Medical cannabis refers to the parts of the herb cannabis used as a physician-recommended form of medicine or herbal therapy, or to synthetic forms of specific cannabinoids such as THC as a physician-recommended form of medicine. The Cannabis plant has a long history of use as medicine, with historical evidence dating back to 2737 BCE. Cannabis is one of the 50 “fundamental” herbs of traditional Chinese medicine, and is prescribed for a broad range of indications.
Use
Cannabis as illustrated in Köhler’s book of medicinal plants from 1897
Medical cannabis is illegal in most countries. A number of governments, including the U.S. Federal Government, allow treatment with one or more specific low doses of synthetic cannabinoids for one or more disorders.
Supporters of medical cannabis argue that cannabis does have several well-documented beneficial effects. Among these are: the amelioration of nausea and vomiting, stimulation of hunger in chemotherapy and AIDS patients, lowered intraocular eye pressure (shown to be effective for treating glaucoma), as well as gastrointestinal illness. Its effectiveness as an analgesic has been suggested—and disputed—as well.
There are several methods for administration of dosage, including vaporizing or smoking dried buds, drinking, or eating extracts, and taking capsules. The comparable efficiency of these methods was the subject of an investigative study conducted by the National Institutes of Health.
Synthetic cannabinoids are available as prescription drugs in some countries. Examples are Marinol (The United States and Canada) and Cesamet (Canada, Mexico, the United Kingdom, and the United States).
While utilizing cannabis for recreational purposes is illegal in many parts of the world, many countries are beginning to entertain varying levels of decriminalization for medical usage (the medical marijuana movement), including Canada, Austria, Germany, Switzerland, the Netherlands, Czech Republic, Spain, Israel, Italy, Finland, and Portugal. In the United States, federal law outlaws all use of herb parts from Cannabis, while some states have approved use of herb parts from Cannabis as medical cannabis in conflict with federal law. The United States Supreme Court has ruled in United States v. Oakland Cannabis Buyers’ Coop and Gonzales v. Raich that the federal government has a right to regulate and criminalize cannabis, even for medical purposes. A person can therefore be prosecuted for a cannabis-related crime even if it is medical cannabis that is legal according to the laws of this state.
Clinical applications
“Victoria”, the United States’ first legal medical marijuana plant grown by The Wo/Men’s Alliance for Medical Marijuana.[citation needed]
A 2002 review of medical literature by Franjo Grotenhermen states that medical cannabis has established effects in the treatment of nausea, vomiting, premenstrual syndrome, unintentional weight loss, insomnia, and lack of appetite. Other “relatively well-confirmed” effects were in the treatment of “spasticity, painful conditions, especially neurogenic pain, movement disorders, asthma, [and] glaucoma”.
Preliminary findings indicate that cannabis-based drugs could prove useful in treating inflammatory bowel disease, migraines, fibromyalgia, and related conditions.
Medical cannabis has also been found to relieve certain symptoms of multiple sclerosis and spinal cord injuries by exhibiting antispasmodic and muscle-relaxant properties as well as stimulating appetite.
Other studies state that cannabis or cannabinoids may be useful in treating alcohol abuse, amyotrophic lateral sclerosis, collagen-induced arthritis, asthma, atherosclerosis, bipolar disorder, colorectal cancer, HIV-Associated Sensory Neuropathy depression, dystonia, epilepsy, digestive diseases, gliomas, hepatitis C, Huntington’s disease, leukemia, skin tumors, methicillin-resistant Staphylococcus aureus (MRSA), Parkinson’s disease, pruritus, posttraumatic stress disorder (PTSD), psoriasis, sickle-cell disease, sleep apnea, and anorexia nervosa. Controlled research on treating Tourette syndrome with a synthetic version of tetrahydrocannabinol, (brand name Marinol) (the main psychoactive chemical found in cannabis), showed the patients taking Marinol had a beneficial response without serious adverse effects; other studies have shown that cannabis “has no effects on tics and increases the individuals inner tension”. Case reports found that cannabis helped reduce tics, but validation of these results requires longer, controlled studies on larger samples.
