Alternative names
4-MEC
IUPAC Name
2-(Ethylamino)-1-(4-methylphenyl)propan-1-one
Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Chemically, 4-methylethcathinone (4-MEC) is 2-(ethylamino)-1-(4- methylphenyl)propan-1-one. 4-MEC has a chiral centre giving rise to an enantiomeric pair of (S)-4-MEC and (R)-4-MEC isomers.
Previous review
A critical review report on 4-MEC was discussed in June 2014 at the thirty- sixth meeting of the WHO ECDD. The Committee recommended that 4-MEC not be placed under international control at that time due to insufficiency of data regarding dependence, abuse and risks to public health, but be kept under surveillance. 4-MEC continues to appear as a psychostimulant with monoamine transporter activity with indications of abuse liability. New data that had emerged from in vitro and in vivo studies since the thirty-sixth ECDD meeting prompted the current critical review.
Similarity to known substances and effects on the central nervous system
4-MEC has a homologue, mephedrone (4-methylmethcathinone), which is listed as a Schedule II substance under the 1971 United Nations Convention on Psychotropic Substances. Similar to controlled psychostimulants, 4-MEC elevates extracellular neurotransmitter levels, most notably, dopamine, norepinephrine (noradrenaline) and serotonin. Also, in rodents, 4-MEC increases locomotor activity and produces sensitization, fully substitutes for the discriminative stimulus effects of cocaine and (in one of two reports) also of methamphetamine, establishes conditioned place preference, and reduces thresholds of intracranial self-stimulation. User reports of negative effects associated with 4-MEC mention excessive sweating, nausea, vomiting, jaw clenching, heart palpitations, loss of sight and migraine. The number of case reports that demonstrate a causal relationship between 4-MEC consumption and fatal intoxication is limited. This profile is consistent with amphetamine-like effects and it is likely that 4-MEC would produce adverse effects consistent with those associated with amphetamine.
Dependence potential
No controlled laboratory studies of the dependence potential of 4-MEC in animal or human subjects have been reported. Urge to re-dose when using 4-MEC was considered weak and short-lived with low incidence of negative after-effects (compared to mephedrone), although users with a history of synthetic cathinone use and less potent experiences with 4-MEC reported higher and more frequent dosing.
Actual abuse and/or evidence of likelihood of abuse
The ability of 4-MEC to occasion the discriminative stimulus effects of cocaine, and at least in one study, methamphetamine, suggests the ability to produce their subjective effects and associated abuse potential. 4-MEC’s ability to induce conditioned place preference and reduce intracranial self-stimulation thresholds, and to increase locomotor activity and produce sensitization to it, is consistent with this prediction. Controlled studies on the abuse potential of 4-MEC have not been conducted in humans. 4-MEC has been detected worldwide and is marketed as a "research chemical"; it has also been detected as a constituent in branded products available for purchase via the Internet and from brick-and- mortar shops. Responses to the UNODC questionnaire on NPS (up to 2012) revealed that 4-MEC was ranked fourth with regard to numbers of reports received. User reports suggest that 4 MEC produces euphoria, a sense of well- being and psychostimulant effects. A survey of a group of injecting drug users of NPS reported that 4-MEC was injected more often per day compared to what might be expected from heroin use. A number of countries in various regions have placed 4-MEC under national control.
Therapeutic usefulness
There are no known approved therapeutic applications for 4-MEC.
Recommendation
The Committee considered that the degree of risk to public health and society associated with the abuse of 4-MEC (2-(ethylamino)-1-(4-methylphenyl)propan- 1-one) is substantial. Therapeutic usefulness has not been recorded. It recognized that 4-MEC has similar abuse and similar ill-effects to substances in Schedule II of the UN Convention on Psychotropic Substances of 1971. The Committee considered that there is sufficient evidence that 4-MEC is being or is likely to be abused so as to constitute a public health and social problem warranting the placing of the substance under international control. As per the Guidance on the WHO review of psychoactive substances for international control (2), higher regard was accorded to the substantial public health risk than to the lack of therapeutic usefulness. The Committee recommended that 4-MEC be placed in Schedule II of the UN Convention on Psychotropic Substances of 1971.
