IUPAC Name
[1-(5-Fluoropentyl)-1H-indol-3-yl](2,2,3,3-
tetramethylcyclopropyl)methanone
Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Chemically, XLR-11 is [1-(5-fluoropentyl)-1H-indol-3-yl] (2,2,3,3-tetramethylcyclopropyl)methanone.
Previous review
XLR-11 has not previously been pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to WHO’s attention that XLR-11 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
Metabolites of XLR-11 include UR-144, a compound recognized for its own abuse potential. XLR-11 binds to cannabinoid CB1 and CB2 receptors with greater affinity than THC. XLR-11 acts as a full agonist at both these receptors. XLR-11 produces all four effects in the THC tetrad test in the mouse, all components of which, except catalepsy, are antagonized by the CB1 receptor antagonist, rimonabant. Adverse effects associated with XLR-11 use include nausea, vomiting, low body temperature, rigid muscle tone, back and abdominal pain, hypertension, slurred speech, lack of convergence, and body and eyelid tremors. Of particular concern was the reported association of XLR-11 use and acute kidney injury in users who had been hospitalized. Analytically determined use of XLR-11 has been confirmed in DUID cases. Confirmed presence of XLR-11 has been associated with two deaths.
Dependence potential
No controlled studies in humans or laboratory animals regarding the potential physical dependence or tolerance effects of XLR-11 have been reported.
Actual abuse and/or evidence of likelihood of abuse
XLR-11 produces THC-like discriminative stimulus effects in mice and rats indicating that it would be able to produce THC’s subjective effects and that it is likely have a similar abuse potential. The discriminative stimulus effects of XLR- 11 are antagonized by rimonabant. XLR-11 is often sold in the form of herbal mixtures designed for smoking purposes. XLR-11 has been encountered in seizures or as an abused substance in a number of countries in different regions. XLR-11 has been placed under national control in a number of countries and different regions.
Therapeutic usefulness
There are no approved therapeutic applications for the clinical use of XLR-11.
Recommendation
The Committee considered that the degree of risk to public health and society associated with the abuse of XLR-11 ([1-(5-fluoropentyl)-1H-indol- 3-yl](2,2,3,3-tetramethylcyclopropyl)methanone) is substantial. Therapeutic usefulness has not been recorded. It recognized that XLR-11 has similar abuse and similar ill-effects to substances in Schedule II of the UN Convention on Psychotropic Substances of 1971, such as JWH-018 and AM-2201. The Committee considered that there is sufficient evidence that XLR-11 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 XLR-11 be placed in Schedule II under the UN Convention on Psychotropic Substances of 1971.
Chemically, XLR-11 is [1-(5-fluoropentyl)-1H-indol-3-yl] (2,2,3,3-tetramethylcyclopropyl)methanone.
Previous review
XLR-11 has not previously been pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to WHO’s attention that XLR-11 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
Metabolites of XLR-11 include UR-144, a compound recognized for its own abuse potential. XLR-11 binds to cannabinoid CB1 and CB2 receptors with greater affinity than THC. XLR-11 acts as a full agonist at both these receptors. XLR-11 produces all four effects in the THC tetrad test in the mouse, all components of which, except catalepsy, are antagonized by the CB1 receptor antagonist, rimonabant. Adverse effects associated with XLR-11 use include nausea, vomiting, low body temperature, rigid muscle tone, back and abdominal pain, hypertension, slurred speech, lack of convergence, and body and eyelid tremors. Of particular concern was the reported association of XLR-11 use and acute kidney injury in users who had been hospitalized. Analytically determined use of XLR-11 has been confirmed in DUID cases. Confirmed presence of XLR-11 has been associated with two deaths.
Dependence potential
No controlled studies in humans or laboratory animals regarding the potential physical dependence or tolerance effects of XLR-11 have been reported.
Actual abuse and/or evidence of likelihood of abuse
XLR-11 produces THC-like discriminative stimulus effects in mice and rats indicating that it would be able to produce THC’s subjective effects and that it is likely have a similar abuse potential. The discriminative stimulus effects of XLR- 11 are antagonized by rimonabant. XLR-11 is often sold in the form of herbal mixtures designed for smoking purposes. XLR-11 has been encountered in seizures or as an abused substance in a number of countries in different regions. XLR-11 has been placed under national control in a number of countries and different regions.
Therapeutic usefulness
There are no approved therapeutic applications for the clinical use of XLR-11.
Recommendation
The Committee considered that the degree of risk to public health and society associated with the abuse of XLR-11 ([1-(5-fluoropentyl)-1H-indol- 3-yl](2,2,3,3-tetramethylcyclopropyl)methanone) is substantial. Therapeutic usefulness has not been recorded. It recognized that XLR-11 has similar abuse and similar ill-effects to substances in Schedule II of the UN Convention on Psychotropic Substances of 1971, such as JWH-018 and AM-2201. The Committee considered that there is sufficient evidence that XLR-11 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 XLR-11 be placed in Schedule II under 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