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EMBO Rep. Jul 2003; 4(7): 651–653.
PMCID: PMC1326332
Science and Society
Analysis

Does marijuana have a future in pharmacopoeia?

Summary

Although recent research backs the therapeutic benefits of cannabis, its adverse effects and the risk of addiction push against the legalization of the drug for medical use

Its Latin name in botanical classification is Cannabis sativa L. but most people know it as marijuana, grass, pot, dope or weed, mainly when referring to its recreational use. Recently, this green plant, which grows up to five metres, has acquired a new name: 'the aspirin of the new century', reflecting hopes that cannabis could be used to treat a variety of ailments, ranging from migraine to cancer (Baker et al., 2003). By discovering how the active ingredients of the plant exert their effect on the human metabolism, scientists think that cannabis could have great potential for the development of new drugs. But whether or not the beneficial effects of marijuana are further supported by biomedical research, those counting on them will nevertheless have to face the legal aspects of using the drug in their countries. Indeed, the negative aspects of the plant, mainly the risk of addiction, are the reasons why most countries have outlawed the growth, possession and consumption of cannabis. The debate about the health benefits of cannabis is thus lost in a bitter clash between authorities that enforce strict laws against its use and proponents pushing for its legalization.

The many beneficial aspects of cannabis are not a new discovery—the plant has a long tradition in medicine that originated in oriental and Middle Eastern countries. The Chinese documented its medicinal value more than 4,000 years ago, using seeds, leaves and sap as sedatives or painkillers and to treat fevers, nausea and ulcers. Ancient herbalists made unguents for burns and other wounds from its roots. Galen, and other physicians of the classical and Hellenistic eras, also noted cannabis as a remedy, and the Arabs started using the plant as early as the mid-1200s. Although there is evidence of cannabis use in Europe from the thirteenth century, after Marco Polo returned from his journey to the east in 1297, its medical use became more popular in the nineteenth century, when the British physician William B. O'Shaugnessy brought back an account of the remarkable effects of this plant from India. Even Queen Victoria is said to have sipped marijuana tea prescribed by her court physician to treat menstrual cramps.

The debate about the health benefits of cannabis is thus lost in a bitter clash between authorities that enforce strict laws against its use and proponents pushing for its legalization

Such anecdotal claims of the healing properties of cannabis are now supported by modern research on the metabolism of cannabinoids—the active components of the plant—and their potential use in medicine. The plant contains more than 60 active compounds, of which the most psychoactive ingredient is Δ9-tetrahydrocannabinol (THC), which was first identified in the 1940s and first synthesized in 1965. THC mainly recognizes a receptor of the central nervous system called CB1, the cannabinoid receptor, which is involved in the regulation of synaptic transmission of excitatory and inhibitory neural circuits. Dronabinol, a synthetic form of THC, was approved by the US Food and Drug Administration to stimulate the appetite of AIDS patients and to treat their anorexia and associated weight loss. The same drug has been indicated for the treatment of nausea and vomiting associated with cancer chemotherapy. Cannabis also helps in the treatment of patients suffering from glaucoma, one of the most common causes of blindness, by reducing fluid pressure in the eye. Injections of synthetic THC eradicated malignant brain tumours in rats, suggesting that cannabinoids may even protect against the development of certain types of tumours (Galve-Roperh et al., 2000). Also of great interest is the ability of cannabis to mitigate symptoms of multiple sclerosis (MS), such as muscle spasms and spasticity (Baker et al. 2000).

But to claim that smoking marijuana solves many of your health problems is certainly not true, thinks Daniele Piomelli, Professor of Pharmacology at the University of California, Irvine, USA. “Although I am not against the compassionate use of cannabis in certain conditions, such as cancer anorexia or MS, where there is a great deal of evidence for its effectiveness,” he said, “if you want a selective and safe medication, in most cases cannabis is not for you.” Indeed, cannabis smoke can induce unpleasant effects such as panic and paranoia, hallucinations, increase in heart rate and lowering of blood pressure, and it leads to amotivational syndrome. Chronic marijuana smoking adversely affects short-term memory and cognitive abilities. Young adults who smoke cannabis have a slightly higher risk of developing psychosis and the frequent use of marijuana may promote a recurrence of schizophrenia in people who are vulnerable to this condition. In animal tests, THC also lowered testosterone production and reduced sperm production, motility and viability.

