Advertisement

Drugs

, Volume 25, Supplement 1, pp 52–62 | Cite as

Review of Cannabinoids and their Antiemetic Effectiveness

  • Beverly J. Vincent
  • Debra J. McQuiston
  • Lawrence H. Einhorn
  • Catherine M. Nagy
  • Mary J. Brames
Article

Summary

Marijuana has been used for over 2 centuries. Its major psychoactive constituent, delta-9-tetrahydrocannabinol (THC) was isolated in 1964 and first used to control nausea and vomiting during chemotherapy in the 1970s.

THC has cardiovascular, pulmonary and endocrinological effects as well as actions on the central nervous system. Alterations in mood, memory, motor coordination, cognitive ability, sensorium, spatial- and self-perception are commonly experienced. The precise antiemetic mechanism is unknown. THC and nabilone act at a number of sites within the central nervous system. Cannabinoids have also been shown to inhibit prostaglandin synthesis in vitro.

In controlled clinical trials, THC is superior to placebo and prochlorperazine in antiemetic effectiveness. Effectiveness of THC correlates to a ‘high’ experienced by the patient. A variety of chemotherapy regimens respond to THC including high-dose methotrexate and the doxorubicin, cyclophosphamide, fluorouracil combination. Cisplatin is more resistant. Side effects are generally well tolerated but may limit THC use in the elderly or when high doses are administered.

Nabilone, a synthetic cannabinoid, is also an effective antiemetic which is more active than prochlorperazine in preventing chemotherapy-induced emesis, including cisplatin-containing regimens. Side effects are similar to THC and may be dose-limiting.

Levonantradol, another synthetic cannabinoid, is an effective antiemetic. It may provide more flexibility in the outpatient setting since it can be administered orally or intramuscularly. Most side effects are mild except for dysphoria which may be dose-limiting.

