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Medical cannabis
This entry was posted on March 26, 2018.
Dried cannabis bud can be used for medical therapy.
Medical cannabis, or medical marijuana, is cannabis and cannabinoids that are recommended by doctors for their patients.[1][2] The use of cannabis as medicine has not been rigorously tested due to production restrictions and other governmental regulations.[3] Limited evidence suggests cannabis can: reduce nausea and vomiting during chemotherapy, improve appetite in people with HIV/AIDS, and reduce chronic pain and muscle spasms.[4][5][6]
Short-term use increases the risk of both minor and major adverse effects.[5] Common side effects include dizziness, feeling tired, vomiting, and hallucinations.[5] Long-term effects of cannabis are not clear.[5] Concerns include memory and cognition problems, risk of addiction, schizophrenia in young people, and the risk of children taking it by accident.[4]
The Cannabis plant has a history of medicinal use dating back thousands of years across many cultures.[7] The use of medical cannabis is controversial. A number of medical organizations have requested removal of cannabis from the list of Schedule I controlled substances, followed by regulatory and scientific review.[8][9] Others such as the American Academy of Pediatrics oppose the legalization of medical cannabis.[10]
Medical cannabis can be administered through a variety of methods, including capsules, lozenges, tinctures, dermal patches, oral or dermal sprays, cannabis edibles, and vaporizing or smoking dried buds. Synthetic cannabinoids, such as dronabinol and nabilone, are available for prescription use in some countries. Countries that allow the medical use of whole-plant cannabis include Canada, Chile, Colombia, Germany, Greece, Israel, Italy, the Netherlands, Poland, Peru, and Uruguay. Australia has passed legislation to allow the medical use of cannabis in some states. In the United States, 29 states and the District of Columbia have legalized cannabis for medical purposes, beginning with California in 1996. Although cannabis remains prohibited for any use at the federal level, the Rohrabacher–Farr amendment was enacted in December 2014, limiting the ability of federal law to be enforced in states where medical cannabis has been legalized.
Medical uses
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Cannabis as illustrated in Köhler's Book of Medicinal Plants, 1897
Medical cannabis has several potential beneficial effects.[5] Evidence is moderate that it helps in chronic pain and muscle spasms.[5] Low quality evidence suggests its use for reducing nausea during chemotherapy, improving appetite in HIV/AIDS, improving sleep, and improving tics in Tourette syndrome.[5] When usual treatments are ineffective, cannabinoids have also been recommended for anorexia, arthritis, migraine, and glaucoma.[14]
It is recommended that cannabis use be stopped in pregnancy.[15]
Nausea and vomiting
Medical cannabis is somewhat effective in chemotherapy-induced nausea and vomiting (CINV)[4][14] and may be a reasonable option in those who do not improve following preferential treatment.[16] Comparative studies have found cannabinoids to be more effective than some conventional antiemetics such as prochlorperazine, promethazine, and metoclopramide in controlling CINV,[17] but these are used less frequently because of side effects including dizziness, dysphoria, and hallucinations.[18][19] Long-term cannabis use may cause nausea and vomiting, a condition known as cannabinoid hyperemesis syndrome.[20]
A 2016 Cochrane review said that cannabinoids were "probably effective" in treating chemotherapy-induced nausea in children, but with a high side effect profile (mainly drowsiness, dizziness, altered moods, and increased appetite). Less common side effects were "occular problems, orthostatic hypotension, muscle twitching, pruritis, vagueness, hallucinations, lightheadedness and dry mouth".[21]
HIV/AIDS
Evidence is lacking for both efficacy and safety of cannabis and cannabinoids in treating patients with HIV/AIDS or for anorexia associated with AIDS. As of 2013, current studies suffer from effects of bias, small sample size, and lack of long-term data.[22]
Pain
A 2017 review found moderate to high quality evidence for effectiveness of cannabis in relieving chronic pain in several conditions, particularly when inhaled.[23] Another review found tentative evidence for use of cannabis in treating peripheral neuropathy, but little evidence of benefit for other types of long term pain.[24]
When cannabis is inhaled to relieve pain, blood levels of cannabinoids rise faster than when oral products are used, peaking within three minutes and attaining an analgesic effect in seven minutes.[23] A 2014 review found limited and weak evidence that smoked cannabis was effective for chronic non-cancer pain.[25] A 2015 meta-analysis found that inhaled medical cannabis was effective in reducing neuropathic pain in the short term for one in five to six patients.[26] Another 2015 review found limited evidence that medical cannabis was effective for neuropathic pain when combined with traditional analgesics.[27]
A 2011 review considered cannabis to be generally safe,[28] and in palliative care, its use appears safer than opioids.[29]
Neurological problems
The efficacy of cannabis in treating neurological problems, including multiple sclerosis (MS), epilepsy, and movement problems, is not clear.[30] Studies of the efficacy of cannabis for treating multiple sclerosis have produced varying results. The combination of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) extracts give subjective relief of spasticity, though objective post-treatment assessments do not reveal significant changes.[31] Evidence also suggests that oral cannabis extract is effective for reducing patient-centered measures of spasticity.[32] A trial of cannabis is deemed to be a reasonable option if other treatments have not been effective.[4][by whom?] Its use for MS is approved in ten countries.[4][33] A 2012 review found no problems with tolerance, abuse or addiction.[34]
Posttraumatic stress disorder
There is tentative evidence that medical cannabis is effective at reducing posttraumatic stress disorder symptoms, but, as of 2015[update], there is insufficient evidence to confirm its effectiveness for this condition.
