) Explaining conflict between approach and avoidance motivations (compulsion), and how psilocybin may help
• (39:26) 5-HT7 receptor, the paraventricular thalamic nucleus, and compulsive behaviour
• (42:10) Microdosing psilocybin, placebo or no?
• (44:22) Debating the value of removing the psychedelic effect from psychedelic drugs
• (50:39) Why human research suggestion microdosing benefits are placebo, while animal studies show biological cause and effect
• (55:50) Patreon thanks and info
• (58:28) Psilocybin Microdosing, what the science says it is and isn't likely to help with
• (1:00:53) psilocybin microdosing DO NOT make you more productive or creative, science says
• (1:03:42) What science suggestion psilocybin microdosing is likely to help us with
• (1:04:45) The neuroplasticity from psilocybin microdoses may harm an otherwise healthy person
• (1:08:52) microdosing research is being polluted by a lack of specificity
• (1:15:05) The 2024 FDA denial of MDMA was a good thing for psychedelic science
• (1:16:09) What research is next for Palner
• (1:17:49) How to stay connected with Palner's work
• (1:18:51) Closing
• (1:19:50) Integration coaching