IUPAC Name
Naphthalene-1-yl(1-pentyl-1H-indol-3-yl)methanone
Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Naphthalen-1-yl(1-pentyl-1H-indol-3-yl)methanone, is also referred to as JWH- 018.
Previous review
JWH-018 had not been previously pre-reviewed or critically reviewed by the Committee. A direct critical review was proposed based on information brought to WHO’s attention that JWH-018 is clandestinely manufactured, poses an especially serious risk to public health and society, and has no recognized therapeutic use by any party. Preliminary data collected from the literature and from different countries 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
The aminoalkylindole JWH-018 is a full cannabinoid agonist with low nanomolar binding affinity at cannabinoid receptors type 1 and type 2 (CB1 and CB2 receptors). It also appears that some slight selectivity is observed towards the CB2 receptor. Its interaction with these receptor subtypes correlates with a psychopharmacological profile that is shared with delta-9-tetrahydrocannabinol (THC), which is less potent in a number of assays than JWH-018. Analytically confirmed cases of adverse effects, including non-fatal and fatal intoxications, have been reported in addition to instances of driving under the influence of the substance. Seizures, tachycardia and hypertension have been noted.
Dependence potential
There is some evidence to suggest that synthetic cannabinoid receptor agonists may be able to produce tolerance and withdrawal symptoms when substance use is abruptly discontinued following regular use of high doses. Further detailed studies of these properties of JWH-018 are warranted. The urge for re-dosing has also been associated with JWH-018.
Actual abuse and/or evidence of likelihood of abuse
Reports obtained from animal studies (e.g. drug discrimination) indicate the ability of JWH-018 to mimic effects typically observed with THC. Survey data indicate that JWH-018, like a range of other synthetic cannabinoids, shows THC- like effects in humans. In a WHO survey, 25 Member States confirmed that there was recreational/harmful use of JWH-018.
Therapeutic usefulness
JWH-018 has no recorded therapeutic applications or medical use. Within the research setting, anti-inflammatory and chemopreventive properties of JWH-018 have been reported.
Recommendation
The Committee noted the challenges associated with the evidence base concerning the substance. It also noted analytically confirmed cases of non-fatal and fatal intoxications involving JWH-018. The Committee therefore considered that the degree of risk to public health associated with the abuse liability of JWH-018 is substantial. Therapeutic usefulness has not been recorded. As per the Guidance on the WHO review of psychoactive substances for international control (4), higher regard was accorded to the substantial public health risk than to the lack of therapeutic usefulness.1 The Committee recommended that JWH-018 be placed under international control in Schedule II of the 1971 Convention.
Naphthalen-1-yl(1-pentyl-1H-indol-3-yl)methanone, is also referred to as JWH- 018.
Previous review
JWH-018 had not been previously pre-reviewed or critically reviewed by the Committee. A direct critical review was proposed based on information brought to WHO’s attention that JWH-018 is clandestinely manufactured, poses an especially serious risk to public health and society, and has no recognized therapeutic use by any party. Preliminary data collected from the literature and from different countries 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
The aminoalkylindole JWH-018 is a full cannabinoid agonist with low nanomolar binding affinity at cannabinoid receptors type 1 and type 2 (CB1 and CB2 receptors). It also appears that some slight selectivity is observed towards the CB2 receptor. Its interaction with these receptor subtypes correlates with a psychopharmacological profile that is shared with delta-9-tetrahydrocannabinol (THC), which is less potent in a number of assays than JWH-018. Analytically confirmed cases of adverse effects, including non-fatal and fatal intoxications, have been reported in addition to instances of driving under the influence of the substance. Seizures, tachycardia and hypertension have been noted.
Dependence potential
There is some evidence to suggest that synthetic cannabinoid receptor agonists may be able to produce tolerance and withdrawal symptoms when substance use is abruptly discontinued following regular use of high doses. Further detailed studies of these properties of JWH-018 are warranted. The urge for re-dosing has also been associated with JWH-018.
Actual abuse and/or evidence of likelihood of abuse
Reports obtained from animal studies (e.g. drug discrimination) indicate the ability of JWH-018 to mimic effects typically observed with THC. Survey data indicate that JWH-018, like a range of other synthetic cannabinoids, shows THC- like effects in humans. In a WHO survey, 25 Member States confirmed that there was recreational/harmful use of JWH-018.
Therapeutic usefulness
JWH-018 has no recorded therapeutic applications or medical use. Within the research setting, anti-inflammatory and chemopreventive properties of JWH-018 have been reported.
Recommendation
The Committee noted the challenges associated with the evidence base concerning the substance. It also noted analytically confirmed cases of non-fatal and fatal intoxications involving JWH-018. The Committee therefore considered that the degree of risk to public health associated with the abuse liability of JWH-018 is substantial. Therapeutic usefulness has not been recorded. As per the Guidance on the WHO review of psychoactive substances for international control (4), higher regard was accorded to the substantial public health risk than to the lack of therapeutic usefulness.1 The Committee recommended that JWH-018 be placed under international control in Schedule II of the 1971 Convention.
ECDD Recommendation
Inclusion in Schedule II of the 1971 Convention on Psychotropic Substances
Link to full TRS
who_trs_991_eng.pdf1.3 MB
MS Questionnaire Report