Acute Mind-Altering Effects of Psilocybin Managed With Clinician Oversight

The main potential adverse effects (AEs) associated with psilocybin use include its acute mind-altering effects, which generally wear off after 6 hours following drug administration, according to Michael P. Bogenschutz, MD.

CancerNetwork® spoke with Bogenschutz, director of the NYU Langone Center for Psychedelic Medicine and professor of Psychiatry at NYU Grossman School of Medicine, about potential toxicities and adverse effects associated with psilocybin use for patients with cancer in the context of a pooled analysis of 2 phase 2 trialsthat he and coauthors published in Nature Mental Health.¹

Bogenschutz began by outlining potential acute mind-altering effects associated with psilocybin, explaining that patients may enter a fearful or overwhelmed state after treatment. Additionally, patients may report other distressing transient thoughts.

He expressed that although the effects can be dramatic, they typically resolve within the acute period, highlighting that a patient’s state of consciousness is typically restored after approximately 6 hours following administration. Furthermore, Bogenschutz described that residual symptoms were uncommon, but that the presence of a skilled clinician with a patient for the entirety of the drug administration, encompassing approximately 8 hours following dosing, was recommended.

Bogenschutz then outlined sympathomimetic effects associated with psilocybin use, which he expressed may result in an increase of up to 20 points in systolic pressure and 15 points in diastolic pressure. Furthermore, he expressed that a patient’s heart rate could increase to no higher than 100 beats per minute, which may pose risks for patients with coronary artery disease or those at a high risk of stroke.

He then reiterated that from a physiological standpoint, psilocybin is safe as a means of treating patients with mental health concerns.

No serious AEs were observed in either trial (NCT00957359, NCT00465595) included in the pooled analysis study.^2,3 Additionally, both trials reported non-clinically significant elevations in blood pressure and heart rate as well as transient psychological symptoms, which were consistent with prior trials evaluating psilocybin.

Transcript:

There are risks and potential adverse effects [with psilocybin]––the main ones have to do with the acute mind-altering effects of the drug. During a session, [a patient’s] state of consciousness is altered quite dramatically. Some patients––it is not predictable who it might be––can become quite overwhelmed or fearful. [They may] fear that they are losing their mind or that they are, in fact, dying, or have other kinds of transient paranoid thoughts or delusional or strange ideas.

Those [mind-altering effects] almost always resolve within the acute period. Once the drug effects wear off, after 6 hours or so, most people are back to a perfectly normal state of consciousness. There are occasionally residual symptoms that can take longer to resolve, but that is uncommon. It is quite common for people to have strong and sometimes distressing emotional states during the acute phase of the treatment. That is why it is important to have skilled clinicians with the patient for the entirety of the drug administration session, which is usually 8 hours or so. Beyond that, the medical risks of psilocybin are quite low in [patients who are] carefully screened.

There is not a lot of toxicity. The main potential issues are moderate sympathomimetic effects [with] psilocybin. Blood pressure may go up by 20 points for systolic [blood pressure] and 15 for diastolic [blood pressure], on average––it varies. Heart rate will go up a bit, usually not above 100 [beats per minute], but that puts some strain on the heart. People with coronary artery disease or high risk of stroke, generally, have been excluded from the trials with psilocybin. Other than that, physiologically speaking, it is a safe drug as far as we know.

References

1. Petridis PD, Grinband J, Agin-Liebes G, et al. Psilocybin-assisted psychotherapy improves psychiatric symptoms across multiple dimensions in patients with cancer. Nat Mental Health. 2024;2:1408-1414. doi:10.1038/s44220-024-00331-0
2. Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J. Psychopharmacol. 2016;30(12):1165-1180. doi:10.1177/0269881116675512