Although most of the current clinical use of cannabis concentrates on symptom management, researchers have increasingly become interested in the metabolic and neurological processes triggered by cannaboids. “The greatest potential offered by cannabis lies in the glimpse it offers to a signalling system, the endocannabinoid system, which can be modulated pharmacologically in various selective ways and which may well open up a new generation of endocannabinoid-based therapeutic drugs,” Piomelli said. The biology of the cannabinoids suggests that there might be other benefits in the treatment of neurological disorders, especially in slowing the progression of neurodegenerative diseases. For example, sustained receptor stimulation by cannabinoids can make up for the gradual loss of the CB1 receptor, which is associated with the onset of Huntington's disease. Through understanding and exploiting the biology of cannabinoids, researchers may in fact be able to bypass the main problem with the use of cannabis as a medicine: the impossibility of dissociating the potential therapeutic activities from the adverse effects. Researchers are now trying to design drugs that might work as agonists or antagonists of the endogenous cannabinoid system without the side-effects, with some evidence emerging in the treatment of anxiety (Kathuria et al., 2003).

...“if you want a selective and safe medication [...] cannabis is not for you.”

But major difficulties in using cannabis as a medicine are dosage and route of administration. At present, dronabinol, the commercial form of THC, is administered orally. But this is not the most effective route as cannabinoids are readily soluble in fats and are subject to considerable metabolism in the liver, leading to quick degradation. Smoking marijuana has a more rapid effect, but it is diffi-cult to dose and can cause smoking-related diseases, and probably lung cancer, to the same degree that cigarettes do. “I am not a strong believer of inhaled cannabis as a drug,” Piomelli said, “it contains too many unknown and potentially toxic compounds and smoking, the most effective mode of administration, is dangerous and unacceptable to many people.”An external file that holds a picture, illustration, etc.
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The biggest concern about the consumption of cannabis is the possibility of it constituting a 'gateway' to harder drugs. A recent study by Australian scientists provides new arguments for those who call for a ban on the use of cannabis, whether recreational or medical. The researchers from the Queensland Institute of Medical Research in Brisbane investigated the drug habits of 311 pairs of same-sex twins, including 136 identical twins, and found that the early marijuana smokers were up to five times more likely to move on to harder drugs than their twins (Lynskey et al., 2003). This provides further arguments for those who seek a complete ban on the growth, trade and consumption of cannabis, among them the current US administration, who recently escalated their war on pot.

Indeed, the USA already has some of the harshest laws on cannabis, which date back more than half a century. The first official ban on marijuana was the 1937 Cannabis Tax Act, the culmination of a campaign by Harry Anslinger, head of the Federal Bureau of Narcotics. Anslinger, a prohibitionist, made the public believe that marijuana was addictive and caused violent crimes, psychosis and mental deterioration. In 1970, the Controlled Substances Act put marijuana into the Schedule I category, together with heroin, LSD and other hallucinogenic amphetamines, as a drug of high potential for abuse and no medicinal use. Nowadays, growing a single plant of marijuana or possession of a single joint is illegal by US federal law and the number of marijuana arrests each year approaches 750,000.An external file that holds a picture, illustration, etc.
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However, in a 1996 state-wide referendum, California adopted a new law, known as Proposition 215, which legalizes the growth and consumption of marijuana for medicinal purposes. California was soon followed by Alaska, Arizona, Colorado, Hawaii, Maine, Nevada, Oregon and Washington. Particularly in California, where the climate is better suited for growing marijuana than in, say, Maine, under the patronage of the state or city councils, people started growing plants and selling marijuana to seriously ill people.

