The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability

This study (n=9) tested the tolerability of psilocybin in an fMRI environment, and found high levels of tolerability. It found that full-dose psychedelic studies with fMRI equipment are viable.

Abstract

“This study sought to assess the tolerability of intravenously administered psilocybin in healthy, hallucinogen-experienced volunteers in a mock-magnetic resonance imaging environment as a preliminary stage to a controlled investigation using functional magnetic resonance imaging to explore the effects of psilocybin on cerebral blood flow and activity. The present pilot study demonstrated that up to 2 mg of psilocybin delivered as a slow intravenous injection produces short-lived but typical drug effects that are psychologically and physiologically well tolerated. With appropriate care, this study supports the viability of functional magnetic resonance imaging work with psilocybin.”

Authors: Robin L. Carhart-Harris, Tim M. Williams, Ben Sessa, Robin J. Tyacke, Ann S. Rich, Amanda Feilding & David J. Nutt

Summary

This pilot study examined the tolerability of intravenously administered psilocybin in healthy, hallucinogen-experienced volunteers in a mock-magnetic resonance imaging environment. The study supports the viability of functional magnetic resonance imaging work with psilocybin.

Introduction

Psilocybin is a tryptamine hallucinogen that was used as an adjunct to psychoanalytic psychotherapy in the late 1950s, but was withdrawn due to adverse events. Only in the last 15 years have clinical researchers begun to work with this group of compounds.

To assess the tolerability of psilocybin in a mock-fMRI setting, healthy, hallucinogen-experienced volunteers were administered intravenously. The results indicated that psilocybin had a fast onset and brief duration of subjective effects.

Methods

Subjects

Nine subjects participated in a study approved by an NHS Research Ethics Committee. They were physically and mentally healthy and had taken a hallucinogenic drug on at least one occasion without adverse reaction.

Screening

Subjects were screened in a clinical research unit in the Bristol Royal Infirmary and completed a psychiatric assessment, including an electrocardiogram, routine blood tests, and urine test for drugs of abuse and pregnancy.

Drug session

Three subjects received 1.5 mg psilocybin, six participants received 2 mg psilocybin after establishing the tolerability of the lower dose, all sessions took place in a clinical research unit in the Bristol Royal Infirmary.

On arrival, subjects were cannulated, habituated to the mock-scanner, and allowed to move around. An auditory recording of fMRI scanner noise was played in the last three dosing sessions.

Subjects remained in the mock-scanner for 25 min and gave retrospective ratings for how they felt when the drug effects were most intense. Subjects were given a 94-item self-rated questionnaire that measures five key dimensions: oceanic boundlessness, anxious ego dissolution, visionary restructuralization, audio alterations, and reduced vigilance. They were contacted 14 days after having received the drug for an informal check-up.

Result

Demographics and personality factors

Nine subjects participated in this study, seven males and two females. All subjects had used psilocybin mushrooms before and gave relatively low, clinically non-significant ratings on the BDI and STAI.

Acute effects

Three subjects received 1.5 mg psilocybin. They described a fast onset, a pleasant ‘meditative’ state, sensations of warmth and mild proprioceptive and visual distortions, and a heart rate and blood pressure increase that subsided after approximately 5 min.

Post-drug ratings

Subjects gave mean ratings for ‘happy’ and ‘relaxed’ after 1.5 mg and 2 mg of psilocybin, and for ‘anxiety’ and ‘confusion’ after 1.5 mg and 2 mg of psilocybin, respectively. When compared against the pre-drug baseline, none of these ratings had significantly increased or decreased. Two subjects gave quite high ratings for ‘anxiety’ at peak effects, but neither reported discomfort or distress, and both reported having found the experience pleasant.

Follow-up

No significant changes in psychiatric ratings were observed 14 days after the drug experience, and no persistent adverse events were reported.

Discussion

Summary of findings

In a mock-MRI setting, intravenously administered psilocybin produced strong subjective effects with a faster onset and longer duration of effects. No acute or subacute adverse phenomena were reported.

Implications

This pilot investigation was designed to assess the tolerability of psilocybin in a potentially anxiogenic environment. It was reassuring to discover that all subjects responded well to the drug in this environment, and the enclosed environment seemed reasonably well suited to the experience.

Intravenous psilocybin is subject to a steep dose-response curve, and doses greater than 2 mg are associated with increased risk of adverse events.

Conclusions

Intravenous psilocybin administered in doses up to 2 mg was well-tolerated in healthy, hallucinogen-experienced volunteers in a mock-fMRI setting.