Page 11 - Jan_Feb_2023_Newsletter

Written by Dr. Alison McInnes, VP of Scientific Affairs at Osmind.

A recent Economist headline read: “Psychedelics are breaking through to mainstream consciousness.”
With so much hype, we need to stay informed and provide our patients with accurate information—
especially if they are also taking traditional treatments like SSRIs. Meanwhile, novel drugs like Aticaprant
that target the transdiagnostic symptom of anhedonia rather than the syndrome of depression are opening
the door to precision psychiatry.

As psychedelics continue to gain popularity and demonstrate more real-world evidence, all psychi-
atrists should be prepared for this new wave of breakthrough mental health treatments.

To help us make sense of it all, I interviewed two local experts in the field: Dr. Kelan Thomas and Dr. Boris
Heifets. I also distilled my learnings from the latest ACNP conference.

In this three-part article series, you’ll learn:
• What you need to know about interaction effects between psychedelics and SSRIs

• Separating hype from evidence

• Key takeaways regarding clinical trials for psychedelics that could affect future practice
• How drug development is now moving to target symptoms with biological correlates rather than syn-
dromes with ill-defined biology. This may be a harbinger of the evolution of the DSM.

Psychopharmacology of Psychedelics: What Every Psychiatrist

Needs to Tell Their Patients on SSRIs

The following is an interview with psychiatric pharmacist Kelan Thomas, Associate Professor at
Touro University California College of Pharmacy, concerning a practical guide to drug interactions
between common antidepressants and psychedelics focusing on MDMA and psilocybin.

AM: Welcome, let’s start with psilocybin. How does it work, how is it metabolized, and what poten-
tial drug interactions might occur for persons on antidepressants?

KT: Psilocybin, which is rapidly dephosphorylated to psilocin, is a partial agonist at the 5-HT2A receptor.
We think this activity leads to downstream effects on glutamatergic neurotransmission, resulting in en-
hanced neuroplasticity and changes in neural network connectivity that have been related to improvements
in anxiety and depression symptoms.

Psilocin is then mostly metabolized via glucuronidation enzymes, but there may also be other relevant en-
zymes involved, like MAO-A and CYP2D6, similar to metabolism of other tryptamines like DMT and LSD.
The good news is that there aren’t a lot of psychiatric medications that seem to have clinically significant
pharmacokinetic drug interactions with psilocybin.

Continued on page 12

NORTHERN CALIFORNIA PSYCHIATRIC SOCIETY Page 11 January / February 2023