The biggest concern about the consumption of cannabis is the possibility of it constituting a 'gateway' to harder drugs

One of them was Ed Rosenthal from Oakland (CA, USA), author of more of a dozen books on marijuana cultivation. But earlier this year, Rosenthal found himself in the middle of a serious juridical clash between the State of California and the federal administration in Washington. In cracking down on illegal drug trafficking, federal agents seized and destroyed marijuana fields all over California. Rosenthal was arrested on charges of marijuana cultivation and conspiracy by federal laws and now faces a lawsuit that could bring him a life sentence. He claims that “laws controlling the use of marijuana are more harmful to society than what they intend to regulate. Those who think that marijuana is not a medicine and that those advocating its medical use have only the legalization of the drug on their agenda are either liars or ignorant. The medical potential of cannabis is enormous and it is well documented.” Rosenthal is not the only one. Fearing prosecution in their country, an increasing number of Americans convicted for drug use and claiming to be seriously ill moved to Canada and applied for political asylum. Marijuana is illegal in both countries, but Canada has legalized possession of the drug for chronically ill people and has just introduced a bill that will decriminalize possession of up to 15 g of marijuana.

In Europe too, the growth, possession and consumption of cannabis is not legal, with the exception of The Netherlands. But many countries, including Germany, Denmark, Belgium, Finland, Spain and Italy, have shown during the past ten years a clear tendency to ease drug policy and decriminalize personal possession and use (see the European Monitoring Centre for Drugs and Drug Addiction website: www.emcdda.org). The UK, which probably has the harshest drug law enforcement in Europe—and the highest level of drug use and addiction—may also soon make a big step towards the legalization of cannabis as a therapeutic drug. Cannabis was first outlawed and declared to be of no medical benefit in the UK in 1971 with the Misuse of Drugs Act, but patients continued to purchase cannabis on the black market for self-medication. This 'patient-led investigation' showed various benefits for sufferers of many disorders and, after having assessed all the evidence, the House of Lords regarded the therapeutic potential of cannabis for MS as the best-supported case and warranting further investigation. Funded by the Medical Research Council, and co-ordinated among others by Alan Thompson from University College London and John Zajicek from the Derriford Hospital in Plymouth, UK, the largest trial on MS since 2001, with 660 patients, has now been conducted, and the results are expected later this summer. Should these show an acceptable level of benefit from cannabis, the UK government is likely to rethink legalization, but only for medical use.

Be it in the USA, the UK or elsewhere, the study of the potential medical use of cannabis is still very contradictory. Although some evidence exists, proponents still need more valid and unequivocal clarification, without which it is going to be hard to convince governments to lift restrictions. The main problem in this inconclusive and controversial debate—whether presented by conservative politicians or ex-hippie activists looking for legalization of the drug—is that there are more opinions than facts. “An unfortunate consequence of this polarization of opinion has been the absence of any consensus on what health information the medical profession should give to patients who are users or potential users of cannabis,” commented Wayne Hall and Nadia Solowij, from the University of New South Wales in Australia, in The Lancet (1998).

References

  • Baker D, Pryce G., Croxford J.L., Brown P., Pertwee R.G., Huffman J.W. & Layward L. (2000) Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature, 404, 84–87. [PubMed]
  • Baker D, Pryce G., Giovannoni G. & Thompson A.J. (2003) The therapeutic potential of cannabis. The Lancet Neurology, 2, 291–298. [PubMed]
  • Galve-Roperh I., Sánchez C. Cortés M.L., Gómez del Pulgar T., Izquierdo M. & Guzmán M. (2000) Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nature Med., 6, 313–319. [PubMed]
  • Hall W. & Solowij N. (1998) Adverse effects of cannabis. Lancet, 352, 1611–1616. [PubMed]
  • Kathuria S. et al. . (2003) Modulation of anxiety through blockade of anandamide hydrolysis. Nature Med., 9, 76–81. [PubMed]
  • Lynskey M.T., Heath A.C., Bucholz K.K., Slutske W.S., Madden P.A.F., Nelson E.C., Statham D.J. & Martin N.G. (2003) Escalation of drug use in early-onset cannabis users vs co-twin controls. JAMA, 289, 427–433. [PubMed]

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