NABILONE-DEA SCHEDULE II
Synonym(s):LY-109514
- CAS NO.:51022-71-0
- Empirical Formula: C24H36O3
- Molecular Weight: 372.54
- MDL number: MFCD00941490
- EINECS: 637-087-5
- SAFETY DATA SHEET (SDS)
- Update Date: 2023-05-29 13:57:48
What is NABILONE-DEA SCHEDULE II?
Absorption
Nabilone appears to be completely absorbed from the human gastrointestinal tract when administered orally. Following oral administration of a 2 mg dose of radiolabeled nabilone, peak plasma concentrations of approximately 2 ng/mL nabilone and 10 ng equivalents/mL total radioactivity are achieved within 2.0 hours.
Toxicity
Symptoms of overdose include difficulty in breathing, hallucinations, mental changes (severe), nervousness or anxiety (severe). Monkeys treated with Nabilone at doses as high as 2mg/kg/day for a year experienced no significant adverse events. This result contrasts with the finding in a planned 1-year dog study that was prematurely terminated because of deaths associated with convulsions in dogs receiving as little as 0.5mg/kg/day. The earliest deaths, however, occurred at 56 days in dogs receiving 2mg/kg/day. The unusual vulnerability of the dog is not understood; it is hypothesised, however, that the explanation lies in the fact that the dog differs markedly from other species (including humans) in its metabolism of Nabilone.
Chemical properties
White to Off-White Solid
Originator
Cesamet,Lilly,Canada,1982
The Uses of NABILONE-DEA SCHEDULE II
A labelled synthetic cannabinoid with antiemetic, antiglaucoma, and CNS activity. Antiemetic. Controlled substance (hallucinogen).
The Uses of NABILONE-DEA SCHEDULE II
A synthetic cannabinoid with antiemetic, antiglaucoma, and CNS activity. Antiemetic. Controlled substance (hallucinogen).
Indications
Nabilone is indicated for the treatment of the nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. This restriction is required because a substantial proportion of any group of patients treated with Nabilone can be expected to experience disturbing psychotomimetic reactions not observed with other antiemetic agents.
Background
Nabilone (marketed as Cesamet) is a synthetic form of delta-9-tetrahydrocannabinol (Δ?-THC), the primary psychoactive component of cannabis (marijuana). Although structurally distinct from THC, nabilone mimics THC's structure and pharmacological activity through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors, however it is considered to be twice as active as Δ?-THC. Nabilone is approved by the FDA for the treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments .
Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two most abundant cannabinoids found naturally in the resin of the marijuana plant, both of which are pharmacologically active due to their interaction with cannabinoid receptors that are found throughout the body . While both CBD and THC are used for medicinal purposes, they have different receptor activity, function, and physiological effects. If not provided in their activated form (such as through synthetic forms like Nabilone or Dronabinol), THC and CBD are obtained through conversion from their precursors, tetrahydrocannabinolic acid-A (THCA-A) and cannabidiolic acid (CBDA), through decarboxylation reactions. This can be achieved through heating, smoking, vaporization, or baking of dried unfertilized female cannabis flowers.
From a pharmacological perspective, Cannabis' diverse receptor profile explains its potential application for such a wide variety of medical conditions. Cannabis contains more than 400 different chemical compounds, of which 61 are considered cannabinoids, a class of compounds that act upon endogenous cannabinoid receptors of the body . The endocannabinoid system is widely distributed throughout the central and peripheral nervous system (via the Cannabinoid Receptors CB1 and CB2) and plays a role in many physiological processes such as inflammation, cardiovascular function, learning, pain, memory, stress and emotional regulation, and the sleep/wake cycle among many others . CB1 receptors are found in both the central and peripheral nervous system, and are most abundant in the hippocampus and amygdala, which are the areas of the brain responsible for short-term memory storage and emotional regulation. CB2 receptors are mainly located in the peripheral nervous system and can be found on lymphoid tissue where they are involved in regulation of immune function .
In Canada, the United States, the United Kingdom and Mexico, nabilone is marketed as Cesamet. It was approved in 1985 by the United States FDA for treatment of chemotherapy-induced nausea and vomiting that has not responded to conventional antiemetics. Though it was approved by the FDA in 1985, the drug only began marketing in the United States in 2006. It is also approved for use in treatment of anorexia and weight loss in patients with AIDS.
Nabilone is a racemate consisting of the (S,S) and the (R,R) isomers.
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.
Pharmacokinetics
Nabilone is a cannabinoid with therapeutic uses. It is an analog of dronabinol (also known as tetrahydrocannabinol or THC), the psychoactive ingredient in cannabis. Although structurally distinct from THC, nabilone mimics THC's structure and pharmacological activity through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors, however it is considered to be twice as active as Δ?-THC.
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
Hepatic. Two metabolic pathways have been suggested. The major pathway probably involves the direct oxidation of Nabilone to produce hydroxylic and carboxylic analogues. These compounds are thought to account for the remaining plasma radioactivity when carbinol metabolites have been extracted.
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.
Properties of NABILONE-DEA SCHEDULE II
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 information for NABILONE-DEA SCHEDULE II
Signal word | Warning |
Pictogram(s) |
Exclamation Mark Irritant GHS07 Health Hazard GHS08 |
GHS Hazard Statements |
H302:Acute toxicity,oral H336:Specific target organ toxicity,single exposure; Narcotic effects H361:Reproductive toxicity |
Precautionary Statement Codes |
P202:Do not handle until all safety precautions have been read and understood. P261:Avoid breathing dust/fume/gas/mist/vapours/spray. P264:Wash hands thoroughly after handling. P264:Wash skin thouroughly after handling. P270:Do not eat, drink or smoke when using this product. P301+P312:IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. P308+P313:IF exposed or concerned: Get medical advice/attention. |
Computed Descriptors for NABILONE-DEA SCHEDULE II
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