Cannabidiol Supplements Benefits
Are you considering cannabidiol supplements because you’ve heard nothing but positive things about the CBD benefits that they provide? Have you heard from a friend or family member that they started taking CBD and have since then stopped suffering from a common ailment like stress, anxiety, pain or sleep insomnia? If so, you might be looking for some validation to the claims you have heard.
Adverse effects
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American medical hashish
Medical use
There is insufficient data to draw strong conclusions about the safety of medical cannabis.[36] Typically, adverse effects of medical cannabis use are not serious.[4] These include: tiredness, dizziness, cardiovascular, psychoactive effects, and increased appetite. Tolerance to these effects develops over a period of days or weeks. The amount of cannabis normally used for medicinal purposes is not believed to cause any permanent cognitive impairment in adults, though long-term treatment in adolescents should be weighed carefully as they are more susceptible to these impairments. Withdrawal symptoms are rarely a problem with controlled medical administration of cannabinoids. The ability to drive vehicles or to operate machinery may be impaired until a tolerance is developed.[16] Although supporters of medical cannabis say that it is safe,[36] further research is required to assess the long-term safety of its use.[18][37]
Dry Herb Vaporizers
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Recreational use
According to the United States Department of Health and Human Services, there were 455,000 emergency room visits associated with cannabis use in 2011. These statistics include visits in which the patient was treated for a condition induced by or related to recent cannabis use. The drug use must be "implicated" in the emergency department visit, but does not need to be the direct cause of the visit. Most of the illicit drug emergency room visits involved multiple drugs. In 129,000 cases, cannabis was the only implicated drug.
Effects of chronic use may include bronchitis, a cannabis dependence syndrome, and subtle impairments of attention and memory. These deficits persist while chronically intoxicated.[38] Compared to non-smokers, people who smoked cannabis regularly in adolescence exhibit reduced connectivity in specific brain regions associated with memory, learning, alertness, and executive function.[43] One study suggested that sustained heavy, daily, adolescent onset cannabis use over decades is associated with a decline in IQ by age 38, with no effects found in those who initiated cannabis use later, or in those who ceased use earlier in adulthood.
There has been a limited amount of studies that have looked at the effects of smoking cannabis on the respiratory system. Chronic heavy marijuana smoking is associated with coughing, production of sputum, wheezing, coughing, and other symptoms of chronic bronchitis. Regular cannabis use has not been shown to cause significant abnormalities in lung function.
Cannabis smoke contains thousands of organic and inorganic chemical compounds. This tar is chemically similar to that found in tobacco smoke,[47] and over fifty known carcinogens have been identified in cannabis smoke,[48] including; nitrosamines, reactive aldehydes, and polycylic hydrocarbons, including benz[a]pyrene.[49] Light and moderate use of cannabis is not believed to increase risk of lung or upper airway cancer. Evidence for causing these cancers is mixed concerning heavy, long-term use. In general there are far lower risks of pulmonary complications for regular cannabis smokers when compared with those of tobacco.[46] Combustion products are not present when using a vaporizer, consuming THC in pill form, or consuming cannabis edibles.
