5F-ADB/5F-MDMB-PINACA

Substance identification
Chemically, 5F-ADB (also known as 5F-MDMB-PINACA) is methyl (2S)-2- {[1-(5-fluoropentyl)-1H-indazole-3-carbonyl]amino}-3,3-dimethylbutanoate. 5F-ADB contains a chiral centre at the C-2 carbon of the oxobutan-2-yl side chain, so that two enantiomers exist: (R)-5F-ADB and (S)-5F-ADB.

Previous review
5F-ADB has not been previously pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to WHO’s attention that 5F-ADB is clandestinely manufactured, of especially serious risk to public health and society, and of 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.

17 Similarity to known substances and effects on the central nervous system 5F-ADB is a synthetic cannabinoid receptor agonist. It has an indazole core, which is a common structural feature in a number of the SCRAs. 5F-ADB has potent binding affinity for the CB1 receptor, and a greater potency than THC and MDMB-CHMICA, both of which are listed as Schedule II substances in the UN Convention on Psychotropic Substances 1971. 5F-ADB significantly increases the spontaneous firing rate of dopaminergic neurons, an effect that is blocked when the CB1 antagonist AM251 is present, indicating a CB1 receptor-mediated increase in dopaminergic activity.

5F-ADB appears to have similar effects to other SCRA substances in the individual user. In 2016, 35 cases of acute intoxication of people with confirmed exposure to 5F-ADB were reported to the EMCDDA. In five additional published cases of nonfatal intoxication, in which 5F-ADB was analytically confirmed, central nervous system effects including psychomotor agitation, confusion, altered consciousness, vomiting, headache, dizziness, dilated pupils, acute psychosis and anxiety were observed.

Dependence potential
No controlled, experimental studies directly pertinent to the dependence potential of 5F-ADB in either laboratory animals or human subjects are available.

Actual abuse and/or evidence of likelihood of abuse
Similar to other SCRAs, 5F-ADB is found as a constituent in herbal mixtures that are sold under a variety of product names as legal alternatives to cannabis. The most common way of using it is by smoking or vaping through an e-cigarette.

5F-ADB has been widely available on the European market since 2014. The compound has been seized in the form of powder, herbal material, liquids and blotters. More than 1700 seizures have been reported in Europe alone. 5F-ADB seizures have also been reported from Indonesia, Japan, Kazakhstan, the Russian Federation and Ukraine.

Thirty-five cases of acute intoxication and 28 deaths were reported to the EMCDDA following confirmed exposure to 5F-ADB, either alone or in combination with other substances. In at least 20 of the 28 deaths, 5F-ADB was either the cause of death or contributed to death. Cases of impaired driving and deaths involving 5F-ADB have also been reported from Japan.

Therapeutic usefulness
5F-ADB has no approved medical or veterinary use.

Recommendation
5F-ADB is a synthetic cannabinoid receptor agonist. It has cannabimimetic effects that are more potent than those of THC and MDMB-CHMICA, which are listed as Schedule II substances in accordance with the Convention on Psychotropic Substances of 1971. Its mode of action suggests the potential for dependence and likelihood of abuse. There is evidence of an increase in the number of people using 5F-ADB in many countries and fatal and nonfatal intoxication has resulted. This substance causes substantial harm and has no therapeutic usefulness. The Committee recommended that 5F-ADB, also known as 5F-MDMB-PINACA (Methyl (2S)-2-{[1-(5-fluoropentyl)-1H-indazole-3-carbonyl]amino}-3,3- dimethylbutanoate) be placed in Schedule II under the UN Convention on Psychotropic Substances of 1971.