Medical cannabis

Medical cannabis refers to the use of parts of the herb cannabis (also referred to as medical marijuana) 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 from which the cannabis drug is derived has a long history of medicinal use, with evidence dating back to 2,737 BCE.^[1] Synthetic cannabinoids, such as Marinol and Cesamet, are available as prescription drugs in some countries. A number of studies, some disputed, claim that medical cannabis relieves symptoms and is helpful in the treatment of many diseases.

Contents 1 Use 2 Clinical applications 3 Recent studies 3.1 Safety of cannabis 3.2 Glaucoma 3.3 Spasticity in multiple sclerosis 3.4 Alzheimer's disease 3.5 Mental disorders 3.6 Lung cancer and chronic obstructive pulmonary disease 3.7 Breast cancer 3.8 HIV/AIDS 3.9 Brain cancer 3.10 Opioid dependence 3.11 Controlling ALS symptoms 3.12 Treatment of inflammatory skin disease 4 Medicinal compounds 4.1 Tetrahydrocannabinol 4.2 Cannabidiol 4.3 Cannabinol 4.4 β-Caryophyllene 4.5 Cannabigerol 5 Pharmacologic THC and THC derivatives 6 Criticism 7 Harm reduction 8 Organizational positions 9 History 9.1 Ancient China and Taiwan 9.2 Ancient Egypt 9.3 Ancient India 9.4 Ancient Greece 9.5 South East Asia 9.6 Medieval Islamic world 10 Modern history 11 National and international regulations 11.1 Africa 11.2 Austria 11.3 Canada 11.4 Germany 11.5 Spain 11.6 United Kingdom 11.7 United States 12 See also 13 References 14 Further reading 15 External links

Use

The medicinal value of cannabis is controversial. A large majority of national governments do not recognize the use of plant parts from the plant Cannabis Sativa as something that doctors can recommend to their patients. A number of these governments, including the U.S. Federal Government, allow treatment with one or more specific synthetic cannabinoids for one or more disorders.

Supporters of medical cannabis argue that cannabis does have several well-documented beneficial effects.^[2][3][4][5] 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 efficacy of these methods was the subject of an investigative study^[5] 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, including Canada, Austria, Germany, 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

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".^[6]

Preliminary findings indicate that cannabis-based drugs could prove useful in treating inflammatory bowel disease, migraines, fibromyalgia, and related conditions.^[7]

Medical cannabis has also been found to relieve certain symptoms of multiple sclerosis^[8] and spinal cord injuries^[9][10][11] 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,^[12] amyotrophic lateral sclerosis,^[13][14] collagen-induced arthritis,^[15] asthma,^[16] atherosclerosis,^[17] bipolar disorder,^[18][19] colorectal cancer,^[20] HIV-Associated Sensory Neuropathy^[21] depression,^{[22][23][24][25]} dystonia,^[26] epilepsy,^[27][28][29] digestive diseases,^[30] gliomas,^[31][32] hepatitis C,^[33] Huntington's disease,^[34] leukemia,^[35] skin tumors,^[36] methicillin-resistant Staphylococcus aureus (MRSA),^[37] Parkinson's disease,^[38] pruritus,^[39][40] posttraumatic stress disorder (PTSD),^[41] psoriasis,^[42] sickle-cell disease,^[43] sleep apnea,^[44] and anorexia nervosa.^[45] 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;^[46][47] other studies have shown that cannabis "has no effects on tics and increases the individuals inner tension".^[48] Case reports found that marijuana helped reduce tics, but validation of these results requires longer, controlled studies on larger samples.^[49][50]

A study done by Craig Reinarman surveyed among why people in California used medical marijuana and it found many reasons why people had used medical marijuana. It was used to relieve pain, muscle spasms, headaches, anxiety, nausea, vomiting, depression, cramps, panic attacks, diarrhea, and itching. Others used medical marijuana 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. ^[51]

Recent studies

Safety of cannabis

According to an approved statement from the US Department of Justice in 1988, "Nearly all medicines have toxic, potentially lethal effects. But marijuana is not such a substance. There is no record in the extensive medical literature describing a proven, documented cannabis-induced fatality. In practical terms, marijuana cannot induce a lethal response as a result of drug-related toxicity."^[52]