A study done by Craig Reinarman surveyed among why people in California used cannabis and it found many reasons why people had used cannabis. It was used to relieve pain, muscle spasms, headaches, anxiety, nausea, vomiting, depression, cramps, panic attacks, diarrhea, and itching. Others used cannabis to improve sleep, relaxation, appetite, concentration or focus, and energy. Some patients used it to prevent medication side effects, anger, involuntary movements, and seizures, while others used it as a substitute for other prescription medications and alcohol.
Recent studies
Safety of cannabis
Various strains of medical marijuana in front of a vaporizer
Cannabis smoke contains thousands of organic and inorganic chemical compounds. This tar is chemically similar to that found in cigarette smoke and includes many of the same carcinogens.
Deaths attributed directly to cannabis usage are infrequent but have been documented. Cannabis related deaths are more widespread.
From January 1997 to June 2005, the U.S. Food and Drug Administration (FDA) reported zero deaths caused by the primary use of cannabis. In contrast, common FDA-approved drugs which are often prescribed in lieu of cannabis (such as anti-emetics and anti-psychotics), were the primary cause of 10,008 deaths.The cannabinoid THC has an extremely low toxicity and the amount that can enter the body through the consumption of cannabis plants poses no threat of death.
Cannabis smoke contains substances that can damage DNA and increase the risk of cancer just like tobacco smoke, though no definitive link between cannabis and cancer has been found. Cancer causing chemicals in cannabis smoke have been found in amounts 50% higher than those found in tobacco smoke. According to the British Lung Foundation, smoking three to four joints (cannabis cigarettes) a day has been found to be associated with the same degree of damage to tissue in the airways of the lung as 20 or more tobacco cigarettes a day.
The Journal of the American Medical Association released findings from a 20-year study that bolstered evidence that cannabis doesn’t do the kind of damage tobacco does. Analysis of over 5,000 smokers showed that cannabis did not appear to harm lung function, although cigarettes did. Cigarette smokers’ scores worsened steadily over the course of the study. Participants who smoked up to 1 joint daily for 7 years, or 1 joint weekly for 20 years, were not linked with worse scores. Dr Donald Tashkin suggested the reason for this might be that cannabis helps fight inflammation and may counteract the effects of irritating chemicals in the drug. The study concluded: “Occasional and low cumulative marijuana use was not associated with adverse effects on pulmonary function”.
Cannabis usage has been shown to negatively affect the ability to drive safely. The British Medical Journal recently indicated that “Drivers who consume cannabis within three hours of driving are nearly twice as likely to cause a vehicle collision as those who are not under the influence of drugs or alcohol”
Glaucoma
Medical cannabis in edible form
In glaucoma, cannabis and THC have been shown to reduce intra-ocular pressure (IOP) by an average of 24% in people with normal IOP who have visual-field changes. In studies of healthy adults and glaucoma patients, IOP was reduced by an average of 25% after smoking a cannabis “cigarette” that contained approximately 2% THC—a reduction as good as that observed with most other medications available today, according to a review by the Institute of Medicine.
In a separate study, the use of cannabis and glaucoma was tested and found that the duration of smoked or ingested cannabis or other cannabinoids is very short, averaging 3 to 3.5 hours. Their results showed that for cannabis to be a viable therapy, the patient would have to take in cannabis in some form every 3 hours. They said that for ideal glaucoma treatment it would take two times a day at most for compliance purposes from patients.
Spasticity in multiple sclerosis
Medical cannabis
A review of six randomized controlled trials of a combination of THC and CBD extracts for the treatment of multiple sclerosis (MS) related muscle spasticity reported, “Although there was variation in the outcome measures reported in these studies, a trend of reduced spasticity in treated patients was noted.” The authors postulated that “cannabinoids may provide neuroprotective and anti-inflammatory benefits in MS.” A small study done on whether or not cannabis could be used to control tremors of MS patients was conducted. The study found that there was no noticeable difference of the tremors in the patients. Although there was no difference in the tremors the patients felt as if their symptoms had lessened and their quality of life had improved. The researchers concluded that the mood enhancing or cognitive effects that cannabis has on the brain could have given the patients the effect that their tremors were getting better.
