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From folklore to valid science Over the past few decades there has been widening interest in the viable medicinal uses of cannabis (marijuana). The National Institutes of Health (NIH), the Institute of Medicine and the Food and Drug Administration have all issued statements calling for further investigation. Cannabis has enjoyed a reputation as a therapeutic in many cultures for thousands of years. However its use in Western medicine died out in the 1930s over fears regarding its abuse potential. In the last decade there has been considerable advances in the understanding of the scientific basis of cannabinoid therapeutics, leading to a resurgence of interest in potential medicinal applications. Historically cannabis has been a valuable source of hemp fiber for many thousands of years. One of the first references to the medicinal use of cannabis may be found in Chinese pharmacopoeia dating to 2800 BC, documenting its use for pain relief. Indian writings in the Athera Veda dating to about 2000 BC, also refer to the therapeutic effects of cannabis. There is archeological evidence from Israel that cannabis was used therapeutically during childbirth. In the Greek and Roman eras, both the Herbal of Dioscorides and the writings of Galen refer to the therapeutic effects of cannabis. Cannabis came to western medicine far later when army physician William O’Shaughnessy used it medicinally in 1842. U.S. physicians frequently used it medicinally until it was made illegal in 1937. The recent discovery of a specific receptor system in our brains and nerves has led the progression of our understanding of the actions of cannabis from folklore to valid science. It now appears that the “cannabinoid” system evolved with our species and is intricately involved in normal human physiology, specifically in the control of movement, pain, memory and appetite, among others. Dense receptor concentrations have been found in the parts of the brain that control motor tone, coordination and mood state. Low concentrations are found in the brainstem, accounting for the remarkably low toxicity. Lethal doses in humans have not been described. Marijuana is a complex plant, with several types of subtypes of cannabis, each containing over 400 chemicals. Approximately 60 are chemically classified as cannabinoids. The cannabinoids are fat-soluble and will not dissolve in water. Structurally similar compounds, known as flavinoids, are also found in chocolate. Among the most psychoactive of the cannabinoids is the well-known delta-9-tetrahydrocannabinol, or THC, the active ingredient in dronabinol, which can be obtained by prescription. Other major cannabinoids include cannabidiol (CBD) and cannabinol (CBN), both of which may modify the actions of THC or have distinct effects of their own. CBD is not psychoactive but has significant anticonvulsant, sedative, and other pharmacological activity likely to interact with THC. At least two “internal” compounds manufactured in our body have been identified as cannabinoids. There are likely more. The roles of these internal cannabinoids have been only partially clarified but available evidence suggests they function as nerve messengers and may modulate nerve transmission. Signaling by the cannabinoid system appears to represent a mechanism by which nerves can communicate backwards across synapses to modulate their inputs. Cannabinoids appear to allow nerves to adjust the frequency of their input, much like adjusting the volume on your television. This may be the mechanism by which they help control pain and spasticity. As we are developing an increased understanding of the physiological function of cannabinoids it is becoming evident that they may be involved in the pathology of some diseases, particularly neurological disorders. Cannabinoids may induce both growth and death in a number of cells, including neurons. In the central nervous system (CNS), most of the experimental evidence indicates that cannabinoids may protect neurons from damage induced by toxic and traumatic insults. This “neuroprotective” effect of cannabinoids may have potential clinical relevance for the treatment of neurodegenerative disorders, including CMT, as well as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson’s disease, and injuries incurred when the brain is deprived of oxygen such as in a stroke. Oxidation is like rust on iron. It occurs when cells accumulate “free radicals” which are unpaired oxygen atoms. These are very toxic to cells and occur in physical injury as well as aging and some diseases. Well known anti-oxidants which many of us take include alpha-tocopherol (vitamin E), ascorbic acid (Vitamin C), flaxseed oil, beta-carotene (vitamin A), pychnogenols, and selenium, among others. Anti-oxidants bind up free radicals and prevent them from damaging cells. Recent studies have demonstrated the neuroprotective effects of synthetic, non-psychotropic cannabinoids, which appear to protect neurons from chemically-induced toxicity. Direct measurement of oxidative stress reveals that cannabinoids prevent cell death by anti-oxidation. The anti-oxidative property of cannabinoids is confirmed by their ability to antagonize oxidative stress and consequent cell death induced by the powerful oxidant poison, retinoid anhydroretinol. The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat brain nerve cells exposed to toxic levels of the excitatory neurotransmitter glutamate. Glutamate toxicity was reduced by both CBD (nonpsychoactive), and THC. CBD was more protective against glutamate neurotoxicity than either vitamin C or E. In addition, cannabinoids produce analgesia (pain relief) by modulating brain activity in a manner similar to, but pharmacologically distinct from, that of morphine and other opioids. Cannabinoids have been shown to produce an anti-inflammatory effect by inhibiting the production and action of tumor necrosis factor (TNF) and other acute phase cytokines, which are chemicals our body produces to help control inflammation and modulate our immune system. A growing number of strategies for separating sought-after therapeutic effects of cannabinoid receptor agonists from the unwanted consequences of cannabinoid receptor activation are now emerging. This will hopefully allow for the refinement of cannabinoids with high therapeutic potential and would facilitate designing maximally therapeutic drugs from the cannabinoid family. Effective delivery systems are also needed. Because the cannabinoids are volatile, they will vaporize at a temperature much lower than actual combustion. Thus heated air can be drawn through marijuana and the active compounds will vaporize, which can then be inhaled. Theoretically this removes most of the health hazards of smoking, although this has not been well studied. Recently, pharmacologically active, aerosolized forms of THC have been developed. This was done via a small particle nebulizer that generated an aerosol that could penetrate deeply into the lungs. There are currently ongoing trials in Canada and the U.K. using a form of oral cannabis. From a regulatory perspective, the scientific process should be allowed to evaluate the potential therapeutic effects of cannabis, dissociated from any societal debate over any potential deleterious effects of recreational or nonmedical marijuana use. This class of compounds not only holds tremendous therapeutic potential for neurological disease but also continues to be confirmed as having remarkably low toxicity. Dr. Gregory T. Carter is a physiatrist. He is medical director of the Providence Rehabilitation Hospital, in Chehalis, Washington, U.S.A. Donations for his research into CMT may be sent to Charcot-Marie-Tooth Fund, c/o Providence HealthCare Foundation, 914 S. Schuber Rd., Centralia, WA 98531, U.S.A. The fund is a not for profit tax exempt 501 C3 organization. Linda here - If you are interested in trying cannabis for pain or spasm but do not want to smoke it, it can be ingested but a little goes a long way, or look up a vaporizer called the Eterra at www.Eterra.com on the Internet.
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