There is serious suspicion among cardiologists, spurring research but falling short of definitive proof, that cannabis use has the potential to contribute to cardiovascular disease.[50] Cannabis is believed to be an aggravating factor in rare cases of arteritis, a serious condition that in some cases leads to amputation. Because 97% of case-reports also smoked tobacco, a formal association with cannabis could not be made. If cannabis arteritis turns out to be a distinct clinical entity, it might be the consequence of vasoconstrictor activity observed from delta-8-THC and delta-9-THC.[51] Other serious cardiovascular events including myocardial infarction, stroke, sudden cardiac death, and cardiomyopathy have been reported to be temporally associated with cannabis use. Research in these events is complicated because cannabis is often used in conjunction with tobacco, and drugs such as alcohol and cocaine.[52] These putative effects can be taken in context of a wide range of cardiovascular phenomena regulated by the endocannabinoid system and an overall role of cannabis in causing decreased peripheral resistance and increased cardiac output, which potentially could pose a threat to those with cardiovascular disease.[53]
Cannabis usually causes no tolerance or withdrawal symptoms except in heavy users. In a survey of heavy users 42.4% experienced withdrawal symptoms when they tried to quit marijuana such as craving, irritability, boredom, anxiety and sleep disturbances.[54] About 9% of those who experiment with marijuana eventually become dependent. The rate goes up to one in six among those who begin use as adolescents, and one-quarter to one-half of those who use it daily according to a NIDA review.[43] A 2013 review estimates daily use is associated with a 10-20% rate of dependence.[4] The highest risk of cannabis dependence is found in those with a history of poor academic achievement, deviant behavior in childhood and adolescence, rebelliousness, poor parental relationships, or a parental history of drug and alcohol problems.[55]
A 2013 literature review found that exposure to marijuana had biologically-based physical, mental, behavioral and social health consequences and was "associated with diseases of the liver (particularly with co-existing hepatitis C), lungs, heart, and vasculature".[56]
Cognitive effects
A 2011 systematic review evaluated published studies of the acute and long-term cognitive effects of cannabis. THC intoxication is well established to impair cognitive functioning on an acute basis, including effects on the ability to plan, organize, solve problems, make decisions, and control impulses. The extent of this impact may be greater in novice users, and paradoxically, those habituated to high-level ingestion may have reduced cognition during withdrawal. Studies of long-term effects on cognition have provided conflicting results, with some studies finding no difference between long-term abstainers and never-users and others finding long-term deficits. The discrepancies between studies may reflect greater long-term effects among heavier users relative to occasional users, and greater duration of effect among those with heavy use as adolescents compared to later in life.[57] A second systematic review focused on neuroimaging studies found little evidence supporting an effect of cannabis use on brain structure and function.[58] A 2003 meta-analysis concluded that any long-term cognitive effects were relatively modest in magnitude and limited to certain aspects of learning and memory.[59]
Impact on psychosis
Exposure to THC can cause acute transient psychotic symptoms in healthy individuals and people with schizophrenia.[12]
A 2007 meta analysis concluded that cannabis use reduced the average age of onset of psychosis by 2.7 years relative to non-cannabis use.[60] A 2005 meta analysis concluded that adolescent use of cannabis increases the risk of psychosis, and that the risk is dose-related.[61] A 2004 literature review on the subject concluded that cannabis use is associated with a two-fold increase in the risk of psychosis, but that cannabis use is "neither necessary nor sufficient" to cause psychosis.[62] A French review from 2009 came to a conclusion that cannabis use, particularly that before age 15, was a factor in the development of schizophrenic disorders.[63]
Some studies have suggested that cannabis users have a greater risk of developing psychosis than non-users. This risk is most pronounced in cases with an existing risk of psychotic disorder.[64][65] A 2005 paper from the Dunedin study suggested an increased risk in the development of psychosis linked to polymorphisms in the COMT gene.[66] However, a more recent study cast doubt on the proposed connection between this gene and the effects of cannabis on the development of psychosis.[67]
A 2008 German review reported that cannabis was a causal factor in some cases of schizophrenia and stressed the need for better education among the public due to increasingly relaxed access to cannabis.[68]
Other potential long-term effects
A 2008 National Institutes of Health study of 19 chronic heavy marijuana users with cardiac and cerebral abnormalities (averaging 28 g to 272 g (1 to 9+ oz) weekly) and 24 controls found elevated levels of apolipoprotein C-III (apoC-III) in the chronic smokers.[69] An increase in apoC-III levels induces the development of hypertriglyceridemia.
Pharmacology
The genus Cannabis contains two species which produce useful amounts of psychoactive cannabinoids: Cannabis indica and Cannabis sativa, which are listed as Schedule I medicinal plants in the US;[4] a third species, Cannabis ruderalis, has few psychogenic properties.[4] Cannabis contains more than 460 compounds;[7] at least 80 of these are cannabinoids[70][71] – chemical compounds that interact with cannabinoid receptors in the brain.[4] As of 2012, more than 20 cannabinoids were being studied by the U.S. FDA.[72]
The most psychoactive cannabinoid found in the cannabis plant is tetrahydrocannabinol (or delta-9-tetrahydrocannabinol, commonly known as THC).[7] Other cannabinoids include delta-8-tetrahydrocannabinol, cannabidiol (CBD), cannabinol (CBN), cannabicyclol (CBL), cannabichromene (CBC) and cannabigerol (CBG); they have less psychotropic effects than THC, but may play a role in the overall effect of cannabis.[7] The most studied are THC, CBD and CBN.[56]
CB1 and CB2 are the primary cannabinoid receptors responsible for several of the effects of cannabinoids, although other receptors may play a role as well. Both belong to a group of receptors called G protein-coupled receptors (GPCRs). CB1 receptors are found in very high levels in the brain and are thought to be responsible for psychoactive effects.[73] CB2 receptors are found peripherally throughout the body and are thought to modulate pain and inflammation.[74]
Absorption
Cannabinoid absorption is dependent on its route of administration.
