Nabilone
(6aR,10aR)-1-hydroxy-6,6-dimethyl-3-(2-methyloctan-2-yl)-7,8,10,10a-tetrahydro-6aH-benzo[c]chromen-9-one
Overview
Nabilone belongs to Cannabinoids.
Effects
- Cannabis-like effects: relaxation, euphoria (or dysphoria/anxiety), altered perception of time and surroundings, and drowsiness, alongside relief of nausea.
- Physical effects: dry mouth, dizziness, a faster heart rate, light-headedness on standing, unsteadiness and impaired coordination.
- At higher doses or in susceptible people: confusion, disorientation, depersonalization and, uncommonly, hallucinations or panic.
Dosing & duration
Oral (capsules): prescription antiemetic, taken as a course around chemotherapy. Figures are therapeutic (prescribing) ranges, not a recreational guide.. Nabilone is a prescription medicine dosed by a clinician. It is fully psychoactive, so doses are kept low and titrated, and patients should not drive until they know how it affects them and should avoid alcohol and other sedatives. It is typically started the night before or a couple of hours before chemotherapy.
Dose ranges
1–2 mg twice daily
6 mg/day (in divided doses)
Duration
≈1–1.5 h (oral)
Effects last several hours, metabolite effects can persist longer
Drowsiness, dry mouth and light-headedness may linger
Chemical & Physical Properties
| Formula | C24H36O3 |
| Molar mass | 372.5 g/mol |
| State | Solid |
| Melting point | Not reported |
| Boiling point | Not reported |
| Density | Not reported |
| Vapor pressure | Not reported |
| pKa | Not reported |
| LogP | 6.8 (highly lipophilic) |
| Solubility | Practically insoluble in water (~4.9×10⁻⁴ g/L) |
| Refractive index | Not reported |
Identifiers & Synonyms
| CAS | 51022-71-0 |
| CAS (enantiomer) | |
| PubChem CID | 5284592 |
| InChIKey | GECBBEABIDMGGL-RTBURBONSA-N |
| InChI | InChI=1S/C24H36O3/c1-6-7-8-9-12-23(2,3)16-13-20(26)22-18-15-17(25)10-11-19(18)24(4,5)27-21(22)14-16/h13-14,18-19,26H,6-12,15H2,1-5H3/t18-,19-/m1/s1 |
| SMILES | CCCCCCC(C)(C)C1=CC(=C2[C@@H]3CC(=O)CC[C@H]3C(OC2=C1)(C)C)O |
Synonyms
- Cesamet
- Canemes
Pharmacodynamics & Biochemistry
Nabilone (Cesamet) is a synthetic cannabinoid: a close structural analogue of Δ⁹-THC (a ketone analogue of a THC metabolite) developed as a prescription antiemetic. Like THC it is an agonist at the CB1 and CB2 cannabinoid receptors, but it binds with higher affinity and greater efficacy: at human receptors its Kᵢ is about 4 nM (CB1) and 6 nM (CB2), roughly an order of magnitude tighter than THC, though it is still best described as a partial agonist. Its antiemetic action comes from CB1 activation in the brainstem and higher centres that control nausea and vomiting. The same central CB1 agonism produces its psychoactive, cannabis-like effects (relaxation, euphoria or dysphoria, altered perception) and its sedative, appetite- and mood-modulating actions. It is fully psychoactive, which limits dosing and is why it is used when standard antiemetics fail. Nabilone is administered as a racemate of its two trans enantiomers, (6aR,10aR)-(−) and (6aS,10aS)-(+), shown below. It is extensively metabolised in the liver by several cytochrome-P450 enzymes to a number of (incompletely characterised) metabolites. The parent has a short (~2 h) plasma half-life while its metabolites persist much longer (~35 h), and oral bioavailability is limited (~20%) by first-pass metabolism.
Biological targets
- CB1
- CB2
Binding & functional measurements
| Target | Measurement | Species |
|---|---|---|
| CB1 receptor | pKi 8.4 | Human |
| CB2 receptor | pKi 8.2 | Human |
Pharmacokinetics
| Bioavailability | Oral ≈20% (extensive first-pass metabolism) |
| Tmax | Not reported |
| Half-life | Parent ≈2 h, identified metabolites ≈35 h |
| Vd | Not reported |
| Protein binding | High (~97%, similar to THC) |
| Metabolism | Hepatic, by multiple CYP450 enzymes, to several incompletely characterised metabolites |
| Excretion | Mainly biliary/faecal, with some renal |
Toxicology & Safety
Not reported
Nabilone is fully psychoactive, and its commonest problems are central-nervous-system effects: dizziness/vertigo, drowsiness, dry mouth, ataxia, headache, disorientation, depersonalization and euphoria or dysphoria. At higher doses it can cause anxiety, confusion, and, uncommonly, hallucinations or a psychotic reaction, so it is avoided or used cautiously in people with a history of psychosis or serious psychiatric illness. It can cause a fast heart rate and orthostatic (standing) drops in blood pressure, so caution is needed in cardiovascular disease and in the elderly, who are more sensitive. Its sedation and impairment add to those of alcohol, benzodiazepines and other depressants, and patients should not drive until they know how it affects them. Tolerance and some dependence can develop with sustained use. Effects are long-lasting because of the persistent metabolites.[3]
Legal Status
US: Schedule II. UK: Schedule 2 (Class B). DE: BtMG Anlage III
Interactions & Contraindications
Drug interactions
Contraindications
No interactions or contraindications listed.
Usage & Context
- A prescription antiemetic: its FDA/EMA-approved use is for nausea and vomiting caused by cancer chemotherapy in patients who have not responded adequately to conventional antiemetics.
- Used off-label for chronic and neuropathic pain, fibromyalgia, multiple-sclerosis spasticity, and to help appetite, anxiety or sleep: a synthetic alternative to herbal cannabis with a defined, standardised dose.
- It is not a recreational-market drug in the way herbal cannabis is, but it is psychoactive and controlled.
Sources & Evidence
- PubChem: Nabilone (CID 5284592) — identifiers & computed properties
- IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb): nabilone (ligand 9071) — human CB1 Kᵢ ≈4 nM, CB2 ≈6 nM CC BY-SA 4.0
- Wikipedia: Nabilone — synthetic cannabinoid (racemate of trans isomers), CB1/CB2 partial agonism, PK (t½ 2 h/metabolites 35 h), uses, adverse effects & legal status CC BY-SA 4.0
- DEA Diversion Control Division: Controlled Substance Schedules (nabilone is Schedule II)
- GOV.UK: Controlled drugs list — nabilone is a Schedule 2 / Class B controlled drug (Misuse of Drugs legislation) OGL v3.0
- Blaazer AR, Lange JH, van der Neut MA, et al. (2011). Novel indole and azaindole (pyrrolopyridine) cannabinoid (CB) receptor agonists: design, synthesis, structure-activity relationships, physicochemical properties and biological activity. Eur J Med Chem 46:5086-98.
PMID 21885167 · doi:10.1016/j.ejmech.2011.08.021