JWH-073

Substance identification
Chemically, JWH-073 is (1-butyl-1H-indol-3-yl)(1-naphthyl)methanone.

Previous review
During its thirty-sixth meeting, the WHO ECDD had discussed the critical review report on JWH-073 and concluded that owing to the insufficiency of data regarding dependence, abuse and risks to public health, JWH-073 should not be placed under international control at that time but be kept under surveillance. New information on its pharmacology and abuse potential warranted an update of the critical review report for discussion at the thirty-eighth meeting of the ECDD.

Similarity to known substances and effects on the central nervous system
JWH-073 is a homologue of JWH-018, which has been included in Schedule II of the Convention on Psychotropic Substances of 1971 since 2015. JWH-073 binds to the CB1 and CB2 cannabinoid receptors and exhibits functional in vitro activity. Several metabolites of JWH-073 also bind to the CB1 receptor. Similar to THC, JWH-073 induces marked hypothermia in mice, increases the pain threshold to both noxious mechanical and thermal stimuli, causes catalepsy, reduces motor activity, and stimulates dopamine release in the nucleus accumbens in a dose-dependent manner after systemic administration. In addition, it impairs sensorimotor responses (visual, acoustic and tactile), causes seizures, myoclonia and hyperreflexia, and promotes aggression. All these effects are fully prevented by the selective CB1 receptor antagonist/inverse agonist, AM251. Repeated administration of JWH-073 can induce tolerance to some of its effects, and repeated administration of THC can produce cross-tolerance to some of the effects of JWH-073. Users have reported anxiety, tremulousness and palpitations. One user reported that she felt like she was "becoming psychotic". Potency is reported to be about half that of JWH-018. There have been several reports of patients presenting with analytically confirmed JWH-073 consumption. These patients exhibited some of the following signs: chest pain, tachycardia followed by bradycardia, hypertension, agitation, paranoia and delusions, abdominal cramps with nausea and vomiting, anxiety and tremulousness. However, these reports typically involved the presence of other drugs and it is difficult to draw a direct linkage between these adverse effects and JWH-073. No fatal cases in which JWH-073 was detected in postmortem samples have been reported so far.

Dependence potential
No controlled studies in humans or laboratory animals regarding the potential physical dependence or tolerance effects of JWH-073 have been reported.

Actual abuse and/or evidence of likelihood of abuse
In rats and rhesus monkeys, JWH-073 produces the discriminative stimulus effects of THC. Additionally, both THC and JWH-073 substitute for the discriminative stimulus effects of JWH-018 in mice. Repeated administration of THC, however, produces tolerance to its discriminative effects in rhesus monkeys, but not cross- tolerance to JWH-073. In common with THC, JWH-073 is not self-administered by rats.

JWH-073 is sold over the Internet and has been sold as an additive in commercially available "herbal mixtures". It is sold as a powder or, when sold in herbal mixtures, the chemical has been sprayed onto plant material (e.g. damiana (Turnera diffusa)). Based on user reports and on the dosage forms offered, the primary route of administration is inhalation either by smoking the herbal mixture as a "joint" or using a vaporizer, bong or pipe. Abuse has been reported in a number of countries in different regions. A number of countries in different regions have placed JWH-073 under national control.

Therapeutic usefulness
There are no known approved therapeutic applications for JWH-073.

Recommendation
The available pharmacodynamic data related to JWH-073 (1-butyl-1H-indol-3- yl)(1-naphthyl)methanone) demonstrate that this substance has the capacity to produce some effects similar to its homologue, JWH-018, which is included in Schedule II of the UN Convention on Psychotropic Substances of 1971. However, the data currently available do not make it possible to establish a direct link between JWH-073 abuse and appearance of public health and social problems that would be a requirement for placing this substance under international control. It is therefore recommended not to place JWH-073 under international control but to continue to keep it under surveillance.