From January 1997 to June 2005, the U.S. Food and Drug Administration (FDA) reported zero deaths caused by the primary use of marijuana. Through that time period, 279 deaths were reported where marijuana was a possible "concomitant" drug used in conjunction with other drugs at the time of death. In contrast, common FDA-approved drugs which are often prescribed in lieu of marijuana (such as anti-emetics and anti-psychotics), were the primary cause of 10,008 deaths.^[53]

Glaucoma

In glaucoma, marijuana 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 marijuana 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.^[54]

In a separate study, the use of marijuana and glaucoma was tested and found that the duration of smoked or ingested marijuana or other cannabinoids is very short, averaging 3 to 3.5 hours. Their results showed that for marijuana 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. ^[55]

Spasticity in multiple sclerosis

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."^[56] A small study done on whether or not marijuana 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.^[57][58]

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.^[59] Cannabinoids can also potentially prevent or slow the progression of Alzheimer's disease by reducing tau protein phosphorylation, oxidative stress, and neuroinflammation.^[60]

Mental disorders

There has been evidence that smoking marijuana can have a positive effect on disorders such as Schizophrenia, bipolar disorder, or depression. In patients with bipolar disorder subjects have been shown to actually become better after smoking marijuana increasing the rate at which these patients go from high to low. In the case of depression many users have reported that their moods have become better. Research done on lab rats and animals has shown that marijuana can act as an anti-depressant but in other studies done on humans this is not the case, actually pushing the subjects further into their depression. 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 schizophrenics were more likely to be drawn to marijuana.^[61]

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".^[62]

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.^[63]

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. Several subsequent studies have found results suggesting the reverse, however many of these were not completed with proper scientific controls and have subsequently been discredited. 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.^[64]

Tashkin, a pulmonologist who has studied marijuana for 30 years, said, "It's possible that tetrahydrocannabinol (THC) in marijuana smoke may encourage apoptosis, or programmed cell death, causing cells to die off before they have a chance to undergo malignant transformation". He further commented that "We hypothesized that there would be a positive association between marijuana 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."^[65][66]

• 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.^[67]

• A 2008 study by Hii, Tam, Thompson, and Naughton found that marijuana smoking leads to asymmetrical bullous disease, often in the setting of normal CXR and lung function. In subjects who smoke marijuana, these pathological changes occur at a younger age (approximately 20 years earlier) than in tobacco smokers.^[68]

• Researchers from the University of British Columbia presented a study at the American Thoracic Society 2007 International Conference showing that smoking marijuana and tobacco together more than tripled the risk of developing COPD over just smoking tobacco alone.^[69] 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 marijuana synergistically increased the risk of respiratory symptoms and COPD. Smoking only marijuana, however, was not associated with an increased risk of respiratory symptoms of COPD.^[70][71] In a related commentary, pulmonary researcher Donald Tashkin wrote, "...we can be close to concluding that marijuana smoking by itself does not lead to COPD".^[72]

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.^[73] 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.^[73]

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 marijuana has a clear medical benefit in HIV-positive patients.^[74][75] 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.^[76] 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.^[77] 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.^[78]

Brain cancer

A study by Complutense University of Madrid found the chemicals in marijuana promotes 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.^[79] 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.^[79]

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.^[80] 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.^[80]

In humans, drug treatment subjects who use cannabis intermittently are found to be more likely to adhere to treatment for opioid dependence.^[81] Historically, similar findings were reported by Edward Birch, who, in 1889, reported success in treating opiate and chloral addiction with cannabis.^[82]

Controlling ALS symptoms

Recent research has been conducted on if the use of marijuana could control some of the symptoms of ALS or Lou Gehrig Disease. A survey was conducted on 131 people who suffered from ALS. The survey asked if the subjects had used marijuana 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 MS (Amtmann et al. 2004).^[57]

Treatment of inflammatory skin disease

The abundant distribution of cannabinoid receptors on skin nerve fibers and mast cells provides implications for an anti-inflammatory, anti-nociceptive action of cannabinoid receptor agonists and suggests their putatively broad therapeutic potential^[83]

Medicinal compounds

Cannabis contains over 300 compounds. At least 66 of these are cannabinoids,^[84][85] 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.^[86] Cannabinoids can serve as appetite stimulants, antiemetics, antispasmodics, and have some analgesic effects.^[87] Five important cannabinoids found in the cannabis plant are tetrahydrocannabinol, cannabidiol, cannabinol, β-caryophyllene, and cannabigerol.

