Journal of Psychopharmacology最新文献

{"title":"Adverse event monitoring, assessment, and reporting in nutraceutical and phytoceutical trials for pediatric neuropsychiatric conditions: A systematic review.","authors":"Kalee Lodewyk, Darren B Courtney, Alexa Bagnell, Amanda S Newton","doi":"10.1177/02698811251344683","DOIUrl":"https://doi.org/10.1177/02698811251344683","url":null,"abstract":"<p><strong>Background: </strong>Natural treatments may be used as an alternative or adjunct treatment for childhood neuropsychiatric disorders. Knowledge of benefits and harms is needed to inform use guidelines. We aimed to systematically identify how and which adverse events are monitored, assessed, and reported in pediatric trials that tested nutraceutical and phytoceutical treatments.</p><p><strong>Methods: </strong>We searched MEDLINE, Embase, PsycINFO, ProQuest Dissertations and Theses Global, Cochrane Library, and Google Scholar from 2012 to 2024. Eligible studies included nutraceutical and phytoceutical trials, experimental or quasi-experimental in design, involving children or adolescents (age 4-19 years) with neuropsychiatric conditions.</p><p><strong>Results: </strong>Ninety-eight trials were included with 75 reported as completed (77%). The most common natural treatment tested was polyunsaturated fatty acids (36%, 35/98). Most trials focused on treating attention-deficit/hyperactivity disorder (59%, 58/98) or autism spectrum disorder (21%, 21/98). Investigators from 74/98 trials (76%) reported methods that indicated adverse event monitoring. For these trials, events defined a priori for monitoring were identified in 43% (32/74), methods for collecting and recording events were described in 68% (50/74), and assessment of event severity and attribution was described in 49% (36/74) and 26% (19/74), respectively. Over 100 different adverse events were reported across completed trials. The most common events reported were gastrointestinal distress (65%, 49/75) and headache (33%, 25/75).</p><p><strong>Conclusions: </strong>We found variability in monitoring, assessing, and reporting adverse events in pediatric trials of natural treatments. The adverse events identified in this review reinforces that specific events should be prospectively monitored in future trials.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251344683"},"PeriodicalIF":4.5,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618697","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":"A systematic review and narrative summary of the therapeutic potential of classic serotonergic psychedelics for smoking cessation and reduction.","authors":"Dillon L Glenn, Seung Hee Choi, Rick S Zimmerman","doi":"10.1177/02698811251353251","DOIUrl":"https://doi.org/10.1177/02698811251353251","url":null,"abstract":"<p><strong>Background: </strong>Classic serotonergic psychedelics are 5-HT2A partial agonists that induce non-ordinary states of consciousness. Many have demonstrated anti-addictive properties; however, their impact on smoking behaviors remains under-researched. This review provides a synthesis of the therapeutic potential of these compounds in promoting smoking cessation and reduction.</p><p><strong>Methods: </strong>A systematic review of peer-reviewed studies on psychedelics and smoking outcomes, published in English, was conducted. Database searches of PubMed, CINAHL, PsycINFO, and EMBASE resulted in 3547 records. ASReview, an open-source machine-learning tool, was used to improve the screening process. Abstract and initial review screening excluded 2336 articles, leaving 29 full-text articles for review. After further exclusion based on the inclusion of psychedelics and reported outcomes, eight studies were included in the analysis. All studies were assessed for risk of bias using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool.</p><p><strong>Results: </strong>Heterogeneity in the data was observed. All studies showed a serious risk of bias. Psilocybin was the most frequently reported compound (<i>n</i> = 7), followed by lysergic acid diethylamide (LSD; <i>n</i> = 5), mescaline (<i>n</i> = 4), ayahuasca (<i>n</i> = 4), peyote (<i>n</i> = 2), and N,N-dimethyltryptamine (<i>n</i> = 1). Psilocybin, LSD, and ayahuasca revealed preliminary therapeutic potential for facilitating smoking cessation.</p><p><strong>Conclusions: </strong>Current literature on psychedelics' anti-addictive effects on smoking behaviors is promising but limited by weak study designs and low generalizability. Future research should allow for stronger sampling methods to improve statistical power and include comparative groups within experimental or quasi-experimental designs to strengthen inference for causal mechanisms between drug and nondrug influences on smoking outcomes.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251353251"},"PeriodicalIF":4.