SUMMARY:
Cannabis as grown would not meet the EU Rules’ for medical acceptability; UK is a signatory to these. It has already been rejected by several authorities, including the BMA. In particular, smoking as a means of delivery has been universally rejected. Extracts are under trial, but experience with the extract so far approved has been mixed; most doctors only use it as a last resort. Interest in cannabis comes in part from the genuinely ill, expectations having been raised by ‘recreational use’ lobbyists. Political or treatment expediencies must not compromise medical standards for safety and efficacy.
E.U. Rules [1] set out various criteria for the acceptance of a drug for medical use, these include:
1. All active ingredients have to be identified and their chemistry determined. They have to be tested for purity with limits set for all impurities including pesticides, microbes & fungi and their products. These tests have to be validated and reproduced if necessary in an official laboratory.
The cannabis plant contains some 400 chemicals, a multiplicity of ingredients that vary with habitat – impossible to standardise and often contaminated with microbes, fungi or pesticides.[2]
2. Animal testing will include information on fertility, embryo toxicity, immuno-toxicity, mutagenic and carcinogenic potential. Risks to humans, especially pregnant women and lactating mothers, will be evaluated.
Cannabis has been shown to reduce sperm production.[3] Babies born to cannabis-using mothers are smaller, have learning and behavioural problems and are 10 times more likely to develop one form of leukaemia.[4] The immune system is impaired.[5] Smoking herbal cannabis results in the inhalation of three times as much tar as from a tobacco cigarette.[6]
3. Adequate safety and efficacy trials must be carried out. They must state the method of administration and report on the results from different groups, i.e. healthy volunteers, patients, special groups of the elderly, people with liver and kidney problems and pregnant women. Adverse drug reactions (ADR) have to be stated and include any effects on driving or operating machinery.
Presumably it is envisaged that cannabis would be smoked. No medicine prescribed today is smoked. Concentration, motor.coordination and memory are all badly affected.[7] Changes in the brain have been observed[8] and U.S.A. clinics are now coping with more cases of psychosis caused by cannabis than by any other drug. It is essential to note that the content of THC (Tetrahydrocannabinol – the psychoactive ingredient in cannabis) is on average ten times higher than it was in the 1960s.[9] The fat.soluble THC lingers in the body for weeks [10] and the ability to drive safely is impaired for at least 24 hours after smoking cannabis. [11] Although ten times as many people use alcohol, cannabis is implicated in a similar number of road accidents. [12]
4. The drug must be accepted by qualified experts. Their detailed reports need to take account of all the relevant scientific literature and the potential of the drug to cause dependence.
There are numerous accounts of both psychological and physical dependencies in cannabis use. [13] Some 77000 people are admitted annually to hospitals in U.S.A for cannabis dependence, 8000 of them as emergencies. [14] To date there are over 12000 scientific publications relating to cannabis. [15]
THC has already undergone all the medical tests. It is available on prescription in tablet form for the relief of nausea from chemotherapy and appetite stimulation in AIDS patients. However Marinol (USA) and Nabilone (UK), synthetic forms of THC and identical in action to it, are not the first drugs of choice among oncologists in Washington D.C. ranking only 9th in the treatment of mild nausea and 6th for more severe nausea. [16] The warning on nabilone reads:
“THC encourages both physical and psychological dependence and is highly abusable. It causes mood changes, loss of memory, psychoses, impairment of co-ordination and perception, and complicates pregnancy”.
Other Cannabinoids: Cannabis contains around 60 cannabinoids that are unique to the plant. Some of these could be similarly extracted, purified and tested for safety and efficacy. In the report ‘Therapeutic Uses Of Cannabis’ (BMA, 1997) the British Medical Association said, “It is considered here that cannabis is unsuitable for medical use. Such use should be confined to known dosages of pure or synthetic cannabinoids given singly or sometimes in combination”
WHAT THE EXPERTS HAVE SAID
Dr. Eric Voth MD, FACP (Chairman of the International Drug Strategy Institute) said in a letter to the editor of the New England Journal of Medicine (Jan 1997),
“Long term effects aside, contaminants, purity, standardisation of dose etc are all reasons to not use an impure herb as a medicine. Whether terminal or not, should we support smoking Foxglove plant to obtain Digoxin for heart failure, or Yew tree bark to obtain Taxol for breast cancer? If so, then supporters of smoked marijuana better be ready to support smoking tobacco for weight control and anxiety. We must have compassion for the sick and suffering and we must offer them reliable and quality medicine, not crude substances that threaten their well being”
Glaucoma: The pressure in the eye caused by this condition can be reduced by smoking cannabis but Professor Keith Green, Director of Ophthalmic Research at the Medical College of Georgia said some 6 ‘joints’ a day would be required, rendering the patient effectively ‘stoned’ and incapable of useful activities.