Tetrahydrocannabinol

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.^[88] THC is believed to interact with parts of the brain normally controlled by the endogenous cannabinoid neurotransmitter, anandamide.^[89][90] Anandamide is believed to play a role in pain sensation, memory, and sleep.

Cannabidiol

Cannabidiol (CBD), is a major constituent of medical cannabis. CBD represents up to 40% of extracts of the medical cannabis plant.^[91] Cannabidiol has been shown to relieve convulsion, inflammation, anxiety, cough and congestion, nausea, and inhibits cancer cell growth.^[92] Recent studies have shown cannabidiol to be as effective as atypical antipsychotics in treating schizophrenia.^[93] 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.^[56][92][94]

Cannabinol

Cannabinol (CBN) is a therapeutic cannabinoid found in Cannabis sativa and Cannabis indica.^[95] It is also produced as a metabolite, or a breakdown product, of tetrahydrocannabinol (THC).^[96] CBN acts as a weak agonist of the CB₁ and CB₂ receptors, with lower affinity in comparison to THC.^[97][98]

β-Caryophyllene

Part of the mechanism by which medical cannabis has been shown to reduce tissue inflammation is via the compound β-caryophyllene.^[99] A cannabinoid receptor called CB2 plays a vital part in reducing inflammation in humans and other animals.^[99] β-Caryophyllene has been shown to be a selective activator of the CB2 receptor.^[99] β-Caryophyllene is especially concentrated in cannabis essential oil, which contains about 12–35% β-caryophyllene.^[99]

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.^[100][101]

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 optomologist, Dr. Albert Lockhart and Dr. Manley E. West, and began distribution in 1987.^[102][103] As of 2003, it was still being distributed in the United Kingdom, several US states, and several Caribbean nations.^[104]

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.^[103][105]

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.^[106][107] 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.^{[108][109][110]} 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."^[111]

Medication	Approval	Country	Licensed indications	Cost
Nabilone	1985	USA, Canada	Nausea of cancer chemotherapy that has failed to respond adequately to other antiemetics	$4000.00 U.S. for a year's supply (in Canada)[112]
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	$652 U.S. for 30 doses @ 10 mg online[113]
	1992	USA	Anorexia associated with AIDS–related weight loss[114]
Sativex	1995	Canada	Adjunctive treatment for the symptomatic relief of neuropathic pain in multiple sclerosis in adults	$9,351 Canadian per year[115]
	1997	Canada	Pain due to cancer

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 marijuana patients can use vaporizers, where the essential marijuana compounds are extracted and inhaled. This is somewhat similar to steaming vegetables to avoid cancerous by-products that are produced at higher temperatures. In addition, edible marijuana, 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 marijuana 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. Furthermore, there is currently sound evidence that smoked marijuana is harmful."^[116] The National Institute on Drug Abuse NIDA state that "Marijuana itself is an unlikely medication candidate for several reasons: (1) it is an unpurified plant containing numerous chemicals with unknown health effects; (2) it is typically consumed by smoking further contributing to potential adverse effects; and (3) its cognitive impairing effects may limit its utility".^[117]

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 marijuana 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 marijuana, 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.^[118][119]

Marinol was less effective than the steroid megestrol in helping cancer patients regain lost appetites.^[120] 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.^[121]

"Citing the dangers of marijuana 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.^[122][123]

Harm reduction

The harm caused by smoking can be minimized or eliminated by the use of a vaporizer^[124] 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.^[125]

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.^[126]

Organizational positions

A number of medical organizations have endorsed reclassification of marijuana to allow for further study. These include, but are not limited to:

• The American Medical Association^{[58][127][128]}
• The American College of Physicians – America's second largest physicians group^[129]
• Leukemia & Lymphoma Society – America's second largest cancer charity^[130]
• American Academy of Family Physicians opposes the use of marijuana except under medical supervision^[131]

Other medical organizations recommend a halt to using marijuana as a medicine in U.S.