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608645","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":"Unequal representation? A cross-sectional analysis of age, sex, race, and ethnicity in clinical trials of classic psychedelics.","authors":"Damian Swieczkowski, Aleksander Kwaśny, Patrycja Ciurkowska, Michal Pruc, Lukasz Szarpak, Wiesław Jerzy Cubała","doi":"10.1177/02698811251353250","DOIUrl":"https://doi.org/10.1177/02698811251353250","url":null,"abstract":"<p><strong>Background: </strong>Although classic psychedelic trials show therapeutic potential, the limited diversity of participants raises concerns about generalizability and safety.</p><p><strong>Aims: </strong>This study assesses the representation of race, ethnicity, and sex in interventional clinical trials of psilocybin and lysergic acid diethylamide (LSD) to evaluate disparities in participant diversity.</p><p><strong>Methods: </strong>We conducted a cross-sectional analysis of interventional trials registered on ClinicalTrials.gov up to 12 January 2025 that focused on classic psychedelics (psilocybin, psilocin, LSD, DMT, 5-MeO-DMT, and mescaline). Eligible trials were phases 2-4 and targeted psychiatric disorders or symptoms. Trials involving only healthy participants were excluded. Two reviewers extracted trial-level data independently; discrepancies were resolved by consensus.</p><p><strong>Results: </strong>Nine eligible trials included eight with psilocybin and one with LSD. In the psilocybin trials (<i>n</i> = 501), the age of participants ranged from 34.3 to 56.3 years; 47.7% were women. White participants accounted for 87.2%, while Black participants accounted for 3.0%, and Asian individuals accounted for 5.0%. Ethnicity was reported in 4 of 8 psilocybin trials (<i>n</i> = 134), with 13.4% identifying as Hispanic or Latino. In four U.S.-only trials(<i>n</i> = 139), participation-to-population ratios (PPRs) confirmed the underrepresentation of Black (PPR = 0.317) and Asian participants (PPR = 0.799). The LSD trial (<i>n</i> = 11) included older adults (average age: 51.7 years) who did not provide any information on race or origin.</p><p><strong>Conclusions: </strong>The limited diversity in psychedelic trials demonstrates the need for broader recruitment. Without better representation, the safety and efficacy of these therapies remain uncertain. Standardized reporting and targeted strategies are essential to ensure equity.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251353250"},"PeriodicalIF":4.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608646","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":"The effect of betahistine on weight-related and metabolic measures in patients with schizophrenia treated with olanzapine and risperidone.","authors":"Najmeh Abbasi Jannatabadi, Maryam Emadzadeh, Mohammad Reza Fayyazi Bordbar, Seyed Ahmad Mohajeri, Mahsa Nahidi","doi":"10.1177/02698811251346696","DOIUrl":"https://doi.org/10.1177/02698811251346696","url":null,"abstract":"<p><strong>Background: </strong>Drugs for psychosis can cause weight gain and metabolic disorders in schizophrenia. Given its partial agonistic activity at histamine receptors, betahistine could shape the effects of drugs for psychosis on weight gain and food intake. This study evaluates the effect of betahistine administration on anthropometric indices and symptoms of schizophrenia in schizophrenic patients.</p><p><strong>Methods: </strong>This randomized controlled trial was conducted on schizophrenic patients between 2020 and 2022. After stratification based on the type of treatment (olanzapine (<i>n</i> = 28) or risperidone (<i>n</i> = 28)), patients of each stratum were randomly divided into two groups (betahistine or placebo). The duration of the intervention was 12 weeks. Betahistine was started at 8 mg/day and gradually increased to 48 mg in 11 days. Anthropometric indices were measured monthly, while fasting blood glucose, lipid profile, TSH, and Positive and Negative Syndrome Scale (PANSS) were assessed at baseline and 12 weeks.</p><p><strong>Results: </strong>All anthropometric measures improved in patients receiving betahistine, except for increased waist circumference in those receiving olanzapine + betahistine. Triglyceride levels were significantly reduced in the olanzapine + betahistine subgroup compared to the placebo group (-12.14 ± 15.49 vs -0.28 ± 9.31; <i>p</i> = 0.021). Moreover, PANSS decreased significantly in all groups during the study, but the difference between groups was not significant.</p><p><strong>Conclusion: </strong>The addition of betahistine appears to be well tolerated and positively influences anthropometric indices. These findings suggest that betahistine may help mitigate some of the metabolic side effects of drugs for psychosis, although further research is needed to confirm these effects and to explore the optimal dosage.</p><p><strong>Trial registration number: </strong>IRCT20191223045870N1 in Iranian Registry of Clinical Trials (https://irct.behdasht.gov.ir/).</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251346696"},"PeriodicalIF":4.