Ana Deutsch, Connor J Haggarty, Gavin N Petrie, Matthew N Hill, Anya K Bershad, Harriet de Wit, Leah M Mayo
{"title":"甲基苯丙胺和3,4-亚甲基二氧基甲基苯丙胺对外周内源性大麻素浓度的影响：一项健康成人的研究。","authors":"Ana Deutsch, Connor J Haggarty, Gavin N Petrie, Matthew N Hill, Anya K Bershad, Harriet de Wit, Leah M Mayo","doi":"10.1007/s00213-025-06888-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale: </strong>Stimulant drugs such as methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) can impact neurobiological systems implicated in stress, reward processing, and drug use. Although recent preclinical evidence implicates the endocannabinoid (eCB) system in these processes, little is known about the acute effects of stimulants on eCB levels in humans.</p><p><strong>Objectives: </strong>The aim of the present study was to investigate the effects of acute administration of the prototypical psychostimulant MA and the psychostimulant-empathogen MDMA on circulating eCB levels in healthy adults.</p><p><strong>Methods: </strong>Using a within-subject, double-blind design, this study assessed the acute effects of MA (20 mg), MDMA (100 mg), and placebo on plasma eCB levels in healthy human participants (N = 22) during three separate sessions. Blood samples assessing concentrations of the eCBs anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) were collected between 150- and 180-minutes post-drug administration, and subjective measures of drug effects were collected at regular intervals.</p><p><strong>Results: </strong>MA, but not MDMA, was associated with significantly lower 2-AG plasma concentrations compared to placebo. Neither drug impacted AEA concentrations. However, during the placebo condition, higher AEA concentrations were correlated with disliking the 'drug effects', suggesting a possible relationship between AEA levels and negative expectations of subjective drug effects.</p><p><strong>Conclusions: </strong>These findings provide novel insights into how stimulant drugs act on the eCB system and may help to develop treatments for SUDs.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The effect of methamphetamine and 3,4-methylenedioxymethamphetamine on peripheral endocannabinoid concentrations: a study in healthy adults.\",\"authors\":\"Ana Deutsch, Connor J Haggarty, Gavin N Petrie, Matthew N Hill, Anya K Bershad, Harriet de Wit, Leah M Mayo\",\"doi\":\"10.1007/s00213-025-06888-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Rationale: </strong>Stimulant drugs such as methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) can impact neurobiological systems implicated in stress, reward processing, and drug use. Although recent preclinical evidence implicates the endocannabinoid (eCB) system in these processes, little is known about the acute effects of stimulants on eCB levels in humans.</p><p><strong>Objectives: </strong>The aim of the present study was to investigate the effects of acute administration of the prototypical psychostimulant MA and the psychostimulant-empathogen MDMA on circulating eCB levels in healthy adults.</p><p><strong>Methods: </strong>Using a within-subject, double-blind design, this study assessed the acute effects of MA (20 mg), MDMA (100 mg), and placebo on plasma eCB levels in healthy human participants (N = 22) during three separate sessions. Blood samples assessing concentrations of the eCBs anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) were collected between 150- and 180-minutes post-drug administration, and subjective measures of drug effects were collected at regular intervals.</p><p><strong>Results: </strong>MA, but not MDMA, was associated with significantly lower 2-AG plasma concentrations compared to placebo. Neither drug impacted AEA concentrations. 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The effect of methamphetamine and 3,4-methylenedioxymethamphetamine on peripheral endocannabinoid concentrations: a study in healthy adults.
Rationale: Stimulant drugs such as methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) can impact neurobiological systems implicated in stress, reward processing, and drug use. Although recent preclinical evidence implicates the endocannabinoid (eCB) system in these processes, little is known about the acute effects of stimulants on eCB levels in humans.
Objectives: The aim of the present study was to investigate the effects of acute administration of the prototypical psychostimulant MA and the psychostimulant-empathogen MDMA on circulating eCB levels in healthy adults.
Methods: Using a within-subject, double-blind design, this study assessed the acute effects of MA (20 mg), MDMA (100 mg), and placebo on plasma eCB levels in healthy human participants (N = 22) during three separate sessions. Blood samples assessing concentrations of the eCBs anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) were collected between 150- and 180-minutes post-drug administration, and subjective measures of drug effects were collected at regular intervals.
Results: MA, but not MDMA, was associated with significantly lower 2-AG plasma concentrations compared to placebo. Neither drug impacted AEA concentrations. However, during the placebo condition, higher AEA concentrations were correlated with disliking the 'drug effects', suggesting a possible relationship between AEA levels and negative expectations of subjective drug effects.
Conclusions: These findings provide novel insights into how stimulant drugs act on the eCB system and may help to develop treatments for SUDs.
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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