Alzheimer’s disease
Research done by the Scripps Research Institute in California shows that the active ingredient in marijuana, THC, prevents the formation of deposits in the brain associated with Alzheimer’s disease. THC was found to prevent an enzyme called acetylcholinesterase from accelerating the formation of “Alzheimer plaques” in the brain more effectively than commercially marketed drugs. THC is also more effective at blocking clumps of protein that can inhibit memory and cognition in Alzheimer’s patients, as reported in Molecular Pharmaceutics. Cannabinoids can also potentially prevent or slow the progression of Alzheimer’s disease by reducing tau protein phosphorylation, oxidative stress, and neuroinflammation.
Breast cancer
According to a 2007 study at the California Pacific Medical Center Research Institute, cannabidiol (CBD) may stop breast cancer from spreading throughout the body. These researchers believe their discovery may provide a non-toxic alternative to chemotherapy while achieving the same results minus the painful and unpleasant side effects. The research team says that CBD works by blocking the activity of a gene called Id-1, which is believed to be responsible for a process called metastasis, which is the aggressive spread of cancer cells away from the original tumor site.
HIV/AIDS
Investigators at Columbia University published clinical trial data in 2007 showing that HIV/AIDS patients who inhaled cannabis four times daily experienced substantial increases in food intake with little evidence of discomfort and no impairment of cognitive performance. They concluded that smoked cannabis has a clear medical benefit in HIV-positive patients. In another study in 2008, researchers at the University of California, San Diego School of Medicine found that marijuana significantly reduces HIV-related neuropathic pain when added to a patient’s already-prescribed pain management regimen and may be an “effective option for pain relief” in those whose pain is not controlled with current medications. Mood disturbance, physical disability, and quality of life all improved significantly during study treatment. Despite management with opioids and other pain modifying therapies, neuropathic pain continues to reduce the quality of life and daily functioning in HIV-infected individuals. Cannabinoid receptors in the central and peripheral nervous systems have been shown to modulate pain perception. No serious adverse effects were reported, according to the study published by the American Academy of Neurology. A study examining the effectiveness of different drugs for HIV associated neuropathic pain found that smoked Cannabis was one of only three drugs that showed evidence of efficacy.
Brain cancer
A study by Complutense University of Madrid found the chemicals in cannabis promote the death of brain cancer cells by essentially helping them feed upon themselves in a process called autophagy. The research team discovered that cannabinoids such as THC had anticancer effects in mice with human brain cancer cells and in people with brain tumors. When mice with the human brain cancer cells received the THC, the tumor shrank. Using electron microscopes to analyze brain tissue taken both before and after a 26- to 30-day THC treatment regimen, the researchers found that THC eliminated cancer cells while leaving healthy cells intact. The patients did not have any toxic effects from the treatment; previous studies of THC for the treatment of cancer have also found the therapy to be well tolerated. However, the mechanisms which promote THC’s tumor cell–killing action are unknown.
Opioid dependence
Injections of THC eliminate dependence on opiates in stressed rats, according to a research team at the Laboratory for Physiopathology of Diseases of the Central Nervous System (France) in the journal Neuropsychopharmacology. Deprived of their mothers at birth, rats become hypersensitive to the rewarding effect of morphine and heroin (substances belonging to the opiate family), and rapidly become dependent. When these rats were administered THC, they no longer developed typical morphine-dependent behavior. In the striatum, a region of the brain involved in drug dependence, the production of endogenous enkephalins was restored under THC, whereas it diminished in rats stressed from birth which had not received THC. Researchers believe the findings could lead to therapeutic alternatives to existing substitution treatments.
In humans, drug treatment subjects who use cannabis intermittently are found to be more likely to adhere to treatment for opioid dependence. Historically, similar findings were reported by Edward Birch, who, in 1889, reported success in treating opiate and chloral addiction with cannabis.
Controlling ALS symptoms
Recent research has been conducted on if the use of cannabis could control some of the symptoms of ALS or Lou Gehrig’s Disease. A survey was conducted on 131 people who suffered from ALS. The survey asked if the subjects had used cannabis in the last 12 months to control some of their symptoms. The survey resulted in 13 people who had used the drug in some form to control symptoms. The survey results found that cannabis was moderately effective in reducing symptoms of appetite loss, depression, pain, spasticity, drooling and weakness and the longest relief reported was for depression. The pattern of symptom relief was consistent with those reported by people with other conditions, including multiple sclerosis (Amtmann et al. 2004).