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584257","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":"Evaluating the impact of cannabis oil for autistic children with and without concomitant medications: Insights from an open-label study.","authors":"Nir Treves, Adi Dagan, Elkana Kohn, Ariela Hazan, Matityahu Berkovitch, Ibrahim Abu-Kishk, Netanel Agajani, Dana Barchel, Eli Heyman, Mirit Lazinger, Inbar Hartmann, Orit Stolar","doi":"10.1177/02698811251332841","DOIUrl":"https://doi.org/10.1177/02698811251332841","url":null,"abstract":"<p><strong>Background: </strong>Although only two drugs are FDA approved for autism spectrum disorder (ASD), clinical practice treatment includes off-label use of medications to address the troubling symptoms of ASD. Several trials showed the beneficial effects of medical cannabis for alleviating symptoms of ASD. However, data are lacking regarding its safety and effectiveness as a single agent compared to add-on therapy.</p><p><strong>Aims: </strong>To compare the safety and effectiveness of medical cannabis as a monotherapy and add-on therapy in autistic children.</p><p><strong>Methods: </strong>An open-label trial recruiting autistic children was performed and treated with medical cannabis oil with a THC:CBD ratio of 1:20, respectively. Tests were conducted at baseline and after 6 months of therapy. A secondary analysis was done to compare physical and behavior parameters, using tests such as Autism Diagnostic Observation Schedule and Wechsler tests in the two groups.</p><p><strong>Results: </strong>Out of 109 participants, 81 completed the treatment. Thirty received cannabis as add-on therapy to a pre-existing treatment, whereas 51 received cannabis as monotherapy, with no observed differences in baseline characteristics between the groups. The mean maximal CBD dose was 3.1 mg/kg/day in the monotherapy group, compared to 2.8 mg/kg/day in the add-on group (<i>p</i> = 0.40). In patients treated with drugs for psychosis, the mean maximal dose was 2.48 mg/kg/day (<i>p</i> = 0.12). No differences were observed in most physical and behavioral parameters. In addition, no differences in CBD blood levels were observed.</p><p><strong>Conclusions: </strong>Add-on cannabis therapy is as safe as monotherapy treatment, without significant differences in efficacy.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251332841"},"PeriodicalIF":4.5,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560415","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":"Examining mystical experiences as a predictor of psilocybin-assisted psychotherapy for treatment-resistant depression.","authors":"Ryan M Brudner, Erica Kaczmarek, Marc G Blainey, Christian Schulz-Quach, Shakila Meshkat, Zoe Doyle, Orly Lipsitz, Hilary Offman, Rickinder Sethi, Geneva Weiglein, Roger S McIntyre, Joshua D Rosenblat","doi":"10.1177/02698811251346697","DOIUrl":"https://doi.org/10.1177/02698811251346697","url":null,"abstract":"<p><strong>Background: </strong>Psilocybin-assisted psychotherapy (PAP) is a promising treatment for various psychiatric disorders. However, the exact biological and psychological mechanisms of action of PAP remain to be determined. Examining predictors of PAP outcomes may help identify necessary processes for positive treatment outcomes. Mystical experiences are considered a key aspect of the subjective effects of ingesting psilocybin. Mystical experiences have been observed to be possibly predictive of positive outcomes in psilocybin treatments. Therefore, some argue that mystical-type experiences are necessary to achieve therapeutic benefits.</p><p><strong>Aims: </strong>The current study examines mystical experiences as a predictor of antidepressant treatment outcomes in PAP, in a complex clinical sample.</p><p><strong>Methods: </strong>Participants included 31 individuals with a primary diagnosis of major depressive disorder (MDD) or Bipolar II Disorder (BDII), with treatment resistance to symptoms of their disorder. Participants had one, two, or three PAP treatments with a fixed dose of 25 mg of psilocybin. Depressive symptoms were measured at baseline, at a pre-dose visit and at 2 weeks post-dosing. The presence of mystical experiences was measured on the dosing day after the acute effects had resolved.</p><p><strong>Results: </strong>For the first psilocybin dose, participants with greater levels of mystical experiences exhibited a greater antidepressant effect from PAP. This effect was not found at the second or third doses.</p><p><strong>Conclusion: </strong>These results provide preliminary support for the hypothesis that mystical experiences have therapeutic importance in PAP and extend the literature to include a clinical sample of individuals with treatment-resistant depression in the context of MDD or BDII.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251346697"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540597","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":"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":"736-743"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","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}