Multiple Sclerosis: Dr. Donald Silberg, Chief of Neurology, Pennsylvania school of Medicine said, “I have not found any legitimate or scientific works which show that marijuana is medically effective in treating Multiple Sclerosis or spasticity. The use of marijuana especially for long-term treatment would be worse than the illness itself”
DOES THE PUBLIC REALLY WANT THIS?
Nov 1996: Proposition 200 permitted physicians in Arizona to prescribe pure marijuana with no limitation on the age of the patient or disorder involved.
Jan 1997: A public opinion poll revealed that 85% of registered voters believed that proposition 200 should be changed and 60% wanted it repealed, 70% said it gave children the impression that drugs are OK for recreational use. [17]
HOW DID THE CAMPAIGN GET STARTED?
In 1979: Keith Stroup, an American pot-using lawyer, and the then head of NORML (National Organisation for Reform of Marijuana Laws) said, “We will use the medical marijuana argument as a red herring to give pot a good name.” [18]
Early 1990s Richie Cowan, Stroup’s successor at NORML, echoed him when he said, “Medical marijuana is our strongest suit. It is our point of leverage which will move us toward the legalisation of marijuana for personal use.” [19]
A LAST WORD FROM DR. ERIC VOTH
“We cannot by-pass the usual safety and efficacy process of the FDA (Food and Drugs Administration) because of the hue and cry of a self-preserving drug culture which seeks to add medicinal applications of marijuana, mixed messages of legalisation of illegal drugs, harm reduction and tolerance of drug use.” [20]
REFERENCES
1. The Rules Governing Medicinal Products in the European Union, Vols 2A & 2B. Europe Publications, Luxembourg, 1998.
2. Jenike MA. Drug Abuse. In Rubenstein E, Federman DD (eds) Scientific American Medicine, Inc. 1993. Therapeutic Uses of Cannabis, BMA, 1997.
3. Issidorides MR. Observations in chronic hashish users. In Nahas GG & Paton WDM (Eds). Marijuana: Biological Effects &c. 1979. Stephanis CN & Issidorides MR. Cellular effects of chronic cannabis use in man. In Nahas GG & Paton WDM (Eds), Marijuana: Chemistry, Biochemistry and Cellular Effects. 1976. Nahas GG and Paton WDM (Eds). Marijuana: Biological Effects, Analysis, Metabolism, Cellular Responses, Reproduction and Brain. Pergamon, NY, 1979.
4. Hingson R, Alpert JJ, Day N et al. Effects of maternal drinking and marijuana use on foetal growth and development. Paediatrics. 1982. Quas QH, Mariano E, Milman DH et al. Abnormalities in offspring associated with prenatal marijuana exposure. Dev. Pharm. Thera. 1985. Day NL, Richardson GA, Goldschmidt L et al. Effect of prenatal marijuana exposure on the cognitive development of offspring at age three. Neurotox. Teratol. 1994. Fried PA & Watkinson B. 36 and 48 month neurobehavioral follow up of children prenatally exposed to marijuana, cigarettes and alcohol. Developmental & Behavioral Pediatrics,1990. Robinson LL, Buchley JD, Daigle AE et al. Maternal drug use and risk of childhood non-lymphoblastic leukaemia among offspring: An epidemiological investigation implicating marijuana. Cancer. 1989. Ward NI et al. factors in human foetal development. Jour. Nutrit. Med. 1990.
