Nabilone

Nabilone

Systematic (IUPAC) name
(6aR,10aR)-rel-1-hydroxy-6,6-dimethyl-3-(2-methyloctan-2-yl)-
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a607048
Pregnancy cat.	C(US)
Legal status	Schedule II (US)
Routes	Oral form (PO)- capsule
Pharmacokinetic data
Bioavailability	20% after first-pass by the liver
Protein binding	similar to THC (+/-97%)
Half-life	2 hours, with metabolites around 35 hours.
Identifiers
CAS number	51022-71-0 Y
ATC code	A04AD11
PubChem	CID 5284592
DrugBank	APRD01127
ChemSpider	4447641 Y
UNII	2N4O9L084N Y
KEGG	D05099 N
ChEMBL	CHEMBL947 Y
Chemical data
Formula	C24H36O3
Mol. mass	372.541 g/mol
SMILES	eMolecules & PubChem
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 Y Key:GECBBEABIDMGGL-RTBURBONSA-N Y
N(what is this?)  (verify)

Nabilone is a synthetic cannabinoid with therapeutic use as an antiemetic and as an adjunct analgesic for neuropathic pain. It is a synthetic cannabinoid, which mimics the main ingredient of cannabis (THC). Chemically, nabilone is similar to the active ingredient found in naturally occurring Cannabis sativa L. ^[1]

In Canada, the United States, the United Kingdom and Mexico, nabilone is marketed as Cesamet. It was approved in 1985 by the U.S. Food and Drug Administration (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.

Although it doesn't have the official indication (except in Mexico), nabilone is widely used as an adjunct therapy for chronic pain management. Numerous trials and case studies have demonstrated various benefits for condition such as fibromyalgia^[2] and multiple sclerosis.^[3]

Nabilone is a racemic mixture consisting of the (S,S) and the (R,R) isomers ("trans").

Clinical trials

The main settings that have seen published clinical trials of nabilone include movement disorders such as Parkinson's syndrome, chronic pain, dystonia and spasticity neurological disorders, fibromyalgia, multiple sclerosis, and the nausea of cancer chemotherapy.

A study comparing nabilone with metoclopramide, conducted before the development of modern 5-HT3 antagonist anti-emetics such as ondansetron, revealed that patients taking cisplatin chemotherapy preferred metoclopramide, while patients taking carboplatin chemotherapy preferred nabilone to control nausea and vomiting. ^[4] Another study compared nabilone alone to nabilone with dexamethasone. The study found that the combination worked better than the single medication. ^[5] An older study revealed that nabilone was more effective than prochlorperazine in controlling nausea, though in this study, only 9% of nabilone patients had complete resolution of symptoms. ^[6] A follow-up to this study revealed similar findings. ^[7]

One study compared the efficacy and tolerability of nabilone with that of dihydrocodeine in the treatment of neuropathic pain.^[8] The authors found that nabilone was not as effective as dihydrocodeine in controlling pain, and caused a higher incidence of minor adverse drug reactions than did dihydrocodeine. One critic of the study has suggested that nabilone might be best suited for the treatment of patients suffering from central and spasticity-related pain, for which there is stronger evidence for the benefits of cannabinoid therapy; however, these patients made up only a small fraction of the study's population, and the study was not designed to identify subgroups which might have responded more favorably to treatment than others.^[9]

A clinical trial performed in Canada reviewed the use of nabilone to treat nightmares in individuals suffering from post-traumatic stress syndrome^[10]. The study found that nighttime administration of nabilone reduced the frequency and/or intensity of nightmares in 34 out of 47 (72%) of patients, with 28 reporting complete cessation of nightmares^[10]. This study is limited to the extent that there was no placebo control, but warrants future investigation into the use of cannabinoid therapy in the treatment of post-traumatic stress syndrome and other disorders involving recurrent nightmares.

References

1. ^ "How to use Cesamet". Artek LLC. 2008. http://patientsville.com/labels/cesamet_label.htm. 
2. ^ Skrabek RQ, Galimova L, Ethans K, Perry D (2008). "Nabilone for the treatment of pain in fibromyalgia". J Pain 9 (2): 164–73. doi:10.1016/j.jpain.2007.09.002. PMID 17974490. 
3. ^ Wissel J, Haydn T, Müller J, Brenneis C, Berger T, Poewe W, Schelosky LD. (2006). "Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain : a double-blind placebo-controlled cross-over trial". J Neurol. 253 (10): 1337–41. doi:10.1007/s00415-006-0218-8. PMID 16988792. 
4. ^ Cunningham D, Bradley C, Forrest G, Hutcheon A, Adams L, Sneddon M, Harding M, Kerr D, Soukop M, Kaye S (1988). "A randomized trial of oral nabilone and prochlorperazine compared to intravenous metoclopramide and dexamethasone in the treatment of nausea and vomiting induced by chemotherapy regimens containing cisplatin or cisplatin analogues". Eur J Cancer Clin Oncol 24 (4): 685–9. doi:10.1016/0277-5379(88)90300-8. PMID 2838294. 
5. ^ Niiranen A, Mattson K (1987). "Antiemetic efficacy of nabilone and dexamethasone: a randomized study of patients with lung cancer receiving chemotherapy". Am J Clin Oncol 10 (4): 325–9. doi:10.1097/00000421-198708000-00014. PMID 3039831. 
6. ^ Herman T, Einhorn L, Jones S, Nagy C, Chester A, Dean J, Furnas B, Williams S, Leigh S, Dorr R, Moon T (1979). "Superiority of nabilone over prochlorperazine as an antiemetic in patients receiving cancer chemotherapy". N Engl J Med 300 (23): 1295–7. doi:10.1056/NEJM197906073002302. PMID 375088. 
7. ^ Einhorn L, Nagy C, Furnas B, Williams S (1981). "Nabilone: an effective antiemetic in patients receiving cancer chemotherapy". J Clin Pharmacol 21 (8-9 Suppl): 64S–69S. PMID 6271844. 
8. ^ Frank B, Serpell MG, Hughes J, Matthews JN, Kapur D. "Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study." British Medical Journal. 2008 Jan 8. [Epub ahead of print]. PMID 18182416. doi:10.1136/bmj.39429.619653.80
9. ^ Cohen SP. "Cannabinoids for chronic pain." British Medical Journal. 2008 Jan 8. [Epub ahead of print]. PMID 18182415. doi:10.1136/bmj.39434.444583.80
10. ^ ^{a b} Fraser, GA (2009). "The Use of a Synthetic Cannabinoid in the Management of Treatment-Resistant Nightmares in Posttraumatic Stress Disorder (PTSD)". CNS Neurosci Ther 15 (1): 84–88. doi:10.1111/j.1755-5949.2008.00071.x. PMID 19228182.