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Medical cannabis

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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 using a variety of methods, including liquid tinctures, vaporizing or smoking dried buds, eating cannabis edibles, taking capsules, using lozenges, dermal patches, or oral/dermal sprays. Synthetic cannabinoids are available as prescription drugs in some countries; examples include: dronabinol and nabilone. Recreational use of cannabis is illegal in most parts of the world, but the medical use of cannabis is legal in a number of countries, some of which include Canada, Chile, Colombia, Germany, Greece, Israel, Italy, the Netherlands, Poland, Peru, and Uruguay. Australia has passed laws to allow the use of cannabis for medical and scientific purposes in some states. In the United States, 29 states and the District of Columbia have passed legislation permitting the possession, use, and distribution of medical cannabis in some form. 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.

Classification

Many different cannabis strains are collectively called medical cannabis. Since many varieties of the cannabis plant and plant derivatives all share the same name, the term medical cannabis is ambiguous and can be misunderstood. A Cannabis plant includes more than 400 different chemicals, of which about 70 are cannabinoids.[11] In comparison, typical government-approved medications contain only one or two chemicals.[11] The number of active chemicals in cannabis is one reason why treatment with cannabis is difficult to classify and study.[11]

A 2014 review stated that the variations in ratio of CBD-to-THC in botanical and pharmaceutical preparations determines the therapeutic vs psychoactive effects (CBD attenuates THC's psychoactive effects[12]) of cannabis products.[13]

Medical uses

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

Tentative evidence suggests cannabis maybe useful for peripheral neuropathy but evidence of benefit is lacking for other types of long term pain.[23] A 2009 review states it was unclear if the benefits were greater than the risks,[24] while a 2011 review considered it generally safe for this use.[25] In palliative care the use appears safer than that of opioids.[26] A 2014 review found limited and weak evidence that smoked cannabis was effective for chronic non-cancer pain. The review recommended that it be used for people for whom cannabinoids and other analgesics were not effective.[27] A 2015 review found moderate quality evidence that cannabinoids were effective for chronic pain.[5] 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.[28] Another 2015 systematic review and meta-analysis found limited evidence that medical cannabis was effective for neuropathic pain when combined with traditional analgesics.[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, there is insufficient evidence to confirm its effectiveness for this condition.[35]

Adverse effects

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]

Recreational use

Tetrahydrocannabinol (THC), the principal psychoactive constituent of the cannabis plant, has low toxicity while the LD50 (dose of THC needed to kill 50% of tested rodents) is high. Acute effects may include anxiety and panic, impaired attention, and memory (while intoxicated), an increased risk of psychotic symptoms, and possibly increased risk of accidents if a person drives a motor vehicle while intoxicated.[38] Psychotic episodes are well-documented and typically resolve within minutes or hours. There have been few reports of symptoms lasting longer.[39][40]

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.[41] In 129,000 cases, cannabis was the only implicated drug.[42][43]

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] There is little evidence that cognitive impairments persist in adult abstinent cannabis users.[44] 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.[45]

There has been a limited amount of studies that have looked at the effects of smoking cannabis on the respiratory system.[46] Chronic heavy marijuana smoking is associated with coughing, production of sputum, wheezing, coughing, and other symptoms of chronic bronchitis.[38] Regular cannabis use has not been shown to cause significant abnormalities in lung function.[47]

Cannabis smoke contains thousands of organic and inorganic chemical compounds. This tar is chemically similar to that found in tobacco smoke,[48] and over fifty known carcinogens have been identified in cannabis smoke,[49] including; nitrosamines, reactive aldehydes, and polycylic hydrocarbons, including benz[a]pyrene.[50] 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.[47] 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.[51] 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.[52] 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.[53] 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.[54]

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.[55] 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.[56]

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".[57]

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.[58] A second systematic review focused on neuroimaging studies found little evidence supporting an effect of cannabis use on brain structure and function.[59] 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.[60]

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.[61] A 2005 meta analysis concluded that adolescent use of cannabis increases the risk of psychosis, and that the risk is dose-related.[62] 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.[63] 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.[64]

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.[65][66] A 2005 paper from the Dunedin study suggested an increased risk in the development of psychosis linked to polymorphisms in the COMT gene.[67] However, a more recent study cast doubt on the proposed connection between this gene and the effects of cannabis on the development of psychosis.[68]

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.[69]

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.[70] 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[71][72]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.[73]

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.[57]

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.[74] CB2 receptors are found peripherally throughout the body and are thought to modulate pain and inflammation.[75]

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.[76] 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.[77]

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.[77]

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.[78] Rectal administration in monkeys doubled bioavailability to 13.5% and achieved peak blood concentrations within 1 to 8 hours after administration.[76]

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.[76][79] 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.[80] 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.[79][81][82]