5. Cabral GA. Marijuana decreases macrophage anti-viral and anti-tumour activities. Advances in Biosciences,
80. 1991. Cabral GA & Vasquez R. Delta-9-tetrahydrocannabinol suppresses macrophage extrinsic anti-herpes virus activity. Proc. Exper. Biol. Med. 1992. Cabral GA et al. Proc. Soc. Exper. Med. Biol. 1986. Gross G, Roussaki A, Ikenberg H & Drees N. Genital warts do not respond to systemic recombinant interferon alfa-2 treatment during cannabis consumption. Dermatologia. 1991. Leuchtenberger C. Effects of marijuana smoke on cellular biochemistry, utilising in vitro test systems. Adverse health and behavioural consequences of cannabis use. Addiction Research Foundation Press. Toronto, Canada. 1982. Morahan et al. Effects of cannabinoids on host resistance to Listeria monocytogenes and Herpes simplex virus. Infect. Immunol. 23. 1979. Munson & Fehr. Immunological effects of cannabis. Adverse health and behavioural consequences of cannabis use. Addiction Research Foundation Press. Toronto, Canada. 1982. Polen MR et al. Health care use by frequent marijuana smokers who do not use tobacco. Western Jour. Med. 158. 1993. Specter S, Lancz G, Djev J et al. Advances in Exper. Med. Biol. 1991. Zimmerman AM & Raj AY. Influences of cannabinoids on somatic cells in vivo. Pharmacology 21. 1980.
6. Therapeutic Uses of Cannabis, BMA, 1997. Broom JW et al. Respiratory effects of non-tobacco cigarettes. BMJ, 1987. Caplan GA, Brigham BA. Marijuana smoking and carcinoma of the tongue. Cancer. 1990. Donald PJ. Marijuana and upper respiratory tract malignancy in young patients. Adv. Exp. Med. Biol. 1991. Ferguson RP, Hasson J & Walker S. Metastasic lung cancer in a young marijuana smoker. JAMA. 1989. Marijuana and Health. National Academy of Sciences, Institute of Medicine Report. Washington DC. 1982. Marijuana Rescheduling Petition by NORML Denied by DEA. Federal Register Vol. 54, No 249. 29 Dec 1989. Polen MR et al. Health care use by frequent marijuana smokers who do not use tobacco. Western Jour. Med. 158. 1993. Schwartz RH. American Journ. Dis. Child. 143(6); p 644. 1989. Tashkin DP et al. Respiratory symptoms and lung function in habitual smokers of marijuana alone, smokers of marijuana and tobacco, smokers of tobacco alone and non-smokers. American Review of Respiratory Diseases. 1987. Tashkin DP et al. Longitudinal changes in respiratory systems and lung function in non-smokers, tobacco smokers and heavy habitual smokers of marijuana with or without tobacco. An International Research Report. Proceedings of the Melbourne Symposium on Cannabis, September 1987 (see also Amer. Review of Respiratory Diseases, 1987). Taylor FM. Marijuana as a potential respiratory tract carcinogen: A retrospective analysis of a community hospital population. Southern Med. Jour. 1988. Tennant FS, Guerry RL & Henderson RL. Histopathological & clinical abnormalities of the respiratory system in chronic hashish smokers. Subst. Alcohol Actions Misuse. 1980 Wengen DF. Marijuana and malignant tumours of the upper aerodigestive tract in young patients: On the risk assessment of marijuana. Laryngorhinotologie. 1993.
7. Polen MR et al. Health care use by frequent marijuana smokers who do not use tobacco. Western Jour. Med.158. 1993. Schwartz RH. Persistent impairment of short-term memory associated with heavy marijuana use.Committees of Correspondence – Drug Prevention Newsletter. June 1990. Solowij N, Michie PT & Fox AM Differential impairments of selective attention due to frequency and duration of Cannabis use. Biol. Psychiatry1995. Solowij N. Do cognitive impairments recover following cessation of Cannabis use? Life Sciences Vol. 56. 1995. Varma VK, Malhotra AK, Dang R, et al. Cannabis and cognitive functions: a prospective study. Drug Alcohol Depend. 1988.
8. Devane WA et al. Isolation and structure of a brain constituent that binds to the cannabmoid receptor. Science.1992. Lex BW, Griffin ML, et al. Alcohol, marijuana and mood status in young women. International Journal of the Addictions. 1989. Mathew RJ. Middle cerebral artery velocity during upright posture after marijuana smoking. Acta Psych. Scand. 1992. Nahas GG. Historical outlook of the psychopathology of Cannabis. In Cannabis: Physiopathology, Epidemiology, Detection. CRC Press, 1993. Nahas G & Latour C. The human toxicity of marijuana. The Medical Journal of Australia. 1992.
