1.0 Introduction
Cannabinoids are a group of terpenophenolic compounds present in Cannabis sativa (commonly known as marijuana) and are structurally related to tetrahydrocannabinol (THC). The discovery of Endocannabinoids (endogenous cannabinoids), which occur naturally in the nervous system, where they bind to cannabinoid receptors (CB1) and also in the immune cells receptors CB2 led to speculations that plant and synthetic Cannabinoids could be useful therapeutically and particularly in neuropharmacology. Therefore there have been efforts to understand the roles and mechanism of action of endocannabinoids in modulating the neuronal function and the development of synthetic cannabinoids for clinical use. Synthetic THC analogs have been made in the laboratory and marketed as dronabinol and nabilone both approved by FDA for treatment of severe nausea and wasting syndrome. Other used derivatives include Cannabidiol, Cannabinol, β-Caryophyllene and Cannabigerol. However, the main potential problem that arises in this regimen is the possibility of misuse since there is no much regulation of legalized drugs (cannabinoid synthetic analogues) due to the ready availability of the illegal cannabinoid. Despite the legal, moral and religious restriction of the use of cannabinoid there is enormous evidence on the potential clinical use of cannabinoid.
3.0 Clinical uses of cannabinoids and potential uses
The active ingredient in cannabis sativa (Δ9-THC) has been used in the management of Alzheimer’s disease (AD). Δ9-THC slows down the progression to AD by reducing oxidative stress, neuro-inflammation and tau phosphorylation. It also inhibits the enzyme acetylcholinesterase responsible for formation of amyloid plaques in the brain that inhibit cognition and memory (NORML). The synthetic cannabinoid drugs work in much the same way as donepezil and tacrine in the treatment of the symptoms and progression of Alzheimer disease.
Δ9-THC acts as a CB1 receptor agonist in reducing intraocular pressure in glaucoma. In this treatment, marijuana is smoked twice a day at most so that it does not become abusive. The efficacy of smoking the marijuana cigarette is as good as most available glaucoma medications . Cannabinoids can also delay progression of Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease that causes loss of motor neurons in the spinal cord, brain stem, and motor cortex. Cannabinoids also alleviate pain, appetite loss, depression and drooling associated with ALS. Marijuana preparation called cannabiniod has also been used as a CB1 receptor agonist among HIV/AIDS patients where it stimulates appetite to counter excessive weight loss and also to manage chronic pain associated with many other diseases such as cancer. Since CB1 receptors modulate pain perception, marijuana in combination with other analgesic drugs has also been used to reduce neuropathic pain. Inhaled cannabis is the form used in these treatments because the plant extract has shown to have better results than derivatives.
Cannabidiol is also a regimen for management of neuropathic pain associated with Multiple Sclerosis (MS) and pain occurring in terminally ill patients suffering from chronic cancer. A formulation consisting of 50/50 Δ9-THC and cannabidiol (sativex) has been used to manage pain in cancer patients and neuropathic pain in MS. Cannabinoids enhance the mood of MS patients and improve the quality of life by reducing inflammation and pain associated with muscle spasm. Cannabidiol is a drug formulation containing Δ9-THC and a plant-derived cannabinoid. It is renowned for its lack of psychotropic effects. Cannabidiol may also prevent spread of breast cancer to the rest of the body in addition to offering chemotherapeutic effect without unpleasant side effects. Cannabidiol blocks the active gene responsible for inducing metastasis of cancer cells therefore containing the cancer in one location for uncomplicated radiotherapy treatment.
Cannabinoids such as THC have anticancer effect on brain cancer. Tumor cells in people with brain cancer were observed to shrink on THC treatment without causing any toxic effects. The cancer cells feed upon themselves in an autophagy process without affecting the healthy cells, thus reducing cancer cells . Other clinical use of cannabinoids and their synthetic derivatives include anti-inflammatory, anticonvulsant, anesthetic, hypnotic, antaparasitic, tranquilizer, antibiotic, diuretic, prodigestive, expectorant, aphrodisiac and appetite stimulant.
3.0 Problems of clinical use of cannabinoids
In spite of their clinical potencies, cannabinoids may have life threatening side effetcs in users that naively use the legal cannabis derived drugs . Smoking as a drug delivery method can have toxic effects in addition to having high potential for abuse. Furthermore, smoking of marijuana has proven toxic effects such as impaired cognitive function, therefore using it as a therapeutic agent has been termed unethical and illegal in some countries. The lack of clinical research medical value of smoked marijuana and its documented toxicity have made its clinical use improbable. Continued use of cannabis has also shown to increase risk of psychotic disorders and increased risk of lung cancer and chronic obstructive pulmonary disease.
Some of the effects of cannabinoids can be reversed by CB1 antagonists such as Rimonabant (also called SR141716). Rimonabant was initially developed to reduce appetite in obese individuals but there is evidence that it can be used to prevent cigarette and marijuana addiction. It has also been speculated that the drug can be used to reduce the negative effects of cannabinoids such impairment of short-term memory, cardiovascular effects and psychoactivity. As such it has been suggested that cannabinoids can be combined with Rimonabant to reduce the side effects of cannabinoid. However the drug has been withdrawn in most countries, including in Europe and America, due to the unacceptable side effects such as causing suicidal tendencies and depression . In addition Rimonabant targets and interfere with the endocannabinoid pathway which is responsible for pain tolerance, pleasure regulation and relaxation. The endocannabinoid system shields the brain in certain situations such as in head injury and stroke thus the use of Rimonabant could exacerbate brain damage. There is currently no sufficient data on the long term effects of Rimonabant on the endocannabinoid system. There is evidence that the drug can also aggravate the symptoms of MS.
4.0 Conclusion
Use of cannabinoids in clinical therapy is a sky-rocketing field in neuropharmacology and its growth is astonishing because of the prejudice held that cannabis is a hard drug usually for backstreet use. Its welcome into the pharmacology industry will be propagated by more documented research and regulation in their use. The evident toxic effects of cannabis abuse and its illegalization have made the current use of cannabinoids in clinical therapy unwelcomed. In addition, marketing of the herb by pharmaceutical industries may bring a problem since patenting is not possible. However, cannabinoids hold a future in the clinical world as a drug of choice in many diseases.
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