Medicinal compounds
Cannabis contains 483 compounds. At least 80 of these are cannabinoids, which are the basis for medical and scientific use of cannabis. This presents the research problem of isolating the effect of specific compounds and taking account of the interaction of these compounds. Cannabinoids can serve as appetite stimulants, antiemetics, antispasmodics, and have some analgesic effects. Six important cannabinoids found in the cannabis plant are tetrahydrocannabinol, tetrahydrocannabinolic acid, cannabidiol, cannabinol, β-caryophyllene, and cannabigerol.
Tetrahydrocannabinol
Main article: Tetrahydrocannabinol
Chemical structure of tetrahydrocannabinol (THC)
Tetrahydrocannabinol (THC) is the primary compound responsible for the psychoactive effects of cannabis. The compound is a mild analgesic, and cellular research has shown the compound has antioxidant activity. THC is believed to interact with parts of the brain normally controlled by the endogenous cannabinoid neurotransmitter, anandamide. Anandamide is believed to play a role in pain sensation, memory, and sleep.
Cannabidiol
Main article: Cannabidiol
Cannabidiol has been shown to relieve convulsions, inflammation, anxiety, cough, congestion and nausea, and it inhibits cancer cell growth.
Cannabidiol (CBD) is a major constituent of medical cannabis. CBD represents up to 40% of extracts of medical cannabis.Cannabidiol has been shown to relieve convulsion, inflammation, anxiety, cough, congestion and nausea, and it inhibits cancer cell growth. Recent studies have shown cannabidiol to be as effective as atypical antipsychotics in treating schizophrenia. Because cannabidiol relieves the aforementioned symptoms, cannabis strains with a high amount of CBD may benefit people with multiple sclerosis, frequent anxiety attacks and Tourette syndrome.
Cannabinol
Main article: Cannabinol
Structure of Cannabinol
Cannabinol (CBN) is a therapeutic cannabinoid found in Cannabis sativa and Cannabis indica. It is also produced as a metabolite, or a breakdown product, of tetrahydrocannabinol (THC). CBN acts as a weak agonist of the CB1 and CB2 receptors, with lower affinity in comparison to THC.
β-Caryophyllene
Main article: Caryophyllene
Chemical structure of β-caryophyllene
Part of the mechanism by which medical cannabis has been shown to reduce tissue inflammation is via the compound β-caryophyllene. A cannabinoid receptor called CB2 plays a vital part in reducing inflammation in humans and other animals. β-Caryophyllene has been shown to be a selective activator of the CB2 receptor. β-Caryophyllene is especially concentrated in cannabis essential oil, which contains about 12–35% β-caryophyllene.
Cannabigerol
Main article: Cannabigerol
Like cannabidiol, cannabigerol is not psychoactive. Cannabigerol has been shown to relieve intraoccular pressure, which may be of benefit in the treatment of glaucoma.
Cannabigerol.
Pharmacologic THC and THC derivatives
In the USA, the FDA has approved several cannabinoids for use as medical therapies: dronabinol (Marinol) and nabilone. These medicines are taken orally.
These medications are usually used when first line treatments for nausea and vomiting associated with cancer chemotherapy fail to work. In extremely high doses and in rare cases “psychotomimetic” side effects are possible. The other commonly used antiemetic drugs are not associated with these side effects.
Canasol is a cannabis-based medication for glaucoma that relieves intraocular pressure symptoms associated with late-stage glaucoma.
It was created by an ophthalmologist, Dr. Albert Lockhart and Dr. Manley E. West, and began distribution in 1987. As of 2003, it was still being distributed in the United Kingdom, several US states, and several Caribbean nations.
It is notable for being one of the first cannabis-containing pharmaceuticals to be developed for the modern pharmaceutical market and being one of the few such pharmaceuticals to have ever been legally marketed in the United States.
The prescription drug Sativex, an extract of cannabis administered as a sublingual spray, has been approved in Canada for the adjunctive treatment (use along side other medicines) of both multiple sclerosis and cancer related pain. Sativex has also been approved in the United Kingdom, New Zealand, and the Czech Republic, and is expected to gain approval in other European countries. William Notcutt is one of the chief researchers that has developed Sativex, and he has been working with GW and founder Geoffrey Guy since the company’s inception in 1998. Notcutt states that the use of MS as the disease to study “had everything to do with politics.”
