Therapeutic properties of cannabinoid drugs and marijuana in several disorders: A narrative review (original) (raw)
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Adverse effects of medical cannabinoids: a systematic review
Canadian Medical Association Journal, 2008
C annabis (Cannabis sativa) is widely used as a recreational drug, with an estimated worldwide annual prevalence (defined as use at least once per year) of 160 million. 1 Cannabis preparations have also been used medicinally for thousands of years. In the past 40 years the active ingredients of cannabis, Δ-9-tetrahydrocannabinol and cannabidiol, and other derivatives (termed "cannabinoids") have been identified and characterized, 2 and it is becoming clear that cannabinoids have considerable therapeutic potential. 3 In Canada, 4 cannabinoid products are currently available for medical use, more than in any other country worldwide. These are: a herbal cannabis extract (marketed as Sativex [GW Pharmaceuticals], which contains Δ-9-tetrahydrocannabinol and cannabidiol in an oromucosal spray); dronabinol (synthetic Δ-9-tetrahydrocannabinol, marketed as Marinol [Solvay Pharmaceuticals]); nabilone (a synthetic derivative of Δ-9tetrahydrocannabinol, marketed as Cesamet [Valeant Pharmaceuticals International]); and the herbal form of cannabis (available legally through the Medical Marijuana Access Regulations). 4,5 In Canada, dronabinol and nabilone are indicated for chemotherapy-induced nausea and vomiting, dronabinol is approved for HIV-associated anorexia, and oromucosal Δ-9tetrahydrocannabinol-cannabidiol is conditionally approved for neuropathic pain in multiple sclerosis and cancer pain. The efficacy of these cannabinoid medicines has been evaluated in randomized controlled trials. In addition, the use of cannabinoids as antiemetics has been systematically reviewed, and potential efficacy has been suggested. 6 There has also been considerable interest in the use of cannabinoids as adjunctive therapy for pain management, and several small randomized controlled trials have been published recently. Dronabinol and oromucosal Δ-9-tetrahydrocannabinolcannabidiol have been proven effective for central neuropathic pain associated with multiple sclerosis. 7-11 Oromucosal Δ-9-tetrahydrocannabinol-cannabidiol reduced pain associated with rheumatoid arthritis, 12 and nabilone was effective for pain associated with fibromyalgia. 13 A recent review supported further consideration of cannabinoids for Research
Review: Cannabinoids as Medicinals
Current Addiction Reports
Purpose of review There have been many debates, discussions, and published writings about the therapeutic value of cannabis plant and the hundreds of cannabinoids it contains. Many states and countries have attempted, are attempting, or have already passed bills to allow legal use of cannabinoids, especially cannabidiol (CBD), as medicines to treat a wide range of clinical conditions without having been approved by a regulatory body. Therefore, by using PubMed and Google Scholar databases, we have reviewed published papers during the past 30 years on cannabinoids as medicines and comment on whether there is sufficient clinical evidence from well-designed clinical studies and trials to support the use of CBD or any other cannabinoids as medicines. Recent findings Current research shows that CBD and other cannabinoids currently are not ready for formal indications as medicines to treat a wide range of clinical conditions as promoted except for several exceptions including limited use of CBD for treating two rare forms of epilepsy in young children and CBD in combination with THC for treating multiplesclerosis-associated spasticity. Summary Research indicates that CBD and several other cannabinoids have potential to treat multiple clinical conditions, but more preclinical, and clinical studies and clinical trials, which follow regulatory guidelines, are needed to formally recommend CBD and other cannabinoids as medicines.
Archives of General Psychiatry, 2000
Three focal concerns in evaluating the medical use of marijuana are: 1. Evaluation of the effects of isolated cannabinoids; 2. Evaluation of the risks associated with the medical use of marijuana; and 3. Evaluation of the use of smoked marijuana. EFFECTS OF ISOLATED CANNABINOIDS Cannabinoid Biology Much has been learned since the 1982 IOM report Marijuana and Health. Although it was clear then that most of the effects of marijuana were due to its actions on the brain, there was little information about how THC acted on brain cells (neurons), which cells were affected by THC, or even what general areas of the brain were most affected by THC. In addition, too little was known about cannabinoid physiology to offer any scientific insights into the harmful or therapeutic effects of marijuana. That all changed with the identification and characterization of cannabinoid receptors in the 1980s and 1990s. During the past 16 years, science has advanced greatly and can tell us much more about the potential medical benefits of cannabinoids. Conclusion: At this point, our knowledge about the biology of marijuana and cannabinoids allows us to make some general conclusions: o Cannabinoids likely have a natural role in pain modulation, control of movement, and memory. o The natural role of cannabinoids in immune systems is likely multi-faceted and remains unclear. o The brain develops tolerance to cannabinoids. o Animal research demonstrates the potential for dependence, but this potential is observed under a narrower range of conditions than with benzodiazepines, opiates, cocaine, or nicotine. o Withdrawal symptoms can be observed in animals but appear to be mild compared to opiates or benzodiazepines, such as diazepam (Valium). Conclusion: The different cannabinoid receptor types found in the body appear to play different roles in normal human physiology. In addition, some effects of cannabinoids appear to be independent of those receptors. The variety of mechanisms through which cannabinoids can influence human physiology underlies the variety of potential therapeutic uses for drugs that might act selectively on different cannabinoid systems. Recommendation 1: Research should continue into the physiological effects of synthetic and plant-derived cannabinoids and the natural function of cannabinoids found in the body. Because different cannabinoids appear to have different effects, cannabinoid research should include, but not be restricted to, effects attributable to THC alone. Efficacy of Cannabinoid Drugs The accumulated data indicate a potential therapeutic value for cannabinoid drugs, particularly for symptoms such as pain relief, control of nausea and vomiting, and appetite stimulation. The therapeutic effects of cannabinoids are best established for THC, which is generally one of the two most abundant of the cannabinoids in marijuana. (Cannabidiol is generally the other most abundant cannabinoid.) The effects of cannabinoids on