Sex differences in the acute effects of oral THC: a randomized, placebo-controlled, crossover human laboratory study.

IF 3.5 3区 医学 Q2 NEUROSCIENCES Psychopharmacology Pub Date : 2024-10-01 Epub Date: 2024-06-04 DOI:10.1007/s00213-024-06625-6
Ardavan Mohammad Aghaei, Lia Urban Spillane, Brian Pittman, L Taylor Flynn, Joao P De Aquino, Anahita Bassir Nia, Mohini Ranganathan
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Abstract

Rationale: Recent reports have shown increased cannabis use among women, leading to growing concerns about cannabis use disorder (CUD). While there is preclinical evidence suggesting biological sex influences cannabinoid effects, human research remains scant. We investigated sex differences in the acute response to oral tetrahydrocannabinol (THC) in humans.

Methods: 56 healthy men and women with prior exposure to cannabis but no history of CUD participated in a randomized, placebo-controlled, human laboratory study where they received a single 10 mg dose of oral THC (dronabinol). Subjective psychoactive effects were assessed by the visual analog scale of "high", psychotomimetic effects by the Clinician-Administered Dissociative Symptoms Scale and Psychotomimetic States Inventory, verbal learning and memory by Rey Auditory Verbal Learning Test (RAVLT), and physiological effects by heart rate. Outcomes were regularly measured on the test day, except for the RAVLT, which was assessed once. Peak differences from baseline were analyzed using a nonparametric method for repeated measures.

Results: Oral THC (10 mg) demonstrated significant dose-related effects in psychotomimetic and physiological domains, but not in RAVLT outcomes. A notable interaction between THC dose and sex emerged concerning the subjective "high" scores, with women reporting heightened sensations (p = 0.05). No other significant effects of sex and THC dose interaction were observed.

Conclusion: Oral THC (10 mg) yields similar acute psychotomimetic and physiological effects across sexes, but women may experience a pronounced subjective psychoactive effect. Further research is needed to identify individual vulnerabilities and facilitate tailored interventions addressing CUD.

Clinicaltrials: GOV REGISTRATION: https://clinicaltrials.gov/study/NCT02781519?term=Ranganathan&intr=THC&rank=3 .

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口服四氢大麻酚急性效应的性别差异:一项随机、安慰剂对照、交叉人体实验室研究。
理由:最近的报告显示,女性使用大麻的人数有所增加,导致人们越来越关注大麻使用障碍 (CUD)。虽然有临床前证据表明生物性别会影响大麻素的作用,但人体研究仍然很少。我们调查了人类对口服四氢大麻酚(THC)急性反应的性别差异。方法:56 名健康的男性和女性参加了一项随机、安慰剂对照的人体实验室研究,他们之前接触过大麻,但没有 CUD 病史,研究人员让他们口服单次 10 毫克剂量的四氢大麻酚(屈大麻酚)。主观精神作用通过 "兴奋 "视觉模拟量表进行评估,拟精神作用通过临床医师管理的分离症状量表和拟精神状态量表进行评估,言语学习和记忆通过雷伊听觉言语学习测试(RAVLT)进行评估,生理作用通过心率进行评估。除了雷伊听觉言语学习测试(RAVLT)只评估一次外,其他结果均在测试当天进行定期测量。与基线相比的峰值差异采用非参数方法进行重复测量分析:结果:口服四氢大麻酚(10 毫克)在拟精神和生理领域表现出显著的剂量相关效应,但在 RAVLT 结果中却没有。在主观 "兴奋 "得分方面,THC剂量与性别之间存在明显的交互作用,女性的感觉更强烈(p = 0.05)。没有观察到性别与 THC 剂量相互作用的其他明显影响:结论:口服 THC(10 毫克)可产生类似的急性拟精神作用和生理效应,但女性可能会体验到明显的主观精神作用。需要进一步开展研究,以确定个体的脆弱性,并促进针对 CUD 的定制干预措施:gov 注册:https://clinicaltrials.gov/study/NCT02781519?term=Ranganathan&intr=THC&rank=3 。
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来源期刊
Psychopharmacology
Psychopharmacology 医学-精神病学
CiteScore
7.10
自引率
5.90%
发文量
257
审稿时长
2-4 weeks
期刊介绍: Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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