View source for Nabilone

{{Short description|Synthetic cannabinoid}}
{{cs1 config|name-list-style=vanc}}
{{Drugbox
| Watchedfields = changed
| verifiedrevid = 462257989
| IUPAC_name = ''rel''-(6a''R'',10a''R'')-1-Hydroxy-6,6-dimethyl-3-(2-methyloctan-2-yl)-6,6a,7,8,10,10a-hexahydro-9''H''-benzo[''c'']chromen-9-one
| image = Nabilone2.svg
| image_class = skin-invert-image
| alt = Skeletal formula of nabilone
| image2 = Nabilone molecule spacefill.png
| image_class2 = bg-transparent
| alt2 = Space-filling model of the nabilone molecule
| caption = Top: (''R'',''R'')-(−)-nabilone,<br />Center: (''S'',''S'')-(+)-nabilone,<br />Bottom: Space-filling model of (''R'',''R'')-(−)-nabilone

<!--Clinical data-->| tradename = Cesamet, others
| Drugs.com = {{drugs.com|monograph|nabilone}}
| MedlinePlus = a607048
| pregnancy_US = C
| pregnancy_category = 
| legal_AU = Schedule 8
| legal_DE = Anlage III
| legal_US = Schedule II
| legal_CA = Schedule II
| legal_UK = POM
| legal_status = Rx-only
| routes_of_administration = [[Oral administration|By mouth]]

<!--Pharmacokinetic data-->| bioavailability = 20% after [[First pass effect|first-pass by the liver]]
| protein_bound = similar to THC (±97%)
| metabolism = 
| elimination_half-life = 2 hours, with metabolites around 35 hours

<!--Identifiers-->| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 51022-71-0
| ATC_prefix = A04
| ATC_suffix = AD11
| ATC_supplemental = 
| PubChem = 5284592
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00486
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4447641
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 2N4O9L084N
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D05099
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 947
| synonyms = 
| class = [[Cannabinoid]]

<!--Chemical data-->| C = 24
| H = 36
| O = 3
| SMILES = O=C3CC[C@@H]1[C@H](c2c(OC1(C)C)cc(cc2O)C(C)(C)CCCCCC)C3
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = GECBBEABIDMGGL-RTBURBONSA-N
}}

'''Nabilone''', sold under the brand name '''Cesamet''' among others, is a [[synthetic cannabinoid]] with [[medical cannabis|therapeutic use]] as an [[antiemetic]] and as an adjunct [[analgesic]] for [[neuropathic pain]].<ref name="AdisInsight">{{Cite web|url=https://adisinsight.springer.com/drugs/800025856|title=Nabilone - AdisInsight}}</ref><ref name="Drugs.com">{{Cite web|url=https://www.drugs.com/international/nabilone.html|title = Nabilone Advanced Patient Information}}</ref> It mimics [[tetrahydrocannabinol]] (THC), the primary psychoactive compound found naturally occurring in ''[[Cannabis]]''.<ref name=USlabel2006>{{cite web|title=Nabilone label |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/018677s011lbl.pdf |publisher=FDA|date=May 2006}}</ref>

The [[Food and Drug Administration]] (FDA) in the [[United States]] has indicated nabilone for chemotherapy-induced nausea/vomiting. In other countries, such as [[Canada]], it is widely used as an adjunct therapy for [[pain management|chronic pain management]]. Numerous trials and case studies have demonstrated modest effectiveness for relieving [[fibromyalgia]]<ref name=pain/> and [[multiple sclerosis]].<ref>{{cite journal | vauthors = Wissel J, Haydn T, Müller J, Brenneis C, Berger T, Poewe W, Schelosky LD | title = Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain : a double-blind placebo-controlled cross-over trial | journal = Journal of Neurology | volume = 253 | issue = 10 | pages = 1337–41 | date = October 2006 | pmid = 16988792 | doi = 10.1007/s00415-006-0218-8 | s2cid = 24206300 | type = Research article }}</ref><ref>{{cite journal | vauthors = Nielsen S, Germanos R, Weier M, Pollard J, Degenhardt L, Hall W, Buckley N, Farrell M | title = The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews | journal = Current Neurology and Neuroscience Reports | volume = 18 | issue = 2 | pages = 8 | date = February 2018 | pmid = 29442178 | doi = 10.1007/s11910-018-0814-x | hdl = 2123/18910 | s2cid = 3375801 | hdl-access = free }}</ref>

==Medical uses==
Nabilone is used to treat nausea and vomiting in people under [[chemotherapy]].<ref name=USlabel2006/><ref name=UKlabel2014>{{cite web|title=Nabilone Summary of Product Characteristics (SPC) - (eMC)|url=https://www.medicines.org.uk/emc/medicine/20515|publisher=UK Electronic Medicines Compendium|date=August 2014|access-date=2016-11-17|archive-date=2017-12-22|archive-url=https://web.archive.org/web/20171222061728/https://www.medicines.org.uk/emc/medicine/20515|url-status=dead}}</ref>

