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Nabilone

From Wikipedia, the free encyclopedia
Synthetic cannabinoid

Pharmaceutical compound
Nabilone
Skeletal formula of nabilone
Space-filling model of the nabilone molecule
Top: (R,R)-(−)-nabilone,
Center: (S,S)-(+)-nabilone,
Bottom: Space-filling model of (R,R)-(−)-nabilone
Clinical data
Trade namesCesamet, others
AHFS/Drugs.comMonograph
MedlinePlusa607048
Routes of
administration
By mouth
Drug classCannabinoid
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability20% afterfirst-pass by the liver
Protein bindingsimilar to THC (±97%)
Eliminationhalf-life2 hours, with metabolites around 35 hours
Identifiers
  • rel-(6aR,10aR)-1-Hydroxy-6,6-dimethyl-3-(2-methyloctan-2-yl)-6,6a,7,8,10,10a-hexahydro-9H-benzo[c]chromen-9-one
CAS Number
PubChemCID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
ECHA InfoCard100.164.824Edit this at Wikidata
Chemical and physical data
FormulaC24H36O3
Molar mass372.549 g·mol−1
3D model (JSmol)
  • O=C3CC[C@@H]1[C@H](c2c(OC1(C)C)cc(cc2O)C(C)(C)CCCCCC)C3
  • 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 checkY
  • Key:GECBBEABIDMGGL-RTBURBONSA-N checkY
  (verify)

Nabilone, sold under the brand nameCesamet among others, is asynthetic cannabinoid withtherapeutic use as anantiemetic and as an adjunctanalgesic forneuropathic pain.[1][2] It mimicstetrahydrocannabinol (THC), the primary psychoactive compound found naturally occurring inCannabis.[3]

TheFood and Drug Administration (FDA) in theUnited States has indicated nabilone for chemotherapy-induced nausea/vomiting. In other countries, such asCanada, it is widely used as an adjunct therapy forchronic pain management. Numerous trials and case studies have demonstrated modest effectiveness for relievingfibromyalgia[4] andmultiple sclerosis.[5][6]

Medical uses

[edit]

Nabilone is used to treat nausea and vomiting in people underchemotherapy.[3][7]

Nabilone has shown modest effectiveness in relievingfibromyalgia.[4] A 2011 systematic review of cannabinoids for chronic pain determined there was evidence of safety and modest efficacy for some conditions.[8]

The main settings that have seen published clinical trials of nabilone include movement disorders such asparkinsonism, chronic pain,dystonia andspasticity neurological disorders, multiple sclerosis, and the nausea of cancer chemotherapy. Nabilone is also effective in the treatment ofinflammatory bowel disease, especiallyulcerative colitis.

In one study of current daily users of cannabis, oral nabilone at 4, 6, and 8 mg produced sustained and dose-dependent mood elevation andpsychomotor slowing comparable to 10 or 20 mg oraldronabinol (THC). Nabilone had a slower onset of peak action and a greater dose-dependence of effects, which the investigators attributed to greater bioavailability.[9]

A study comparing nabilone withmetoclopramide, conducted before the development of modern5-HT3 antagonistanti-emetics such asondansetron, revealed that patients takingcisplatin chemotherapy preferredmetoclopramide, while patients takingcarboplatin preferred nabilone to control nausea and vomiting.[10][11]

Nabilone is sometimes used fornightmares inpost-traumatic stress disorder, but there have not been studies longer than nine weeks, so effects of longer-term use are not known.[12] Nabilone has also been used for medication overuse headache.[13]

Side effects

[edit]

In the treatment offibromyalgia,adverse effects limit the useful dose.[4] Adverse effects of nabilone include, but are not limited to:dizziness/vertigo,euphoria,drowsiness,dry mouth,ataxia,sleep disturbance,headache,nausea,disorientation,depersonalization,hallucinations, andasthenia.[3]

Pharmacology

[edit]

Pharmacodynamics

[edit]

Nabilone is apartial agonist of thecannabinoidCB1 andCB2 receptors.[14][15]

Pharmacokinetics

[edit]

Nabilone is given in 1 or 2 mg doses multiple times a day up to a total of 6 mg. It is completelyabsorbed fromoral administration and highlyplasma protein bound. Multiplecytochrome P450enzymes extensivelymetabolize nabilone to variousmetabolites that have not been fully characterized.[3]

Chemistry

[edit]

Nabilone is aracemic mixture consisting of (S,S)-(+)- and (R,R)-(−)-isomers.

