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Cancer chemotherapy

The drugs used to treat cancer are among the most powerful, and most toxic, chemicals used in medicine. They kill both cancer cells and healthy cells, producing extremely unpleasant and dangerous side effects. The most common is days or weeks of vomiting, retching, and nausea after each treatment. The feeling of loss of control is highly depressing, and patients find it very difficult to eat anything, and lose weight and strength. People find it more and more difficult to sustain the will to live, and many chose to discontinue treatment, preferring death to treatment.

Cannabis can be used as an antiemetic, a drug which relieves nausea and allows patients to eat and live normally. Despite great advances in the last few years of antiemetic research, cannabis is safer, cheaper and often more effective than standard synthetic antiemetics. Smoking cannabis can be more effective than taking it (or its synthetic derivatives such as Marinol) orally as patients it difficult to keep anything down long enough for it to have an effect. Smoking cannabis produces an immediate effect, and patients find it easier to control the dosage. Additionally the euphoric properties act as an anti-depressant, and the hunger and enjoyment of food properties ('the munchies') make weight gain easy, and these increase the chances of recovery.

The method by which chemotherapy generates nausea and vomiting is not entirely certain, although studies point to it being caused by receptor stimulation in the central nervous system or gastrointestinal tract. However, cannabis as an antiemetic seems to work via a different mechanism than the currently-used antiemetic drugs in this field (such as corticosteroids). It is therefore worthy of investigation whether a combination of cannabinoids and existing therapies may benefit the patient more than either of the two taken separately. It also suggests that patients who do not respond well to traditional antiemetic medications may find greater benefit with cannabis-based drugs.

A relatively large number of studies have been done on the anti-emetic properties of cannabis in regard to the negative effects of chemotherapy. Almost invariably cannabis (and some of its constituent cannabinoids) have been found effective. As a result of this, in 1985 the US FDA licenced synthetic THC (Dronabinol) for these symptoms. In the UK however it is not licensed in this way. It is actually possible to prescribe Dronabinol to patients in the UK, but only on an individual basis. This is very rarely done, perhaps not surprisingly given the large amount of administrative obstacles that need to be overcome.

However, in 1982 Nabilone (an analogue of delta-9-THC) was licensed in the UK to allow it to be prescribed for nausea following chemotherapy, as long as other treatment was ineffective and that it was solely used within a hospital environment.

In terms of efficacy, cannabis has several competitors as an antiemetic. However, the Institute of Medicine's 1999 report summed it up nicely when it stated that 'the critical issue is not whether marijuana of cannabinoid drugs might be superior to the new drugs, but rather whether there is a group of patients who might obtain added or better relief from marijuana or cannabinoid drugs'.

Both scientific research and testimonies of currently-criminalised users seem to state that this group of patients does indeed exist.

The treatment of nausea and vomiting is not the only way in which cannabis can help cancer sufferers. Both the analgesic (pain-relieving) and appetite-stimulating qualities of cannabis can make a patient's life both longer and far more bearable.

Several cannabis-related medications have been tested for their effects on nausea caused by chemotherapy, including delta-9-THC, delta-8-THC, Nabilone, Levonantradol and BRL-4664, as well as 'natural' cannabis

THC was almost always found to produce significant antiemetic properties. One of the first studies was by Sallan et al (1975). The study compared oil-based capsules containing THC given to 20 patients both before and after chemotherapy treatment. Fourteen of the patients found THC to be an effective antiemetic. Chang et al (1979) found that THC was an effective antiemetic to counteract the nauseous effects of the methotrexate medication used in chemotherapy, with 14 out of 15 patients reporting some relief of nausea and vomiting. Two years later Chang et al found that it was also effective in patients undergoing treatment with anthracyclines (which produce a higher level of emetic behaviour) albeit to a limited extent. Lucas et al (1980) gave THC to 53 patients to whom other treatments were unsatisfactory. 10 suffered no vomiting after chemotherapeutic treatment. Another 28 had more than a 50% reduction in vomiting.

Studies by Frytak et al (1979), Orr et al (1980) and Sallan et al (1980) showed a comparison between patients receiving the antiemetic drug prochlorperazine and THC. Typically oral THC was found to be of a similar efficiacy to prochlorperazine. Whilst comparing THC to metoclopramide, Gralla et al (1984) found that THC completely stopped vomiting in 13% of patients, and almost eliminated it in another 27%.

