Psychopharmacology最新文献

{"title":"Behavioral impact of chemogenetic manipulations of 5-HT DRN neurons in transgenic Tph2-iCre rats.","authors":"Nicholas S McCloskey, Chen Li, Lynn G Kirby","doi":"10.1007/s00213-025-06947-z","DOIUrl":"10.1007/s00213-025-06947-z","url":null,"abstract":"<p><strong>Rationale: </strong>Our laboratory has demonstrated that stressors regulate the 5-HT system with consequences in behavioral models of psychiatric disorders including addiction. We have employed behavioral pharmacology methods to show that stressors engage corticotropin-releasing factor afferents to 5-HT dorsal raphe nucleus (DRN) neurons with effects on negative affective state and stress-induced opioid relapse models. Given the ongoing opioid crisis, there remains a need to elucidate the neural mechanisms underlying opioid use disorder with molecular, temporal and spatial precision using newer circuit manipulation strategies in animal models.</p><p><strong>Objectives: </strong>We sought to characterize the behavioral effects of chemogenetic manipulations of 5-HT DRN neurons in male and female Tph2-iCre rats.</p><p><strong>Methods: </strong>Subjects received intra-DRN viral infusions of Cre-dependent inhibitory or excitatory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). Three behavioral paradigms were used to examine the effect of clozapine-N-oxide activation or inhibition of 5-HT DRN neurons: elevated plus maze (EPM), forced swim test (FST), and stress-induced reinstatement of morphine conditioned place preference (CPP).</p><p><strong>Results: </strong>Chemogenetic activation of 5-HT DRN neurons induces anxiety-like behavior in the EPM in a transgenic rat model.</p><p><strong>Conclusions: </strong>This study confirms some of the findings of prior chemo- and optogenetic studies in mice showing a role of 5-HT DRN neurons in anxiety-like behaviors but did not support effects in the FST model or in reinstatement of morphine CPP. Given the growing availability of transgenic rat lines, future studies in transgenic rats are needed to help dissect a complex literature on the behavioral functions of the 5-HT system.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2029-2041"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12958828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C57BL/6N mutation in cytoplasmic FMRP interacting protein 2 regulates nicotine reward in the conditioned place preference test.","authors":"Belle Buzzi, Gina M Fernandez, Amber Baldwin, Alayna Palamar, Belinda Cornes, Vivek Kumar, M Imad Damaj","doi":"10.1007/s00213-026-07154-0","DOIUrl":"https://doi.org/10.1007/s00213-026-07154-0","url":null,"abstract":"<p><p>Tobacco use is the leading preventable cause of death in the United States. Among the factors that contribute to tobacco initiation, use, and dependence, genetics may exert a strong influence. In mouse models, genetic differences between strains have been studied to investigate the potential drivers for these states. Previous reports indicate that C57BL/6 J (B6J) and C57BL/6N (B6N) mouse substrains show varying behavioral responses towards both natural and drug rewards. However, nicotine reward as assessed by preference for nicotine in the conditioned place preference (CPP) test has not yet been evaluated. Additionally, a point mutation in the cytoplasmic FMRP interacting protein 2 (Cyfip2) gene has been regarded as a potential underlying factor towards these substrain differences. Here, we compare the response to nicotine between B6J and B6N mouse substrains and establish a genetic correlation between Cyfip2 expression and nicotine preference in the brain. We also examine the effects of this mutation on nicotine preference between these substrains. We report reduced preference for nicotine in B6N mice compared to B6J mice and a negative correlation between nicotine CPP scores and Cyfip2 expression in both the hippocampus and prefrontal cortex. In our investigation of the Cyfip2 variant, we found that B6J mice carrying the B6N Cyfip2 mutation showed a lower preference for nicotine while B6N mice carrying the B6J Cyfip2 mutation showed increased preference. This study establishes substrain differences in preference for nicotine in the CPP test and a mutation in the Cyfip2 as the causal variant for this behavior.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857731","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":"Pilot study comparing the effects of high dose THC to high dose psilocybin and placebo in the set and setting of a classic psychedelic therapy session.","authors":"Frederick S Barrett, David Wolinsky, Zach Daily, Joseph Ciancio, Kristy Arthur, Ryan Vandrey","doi":"10.1007/s00213-026-07138-0","DOIUrl":"https://doi.org/10.1007/s00213-026-07138-0","url":null,"abstract":"<p><strong>Rationale: </strong>Delta-9-tetrahydrocannabinol (Δ9-THC) has been reported to evoke psychedelic-like experiences at high doses in some individuals. However, the doses of Δ9-THC that occasion such effects and the phenomenology of these experiences are poorly understood.