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.[83] 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.[84]

Next, 11-OH-THC is metabolized in the liver into 11-COOH-THC, which is the second metabolic product of THC.[85] 11-COOH-THC is not psychoactive.[83]

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.[83] 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.[77]

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.[77] The terminal half-life is approximately 25–36 hours.[86]

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.[87] Similar to delta-9-THC, a majority of CBD is excreted in feces and some in the urine.[77] The terminal half-life is approximately 18–32 hours.[88]

Administration

Illustrating various forms of medicinal cannabis

Smoking is the means of administration of cannabis for many consumers,[89] 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.[89]

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".[89]

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.[90] 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."[90]

History

Ancient

Cannabis, called (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.[91] 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."[92] 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.[93] Cannabis is one of the 50 "fundamental" herbs in traditional Chinese medicine.[94]

The Ebers Papyrus (c. 1550 BCE) from Ancient Egypt describes medical cannabis.[95] The ancient Egyptians used hemp (cannabis) in suppositories for relieving the pain of hemorrhoids.[96]

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.[97]

The Ancient Greeks used cannabis to dress wounds and sores on their horses,[98] and in humans, dried leaves of cannabis were used to treat nose bleeds, and cannabis seeds were used to expel tapeworms.[98]

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.[99]

Modern

An Irish physician, William Brooke O'Shaughnessy, is credited with introducing cannabis to Western medicine.[100] O'Shaughnessy discovered cannabis in the 1830s while living abroad in India, where he conducted numerous experiments investigating its medical utility.[101] 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.[102] Cannabis was entered into the United States Pharmacopeia in 1850.[101]

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.[102] 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.[102]

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.[103] 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.[102]

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.[104] In 1996, California became the first U.S. state to legalize medical cannabis in defiance of federal law.[105] In 2001, Canada became the first country to adopt a system regulating the medical use of cannabis.[106]

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,[107] Chile,[107] Colombia,[107] Croatia,[108] Cyprus,[109] Czech Republic,[107] Jamaica,[107] Finland,[110] Germany,[111] Greece,[112] Israel,[113] Italy,[114] Macedonia,[115] the Netherlands,[107] Poland,[116] Peru,[117] Romania,[118] and Uruguay[107] 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.[119] Countries with more relaxed laws include Uruguay,[107] the Netherlands,[107] and Spain,[120] where cannabis can be obtained without need for a prescription. In Mexico, THC content of medical cannabis is limited to one percent.[121] The same limit applies in Switzerland, but no prescription is required to purchase.[122] In the United States[123] and Australia,[124] 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.[125]

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."[125]

United States

As of April 2017, 29 states and the District of Columbia have legalized the medical use of cannabis, and another 18 have passed laws allowing the use of CBD products.[123] 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.[126]

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][127] Marijuana vending machines for selling or dispensing cannabis are in use in the United States and are planned to be used in Canada.[128] In 2014, the startup Meadow began offering on-demand delivery of medical marijuana in the San Francisco Bay Area, through their mobile app.[129]

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.[130] 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.[131]

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,[132] American Medical Student Association,[133] National Multiple Sclerosis Society,[134] Epilepsy Foundation,[135] and Leukemia & Lymphoma Society.[136]

Organizations that have issued statements in opposition to the legalization of medical cannabis include the American Academy of Pediatrics,[10] American Psychiatric Association,[137] and American Society of Addiction Medicine.[138] However, the AAP also supports rescheduling for the purpose of facilitating research.[10]

The American Medical Association[139] and American College of Physicians[140] 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[141] and American Psychological Association[142] 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.[143] The report authors suggested rather that medical cannabis users occupied a "continuum" between medical and nonmedical use.[143]

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 III, meaning it has some potential for dependence. Nabilone, a synthetic cannabinoid, is Schedule II, indicating high potential for side effects and addiction.[73] 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,[73] is not approved in the United States, but is approved in several European countries, Canada, and New Zealand as of 2013.[4]

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
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.[73] 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.[142] 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][141][142]

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 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).[89] 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".[89] The sample size was small and a high number of individuals either dropped out of the study or were excluded.[89] 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.[89] The authors of the original studies acknowledged few significant results after Bonferroni correction.[89]

Cannabinoid medication might be useful in the treatment of the symptoms in patients with TS,[89] 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".[89]

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 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.[31][188]