With regard to the lesser-studied variants of THC, McCarthy et al (1984) found that a metabolite of THC, 11-OH-THC was less effective as an antiemetic than THC. Razden (1986) however found that delta-8-THC completely prevented any emesis in 8 children undergoing chemotherapy. Moreover, delta-8-THC is significantly less psychoactive than delta-9-THC and very few side-effects were reported.

As stated, the synthetic cannabinoids Nabilone and Levonantradol have also been investigated (Steele et al 1980 and Tyson et al 1985 respectively). These produced similarly effective antiemetic results to THC. Herman et al (1979) found that medicating with Nabilone was significantly more effective that treatment with the standard antiemetic prochlorperazine.

Staquet et al (1981) investigated another THC homologue known as BRL-4664. This too showed some antiemetic effect.

Vincigeurra et al (1988) found that 78% of 56 patients with nausea who were resistant to standard drugs became symptom free through inhaling cannabis. All of these found that cannabis was either a 'moderately effective' or 'highly effective' form of therapy.

The method of administration for medicinal cannabis can be of importance. Firstly, patients suffering severe vomitting may not be able to keep orally-given cannabis down long enough to have effect. Inhalation, whether by smoking or other means, removes this obstacle, and studies such as Ohlsson's (1980) have shown that the effects of inhaled cannabis start much sooner (almost immediately) than if it is taken orally.

Levitt et al (1984) compared chemotherapy patients given either oral THC or smoked cannabis. Both appeared to have similar antiemetic effectiveness, with about 25% of each group gaining total control of emesis. In a post-treatment survey, 35% of patients slightly preferred receiving oral THC, 20% preferred smoking cannabis and 45% had no preference.

On the other hand, Chang et al (1979) found that smoking cannabis rather than taking it orally seemed more effective. In addition, a report published by the Board of Pharmacy in Tennessee (1983) found a 23% higher success rate in those patients who smoked cannabis rather than those who took oral THC. McNeill (1983) found the same overall result. 75% of patients who took any form of THC showed a significant improvement in their condition. When routes of administration were taken into account it was found that 90% of those who inhaled cannabis showed and improvement, compared to 60% of those who took it orally. Likewise Vincigeurra et al's (1988) study also found inhaled cannabis to have advantages over THC taken orally.

There seems to be no definite answer as to whether or not the psychoactive effects of cannabis play a part in its antiemetic effectiveness. Gralla et al (1984) reported no correlation between the psychoactive effects (in terms of euphoria or dysphoria) and the effectiveness of the antiemetic properties. Sallan et al (1980) reported the opposite!

On a less pharmacological note, Doblin and Kleiman (1991) sent a questionnaire to US oncologists (cancer specialists). 44% of the respondents had recommended illegal use of cannabis and half of them would prescribe it if it were legal.

The Institute of Medicine's report (1999) concluded that after reviewing the most valid trials, 'the evidence indicated that cannabinoids reduce emesis in about one quarter of patients receiving cancer chemotherapy' and that 'the side effects associated with cannabinoid use are generally tolerable'. Likewise, in a review of the research conducted by Hall et al (1994), it was concluded that '...THC is superior to placebo, and equivalent in effectiveness to other widely-used anti-emetic drugs...' when used to medicate these symptoms.

Annual Report (1983): Evaluation of Marijuana and Tetrahydrocannabinol in Treatment of Nausea and/or Vomiting Associated with Cancer Chemotherapy Unresponsive to Conventional Anti-Emetic Therapy: Efficacy and Toxicity, Board of Pharmacy, State of Tennessee 5;

Chang et al., (1979) Delta-9-THC as an Antiemetic in Cancer Patients Receiving High Dose methotrexate. Ann. Internal Med. 91 819-824

Chang AK, Shiling DJ, Stillman RC, Goldberg NH, Seipp CA, Barofsky I, Rosenberg SA. (1981) A prospective evaluation of delta-9-tetrahydrocannabinol as an antiemetic in patients receiving adriamycin and cytoxan chemotherapy. Cancer 47:1746-51.

Doblin and Kleiman, (1991) Marihuna as Anti-emetic medicine: A Survey of Oncologists' Attitudes and Experiences. J. Cli. Oncology 9 1275-1280

Frytak S. Moertel CG, O'Fallon J. et al. (1979) Delta-9-tetrahydrocannabinol as an antiemetic in patients treated with cancer chemotherapy: a double comparison with prochloperazine and a placebo. Annals of Internal Medicine 91 :825-830.

