Journal of Psychopharmacology最新文献

{"title":"Corrigendum: Is psychedelic use associated with cancer? Interrogating a half-century-old claim using contemporary population-level data.","authors":"","doi":"10.1177/02698811241286656","DOIUrl":"10.1177/02698811241286656","url":null,"abstract":"","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"509"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-dose psilocybin therapy for alcohol use disorder: Pharmacokinetics, feasibility, safety and efficacy in an open-label study.","authors":"Mathias Ebbesen Jensen, Dea Siggaard Stenbæk, Catharina Dragsted Messell, Emil Deleuran Poulsen, Tibor V Varga, Patrick McDonald Fisher, Marie Katrine Klose Nielsen, Sys Stybe Johansen, Nora D Volkow, Gitte Moos Knudsen, Anders Fink-Jensen","doi":"10.1177/02698811251319457","DOIUrl":"10.1177/02698811251319457","url":null,"abstract":"<p><strong>Background: </strong>Psilocybin, a serotonin 2A receptor agonist with psychedelic properties, shows promise as a novel treatment for alcohol use disorder (AUD). While current studies involve two dosing sessions, the effects of a single dose have not been investigated.</p><p><strong>Aims: </strong>To investigate the pharmacokinetics, feasibility, safety and efficacy of single-dose psilocybin therapy in AUD.</p><p><strong>Methods: </strong>This open-label, single-group study investigated single-dose psilocybin therapy in 10 treatment-seeking adults (8 men and 2 women; median age 44 years) with severe AUD. The treatment involved two preparation sessions, a high-dose psilocybin session (25 mg) and two integration sessions. Pharmacokinetics were determined by noncompartmental analysis, and changes in alcohol consumption, craving and self-efficacy, were assessed using a linear mixed model.</p><p><strong>Results: </strong>Notable between-participant pharmacokinetic variations were observed, with peak plasma psilocin concentrations ranging from 14 to 59 µg/L. Alcohol consumption significantly decreased over the 12 weeks following psilocybin administration. Heavy drinking days were reduced by 37.5 percentage points (95% CI: -61.1 to -13.9, <i>p</i> = 0.005), and drinks per day decreased by 3.4 drinks (95% CI: -6.5 to -0.3, <i>p</i> = 0.03). This was corroborated by reports of rapid and sustained reductions in craving and increases in self-efficacy.</p><p><strong>Conclusions: </strong>Despite pharmacokinetic variations, a single 25 mg psilocybin dose was safe and effective in reducing alcohol consumption in AUD patients. Larger randomised, placebo-controlled, single-dose AUD trials are warranted.</p><p><strong>Clinical trial registration: </strong>https://clinicaltrials.gov/study/NCT04718792.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"463-473"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pictorial representation of illness and self measure (PRISM): A putative transdiagnostic tool for evaluating therapeutic effects of psychedelic treatments.","authors":"Niloufar Pouyan, Jacob S Aday, Steven E Harte, Chelsea M Kaplan, David A Williams, Nicolas G Glynos, Moss Herberholz, Daniel J Kruger, Julie Barron, George A Mashour, Daniel J Clauw, Katrin H Preller, Andrew Schrepf, Kevin F Boehnke","doi":"10.1177/02698811251330763","DOIUrl":"10.1177/02698811251330763","url":null,"abstract":"<p><strong>Background: </strong>Patients with refractory conditions often identify themselves with their illness, which affects multiple aspects of their lives. The pictorial representation of illness and self measure (PRISM) is a tool used to assess the enmeshment of individuals' perception of self with a particular medical condition, broadly termed self-condition enmeshment.</p><p><strong>Aims: </strong>This study aimed to evaluate changes in PRISM scores and how these changes relate to symptom changes following naturalistic psychedelic use.</p><p><strong>Methods: </strong>In this survey, we retrospectively assessed changes in PRISM scores in 297 individuals who self-engaged in naturalistic psychedelic use for therapeutic purposes. Participants also completed the Patient Global Impression of Change (PGIC) scale to report symptom changes resulting from their perceived most salient psychedelic experience (MSPE).