Journal of Psychopharmacology最新文献

{"title":"Oral esketamine for patients with severe treatment-resistant depression: Effectiveness, safety, and tolerability of a six-week open-label treatment program.","authors":"Jolien Ke Veraart, Sanne Y Smith-Apeldoorn, Annemarie van der Meij, Jan Spijker, Robert A Schoevers, Jeanine Kamphuis","doi":"10.1177/02698811251332831","DOIUrl":"https://doi.org/10.1177/02698811251332831","url":null,"abstract":"<p><strong>Background: </strong>Oral esketamine for patients with treatment-resistant depression (TRD) could offer certain advantages over other routes, such as intravenous or intranasal, but it has not been systematically studied in a real-world setting.</p><p><strong>Aims: </strong>Here we present results from a relatively large naturalistic study to evaluate the effectiveness, tolerability, and safety of oral esketamine in patients with TRD.</p><p><strong>Methods: </strong>One hundred eighty-five adults with severe TRD (average of 8.1 antidepressant trials plus electroconvulsive therapy in 63% without beneficial outcome) received oral esketamine treatment twice-weekly for 6 weeks with individually titrated doses ranging from 0.5 to 3 mg/kg. Outcome measures included change from baseline to week 6 on the Hamilton Depression Rating Scale (HDRS₁₇), Minimal Clinically Important Difference (MCID), response, remission, self-reported symptom improvement, functioning, and side effects.</p><p><strong>Results: </strong>Oral esketamine treatment improved depressive symptom severity on the HDRS₁₇ from 21.2 to 15.8 (<i>p</i> < 0.001). MCID, response, and remission rates were 47.1%, 26.8% and 15.6% respectively. In 45.9% of participants, treatment was continued after 6 weeks to maintain initial positive effects. Side effects were reported frequently but were overall well tolerated. The drop-out rate was 7.6%. We found no significant adverse effects associated with urinary tract or cognition.</p><p><strong>Conclusions: </strong>Repeated treatment with oral esketamine is effective in improving depressive symptom severity in highly treatment-resistant depressive patients. It is safe, well tolerated, and patient-friendly. Considering the level of treatment resistance, outcomes were in the range of studies investigating other routes of (es)ketamine administration.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251332831"},"PeriodicalIF":4.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004897","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":"Psilocybin and ketamine affect novel neuropeptides gene expression in the rat hypothalamus.","authors":"Artur Pałasz, Marta Pukowiec, Katarzyna Bogus, Aleksandra Suszka-Świtek, Łukasz Filipczyk, Kinga Mordecka-Chamera, John J Worthington, Maria Sygidus, Adam Wojtas, Agnieszka Bysiek, Krystyna Gołembiowska","doi":"10.1177/02698811251330783","DOIUrl":"https://doi.org/10.1177/02698811251330783","url":null,"abstract":"<p><strong>Objective: </strong>Psychedelics are able to trigger highly intense and profound alterations in self-consciousness, perception, affective, and cognitive processes. Indeed, recent studies show that ketamine and psilocybin could be used as fast-acting antidepressants. However, the molecular and neurochemical mechanisms of these psychedelics and their actions at the level of diverse brain structures remains so far unclear. Hypothalamic neuropeptides are involved in a wide spectrum of neuronal activities being responsible for the central control of all fundamental autonomic functions.</p><p><strong>Methods: </strong>The purpose of this exploratory pilot study was to assess the gene expression of both classical and novel neuropeptides, including nesfatin-1, phoenixin (PNX), spexin (SPX), neuromedin U (NMU), neuropeptide S (NPS), and their known receptors in the hypothalamus of male Wistar-Han rats subjected to single injections of psilocybin (dose 2 or 10 mg/kg) and ketamine (dose10 mg/kg). Total mRNA was isolated from homogenized tissue and real-time PCR was used for estimation of related gene expression.</p><p><strong>Results: </strong>It was found that a single administration of the higher dose of psilocybin increased the mRNA expression of most noncanonical neuropeptides examined in the study, with only the case of NMU there with a decrease in gene expression. Interestingly, psilocybin administration also increased mRNA expression of the serotonin receptors: 5-HT1A, 5-HT2A, and 5-HT2B, but not 5HT-2C. In contrast, the effect of ketamine on the expression of neuropeptides was much more limited compared to psilocybin, only increasing transcripts of NUCB2, GPR173, and POMC were demonstrated.</p><p><strong>Conclusions: </strong>These results suggest for the first time that selected psychedelics may enhance the signaling of 5-HT2A receptors or inhibit NMDA receptor activity, affecting neuropeptide signaling and serotonin transmission in the rat hypothalamus, which may contribute to a better understanding of psychedelic action in the brain.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251330783"},"PeriodicalIF":4.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041303","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":"https://doi.org/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":"Repeated administration of L-alanine to mice reduces behavioural despair and increases hippocampal mammalian target of rapamycin signalling: Analysis of gender and metabolic effects.","authors":"Abdullah Aziz, Carolina Fernandes Ferreira Alves Costa, Erying Zhao, Daniel Radford-Smith, Fay Probert, Daniel Clive Anthony, Philip William John Burnet","doi":"10.1177/02698811251332838","DOIUrl":"https://doi.org/10.1177/02698811251332838","url":null,"abstract":"<p><strong>Background: </strong>The amino acid L-alanine, has been shown to be elevated in biofluids during major depression but its relevance remains unexplored.</p><p><strong>Aim: </strong>We have investigated the effects of repeated L-alanine administration on emotional behaviours and central gene expression in mice.</p><p><strong>Methods: </strong>Mice received a daily, 2-week intraperitoneal injection of either saline or L-alanine at 100 or 200 mg/kg and were exposed to the open field, light-dark box and forced swim test. The expression of L-alanine transporters (asc-1, ASCT2), glycine receptor subunits (GlyRs), NMDA receptor subunits (GluNs) mRNAs were measured, together with western blots of the signalling protein mammalian target of rapamycin (mTOR). Since L-alanine modulates glucose homeostasis, peripheral and central metabolomes were evaluated with ¹H-NMR.</p><p><strong>Results: </strong>L-alanine administration at 100 mg/kg, but not at 200 mg/kg, to both male and female mice increased latency to float and reduced floating time in the forced swim test, but had no effect on anxious behaviour in the open field and light-dark box tests. There was a significant reduction in mRNAs encoding asc-1 and ASCT2 and GluN2B in the hippocampus of mice following 100 mg/kg L-alanine only. On western blots, hippocampal GluN2B immunoreactivity was reduced, but mTOR signalling was increased in the 100 mg/kg L-alanine group. 1H-NMR revealed gender-specific changes in the forebrain, plasma and liver metabolomes only at 200 mg/kg of L-alanine.</p><p><strong>Conclusions: </strong>Our data suggest that L-alanine may have antidepressant-like effect that may involve the modulation of glutamate neurotransmission independently of metabolism. In major depression, therefore, elevated L-alanine may be a homeostatic response to pathophysiological processes, though this will require further investigation.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251332838"},"PeriodicalIF":4.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970798","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}