A Phase I trial to inform clinical protocols for the safe administration of psilocybin-assisted psychotherapy

Abstract

This Phase I trial aims to inform the development of safety protocols for psilocybin-assisted therapy. Psychedelics, including psilocybin, are increasingly being recognized as a successful treatment option for many mental health concerns. In order to decrease the risks associated with its clinical use, more data is required regarding its physiological effects in healthy individuals. Safety assessments (heart rate, blood pressure, temperature, and ECG data), as well as adverse event evaluations were the primary outcome measures used to assess the physiological effects of 25 mg of psilocybin extract administered to 14 healthy individuals. We hypothesized that there would be a transient, clinically insignificant rise in both blood pressure and heart rate that would not result in any long-term adverse effects. No unexpected effects were observed, blood pressure and heart rate returned to normal as drug effects waned, and all participants had normal two-month follow-ups. Mean peak systolic and diastolic blood pressures during the psilocybin session were 145.93 (SD = 19.01) and 93.93 (SD = 9.75), respectively. While this represents a significant increase from baseline (p < 0.0001), a healthy cardiovascular system is capable of tolerating such levels for a longer time period than the brief duration of drug effects. Therefore, we suggest implementing focused and limited screening protocols to balance patient safety and accessibility. Secondary outcomes of this trial centered on the subjective effects of psilocybin, assessed via the QIDS-SR16 and the MEQ-30. There was a statistically significant decrease in QIDS-SR16 scores from baseline scores (M = 3.50, SD = 2.35) to eight-week follow-up scores (M = 1.86, SD = 0.86), p = 0.018. Mean MEQ-30 scores, assessed on day two and seven after the psilocybin session, indicate participants had full mystical experiences.

Ketamine induces multiple individually distinct whole-brain functional connectivity signatures

“…In addition, we did not regress out physiological measures. There is a large body of evidence to suggest that heart rate and blood pressure impact resting-state functional connectivity, and sub-anesthetic doses of ketamine and moderate doses of psilocybin and LSD have all been shown to increase heart rate and blood pressure ( Chang et al, 2013 ; Nikolaou et al, 2016 ; de la Cruz et al, 2019 ; Riva-Posse et al, 2018 ; Bennett et al, 2023 ; Isbell, 1959 ). While to date no studies have directly compared the physiological effects of all three drugs, there is evidence that LSD and psilocybin have distinct effects on blood pressure and heart rate ( Holze et al, 2022 ).…”

Experiential Training in Psychedelic‐Assisted Therapy: A Risk‐Benefit Analysis

“…Two clinical trials sponsored by ATMA Journey Centers, a private firm based in Calgary, Canada, have been designed with secondary objectives to assess the safety of psilocybin and explore psychological outcomes in licensed medical professionals undergoing PAT in a clinical setting. 42 In 2023, the Canadian firm Numinus received approval for a trial of experiential training using psilocybin. 43 And the Swiss Society for Psycholytic Therapy and University Hospital of Basel, in Switzerland, are presently enrolling participants in a clinical trial entitled The Role of Personal Experience for the Therapeutic Attitude in the Context of Substance-Assisted Therapy Training.…”