</p><p><strong>Results: </strong>PGIC scores indicated that the majority of participants with depression (95.4%), posttraumatic stress disorder (98.36%), and anxiety (94.87%) reported symptom improvement following naturalistic psychedelic use. There was a significant decrease (<i>p</i> = 4.65 × 10^-25) in PRISM scores after MSPE compared to their PRISM scores before MSPE, indicating that individuals experienced a reduced identification of their identity with their condition following psychedelic use. PRISM change scores were also correlated with PGIC scores across all conditions (ρ = 0.41, <i>p</i> = 1.64 × 10^-11), indicating that reductions in self-condition enmeshment were associated with symptom improvement.</p><p><strong>Conclusions: </strong>Our results suggest that PRISM has transdiagnostic sensitivity for investigating the effects of psychedelics on self-perception. Interpretation is limited by convenience sampling, potential positive bias, retrospective reporting, and unclear doses and settings with natural psychedelic use.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"489-498"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic effects of resveratrol on memory deficits in offspring of sleep-deprived rats: Involvement of hippocampal BDNF-TrkB pathways.","authors":"Mohammad-Hossein Mohammadi-Mahdiabadi-Hasani, Maryam Farahmandfar, Mohammad-Reza Zarrindast, Mohammad Nasehi, Anahita Torkaman-Boutorabi, Gholamreza Hassanzadeh","doi":"10.1177/02698811251334034","DOIUrl":"https://doi.org/10.1177/02698811251334034","url":null,"abstract":"<p><strong>Background: </strong>Maternal sleep deprivation (MSD) is a significant public health issue that adversely affects neurogenesis and synaptic plasticity in offspring, resulting in cognitive deficits in learning and memory. Resveratrol, an antioxidant with neuroprotective and anti-inflammatory properties, may help mitigate these effects. This study investigates resveratrol's potential to counteract the negative impacts of MSD on neurodevelopment in male Wistar rat offspring.</p><p><strong>Methods: </strong>Ninety-six male Wistar rat offspring and 36 pregnant rats were used. Total MSD was induced using the water box device on gestational days 7, 11, and 17. Pregnant rats received resveratrol at doses of 25 or 50 mg/kg every 12 h during the sleep deprivation period. After parturition, offspring were divided into 12 groups for assessment at two months of age. Social interaction tests evaluated social memory, while the Morris water maze test assessed spatial learning and memory. Brain samples were prepared for Nissl staining, and brain-derived neurotrophic factor (BDNF) and tyrosine-protein kinase (TrkB) expression levels in the hippocampus were measured using western blotting.</p><p><strong>Results: </strong>Our findings indicate that the MSD group exhibited decreased BDNF/TrkB expression and increased neuronal damage in the hippocampus, which led to disrupted spatial and social memory compared to the control group. Subsequently, resveratrol administration, especially at a dose of 50 mg/kg during pregnancy, significantly reversed MSD's detrimental effects on cognitive function in offspring.</p><p><strong>Conclusion: </strong>Our results provide novel evidence of resveratrol's neuroprotective effects in rat pregnancy models of MSD, suggesting its potential for developing therapeutic interventions targeting prenatal neurodegenerative disorders.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251334034"},"PeriodicalIF":4.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peri-traumatic consumption of classic psychedelics is associated with lower anxiety and post-traumatic responses 3 weeks after exposure.","authors":"Einat Karp Barnir, Zohar Rubinstein, Rany Abend, Shaul Lev-Ran, Lia Naor, Mario Mikulincer","doi":"10.1177/02698811251334025","DOIUrl":"https://doi.org/10.1177/02698811251334025","url":null,"abstract":"<p><p>Emerging evidence indicates the therapeutic potential of psychedelic compounds for post-traumatic stress, yet the mechanisms mediating their effects remain unclear. Delineating the effect of psychedelics on traumatic memory formation could shed light