Smoking is by far the most common form of administration. Inhalation of the smoke quickly and efficiently delivers the drug from the lungs to the brain. Smoked THC has a bioavailability of approximately 25% and a rapid time to peak plasma levels of 6 to 10 minutes. Bioavailability varies between individuals depending on the number, duration and spacing of puffs, hold time, and inhalation volume.[75] Inhaled and vaporized THC have similar absorption profiles to smoked THC, with a bioavailability ranging from 10 to 35%. Oral administration has the lowest bioavailability of approximately 6%, variable absorption depending on the vehicle used, and the longest time to peak plasma levels (2 to 6 hours) compared to smoked or vaporized THC.[76]
Similar to THC, CBD has poor oral bioavailability, approximately 6%. The low bioavailability is largely attributed to significant first-pass metabolism in the liver and erratic absorption from the gastrointestinal tract. However, oral administration of CBD has a faster time to peak concentrations (2 hours) than THC.[76]
Due to the poor bioavailability of oral preparations, alternative routes of administration have been studied, including sublingual and rectal. These alternative formulations maximize bioavailability and reduce first-pass metabolism. Sublingual administration in rabbits yielded bioavailability of 16% and time to peak concentration of 4 hours.[77] Rectal administration in monkeys doubled bioavailability to 13.5% and achieved peak blood concentrations within 1 to 8 hours after administration.[75]
Distribution
Like cannabinoid absorption, distribution is also dependent on route of administration. Smoking and inhalation of vaporized cannabis have better absorption than do other routes of administration, and therefore also have more predictable distribution.[75][78] THC is highly protein bound once absorbed, with only 3% found unbound in the plasma. It distributes rapidly to highly vascularized organs such as the heart, lungs, liver, spleen, and kidneys, as well as to various glands. Low levels can be detected in the brain, testes, and unborn fetuses, all of which are protected from systemic circulation via barriers.[79] THC further distributes into fatty tissues a few days after administration due to its high lipophilicity, and is found deposited in the spleen and fat after redistribution.[78][80][81]
Metabolism
Metabolism of THC to 11-COOH-THC
Delta-9-THC is the primary molecule responsible for the effects of cannabis. Delta-9-THC is metabolized in the liver and turns into 11-OH-THC.[82] 11-OH-THC is the first metabolic product in this pathway. Both Delta-9-THC and 11-OH-THC are psychoactive. The metabolism of THC into 11-OH-THC plays a part in the heightened psychoactive effects of edible cannabis.[83]
Next, 11-OH-THC is metabolized in the liver into 11-COOH-THC, which is the second metabolic product of THC.[84] 11-COOH-THC is not psychoactive.[82]
Ingestion of edible cannabis products lead to a slower onset of effect than the inhalation of it because the THC travels to the liver first through the blood before it travels to the rest of the body. Inhaled cannabis can result in THC going directly to the brain, where it then travels from the brain back to the liver in recirculation for metabolism.[82] Eventually, both routes of metabolism result in the metabolism of psychoactive THC to inactive 11-COOH-THC.