</p><p><strong>Objectives: </strong>This brief report presents preliminary findings from a pilot human laboratory study that directly compared the acute effects of Δ9-THC and psilocybin under set (expectancy) and setting (context) conditions of a typical psychedelic clinical trial.</p><p><strong>Methods: </strong>Four healthy adults (ages 31-47, 3 F) received oral administration of placebo, psilocybin (25 mg), and 25 mg Δ9-THC, and two of these participants also received 50 mg Δ9-THC, in a double-blind, placebo-controlled, within-subject crossover study. Δ9-THC was administered as either synthetic Δ9-THC (dronabinol) or a whole-plant cannabis distillate extract (89.9% Δ9-THC). Subjective effects, cardiovascular measures, and safety were monitored throughout each session. Participants were asked after each session what drug they thought they had received.</p><p><strong>Results: </strong>25 mg Δ9-THC in both forms yielded a subjective experience similar to 25 mg psilocybin. Dronabinol was mistaken for a classic hallucinogen by both a psychedelic-naïve and a psychedelic-experienced participant.</p><p><strong>Conclusions: </strong>These preliminary data suggest that a 25 mg oral dose of pure, synthetic Δ9-THC can be mistaken for a classic hallucinogen, and that oral Δ9-THC can elicit a psychedelic-like experience under set and setting conditions of a typical psychedelic clinical trial. While limited by sample size, these initial results provide insights into the comparative psychopharmacology of Δ9-THC and psilocybin as well as the potentially substantial impact of set and setting on subjective effects of psychoactive drugs.</p><p><strong>Trial registration: </strong>This trial was registered at ClinicalTrials.gov (NCT06772753) on January 13, 2025.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831985","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":"Efficacy and tolerability of ketamine in moderate to severe obsessive-compulsive disorder: a systematic review.","authors":"Shayan Eghdami, Mahsa Boroon, Amir-Abbas Keshavarz-Akhlaghi, Mohammadreza Shalbafan","doi":"10.1007/s00213-026-07155-z","DOIUrl":"https://doi.org/10.1007/s00213-026-07155-z","url":null,"abstract":"<p><strong>Background: </strong>Approximately 40-60% of patients with obsessive-compulsive disorder (OCD) fail to respond to standard serotonergic and behavioral therapies. This systematic review evaluates the efficacy, durability, and safety of ketamine, a glutamate modulator, for moderate to severe OCD.</p><p><strong>Methods: </strong>Following PRISMA guidelines, we searched electronic databases through January 2026 for studies treating moderate-to-severe OCD with ketamine. Fifteen studies were included (three RCTs, four open-label trials, and eight case reports), comprising 118 participants.</p><p><strong>Results: </strong>Randomized trials demonstrated that single-dose intravenous ketamine (0.5 mg/kg) yields rapid anti-obsessional response rates of 50-60%. However, benefits from monotherapy were typically transient, often dissipating within one week. Conversely, protocols integrating ketamine with concurrent exposure and response prevention (ERP) reported sustained remission lasting weeks to months, suggesting a synergistic effect. While intravenous and oral routes were effective, intranasal administration faced high refusal rates due to contamination fears. Safety analysis identified a specific signal of delayed-onset dysphoria and suicidal ideation (24-48 hours post-infusion) in a subset of patients, distinct from depression trials.</p><p><strong>Conclusion: </strong>Ketamine may provide positive but short-lived symptom relief for moderate to severe OCD when used as a standalone intervention. Its clinical utility may be greatest when used as a pharmacological adjunct to behavioral therapy, potentially creating a therapeutic window that may facilitate effective ERP. Clinicians should implement extended monitoring for delayed psychiatric adverse events. Further longitudinal and mechanistic studies are warranted to delineate ketamine's optimal dosing parameters, timing, and integration strategies within multimodal OCD treatment frameworks.