Psychopharmacology
October 1, 2024
Ardavan Mohammad Aghaei, Lia Urban Spillane, Brian Pittman et al.
9 citations
After a single 10 mg oral dose of THC, women reported a heightened subjective feeling of being 'high' compared to men, while psychotomimetic and physiological effects were similar across sexes. No sex differences appeared in verbal learning and memory. The findings suggest that women may experience a more pronounced subjective psychoactive response to THC, pointing to individual vulnerabilities that could inform tailored interventions for cannabis use disorder.
British Journal of Clinical Pharmacology
December 1, 2024
Jeremy Weleff, Julio C Nunes, Gabriel P. A. Costa et al.
8 citations
Chronic pain and opioid use disorder (OUD) are two interconnected public health crises that lack effective treatments. This review examines whether psychedelics could serve as novel therapeutics by acting on shared brain mechanisms underlying both conditions. Preclinical and human evidence suggests psychedelics may reverse pain- and opioid-induced neuroadaptations like central sensitization. The authors map how psychedelics could modulate overlapping dimensions of pain (sensory, affective, cognitive) and opioid-related phenomena (craving, withdrawal). They note a scarcity of controlled studies but propose mechanistic insights and methodological guidelines for future clinical trials. The goal is to accelerate development of alternatives to opioids amid the escalating crisis.
The American Journal on Addictions
May 1, 2024
Michael Rogan, Julio C Nunes, Catherine Z Xie et al.
2 citations
Greater childhood trauma is linked to lower aversive effects from higher doses of THC in people being treated with methadone for opioid use disorder. In a placebo-controlled crossover trial with 25 participants, those with more childhood trauma reported fewer negative subjective effects after taking 20 mg of oral THC. This reduced sensitivity to THC's aversive effects may contribute to increased cannabis use among individuals with opioid use disorder. The findings highlight the importance of assessing childhood trauma in opioid use disorder treatment and research.
bioRxiv (Cold Spring Harbor Laboratory)
March 10, 2026
Gabriele Floris, Sarah J. Jefferson, Jocelyne Rondeau et al.
Combining psilocybin with a phosphodiesterase-9 inhibitor (PDE9i) reduces psychedelic-like effects in mice—measured by head twitch response—while preserving antidepressant effects against chronic stress. Proteomic analysis of the medial prefrontal cortex revealed enhanced synaptogenesis and reduced GPCR signaling pathways with the combination versus psilocybin alone. This suggests a potential strategy for developing serotonergic antidepressants that maintain efficacy without the intense psychedelic experience, which currently limits scalability of psilocybin therapy.
October 30, 2023
Jeremy Weleff, Julio C Nunes, Gabriel P. A. Costa et al.
Psychedelics show promise for treating chronic pain and opioid use disorder (OUD) by acting on shared brain mechanisms that underlie both conditions. Preclinical and human evidence suggests psychedelics may reverse pain- and opioid-induced neuroadaptations such as central sensitization. The review describes how psychedelics could modulate sensory, affective, and cognitive dimensions of pain alongside opioid craving and withdrawal. Despite the clinical need, controlled studies on pain management alternatives for people with OUD or on long-term opioid therapy remain scarce. The authors propose mechanistic insights and methodological considerations for future translational studies and clinical trials to accelerate development of novel therapeutics amid the opioid crisis.
Journal of Psychiatric Research
September 1, 2024
Noah R Wolkowicz, Mehmet Sofuoglu, Brian Pittman et al.
Attentional bias (AB) toward pain and opioid cues may be altered by delta-9-tetrahydrocannabinol (THC) in adults with opioid use disorder (OUD) receiving methadone. In a crossover trial, 27 participants received single oral doses of 10 mg THC, 20 mg THC, or placebo. Among those on high methadone doses (≥90 mg/day), 10 mg THC increased AB toward opioid cues, while 20 mg THC decreased it. Those on low methadone doses showed more variable opioid-related AB after THC. These preliminary results suggest THC produces dose-dependent effects on attention to opioid cues, warranting further study of cannabinoids in OUD.
Psychopharmacology
September 1, 2019
Swapnil Gupta, Joao P De Aquino, Deepak C D'Souza et al.
In healthy individuals who respond to THC, pre-treatment with the antipsychotic haloperidol reduces the psychosis-like effects of THC. Among 10 THC responders, THC-induced increases in positive symptoms (measured by the PANSS) were lower after haloperidol (average increase of 1.1 points) than after placebo (average increase of 2.9 points). This suggests that dopamine signaling may play a role in the psychosis-like effects of cannabinoids.