on target therapeutic mechanisms. Here, we report on 343 adult survivors of a single, large-scale terrorist attack taking place during a festival in which different psychedelic compounds were consumed, in whom levels of anxiety and post-traumatic symptoms were assessed 3 weeks following the attack. Findings indicated that those who were under the influence of classic psychedelics during the attack reported significantly lower levels of anxiety and post-traumatic responses compared to those who were under the influence of 3,4-methylenedioxymethamphetamine and those who consumed no psychedelics. Furthermore, the protective effects of classic psychedelics for post-traumatic responses manifested more strongly among participants who did not consume additional recreational substances alongside psychedelics. These findings suggest that pharmacologic targets of classic psychedelics may modulate the formation of enduring trauma memories and confer a protective effect against the development of post-traumatic stress and anxiety responses.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251334025"},"PeriodicalIF":4.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Daily supplementation with lemon verbena extract decreases subjective energy and parental reports of hyperactivity in children displaying sub-clinical attention deficit hyperactivity disorder-type behaviours: A randomised controlled trial.","authors":"Philippa A Jackson, Ellen F Smith, Joanne Forster, Jessica Greener, Anna Small, David O Kennedy, Cynthia G Suarez, Andressa Blainski, Ivo Pischel","doi":"10.1177/02698811251324574","DOIUrl":"https://doi.org/10.1177/02698811251324574","url":null,"abstract":"<p><strong>Background: </strong>Current treatment options for attention deficit hyperactivity disorder (ADHD) are limited by factors such as adherence and cost, whilst no treatment options are available for sub-clinical or undiagnosed ADHD. Herbal preparations may therefore offer an alternative approach to the management of symptoms; <i>Aloysia citriodora</i> Paláu (lemon verbena) is a promising candidate.</p><p><strong>Aim: </strong>To assess the behavioural, cognitive, psychological and physiological effects of 56 days of supplementation with lemon verbena extract (LVE) in children exhibiting symptoms of ADHD at the sub-clinical level.</p><p><strong>Methods: </strong>This exploratory study followed a randomised, double-blind parallel groups design wherein 120 healthy participants aged 8-17 years received 15 mg/kg bw/d LVE or matched placebo for 56 days. Behavioural, cognitive, mood and physiological measures were collected in the lab at baseline and 28 and 56 days post-dose. Parents also evaluated the child's behaviour throughout the study.</p><p><strong>Results: </strong>Participants who received LVE reported greater subjective fatigue, defined as reduced energy levels according to the Profile of Mood States subscale, without impairments in cognitive performance across the 56-day intervention and lower depression symptoms on day 56, compared to placebo. The effect of LVE on parent ratings of hyperactive/impulsive behaviour also approached significance with fewer concerns being reported following the active treatment. Exploratory analyses showed further benefits to cognition and mood.</p><p><strong>Conclusions: </strong>This study revealed novel, beneficial effects of LVE supplementation in children exhibiting a high frequency of behaviours characteristic of ADHD. Overall, LVE was safe and well-tolerated by participants, with no unexpected safety events.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251324574"},"PeriodicalIF":4.5,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and pharmacodynamics of sublingual microdosed lysergic acid diethylamide in healthy adult volunteers.","authors":"James D Morse, Soo Hee Jeong, Robin J Murphy, Suresh D Muthukumaraswamy, Rachael L Sumner","doi":"10.1177/02698811251330747","DOIUrl":"https://doi.org/10.1177/02698811251330747","url":null,"abstract":"<p><strong>Introduction: </strong>Microdosing is the practice of taking psychedelic drugs at doses that produce no or minimal perceptible subjective or behavioural effects. This study investigated the pharmacokinetics and pharmacodynamics of microdosed lysergic acid diethylamide (LSD).