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MARIJUANA AND TETRAHYDROCANNABINOL (THC): NEWS AND VIEWS

A sympos;um '~oks at the pharmacology and toxicity In July 197£ a 'S.~mposium on Marijuana' was held in Reims, France. The active metabolite THC is fat-soluble, and 50 % is absorbed into tl' ~ blood stream on smoking, 5·10% on oral ingestion. It disappears rapidly from the blood into numerous body compartmentf and with an elimination half-life of 7 days, it takes 30 days to be excreted as metabolites in the urine (15 %) and the faeces (40· sr %), with some 15 % undergoing enterohepatic recirculation. THC adversely affects cell division acting on the cell and nuclear membranes to inhibit transpOrt of substances required for RNA, DNA and protein synthesis. Marijuana damages the lung, causing decreased vital capacity and increasing airway obstruction.

Animal and human studies show impairment of spermatogenesis, with oligospermia, increased abnormal forms and decreased motility, by direct action on germinal epithelium and intermittent suppression of gonadotrophins, FSH and LH. Decreased levels of FSH, LH and prolactin have been seen in females with disruption of the menstrual cycle. THC is embryotoxic in animals, disrupting placental function and circulation. In the brain, biochemical changes and impaired function have been reported in animals but the effect in man is still controversial. Impaired memory recall has been seen, and considerable tolerance develops on continuous use. There is no severe acute withdrawal syndrome and no great physical dependence. Schizophrenics, epileptics, adolescents with developing neurohormonal systems and women of childbearing age should avoid marijuana and its derivatives. Clinical trials have been carried out: in glaucoma, whereby THC proved no better than pilocarpine or ~-blockers, and in treating nausea with cancer therapy, when it was proved no better than phenothiazines. Nahas, G.G.: Journal of the American Medical Association 242: 2775 (21 Dec 1979)

And now pot for cancer patients: how enlightened can the authorities be 7 'No, no!' said the Queen. 'Sentence first- verdict afterwards '. Even Alice in Wonderland would have been challenged by the topsy turvy world of medicine and marijuana. Clinical trials have already begun to show the value of marijuana or its derivative delta-9-tetrahydrocannabinol (THC), as an antiemetic, an appetite stimulant and an antidepressant for the relief of patients receiving cancer chemotherapy. A recent study (in press) of 41 cancer patients refractory to standard antiemetics and given THC 8-12 hours prior to chemotherapy, showed good results in over two thirds of the patients, and few gastrointestinal problems in those receiving massive doses of myelosuppressive therapy. Another synthetic cannabinoid, nabilone, showed promising results before being withdrawn due to chronic toxicity. Two recent st,udies ofTHC in cancer patients [See lnpharma 219: 7 (J 2 Jan 1980A have conftrmed the earlier fmdings. In I, THC provided 'substantial therapeutic benefit and minimal toxicity' when given orally and supplemented with THC-containing cigarettes, in patients with osteosarcoma receiving methotrexate. The report cannot be faulted other than for understating both the magnitude of emesis in cancer treatment and the prospect of the physician obtaining the preparation. In the second study, THC was as effective as prochlorperazine but more toxic. The dosage given. however, produced high peak blood levels and long periods with undetectable levels. These results may have been better with lower, more frequent doses. Results, then, indicate that THC (the only viable candidate so far) is effective against drug-induced nausea and vomiting, although there may be varying sensitivities: older people who have refrained from intoxicating beverages seem more likely to experience dysphoria. Nonetheless psychological reactions spontaneously dissipate within hours.

Impediments to its use and further development If the results are accepted, how does one prescribe THC for the cancer patient. In the US, the 'schedule l' classiftcation (no accepted medical use, high abuse potential) ' . . . puts THC beyond the reach of all but the most persistent investigators . .. ' In a recent review the FDA, the Alcohol, Drug Abuse and Mental Health Administration, and the Department of Health, Education and Welfare ' . . . totally ignored positive results in reputable reference sources in categorically concluding that "marijuana extracted and synthetic THC have no currently accepted medical use in treatment in the United States n.' No doubt it is politically unappealing for federal agencies to have to admit that marijuana derivatives may have some medicinal value. Furthermore, the pharmaceutical industry has been hesitant in developing and marketing a non-patentable and controversial drug, understandably since THC itself would take 2-5 years and up to $57 million. In the meantime patients are still 'vomiting their guts out', and a short term solution might be to deregulate THC to schedule II and for the FDA to approve its distribution via an existing programme of the National Cancer Institute, which would simply require physicians to report all adverse drug reactions, a reasonable precaution at this time. Laszlo, J .: Annals of Internal Medicine 91 : 916 (Dec .1979)

2 INVHARMA 19 Jan 1980 0156-2703/80/0119-0002 $00.50/0 © ADIS Press