The Safety Profile and Dose-Response Effects of 3-Methylmethcathinone: Impact on Vital Signs and Affective States

Background: Recreational use of the novel psychoactive substance known as 3-MMC or 3-Methylmethcathinone, a synthetic psychostimulant, has surged in the past decade, raising public health concerns. Common in nightlife and chemsex settings, it is linked to elevated heart rate, blood pressure, and body temperature, posing cardiovascular risks, while its euphoric and stimulating effects increase its abuse potential. This first clinical phase 1 study investigates 3-MMC's safety and doseresponse effects, hypothesizing dose-dependent increases in heart rate, blood pressure, body temperature, arousal, and elation in healthy volunteers. Methods: A double-blind, placebo-controlled, within-subjects design was used, involving four test days where participants received escalating oral doses of 3-MMC (25 mg, 50 mg, 100 mg—ranging from low to moderate based on prior reports) and placebo. Twelve healthy volunteers were recruited through advertisements at Maastricht University. Physiological...Show moreBackground: Recreational use of the novel psychoactive substance known as 3-MMC or 3-Methylmethcathinone, a synthetic psychostimulant, has surged in the past decade, raising public health concerns. Common in nightlife and chemsex settings, it is linked to elevated heart rate, blood pressure, and body temperature, posing cardiovascular risks, while its euphoric and stimulating effects increase its abuse potential. This first clinical phase 1 study investigates 3-MMC's safety and doseresponse effects, hypothesizing dose-dependent increases in heart rate, blood pressure, body temperature, arousal, and elation in healthy volunteers. Methods: A double-blind, placebo-controlled, within-subjects design was used, involving four test days where participants received escalating oral doses of 3-MMC (25 mg, 50 mg, 100 mg—ranging from low to moderate based on prior reports) and placebo. Twelve healthy volunteers were recruited through advertisements at Maastricht University. Physiological measures including heart rate, blood pressure, and body temperature were recorded using standardized methods, and affective states were assessed using the Profile of Mood States (POMS) questionnaire. Linear mixedeffects models in SPSS were employed to analyze the dose-dependent effects. Results: Significant positive main effects of 3-MMC dose on heart rate (p < .001), systolic (p < .001) and diastolic blood pressure (p < .001) confirm the hypothesized dose-dependent increases. A significant effect on body temperature (p = .014) was found, though non-monotonic, not in support of the hypothesis. For arousal (p = .009) and elation (p = .017), significant positive dose effects, negative time effects, and dose-time interactions supported hypothesized dose-dependent increases, and revealed decreases over time. Conclusion: Results indicate that 25 mg and 50 mg doses are safe with no significant acute adverse effects, while 100 mg doses may exceed a threshold where risks increase. By establishing this dose-effect relationship, the study supports development of harm reduction strategies, public health initiatives, and targeted overdose prevention, informing safer use guidelines and policy-making.Show less

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The Safety Profile and Dose-Response Effects of 3-Methylmethcathinone: Impact on Vital Signs and Affective States