Keywords

Prochlorperazine Nabilone Antiemetic Effect Tetrahydrocannabinol Antiemetic Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Agurell, S.; Levander, S.; Binder, M.; Bader-Bartfai, A.; Gustafsson, B.; Leander, K.; Lindgren, J.; Ohlsson, A. and Tobisson, B.: Pharmacokinetics of delta-8-tetrahydrocannabinol (Delta-6-tetrahydrocannabinol) in man after smoking — relations to physiological and psychological effects; in Braude and Szara (Eds) Pharmacology of Marihuana, pp.49–61 (Raven Press, New York 1976Google Scholar
  2. Benowitz, N.L. and Jones, R.T.: Cardiovascular and metabolic considerations in prolonged cannabinoid administration in man. Journal of Clinical Pharmacology 21: 214S–222S (1981)PubMedGoogle Scholar
  3. Burstein, S.H.: Prostaglandins and cannabis IV: A biochemical basis for therapeutic applications; in Cohen and Stillman (Eds) The Therapeutic Potential of Marijuana, pp.19–33 (Plenum Medical Book Company, New York and London 1976)CrossRefGoogle Scholar
  4. Chang, S.E.; Shiling, D.J.; Stillman, R.C.; Goldberg, N.H.; Seipp, C.A.; Barofsky, I.; Simon, R.M. and Rosenberg, S.A.: Delta-9-tetrahydrocannabinol as an antiemetic in cancer patients receiving high-dose methotrexate. Annals of Internal Medicine 91: 819–824 (1979)PubMedGoogle Scholar
  5. Chopra, G.S.: Studies on psycho-clinical aspects of long-term marijuana use in 124 cases. International Journal of The Addiction 8: 1015–1026 (1973)Google Scholar
  6. Cronin, CM.; Sallan, S.E.; Gelber, R.; Lucas, U.S. and Laszlo, J.: Antiemetic effect of intramuscular levonantradol in patients receiving anti-cancer chemotherapy. Journal of Clinical Pharmacology 21: 43S–50S (1981)PubMedGoogle Scholar
  7. Einhorn, L.H.: Comparison of nabilone and placebo in patients receiving cancer chemotherapy. (Unpublished study, 1982.)Google Scholar
  8. Ekert, H.; Waters, K.D.; Jurk, I.H.; Mobilia, J. and Loughman, P.: Amelioration of cancer chemotherapy-induced nausea and vomiting by delta-9-tetrahydrocannabinol. Medical Journal of Australia 2: 657–659 (1979)PubMedGoogle Scholar
  9. Frytak, S.; Moertel, C.G.; O’Fallon, J.R.; Rubin, J.; Creagan, E.T.; O’Connell, M.J.; Schutt, A.J. and Schwartau, N.W.: Delta-9-tetrahydrocannabinol as an antiemetic for patients receiving cancer chemotherapy. Annals of Internal Medicine 91: 825–830 (1979)PubMedGoogle Scholar
  10. Gaoni, Y. and Mechoulam, R.: Isolation, structure and partial synthesis of an active constituent of hashish. Journal of The American Chemistry Society 86: 1646–1647 (1964)CrossRefGoogle Scholar
  11. Garb, S.: Cannabinoids in the management of severe nausea and vomiting from cancer chemotherapy: Some additional considerations. Journal of Clinical Pharmacology 21: 57S–59S (1981)PubMedGoogle Scholar
  12. Garb, S.; Beers, A.L. and Bograd, M.: Two-pronged studies of tetrahydrocannabinol (THC) prevention of vomiting from cancer chemotherapy. IRCS Medical Science 2: 203–204 (1980)Google Scholar
  13. Gralla, R.J.; Tyson, L.B.; Clark, R.A.; Bordin, L.A.; Kelsen, D.P. and Kalman, L.B.: Antiemetic trials with high dose metoclopramide: Superiority over THC, and preservation of efficacy in subsequent chemotherapy courses. Proceedings of the American Society of Clinical Oncology 1: 58 (1982)Google Scholar
  14. Herman, T.S.; Einhorn, L.H. and Jones, S.E.: Superiority of nabilone over prochlorperazine as an antiemetic in patients receiving cancer chemotherapy. New England Journal of Medicine 300: 1295–1297 (1979)PubMedCrossRefGoogle Scholar
  15. Herman, T.S.; Jones, S.E.; Dean, J.; Leigh, S.; Dorr, R.; Moon, T.E. and Salmon, S.E.: Nabilone: A potent antiemetic cannabinol with minimal euphoria. Biomedicine 27: 331–334 (1977)PubMedGoogle Scholar
  16. Hermbree, W.C.; Nahas, G.G. and Huang, H.F.S.: Changes in human spermatozoa associated with high dose marijuana smoking; in Nahas and Paton (Eds) Marihuana: Biological Effects, pp.429–439 (Pergamon Press, New York, 1979Google Scholar
  17. Hoffman, D.; Brunnemann, K.D.; Gori, G.B. and Wynder, E.L.: On the carcinogenicity of marihuana smoke. Research Advanced Phytochemistry 9: 63–81 (1975)CrossRefGoogle Scholar
  18. Hollister, L.E.: Marihuana in man: Three years later. Science 171: 21–29 (1971)CrossRefGoogle Scholar
  19. Homesley, H.D.; Gainey, J.; Jobson, V.W.; Spurr, C.; Welander, C.E.; Muss, H.B. and Kimball, J.: Failure of delta-9-tetrahydrocannabinol and prochlorperazine to control chemotherapy induced nausea and vomiting. Proceedings of the American Society of Clinical Oncology 1: 67 (1982) (Abstract).Google Scholar
  20. Jaffe, J.H.: Drug addiction and drug abuse; in Gilman, Goodman and Gilman (Eds) The Pharmacological Basis of Therapeutics, pp.561–563 (McMillan Publishing Company, New York 1980Google Scholar
  21. Jones, R.T.; Marihuana-induced ‘high’ influence of expectation, setting and previous drug experience. Pharmacology Review 23: 359–369 (1971)Google Scholar