Excretion
Due to the large propensity of THC and CBD being hepatically metabolized, a majority of their metabolites are excreted via feces than in the urine.[76]
After delta-9-THC is hydroxylated into 11-OH-THC via CYP2C9, CYP2C19, and CYP3A4, it undergoes phase II metabolism into more than 30 metabolites. A majority of these metabolites are products of glucuronidation. Approximately 65% is excreted in feces and 25% in the urine, while the remaining 10% is excreted by other means.[76] The terminal half-life is approximately 25–36 hours.[85]
CBD is hydroxylated by P450 liver enzymes into 7-OH-CBD. Its metabolites are products of primarily CYP2C19 and CYP3A4 activity, with potential activity of CYP1A1, CYP1A2, CYP2C9, and CYP2D6.[86] Similar to delta-9-THC, a majority of CBD is excreted in feces and some in the urine.[76] The terminal half-life is approximately 18–32 hours.[87]
Administration
Illustrating various forms of medicinal cannabis
Smoking is the means of administration of cannabis for many consumers,[88] and the most common method of medical cannabis consumption in the US as of 2013.[4] It is difficult to predict the pharmacological response to cannabis because concentration of cannabinoids varies widely as there are different ways of preparing cannabis for consumption (smoked, applied as oils, eaten, infused into other foods, or drunk) and a lack of production controls.[4] The potential for adverse effects from smoke inhalation makes smoking a less viable option than oral preparations.[88]
Cannabis vaporizers have gained popularity because of the perception among users that less harmful chemicals are ingested when components are inhaled via aerosol rather than smoke.[4]
Cannabinoid medicines are available in pill form (dronabinol and nabilone) and liquid extracts formulated into an oromucosal spray (nabiximols).[4] Oral preparations are "problematic due to the uptake of cannabinoids into fatty tissue, from which they are released slowly, and the significant first-pass liver metabolism, which breaks down Δ9THC and contributes further to the variability of plasma concentrations".[88]
The US Food and Drug Administration (FDA) has not approved smoked cannabis for any condition or disease as it deems evidence is lacking concerning safety and efficacy of cannabis for medical use.[89] The FDA issued a 2006 advisory against smoked medical cannabis stating: "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."[89]
History
Ancient
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.[90] The botanist Hui-lin Li wrote that in China, "The use of Cannabis in medicine was probably a very early development. Since ancient humans used hemp seed as food, it was quite natural for them to also discover the medicinal properties of the plant."[91] Emperor Shen-Nung, who was also a pharmacologist, wrote a book on treatment methods in 2737 BCE that included the medical benefits of cannabis. He recommended the substance for many ailments, including constipation, gout, rheumatism, and absent-mindedness.[92] Cannabis is one of the 50 "fundamental" herbs in traditional Chinese medicine.[93]
The Ebers Papyrus (c. 1550 BCE) from Ancient Egypt describes medical cannabis.[94] The ancient Egyptians used hemp (cannabis) in suppositories for relieving the pain of hemorrhoids.[95]
Surviving texts from ancient India confirm that cannabis' psychoactive properties were recognized, and doctors used it for treating a variety of illnesses and ailments, including insomnia, headaches, gastrointestinal disorders, and pain, including during childbirth.[96]
The Ancient Greeks used cannabis to dress wounds and sores on their horses,[97] and in humans, dried leaves of cannabis were used to treat nose bleeds, and cannabis seeds were used to expel tapeworms.[97]
In the medieval Islamic world, Arabic physicians made use of the diuretic, antiemetic, antiepileptic, anti-inflammatory, analgesic and antipyretic properties of Cannabis sativa, and used it extensively as medication from the 8th to 18th centuries.[98]
Modern
An Irish physician, William Brooke O'Shaughnessy, is credited with introducing cannabis to Western medicine.[99] O'Shaughnessy discovered cannabis in the 1830s while living abroad in India, where he conducted numerous experiments investigating its medical utility.[100] Noting in particular its analgesic and anticonvulsant effects, O'Shaughnessy returned to England with a supply of cannabis in 1842, after which its use spread through Europe and the United States.[101] Cannabis was entered into the United States Pharmacopeia in 1850.[100]
The use of cannabis in medicine began to decline by the end of the 19th century, due to difficulty in controlling dosages and the rise in popularity of synthetic and opium-derived drugs.[101] Also, the advent of the hypodermic syringe allowed these drugs to be injected for immediate effect, in contrast to cannabis which is not water-soluble and therefore cannot be injected.[101]
In the United States, the medical use of cannabis further declined with the passage of the Marihuana Tax Act of 1937, which imposed new regulations and fees on physicians prescribing cannabis.[102] Cannabis was removed from the U.S. Pharmacopeia in 1941, and officially banned for any use with the passage of the Controlled Substances Act of 1970.[101]
Cannabis began to attract renewed interest as medicine in the 1970s and 1980s, in particular due to its use by cancer and AIDS patients who reported relief from the effects of chemotherapy and wasting syndrome.[103] In 1996, California became the first U.S. state to legalize medical cannabis in defiance of federal law.[104] In 2001, Canada became the first country to adopt a system regulating the medical use of cannabis.[105]
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Cannabis indica fluid extract, American Druggists Syndicate, pre-1937.
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An advertisement for cannabis americana distributed by a pharmacist in New York in 1917
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The Ebers Papyrus (c. 1550 BCE) from Ancient Egypt has a prescription for medical marijuana applied directly for inflammation.
Society and culture
Legal status
Worldwide laws on cannabis possession for medical purposes as of 2017.
Legal or essentially legal
Decriminalized
Illegal but often unenforced
Illegal
No information
Countries that have legalized the medical use of cannabis include Canada,[106] Chile,[106] Colombia,[106] Croatia,[107] Cyprus,[108] Czech Republic,[106] Jamaica,[106] Finland,[109] Germany,[110] Greece,[111] Israel,[112] Italy,[113] Macedonia,[114] the Netherlands,[106] Poland,[115] Peru,[116] Romania,[117] and Uruguay[106] Other countries have more restrictive laws allowing for the use of specific cannabinoids only, such as France and the United Kingdom which have approved the use of Sativex.[118] Countries with more relaxed laws include Uruguay,[106] the Netherlands,[106] and Spain,[119] where cannabis can be obtained without need for a prescription. In Mexico, THC content of medical cannabis is limited to one percent.[120] The same limit applies in Switzerland, but no prescription is required to purchase.[121] In the United States[122] and Australia,[123] the legality of medical cannabis varies by state.
