Assessing the Safety Profile, Drug-Drug Interactions of Ketamine, MDMA, Psilocybin With Other Psychiatric Medications

Pharmacy Times interviewed Kelan Thomas, PharmD, MS, associate professor of clinical sciences at Touro University California College of Pharmacy, on his recent presentations at Insight 2021 and the virtual Sana Symposium on psychedelic adverse effects and drug-drug interactions.

Alana Hippensteele: So, Kelan, why is the topic of psychedelic adverse effects and drug-drug interactions an area of importance in this fast developing field?

Kelan Thomas: Yeah, so as drugs like MDMA and psilocybin are going through the FDA approval process and the emergence of ketamine being used in psychopsychiatric indications, it's becoming more critical to think about how these are going to integrate with our existing psychiatric medications in particular, and how can we sort of mitigate any risks.

There are potential efficacy changes based on which psychiatric medications would be used before or with the psychedelics, so really answering these questions of how are these new treatment therapies in this new treatment paradigm, and how is it going to integrate with our existing psychiatric and mental health care systems.

Alana Hippensteele: Right. What are some key points that the current scientific literature demonstrates regarding the pharmacodynamics and pharmacokinetics of psilocybin, MDMA, and ketamine?

Kelan Thomas: Yeah, so with respect to those 3 medications, MDMA tends to have the most possible adverse effects and drug interactions. The adverse effect piece is coming a lot from its amphetamine-like effects and more substantial increases in heart rate and blood pressure depending on what the dose is and how it's used.

So, if you increase the drug exposure, there may be some changes there, and it also has a lot of potential drug interactions because it's essentially metabolized by many different cytochrome P450 (CYP) enzymes.

So, then, it can be multi-directional; it's also an autoinhibitor of CYP2D6, which is a very common enzyme for drug interactions. So not only could other drugs increase or decrease the levels of MDMA, but MDMA could also increase or decrease the levels of other drugs that people are taking.

Alana Hippensteele: Right. What is currently known about the safety profile of psilocybin, MDMA, and ketamine?

Kelan Thomas: Yeah, so of those, I would say that psilocybin is probably one of the safest. It doesn't tend to have as much blood pressure and heart rate increase as the other 2 can, and ketamine, actually esketamine, its main contraindication is to not give it to people who have arteriovenous malformation, so that's a contraindication.

So, people that have underlying risks of cardiovascular disease, stroke risk, blood pressure, these may be something to consider and monitor as people are taking these, and that risk needs to be evaluated.

But psilocybin, I mean, people have taken it hundreds of times at the psychedelic dose and there doesn't seem to be much of a risk there. It also doesn't seem to have much risk with drug interactions. It's mostly metabolized by the UDP-glucuronosyltransferase enzymes or glucuronidation enzymes that don't have the same level of drug-drug interaction risk as the other 2.

Alana Hippensteele: Yeah, absolutely. Thank you so much for taking the time to speak with me today, Kelan.

Kelan Thomas: Sure, thank you.