IUPAC Name
(RS)-2-methylamino-1-(4-methylphenyl)propan-1-one
Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Mephedrone (4-methylmethcathinone, 4-MMC) is chemically (R,S)-2-(methyl- amino)-1-(4-methylphenyl)propan-1-one.
Previous review
Mephedrone had not been previously pre-reviewed or critically reviewed by the Committee. A direct critical review was proposed based on information brought to WHO’s attention that mephedrone is clandestinely manufactured, poses an especially serious risk to public health and society, and has no recognized therapeutic use by any party. Preliminary data collected from the literature and from different countries indicated that this substance may cause substantial harm. Furthermore, a notification to the Secretary-General had been made by the United Kingdom of Great Britain and Northern Ireland concerning a proposed recommendation for international control of mephedrone (4-methylmethcathinone), under Article 2, paragraphs 1 and 3 of the Convention on Psychotropic Substances, 1971.
Similarity to known substances and effects on the central nervous system
Mephedrone is a ring-substituted analogue of methcathinone. Key features related to the mechanisms of action are comparable with psychostimulants and medicinal products that target the monoaminergic system. In vitro studies indicate that mephedrone may act as a non-selective substrate at transporters of serotonin, dopamine and norepinephrine, similar to MDMA. Although its catecholamine-related properties appear to be less pronounced than those observed with methamphetamine, the behavioural profile of mephedrone was observed overall to be comparable with amphetamine-type psychostimulants. Mephedrone appears to show a profile with abuse liability. Adverse effects reported in connection with mephedrone use pointed towards the observation of a psychostimulant-type toxidrome and include tachycardia, hypertension, agitation, paranoia, hallucinations and insomnia. Non-fatal and fatal intoxications involving mephedrone have been reported.
Dependence potential
No detailed clinical studies in humans are available. Reports obtained from surveys and casework indicated that mephedrone consumption might be associated with the potential to produce cravings and dependence. Further studies are warranted to elucidate the psychological or physical mechanisms of dependence.
Actual abuse and/or evidence of likelihood of abuse
Self-administration studies in animals indicated a propensity for self- administration and abuse liability. In humans, mephedrone use was reported to show psychostimulant-like effects and an association with binge use (i.e. repeated use of the drug within a short period of time) was noted. In a WHO survey, 21 Member States confirmed recreational/harmful use of mephedrone.
Therapeutic usefulness
Mephedrone has no recorded therapeutic applications or medical use.
Recommendation
The Committee considered that the degree of risk to public health and society associated with the abuse liability of mephedrone is substantial. Therapeutic usefulness has not been recorded. The Committee considered that the evidence of its abuse warranted its placement under international control. As per the Guidance on the WHO review of psychoactive substances for international control (4), higher regard was accorded to the substantial public health risk than to the lack of therapeutic usefulness.1 The Committee recommended that mephedrone be placed in Schedule II of the 1971 Convention.
Mephedrone (4-methylmethcathinone, 4-MMC) is chemically (R,S)-2-(methyl- amino)-1-(4-methylphenyl)propan-1-one.
Previous review
Mephedrone had not been previously pre-reviewed or critically reviewed by the Committee. A direct critical review was proposed based on information brought to WHO’s attention that mephedrone is clandestinely manufactured, poses an especially serious risk to public health and society, and has no recognized therapeutic use by any party. Preliminary data collected from the literature and from different countries indicated that this substance may cause substantial harm. Furthermore, a notification to the Secretary-General had been made by the United Kingdom of Great Britain and Northern Ireland concerning a proposed recommendation for international control of mephedrone (4-methylmethcathinone), under Article 2, paragraphs 1 and 3 of the Convention on Psychotropic Substances, 1971.
Similarity to known substances and effects on the central nervous system
Mephedrone is a ring-substituted analogue of methcathinone. Key features related to the mechanisms of action are comparable with psychostimulants and medicinal products that target the monoaminergic system. In vitro studies indicate that mephedrone may act as a non-selective substrate at transporters of serotonin, dopamine and norepinephrine, similar to MDMA. Although its catecholamine-related properties appear to be less pronounced than those observed with methamphetamine, the behavioural profile of mephedrone was observed overall to be comparable with amphetamine-type psychostimulants. Mephedrone appears to show a profile with abuse liability. Adverse effects reported in connection with mephedrone use pointed towards the observation of a psychostimulant-type toxidrome and include tachycardia, hypertension, agitation, paranoia, hallucinations and insomnia. Non-fatal and fatal intoxications involving mephedrone have been reported.
Dependence potential
No detailed clinical studies in humans are available. Reports obtained from surveys and casework indicated that mephedrone consumption might be associated with the potential to produce cravings and dependence. Further studies are warranted to elucidate the psychological or physical mechanisms of dependence.
Actual abuse and/or evidence of likelihood of abuse
Self-administration studies in animals indicated a propensity for self- administration and abuse liability. In humans, mephedrone use was reported to show psychostimulant-like effects and an association with binge use (i.e. repeated use of the drug within a short period of time) was noted. In a WHO survey, 21 Member States confirmed recreational/harmful use of mephedrone.
Therapeutic usefulness
Mephedrone has no recorded therapeutic applications or medical use.
Recommendation
The Committee considered that the degree of risk to public health and society associated with the abuse liability of mephedrone is substantial. Therapeutic usefulness has not been recorded. The Committee considered that the evidence of its abuse warranted its placement under international control. As per the Guidance on the WHO review of psychoactive substances for international control (4), higher regard was accorded to the substantial public health risk than to the lack of therapeutic usefulness.1 The Committee recommended that mephedrone be placed in Schedule II of the 1971 Convention.
ECDD Recommendation
Inclusion in Schedule II of the 1971 Convention on Psychotropic Substances
Link to full TRS
who_trs_991_eng.pdf1.3 MB
MS Questionnaire Report