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:
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.[124]
The convention thus allows countries to outlaw cannabis for all non-research purposes but lets nations choose to allow use for 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."[124]
United States
As of April 2017, 29 states and the District of Columbia have legalized the medical use of cannabis, and another 17 have passed laws allowing the use of CBD products.[122] Cannabis remains illegal at the federal level by way of the Controlled Substances Act, under which cannabis is classified as a Schedule I drug with a high potential for abuse and no accepted medical use. In December 2014, however, the Rohrabacher–Farr amendment was signed into law, prohibiting the Justice Department from prosecuting individuals acting in accordance with state medical cannabis laws.[125]
Economics
Distribution
The method of obtaining medical cannabis varies by region and by legislation. In the US, most consumers grow their own or buy it from marijuana dispensaries in the 29 states and the District of Columbia that permit the use of medical cannabis.[4][126] Marijuana vending machines for selling or dispensing cannabis are in use in the United States and are planned to be used in Canada.[127] In 2014, the startup Meadow began offering on-demand delivery of medical marijuana in the San Francisco Bay Area, through their mobile app.[128]
Insurance
In the United States, health insurance companies may not pay for a medical marijuana prescription as the Food and Drug Administration must approve any substance for medicinal purposes. Before this can happen, the FDA must first permit the study of the medical benefits and drawbacks of the substance, which it has not done since it was placed on Schedule I of the Controlled Substances Act in 1970. Therefore, all expenses incurred fulfilling a medical marijuana prescription will possibly be incurred as out-of-pocket.[129] However, the New Mexico Court of Appeals has ruled that workers' compensation insurance must pay for prescribed marijuana as part of the state's Medical Cannabis Program.[130]
Positions of medical organizations
Medical organizations that have issued statements in support of allowing access to medical cannabis include the American Nurses Association,[8] American Public Health Association,[131] American Medical Student Association,[132] National Multiple Sclerosis Society,[133] Epilepsy Foundation,[134] and Leukemia & Lymphoma Society.[135]
Organizations that have issued statements in opposition to the legalization of medical cannabis include the American Academy of Pediatrics,[10] American Psychiatric Association,[136] and American Society of Addiction Medicine.[137] However, the AAP also supports rescheduling for the purpose of facilitating research.[10]
The American Medical Association[138] and American College of Physicians[139] do not take a position on the legalization of medical cannabis, but have called for the Schedule I classification of cannabis to be reviewed. The American Academy of Family Physicians similarly does not take a position, but does support rescheduling in order to facilitate research.[9] The American Cancer Society[140] and American Psychological Association[141] have noted the obstacles that exist for conducting research on cannabis, and have called on the federal government to better enable scientific study of the drug.
Recreational use
The authors of a report on a 2011 survey of medical cannabis users say that critics have suggested that some users "game the system" to obtain medical cannabis ostensibly for treatment of a condition, but then use it for nonmedical purposes – though the truth of this claim is hard to measure.[142] The report authors suggested rather that medical cannabis users occupied a "continuum" between medical and nonmedical use.[142]
Brand names
In the US, the FDA has approved two oral cannabinoids for use as medicine: dronabinol and nabilone.[4] Dronabinol, synthetic THC, is listed as Schedule II.[143] Nabilone, a synthetic cannabinoid, is also Schedule II, indicating high potential for side effects and addiction.[72] Both received approval for sale in the US in 1985, under the brand names Marinol and Cesamet.[144] Nabiximols, an oromucosal spray derived from two strains of Cannabis sativa and containing THC and CBD,[72] is not approved in the United States, but is approved in several European countries, Canada, and New Zealand as of 2013.[4] As of 2018, medical marijuana in Canada is being legally distributed to registered patients in bud, drops and capsule forms by such companies as Canopy Growth Corp. and Aurora Cannabis.