• The American Society of Addiction Medicine^[122][123]

History

Ancient China and Taiwan

Cannabis, called má 麻 (meaning "hemp; cannabis; numbness") or dàmá 大麻 (with "big; great") in Chinese, was used in Taiwan for fiber starting about 10,000 years ago.^[132] The botanist Li Hui-Lin wrote that in China, "The use of Cannabis in medicine was probably a very early development. Since ancient men used hemp seed as food, it was quite natural for them to also discover the medicinal properties of the plant."^[133] The oldest Chinese pharmacopeia, the (ca. 100 CE) Shennong Bencaojing 神農本草經 ("Shennong's Materia Medica Classic"), describes dama "cannabis".

The flowers when they burst (when the pollen is scattered) are called 麻蕡 [mafen] or 麻勃 [mabo]. The best time for gathering is the 7th day of the 7th month. The seeds are gathered in the 9th month. The seeds which have entered the soil are injurious to man. It grows in [Taishan] (in [Shandong] ...). The flowers, the fruit (seed) and the leaves are officinal. The leaves and the fruit are said to be poisonous, but not the flowers and the kernels of the seeds.^[134]

In the early 3rd century CE, Hua Tuo was the first person known to use cannabis as an anesthetic. He reduced the plant to powder and mixed it with wine for administration.^[135] Elizabeth Wayland Barber says the Chinese evidence "proves a knowledge of the narcotic properties of Cannabis at least from the 1st millennium B.C." when ma was already used in a secondary meaning of "numbness; senseless." "Such a strong drug, however, suggests that the Chinese pharmacists had now obtained from far to the southwest not THC-bearing Cannabis sativa but Cannabis indica, so strong it knocks you out cold.^[136]

Cannabis is one of the 50 "fundamental" herbs in traditional Chinese medicine,^[137] and is prescribed to treat diverse indications.

Every part of the hemp plant is used in medicine; the dried flowers (勃), the achenia (蕡), the seeds (麻仁), the oil (麻油), the leaves, the stalk, the root, and the juice. The flowers are recommended in the 120 different forms of (風 feng) disease, in menstrual disorders, and in wounds. The achenia, which are considered to be poisonous, stimulate the nervous system, and if used in excess, will produce hallucinations and staggering gait. They are prescribed in nervous disorders, especially those marked by local anaesthesia. The seeds, by which is meant the white kernels of the achenia, are used for a great variety of affections, and are considered to be tonic, demulcent, alterative, laxative, emmenagogue, diuretic, anthelmintic, and corrective. They are made into a congee by boiling with water, mixed with wine by a particular process, made into pills, and beaten into a paste. A very common mode of exhibition, however, is by simply eating the kernels. It is said that their continued use renders the flesh firm and prevents old age. They are prescribed internally in fluxes, post-partum difficulties, aconite poisoning, vermillion poisoning, constipation, and obstinate vomiting. Externally they are used for eruptions, ulcers, favus, wounds, and falling of the hair. The oil is used for falling hair, sulfur poisoning, and dryness of the throat. The leaves are considered to be poisonous, and the freshly expressed juice is used as an anthelmintic, in scorpion stings, to stop the hair from falling out and to prevent it from turning grey. They are especially thought to have antiperiodic properties. The stalk, or its bark, is considered to be diuretic, and is used with other drugs in gravel. The juice of the root is used for similar purposes, and is also thought to have a beneficial action in retained placenta and post-partum hemorrhage. An infusion of hemp (for the preparation of which no directions are given) is used as a demulcent drink for quenching thirst and relieving fluxes.^[138]

“Medical use of cannabis included, rheumatism, intestinal constipation, female reproductive system disorders, malaria, and other uses” (Zuardi, 2006, 4).

Ancient Egypt

The Ebers Papyrus (ca. 1,550 BCE) from Ancient Egypt describes medical marijuana.^[139] Other ancient Egyptian papyri that mention medical marijuana are the Ramesseum III Papyrus (1700 BC), the Berlin Papyrus (1300 BC) and the Chester Beatty Medical Papyrus VI (1300 BC).^[140] The ancient Egyptians even used hemp (cannabis) in suppositories for relieving the pain of hemorrhoids.^[141] Around 2,000 B.C., the ancient Egyptians used cannabis to treat sore eyes. ^[142] The egyptologist Lise Manniche notes the reference to "plant medical marijuana" in several Egyptian texts, one of which dates back to the eighteenth century BCE^[143]

Ancient India

Surviving texts from ancient India confirm that cannabis' psychoactive properties were recognized, and doctors used it for a variety of illnesses and ailments. These included insomnia, headaches, a whole host of gastrointestinal disorders, and pain: cannabis was frequently used to relieve the pain of childbirth.^[144]

In India, the use of cannabis was widely disseminated, both as a medicine and as a recreational drug. Such a broad use may be due to the fact that cannabis maintained a straight association with religion, which assigned sacred virtues to the plant” (Zuardi, 2006, 3).