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831968","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":"Effects of withdrawal from intermittent vs. long access cocaine self-administration on nucleus accumbens calcium permeable AMPA receptor transmission and incubation of craving in female and male rats.","authors":"Amanda M Catalfio, Tracy L Fetterly, Megan Wickens, Terry E Robinson, Carrie R Ferrario","doi":"10.1007/s00213-026-07152-2","DOIUrl":"https://doi.org/10.1007/s00213-026-07152-2","url":null,"abstract":"<p><strong>Rationale: </strong>Following the discontinuation of long access (LgA) to cocaine self-administration rats show a time-dependent increase in motivation for drug (\"incubation of craving\") thought to be mediated by enhancements in transmission via nucleus accumbens (NAc) calcium-permeable AMPA receptors (CP-AMPARs). Intermittent access (IntA) to cocaine produces even more robust addiction-like behavior than LgA, but it is not known if this produces comparable incubation of craving and effects on CP-AMPARs.</p><p><strong>Methods: </strong>Rats underwent 5 days of short access training followed by 10 days of LgA or IntA cocaine self-administration; drug naïve rats served as controls. Some rats were used for within-subject incubation testing at withdrawal days 1, 30 and 45, while others were used to measure the effects of LgA and IntA experience on CP-AMPAR-mediated transmission at withdrawal day 30-35.</p><p><strong>Results: </strong>IntA and LgA self-administration followed by withdrawal resulted in similar patterns of incubation across both sexes. Additionally, CP-AMPAR-mediated transmission was similarly enhanced in LgA and IntA groups compared to drug naïve animals.</p><p><strong>Conclusions: </strong>Despite much less total cocaine consumption IntA resulted in incubation of craving and enhancements in NAc CP-AMPAR plasticity similar to LgA. This adds to a growing literature demonstrating that the intermittency of cocaine consumption can produce robust neurobehavioral plasticity comparable to LgA, in the absence of high levels of cocaine consumption.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831859","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":"Dexmedetomidine attenuates methamphetamine-induced hyperthermia and hyperlocomotion in male rats and modulates monoamine dynamics in the anterior hypothalamus.","authors":"Tsuyoshi Okada, Seiji Obi, Katsutoshi Shioda, Chikara Yonekawa, Shiro Suda","doi":"10.1007/s00213-026-07153-1","DOIUrl":"https://doi.org/10.1007/s00213-026-07153-1","url":null,"abstract":"<p><strong>Rationale: </strong>Methamphetamine (METH) intoxication is associated with serious complications, including hyperthermia and agitation, which are major contributors to morbidity and mortality. Currently, no established pharmacological interventions are available for these conditions.</p><p><strong>Objectives: </strong>To evaluate the effects of dexmedetomidine (DEX)-an α2-adrenergic receptor agonist-on METH-induced hyperthermia and hyperlocomotion, and explore the underlying mechanisms, with a particular focus on central monoamine dynamics.</p><p><strong>Methods: </strong>Male Wistar rats were administered METH (5 mg/kg, intraperitoneally) following pretreatment with DEX (0.1 or 0.5 mg/kg), guanfacine (α2A agonist), NBP (α2C agonist), or vehicle. Body temperature and locomotor activity were continuously monitored using an implantable telemetry device. In vivo microdialysis in the anterior hypothalamus (AH) was conducted to measure extracellular concentrations of dopamine (DA), noradrenaline (NA), and serotonin (5-HT).</p><p><strong>Results: </strong>DEX dose-dependently attenuated METH-induced hyperthermia and hyperlocomotion. Guanfacine produced comparable suppressive effects, whereas NBP showed no significant efficacy, suggesting predominant involvement of α2A receptors. METH markedly increased extracellular DA, NA, and 5-HT levels in the AH, with NA exhibiting the greatest increase. DEX notably suppressed elevations in DA and NA without significantly impacting 5-HT levels.</p><p><strong>Conclusions: </strong>DEX attenuated METH-induced hyperthermia and behavioral activation, likely via α2A-adrenergic mechanisms. DEX also suppressed METH-induced central monoamine release, particularly NA and DA release, in the anterior hypothalamus. Thus, DEX is a potential therapeutic candidate for managing the severe complications associated with METH intoxication.