CUMYL-4CN-BINACA

Substance identification
CUMYL-4CN-BINACA (1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H- indazole-3-carboxamide) is a synthetic cannabinoid. It is available as a powder, in solution or sprayed on plant material that mimics the appearance of cannabis. It is sold as herbal incense or branded products under a variety of different names.

WHO review history
CUMYL-4CN-BINACA has not been previously pre-reviewed or critically reviewed by the WHO ECDD. A critical review was proposed based on information brought to WHO’s attention that CUMYL-4CN-BINACA poses serious risk to public health and has no recognized therapeutic use.

Similarity to known substances and effects on the central nervous system
CUMYL-4CN-BINACA is similar to other synthetic cannabinoid receptor agonists that are currently scheduled under the Convention on Psychotropic Substances of 1971. It binds to both the CB1 and CB2 cannabinoid receptors with full agonist activity as demonstrated by in vitro studies. The efficacy and potency of CUMYL-4CN-BINACA is substantially greater than that of Δ9-THC and it shares a profile of central nervous system-mediated effects with other synthetic cannabinoids. Data have shown that it produced hypothermia in mice in common with other CB1 cannabinoid receptor agonists.

Dependence potential
No controlled experimental studies examining the dependence potential of CUMYL-4CN-BINACA in humans or animals were available. However, based on its central nervous system action as a full CB1 agonist, CUMYL-4CN-BINACA would be expected to produce dependence in a manner similar to or more pronounced than cannabis.

Actual abuse and/or evidence of likelihood of abuse
Consistent with its CB1 cannabinoid receptor agonist activity, CUMYL-4CN- BINACA fully substituted for Δ9-THC in drug discrimination tests. This suggests that it has abuse potential similar to that of Δ9-THC.

Currently, use of CUMYL-4CN-BINACA has been reported only from Europe, but this may be due to underreporting including through lack of detection in other countries. In Europe, CUMYL-4CN-BINACA has been among the most frequently seized synthetic cannabinoids. It is smoked (as preparations of drug components introduced onto plant material) or vaped (i.e. using an e-cigarette) but owing to the nature of synthetic cannabinoid products, users cannot tell which synthetic cannabinoid is contained within such products.

A number of cases of non-fatal intoxication involving CUMYL-4CN- BINACA have been reported. CUMYL-4CN-BINACA has been analytically confirmed as being present in samples from 11 fatalities and five non-fatal intoxications in Europe. In two cases of fatal intoxication, CUMYL-4CN- BINACA was the only drug present.

Therapeutic usefulness
CUMYL-4CN-BINACA is not known to have any therapeutic use.

Recommendation
CUMYL-4CN-BINACA is a synthetic cannabinoid receptor agonist that is used by smoking plant material sprayed with the substance or inhaling vapour after heating. It has effects that are similar to those of other synthetic cannabinoid receptor agonists placed in Schedule II of the Convention on Psychotropic Substances of 1971. Its mode of action suggests the potential for dependence and the likelihood of abuse. There is evidence that CUMYL-4CN-BINACA has been associated with fatal and non-fatal intoxications in a number of countries. The substance causes substantial harm and has no therapeutic use.

■■ Recommendation: The Committee recommended that CUMYL- 4CN-BINACA (1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H-in- dazole-3-carboxamide) be added to Schedule II of the Convention on Psychotropic Substances of 1971.