</p><p><strong>Methods: </strong>This was a Phase 1 double-blind placebo-controlled parallel-groups trial with 80 healthy male volunteers (four withdrawals due to anxiety). Plasma samples were taken at 0.5, 1, 2, 4 and 6 h after 10 µg sublingual LSD and analysed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). LSD pharmacokinetics were modelled. Population analyses were performed using nonlinear mixed effects models. Heart rate and a visual analogue scale ('feel effect') were used to describe LSD pharmacodynamics. The effect of the relevant cytochrome P450 (CYP) genotype on LSD pharmacokinetics was qualitatively assessed. Plasma and serum levels of brain-derived neurotrophic factor (BDNF) were evaluated.</p><p><strong>Results: </strong>A one-compartment model best described LSD pharmacokinetics. Mean (95% confidence interval): elimination clearance = 7.78 L/h/70 kg (6.75-8.77), central volume of distribution = 32.9 L/70 kg (30.1, 36.0). Maximal concentration (0.20 µg/L), time to maximal concentration (1.51 h) and elimination half-life (3.08 h). The maximal increase in heart rate and visual analogue scale was small (<15%) compared to baseline estimates limiting the modelling. Two of the participants withdrawn from the study due to anxiety had intermediate-weak CYP2D6 activity. CYP2D6, CYP1A6, CYP2B6 and CYP2C9 qualitatively appeared to influence concentration. No evidence of alterations of peripheral BDNF with microdosing was found.</p><p><strong>Conclusion: </strong>This study provides a population pharmacokinetic model and LC-MS/MS assay that can inform clinical and bioequivalence studies. Relevant CYP genotypes should be studied in larger samples as combined potential biomarkers of response. Microdose-sensitive and reliable pharmacodynamic measures are needed.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251330747"},"PeriodicalIF":4.5,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discriminating evidence - use and misuse of the drug-discrimination test in abuse potential assessment of novel CNS drugs.","authors":"David J Heal, Sharon Lesley Smith, Jane Gosden, James Rowlett","doi":"10.1177/02698811251330780","DOIUrl":"10.1177/02698811251330780","url":null,"abstract":"<p><p>Nonclinical testing to predict the abuse potential of central nervous system (CNS) drug candidates is a mandatory part of the safety pharmacology assessment for medications seeking approval for human use. In the \"standard model,\" the drug candidate is tested to determine whether its psychoactive effects generalize to the discriminative cue of an abused drug that animals have been trained to recognize. However, CNS drugs with novel pharmacological mechanisms are challenging, and in response, the regulatory agencies have recommended alternative experimental designs. Variant 1: test the drug candidate in a series of drug-discrimination experiments that exemplify the major classes of abused drugs. Variant 2: use the drug candidate as a training cue. Back-test examples from established classes of abused drugs to see if they generalize to the drug candidate's cue. We critically assessed the pharmacological and translational validity of these protocols. The standard model is underpinned by decades of research and refinement and has the highest degree of translational validity. Question marks exist over the validity of substitution results when the drug candidate has no affinity for known abuse-related targets. Published research does not support the use of either of the alternative models. On the contrary, these models have no pharmacological rationale and, consequently, no translational validity. The review contains a decision tree on the appropriate application of the standard drug-discrimination model, together with recommendations for adapting the test when characterizing the psychoactive properties of drug candidates acting on novel CNS targets.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251330780"},"PeriodicalIF":4.