APINACA

Substance identification
APINACA (N-(adamantan-1-yl)-1-pentyl-1H-indazole-3-carboxamide), also known as AKB-48, is a synthetic cannabinoid. It has been found as a white powder, in solution or sprayed on plant material.

WHO review history
APINACA (AKB-48) was reviewed at the 36th meeting of WHO Expert Committee on Drug Dependence and has been under surveillance by WHO since that time. The present critical review updates the previous review.

Similarity to known substances and effects on the central nervous system
APINACA binds as a full agonist to CB1 and CB2 cannabinoid receptors. It shares similar molecular mechanisms and functional properties with other synthetic cannabinoid receptor agonists that are currently controlled under the Convention on Psychotropic Substances of 1971.

In preclinical studies in mice, APINACA produced neurological signs, including convulsions, hyperreflexia, myoclonus and aggression.

No information was available in either controlled studies or case reports on the effects of APINACA on the human central nervous system.

Dependence potential
No controlled experimental studies on the dependence potential of APINACA in either human subjects or laboratory animals are available. In view of its action on the central nervous system as a full CB1 agonist, APINACA would be expected to produce dependence in a manner similar to other synthetic cannabinoids.

Actual abuse and/or evidence of likelihood of abuse
In drug discrimination tests in animals predictive of subjective effects in humans, APINACA shows typical cannabinoid-like effects and would therefore be likely to be abused. APINACA also stimulates dopamine release in the nucleus accumbens in mice, suggesting that its abuse potential is similar to that of other psychoactive cannabinoids.

Use of APINACA has been reported from five regions and 20 countries since 2015. It has been identified in seized materials and has been detected in the blood of impaired drivers. Data on seized material, however, indicates that use of APINACA has decreased in a number of countries.

Therapeutic usefulness
APINACA is not known to have any therapeutic use.

Recommendation
APINACA (N-(adamantan-1-yl)-1-pentyl-1H-indazole-3-carboxamide; also known as AKB-48) is a synthetic cannabinoid receptor agonist. While it may potentially have effects that are similar to those of other synthetic cannabinoids, information on its effects in humans is currently lacking. The magnitude of the public health problem associated with use of APINACA may not be great as the use of this substance has declined.

■ Recommendation: The Committee recommended that APINACA (N-(adamantan-1-yl)-1-pentyl-1H-indazole-3-carboxamide) be kept under surveillance.