Skip to main content
SpringerLink
Log in

Review of Cannabinoids and their Antiemetic Effectiveness

  • Published:
Drugs Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • 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 1976

    Google Scholar 

  • 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)

    PubMed  CAS  Google Scholar 

  • 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)

    Chapter  Google Scholar 

  • 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)

    PubMed  CAS  Google Scholar 

  • 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)

    CAS  Google Scholar 

  • 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)

    PubMed  CAS  Google Scholar 

  • Einhorn, L.H.: Comparison of nabilone and placebo in patients receiving cancer chemotherapy. (Unpublished study, 1982.)

  • 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)

    PubMed  CAS  Google Scholar 

  • 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)

    PubMed  CAS  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

  • 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)

    PubMed  CAS  Google Scholar 

  • 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 

  • 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 

  • 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)

    Article  PubMed  CAS  Google Scholar 

  • 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)

    PubMed  CAS  Google Scholar 

  • 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, 1979

    Google Scholar 

  • 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)

    Article  Google Scholar 

  • Hollister, L.E.: Marihuana in man: Three years later. Science 171: 21–29 (1971)

    Article  Google Scholar 

  • 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 

  • 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 1980

    Google Scholar 

  • Jones, R.T.; Marihuana-induced ‘high’ influence of expectation, setting and previous drug experience. Pharmacology Review 23: 359–369 (1971)

    CAS  Google Scholar 

  • 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)

    PubMed  CAS  Google Scholar 

  • Krupp, P. and Wesp, M.: Inhibition of prostaglandin synthetase by psychotropic drugs. Experientia 31: 330–331 (1975)

    Article  PubMed  CAS  Google Scholar 

  • 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)

    PubMed  CAS  Google Scholar 

  • Lemberger, L.; Axelrod, J. and Kopin, I.J.: New York Academy of Science Conference on Marijuana. Abstract 12 1971

  • Lemberger, L. and Rowe, H.: Clinical pharmacology of nabilone, a cannabinol derivative. Clinical Pharmacology and Therapeutics 18: 720–726 (1975)

    PubMed  CAS  Google Scholar 

  • 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)

    CAS  Google Scholar 

  • 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 

  • 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)

    Article  PubMed  Google Scholar 

  • 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 1978

    Google Scholar 

  • Martin, B.: Abnormal Psychology: Clinical and Scientific Perspectives, pp.507–508 (Holt, Rinehart and Winston, New York 1977

    Google Scholar 

  • Mechoulam, R. (Ed): Marihuana: Chemistry, Pharmacology and Metabolism (Academic Press, New York 1973

    Google Scholar 

  • 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)

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Orr. L.E.; McKerman, J.F. and Bloone, B.: Antiemetic effect of tetrahydrocannabinol. Archives of Internal Medicine 140: 1431–1433 (1980)

    Article  PubMed  CAS  Google Scholar 

  • 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)

    PubMed  CAS  Google Scholar 

  • Petersen, R.C.: Marijuana and Health. National Institute for Drug Abuse and Research. Monograph 31 pp.1–51 (Department of Health and Human Services, 1980

  • 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)

    Article  PubMed  CAS  Google Scholar 

  • 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)

    Article  PubMed  CAS  Google Scholar 

  • Shepard, R.M.: Pharmacokinetics of levonantradol in laboratory animals and man. Journal of Clinical Pharmacology 21: 190S–200S (1981)

    PubMed  CAS  Google Scholar 

  • 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 

  • 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)

    PubMed  CAS  Google Scholar 

  • 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 

  • Wahlqvist, M.; Nilsson, I.M.; Sandberg, F.; Agurell, S. and Grandstand, B.: Biochemical Pharmacology 19: 2579–2584 (1970)

    Article  PubMed  CAS  Google Scholar 

  • 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)

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Indiana University, Indianapolis, Indiana

    Beverly J. Vincent, Debra J. McQuiston, Lawrence H. Einhorn, Catherine M. Nagy & Mary J. Brames

Authors
  1. Beverly J. Vincent
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Debra J. McQuiston
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lawrence H. Einhorn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Catherine M. Nagy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mary J. Brames
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vincent, B.J., McQuiston, D.J., Einhorn, L.H. et al. Review of Cannabinoids and their Antiemetic Effectiveness. Drugs 25 (Suppl 1), 52–62 (1983). https://doi.org/10.2165/00003495-198300251-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-198300251-00006

Keywords

Search

Navigation