{"title":"Ethanol-induced rapid eye movement sleep suppression in rats: Comparison with subtype-selective GABA_A receptor compounds.","authors":"Jaren A Reeves-Darby, Lais F Berro, Heather L Hembree, James P Shaffery, James K Rowlett, Dishary Sharmin, Prithu Mondal, James M Cook, Donna M Platt","doi":"10.1177/02698811251344682","DOIUrl":"10.1177/02698811251344682","url":null,"abstract":"<p><strong>Background: </strong>Alcohol use disorder patients experience reductions in rapid eye movement (REM) sleep and other sleep problems. Little is known about the pharmacological mechanism(s) involved in this effect.</p><p><strong>Aims: </strong>This study compared sleep-wake states and electroencephalography (EEG) spectral power following exposure to ethanol and GABA_A receptor (GABA_AR) compounds with varying subtype selectivity.</p><p><strong>Methods: </strong>Sprague-Dawley rats received ethanol or subtype-selective GABA_AR compounds, followed by EEG/electromyography (EMG) recordings for 12 h. These recordings were analyzed for sleep-wake state and EEG spectral power.</p><p><strong>Results: </strong>Sleep-wake state analysis demonstrated that ethanol, the nonselective compound alprazolam, the α1-selective compound zolpidem, the α2/3-selective compound KRM-II-81, and the α5-selective compound MP-III-022 produced decreases in REM sleep. By contrast, the α4/6-selective compound, gaboxadol, only increased time spent in slow-wave sleep (SWS). KRM-II-81 was the only compound to produce increases in time spent awake. The EEG spectral power analysis revealed that all compounds produced a unique signature, but none produced a signature similar to ethanol.</p><p><strong>Conclusions: </strong>Analysis of sleep-wake states after administration of ethanol or GABA_AR compounds with varying subtype selectivity suggests that positive modulation of α1, 2, 3, and/or 5 subunit-containing GABA_ARs is sufficient to suppress REM sleep, and any or all may be involved in ethanol-induced REM sleep suppression. Also, our study suggests that α4/6 subunit-containing GABA_ARs may be involved in ethanol-induced increases in SWS. The lack of similarity between ethanol and the GABA_AR compounds in the pharmaco-EEG analysis suggests that neurotransmitter systems besides the GABAergic system are likely involved in the effects of ethanol on EEG spectral power.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"744-755"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333387","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":"Mapping acute alcohol effects on bodily sensations: A cross-dimensional interoceptive approach.","authors":"Mateo Leganes-Fonteneau, Olivier Desmedt, Micah G Allen, Reinout W Wiers, Pierre Maurage","doi":"10.1177/02698811251338223","DOIUrl":"10.1177/02698811251338223","url":null,"abstract":"<p><strong>Background: </strong>Interoceptive processes may underlie maladaptive patterns of alcohol use. Bodily sensations experienced during alcohol intoxication could therefore reveal distinct mechanistic components relevant for addiction theory and research. Here, we apply novel tools to examine how intoxication impacts somatic awareness using bodily maps and a cardiac interoception task.</p><p><strong>Methods: </strong>In a double-blind, within-subjects, placebo-controlled study, social drinkers (<i>n</i> = 37, 17 female) were administered 0.4 g/kg of alcohol. We measured changes in self-reported bodily sensations during the ascending and descending limbs of the blood-alcohol curves using the emBODY tool. Additionally, we recorded biphasic measures of subjective alcohol effects (sedation and stimulation), changes in heart rate, and assessed psychophysical measures of cardiac beliefs using the heart rate discrimination task.</p><p><strong>Results: </strong>Acute alcohol administration altered bodily sensations, reflected by strong sensations in the chest, limbs, and head, with lesser effects in the placebo condition. Linear-mixed models examined correlates of bodily sensations across conditions. Extent of bodily sensations correlated with heart rate changes and breath alcohol content. In the ascending limb, bodily sensations negatively correlated with subjective stimulation and positively with sedation. Finally, extent of bodily sensations correlated with the metacognitive sensitivity of cardiac beliefs, suggesting a cross-dimensional integration between sensations and interoceptive awareness.</p><p><strong>Discussion: </strong>These findings highlight the value of bodily mapping in psychopharmacology, as interoceptive components of alcohol intoxication may provide a somatic basis for addiction. We interpret our results through low-sensitivity models, suggesting individuals with reduced bodily sensations during intoxication may face elevated risk for alcohol use disorder, a hypothesis that will be examined in future research.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"682-693"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101112","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":"629-651"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267871/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}