Johannes G Ramaekers, Johannes T Reckweg, Natasha L Mason, Kim Pc Kuypers, Stefan W Toennes, Eef L Theunissen
{"title":"低至中等剂量的3-甲基甲卡西酮(3-MMC)在健康志愿者中产生镇痛作用:一项设计药物的原理证明研究。","authors":"Johannes G Ramaekers, Johannes T Reckweg, Natasha L Mason, Kim Pc Kuypers, Stefan W Toennes, Eef L Theunissen","doi":"10.1007/s00213-025-06798-8","DOIUrl":null,"url":null,"abstract":"<p><p>3-Methylmethcathinone (3-MMC) is a synthetic cathinone that has been scheduled in many jurisdictions after it appeared on the consumer market as a designer drug or \"legal high\". At present, there are no medical applications for synthetic cathinones, but in the past cathinone and other compounds that are structurally related to amphetamine have been evaluated and recognized for their intrinsic analgesic quality. The present study aimed to assess the analgesic effects of low to moderate doses (25, 50 and 100 mg) of 3-MMC in healthy volunteers (N = 14) in a cross-over, placebo-controlled study. Participants were repeatedly exposed to experimental pain for up to 5 h after dosing in pressure pain threshold (PPT) and cold pressor test (CPT) paradigms. A profile of mood states questionnaire was used to assess the subjective effects of 3-MMC. Overall, 3-MMC produced dose-related elevations in pressure pain threshold and reduced subjective painfulness and unpleasantness in both experimental pain models. The analgesic effects of 3-MMC were most prominent after the 50 and 100 mg dose and persisted consistently for up to 5 h after dosing. 3-MMC also produced dose-related increments in mood that were prominent at 1 h, but not at 5 h after dosing. It is concluded that 3-MMC produces prolonged analgesic effects at doses that appear low enough to avoid a challenging subjective experience and that have been associated with a benign side effect profile. The present data warrant further research into the analgesic effects of low to moderate doses of 3-MMC in patient populations.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Low to moderate doses of 3-methylmethcathinone (3-MMC) produce analgesic effects in healthy volunteers: a proof of principle study with a designer drug.\",\"authors\":\"Johannes G Ramaekers, Johannes T Reckweg, Natasha L Mason, Kim Pc Kuypers, Stefan W Toennes, Eef L Theunissen\",\"doi\":\"10.1007/s00213-025-06798-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>3-Methylmethcathinone (3-MMC) is a synthetic cathinone that has been scheduled in many jurisdictions after it appeared on the consumer market as a designer drug or \\\"legal high\\\". At present, there are no medical applications for synthetic cathinones, but in the past cathinone and other compounds that are structurally related to amphetamine have been evaluated and recognized for their intrinsic analgesic quality. The present study aimed to assess the analgesic effects of low to moderate doses (25, 50 and 100 mg) of 3-MMC in healthy volunteers (N = 14) in a cross-over, placebo-controlled study. Participants were repeatedly exposed to experimental pain for up to 5 h after dosing in pressure pain threshold (PPT) and cold pressor test (CPT) paradigms. A profile of mood states questionnaire was used to assess the subjective effects of 3-MMC. Overall, 3-MMC produced dose-related elevations in pressure pain threshold and reduced subjective painfulness and unpleasantness in both experimental pain models. The analgesic effects of 3-MMC were most prominent after the 50 and 100 mg dose and persisted consistently for up to 5 h after dosing. 3-MMC also produced dose-related increments in mood that were prominent at 1 h, but not at 5 h after dosing. It is concluded that 3-MMC produces prolonged analgesic effects at doses that appear low enough to avoid a challenging subjective experience and that have been associated with a benign side effect profile. 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Low to moderate doses of 3-methylmethcathinone (3-MMC) produce analgesic effects in healthy volunteers: a proof of principle study with a designer drug.
3-Methylmethcathinone (3-MMC) is a synthetic cathinone that has been scheduled in many jurisdictions after it appeared on the consumer market as a designer drug or "legal high". At present, there are no medical applications for synthetic cathinones, but in the past cathinone and other compounds that are structurally related to amphetamine have been evaluated and recognized for their intrinsic analgesic quality. The present study aimed to assess the analgesic effects of low to moderate doses (25, 50 and 100 mg) of 3-MMC in healthy volunteers (N = 14) in a cross-over, placebo-controlled study. Participants were repeatedly exposed to experimental pain for up to 5 h after dosing in pressure pain threshold (PPT) and cold pressor test (CPT) paradigms. A profile of mood states questionnaire was used to assess the subjective effects of 3-MMC. Overall, 3-MMC produced dose-related elevations in pressure pain threshold and reduced subjective painfulness and unpleasantness in both experimental pain models. The analgesic effects of 3-MMC were most prominent after the 50 and 100 mg dose and persisted consistently for up to 5 h after dosing. 3-MMC also produced dose-related increments in mood that were prominent at 1 h, but not at 5 h after dosing. It is concluded that 3-MMC produces prolonged analgesic effects at doses that appear low enough to avoid a challenging subjective experience and that have been associated with a benign side effect profile. The present data warrant further research into the analgesic effects of low to moderate doses of 3-MMC in patient populations.
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.