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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\u00a0mg) of 3-MMC in healthy volunteers (<jats:italic>N<\/jats:italic>\u2009=\u200914) in a cross-over, placebo-controlled study. Participants were repeatedly exposed to experimental pain for up to 5\u00a0h 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\u00a0mg dose and persisted consistently for up to 5\u00a0h after dosing. 3-MMC also produced dose-related increments in mood that were prominent at 1\u00a0h, but not at 5\u00a0h 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.<\/jats:p>","DOI":"10.1007\/s00213-025-06798-8","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T23:01:00Z","timestamp":1746054060000},"page":"2293-2301","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"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"],"prefix":"10.1007","volume":"242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4553-376X","authenticated-orcid":false,"given":"Johannes G","family":"Ramaekers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes T","family":"Reckweg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha L","family":"Mason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim PC","family":"Kuypers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan W","family":"Toennes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eef L","family":"Theunissen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,1]]},"reference":[{"key":"6798_CR1","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1007\/s00204-014-1278-7","volume":"89","author":"AM Araujo","year":"2015","unstructured":"Araujo AM, Valente MJ, Carvalho M, Dias da Silva D, Gaspar H, Carvalho F, de Lourdes Bastos M, de Guedes P (2015) Raising awareness of new psychoactive substances: chemical analysis and in vitro toxicity screening of \u2018legal high\u2019 packages containing synthetic Cathinones. 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