Ancient Greece

The Ancient Greeks used cannabis not only for human medicine, but also in veterinary medicine to dress wounds and sores on their horses.^[145]

In humans, dried leaves of cannabis were used to treat nose bleeds, and cannabis seeds were used to expel tapeworms.^[145] The most frequently described use of cannabis in humans was to steep green seeds of cannabis in either water or wine, later taking the seeds out and using the warm extract to treat inflammation and pain resulting from obstruction of the ear.^[145]

In the 5th century BCE Herodotus, a Greek historian, described how the Scythians of the Middle East used cannabis in steam baths.^[145]

South East Asia

Patani from Asia are primary natural producers of the diuretic, antiemetic, antiepileptic, anti-inflammatory, pain killing and antipyretic properties of Cannabis sativa, and used it extensively for 'Kopi Kapuganja' and 'Pecel Ganja', as recreation food, drinks and relaxing medication for centuries.

Medieval Islamic world

In the medieval Islamic world, Arabic physicians made use of the diuretic, antiemetic, antiepileptic, anti-inflammatory, pain killing and antipyretic properties of Cannabis sativa, and used it extensively as medication from the 8th to 18th centuries.^[146]

Modern history

An Irish physician, William Brooke O'Shaughnessy, is credited with introducing the therapeutic use of cannabis to Western medicine. He was Assistant-Surgeon and Professor of Chemistry at the Medical College of Calcutta, and conducted a cannabis experiment in the 1830s, first testing his preparations on animals, then administering them to patients in order to help treat muscle spasms, stomach cramps or general pain.^[147]

Cannabis as a medicine became common throughout much of the Western world by the 19th century. It was used as the primary pain reliever until the invention of aspirin.^[148] Modern medical and scientific inquiry began with doctors like O'Shaughnessy and Moreau de Tours, who used it to treat melancholia and migraines, and as a sleeping aid, analgesic and anticonvulsant. At the local level authorities introduced various laws that required the mixtures that contained cannabis, that was not sold on prescription, must be marked with warning labels under the so-called poison laws.^[149]

A Swedish lexicon printed in 1912 describes cannabis drug and cannabis extract as a now with us deserted method for medical treatment.^[150]

Later in the century, researchers investigating methods of detecting cannabis intoxication discovered that smoking the drug reduced intraocular pressure.^[151] In 1955 the antibacterial effects were described at the Palacký University of Olomouc. Since 1971 Lumír Ondřej Hanuš was growing marijuana for his scientific research on two large fields in authority of the University. The marijuana extracts were then used at the University hospital as a cure for aphthae and haze.^[152] In 1973 physician Tod H. Mikuriya reignited the debate concerning cannabis as medicine when he published "Marijuana Medical Papers". High intraocular pressure causes blindness in glaucoma patients, so he hypothesized that using the drug could prevent blindness in patients. Many Vietnam War veterans also found that the drug prevented muscle spasms caused by spinal injuries suffered in battle.^[153] Later medical use focused primarily on its role in preventing the wasting syndromes and chronic loss of appetite associated with chemotherapy and AIDS, along with a variety of rare muscular and skeletal disorders.

In 1964, Dr. Albert Lockhart and Manley West began studying the health effects of traditional marijuana use in Jamaican communities. They discovered that Rastafarians had unusually low glaucoma rates and local fishermen were washing their eyes with cannibis extract in the belief that it would improve their sight. Lockhart and West developed, and in 1987 gained permission to market, the pharmaceutical Canasol: one of the first to cannabis extracts. They continued to work with cannabis throughout the years, developing more pharmaceuticals and eventually receiving the Jamaican Order of Merit for their work.^[103]

