51022-71-0

White to Off-White Solid

Cesamet,Lilly,Canada,1982

A labelled synthetic cannabinoid with antiemetic, antiglaucoma, and CNS activity. Antiemetic. Controlled substance (hallucinogen).

A synthetic cannabinoid with antiemetic, antiglaucoma, and CNS activity. Antiemetic. Controlled substance (hallucinogen).

A solution of 1.5 g of dl-3-(1',1'-dimethylheptyl)-6,6a,7,8-tetrahydro-1- hydroxy-6,6-dimethyl-9H-dibenzo[b,d]pyran-9-one in 50 ml of anhydrous tetrahydrofuran (THF) was added dropwise to a solution of lithium metal in liquid ammonia at -80°C. Excess lithium metal was added in chunks to the solution as the blue color, indicating free dissolved lithium, disappeared. After the addition was complete, ammonium chloride was added to react with any excess lithium metal still present.
The mixture was then allowed to warm to room temperature in a nitrogen atmosphere during which process the ammonia evaporated. The reaction mixture was then acidified with 1 N aqueous hydrochloric acid, and the organic constituents extracted with ethyl acetate. The ethyl acetate extracts were combined, washed with water and dried. Evaporation of the ethyl acetate under reduced pressure yielded 1.4 g of crude dl-trans-3-(1',1'- dimethylheptyl)-6,6aβ,7,8,10,10aβ-hexahydro-1-hydroxy-6,6-dimethyl-9Hdibenzo[b,d]pyran-9-one. The crude product was chromatographed over 50 g of silica gel from benzene solution and the desired product was eluted in 20 ml fractions with a benzene eluant containing 2% ethyl acetate. Fractions 200 to 240 contained 808 mg of a white crystalline solid comprising purified dltrans-3-(1',1'-dimethylheptyl)-6,6aβ,7,8,10,10aβ-hexahydro-1-hydroxy-6,6- dimethyl-9H-dibenzo[b,d]pyran-9-one. The purified compound melted at 159°C to 160°C after recrystallization from an ethyl acetate-hexane solvent mixture.

Cesamet (Valeant).

Antianxiety

Nabilone is a structural analogue of dronabinol (delta-9- tetrahydrocannabinol), the major active component of cannabis.

Nabilone is a synthetic analogue of THC that has shown particular promise in laboratory models of CUD. Nabilone has better bioavailability, a longer duration of action, and lower abuse liability than dronabinol, and since it produces unique urinary metabolites, researchers can distinguish cannabis use from medication compliance. Haney et al. investigated two doses of nabilone in the human laboratory and showed that this medication significantly decreased a laboratory measure of cannabis relapse and improved mood symptoms of withdrawal, such as irritability. Further, the higher nabilone dose also decreased craving for cannabis, increased quality of sleep, and improved food intake. In 2016, Herrmann et al. used a similar human laboratory design to test the combination of nabilone and the GABAA agonist, zolpidem, hypothesizing that combining nabilone with an efficacious sleep medication may produce more robust reductions in cannabis withdrawal and relapse than those observed with nabilone alone by Haney et al. Zolpidem was also tested alone, and although it improved sleep during cannabis withdrawal relative to placebo, it did not reduce relapse. The combination of zolpidem and nabilone provided a more comprehensive reduction in withdrawal symptoms (negative mood, anorexia, disrupted sleep) and also reduced cannabis relapse. The authors suggest that the majority of these effects are attributable to nabilone. These laboratory findings await confirmation in clinical treatment settings, but the results of these studies demonstrate that nabilone holds considerable promise for CUD treatment.

Synthetic cannabinoid:
Treatment of nausea and vomiting due to chemotherapy

Potentially hazardous interactions with other drugs
Use with caution with other psychoactive medication or CNS depressants

Nabilone is hepatically metabolised. The major pathway probably involves direct oxidation of nabilone to produce hydroxylic and carboxylic analogues. One or more of the metabolites may be active. These compounds are thought to account for the remaining plasma radioactivity when carbinol metabolites have been extracted. Excreted mainly by the biliary route, >60% of the total is eliminated in the faeces and about 25% in the urine.