Chemically, 4-methylethcathinone (4-MEC) is 2-(ethylamino)-1-(4- methylphenyl)propan-1-one. 4-MEC has a chiral centre giving rise to an enantiomeric pair of (S)-4-MEC and (R)-4-MEC isomers.
Previous review
A critical review report on 4-MEC was discussed in June 2014 at the thirty- sixth meeting of the WHO ECDD. The Committee recommended that 4-MEC not be placed under international control at that time due to insufficiency of data regarding dependence, abuse and risks to public health, but be kept under surveillance. 4-MEC continues to appear as a psychostimulant with monoamine transporter activity with indications of abuse liability. New data that had emerged from in vitro and in vivo studies since the thirty-sixth ECDD meeting prompted the current critical review.
Similarity to known substances and effects on the central nervous system
4-MEC has a homologue, mephedrone (4-methylmethcathinone), which is listed as a Schedule II substance under the 1971 United Nations Convention on Psychotropic Substances. Similar to controlled psychostimulants, 4-MEC elevates extracellular neurotransmitter levels, most notably, dopamine, norepinephrine (noradrenaline) and serotonin. Also, in rodents, 4-MEC increases locomotor activity and produces sensitization, fully substitutes for the discriminative stimulus effects of cocaine and (in one of two reports) also of methamphetamine, establishes conditioned place preference, and reduces thresholds of intracranial self-stimulation. User reports of negative effects associated with 4-MEC mention excessive sweating, nausea, vomiting, jaw clenching, heart palpitations, loss of sight and migraine. The number of case reports that demonstrate a causal relationship between 4-MEC consumption and fatal intoxication is limited. This profile is consistent with amphetamine-like effects and it is likely that 4-MEC would produce adverse effects consistent with those associated with amphetamine.
Dependence potential
No controlled laboratory studies of the dependence potential of 4-MEC in animal or human subjects have been reported. Urge to re-dose when using 4-MEC was considered weak and short-lived with low incidence of negative after-effects (compared to mephedrone), although users with a history of synthetic cathinone use and less potent experiences with 4-MEC reported higher and more frequent dosing.
Actual abuse and/or evidence of likelihood of abuse
The ability of 4-MEC to occasion the discriminative stimulus effects of cocaine, and at least in one study, methamphetamine, suggests the ability to produce their subjective effects and associated abuse potential. 4-MEC’s ability to induce conditioned place preference and reduce intracranial self-stimulation thresholds, and to increase locomotor activity and produce sensitization to it, is consistent with this prediction. Controlled studies on the abuse potential of 4-MEC have not been conducted in humans. 4-MEC has been detected worldwide and is marketed as a "research chemical"; it has also been detected as a constituent in branded products available for purchase via the Internet and from brick-and- mortar shops. Responses to the UNODC questionnaire on NPS (up to 2012) revealed that 4-MEC was ranked fourth with regard to numbers of reports received. User reports suggest that 4 MEC produces euphoria, a sense of well- being and psychostimulant effects. A survey of a group of injecting drug users of NPS reported that 4-MEC was injected more often per day compared to what might be expected from heroin use. A number of countries in various regions have placed 4-MEC under national control.
Therapeutic usefulness
There are no known approved therapeutic applications for 4-MEC.
Recommendation
The Committee considered that the degree of risk to public health and society associated with the abuse of 4-MEC (2-(ethylamino)-1-(4-methylphenyl)propan- 1-one) is substantial. Therapeutic usefulness has not been recorded. It recognized that 4-MEC has similar abuse and similar ill-effects to substances in Schedule II of the UN Convention on Psychotropic Substances of 1971. The Committee considered that there is sufficient evidence that 4-MEC is being or is likely to be abused so as to constitute a public health and social problem warranting the placing of the substance under international control. As per the Guidance on the WHO review of psychoactive substances for international control (2), higher regard was accorded to the substantial public health risk than to the lack of therapeutic usefulness. The Committee recommended that 4-MEC be placed in Schedule II of the UN Convention on Psychotropic Substances of 1971.
ECDD Recommendation
Inclusion in Schedule II of the 1971 Convention on Psychotropic Substances
Link to full TRS
9789241210140-eng.pdf426.09 KB
MS Questionnaire Report