• CAM-summaries
  • Alternative medical systems
  • Biologically-based practices
    • Boswellia
    • Cannabinoids
      • What are Cannabinoids?
      • How well do Cannabinoids work?
      • Are Cannabinoids safe?
      • Cannabinoids conclusions
    • Essiac
    • Galavit
    • Laetrile
    • Shark cartilage
    • Ukrain
    • Black cohosh
  • Diet & nutrition
  • Energy medicine
  • Manipulative & body-based practices
  • Mind-body medicine
• CAM systematic reviews
• CAM and the law
• Prevalence of CAM use

What are Cannabinoids?

Originally, all members of a certain class of C21-compounds found in Cannabis sativa and Cannabis indica plants were called "cannabinoids". Nowadays, the term cannabinoids is used for all active substances of plant, animal or endogenous origin that work as agonist ligands at cannabinoid receptors of cells (ref 1). This summary deals with pure cannabinoid products for medical use (medical cannabinoids). It gives an overview of medical cannabinoids as plant-based prescription medicine for symptomatic treatment in cancer therapy.

Cannabis and Cannabinoids

Plant-based cannabinoids are isolated from Cannabis sativa herbs or produced as synthetic cannabinoid analogues. About 500 different substances have been identified in cannabis plants (hemp) so far, almost 70 of which are cannabinoids (ref 1, 2). The four most important classes of natural phytocannabinoids are Δ9-tetrahydrocannabinols (Δ9-THC), cannabidiols, cannabigerols and cannabichromen cannabinoids. Only Δ9-THC is currently available in natural or synthetic form for medical application: Dronabinol (Marinol®) is the (-)-trans-isomer of the natural phytocannabinoid Δ9-THC extracted from cannabis plants that are grown for medical purposes. Nabilone (Cesamet ®, Nabilon®) is a synthetic, ketocannabinoid analogue of THC. Another synthetic THC homologue, levonantradol, was investigated in phase I clinical trials, but serious side effects limited its use (ref 3).

In addition, whole-plant cannabis extracts are available for medical use in some countries containing a mixture of different cannabinoids. As standardised cannabis extracts have been legalised only recently in few European countries and investigations are scarce, these phytopharmaceutical cannabis products are not included in this summary. Nor will the unauthorised and often prohibited use of cannabis herbs and plant preparations (marijuana, hashish, hash oil) be evaluated here.

Treatment description: application and dosage

The medical cannabinoids dronabinol and nabilone are usually taken orally as capsules or oily solution, or are less commonly inhaled using a mechanical device. Rectal, transdermal or sublingual application or parenteral injection remain confined to clinical investigations and are not relevant for clinical practice today. For clinical use, individual dose finding is necessary beginning with 2x2.5 mg dronabinol/day and a recommended maximum daily dose of 5x10 mg dronabinol (ref 4).

History

Medical use of cannabis has a long tradition in different regions and medical systems around the world for several thousand years (ref 6). The therapeutic use of cannabis products is documented in traditional Chinese and Indian (Ayurvedic) medicine as well as in the traditional mediaeval European healing system. Modern Western medicine rediscovered the therapeutic potential of cannabis in the 19th century, and by the beginning of the 20th century, cannabis products were in widespread use as prescription medicine in several Western countries. Due to the increasing use of cannabis as a recreational drug, many countries all over the world put prohibitory legislation into effect, gradually leading to the almost complete elimination of cannabis plant products from medical use. In Europe, the debate about the therapeutic use and potential of cannabinoids in diseases where available treatment is not satisfactory is still ongoing. Current clinical research and usage is concentrated around multiple sclerosis, AIDS and cancer.

Claims of efficacy/mechanisms of action/alleged indications

The medical use of cannabinoids has been advocated for various indications. In cancer patients, medical cannabinoids have been recommended for the symptomatic treatment of anorexia-cachexia-syndrome, nausea and pain, especially in palliative situations.Medical cannabinoids have been claimed to stimulate appetite and food intake and consequently stabilise or increase body weight of patients with advanced cancer and weight loss (anorexia-cachexia-syndrome). An antiemetic effect has also been attributed to cannabinoids in patients receiving chemo-/radiotherapy and in palliative care patients. Furthermore, cannabinoids have been claimed to have an analgesic effect in cancer patients.

Prevalence of use

Data on the prevalence of medical use of cannabinoids is not available for Europe. However, several surveys with convenient samples of self-selected users of cannabinoids and cannabis products for medical purposes have been conducted. Survey participants in different European countries have most commonly reported the use of cannabinoids/cannabis for neurological diseases, for example, multiple sclerosis and chronic pain. In a UK survey, less than 1% used cannabis for cancer (ref 7), while in a Dutch survey 14% reported a malignant disease (ref 8).

Legal issues and providers

Dronabinol is licensed as antiemetic in the US for the treatment of chemotherapy-induced nausea and stimulation of appetite in AIDS patients. It is also marketed by a German pharmaceutical company. Nabilone is manufactured in the UK. Both products may be imported via an international pharmacy. However, trade with cannabinoids is internationally restricted and legal regulations for the medical use of cannabinoids differ between countries.

Special legal requirements have to be met to substantiate an import claim (ref 9).

Cost(s) and expenditures

Costs for medical cannabinoids range between 1 to 5 Euros per milligram depending on the provider. In general, domestic products are cheaper than imported drugs, but are not available in all countries. Monthly expenses for the minimum daily dose of 2x2.5mg dronabinol add up to 150 to 750 Euros for the patient. Some health insurers reimburse the costs, but regulations and practice differ in European countries and between health insurances companies.

References

1. Grotenhermen,F. (2003): Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet, 42:327-360.

2. Guy,G.W., Whittle,B.A., Robson,P.J.(2004): The medicinal uses of cannabis and cannabinoids. Pharmaceutical Press, London.

3. Walsh,D., Nelson,K.A., and Mahmoud,F.A. (2003): Established and potential therapeutic applications of cannabinoids in oncology. Support Care Cancer, 11:137-143.

4. Mutschler,E., Geisslinger,G. , Kroemer, H.K., Schäfer-Korting,M. (Eds.) (2001): Mutschler Arzneimittelwirkungen. Lehrbuch der Pharmakologie und Toxikologie. Wissenschaftliche Verlagsgesellschaft, Stuttgart.

6. Russo,E. (2004): History of cannabis as a medicine. In: The medicinal uses of cannabis and cannabinoids, edited by G.W.Guy, et al, pp. 1-16. Pharmaceutical Press, London.

7. Ware,M.A., Adams,H., and Guy,G.W. (2005): The medicinal use of cannabis in the UK: results of a nationwide survey. Int J Clin Pract., 59:291-295.

8. Gorter,R.W., Butorac,M., Cobian,E.P., and van der,S.W. (2005): Medical use of cannabis in the Netherlands. Neurology, 64:917-919.

9. www.acmed.org [International Organization for Cannabis as Medicine] (visited 15.7.2005)