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavioral effects of three synthetic tryptamine derivatives in rodents.","authors":"Rebecca D Hill, Ritu A Shetty, Nathalie Sumien, Jeanne Priddy, Michael J Forster, Michael B Gatch","doi":"10.1177/02698811251330737","DOIUrl":"https://doi.org/10.1177/02698811251330737","url":null,"abstract":"<p><strong>Aims: </strong>New synthetic tryptamine derivatives have emerged in the underground market. They act on serotonin receptors mimicking the effects of hallucinogenic drugs such as DOM. The DEA has identified three tryptamine derivatives of concern, 5-MeO-DBT, 5-Cl-DMT, and 4-OH-MiPT.</p><p><strong>Methods: </strong>Swiss Webster mice were tested for locomotor activity. Discriminative stimulus effects were tested in male Sprague-Dawley rats trained to discriminate DOM (0.5 mg/kg, 30-min pretreatment) from vehicle (0.9% saline).</p><p><strong>Results: </strong>In the locomotor activity tests, DOM (ED₅₀ = 4.8 mg/kg) produced a 40-100-min depressant phase. 5-MeO-DBT (ID₅₀ = 16.5 mg/kg; ED₅₀ = 0.074 mg/kg) had a 50-min depressant phase and a 100-min stimulant phase. 5-Cl-DMT (ID₅₀ = 12.3 mg/kg; ED₅₀ = 6.1 mg/kg) produced a 20-40-min depressant phase and a 30-min stimulant phase. 4-OH-MiPT (ID₅₀ = 5.8 mg/kg; ED₅₀ = 0.6 mg/kg) had a 30-130-min depressant phase and a 50-minute stimulant phase. In the drug discrimination assay, 4-OH-MIPT (ED₅₀ = 0.77 mg/kg) was fully substituted, whereas 5-Cl-DMT partially substituted for the discriminative stimulus effects produced by DOM (ED₅₀ = 0.23 mg/kg). 5-MeO-DBT failed to substitute for the discriminative stimulus of DOM. 5-CL-DMT and 5-MeO-DBT decreased response rate.</p><p><strong>Conclusion: </strong>The locomotor depressant effects of the three synthetic tryptamine derivatives were similar to DOM, but not as potent. In the drug discrimination assay, only 4-OH-MIPT was substituted fully for DOM. These results support the possibility that 4-OH-MIPT has abuse liability similar to DOM, whereas 5-MeO-DBT and 5-Cl-DMT may not.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251330737"},"PeriodicalIF":4.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabimimetic and discriminative stimulus effects of hexahydrocannabinols in mice.","authors":"Julie A Marusich, Cassandra Prioleau, Luli R Akinfiresoye","doi":"10.1177/02698811251330739","DOIUrl":"https://doi.org/10.1177/02698811251330739","url":null,"abstract":"<p><strong>Background: </strong>Hexahydrocannabinol (HHC) recently appeared on the recreational drug market and is often sold as a legal replacement for Δ⁹-tetrahydrocannabinol (Δ⁹-THC). Users primarily consume HHC for recreational purposes, but adverse effects have been reported. Given the scant literature on HHC, additional research is needed to better understand its effects.</p><p><strong>Aims: </strong>The present study sought to determine whether 9(R)-hexahydrocannabinol [9(R)-HHC] and 9(S)-hexahydrocannabinol [9(S)-HHC] are psychoactive cannabinoids that share behavioral effects with Δ⁹-THC.</p><p><strong>Methods: </strong>Adult male mice were administered 9(R)-HHC, 9(S)-HHC, or Δ⁹-THC and tested in the tetrad battery to examine cannabimimetic effects (i.e., locomotor suppression, antinociception, hypothermia, and catalepsy). Separate mice were trained to discriminate Δ⁹-THC from the vehicle in drug discrimination and subsequently tested with 9(R)-HHC and 9(S)-HHC.</p><p><strong>Results: </strong>Δ⁹-THC and 9(R)-HHC produced cannabimimetic effects in all tetrad measures, and 9(R)-HHC fully substituted for Δ⁹-THC in drug discrimination. Δ⁹-THC and 9(R)-HHC showed similar potency across measures, except that 9(R)-HHC produced more hypothermia than Δ⁹-THC. By contrast, 9(S)-HHC only produced cannabimimetic effects in two tetrad measures, was less potent than Δ⁹-THC, and only partially substituted for Δ⁹-THC in drug discrimination.</p><p><strong>Conclusions: </strong>9(R)-HHC is likely to possess abuse liability in humans, whereas 9(S)-HHC may produce weak Δ⁹-THC-like psychoactivity in humans. The differences in the pharmacology between the two HHC epimers may lead to a range of effects in human users depending on the ratio of the epimers consumed.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251330739"},"PeriodicalIF":4.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}