Nabilone has shown modest effectiveness in relieving [[fibromyalgia]].<ref name=pain>{{cite journal | vauthors = Fine PG, Rosenfeld MJ | title = The endocannabinoid system, cannabinoids, and pain | journal = Rambam Maimonides Medical Journal | volume = 4 | issue = 4 | pages = e0022 | year = 2013 | pmid = 24228165 | pmc = 3820295 | doi = 10.5041/RMMJ.10129 | type = Review }}</ref> A 2011 systematic review of cannabinoids for chronic pain determined there was evidence of safety and modest efficacy for some conditions.<ref>{{cite journal | vauthors = Lynch ME, Campbell F | title = Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials | journal = British Journal of Clinical Pharmacology | volume = 72 | issue = 5 | pages = 735–44 | date = November 2011 | pmid = 21426373 | pmc = 3243008 | doi = 10.1111/j.1365-2125.2011.03970.x }}</ref>

The main settings that have seen published clinical trials of nabilone include movement disorders such as [[parkinsonism]], chronic pain, [[dystonia]] and [[spasticity]] neurological disorders, multiple sclerosis, and the nausea of cancer chemotherapy. Nabilone is also effective in the treatment of [[inflammatory bowel disease]], especially [[ulcerative colitis]].

In one study of current daily users of cannabis, oral nabilone at 4, 6, and 8&nbsp;mg produced sustained and dose-dependent mood elevation and [[Psychomotor retardation|psychomotor slowing]] comparable to 10 or 20&nbsp;mg oral [[dronabinol]] (THC). Nabilone had a slower onset of peak action and a greater dose-dependence of effects, which the investigators attributed to greater bioavailability. <ref>{{cite journal | vauthors = Bedi G, Cooper ZD, Haney M | title = Subjective, cognitive and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers | journal = Addiction Biology | volume = 18 | issue = 5 | pages = 872–81 | date = September 2013 | pmid = 22260337 | pmc = 3335956 | doi = 10.1111/j.1369-1600.2011.00427.x }}</ref>

A study comparing nabilone with [[metoclopramide]], conducted before the development of modern [[5-HT3 antagonist|5-HT<sub>3</sub> antagonist]] [[anti-emetics]] such as [[ondansetron]], revealed that patients taking [[cisplatin]] chemotherapy preferred [[metoclopramide]], while patients taking [[carboplatin]] preferred nabilone to control nausea and vomiting.<ref>{{cite journal | vauthors = Cunningham D, Bradley CJ, Forrest GJ, Hutcheon AW, Adams L, Sneddon M, Harding M, Kerr DJ, Soukop M, Kaye SB | title = 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 | journal = European Journal of Cancer & Clinical Oncology | volume = 24 | issue = 4 | pages = 685–9 | date = April 1988 | pmid = 2838294 | doi = 10.1016/0277-5379(88)90300-8 | type = Randomized controlled trial }}</ref><ref>{{cite journal | vauthors = Smith LA, Azariah F, Lavender VT, Stoner NS, Bettiol S | title = Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy | journal = The Cochrane Database of Systematic Reviews | issue = 11 | pages = CD009464 | date = November 2015 | volume = 2021 | pmid = 26561338 | doi = 10.1002/14651858.CD009464.pub2 | pmc = 6931414 }}</ref>

Nabilone is sometimes used for [[nightmare]]s in [[post-traumatic stress disorder]], but there have not been studies longer than nine weeks, so effects of longer-term use are not known.<ref name=CADTH-2015>{{cite journal | title = Long-term Nabilone Use: A Review of the Clinical Effectiveness and Safety | journal = CADTH Rapid Response Reports | date = Oct 2015 | pmid = 26561692 | url = https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0079568/ }}</ref> Nabilone has also been used for medication overuse headache.<ref>{{cite journal | vauthors = Pini LA, Guerzoni S, Cainazzo MM, Ferrari A, Sarchielli P, Tiraferri I, Ciccarese M, Zappaterra M | title = Nabilone for the treatment of medication overuse headache: results of a preliminary double-blind, active-controlled, randomized trial | journal = [[The Journal of Headache and Pain]] | volume = 13 | issue = 8 | pages = 677–84 | date = November 2012 | pmid = 23070400 | pmc = 3484259 | doi = 10.1007/s10194-012-0490-1 }}</ref>

==Side effects==
In the treatment of [[fibromyalgia]], [[adverse effect]]s limit the useful dose.<ref name="pain" /> Adverse effects of nabilone include, but are not limited to: [[dizziness]]/[[vertigo]], [[euphoria]], [[drowsiness]], [[dry mouth]], [[ataxia]], [[sleep disturbance]], [[headache]], [[nausea]], [[disorientation]], [[depersonalization]], [[Hallucination|hallucinations]], and [[asthenia]].<ref name=USlabel2006/>