9. Information supplied by the US Drug Enforcement Agency (DEA).
10. Therapeutic Uses of Cannabis, BMA, 1997. See also ref. 6.
11. Leirer VO & Yesavage JA. Marijuana carry-over effects on aircraft pilot performance. Aviation Space & Environmental Medicine. 1991.
12. Soderstrom CA, Tniffillis AL et al. Marijuana and alcohol use among 1023 trauma patients: A prospective study. Arch. Surg. Vol.123, June. 1988.
13. Information supplied on the use of MARINOL by Roxane Laboratories Inc., 1989 revision. Aceto MD et al. Cannabinoid-precipitated withdrawal by a selective antagonist SR141716A. European Journal of Pharmacology. 1995. Adams IB and Martin BR. Cannabis: Pharmacology and Toxicology in Animals and Humans. Journal of Addiction. Vol. 91. 1996. Anthony JC and Helger JE.Syndromes of drug abuse and dependence. In Roberts and Regine (Eds) Psychiatric Disorders in America. New York Free Press — Macmillan. 1991. Compton DR, Dewey WL & Martin BR. Cannabis dependence and tolerance production. Advances in Alcohol & Substance Abuse. 1990. Compton DR et al. Cannabinoid structure-activity relationships: correlation of receptor binding and in vivo activities. Journal of Pharmacology and Experimental Therapeutics. 1993 De Fonseca FR, Camera MRA et al. Activation of corticotropin-releasing factor in the limbic system during cannabinoid withdrawal. Science. 1997. Devane WA et al. Determination and characterisation of a cannabinoid receptor in rat brain. Molecular Pharmacology. 1988 Devane WA et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992. Gold MS. Marijuana. Plenum Medical Book Company, New York. 1989. Howlett AC et al. The cannabinoid receptor: biochemical, anatomical and behavioural charactenisation. Trends in Neuroscience. 1990. Jones. Cannabis tolerance and dependence. In Fehr KO and Kalant H (Eds) Adverse Health and Behavioural Consequences of Cannabis Use. Addiction Research Foundation, Toronto. 1982. Kaplan HB, Martin SS et al. Escalation of marijuana use: Application of a general theory of deviant behaviour. Jour. Health & Social Behaviour. 1986. Kaufman E et al. Committee on Drug Abuse of the Council on Psychiatric Services. Position Statement on psychoactive substance use and dependence: update on marijuana and cocaine. American Journal of Psychiatry. 1987. Miller NS and Gold MS. The diagnosis of marijuana (cannabis) dependence. Jour. Subst. Abuse Treatment. 1989. Miller NS, Gold MS & Pottash AC. A 12-step treatment approach for marijuana (cannabis) dependence. Jour. Substance Abuse Treatment. 1989. National Drug & Alcohol Research Centre of Australia Report. August 1997. Poulton et al. New Zealand Medical Journal. Vol.110. 1997. Schuster CR. Alaskans for Drug-free Youth Newsletter. Winter, 1993/94. Schwartz RH. Marijuana: an overview. Pediatric Clinics of North America. 1987. Tanda G, Pontieri FE & Di Chiara G. Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common m1 opioid receptor mechanism. Science. 1997. Tson et al. Physical withdrawal in rats tolerant to delta-9-THC precipitated by a cannabinoid receptor antagonist. European Journal of Pharmacology. 1995.
14. Hart RH. Bitter Grass. Mentor Press, Kansas, USA2.
15. Mississippi University Library.
16. Bonner R. Marijuana Rescheduling Petitions 57. Federal Register 1992, 10499-10508.
17. Public Opinion Poll January 27-31, 1997 taken by Dr Bruce Merrill, Prof. of Mass Communications & Director Medical Research Center, Walter Cronkite School, Arizona State University.
18. K. Stroup (Director of NORML) in an address to audience at Emory University, 1979.
19. Video of Drug Culture Conference celebrating 50th Anniversary of the discovery of LSD, April
1993. Sponsored by NORML and others, San Francisco.
20. Voth EA, MD, International Drug Strategy Institute Position Paper. Medical Applications of Marijuana, 1995.