Safety and cognitive pharmacodynamics following dose escalations with 3-methylmethcathinone (3-MMC): a first in human, designer drug study

In the first human study of 3-methylmethcathinone (3-MMC), a synthetic cathinone designer drug, 14 participants received escalating doses of 25, 50, and 100 mg in a placebo-controlled crossover trial. The drug caused dose-dependent increases in heart rate and blood pressure that were not clinically significant, along with subjective feelings of being high. 3-MMC also enhanced performance across several neurocognitive domains, including processing speed, cognitive flexibility, psychomotor function, attention, and memory, without affecting impulse control. Participants reported mild dissociative and psychedelic effects, decreased appetite, and transient increases in drug liking and wanting. The cardiovascular and psychostimulant profile resembles amphetamine-related compounds. Low to moderate doses were well tolerated and safe, with potential health risks likely only at high or excessive doses.

Study at a glance

Abstract

Abstract 3-Methylmethcathinone (3-MMC) is a designer drug that belongs to the group of synthetic cathinones. The compound has been scheduled in many jurisdictions because of public health concerns associated with excessive use. To date, there are no clinical studies that have evaluated the risk profile of 3-MMC in the recreational range of low to moderate doses. The current, first-in-human study (N=14) assessed the impact of three escalating doses of 3-MMC (25, 50 and 100 mg) on vital signs, neurocognitive function, state of consciousness, appetite and drug desire, in a cross-over, placebo-controlled trial. A battery of neurocognitive tests and questionnaires as well as measures of vital signs were repeatedly administered up to 5 hours after dosing. Overall, 3-MMC caused dose-dependent increases in heart rate and blood pressure, though not of clinical significance, and feelings of subjective high. Additionally, 3-MMC induced dose-related enhancement of task performance across several neurocognitive domains, including processing speed, cognitive flexibility, psychomotor function, attention and memory. Impulse control was not affected by 3-MMC. Participants also reported mild increases in dissociative and psychedelic effects, decreased appetite, and gave greater ratings of liking and wanting for 3-MMC that were transient over time. Overall, the cardiovascular, psychostimulant and psychotomimetic profile of 3-MMC appears consistent with that of compounds structurally related to amphetamine. It is concluded that low to moderate doses of 3-MMC were well tolerated and safe and that potential health risks might only occur at high or excessive doses of 3-MMC.