==Pharmacology==

===Pharmacodynamics===
Nabilone is a [[partial agonist]] of the [[cannabinoid]] [[CB1 receptor|CB<sub>1</sub>]] and [[CB2 receptor|CB<sub>2</sub> receptor]]s.<ref name="pmid33086126">{{cite journal | vauthors = Sholler DJ, Huestis MA, Amendolara B, Vandrey R, Cooper ZD | title = Therapeutic potential and safety considerations for the clinical use of synthetic cannabinoids | journal = Pharmacol Biochem Behav | volume = 199 | issue = | pages = 173059 | date = December 2020 | pmid = 33086126 | pmc = 7725960 | doi = 10.1016/j.pbb.2020.173059 | url = }}</ref><ref name="pmid32791166">{{cite journal | vauthors = Zhornitsky S, Pelletier J, Assaf R, Giroux S, Li CR, Potvin S | title = Acute effects of partial CB1 receptor agonists on cognition - A meta-analysis of human studies | journal = Prog Neuropsychopharmacol Biol Psychiatry | volume = 104 | issue = | pages = 110063 | date = January 2021 | pmid = 32791166 | doi = 10.1016/j.pnpbp.2020.110063 | s2cid = 221092170 | url = }}</ref>

===Pharmacokinetics===
Nabilone is given in 1 or 2&nbsp;mg doses multiple times a day up to a total of 6&nbsp;mg. It is completely [[absorption (pharmacokinetics)|absorbed]] from [[oral administration]] and highly [[plasma protein binding|plasma protein bound]]. Multiple [[cytochrome P450]] [[enzyme]]s extensively [[metabolism|metabolize]] nabilone to various [[metabolite]]s that have not been fully characterized.<ref name=USlabel2006/>

==Chemistry==
Nabilone is a [[racemic mixture]] consisting of (''S'',''S'')-(+)- and (''R'',''R'')-(−)-[[isomer]]s.

==History==
Nabilone was originally developed by [[Eli Lilly and Company]]; and was first approved by [[Health Canada]] in 1981;<ref>{{cite journal | vauthors = Lutge EE, Gray A, Siegfried N | title = The medical use of cannabis for reducing morbidity and mortality in patients with HIV/AIDS | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD005175 | date = April 2013 | pmid = 23633327 | doi = 10.1002/14651858.CD005175.pub3 | pmc = 12127901 }}</ref><ref>{{cite web |url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/equiv/nabilone.html |title=Nabilone |publisher=[[Health Canada]] |access-date=2023-07-01 }}</ref> shortly followed by its approval in [[Mexico]], the [[United Kingdom]], and [[Germany]]. Lilly received FDA approval in 1985 to market it, but withdrew that approval in 1989 for commercial reasons.<ref name=PT2006>{{cite news|title=Valeant returns synthetic cannabinoid to USA|url=http://www.pharmatimes.com/news/valeant_returns_synthetic_cannabinoid_to_usa_996830|work=Pharma Times|date=17 May 2006|language=en}}</ref> [[Valeant Pharmaceuticals]] acquired the rights from Lilly in 2004.<ref name=PT2006/> Valeant tried and failed to get the medication approved by the FDA again in 2005<ref>{{cite news|title=FDA turns down Valeant's anti-nausea drug|url=http://www.pharmatimes.com/news/fda_turns_down_valeants_anti-nausea_drug_995867|work=Pharma Times|date=3 January 2006|language=en}}</ref> and then succeeded in 2006.<ref name=PT2006/>

In 2007, Valeant acquired the [[United Kingdom]] and [[European Union]] rights to market nabilone from Cambridge Laboratories.<ref>{{cite news|title=Cambridge Labs divests nabilone to Valeant - Pharmaceutical industry n|url=http://www.thepharmaletter.com/article/cambridge-labs-divests-nabilone-to-valeant|work=The Pharma Letter|date=February 27, 2007}}</ref>

Nabilone was approved in [[Austria]] to treat [[chemotherapy]]-induced [[nausea]] in 2013; it was already approved in [[Spain]] for the same indication and was legal in [[Belgium]] to treat [[glaucoma]], [[spasticity]] in [[multiple sclerosis]], [[wasting syndrome|wasting]] due to [[AIDS]], and [[chronic pain]].<ref>{{cite web|title=Cannabis Laws & Scheduling in Europe - MedicalMarijuana.eu|url=http://www.medicalmarijuana.eu/legal/|website=MedicalMarijuana.eu|access-date=17 November 2016|archive-date=18 November 2016|archive-url=https://web.archive.org/web/20161118041810/http://www.medicalmarijuana.eu/legal/|url-status=dead}}</ref>

==See also==
* [[List of investigational analgesics]]

==References==
{{Reflist}}


{{Antiemetics}}
{{Appetite stimulants}}
{{Cannabinoids}}
{{Hallucinogens}}
{{Cannabinoid receptor modulators}}

[[Category:Analgesics]]
[[Category:Appetite stimulants]]
[[Category:Benzochromenes]]
[[Category:Cannabinoids]]
[[Category:Cyclic ketones]]
[[Category:Hydroxyarenes]]
[[Category:Hydroxyketones]]