Later, in the 1970s, a synthetic version of THC was produced and approved for use in the United States as the drug Marinol. It was delivered as a capsule, to be swallowed. Patients complained that the violent nausea associated with chemotherapy made swallowing capsules difficult. Further, along with ingested cannabis, capsules are harder to dose-titrate accurately than smoked cannabis because their onset of action is so much slower. Smoking has remained the route of choice for many patients because its onset of action provides almost immediate relief from symptoms and because that fast onset greatly simplifies titration. For these reasons, and because of the difficulties arising from the way cannabinoids are metabolized after being ingested, oral dosing is probably the least satisfactory route for cannabis administration.^[154] Relatedly, some studies have indicated that at least some of the beneficial effects that cannabis can provide may derive from synergy among the multiplicity of cannabinoids and other chemicals present in the dried plant material.^[155] Such synergy is, by definition, impossible with respect to the use of single-cannabinoid drugs like Marinol.

During the 1970s and 1980s, six U.S. states' health departments performed studies on the use of medical cannabis. These are widely considered some of the most useful and pioneering studies on the subject. Voters in eight states showed their support for cannabis prescriptions or recommendations given by physicians between 1996 and 1999, including Alaska, Arizona, California, Colorado, Maine, Michigan, Nevada, Oregon, and Washington, going against policies of the federal government.^[156]

In May 2001, "The Chronic Cannabis Use in the Compassionate Investigational New Drug Program: An Examination of Benefits and Adverse Effects of Legal Clinical Cannabis" (Russo, Mathre, Byrne et al.) was completed. This three-day examination of major body functions of four of the five living US federal cannabis patients found "mild pulmonary changes" in two patients.^[157]

On October 7, 2003, a U.S. patent US 6630507  entitled "Cannabinoids as Antioxidants and Neuroprotectants" was awarded to the United States Department of Health and Human Services, based on research done at the National Institute of Mental Health (NIMH), and the National Institute of Neurological Disorders and Stroke (NINDS). This patent claims that cannabinoids are "useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases. The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and HIV dementia."^[158][159]

National and international regulations

Cannabis is in Schedule IV of the United Nations´ Single Convention on Narcotic Drugs, making it subject to special restrictions. Article 2 provides for the following, in reference to Schedule IV drugs:^[160]

A Party shall, if in its opinion the prevailing conditions in its country render it the most appropriate means of protecting the public health and welfare, prohibit the production, manufacture, export and import of, trade in, possession or use of any such drug except for amounts which may be necessary for medical and scientific research only, including clinical trials therewith to be conducted under or subject to the direct supervision and control of the Party.

The convention thus allows countries to outlaw cannabis for all non-research purposes but lets nations choose to allow medical and scientific purposes if they believe total prohibition is not the most appropriate means of protecting health and welfare. The convention requires that states that permit the production or use of medical cannabis must operate a licensing system for all cultivators,manufacturers and distributors and ensure that the total cannabis market of the state shall not exceed that required "for medical and scientific purposes."^[160]

Africa

Cannabis has been used in Africa since the 15th century. Its use was introduced by Arab traders, somehow connected to India. “In Africa, the plant was used for snake bite, to facilitate childbirth, malaria, fever, blood poisoning, anthrax, asthma, and dysentery.” (Zuardi, 2006, 4) Though African government has tried to limit and stop its use, it still seems to be deeply ingrained, mostly through religious rituals.

Austria

In Austria both Δ⁹-THC and pharmaceutical preparations containing Δ⁹-THC are listed in annex V of the Narcotics Decree (Suchtgiftverordnung).^[161] Compendial formulations are manufactured upon prescription according to the German Neues Rezeptur-Formularium.^[162][163]

On July 9, 2008, the Austrian Parliament approved cannabis cultivation for scientific and medical uses.^[164] Cannabis cultivation is controlled by the Austrian Agency for Health and Food Safety (Österreichische Agentur für Gesundheit und Ernährungssicherheit, AGES).^[165]

Canada

In Canada, the regulation on access to marijuana for medical purposes, established by Health Canada in July 2001, defines two categories of patients eligible for access to medical cannabis. Category 1 covers any symptoms treated within the context of providing compassionate end-of-life care or the symptoms associated with medical conditions listed below:

• severe pain and/or persistent muscle spasms from multiple sclerosis, from a spinal cord injury, from spinal cord disease,
• severe pain, cachexia, anorexia, weight loss, and/or severe nausea from cancer or HIV/AIDS infection,
• severe pain from severe forms of arthritis, or
• seizures from epilepsy.

