Psilocybin induces dose-dependent changes in functional network organization in rat cortex.

Psilocybin produces an altered state of consciousness in humans and is associated with complex spatiotemporal changes in brain networks. Given the emphasis on rodent models for mechanistic studies, there is a need for characterization of the effect of psilocybin on brain-wide network dynamics. Previous rodent studies of psychedelics, using electroencephalogram, have primarily been done with sparse electrode arrays that offered limited spatial resolution precluding network level analysis, and have been restricted to lower gamma frequencies. Therefore, in the study, we used electroencephalographic recordings from 27 sites (electrodes) across rat cortex (n=6 male, 6 female) to characterize the effect of psilocybin (0.1 mg/kg, 1 mg/kg, and 10 mg/kg delivered over an hour) on network organization as inferred through changes in node degree (index of network density) and connection strength (weighted phase-lag index). The removal of aperiodic component from the electroencephalogram localized the primary oscillatory changes to theta (4-10 Hz), medium gamma (70-110 Hz), and high gamma (110-150 Hz) bands, which were used for the network analysis. Additionally, we determined the concurrent changes in theta-gamma phase-amplitude coupling. We report that psilocybin, in a dose-dependent manner, 1) disrupted theta-gamma coupling [p<0.05], 2) increased frontal high gamma connectivity [p<0.05] and posterior theta connectivity [p≤0.049], and 3) increased frontal high gamma [p<0.05] and posterior theta [p≤0.046] network density. The medium gamma frontoparietal connectivity showed a nonlinear relationship with psilocybin dose. Our results suggest that high-frequency network organization, decoupled from local theta-phase, may be an important signature of psilocybin-induced non-ordinary state of consciousness.

Intravenous psilocybin attenuates mechanical hypersensitivity in a rat model of chronic pain.

There is a renewed interest in psychedelic drugs as potential therapeutic agents for the treatment of psychiatric disorders. In particular, psilocybin has shown promise for the treatment of refractory depression1 and major depressive disorder2, and has also been explored as a treatment for tobacco and alcohol abuse3,4. However, despite suggestive evidence5,6, there has been no systematic study to investigate the effectiveness of psilocybin in attenuating indices of chronic pain. To address this gap, we investigated the effect of psilocybin on mechanical hypersensitivity and thermal hyperalgesia in a well-established rat model of formalin-induced, centralized chronic pain7,8 and demonstrate that a single intravenous bolus administration of psilocybin can attenuate mechanical hypersensitivity for 28 days.

Slouching towards engagement: interactions between people using psychedelics naturalistically and their healthcare providers.

Introduction: There is substantial public interest in psychedelics as potential treatments for psychiatric conditions. However, most psychedelics are criminalized under federal law in the USA, so it is unclear whether use occurs with clinical support. Our objective was to assess whether naturalistic psychedelic use occurs with clinical support, interactions between those using psychedelics and healthcare providers (psychiatrist, therapist, or primary physicians), and use characteristics. Methods: We conducted an online, anonymous, confidential, cross-sectional survey of adults reporting psychedelic use (N = 1221) through a psychedelics advocacy event and social media between 9/18/2022 and 11/5/2022. We assessed participant disclosure of psychedelic use with their psychiatric care provider (PsyCP) and/or primary care provider (PCP), desire for provider support, access to support, and rate of taking prescribed psychoactive medications alongside psychedelics. Results: Among participants with such care providers, 22% disclosed psychedelic use to their PCP vs. 58% to their PsyCP. Participants were less confident in PCP vs. PsyCP ability to integrate psychedelics into treatment. Common reasons for nondisclosure included stigma, inadequate provider knowledge, and legal concerns. 23% reported taking psychedelics on the same day as potentially interacting psychiatric medications (e.g., anxiolytics, antidepressants). Despite 81% of participants desiring therapist support during psychedelic experiences, only 15% had received such support. Discussion: Our results show that psychedelic use is generally disconnected from primary and psychiatric clinical care. This disconnection may result in safety issues, including inadequate screening for contraindicated conditions, lack of support during emergent adverse events, and drug interactions. Enhanced clinical education and orienting drug policy towards known harms and benefits of psychedelics is needed.

The Relationship Between Naturalistic Psychedelic Use and Clinical Care in Canada.

Naturalistic psychedelic use among Canadians is common. However, interactions about psychedelic use between patients and clinicians in Canada remain unclear. Via an anonymous survey, we assessed health outcomes and integration of psychedelic use with health care providers (HCP) among Canadian adults reporting past use of a psychedelic. The survey included 2,384 participants, and most (81.2%) never discussed psychedelic use with their HCP. While 33.7% used psychedelics to self-treat a health condition, only 4.4% used psychedelics with a therapist and 3.6% in a clinical setting. Overall, 44.8% (n = 806) of participants were aware of substance testing services, but only 42.4% ever used them. Multivariate regressions revealed that therapeutic motivation, higher likelihood of seeking therapist guidance, and non-binary gender identification were significantly associated with higher odds of discussing psychedelics with one's primary HCP. Having used a greater number of psychedelics, lower age, non-female gender, higher education, and a therapeutic motivation were significantly associated with higher odds of awareness of substance testing. We conclude that naturalistic psychedelic use in Canada often includes therapeutic goals but is poorly connected to conventional healthcare, and substance testing is uncommon. Relevant training and education for HCPs is needed, along with more visible options for substance testing.