Expert: Safety, Efficacy of Psilocybin May Be Negatively Impacted With Microdosing

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: How about microdosing with psilocybin—are there any known benefits or potential risks associated with this method of treatment?

Kelan Thomas: Yeah, so I actually got a really good update by David Erritzoe from the Imperial College of London, who's tried to do this sort of self-blinding study with things like LSD and psilocybin microdosing.

What has been the pattern emerging from the way that they developed this study design is that expectancy bias is the most predictive thing. So, people who thought they were getting psilocybin, essentially, they thought they were getting microdosing, even if they were actually taking placebo those days, anyone who thought they were getting that had improvements in symptoms, but it was not predicted by whether it was placebo or active psilocybin condition, it was predicted by what they thought. So essentially, it's showing how much the placebo effect is real—people expect that something positive is going to happen—those are the people who had positive benefit.

There doesn't seem to be a clear signal that psilocybin microdosing is beneficial for symptomatic treatment, so that's where there's this gap is a lot of people are extrapolating these large macro dose psychedelic dose study findings and thinking, ‘Oh well then, a little bit taking that every few days might be similar.’

We don't really have evidence to suggest that. There's anecdotal evidence—people are writing books about it and claiming that it worked for them, but until we have a robust clinical trial design of a placebo-controlled randomized trial, you can't really draw those conclusions, and it wouldn't meet the threshold of getting FDA approval for microdosing for specific psychiatric indications until that can be demonstrated.

There's also a safety risk that I've written about where a single dose has very low risk of safety problems—a single dose of psilocybin—but if we dose it routinely, it does have potentially have some affinity at this 2b receptor, and the serotonin 2b receptor has been implicated in valvular heart disease for a few other drugs like fenfluramine that were taken off the market.

So, from a safety standpoint, if people are going to start to investigating microdosing of psilocybin, we really need to understand what is that risk in doing pre-clinical toxicology models and things like this to understand is there going to be this heart valve risk, and if there's no benefit, we don't want to be subjecting people to that sort of repeated dosing with potential cardiac valve risk if there's no clear symptomatic benefit for things like depression or anxiety.

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

Kelan Thomas: Sure, thank you.