History

[edit]

Nabilone was originally developed byEli Lilly and Company; and was first approved byHealth Canada in 1981;[16][17] shortly followed by its approval inMexico, theUnited Kingdom, andGermany. Lilly received FDA approval in 1985 to market it, but withdrew that approval in 1989 for commercial reasons.[18]Valeant Pharmaceuticals acquired the rights from Lilly in 2004.[18] Valeant tried and failed to get the medication approved by the FDA again in 2005[19] and then succeeded in 2006.[18]

In 2007, Valeant acquired theUnited Kingdom andEuropean Union rights to market nabilone from Cambridge Laboratories.[20]

Nabilone was approved inAustria to treatchemotherapy-inducednausea in 2013; it was already approved inSpain for the same indication and was legal inBelgium to treatglaucoma,spasticity inmultiple sclerosis,wasting due toAIDS, andchronic pain.[21]

See also

[edit]

References

[edit]
  1. ^"Nabilone - AdisInsight".
  2. ^"Nabilone Advanced Patient Information".
  3. ^abcd"Nabilone label"(PDF). FDA. May 2006.
  4. ^abcFine PG, Rosenfeld MJ (2013)."The endocannabinoid system, cannabinoids, and pain".Rambam Maimonides Medical Journal (Review).4 (4): e0022.doi:10.5041/RMMJ.10129.PMC 3820295.PMID 24228165.
  5. ^Wissel J, Haydn T, Müller J, Brenneis C, Berger T, Poewe W, Schelosky LD (October 2006). "Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain: a double-blind placebo-controlled cross-over trial".Journal of Neurology (Research article).253 (10):1337–41.doi:10.1007/s00415-006-0218-8.PMID 16988792.S2CID 24206300.
  6. ^Nielsen S, Germanos R, Weier M, Pollard J, Degenhardt L, Hall W, Buckley N, Farrell M (February 2018). "The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews".Current Neurology and Neuroscience Reports.18 (2): 8.doi:10.1007/s11910-018-0814-x.hdl:2123/18910.PMID 29442178.S2CID 3375801.
  7. ^"Nabilone Summary of Product Characteristics (SPC) - (eMC)". UK Electronic Medicines Compendium. August 2014. Archived fromthe original on 2017-12-22. Retrieved2016-11-17.
  8. ^Lynch ME, Campbell F (November 2011)."Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials".British Journal of Clinical Pharmacology.72 (5):735–44.doi:10.1111/j.1365-2125.2011.03970.x.PMC 3243008.PMID 21426373.
  9. ^Bedi G, Cooper ZD, Haney M (September 2013)."Subjective, cognitive and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers".Addiction Biology.18 (5):872–81.doi:10.1111/j.1369-1600.2011.00427.x.PMC 3335956.PMID 22260337.
  10. ^Cunningham D, Bradley CJ, Forrest GJ, Hutcheon AW, Adams L, Sneddon M, Harding M, Kerr DJ, Soukop M, Kaye SB (April 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".European Journal of Cancer & Clinical Oncology (Randomized controlled trial).24 (4):685–9.doi:10.1016/0277-5379(88)90300-8.PMID 2838294.
  11. ^Smith LA, Azariah F, Lavender VT, Stoner NS, Bettiol S (November 2015)."Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy".The Cochrane Database of Systematic Reviews.2021 (11) CD009464.doi:10.1002/14651858.CD009464.pub2.PMC 6931414.PMID 26561338.
  12. ^"Long-term Nabilone Use: A Review of the Clinical Effectiveness and Safety".CADTH Rapid Response Reports. Oct 2015.PMID 26561692.[dead link]
  13. ^Pini LA, Guerzoni S, Cainazzo MM, Ferrari A, Sarchielli P, Tiraferri I, Ciccarese M, Zappaterra M (November 2012)."Nabilone for the treatment of medication overuse headache: results of a preliminary double-blind, active-controlled, randomized trial".The Journal of Headache and Pain.13 (8):677–84.doi:10.1007/s10194-012-0490-1.PMC 3484259.PMID 23070400.
  14. ^Sholler DJ, Huestis MA, Amendolara B, Vandrey R, Cooper ZD (December 2020)."Therapeutic potential and safety considerations for the clinical use of synthetic cannabinoids".Pharmacol Biochem Behav.199 173059.doi:10.1016/j.pbb.2020.173059.PMC 7725960.PMID 33086126.
  15. ^Zhornitsky S, Pelletier J, Assaf R, Giroux S, Li CR, Potvin S (January 2021). "Acute effects of partial CB1 receptor agonists on cognition - A meta-analysis of human studies".Prog Neuropsychopharmacol Biol Psychiatry.104 110063.doi:10.1016/j.pnpbp.2020.110063.PMID 32791166.S2CID 221092170.
  16. ^Lutge EE, Gray A, Siegfried N (April 2013)."The medical use of cannabis for reducing morbidity and mortality in patients with HIV/AIDS".The Cochrane Database of Systematic Reviews (4) CD005175.doi:10.1002/14651858.CD005175.pub3.PMC 12127901.PMID 23633327.
  17. ^"Nabilone".Health Canada. Retrieved2023-07-01.
  18. ^abc"Valeant returns synthetic cannabinoid to USA".Pharma Times. 17 May 2006.
  19. ^"FDA turns down Valeant's anti-nausea drug".Pharma Times. 3 January 2006.
  20. ^"Cambridge Labs divests nabilone to Valeant - Pharmaceutical industry n".The Pharma Letter. February 27, 2007.
  21. ^"Cannabis Laws & Scheduling in Europe - MedicalMarijuana.eu".MedicalMarijuana.eu. Archived fromthe original on 18 November 2016. Retrieved17 November 2016.


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