Medication
Approval
Country
Licensed indications
Cost
Nabilone
1985
USA, Canada
Nausea of cancer chemotherapy that has failed to respond adequately to other antiemetics
US$ 4000.00 for a year’s supply (in Canada)
Canasol
1987
USA, Canada, several Caribbean nations
Introcular pressure associated with late-stage Glaucoma
Marinol
1985
USA
Canada (1992)
Nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional treatments
US$ 652 for 30 doses @ 10 mg online
1992
USA
Anorexia associated with AIDS–related weight loss
Sativex
1995
Canada
Adjunctive treatment for the symptomatic relief of neuropathic pain in multiple sclerosis in adults
C$ 9,351 per year
1997
Canada
Pain due to cancer
Difference between Cannabis indica and Cannabis sativa
Cannabis sativa, Cannabis indica, and Cannabis ruderalis
Cannabis indica may have a CBD:THC ratio 4–5 times that of Cannabis sativa. Cannabis strains with relatively high CBD:THC ratios are less likely to induce anxiety than vice versa. This may be due to CBD’s antagonistic effects at the cannabinoid receptors, compared to THC’s partial agonist effect. CBD is also a 5-HT1A receptor agonist, which may also contribute to an anxiolytic effect. This likely means the high concentrations of CBD found in Cannabis indica mitigate the anxiogenic effect of THC significantly. The effects of sativa are well known for its cerebral high, hence used daytime as medical cannabis, while indica are well known for its sedative effects and preferred night time as medical cannabis.
Criticism
One of the major criticisms of cannabis as medicine is opposition to smoking as a method of consumption. However, smoking is no longer necessary due to the development of healthier methods. Today, medicinal cannabis patients can use vaporizers, where the essential cannabis compounds are extracted and inhaled. In addition, edible cannabis, which is produced in various baked goods, is also available, and has demonstrated longer lasting effects.
The United States Food and Drug Administration (FDA) issued an advisory against smoked medical cannabis stating that, “marijuana has a high potential for abuse, has no currently accepted medical use in treatment in the United States, and has a lack of accepted safety for use under medical supervision. The National Institute on Drug Abuse NIDA state that “Marijuana itself is an unlikely medication candidate for several reasons: it is an unpurified plant containing numerous chemicals with unknown health effects; it is typically consumed by smoking further contributing to potential adverse effects; and its cognitive impairing effects may limit its utility”.
The Institute of Medicine, run by the United States National Academy of Sciences, conducted a comprehensive study in 1999 to assess the potential health benefits of cannabis and its constituent cannabinoids. The study concluded that smoking cannabis is not recommended for the treatment of any disease condition, but did conclude that nausea, appetite loss, pain and anxiety can all be mitigated by marijuana. While the study expressed reservations about smoked cannabis due to the health risks associated with smoking, the study team concluded that until another mode of ingestion was perfected that could provide the same relief as smoked cannabis, there was no alternative. In addition, the study pointed out the inherent difficulty in marketing a non-patentable herb. Pharmaceutical companies will not substantially profit unless there is a patent. For those reasons, the Institute of Medicine concluded that there is little future in smoked cannabis as a medically approved medication. The report also concluded that for certain patients, such as the terminally ill or those with debilitating symptoms, the long-term risks are not of great concern.
Marinol was less effective than the steroid megestrol in helping cancer patients regain lost appetites. A phase III study found no difference in effects of an oral cannabis extract or THC on appetite and quality of life (QOL) in patients with cancer-related anorexia-cachexia syndrome (CACS) to placebo. “Citing the dangers of cannabis and the lack of clinical research supporting its medicinal value” the American Society of Addiction Medicine in March 2011 issued a white paper recommending a halt to using marijuana as a medicine in U.S. states where it has been declared legal.
Mental disorders
A study of 50,000 Swedish soldiers who had smoked at least once were twice as likely to develop schizophrenia as those who had not smoked. The study concluded that either smoking caused a higher rate of schizophrenia, or that those with schizophrenia were more likely to be drawn to cannabis.
A study by Keele University commissioned by the British government found that between 1996 and 2005 there had been significant reductions in the incidence and prevalence of schizophrenia. From 2000 onwards there were also significant reductions in the prevalence of psychoses.
