NABILONE-DEA SCHEDULE II Property

Melting point:

155-156°C

Boiling point:

457.4±45.0 °C(Predicted)

Density 

1.029±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: ~18 mg/mL, soluble

form 

solid

pka

pKa in 66% DMF: 13.5(at 25℃)

color 

white

Safety

Hazard Codes 

Xn,F

Risk Statements 

22-36-20/21/22-11

Safety Statements 

36/37/39-45-36/37-16

WGK Germany 

3

RTECS 

HP8756000

DEA Controlled Substances

CSCN: 7379
CAS SCH: II
NARC: N

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H336May cause drowsiness or dizziness

H361Suspected of damaging fertility or the unborn child

Precautionary statements

P202Do not handle until all safety precautions have been read and understood.

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P308+P313IF exposed or concerned: Get medical advice/attention.

NABILONE-DEA SCHEDULE II Chemical Properties,Usage,Production

Chemical Properties

White to Off-White Solid

Originator

Cesamet,Lilly,Canada,1982

Uses

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

Uses

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

Manufacturing Process

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.

brand name

Cesamet (Valeant).

Therapeutic Function

Antianxiety

World Health Organization (WHO)

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

Pharmacology

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.

Clinical Use

Synthetic cannabinoid:
Treatment of nausea and vomiting due to chemotherapy

Drug interactions

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

Metabolism

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.