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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Nabilone

Last Update: October 2, 2021.

OVERVIEW

Introduction

Nabilone is an orally available cannabinoid agonist that is used to treat chemotherapy induced nausea and vomiting and to stimulate appetite, particularly in patients with wasting disease or cachexia. Nabilone is associated with a minimal rate of serum enzyme elevations during therapy and has not been linked to cases of clinically apparent liver injury with jaundice.

Background

Nabilone (Nab’ i lone) is a synthetic cannabinoid which is similar to the principal psychoactive constituent of the marijuana plant (Cannabis sativa). Nabilone is a partial agonist of the cannabinoid receptors which are found in the central nervous system (CB1 receptor), but also peripherally (largely CB2 receptors). Activation of CB receptors results in effects on appetite, mood, cognition, memory and perception. Nabilone therapy has been shown to decrease nausea and vomiting in patients undergoing cancer chemotherapy. Nabilone was approved for use in the United States in 1985 and current indications are prevention of cancer chemotherapy associated nausea and vomiting. Nabilone is available as 1 mg capsules under the brand name Cesamet. The typical adult oral dose is 1 to 2 mg twice daily, the initial dose being 1 to 3 hours before the chemotherapeutic agent is given. Nabilone is usually reserved for patients who fail to response to or are intolerant of conventional antiemetics, such as the serotonin [5-HT3] receptor antagonists. Off-label uses of nabilone include as an appetite stimulant and for chronic pain relief, but its efficacy is not well established for either of these indications. Common side effects include fatigue, sedation, somnolence, dizziness, euphoria, abnormal thinking, paranoid reactions, impairment of driving and operation of heavy equipment, conjunctivitis, diarrhea, nausea, vomiting, abdominal pain, orthostatic hypotension and tachycardia. Rare side effects include hallucinations and seizures. Nabilone is classified as a Schedule II drug, indicating that it has clear potential for physical and psychological dependency and abuse.

Hepatotoxicity

Serum aminotransferase elevations during nabilone therapy are not common, generally mild and similar to the rate in controls who are receiving cancer chemotherapy. There have been no convincing cases of clinically apparent liver injury attributable to nabilone published in the literature and, thus, significant liver injury from nabilone must be exceeding rare, if it occurs at all.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Mechanism of Injury

Nabilone is metabolized by the liver and undergoes extensive first-pass metabolism to both active and inactive metabolites. Despite its hepatic metabolism by CYP microsomal enzymes, it has not been implicated in causing drug-drug interactions. The lack of reported cases of liver injury and low rate of drug-drug interactions due to nabilone may be due to the low doses and limited duration of typical therapy.

Drug Class: Gastrointestinal Agents, Antiemetic Agents

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Nabilone – Cesamet®

DRUG CLASS

Gastrointestinal Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

DRUGCAS REGISTRY NO.MOLECULAR FORMULASTRUCTURE
Nabilone 51022-71-0 C24-H36-O3 image 135001666 in the ncbi pubchem database

ANNOTATED BIBLIOGRAPHY

References updated: 02 October 2021

Abbreviations used: AIDS, acquired immune deficiency syndrome; CB, cannabinoids.

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    (Expert review of hepatotoxicity published in 1999 does not discuss nabilone).
  • Sharkey KA, MacNaughton WK. Antinauseants and antiemetics. Gastrointestinal motility bowel motility and water flux, emesis, and biliary and pancreatic disease. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 934-8.
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    (Among 94 patients with late stage AIDS treated with dronabinol [2.5-5 mg daily] for up to 12 months, there were "no significant changes in hematology or blood chemistry parameters").
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    (Among 300 cases of drug induced liver disease in the US collected between 2004 and 2008, no cases were attributed to cannabinoid agonists or antiemetics).
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  • Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al. United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology. 2015;148:1340–52. [PMC free article: PMC4446235] [PubMed: 25754159]
    (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, none were attributed to nabilone or other antiemetics).
  • Polito S, MacDonald T, Romanick M, Jupp J, Wiernikowski J, Vennettilli A, Khanna M, et al. Safety and efficacy of nabilone for acute chemotherapy-induced vomiting prophylaxis in pediatric patients: A multicenter, retrospective review. Pediatr Blood Cancer. 2018;65:e27374. [PubMed: 30051617]
    (Among 110 pediatric patients treated with nabilone for prevention of chemotherapy induced nausea and vomiting [usually in combination with a serotonin [5-HT3] receptor antagonist], adverse events arose in 34%, most commonly sedation [20%], dizziness [10%] and euphoria [4%], leading to discontinuation in 9%, but without serious adverse events; no mention of ALT elevations or hepatotoxicity).
  • Herrmann N, Ruthirakuhan M, Gallagher D, Verhoeff NPLG, Kiss A, Black SE, Lanctôt KL. Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer's Disease. Am J Geriatr Psychiatry. 2019;27:1161–1173. [PubMed: 31182351]
    (Among 38 elderly patients with Alzheimer disease treated with nabilone [titrated] or placebo for 6 weeks in a crossover trial, nabilone therapy was associated with a slight decrease in agitation but increase in sedation; no mention of ALT elevations or hepatoxicity).
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    (Concise review of the beneficial and adverse effects of cannabis and cannabinoids, 3 of which are FDA approved products, two synthetic agents that are used for prevention of chemotherapy induced nausea and vomiting [nabilone and dronabinol] and one a purified natural product used to treat rare forms of severe epilepsy [cannabidiol]; all of the cannabinoids can cause dizziness, somnolence, euphoria, abnormal thinking, difficulty concentrating, hypotension, hypertension, syncope and tachycardia as well as addiction and dependence with long term use; no mention of ALT elevations or hepatoxicity).
  • Sholler DJ, Huestis MA, Amendolara B, Vandrey R, Cooper ZD. Therapeutic potential and safety considerations for the clinical use of synthetic cannabinoids. Pharmacol Biochem Behav. 2020;199:173059. [PMC free article: PMC7725960] [PubMed: 33086126]
    (Extensive review of the endocannabinoid system and potential therapies for synthetic cannabinoids [CB] and CB receptor antagonists; while there are CB receptors in the liver [predominantly CB2], there is no evidence that the CBs in clinical practice cause liver injury).

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