The authors say this data is “not consistent with the hypothesis that increasing cannabis use in earlier decades is associated with increasing schizophrenia or psychoses from the mid-1990s onwards”.
A 10 year study on 1923 individuals from the general population in Germany, aged 14–24, concluded that cannabis use is a risk factor for the development of incident psychotic symptoms. Continued cannabis use might increase the risk for psychotic disorder.
Lung cancer and chronic obstructive pulmonary disease
The evidence to date is conflicting as to whether smoking cannabis increases the risk of developing lung cancer or chronic obstructive pulmonary disease (COPD) among people who do not smoke tobacco. In 2006 a study by Hashibe, Morgenstern, Cui, Tashkin, et al. suggested that smoking cannabis does not, by itself, increase the risk of lung cancer. Many studies did report a strongly synergistic effect, however, between tobacco use and smoking cannabis such that tobacco smokers who also smoked cannabis dramatically increased their already very high risk of developing lung cancer or chronic obstructive pulmonary disease by as much as 300%. Some of these research results follow below:
In 2006, Hashibe, Morgenstern, Cui, Tashkin, et al. presented the results from a study involving 2,240 subjects that showed non-tobacco users who smoked marijuana did not exhibit an increased incidence of lung cancer or head-and-neck malignancies. These results were supported even among very long-term, very heavy users of marijuana.Tashkin, a pulmonologist who has studied cannabis for 30 years, commenting in news reports in the lay media on the results of the study he co-authored, suggested, “It’s possible that tetrahydrocannabinol (THC) in cannabis smoke may encourage apoptosis, or programmed cell death, causing cells to die off before they have a chance to undergo malignant transformation”. He summarized the results found by his study, saying “We hypothesized that there would be a positive association between cannabis use and lung cancer, and that the association would be more positive with heavier use. What we found instead was no association at all, and even a suggestion of some protective effect.”
A case-control study of lung cancer in adults 55 years of age and younger found that the risk of lung cancer increased 8% (95% confidence interval (CI) 2–15) for each joint-year of cannabis smoking, after adjustment for confounding variables including cigarette smoking, and 7% (95% CI 5–9) for each pack-year of cigarette smoking, after adjustment for confounding variables including cannabis smoking.
A 2008 study by Hii, Tam, Thompson, and Naughton found that cannabis smoking leads to asymmetrical bullous disease, often in the setting of normal CXR and lung function. In subjects who smoke cannabis, these pathological changes occur at a younger age (approximately 20 years earlier) than in tobacco smokers.
Researchers from the University of British Columbia presented a study at the American Thoracic Society 2007 International Conference showing that smoking cannabis and tobacco together more than tripled the risk of developing COPD over just smoking tobacco alone.[unreliable medical source? Similar findings were released in April 2009 by the Vancouver Burden of Obstructive Lung Disease Research Group. The study reported that smoking both tobacco and cannabis synergistically increased the risk of respiratory symptoms and COPD. Smoking only cannabis, however, was not associated with an increased risk of respiratory symptoms of COPD. In a related commentary, pulmonary researcher Donald Tashkin wrote, “…we can be close to concluding that cannabis smoking by itself does not lead to COPD”.
Harm reduction
Aspergillus fumigatus
The harm caused by smoking can be minimized or eliminated by the use of a vaporizer or ingesting the drug in an edible form. Vaporizers are devices that heat the active constituents to a temperature below the ignition point of the cannabis, so that their vapors can be inhaled. Combustion of plant material is avoided, thus preventing the formation of carcinogens such as polyaromatic hydrocarbons, benzene and carbon monoxide. A pilot study led by Donald Abrams of UC San Francisco showed that vaporizers eliminate the release of irritants and toxic compounds, while delivering equivalent amounts of THC into the bloodstream. According to Matthew Seamon and his co-authors “Vaporizers are the optimal route of administration because they allow for rapid and complete absorption with minimal combustible byproducts, often considered the major health risk associated with smoking tobacco.”
In order to kill microorganisms, especially the molds A. fumigatus, A. flavus and A. niger, Levitz and Diamond suggested baking marijuana at 150 °C (302 °F) for five minutes. They also found that tetrahydrocannabinol (THC) was not degraded by this process.
When We Need A Cure The Most