the symptoms studied are generally modest, and in most cases there are more effective medications. However, people vary in their responses to medications, and there will likely always be a subpopulation of patients who do not respond well to other medications. The combination of cannabinoid drug effects (anxiety reduction, appetite stimulation, nausea reduction, and pain relief) suggests that cannabinoids would be moderately well suited for particular conditions, such as chemotherapy-induced nausea and vomiting and AIDS wasting. Defined substances, such as purified cannabinoid compounds, are preferable to plant products, which are of variable and uncertain composition. Use of defined cannabinoids permits a more precise evaluation of their effects, whether in combination or alone. Medications that can maximize the desired effects of cannabinoids and minimize the undesired effects can very likely be identified. Although most scientists who study cannabinoids agree that the pathways to cannabinoid drug development are clearly marked, there is no guarantee that the fruits of scientific research will be made available to the public for medical use. Cannabinoidbased drugs will only become available if public investment in cannabinoid drug research is sustained and if there is enough incentive for private enterprise to develop and market such drugs. Conclusion: Scientific data indicate the potential therapeutic value of cannabinoid drugs, primarily THC, for pain relief, control of nausea and vomiting, and appetite stimulation; smoked marijuana, however, is a crude THC delivery system that also delivers harmful substances. Recommendation 2: Clinical trials of cannabinoid drugs for symptom management should be conducted with the goal of developing rapid-onset, reliable, and safe delivery systems. Influence of Psychological Effects on Therapeutic Effects The psychological effects of THC and similar cannabinoids pose three issues for the therapeutic use of cannabinoid drugs. First, for some patients-particularly older patients with no previous marijuana experience-the psychological effects are disturbing. Those patients report experiencing unpleasant feelings and disorientation after being treated with THC, generally more severe for oral THC than for smoked marijuana. Second, for conditions such as movement disorders or nausea, in which anxiety exacerbates the symptoms, the antianxiety effects of cannabinoid drugs can influence symptoms indirectly. This can be beneficial or can create false impressions of the drug effect. Third, for cases in which symptoms are multifaceted, the combination of THC effects might provide a form of adjunctive therapy; for example, AIDS wasting patients would likely benefit from a medication that simultaneously reduces anxiety, pain, and nausea while stimulating appetite. Conclusion: The psychological effects of cannabinoids, such as anxiety reduction, sedation, and euphoria can influence their potential therapeutic value. Those effects are potentially undesirable for certain patients and situations and beneficial for others. In addition, psychological effects can complicate the interpretation of other aspects of the drug's effect. Recommendation 3: Psychological effects of cannabinoids such as anxiety reduction and sedation, which can influence medical benefits, should be evaluated in clinical trials. RISKS ASSOCIATED WITH MEDICAL USE OF MARIJUANA Physiological Risks Marijuana is not a completely benign substance. It is a powerful drug with a variety of effects. However, except for the harms associated with smoking, the adverse effects of marijuana use are within the range of effects tolerated for other medications. The harmful effects to individuals from the perspective of possible medical use of marijuana are not necessarily the same as the harmful physical effects of drug abuse. When interpreting studies purporting to show the harmful effects of marijuana, it is important to keep in mind that the majority of those studies are based on smoked marijuana, and cannabinoid effects cannot be separated from the effects of inhaling smoke from burning plant material and contaminants. For most people the primary adverse effect of acute marijuana use is diminished psychomotor performance. It is, therefore, inadvisable to operate any vehicle or potentially dangerous equipment while under the influence of marijuana, THC, or any cannabinoid drug with comparable effects. In addition, a minority of marijuana users experience dysphoria, or unpleasant feelings. Finally, the short-term immunosuppressive effects are not well established but, if they exist, are not likely great enough to preclude a legitimate medical use. The chronic effects of marijuana are of greater concern for medical use and fall into two categories: the effects of chronic smoking and the effects of THC. Marijuana smoking is associated with abnormalities of cells lining the human respiratory tract. Marijuana smoke, like tobacco smoke, is associated with increased risk of cancer, lung damage, and poor pregnancy outcomes. Although cellular, genetic, and human studies all suggest that marijuana smoke is an important risk factor for the development of respiratory cancer, proof that habitual marijuana smoking does or does not cause cancer awaits the results of well-designed studies. Conclusion: Numerous studies suggest that marijuana smoke is an important risk factor in the development of respiratory disease. Recommendation 4: Studies to define the individual health risks of smoking marijuana should be conducted, particularly among populations in which marijuana use is prevalent. Marijuana Dependence and Withdrawal A second concern associated with chronic marijuana use is dependence on the psychoactive effects of THC. Although few marijuana users develop dependence, some do. Risk factors for marijuana dependence are similar to those for other forms of substance abuse. In particular, antisocial personality and conduct disorders are closely associated with substance abuse. Conclusion: A distinctive marijuana withdrawal syndrome has been identified, but it is mild and short lived. The syndrome includes restlessness, irritability, mild agitation, insomnia, sleep disturbance, nausea, and cramping. Marijuana as a "Gateway" Drug Patterns in progression of drug use from adolescence to adulthood are strikingly regular. Because it is the most widely used illicit drug, marijuana is predictably the first illicit drug most people encounter. Not surprisingly, most users of other illicit drugs have used marijuana first. In fact, most drug users begin with alcohol and nicotine before marijuana-usually before they are of legal age. not be a problem if the medical use of marijuana were as closely regulated as other medications with abuse potential. Conclusion: Present data on drug use progression neither support nor refute the suggestion that medical availability would increase drug abuse. However, this question is beyond the issues...