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797382","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":"Mesolimbic and mesocortical pathways differentially support fentanyl-context associations.","authors":"Annalisa Montemarano, Hajra Sohail, Laura B Murdaugh, Kyrsten Derr, Farrah A Alkhaleel, Logan D Fox, Samiksha Pandey, Megan E Fox","doi":"10.1007/s00213-026-07151-3","DOIUrl":"10.1007/s00213-026-07151-3","url":null,"abstract":"<p><strong>Rationale: </strong>Synthetic opioids like fentanyl are contributing to unprecedented overdose rates, yet the neural circuitry underlying fentanyl-associated behaviors remains poorly understood. The ventral tegmental area (VTA) projects to both the nucleus accumbens (NAc) and prefrontal cortex (PFC), forming distinct pathways that are implicated in drug-cue associations, though their specific roles in fentanyl-context encoding are not well defined.</p><p><strong>Objectives: </strong>This study aimed to determine how VTA-NAc and VTA-PFC circuits contribute to fentanyl-context associations, and to assess the role of downstream dopamine receptor signaling in fentanyl context-seeking.</p><p><strong>Methods: </strong>Male and female mice underwent fentanyl conditioned place preference (CPP; 0.2 mg/kg). We locally inhibited dopamine D1 or D2 receptors in NAc or PFC during CPP expression. We used fiber photometry calcium imaging to measure activity in VTA-NAc and VTA-PFC projection neurons, and chemogenetic inhibition to suppress activity during CPP expression.</p><p><strong>Results: </strong>Fentanyl CPP expression was attenuated by blocking D1 but not D2 receptors in PFC, and D2 but not D1 receptors in NAc. We found both VTA-NAc and VTA-PFC exhibited increased calcium activity during fentanyl exposure and during entries to the fentanyl-paired context. We further identified a functional role for VTA-NAc, as chemogenetic inhibition of VTA-NAc, but not VTA-PFC, reduced fentanyl context-seeking.</p><p><strong>Conclusions: </strong>While both VTA-NAc and VTA-PFC pathways are recruited by fentanyl exposure, fentanyl context-seeking relies on different downstream dopamine receptors in NAc vs PFC. Further, activity in VTA-NAc functionally supports the expression of fentanyl CPP. Together, these findings indicate that VTA circuits differentially contribute to fentanyl context-seeking.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797362","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":"Dissecting the contribution of mu and kappa opioid receptor signalling in effort and delay-related cost/benefit decision making.","authors":"Jackson D Schumacher, Victor Iancu, Alia M Mahrez, Stan B Floresco","doi":"10.1007/s00213-026-07150-4","DOIUrl":"https://doi.org/10.1007/s00213-026-07150-4","url":null,"abstract":"<p><strong>Rationale: </strong>While novel compounds targeting mu and kappa opioid receptors show promise for treating psychiatric cognitive and motivational deficits, their underlying mechanisms remain unclear. Specifically, we lack a precise understanding of how these receptors regulate reward-related cost-benefit decision-making.</p><p><strong>Objectives: </strong>To determine the contribution of mu and kappa opioid receptor signalling in modulating effort and delay related decisions in male and female rats.</p><p><strong>Methods: </strong>Separate cohorts of rats were well-trained on effort or delay discounting tasks or different reward magnitude discriminations. Effort and delay tasks had rats choose between no-cost, small (2 or 1 pellet) rewards and high-cost larger, 4-pellet reward associated with effort requirements (1-20 lever presses) or delays (0-45 s), that increased across blocks of trials. Magnitude discriminations entailed choice between large and small (or no) rewards of equal cost. Rats then received vehicle or 1-10 mg of antagonists targeting mu (naloxone) or kappa (aticaprant) opioid receptors.</p><p><strong>Results: </strong>Naloxone reduced effort-related choice and response vigor and increased choice latency and omissions in both sexes, though females were more sensitive to lower doses. Aticaprant did not affect effort discounting or other motivational measures on this task. Neither drug affected choice on delay discounting, although both drugs increase choice latencies, and aticaprant increased omissions in females on this task. Naloxone had comparatively muted effects on choice during reward magnitude discriminations, that varied across sex and task.</p><p><strong>Conclusions: </strong>These results point to a selective contribution of mu opioid receptor signalling in modulating reward-related decisions involving effort, but not delay costs.