Inhibition of cisplatin-induced emesis in the pigeon by a non-psychotropic synthetic cannabinoid.

The (+) enantiomer of the synthetic cannabinoid, 7-hydroxy-delta-6-tetrahydrocannabinol, dimethylheptyl homolog (HU-211), possesses significant antimetic efficacy in the pigeon. However, unlike all anti-emetic cannabinoids tested in the past, it is devoid of psychotropic (cannabimimetic) activity. The anti-emetic activity of HU-211 was determined in pigeons given 10 mg/kg i.v. cisplatin, a widely used antitumour agent, which is also a potent emetogenic agent at this dose. This activity was compared with that of delta-1-tetrahydrocannabinol (delta-1-THC). HU-211 pretreatment elicited a dose-related inhibition of cisplatin vomiting, with the optimal dose of HU-211 (2.5 mg/kg) inhibiting emesis by nearly 90%. Delta-1-THC in doses up to 5 mg/kg caused only an insignificant reduction in vomiting. The activity was increased in the presence of cupric chloride (0.8 mg/kg). The optimal dose of delta-1-THC (5.0 mg/kg) with CuCl2 very significantly diminished the total amount of vomitus expelled (up to 90%). However, it failed to inhibit emesis in 50% of all animals tested, did not significantly affect the time of onset of emesis and was highly psychotropic. The optimal dose of HU-211 (2.5 mg/kg) with CuCl2 inhibited emesis by 97%, significantly delayed the time on onset of emesis in the very few animals that did vomit and was completely non-psychotropic. The curve for the antiemetic effect of HU-211 was U-shaped over a narrow dose range. The present report demonstrates that complete separation of psychotropic and antiemetic activities is possible in the cannabinoid series.