Gralla RJ, Tyson LB, Borden LB, et al. (1984) Antiemetic therapy a review of recent studies and a report of a random assignment trial comparing metoclopramide with delta-9-tetrahydrocannabinol. Cancer Treatment Reports 68:163-172.

W. Hall, et al. (1994) The Health and Psychological Consequences of Cannabis Use, Canberra, Australian Government Publishing Service 189.

Herman, T.S., Einhorn, L.H., Jones, S.E., Nagy, C., Chester, A.B., Dean, J.C., Furnas, B., Williams, S.D., Leigh, S.A., Dorr, R.T., and Moon, T.E. (1979) Superiority of nabilone over prochlorperazine as an antiemetic in patients receiving cancer chemotherapy. N. Engl. J. Med. 300: 1295­1298.

House of Lords Select Committee on Science and Technology (1998) Science and Technology - Ninth report. Science and Technology Committee Publications, UK.

Institute of Medicine (1999) Marijuana and medicine: Assessing the science base. National Academy Press

Levitt M, Faiman C, Hawks R. et al. (1984) Randomized double-blind comparison of delta-9- THC and marijuana as chemotherapy antiemetics. Proceedings of the American Society for Clinical Oncology 3:91.

Lucas, V.S.,Jr., and Laszlo, J. (1980) Delta­9­tetrahydrocannabinol for refractor vomiting induced by cancer chemotherapy. J. Am. Med. Assoc. 243: 1241­1243.

McCarthy LE, Flora KP, Vishnuvajjala BR. (1984) Antiemetic properties and plasma concentrations of delta-9-tetrahydrocannabinol against cisplatin vomiting in cats. In: Agurell S. Dewey WL, Willette RE, Editors The Cannabinoids: Chemical, Pharmacologic and Therapeutic Aspects. Orlando, FL: Academic Press. Pp. 859- 870.

McNeill R. (1983), The Lynn Pierson Therapeutic Research Program: A Report on Progress to Date, Behavioral Health Services Division, Health and Environment Department, State of New Mexico, 4;

Ohlsson A, Lindgren J-E, Wahlen A, Agurell S. Hollister L E, Gillespie HK. (1980) Plasma delta-9-tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clinical Pharmacology and Therapeutics 28:409-416.

Orr LE, McKernan JF, Bloome B. (1980). Antiemetic effect of Tetrahydrocannabinol. Compared with placebo and prochlorperazine in chemotherapy-associated nausea and emesis. Archives of Internal Medicine 140:1431 -3.

Razdan RK. (1986) Structure-activity relationships in cannabinoids. Pharmacology Review 38:75-149.

Sallan, S.E., Zinberg, N.E., and Frei, E. (1975) Antiemetic effect of delta­9­tetrahydrocannabinol in patients receiving cancer chemotherapy. N. Engl. J. Med. 293: 795­79

Sallan SE, Cronin CM, Zelen M, et al. (1980) Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine. New England Journal of Medicine 302: 135 - 138.

Staquet, M., Bron, D., Rosencweig, M., and Kenis, Y. (1981) Clinical studies with a THC homolog (BRL­4664) in prevention of cisplatin­induced vomiting. J. Clin. Pharmacol. 21: 60S­63S.

Steele N. Gralla RJ, Braun DW, Jr. (1980) Double-blind comparison of the antiemetic effects of nabilone and prochlorperazine on chemotherapy-induced emesis. Cancer Treatments Report 64:219-224.

Tyson LB, Gralla RJ, Clark RA, et al. (1985) Phase I trial of levonantradol in chemotherapy- induced emesis. American Journal of Clinical Oncology 8:528-532.

Vincigeurra, Moore and Brenan, (1988) Inhalation Marijuana as an Anti-emetic for Cancer Chemotherapy. NY State J. Med. 88 525-527.

Judge Youngs ruling - Docket 86-22
The US Drug Enforcement Agency held hearings in 1987 to determine whether cannabis should be allowed as medicine. Doctors, nurses, patients and academics testified that they had witnessed people using cannabis as a medicine sucessfully. A large part of the report is concerned with cancer chemotheraphy, and it makes astonishing reading.

The Cancer Online Information Sources FAQ has a large number of links to sites which may hold more information of relevance.