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797373","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":"Chronic nicotine vapor-induced enhancement of ethanol drinking-in-the-dark is associated with reduced medial prefrontal cortical activity.","authors":"Timothy G Freels, Jennifer Li, Rebecca G Pavchinskiy, Rubing Zhao-Shea, Gilles E Martin, Andrew R Tapper","doi":"10.1007/s00213-026-07147-z","DOIUrl":"https://doi.org/10.1007/s00213-026-07147-z","url":null,"abstract":"<p><strong>Rationale: </strong>Nicotine vaping is associated with increased alcohol use, including binge drinking, yet the neurobehavioral mechanisms underlying nicotine-alcohol interactions remain poorly understood due to limited translational preclinical models capturing intrapulmonary nicotine exposure effects on binge-like ethanol intake.</p><p><strong>Objectives: </strong>We establish a mouse model combining nicotine vapor exposure (NVE) with drinking-in-the-dark (DID) to examine effects on binge-like ethanol (EtOH) consumption and determine whether these effects are associated with medial prefrontal cortex (mPFC) activity and nicotinic acetylcholine receptor (nAChR) signaling.</p><p><strong>Methods: </strong>Male and female mice were passively exposed to nicotine or vehicle vapor prior to 2-h and 4-h EtOH DID across repeated cycles. EtOH intake, blood ethanol concentrations (BECs), and control solution consumption were measured. Neuronal activation in prelimbic (PrL) and medial orbitofrontal cortex (mOFC) was assessed using c-Fos immunofluorescence. Mecamylamine was used to evaluate nAChR involvement.</p><p><strong>Results: </strong>NVE produced physiologically relevant nicotine exposure and selectively increased EtOH consumption during 2-h and 4-h DID sessions without altering control solution intake. NVE also elevated BECs, which were positively correlated with EtOH consumption. Following DID, NVE was associated with reduced mPFC activity in PrL and mOFC; however, EtOH consumption was inversely correlated specifically with mOFC activity. nAChR blockade attenuated NVE-induced increases in EtOH consumption during 2-h DID only.</p><p><strong>Conclusions: </strong>Passive nicotine vapor exposure enhances binge-like EtOH intake and is associated with reduced mPFC engagement, particularly within mOFC, suggesting a mechanism underlying nicotine-alcohol interactions. These effects are partly mediated by nAChRs, identifying mPFC nAChRs as potential therapeutic targets for nicotine-alcohol polysubstance use.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764952","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":"Investigating sex differences in the acute effects of smoked cannabis: a potency-ranging, controlled administration, human laboratory experiment.","authors":"Madison Wright, Justin Matheson, Adam Zaweel, Christine M Wickens, Patricia Di Ciano, Beth Sproule, Bernard Le Foll, Bruna Brands","doi":"10.1007/s00213-026-07144-2","DOIUrl":"https://doi.org/10.1007/s00213-026-07144-2","url":null,"abstract":"<p><strong>Rationale: </strong>Sex differences in the effects of cannabis have been demonstrated in animals, though the human evidence is more equivocal. In particular, more work is needed to better understand interactions between sex and dose in determining acute pharmacological effects of cannabis, especially at higher potencies of Δ⁹-tetrahydrocannabinol (THC).</p><p><strong>Objectives: </strong>Sex differences were examined following a range of potencies of smoked cannabis (0%/0 mg, 6.25%/47 mg, 12.5%/94 mg, 22.0%/165 mg THC).</p><p><strong>Methods: </strong>Thirty-five adults (18 females; 17 males) who used cannabis 1-5 days/week participated in a within-subject, double-blind, placebo-controlled, randomized, and counterbalanced human laboratory experiment. Analyses compared peak change from baseline scores between females and males for smoking topography, blood and oral fluid THC and metabolites concentrations, vital signs, pharmacokinetic-pharmacodynamic relationships, subjective effects, mood, and cognition.</p><p><strong>Results: </strong>Females and males smoked similar amounts in each condition, yet females spent significantly more time smoking across all conditions. While both sexes achieved similar blood THC concentrations, females had significantly lower oral fluid THC concentrations. Aside from differences in the onset of some peak subjective effects, minimal evidence of sex differences was found in other outcomes, as well as in pharmacokinetic-pharmacodynamic relationships.</p><p><strong>Conclusions: </strong>Our findings indicate inconsistent sex differences in the acute effects of smoked cannabis across a range of potencies. While previous research has examined the influences of sex on the effects of THC, to our knowledge this was the first study to evaluate sex differences testing a large range of smoked cannabis potencies (up to 22%/165 mg THC) under placebo-controlled laboratory conditions.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707548","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}