ESPEN guidelines on nutrition in cancer patients

Δ9-Tetrahydrocannabinol (THC) is the main source of the pharmacological effects caused by the consumption of cannabis, both the marijuana-like action and the medicinal benefits of the plant. However, its acid metabolite THC-COOH, the non-psychotropic cannabidiol (CBD), several cannabinoid analogues and newly discovered modulators of the endogenous cannabinoid system are also promising candidates for clinical research and therapeutic uses. Cannabinoids exert many effects through activation of G-protein-coupled cannabinoid receptors in the brain and peripheral tissues. Additionally, there is evidence for nonreceptor-dependent mechanisms. Natural cannabis products and single cannabinoids are usually inhaled or taken orally; the rectal route, sublingual administration, transdermal delivery, eye drops and aerosols have only been used in a few studies and are of little relevance in practice today. The pharmacokinetics of THC vary as a function of its route of administration. Pulmonary assimilation of inhaled THC causes a maximum plasma concentration within minutes, psychotropic effects start within seconds to a few minutes, reach a maximum after 15–30 minutes, and taper off within 2–3 hours. Following oral ingestion, psychotropic effects set in with a delay of 30–90 minutes, reach their maximum after 2–3 hours and last for about 4–12 hours, depending on dose and specific effect. At doses exceeding the psychotropic threshold, ingestion of cannabis usually causes enhanced well-being and relaxation with an intensification of ordinary sensory experiences. The most important acute adverse effects caused by overdosing are anxiety and panic attacks, and with regard to somatic effects increased heart rate and changes in blood pressure. Regular use of cannabis may lead to dependency and to a mild withdrawal syndrome. The existence and the intensity of possible long-term adverse effects on psyche and cognition, immune system, fertility and pregnancy remain controversial. They are reported to be low in humans and do not preclude legitimate therapeutic use of cannabis-based drugs. Properties of cannabis that might be of therapeutic use include analgesia, muscle relaxation, immunosuppression, sedation, improvement of mood, stimulation of appetite, antiemesis, lowering of intraocular pressure, bronchodilation, neuroprotection and induction of apoptosis in cancer cells.

Pharmacokinetics and Pharmacodynamics of Cannabinoids

Recent years have seen a rapid rise in the medical and recreational use of cannabis: a broad term that can be used to describe the various products and chemical compounds (e.g., marijuana, cannabinoids) derived from different species of the cannabis plant. Despite increased cannabis use and a changing state-level policy landscape, conclusive evidence regarding the shortand long-term health effects—both harms and benefits—of cannabis use remains elusive.

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The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research

Cachexia: pathophysiology and clinical relevance

Cannabinoids - the active components of Cannabis sativa and their derivatives - exert palliative effects in cancer patients by preventing nausea, vomiting and pain and by stimulating appetite. In addition, these compounds have been shown to inhibit the growth of tumour cells in culture and animal models by modulating key cell-signalling pathways. Cannabinoids are usually well tolerated, and do not produce the generalized toxic effects of conventional chemotherapies. So, could cannabinoids be used to develop new anticancer therapies?

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Cannabinoids: potential anticancer agents

PURPOSE: To determine whether dronabinol administered alone or with megestrol acetate was more, less, or equal in efficacy to single-agent megestrol acetate for palliating cancer-associated anorexia. PATIENTS AND METHODS: Four hundred sixty-nine assessable advanced cancer patients were randomized to (1) oral megestrol acetate 800 mg/d liquid suspension plus placebo, (2) oral dronabinol 2.5 mg twice a day plus placebo, or (3) both agents. Eligible patients acknowledged that loss of appetite or weight was a problem and reported the loss of 5 pounds or more during 2 months and/or a daily intake of less than 20 calories/kg of body weight. RESULTS: Groups were comparable at baseline in age, sex, tumor type, weight loss, and performance status. A greater percentage of megestrol acetate-treated patients reported appetite improvement and weight gain compared with dronabinol-treated patients: 75% versus 49% (P = .0001) for appetite and 11% versus 3% (P = .02) for ≥ 10% baseline weight gain. Combination treatment r...

Dronabinol Versus Megestrol Acetate Versus Combination Therapy for Cancer-Associated Anorexia: A North Central Cancer Treatment Group Study

Purpose: To determine whether dronabinol administered alone or with megestrol acetate was more, less, or equal in efficacy to single-agent megestrol acetate for palliating cancer-associated anorexia Patients and Methods: Four hundred sixty-nine assessable advanced cancer patients were randomized to (1) oral megestrol acetate 800 mg/d liquid suspension plus placebo, (2) oral dronabinol 25 mg twice a day plus placebo, or (3) both agents Eligible patients acknowledged that loss of appetite or weight was a problem and reported the loss of 5 pounds or more during 2 months and/or a daily intake of less than 20 calories/kg of body weight Results: Groups were comparable at baseline in age, sex, tumor type, weight loss, and performance status A greater percentage of megestrol acetatetreated patients reported appetite improvement and weight gain compared with dronabinol-treated patients: 75% versus 49% (P 0001) for appetite and 11% versus 3% (P 02) for > 10% baseline weight gain Combination treatment resulted in no significant differences in appetite or weight compared with megestrol acetate alone The Functional Assessment of Anorexia/Cachexia Therapy questionnaire, which emphasizes anorexia-related questions, demonstrated an improvement in quality of life (QOL) among megestrol acetate‐treated and combination-treated patients The single-item Uniscale, a global QOL instrument, found comparable scores Toxicity was also comparable, with the exception of an increased incidence of impotence among men who received megestrol acetate Conclusion: In the doses and schedules we studied, megestrol acetate provided superior anorexia palliation among advanced cancer patients compared with dronabinol alone Combination therapy did not appear to confer additional benefit J Clin Oncol 20:567-573 © 2002 by American Society of Clinical Oncology

Dronabinol V ersus M egestrol A cetate V ersus C ombination Therapy f or C ancer-Associate d A norexia: A N orth C entral Cancer T reatment G roup S tudy

Sarode Pundaleeka

Papers

Dronabinol Versus Megestrol Acetate Versus Combination Therapy for Cancer-Associated Anorexia: A North Central Cancer Treatment Group Study

Dronabinol V ersus M egestrol A cetate V ersus C ombination Therapy f or C ancer-Associate d A norexia: A N orth C entral Cancer T reatment G roup S tudy