Alternative names
5F-AKB-48
IUPAC Name
N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide
Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Chemically, 5F-APINACA is N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide.
Previous review
5F-APINACA has not been previously pre-reviewed or critically reviewed by the Committee. A direct critical review was proposed based on information brought to the attention of WHO that 5F-APINACA 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
5F-APINACA (5F-AKB-48) is an analogue of APINACA (AKB-48) fluorinated on the terminal carbon of the pentyl chain. 5F-APINACA binds to cannabinoid CB1 and CB2 receptors with greater potency than THC and activates the CB1 receptor as a full agonist. 5F APINACA induces a prolonged release of dopamine in the shell of the nucleus accumbens in awake mice. The CB1 cannabinoid receptor antagonist/inverse agonist, AM251, blocks several in vivo effects of 5F-APINACA in mice including its induced spontaneous and stimulated aggressiveness, hypothermic effects and antinociceptive effects. The in vitro binding and functional activity effects of 5F-APINACA, together with its in vivo effects of hypothermia, and cataleptic and antinociceptive effects that are blocked by AM251, are consistent with a THC-like cannabinoid compound. In contrast to THC, high doses of 5F-APINACA induce spontaneous and handling-induced convulsions, hyperreflexia and myoclonus in mice. Anxiety, paranoia, dry mouth, headache and hyperthermia have been reported by users of 5F-APINACA on blogs and forums. Recently, there have been a number of reports of non-fatal intoxications involving 5F-APINACA in several countries. Adverse events described in one analytically confirmed case report were agitation, tachycardia, hypertension, twitching and chest pain.
Dependence potential
No controlled studies in humans or laboratory animals regarding the potential of 5F-APINACA to produce physical dependence or tolerance have been reported. Users report acute physical withdrawal symptoms when attempting to reduce use, including chest pains, chest pressure, tachycardia and palpitations, lower extremity pain and spasms, nausea, sweating, diarrhoea and vomiting, which were easily resolved by resuming smoking of 5F-APINACA. Psychological withdrawal symptoms included insomnia (for more than 3 weeks), internal restlessness, urge to re-dose, anxiety, agitation and paranoia.
Following initial use of between one and four grams per day of herbal mixtures containing 5F-APINACA, users report that the amount used increases quickly. Compulsive re-dosing occurs despite recognition of loss of control, awareness of tolerance and fears about adverse effects. The development of thoughts about smoking and cravings first thing in the morning can occur rapidly following initial patterns of use of 5F-APINACA.
Actual abuse and/or evidence of likelihood of abuse
5F-APINACA is sold over the Internet. It has been detected in commercial or seized products in several countries in different regions. One country reported four DUID cases in which 5F-APINACA was detected. A number of countries are directly controlling 5F-APINACA under national legislation.
Therapeutic usefulness
There are no known approved therapeutic applications for 5F-APINACA.
Recommendation
The Committee considered that the degree of risk to public health and society associated with the abuse of 5F-APINACA (N-(adamantan-1-yl)-1- (5-fluoropentyl)-1H-indazole-3-carboxamide) is substantial. Therapeutic usefulness has not been recorded. It recognized that 5F-APINACA has similar abuse and similar ill-effects to substances in Schedule II of the UN Convention on Psychotropic Substances of 1971. The Committee considered that there is sufficient evidence that 5F-APINACA 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 5F-APINACA be placed in Schedule II under the UN Convention on Psychotropic Substances of 1971.
Chemically, 5F-APINACA is N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide.
Previous review
5F-APINACA has not been previously pre-reviewed or critically reviewed by the Committee. A direct critical review was proposed based on information brought to the attention of WHO that 5F-APINACA 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
5F-APINACA (5F-AKB-48) is an analogue of APINACA (AKB-48) fluorinated on the terminal carbon of the pentyl chain. 5F-APINACA binds to cannabinoid CB1 and CB2 receptors with greater potency than THC and activates the CB1 receptor as a full agonist. 5F APINACA induces a prolonged release of dopamine in the shell of the nucleus accumbens in awake mice. The CB1 cannabinoid receptor antagonist/inverse agonist, AM251, blocks several in vivo effects of 5F-APINACA in mice including its induced spontaneous and stimulated aggressiveness, hypothermic effects and antinociceptive effects. The in vitro binding and functional activity effects of 5F-APINACA, together with its in vivo effects of hypothermia, and cataleptic and antinociceptive effects that are blocked by AM251, are consistent with a THC-like cannabinoid compound. In contrast to THC, high doses of 5F-APINACA induce spontaneous and handling-induced convulsions, hyperreflexia and myoclonus in mice. Anxiety, paranoia, dry mouth, headache and hyperthermia have been reported by users of 5F-APINACA on blogs and forums. Recently, there have been a number of reports of non-fatal intoxications involving 5F-APINACA in several countries. Adverse events described in one analytically confirmed case report were agitation, tachycardia, hypertension, twitching and chest pain.
Dependence potential
No controlled studies in humans or laboratory animals regarding the potential of 5F-APINACA to produce physical dependence or tolerance have been reported. Users report acute physical withdrawal symptoms when attempting to reduce use, including chest pains, chest pressure, tachycardia and palpitations, lower extremity pain and spasms, nausea, sweating, diarrhoea and vomiting, which were easily resolved by resuming smoking of 5F-APINACA. Psychological withdrawal symptoms included insomnia (for more than 3 weeks), internal restlessness, urge to re-dose, anxiety, agitation and paranoia.
Following initial use of between one and four grams per day of herbal mixtures containing 5F-APINACA, users report that the amount used increases quickly. Compulsive re-dosing occurs despite recognition of loss of control, awareness of tolerance and fears about adverse effects. The development of thoughts about smoking and cravings first thing in the morning can occur rapidly following initial patterns of use of 5F-APINACA.
Actual abuse and/or evidence of likelihood of abuse
5F-APINACA is sold over the Internet. It has been detected in commercial or seized products in several countries in different regions. One country reported four DUID cases in which 5F-APINACA was detected. A number of countries are directly controlling 5F-APINACA under national legislation.
Therapeutic usefulness
There are no known approved therapeutic applications for 5F-APINACA.
Recommendation
The Committee considered that the degree of risk to public health and society associated with the abuse of 5F-APINACA (N-(adamantan-1-yl)-1- (5-fluoropentyl)-1H-indazole-3-carboxamide) is substantial. Therapeutic usefulness has not been recorded. It recognized that 5F-APINACA has similar abuse and similar ill-effects to substances in Schedule II of the UN Convention on Psychotropic Substances of 1971. The Committee considered that there is sufficient evidence that 5F-APINACA 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 5F-APINACA 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