BACKGROUND: Review commissioned in 1996 by the Department of Health (DOH). AIMS: Assess therapeutic profile of cannabis and cannabinoids.

METHOD: Medline search, references supplied by DOH and others, and personal communications.

RESULTS AND CONCLUSIONS: Cannabis and some cannabinoids are effective anti-emetics and analgesics and reduce intra-ocular pressure. There is evidence of symptom relief and improved well-being in selected neurological conditions, AIDS and certain cancers. Cannabinoids may reduce anxiety and improve sleep. Anticonvulsant activity requires clarification. Other properties identified by basic research await evaluation. Standard treatments for many relevant disorders are unsatisfactory. Cannabis is safe in overdose but often produces unwanted effects, typically sedation, intoxication, clumsiness, dizziness, dry mouth, lowered blood pressure or increased heart rate. The discovery of specific receptors and natural ligands may lead to drug developments. Research is needed to optimise dose and route of administration, quantify therapeutic and adverse effects, and examine interactions.

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This review highlights the pharmacology, pharmacokinetics, pharmacological actions, therapeutic uses and adverse effects of cannabinoids. The effect of cannabinoids on anaesthesia is mentioned briefly. Important advances have taken place in cannabinoid research over the last few years and have led to the discovery of novel ligands. The possible clinical applications of these ligands and the direction of future research are discussed.

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This review analyses the therapeutic usefulness of Delta(9)-tetrahydrocannabinol and its potential to induce adverse reactions on humans. During the last 30 years an enormous amount of research was carried out resulting in the disclosure of the cannabinoid system in Central Nervous System, with its CB(1) and CB(2) receptors, and the agonist anandamide. Under the clinical point of view, Delta(9)-THC produces some therapeutic benefits which are beyond reasonable doubt. Thus, the effects on nausea/emesis due to cancer chemotherapy, as appetite promoter, on some painful conditions and on symptoms of multiple sclerosis are clearly demonstrated. Delta(9)-THC is not devoid of ill effects. On the cognitive domain it impairs the human capacity to discriminate time intervals and space distances, vigilance, memory and the performance for mental work. On the psychic area Delta(9)-THC may induce unpleasant reactions such as disconnected thoughts, panic reactions, disturbing changes in perception, delusions and hallucinatory experiences. However, the long term effects on the psyche and cognition are not known as there are no reports of prolonged use of Delta(9)-THC. Actually, it has been proposed by WHO that Delta(9)-THC should be rescheduled to schedule IV of the United Nations Convention on Psychotropic Drugs, as it does not constitute a substantial risk to public health and its abuse is rare if at all.

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OBJECTIVES: This study examines the concept of clinical endocannabinoid deficiency (CECD), and the prospect that it could underlie the pathophysiology of migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis.

METHODS: Available literature was reviewed, and literature searches pursued via the National Library of Medicine database and other resources.

RESULTS: Migraine has numerous relationships to endocannabinoid function. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors supporting therapeutic efficacy in acute and preventive migraine treatment. Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects. AEA is tonically active in the periaqueductal gray matter, a migraine generator. THC modulates glutamatergic neurotransmission via NMDA receptors. Fibromyalgia is now conceived as a central sensitization state with secondary hyperalgesia. Cannabinoids have similarly demonstrated the ability to block spinal, peripheral and gastrointestinal mechanisms that promote pain in headache, fibromyalgia, IBS and related disorders. The past and potential clinical utility of cannabis-based medicines in their treatment is discussed, as are further suggestions for experimental investigation of CECD via CSF examination and neuro-imaging.

CONCLUSION: Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.

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