  22. Kanakis, C.; Poujet, J. and Rosen, K.: Lack of cardiovascular effects of delta-9-THC in chemically denervated men. Annals of Internal Medicine 91: 571–574 (1979)PubMedGoogle Scholar
  23. Krupp, P. and Wesp, M.: Inhibition of prostaglandin synthetase by psychotropic drugs. Experientia 31: 330–331 (1975)PubMedCrossRefGoogle Scholar
  24. Laszlo, J.; Lucas, U.S.; Hanson, D.C.; Cronin, C.M.; Sallan, S.E.: Levonantradol for chemotherapy-induced emesis: Phase I–II oral administration. Journal of Clinical Pharmacology 21: 51S–56S (1981)PubMedGoogle Scholar
  25. Lemberger, L.; Axelrod, J. and Kopin, I.J.: New York Academy of Science Conference on Marijuana. Abstract 12 1971Google Scholar
  26. Lemberger, L. and Rowe, H.: Clinical pharmacology of nabilone, a cannabinol derivative. Clinical Pharmacology and Therapeutics 18: 720–726 (1975)PubMedGoogle Scholar
  27. London, S.W.; McCarthy, L.E.; and Borison, H.L.: Suppression of cancer chemotherapy induced vomiting in the cat by nabilone, a synthetic cannabinoid. Proceedings of the Society of Experimental Biological Medicine 160: 437–440 (1979)Google Scholar
  28. Long, A.; Mioduszeuski, J.; Natale, R.: A randomized double-blind crossover comparison of the antiemetic activity of levonantradol and prochlorperazine. Proceedings of the American Society of Clinical Oncology 1: 57 (1982) (Abstract).Google Scholar
  29. Lucas, V.S. and Laszlo, J.: Delta-9-tetrahydrocannabinol for refractory vomiting induced by cancer chemotherapy. Journal of the American Medical Association 243: 1241–1243 (1980)PubMedCrossRefGoogle Scholar
  30. Mahajan, V.K. and Huber, G.L.: Marijuana’s effects on the cardiopulmonary system. Parts 1 and 2. Primary Cardiology 4(6): 54–59 1978 and ibid 4(7): 59–63 1978Google Scholar
  31. Martin, B.: Abnormal Psychology: Clinical and Scientific Perspectives, pp.507–508 (Holt, Rinehart and Winston, New York 1977Google Scholar
  32. Mechoulam, R. (Ed): Marihuana: Chemistry, Pharmacology and Metabolism (Academic Press, New York 1973Google Scholar
  33. Melges, F.T.; Tinklenberg, J.R.; Hollister, L.E. and Gillespie, H.K.: Temporal disintegration and depersonalization during marijuana intoxication. Archives of General Psychiatry 23: 204–210 (1970)PubMedCrossRefGoogle Scholar
  34. Nagy, C.M.; Furnas, B.E.; Einhorn, L.H. and Bond, W.H.: Nabilone antiemetic cross-over study in cancer chemotherapy patients. Proceedings of the American Association for Cancer Research 19: 30 (1978) (Abstract).Google Scholar
  35. Orr. L.E.; McKerman, J.F. and Bloone, B.: Antiemetic effect of tetrahydrocannabinol. Archives of Internal Medicine 140: 1431–1433 (1980)PubMedCrossRefGoogle Scholar
  36. Perez-Reyes, M.; Lipton, M.A.; Timmons, M.C.; Wall, M.E.; Brine, D.R. and Davis, K.H.: Pharmacology of orally administered delta-9-tetrahydrocannabinol. Clinical Pharmacology and Therapeutics 14: 48–55 (1973)PubMedGoogle Scholar
  37. Petersen, R.C.: Marijuana and Health. National Institute for Drug Abuse and Research. Monograph 31 pp.1–51 (Department of Health and Human Services, 1980Google Scholar
  38. Sallan, S.E.: Cronin, C; Zelen, M. and Zinberg, N.E.: Antiemetics in patients receiving chemotherapy for cancer. New England Journal of Medicine 302: 135–138 (1980)PubMedCrossRefGoogle Scholar
  39. Sallan, S.E.; Zinberg, N.E. and Frei, E.: Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. New England Journal of Medicine 293: 795–797 (1975)PubMedCrossRefGoogle Scholar
  40. Shepard, R.M.: Pharmacokinetics of levonantradol in laboratory animals and man. Journal of Clinical Pharmacology 21: 190S–200S (1981)PubMedGoogle Scholar
  41. Stambaugh, J.E.; McAdams, J. and Vreeland, F.: A phase II randomized trial of the antiemetic activity of levonantradol in cancer patients receiving chemotherapy. Proceedings of the American Society of Clinical Oncology 1: 62 (1982) (Abstract).Google Scholar
  42. Steele, N.; Gralla, R.J. and Braun, D.W.: Double-blind comparison of the antiemetic effects of nabilone and prochlorperazine on chemotherapy-induced emesis. Cancer Treatment Reports 64: 219–224 (1980)PubMedGoogle Scholar
  43. Tyson, L.; Gralla, R.J.; Bordin, L.A.; Clark, R.A.; Bosl, G.J. and Young, C.W.: Levonantradol: Dose-finding studies and antiemetic trials in patients treated with cisplatin. Proceedings of the American Society of Clinical Oncolocy 1: 56 (1982) (Abstract).Google Scholar
  44. Wahlqvist, M.; Nilsson, I.M.; Sandberg, F.; Agurell, S. and Grandstand, B.: Biochemical Pharmacology 19: 2579–2584 (1970)PubMedCrossRefGoogle Scholar
  45. Wall, M.E. and Perez-Reyes, M.: The metabolism of delta-9-tetrahydrocannabinol and related cannabinoids in man. Journal of Clinical Pharmacology 21: 178S–189S (1981)PubMedGoogle Scholar

Copyright information

© ADIS Press Australasia Pty Ltd 1983

Authors and Affiliations

  • Beverly J. Vincent
    • 1
  • Debra J. McQuiston
    • 1
  • Lawrence H. Einhorn
    • 1
  • Catherine M. Nagy
    • 1
  • Mary J. Brames
    • 1
  1. 1.Department of MedicineIndiana UniversityIndianapolis

Personalised recommendations