Anorexia can affect up to 90 % of people with advanced cancer. It is a complex symptom associated with changes in taste, lack of hunger at mealtimes and lack of food enjoyment. Associated weight loss is part of the physical decline that occurs as cancer worsens. Weight loss can also occur from cachexia, the increased metabolism of energy due to raised inflammatory cytokines, liver metastases and other factors seen in several advanced cancers. Independent of anorexia, although frequently associated (where it is referred to as the cachexia-anorexia syndrome), it accounts for a significant amount of morbidity and deaths in people with cancer. In particular, quality of life for the patient and the family is significantly affected with this syndrome as it causes anxiety and distress. Therefore, it is important that research into therapies is undertaken, particularly focusing on an understanding of the pharmacokinetic properties of compounds in this cachexic population. Cannabinoids are one such group of therapies that have received a large amount of media focus recently. However, there appears to be a lack on rigorous pharmacokinetic data of these complex and varied compounds in the cachexic population. Similarly, there is a lack of pharmacokinetic data in any population group for the non- tetrahydrocannabinol (THC) and cannabidiol (CBD) cannabinoids (often due to the lack of analytical standards for quantification). This review will thus examine the pharmacokinetics of major cannabinoids i.e. THC and CBD in a cancer population. Overall, based on the current literature, evidence for the use of cannabinoids for the treatment of cancer-related cachexia-anorexia syndrome remains equivocal. A high-quality, rigorous, phase I/II study to elicit pharmacokinetic dose–concentration and concentration–response data, with a clinically acceptable mode of delivery to reduce intrapatient variability and enable more consistent bioavailability is needed in this population.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Reid J, McKenna H, Fitzsimons D, McCance T. The experience of cancer cachexia: a qualitative study of advanced cancer patients and their family members. Int J Nurs Stud. 2009;46(5):606–16.
Poole K, Froggatt K. Loss of weight and loss of appetite in advanced cancer: a problem for the patient, the carer, or the health professional? Palliat Med. 2002;16(6):499–506.
Mantovani G, Madeddu C. Cancer cachexia: medical management. Support Care Cancer. 2010;18(1):1–9.
Yavuzsen T, Davis MP, Walsh D, LeGrand S, Lagman R. Systematic review of the treatment of cancer-associated anorexia and weight loss. J Clin Oncol. 2005;23(33):8500–11.
Miller S, McNutt L, McCann MA, McCorry N. Use of corticosteroids for anorexia in palliative medicine: a systematic review. J Palliat Med. 2014;17(4):482–5.
Ruiz Garcia V, Lopez-Briz E, Carbonell Sanchis R, Gonzalvez Perales JL, Bort-Marti S. Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev. 2013;3:CD004310.
Russo EB. History of cannabis and its preparations in saga, science, and sobriquet. Chem Biodivers. 2007;4(8):1614–48.
Engeli S. Central and peripheral cannabinoid receptors as therapeutic targets in the control of food intake and body weight. Handb Exp Pharmacol. 2012;209:357–81.
Pichard C, Kyle U. Body composition measurements during wasting diseases. Curr Opin Clin Nutr Metab Care. 1998;1(4):357–61.
Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4(8):1770–804.
Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet. 2003;42(4):327–60.
Lindgren JE, Ohlsson A, Agurell S, Hollister L, Gillespie H. Clinical effects and plasma levels of delta 9-tetrahydrocannabinol (delta 9-THC) in heavy and light users of cannabis. Psychopharmacology. 1981;74(3):208–12.
Huestis MA, Sampson AH, Holicky BJ, Henningfield JE, Cone EJ. Characterization of the absorption phase of marijuana smoking. Clin Pharmacol Ther. 1992;52(1):31–41.
Ohlsson A, Widman M, Carlsson S, Ryman T, Strid C. Plasma and brain levels of delta 6-THC and seven monooxygenated metabolites correlated to the cataleptic effect in the mouse. Acta Pharmacol Toxicol (Copenh). 1980;47(4):308–17.
Wall ME, Sadler BM, Brine D, Taylor H, Perez-Reyes M. Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women. Clin Pharmacol Ther. 1983;34(3):352–63.
Guy GW, Robson PJ. A phase I, double-blind, three-way crossover study to assess the pharmacokinetic profile of cannabis based medicine extract (CBME) administered sublingually in variant cannabinoid ratios in normal healthy male volunteers. J Cannabis Ther. 2003;3(4):121–51.
Karschner EL, Darwin WD, Goodwin RS, Wright S, Huestis MA. Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration. Clin Chem. 2011;57(1):66–75.
Agurell S, Leander K. Stability, transfer and absorption of cannabinoid constituents of cannabis (hashish) during smoking. Acta Pharm Suec. 1971;8(4):391–402.
Hunt CA, Jones RT. Tolerance and disposition of tetrahydrocannabinol in man. J Pharmacol Exp Ther. 1980;215(1):35–44.
Kreuz DS, Axelrod J. Delta-9-tetrahydrocannabinol: localization in body fat. Science. 1973;179(4071):391–3.
Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev. 2014;46(1):86–95.