Category 2 is for applicants who have debilitating symptom(s) of medical condition(s), other than those described in Category 1. The application of eligible patients must be supported by a medical practitioner.^[166]

The cannabis distributed by Health Canada is provided under the brand CannaMed by the company Prairie Plant Systems Inc. In 2006, 420 kg of CannaMed cannabis was sold, representing an increase of 80% over the previous year.^[167] However, patients complain of the single strain selection as well as low potency, providing a pre-ground product put through a wood chipper (which deteriorates rapidly) as well as gamma irradation and foul taste and smell.^[168]

It is also legal for patients approved by Health Canada to grow their own cannabis for personal consumption, and it's possible to obtain a production license as a person designated by a patient. Designated producers were permitted to grow a cannabis supply for only a single patient, however. That regulation and related restrictions on supply were found unconstitutional by the Federal Court of Canada in January, 2008. The court found that these regulations did not allow a sufficient legal supply of medical cannabis, and thus forced many patients to purchase their medicine from unauthorized, black market sources. This was the eighth time in the previous ten years that the courts ruled against Health Canada's regulations restricting the supply of the medicine.^[169]

In May, 2009, Health Canada revised their earlier regulations to permit licensed, designated producers to grow cannabis for a maximum of two patients. The move was called a "mockery" of the court's intention by lawyer Ron Marzel, who represented plaintiffs in the successful challenge in Federal Court to Health Canada's previously existing rules. Marzel has announced plans to ask the court to overturn all prohibitions on cannabis use if Health Canada refuses to create regulations that will allow an adequate legal supply for use by medically-authorized patients.^[169]

In Canada there are four forms of medical marijuana. The first one is a cannabis extract called Sativex that contains THC and cannabidiol in a spray form. The second is a synthetic or manmade THC called dronabinol marketed as Marinol. The third also a synthetic version of THC called nabilone that is called Cesamet on the markets. The fourth product is the herbal form of cannabis often referred to as marijuana.^[170]

Germany

In Germany dronabinol was rescheduled 1994 from annex I to annex II of the Narcotics Law (Betäubungsmittelgesetz) in order to ease research; in 1998 dronabinol was rescheduled from annex II to annex III and since then has been available by prescription,^[171] whereas Δ⁹-THC is still listed in annex I.^[172] Manufacturing instructions for dronabinol containing compendial formulations are described in the Neues Rezeptur-Formularium.^[163]

Spain

In Spain, since the late 1990s and early 2000s, medical cannabis underwent a process of progressive decriminalization and legalisation. The parliament of the region of Catalonia is the first in Spain have voted unanimously in 2001 legalizing medical marijuana, it is quickly followed by parliaments of Aragon and the Balearic Islands. The Spanish Penal Code prohibits the sale of cannabis but it does not prohibit consumption (although consumption on the street is fined). Until early 2000, the Penal Code did not distinguish between therapeutic use of cannabis and recreational use, however, several court decisions show that this distinction is increasingly taken into account by the judges. From 2006, the sale of seed is legalized, the sale and public consumption remains illegal, and private cultivation and use are permitted.^[173][174]

Several studies have been conducted to study the effects of cannabis on patients suffering from diseases like cancer, AIDS, multiple sclerosis, seizures or asthma. This research was conducted by various Spanish agencies at the Universidad Complutense de Madrid headed by Manuel Guzman, the hospital of La Laguna in Tenerife led neurosurgeon Luis González Feria or the University of Barcelona.

Several cannabis consumption clubs and user associations have been established throughout Spain. These clubs, the first of which was created in 1991, are non-profit associations who grow cannabis and sell it at cost to its members. The legal status of these clubs is uncertain: in 1997, four members of the first club, the Barcelona Ramón Santos Association of Cannabis Studies, were sentenced to 4 months in prison and a 3000 euro fine, while at about the same time, the court of Bilbao ruled that another club was not in violation of the law. The Andalusian regional government also commissioned a study by criminal law professors on the "Therapeutic use of cannabis and the creation of establishments of acquisition and consumption. The study concluded that such clubs are legal as long as they distribute only to a restricted list of legal adults, provide only the amount of drugs necessary for immediate consumption, and not earn a profit. The Andalusian government never formally accepted these guidelines and the legal situation of the clubs remains insecure. In 2006 and 2007, members of these clubs were acquitted in trial for possession and sale of cannabis and the police were ordered to return seized crops.^[174]