| Generic medication |
Brand name(s) |
Country | Licensed indications |
|---|---|---|---|
| Nabilone | Cesamet | U.S., Canada | Antiemetic (treatment of nausea or vomiting) associated with chemotherapy that has failed to respond adequately to conventional therapy[4] |
| Dronabinol | Marinol | ||
| Syndros | U.S. | Anorexia associated with AIDS–related weight loss[4] | |
| Nabiximols | Sativex | Canada, New Zealand, eight European countries as of 2013 |
Limited treatment for spasticity and neuropathic pain associated with multiple sclerosis and intractable cancer pain.[4] |
As an antiemetic, these medications are usually used when conventional treatment for nausea and vomiting associated with cancer chemotherapy fail to work.[4]
Nabiximols is used for treatment of spasticity associated with MS when other therapies have not worked, and when an initial trial demonstrates "meaningful improvement".[4] Trials for FDA approval in the US are underway.[4] It is also approved in several European countries for overactive bladder and vomiting.[72] When sold under the trade name Sativex as a mouth spray, the prescribed daily dose in Sweden delivers a maximum of 32.4 mg of THC and 30 mg of CBD; mild to moderate dizziness is common during the first few weeks.[145]
Relative to inhaled consumption, peak concentration of oral THC is delayed, and it may be difficult to determine optimal dosage because of variability in patient absorption.[4]
In 1964, Albert Lockhart and Manley West began studying the health effects of traditional cannabis use in Jamaican communities. They developed, and in 1987 gained permission to market, the pharmaceutical "Canasol", one of the first cannabis extracts.[146]
Research
"Victoria", the United States' first legal medical marijuana plant grown by The Wo/Men's Alliance for Medical Marijuana[citation needed]
A 2016 review assess the current status and prospects for development of CBD and CBD-dominant preparations for medical use in the United States, examining its neuroprotective, antiepileptic, anxiolytic, antipsychotic, and antiinflammatory properties.[147]
United States
Research on the medical benefits of cannabis has been hindered by various federal regulations, including its Schedule I classification.[148] To conduct research on cannabis, approval must be obtained from the Food and Drug Administration,[149] and a license must be obtained from the Drug Enforcement Administration specific to Schedule I drugs.[150] The FDA has 30 days to respond to proposals,[151] while the DEA licensing can take over a year to complete.[141] Prior to June 2015, cannabis research also required approval from the US Public Health Service.[152] The PHS review was not performed for any other Schedule I drugs, and had no deadline imposed.[151]
In addition to the FDA and DEA (and former PHS) requirements, the National Institute on Drug Abuse must review and approve all cannabis research.[153] The NIDA is the only source licensed by the federal government for the cultivation and provision of cannabis, and the NIDA will not provide cannabis without first approving the research.[149] This monopoly maintained by the DEA does not exist for other Schedule I drugs,[148] and there is no deadline established for the NIDA review either.[151] The quality and potency of cannabis supplied by NIDA has also been called into question by some researchers.[154][155]
As a result of these requirements that have been imposed in the US, studies involving cannabis have been delayed for years in some cases,[149][152] and a number of medical organizations have called for federal policy to be reformed.[9][10][140][141]
Cancer
Cannabinoids have been shown to exhibit some anti-cancer effects in laboratory experiments, although there has been little research into their use as a cancer treatment in people.[156][157] Laboratory experiments have suggested that cannabis and cannabinoids have anticarcinogenic and antitumor effects,[158] including a potential effect on breast- and lung-cancer cells.[159] The National Cancer Institute reports that as of November 2013[update] there have been no clinical trials on the use of cannabis to treat cancer in people, and only one small study using delta-9-THC that reported potential antitumoral activity.[160] While cannabis may have potential for refractory cancer pain, use as an antiemetic, and as an antitumor agent, much of the evidence comes from outdated or small studies, or animal experiments.[161]
Although there is ongoing research, claims that cannabis has been proved to cure cancer are, according to Cancer Research UK, both prevalent on the internet and "highly misleading".[162]
There is no good evidence that cannabis use helps reduce the risk of getting cancer.[162] Whether smoking cannabis increases cancer risk in general is difficult to establish since it is often smoked mixed with tobacco – a known carcinogen – and this complicates research.[162] Cannabis use is linked to an increased risk of a type of testicular cancer.[163]
The association of cannabis use with head and neck carcinoma may differ by tumor site, with both possible pro- and anticarcinogenic effects of cannabinoids. Additional work is needed to rule out various sources of bias, confounds and misclassification of cannabis exposure.[164]
Dementia
Cannabinoids have been proposed to have the potential for lessening the effects of Alzheimer's disease.[165] A 2012 review of the effect of cannabinoids on brain ageing found that "clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing".[166] A 2009 Cochrane review said that the "one small randomized controlled trial [that] assessed the efficacy of cannabinoids in the treatment of dementia ... [had] ... poorly presented results and did not provide sufficient data to draw any useful conclusions".[167]
Diabetes
