AB-CHMINACA

Substance identification
Chemically, AB-CHMINACA is N-[(2S)-1-Amino-3-methyl-1-oxobutan-2-yl]- 1-(cyclohexylmethyl)-1H-indazole-3-carboxamide. AB-CHMINACA contains a chiral centre at the C-2 carbon of the oxobutan-2-yl side chain, so that two enantiomers exist: (R)-AB-CHMINACA and (S)-AB-CHMINACA. Based on the literature and the most likely precursors to be used, an (S)-configuration of the stereocentre should be expected.

Previous review
AB-CHMINACA has not been previously pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to WHO’s attention that AB-CHMINACA is clandestinely manufactured, poses serious risk to public health and society, and has no recognized therapeutic use by any Party. Preliminary information collected from various sources indicated that this substance may cause substantial harm and that it has no medical use.

Similarity to known substances and effects on the central nervous system
AB-CHMINACA binds to the cannabinoid CB1 receptor and demonstrates in vitro functional agonist activity at the receptor site. It demonstrates activity in all four components of the cannabinoid tetrad assay in mice (activity, catalepsy, hypothermia and analgesia). Across these four components, AB-CHMINACA is 11- to 58-fold more potent than tetrahydrocannabinol (THC) itself. These effects of AB-CHMINACA can be antagonized by the cannabinoid CB1 receptor antagonist, rimonabant. Users of AB-CHMINACA report cannabimimetic effects after smoking the drug. AB-CHMINACA is not readily converted into other internationally controlled substances.

Dependence potential
No controlled, experimental studies examining the dependence potential of AB- CHMINACA in human subjects or laboratory animals were available.

Actual abuse and/or evidence of likelihood of abuse
AB-CHMINACA produces complete, dose-dependent substitution for the discriminative stimulus effects of THC in mice, and is 16 times more potent than THC in this respect, suggesting that it can produce at least some of the subjective and abuse potential effects of synthetic cannabinoid receptor agonists (SCRAs).

AB-CHMINACA is sold and used as a "legal" substitute for cannabis. It is most commonly smoked, or vaped through an e-cigarette. Between 2014 and 2016, seven acute cases of intoxication of people with confirmed exposure to AB-CHMINACA were reported to the EMCDDA. Where details were provided, the clinical features of the poisoning were typical of those reported for SCRAs. Effects of AB-CHMINACA are consistent with those of SCRAs. They include relaxation, euphoria, lethargy, depersonalization, distorted perception of time, impaired motor performance, hallucinations, paranoia, confusion, fear, anxiety, dry mouth, conjunctival injection ("red eyes"), tachycardia, and nausea and vomiting. During a period of less than two weeks in which there was an outbreak of SCRA usage in Florida, the presence of AB-CHMINACA or one of its predicted metabolites, was confirmed in 15 of 21 cases. Some of the patients had acute delirium and seizures. Between 2014 and 2017 a total of 31 deaths of people with confirmed exposure to AB-CHMINACA were reported to the EMCDDA. In at least seven cases, AB-CHMINACA was the cause of death or contributed to the death. In a recent fatal case, in which it was the predominant SCRA present, use of AB-CHMINACA was associated with non-cardiogenic pulmonary oedema.

AB-CHMINACA has also been associated with several instances of impaired driving reported from Hungary, Japan and the United States of America (USA). For instance, in the USA in 2014, AB-CHMINACA was detected in 33 out of 58 people stopped for impaired driving who had tested positive for SCRAs. In recognition of its abuse and associated harm, AB-CHMINACA has been placed under national control in a number of countries in several different regions.

Therapeutic usefulness
There are currently no approved medical or veterinary uses of AB-CHMINACA.

Recommendation
AB-CHMINACA is a synthetic cannabinoid receptor agonist. It is clandestinely manufactured and sold under a variety of brand names. It has cannabimimetic effects that are more potent than those of THC, which is listed as a Schedule II substance in accordance with the Convention on Psychotropic Substances of 1971. Its mode of action suggests the potential for dependence and likelihood of misuse. There is evidence of an increase in the number of people using AB- CHMINACA in many countries and of fatal and nonfatal cases. This substance causes substantial harm and has no therapeutic usefulness. AB-CHMINACA shows similar abuse and similar ill effects to other SCRAs already scheduled in Schedule II of the 1971 Convention. The Committee recommended that AB-CHMINACA (N-[(2S)-1-Amino-3-methyl-1-oxobutan-2-yl]-1- (cyclohexylmethyl)-1H-indazole-3-carboxamide) be placed in Schedule II under the UN Convention on Psychotropic Substances of 1971.