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AM: Let's say that psilocin levels were increased by inhibition of CYP2D6. Other than a more po-
tent, psychedelic experience is there anything else we should be concerned about for our pa-
tients?

KT: Well, I want to point out that there may be more than tenfold variation in the actual concentration of
psilocybin in mushrooms people are obtaining, so it has been tricky to estimate doses for underground
experiences. Regardless, in terms of adverse effects and subjective experience, higher levels of psilocin
just lead to more intense effects.

AM: I've heard that psilocin could cause heart valve damage by agonizing the 5-HT2B receptor.
Could you speak to that?

KT: This is something that I have been very focused on.

Multiple drugs have been removed from the market with that 5-HT2B agonist effect. Even at low doses and
low plasma concentrations, these drugs seem to have a cumulative exposure effect.

We don’t think single doses here and there are an issue. Our concern is if people start taking psilocybin
every day, or even every couple days for months or years at a time, it could be a real problem—due to
constant receptor stimulation and the possible mitogenic effect. We need to investigate this further as pub-
lic use increases.

AM: Robin Carhart-Harris has said publicly that the risk of serotonin toxicity if one ingests psilocy-
bin while taking SSRIs is very low. Do you agree with this as a pharmacist?

KT. From a safety perspective, I completely agree. My colleague Ben Malcolm and I published a review of
the literature and there is a very low risk for toxicity with psilocybin and SSRIs or SNRIs, or really for most
drug combinations out there.

However, a retrospective analysis of data from online forums for classic psychedelic users showed that

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NORTHERN CALIFORNIA PSYCHIATRIC SOCIETY Page 12 January / February 2023