United Kingdom

In the United Kingdom, if you are arrested or taken to court for possession of cannabis, you are asked if there are any mitigating factors to explain why it is in your possession. It is unknown whether this is solely a formality, or if an excuse of medical usage has ever been used successfully to reduce the penalty issued. However, in the United Kingdom, possession of small quantities of cannabis does not usually warrant an arrest or court appearance (street cautions or fines are often given out instead). Under UK law, certain cannabinoids are permitted medically,^[175] but these are strictly controlled with many provisos under the Misuse of Drugs Act 1971 (in the 1985 amendments). The British Medical Associations official stance is "users of cannabis for medical purposes should be aware of the risks, should enroll for clinical trials, and should talk to their doctors about new alternative treatments; but we do not advise them to stop."^[175]

United States

In the United States federal level of government, cannabis per se has been made criminal by implementation of the Controlled Substances Act which classifies marijuana as a Schedule I drug, the strictest classification on par with heroin, LSD and Ecstasy, and the Supreme Court ruled in 2005 that the Commerce Clause of the U.S. Constitution allowed the government to ban the use of cannabis, including medical use. The United States Food and Drug Administration states "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".^[116][176]

Sixteen states have legalized medical marijuana: Alaska,^[177] Arizona,^[178] California,^[179] Colorado,^[180] Hawaii,^[181] Maine,^[182] Michigan,^[183] Montana,^[184] Nevada,^[185] New Jersey,^[186] New Mexico,^[187] Oregon,^[188] Rhode Island,^[189] Vermont,^[190] Virginia,^[191] Washington;^[192] and Washington D.C.^[193] Maryland allows for reduced or no penalties if cannabis use has a medical basis.^{[194][195][196]} Despite its legality in Washington, an employee can be still be fired if they test positive on a drug test, despite having a doctor's recommendation.^[197] California, Colorado, New Mexico, Maine, Rhode Island, Montana, and Michigan are currently the only states to utilize dispensaries to sell medical cannabis. California's medical marijuana industry took in about $2 billion a year and generated $100 million in state sales taxes during 2008^[198] with an estimated 2,100 dispensaries, co-operatives, wellness clinics and taxi delivery services in the sector colloquially known as “cannabusiness”.^[199]

On 19 October 2009 the US Deputy Attorney General issued a US Department of Justice memorandum to "All United States Attorneys" providing clarification and guidance to federal prosecutors in US States that have enacted laws authorizing the medical use of marijuana. The document is intended solely as "a guide to the exercise of investigative and prosecutorial discretion and as guidance on resource allocation and federal priorities." The US Deputy Attorney General David W. Ogden provided seven criteria, the application of which acts as a guideline to prosecutors and federal agents to ascertain whether a patients use, or their caregivers provision, of medical marijuana "represents part of a recommended treatment regiment consistent with applicable state law", and recommends against prosecuting patients using medical cannabis products according to state laws. Not applying those criteria, the Dep. Attorney General Ogden concludes, would likely be "an inefficient use of limited federal resources". The memorandum does not change any laws. Sale of cannabis remains illegal under federal law. The U.S. Food and Drug Administration's position, that marijuana has no accepted value in the treatment of any disease in the United States, has also remained the same.^[200]

The Health and Human Services Division of the federal government holds the patent US 6630507  for medical marijuana. The patent, "Cannabinoids as antioxidants and neuroprotectants", issued October 2003^[158] reads: "Cannabinoids have been found to have antioxidant properties, unrelated to NMDA receptor antagonism. This new found property makes cannabinoids useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases. The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and HIV dementia..."^[201]

See also

References

Further reading

External links

• Medical Cannabis, article by Dr Tato Grasso in www.theglobaldispatches.com.
• Medical cannabis at the Open Directory Project, links to websites about medical cannabis.
• The Center for Medicinal Cannabis Research of the University of California.
• Bibliography on the use of medical cannabis in recent history Advances in the History of Psychology, York University.
• The Forbidden Medicine, an independent site operated by Harvard Medical School faculty members James Bakalar and Lester Grinspoon.
• Cannabis Health Journal Online Medicinal Marijuana magazine based in British Columbia.

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