First human study sheds light on the cognitive and physiological effects of 3-MMC

A new study published in Neuropsychopharmacology suggests that low to moderate doses of a synthetic substance known as 3-methylmethcathinone (3-MMC) produce mild stimulant effects without serious health consequences in healthy adults. Participants reported increases in feelings of being high, showed improvements in performance on several cognitive tasks, and experienced small changes in heart rate and blood pressure that did not pose medical concerns. The findings provide a first glimpse into how this designer compound behaves in the human body when taken at quantities that recreational users often report.

3-MMC is a synthetic compound that is part of the cathinone family of stimulants. Cathinones occur naturally in the leaves of the khat plant, but chemists have created many versions of these compounds in laboratories. 3-MMC is one of the newer varieties that have appeared on the market in the last decade. Some people use it for its energizing qualities, reporting effects such as increased alertness and a sense of euphoria.

Cathinones as a whole have attracted attention because they have been sold online and in certain retail shops, often before being controlled by law. While pharmaceutical drugs must go through many safety tests before they are approved, these synthetic cathinones often appear first in unregulated products. This creates a large gap in knowledge about their short-term and long-term effects on the body. In the case of 3-MMC, only hospital case reports existed until recently, and these mostly involved individuals who had taken high doses or combined the compound with other substances.

The new study was needed to provide a clearer picture of how 3-MMC behaves when taken by adults who do not use extremely large amounts. Without this sort of research, public health officials and medical providers must rely on emergency room data or anecdotal user experiences, which can be misleading. Studies that give volunteers controlled amounts of a substance under medical supervision can help experts better understand its safety, the kind of effects it produces, and any changes in cognitive function or mood.

“At present, there are more novel psychoactive compounds coming out of clandestine lab than out of pipelines of pharmaceutical industries,” said study author Johannes G. Ramaekers, a professor of psychopharmacology at Maastricht University. “While compounds of the latter are carefully screened for safety and efficacy prior to market release, the former are not. Hence there is an incredible lack of basic scientific knowledge on safety, pharmacokinetics and pharmacodynamics of novel psychoactive substances (NPS) or designer drugs, such as 3-MMC.”

To carry out their study, the team recruited 14 healthy adults, of whom 12 completed every session. Participants included both men and women and ranged from 19 to 35 years of age. All had some past experience with stimulant drugs, such as 3,4-methylenedioxymethamphetamine (MDMA) or amphetamine. During four separate visits, each participant received either a placebo or an oral dose of 25, 50, or 100 milligrams of 3-MMC in a staggered schedule.

The sessions took place at least a week apart to avoid leftover effects from one session carrying over into the next. While in the lab, participants completed repeated checks of their blood pressure, heart rate, body temperature, and cognitive performance for up to five hours after ingesting the substance. They also answered questions about whether they felt any changes in their sense of reality and whether they felt hungry, enjoyed the effects of the compound, or wanted more of it.

The findings showed that 3-MMC led to clear, dose-related increases in heart rate and blood pressure, though the measurements stayed in the normal range. At 25 milligrams and 50 milligrams, the effect on vital signs remained minor, with slightly bigger changes observed at 100 milligrams. Participants reported that they felt high, but that feeling was brief and returned to normal as the chemical wore off, usually within a few hours.

This suggests that “low to moderate dose of 3-MMC are safe to use and produce stimulatory effects,” Ramaekers told PsyPost. “High, excessive doses should be avoided though.”

The participants also completed tests of memory, attention, reaction time, and mental flexibility. Performance actually improved on many of these tasks, an outcome that reflects the stimulating impact of the compound on alertness and speed of thought. The improvement was especially noticeable on tests that involved tracking a moving target or quickly matching symbols and digits. Interestingly, there was no evidence of reduced self-control on tasks that measure impulsive actions, which other substances can sometimes amplify.

Beyond these enhancements, participants reported mild shifts in perception. They scored slightly higher on questionnaires that measure sensations related to dissociation or dream-like states, but the levels were far below what one might see with classic hallucinogens. Reports of unwanted effects, such as aches or fatigue, were rare and not alarming.

At the highest dose, participants gave stronger ratings of enjoyment and a desire to take the drug again, while also experiencing a temporary drop in appetite. That pattern points to the possibility that higher doses could encourage repetitive use, although it remains unclear whether individuals might seek to keep taking more over a short time frame.

“I was particularly struck by the very clean dose-effect relations that were found across a broad range of cognitive and neurophysiological measures,” Ramaekers said. “Though it was expected, it does not always turn out this nicely.”

The researchers acknowledged some limitations to their study. The number of participants was relatively small, which might limit the ability to generalize these findings to a broader population. Additionally, the study only examined the effects of a single dose of 3-MMC. Future research should investigate the effects of repeated doses to understand the safety profile of the drug when used more frequently, as is common in recreational settings. Longer studies are also needed to fully understand how the body processes and eliminates 3-MMC over an extended period.

“The present study focuses on single doses,” Ramaekers noted. “We still need to established safety after repeated doses.”

Looking ahead, the researchers are interested in exploring whether 3-MMC, at these low and seemingly safe doses, might have potential benefits, such as pain relief.

“Cathinones have previously been demonstrated to possess analgesic potential at full doses,” Ramaekers explained. “It would be interesting to explore whether 3-MMC at low doses that are safe and do not induce a challenging subjective experience hold analgesic potential as well.”

The study, “Safety and cognitive pharmacodynamics following dose escalations with 3-methylmethcathinone (3-MMC): a first in human, designer drug study,” was authored by Johannes G. Ramaekers, Johannes T. Reckweg, Natasha L. Mason, Kim P. C. Kuypers, Stefan W. Toennes, and Eef L. Theunissen.