There is emerging evidence that cannabidiol may help slow cell damage in diabetes mellitus type 1.[168] There is a lack of meaningful evidence of the effects of medical cannabis use on people with diabetes; a 2010 review concluded that "the potential risks and benefits for diabetic patients remain unquantified at the present time".[169]
Epilepsy
A 2016 review in the New England Journal of Medicine said that although there was a lot of hype and anecdotes surrounding medical cannabis and epilepsy, "current data from studies in humans are extremely limited, and no conclusions can be drawn".[170] The mechanisms by which cannabis may be effective in the treatment of epilepsy remain unclear.[171]
Some reasons for the lack of clinical research have been the introduction of new synthetic and more stable pharmaceutical anticonvulsants, the recognition of important adverse side effects, and legal restrictions to the use of cannabis-derived medicines[172] – although in December 2015, the DEA (United States Drug Enforcement Administration) has eased some of the regulatory requirements for conducting FDA-approved clinical trials on cannabidiol (CBD).[173]
Epidiolex, a cannabis-based product developed by GW Pharmaceuticals for experimental treatment of epilepsy, underwent stage-two trials in the US in 2014.[174]
A 2017 study found that cannabidiol decreased the rate of seizures in those with Dravet syndrome but increased the rate of sleepiness and trouble with the liver.[175]
Glaucoma
In 2009, the American Glaucoma Society noted that while cannabis can help lower intraocular pressure, it recommended against its use because of "its side effects and short duration of action, coupled with a lack of evidence that its use alters the course of glaucoma".[176] As of 2008 relatively little research had been done concerning therapeutic effects of cannabinoids on the eyes.[177]
Tourette syndrome
A 2007 review of the history of medical cannabis said cannabinoids showed potential therapeutic value in treating Tourette syndrome (TS).[178] A 2005 review said that controlled research on treating TS with dronabinol showed the patients taking the pill had a beneficial response without serious adverse effects;[179] a 2000 review said other studies had shown that cannabis "has no effects on tics and increases the individuals inner tension".[180]
A 2009 Cochrane review examined the two controlled trials to date using cannabinoids of any preparation type for the treatment of tics or TS (Muller-Vahl 2002, and Muller-Vahl 2003). Both trials compared delta-9-THC; 28 patients were included in the two studies (8 individuals participated in both studies).[88] Both studies reported a positive effect on tics, but "the improvements in tic frequency and severity were small and were only detected by some of the outcome measures".[88] The sample size was small and a high number of individuals either dropped out of the study or were excluded.[88] The original Muller-Vahl studies reported individuals who remained in the study; patients may drop out when adverse effects are too high or efficacy is not evident.[88] The authors of the original studies acknowledged few significant results after Bonferroni correction.[88]
Cannabinoid medication might be useful in the treatment of the symptoms in patients with TS,[88] but the 2009 review found that the two relevant studies of cannibinoids in treating tics had attrition bias, and that there was "not enough evidence to support the use of cannabinoids in treating tics and obsessive compulsive behaviour in people with Tourette's syndrome".[88]
Other conditions
Anecdotal evidence and pre-clinical research has suggested that cannabis or cannabinoids may be beneficial for treating Huntington's disease or Parkinson's disease, but follow-up studies of people with these conditions have not produced good evidence of therapeutic potential.[181] A 2001 paper argued that cannabis had properties that made it potentially applicable to the treatment of amyotrophic lateral sclerosis, and on that basis research on this topic should be permitted, despite the legal difficulties of the time.[182]
A 2005 review and meta-analysis said that bipolar disorder was not well-controlled by existing medications and that there were "good pharmacological reasons" for thinking cannabis had therapeutic potential, making it a good candidate for further study.[183]
Cannabinoids have been proposed for the treatment of primary anorexia nervosa, but have no measurable beneficial effect.[184] The authors of a 2003 paper argued that cannabinoids might have useful future clinical applications in treating digestive diseases.[185] Laboratory experiments have shown that cannabinoids found in marijuana may have analgesic and anti-inflammatory effects.[159]
In 2014, the American Academy of Neurology reviewed all available findings levering the use of marijuana to treat brain diseases. The result was that the scientific evidence is weak that cannabis in any form serves as medicinal for curing or alleviating neurological disorders. To ease multiple sclerosis patients' stiffness, which may be accomplished by their taking cannabis extract by mouth or as a spray, there is support. The academy has published new guidelines on the use of marijuana pills and sprays in the treatment of MS.[186]
Cannabis is being investigated for its possible use in inflammatory bowel disease but as of 2014[update] there is only weak evidence for its benefits as a treatment.[187]
A 2007 review said cannabidiol had shown potential to relieve convulsion, inflammation, cough, congestion and nausea, and to inhibit cancer cell growth.[188] Preliminary studies have also shown potential over psychiatric conditions such as anxiety, depression, and psychosis.[189] Because cannabidiol relieves the aforementioned symptoms, cannabis strains with a high amount of CBD may benefit people with multiple sclerosis or frequent anxiety attacks.
