This pre-print cross-over, placebo-controlled trial (n=14) assesses the effects of escalating doses of 3-MMC (25, 50, 100mg) on vital signs, neurocognitive function, state of consciousness, appetite, and drug desire. Results show dose-dependent increases in heart rate and blood pressure (not clinically significant), enhanced neurocognitive task performance, and mild dissociative and psychedelic effects. Participants reported decreased appetite and transient increases in liking and wanting 3-MMC. Low to moderate doses were well tolerated and safe, with potential risks associated with high doses.
Abstract of Safety and cognitive pharmacodynamics following dose escalations with 3-MMC
“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.”
Authors: Johannes G. Ramaekers, Johannes T. Reckweg, Natasha L. Mason, Kim P. C. Kuypers, Stefan W. Toennes & Eef L. Theunissen
Summary of Safety and cognitive pharmacodynamics following dose escalations with 3-MMC
3-Methylmethcathinone (3-MMC) is a synthetic cathinone, a class of psychoactive substances derived from the naturally occurring stimulant found in the khat plant. Cathinones, which share structural similarities with amphetamines, were originally explored for medicinal purposes, such as appetite suppression and treatment of depression, during the mid-20th century. More recently, synthetic cathinones have emerged as recreational designer drugs, commonly referred to as “legal highs.” These substances, including 3-MMC, have been associated with psychostimulant effects like increased alertness, euphoria, and reduced appetite.
3-MMC functions as a monoamine transporter substrate, inhibiting the reuptake of neurotransmitters such as dopamine, serotonin, and noradrenaline. It also exhibits affinity for adrenergic and serotonin receptors, which might influence its stimulant and psychoactive properties. Users often compare its effects to MDMA and mephedrone, noting a similar but less intense experience. Recreational use typically involves oral ingestion, nasal insufflation, or intravenous injection, with dosages ranging from 25 mg to over 300 mg, though higher doses are sometimes reported. Despite its popularity, evidence on the safety profile and risk of 3-MMC, particularly at low to moderate doses, remains scarce.
Adverse effects of synthetic cathinones are primarily documented in case studies and include cardiovascular symptoms, such as elevated heart rate and blood pressure, along with psychological effects like agitation and psychomotor impairment. In rare instances, fatalities have been reported, often involving high doses or co-ingestion with other substances. This study aims to address the knowledge gap by assessing the safety and cognitive pharmacodynamics of 3-MMC at doses commonly used recreationally.
Methods
Participants
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https://doi.org/10.1101/2024.11.12.24317168
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Cite this paper (APA)
Ramaekers, J., Reckweg, J. T., Mason, N. L., Kuypers, K. P., Toennes, S. W., & Theunissen, E. L. (2024). Safety and cognitive pharmacodynamics following dose escalations with 3-methylmethcathinone (3-MMC): a first in human, designer drug study. medRxiv, 2024-11.
Study details
Topics studied
Safety
Healthy Subjects
Study characteristics
Original
Placebo-Controlled
Double-Blind
Within-Subject
Randomized
Participants
14
Humans
Institutes
Institutes associated with this publication
Maastricht UniversityMaastricht University is host to the psychopharmacology department (Psychopharmacology in Maastricht) where various researchers are investigating the effects of psychedelics.