Heuberger JA, Guan Z, Oyetayo OO, Klumpers L, Morrison PD, Beumer TL, et al. Population pharmacokinetic model of THC integrates oral, intravenous, and pulmonary dosing and characterizes short- and long-term pharmacokinetics. Clin Pharmacokinet. 2015;54(2):209–19.
Trobec K, Kerec Kos M, von Haehling S, Springer J, Anker SD, Lainscak M. Pharmacokinetics of drugs in cachectic patients: a systematic review. PLoS One. 2013;8(11):e79603.
Barry RE. Malignancy, weight loss, and the small intestinal mucosa. Gut. 1074;15(7):562–70.
King D, Smith ML, Chapman TJ, Stockdale HR, Lye M. Fat malabsorption in elderly patients with cardiac cachexia. Age Ageing. 1996;25(2):144–9.
Fearon K, Preston T. Body composition in cancer cachexia. Infusionstherapie. 1990;17(Suppl 3):63–6.
Morgan ET, Goralski KB, Piquette-Miller M, Renton KW, Robertson GR, Chaluvadi MR, et al. Regulation of drug-metabolizing enzymes and transporters in infection, inflammation, and cancer. Drug Metab Dispos. 2008;36(2):205–16.
Herrington JD, Tran HT, Riggs MW. Prospective evaluation of carboplatin AUC dosing in patients with a BMI> or = 27 or cachexia. Cancer Chemother Pharmacol. 2006;57(2):241–7.
Mouly S, Aymard G, Diquet B, Caulin C, Bergmann JF. Oral ganciclovir systemic exposure is enhanced in HIV-infected patients with diarrhea and weight loss. J Acquir Immune Defic Syndr. 2000;24(4):344–51.
Cvan Trobec K, Kerec Kos M, Trontelj J, Grabnar I, Tschirner A, Palus S, et al. Influence of cancer cachexia on drug liver metabolism and renal elimination in rats. J Cachexia Sarcopenia Muscle. 2015;6(1):45–52.
Trauner M, Fickert P, Stauber RE. Inflammation-induced cholestasis. J Gastroenterol Hepatol. 1999;14(10):946–59.
Slaviero K, Clarke SJ, Rivory L. Inflammatory response: an unrecognised source of variability in the pharmacokinetics and pharmacodynamics of cancer chemotherapy. Lancet Oncol. 2003;4(4):224–32.
Timpone JG, Wright DJ, Li N, Egorin MJ, Enama ME, Mayers J, et al. The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative. AIDS Res Hum Retrovir. 1997;13(4):305–15.
Ekert H, Waters KD, Jurk IH, Mobilia J, Loughnan P. Amelioration of cancer chemotherapy-induced nausea and vomiting by delta-9-tetrahydrocannabinol. Med J Aust. 1979;2(12):657–9.
Regelson W, Butler J, Schulz J, Kirk T, Peek L, Green M. Delta-9-tetrahydrocannabinol (delta-9-THC) as an effective antidepressant and appetite-stimulating agent in advanced cancer patients. In: Braude MS, Szara S, editors. In: Proceedings of an International Conference on the Pharmacology of Cannabis. New York: Raven Press; 1975. p. 269–87.
Nelson K, Walsh D, Deeter P, Sheehan F. A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. J Palliat Care. 1994;10(1):14–8.
Plasse TF, Gorter RW, Krasnow SH, Lane M, Shepard KV, Wadleigh RG. Recent clinical experience with dronabinol. Pharmacol Biochem Behav. 1991;40(3):695–700.
Beal JE, Olson R, Laubenstein L, Morales JO, Bellman P, Yangco B, et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage. 1995;10(2):89–97.
Jatoi A, Windschitl HE, Loprinzi CL, Sloan JA, Dakhil SR, Mailliard JA, et al. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol. 2002;20(2):567–73.
Strasser F, Luftner D, Possinger K, Ernst G, Ruhstaller T, Meissner W, et al. Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. J Clin Oncol. 2006;24(21):3394–400.
Radbruch L, Elsner F, Trottenberg P, Strasser F, Fearon K. Clinical practice guidelines on cancer cachexia in advanced cancer patients. Aachen: Department of Palliative Medicine/European Palliative Care Research Collaborative; 2010.
Brisbois TD, de Kock IH, Watanabe SM, Mirhosseini M, Lamoureux DC, Chasen M, et al. Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial. Ann Oncol. 2011;22(9):2086–93.
No funding was provided for this manuscript. Government funding for rigorous clinical trials in medicinal cannabis use have been provided for research projects in New South Wales, Australia.
Conflicts of interest
Jennifer H. Martin and Stephanie E. Reuter are part of the New South Wales Government-funded phase II project team in clinical pharmacology for a study commencing in 2016. Jennifer H. Martin is funded by the University of Newcastle and Calvary Mater Hospital, NSW, Australia, and Stephanie E. Reuter receives funds from the National Health and Medical Research Council, University of South Australia and University of Newcastle.
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
Cite this article
Reuter, S.E., Martin, J.H. Pharmacokinetics of Cannabis in Cancer Cachexia-Anorexia Syndrome. Clin Pharmacokinet 55, 807–812 (2016). https://doi.org/10.1007/s40262-015-0363-2
- Cancer Cachexia
- Cannabis Extract