Alternative names
α-methylaminovalerophenone
IUPAC Name
(±)-2-(methylamino)-1-phenylpentan-1-one
Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Chemically, pentedrone is 2-(methylamino)-1-phenylpentan-1-one. It has a chiral centre giving rise to two stereoisomers, (S)- and (R)-pentedrone.
Previous review
Pentedrone has 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 pentedrone is clandestinely manufactured, poses a serious risk to public health and society, and has no recognized therapeutic use by any Party.
Similarity to known substances and effects on the central nervous system
Pentedrone is a substituted phenethylamine derivative that belongs to the class of cathinones, many of which are controlled under the Convention on Psychotropic Substances of 1971. It is unlikely that pentedrone could easily be converted into an existing controlled substance. Pentedrone binds to the dopamine and to the noradrenergic transporters and inhibits dopamine and noradrenergic uptake, but binds poorly to the serotonergic transporter and does not meaningfully inhibit serotonergic uptake. It induces climbing behaviour, increases locomotor activity and produces conditioned place preference in mice, and maintains intravenous self-administration in rats. These in vitro and in vivo effects are consistent with a profile similar to an abused stimulant such as methamphetamine. Importantly, it generalizes to cocaine and to methamphetamine in rat discrimination tests, suggesting that it can produce their subjective effects and has an abuse liability similar to these drugs. Non-fatal intoxications have been reported, and pentedrone has been associated with several DUID cases, although typically accompanied by other drugs. Responses to the WHO questionnaire for review of psychoactive substances for the thirty-eighth meeting of the ECDD indicated that the adverse effects experienced by people who present with pentedrone intoxication at emergency departments include impaired consciousness, tachycardia, hypotension, nausea, vertigo, hallucinations, high body temperature and sweating. Users of pentedrone report MDMA-like stimulating effects, such as euphoria, openness and increased sociability and sexual drive.
Pentedrone has been associated with at least six fatalities, although other drugs were present in each case.
Dependence potential
No controlled studies in humans or laboratory animals regarding the potential physical dependence effects of pentedrone have been reported.
Actual abuse and/or evidence of likelihood of abuse
Pentedrone has been detected in commercial products or in biosamples in Canada, several European countries and in the United States. Hundreds of kilograms of pentedrone have been seized in the European Union alone. User reports indicate that pentedrone is administered via the oral, insufflation, inhalation and intravenous routes. Several countries in different regions have placed pentedrone under national control.
Therapeutic usefulness
No therapeutic or medical use has been described for pentedrone.
Recommendation
The Committee considered that the degree of risk to public health and society associated with the abuse of pentedrone (2-(methylamino)-1-phenylpentan-1- one) is substantial. Therapeutic usefulness has not been recorded. It recognized that pentedrone 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 pentedrone 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 pentedrone be placed in Schedule II of the UN Convention on Psychotropic Substances of 1971.
Chemically, pentedrone is 2-(methylamino)-1-phenylpentan-1-one. It has a chiral centre giving rise to two stereoisomers, (S)- and (R)-pentedrone.
Previous review
Pentedrone has 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 pentedrone is clandestinely manufactured, poses a serious risk to public health and society, and has no recognized therapeutic use by any Party.
Similarity to known substances and effects on the central nervous system
Pentedrone is a substituted phenethylamine derivative that belongs to the class of cathinones, many of which are controlled under the Convention on Psychotropic Substances of 1971. It is unlikely that pentedrone could easily be converted into an existing controlled substance. Pentedrone binds to the dopamine and to the noradrenergic transporters and inhibits dopamine and noradrenergic uptake, but binds poorly to the serotonergic transporter and does not meaningfully inhibit serotonergic uptake. It induces climbing behaviour, increases locomotor activity and produces conditioned place preference in mice, and maintains intravenous self-administration in rats. These in vitro and in vivo effects are consistent with a profile similar to an abused stimulant such as methamphetamine. Importantly, it generalizes to cocaine and to methamphetamine in rat discrimination tests, suggesting that it can produce their subjective effects and has an abuse liability similar to these drugs. Non-fatal intoxications have been reported, and pentedrone has been associated with several DUID cases, although typically accompanied by other drugs. Responses to the WHO questionnaire for review of psychoactive substances for the thirty-eighth meeting of the ECDD indicated that the adverse effects experienced by people who present with pentedrone intoxication at emergency departments include impaired consciousness, tachycardia, hypotension, nausea, vertigo, hallucinations, high body temperature and sweating. Users of pentedrone report MDMA-like stimulating effects, such as euphoria, openness and increased sociability and sexual drive.
Pentedrone has been associated with at least six fatalities, although other drugs were present in each case.
Dependence potential
No controlled studies in humans or laboratory animals regarding the potential physical dependence effects of pentedrone have been reported.
Actual abuse and/or evidence of likelihood of abuse
Pentedrone has been detected in commercial products or in biosamples in Canada, several European countries and in the United States. Hundreds of kilograms of pentedrone have been seized in the European Union alone. User reports indicate that pentedrone is administered via the oral, insufflation, inhalation and intravenous routes. Several countries in different regions have placed pentedrone under national control.
Therapeutic usefulness
No therapeutic or medical use has been described for pentedrone.
Recommendation
The Committee considered that the degree of risk to public health and society associated with the abuse of pentedrone (2-(methylamino)-1-phenylpentan-1- one) is substantial. Therapeutic usefulness has not been recorded. It recognized that pentedrone 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 pentedrone 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 pentedrone 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