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VIEWS & REVIEWS -David Jack- The medicinal use of cannabis and cannabinoid research are contentious issues that are able to stir up strong feelings, both for and against the proposals. Some US states have passed laws that allow doctors to recommend cannabis (marijuana) for therapeutic use in certain medical conditions although the federal government has reminded doctors that the material remains an illegal narcotic under federal law. * The Pharmaceutical Sciences Group of the Royal Pharmaceutical Society of Great Britain together with the Multiple Sclerosis Society, recently hosted a meeting on the therapeutic applications of cannabinoids to review evidence for their medical use [London, UK; July 1997]. This meeting took place only a few days after the British Medical Association (BMA) received wide publicity by voting at its annual meeting in Edinburgh to legalise cannabis use. A growing body of scientific evidence suggests that cannabis can be of great benefit to patients suffering from multiple sclerosis (MS) and other conditions associated with intractable pain, especially when linked to muscle spasm and tremor, that are unresponsive to existing licensed drugs, including opioids. Something in the air? 'There is now a real sea of change in attitudes towards cannabis', according to Professor Fred Evans from the School of Pharmacy, London, UK. Cannabis has both central and peripheral effects. The central effects, which include the euphoria that makes the drug popular as a 'recreational' substance, are largely mediated by tetrahydrocannabinol. Cannabis also contains a number of other active components and those that have been studied in the greatest detail include the powerful peripheral analgesic cannabidiol as well as cannabinol, cannabigerol and olivetol [see table]. Nabilone and dronabinol are synthetic cannabinoids that have been licensed in many countries. Their primary indication is as antiemetics for the treatment of nausea and vomiting that occurs in patients after chemo- and radiotherapy for cancer. However, in many cases these agents have now been replaced by ondansetron for this indication. Other potential uses for cannabis/cannabinoids include: • restoring appetite • reversing severe weight loss in patients with AIDS and some cancers • treating glaucoma. * Seelnphamta 1064: 7, 23 Nov 1996; 800484041,lnphamta l(JJO: 5, 18 Jan 1997; 8004949fJ7 and Irrphanna 1080: 5, 29 Mar 1997; 800521714 1173-832419711098-00031$01 . 00° Adi. International Limited 1997. All right. reserved Altered states The existence of a cannabinoid receptor was identified in 1988 and we now know that there are two types of cannabinoid receptors, CB 1 and CB2, said Dr Roger Pertwee from the Institute of Medical Sciences, Aberdeen University, UK. The latter is not found in neuronal tissue and so is a more attractive target for pharmaceutical companies who wish to avoid producing compounds with the CNS effects of cannabis, speculated Dr Pertwee. Eli Lilly and Elf-Sanofi are both active in this area with a number of phase I candidates including LY-320135, SR-141716A and SR-144528, he added. Give it a go! There is now a strong case for properly conducted clinical trials of cannabis andlor its derivatives in order to confmn. efficacy, quantify adverse effects, and to assess the risk:benefit ratio as well as to determine whether a combination of cannabinoids is more effective than any of the individual components, according to Dr Pertwee. Limited data is available from well controlled clinical trials regarding the use of cannabis or cannabinoids in patients, but anecdotal evidence of beneficial effects in dystonia, chronic pain, glaucoma and a variety of inflammatory conditions is available. Cannabinoids have been thoroughly studied in a variety of animal experiments and positive effects have been reported in animal models of MS and auto- immune encephalomyelitis, said Dr Pertwee. Some data from animal studies suggest that tolerance to the effects of cannabinoids develops, but whether this will happen in patients is not currently known, he added. An option in chronic pain? Nabilone is being tested in patients with chronic pain, although this is not an approved indication for the drug. Nabilone has been used in a number of patients suffering chronic pain associated with MS spinal conditions, peripheral neuropathy and central neurogenic pain, by Dr William Notcutt, a consultant anaesthetist at the James Paget Hospital, Great Yarmouth, UK. Pain relief was reported in 18143 patients, he added. While this was not a properly controlled clinical trial, many of the patients freely admitted that they derived great benefit from nabilone therapy when nothing else would help, said Dr Notcutt. Interestingly, many of these patients had also tried cannabis of their own accord and all preferred it over nabilone, he added. The benefits associated with Inpharma- 2 Aug 1997 No. 1098 3