JAMA, 2015
IMPORTANCE Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear. OBJECTIVE To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids.
Cannabinoids in health and disease
Dialogues in clinical neuroscience, 2007
Cannabis sativa L. preparations have been used in medicine for millenia. However, concern over the dangers of abuse led to the banning of the medicinal use of marijuana in most countries in the 1930s. Only recently, marijuana and individual natural and synthetic cannabinoid receptor agonists and antagonists, as well as chemically related compounds, whose mechanism of action is still obscure, have come back to being considered of therapeutic value. However, their use is highly restricted. Despite the mild addiction to cannabis and the possible enhancement of addiction to other substances of abuse, when combined with cannabis, the therapeutic value of cannabinoids is too high to be put aside. Numerous diseases, such as anorexia, emesis, pain, inflammation, multiple sclerosis, neurodegenerative disorders (Parkinson's disease, Huntington's disease, Tourette's syndrome, Alzheimer's disease), epilepsy, glaucoma, osteoporosis, schizophrenia, cardiovascular disorders, cancer...
Cannabis therapy in neurological disorders: Recent advances and perspectives
2020
Both phytocannabinoids (Δ9-tetrahydrocannabinol, cannabidiol) and synthetic derivatives (nabilone, dronabinol) showed therapeutic benefits in some neurological disorders. Cannabis inhalation was reported to attenuate several symptoms (rigidity, bradykinesia, tremor) in Parkinson’s disease. A significant reduction in monthly seizures in patients with epilepsy has been noted for cannabidiol, while administration of Δ9-tetrahydrocannabinol resulted in benefits on psychomotor agitation in patients suffering from Alzheimer’s disease. Although there are clinical studies supporting the use of cannabis preparations as adjuvant therapy in neurological disorders, more investigations are needed to assess their safety and efficacy.
The therapeutic potential of cannabis
The Lancet Neurology, 2003
Research of the cannabinoid system has many similarities with that of the opioid system. In both instances, studies into drug-producing plants led to the discovery of an endogenous control system with a central role in neurobiology. Few compounds have had as much positive press from patients as those of the cannabinoid system. While these claims are investigated in disorders such as multiple sclerosis spasticity and pain, basic research is discovering interesting members of this family of compounds that have previously unknown qualities, the most notable of which is the capacity for neuroprotection. Large randomised clinical trials of the better known compounds are in progress. Even if the results of these studies are not as positive as many expect them to be, that we are only just beginning to appreciate the huge therapeutic potential of this family of compounds is clear.
2021
Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.
Future of Cannabis and Cannabinoids in Therapeutics
Journal of Cannabis Therapeutics, 2004
This study reviews human clinical experience to date with several synthetic cannabinoids, including nabilone, levonantradol, ajulemic acid (CT3), dexanabinol (HU-211), HU-308, and SR141716 (Rimonabant ®). Additionally, the concept of "clinical endogenous cannabinoid deficiency" is explored as a possible factor in migraine, idiopathic bowel disease, fibromyalgia and other clinical pain states. The concept of analgesic synergy of cannabinoids and opioids is addressed. A cannabinoid-mediated improvement in night vision at the retinal level is discussed, as well as its potential application to treatment of retinitis pigmentosa and other conditions. Additionally noted is the role of cannabinoid treatment in neuroprotection and its application to closed head injury, cerebrovascular accidents, and CNS degenerative diseases including Alzheimer, Huntington, Parkinson diseases and ALS. Excellent clinical results employing cannabis based medicine extracts (CBME) in spasticity and spasms of MS suggests extension of such treatment to other spasmodic and dystonic conditions. Finally, controversial areas of cannabinoid treatment in obstetrics, gynecology and pediatrics are addressed along with a rationale for such interventions.