See also

References

  1. ^ Murnion, B (December 2015). "Medicinal cannabis". Australian prescriber. 38 (6): 212–5. doi:10.18773/austprescr.2015.072. PMC 4674028Freely accessible. PMID 26843715. 
  2. ^ "What is medical marijuana?". National Institute of Drug Abuse. July 2015. Retrieved 19 April 2016. The term medical marijuana refers to using the whole unprocessed marijuana plant or its basic extracts to treat a disease or symptom. 
  3. ^ "Release the strains". Nature Medicine. 21: 963. 4 September 2015. doi:10.1038/nm.3946. Retrieved 8 September 2015. 
  4. ^ a b c d e f g h i j k l m n o p q r s t u v w x Borgelt, LM; Franson, KL; Nussbaum, AM; Wang, GS (February 2013). "The pharmacologic and clinical effects of medical cannabis" (PDF). Pharmacotherapy. 33 (2): 195–209. doi:10.1002/phar.1187. PMID 23386598. 
  5. ^ a b c d e f g h Whiting, PF; Wolff, RF; Deshpande, S; Di Nisio, M; Duffy, S; Hernandez, AV; Keurentjes, JC; Lang, S; Misso, K; Ryder, S; Schmidlkofer, S; Westwood, M; Kleijnen, J (23 June 2015). "Cannabinoids for Medical Use: A Systematic Review and Meta-analysis". JAMA. 313 (24): 2456–2473. doi:10.1001/jama.2015.6358. PMID 26103030. 
  6. ^ Jensen, Bjorn; Chen, Jeffrey; Furnish, Tim; Wallace, Mark (1 September 2015). "Medical Marijuana and Chronic Pain: a Review of Basic Science and Clinical Evidence". Current Pain and Headache Reports. 19 (10). doi:10.1007/s11916-015-0524-x. 
  7. ^ a b c d Ben Amar M (2006). "Cannabinoids in medicine: a review of their therapeutic potential". Journal of Ethnopharmacology (Review). 105 (1–2): 1–25. doi:10.1016/j.jep.2006.02.001. PMID 16540272. 
  8. ^ a b Therapeutic Use of Marijuana and Related Cannabinoids (PDF), American Nurses Association, 2016 
  9. ^ a b c "Marijuana -- AAFP Policies". aafp.org. Retrieved 30 July 2017. 
  10. ^ a b c d American Academy of Pediatrics Reaffirms Opposition to Legalizing Marijuana for Recreational or Medical Use, American Academy of Pediatrics, 26 January 2015, retrieved 30 July 2017 
  11. ^ a b c Consumer Reports (28 April 2016). "Up in Smoke: Does Medical Marijuana Work?". Consumer Reports. Retrieved 24 May 2016. 
  12. ^ a b Schubart CD, Sommer IE, Fusar-Poli P, de Witte L, Kahn RS, Boks MP (2014). "Cannabidiol as a potential treatment for psychosis" (PDF). European Neuropsychopharmacology. 24 (1): 51–64. doi:10.1016/j.euroneuro.2013.11.002. PMID 24309088. 
  13. ^ Barbara S. Koppel MD FAAN; John C.M. Brust MD FAAN; Terry Fife MD FAAN; Jeff Bronstein MD PhD; Sarah Youssof MD; Gary Gronseth MD FAAN; David Gloss MD (2014). "Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders". Neurology. 82 (17): 1556–1563. doi:10.1212/WNL.0000000000000363. PMC 4011465Freely accessible. PMID 24778283. 
  14. ^ a b Sachs J, McGlade E, Yurgelun-Todd D (2015). "Safety and Toxicology of Cannabinoids". Neurotherapeutics. 12 (4): 735–746. doi:10.1007/s13311-015-0380-8. PMC 4604177Freely accessible. PMID 26269228. 
  15. ^ Committee on Obstetric Practice (July 2015). "Committee Opinion No. 637: Marijuana Use During Pregnancy and Lactation". Obstetrics & Gynecology. 126 (1): 234–238. doi:10.1097/01.AOG.0000467192.89321.a6. 
  16. ^ a b Grotenhermen, F; Müller-Vahl, K (July 2012). "The therapeutic potential of cannabis and cannabinoids". Deutsches Arzteblatt international. 109 (29–30): 495–501. doi:10.3238/arztebl.2012.0495. PMC 3442177Freely accessible. PMID 23008748. 
  17. ^ Bowles DW, O'Bryant CL, Camidge DR, Jimeno A (July 2012). "The intersection between cannabis and cancer in the United States". Crit. Rev. Oncol. Hematol. (Review). 83 (1): 1–10. doi:10.1016/j.critrevonc.2011.09.008. PMID 22019199. 
  18. ^ a b Wang T, Collet JP, Shapiro S, Ware MA (June 2008). "Adverse effects of medical cannabinoids: a systematic review". CMAJ (Review). 178 (13): 1669–78. doi:10.1503/cmaj.071178. PMC 2413308Freely accessible. PMID 18559804. 
  19. ^ Jordan K, Sippel C, Schmoll HJ (September 2007). "Guidelines for antiemetic treatment of chemotherapy-induced nausea and vomiting: past, present, and future recommendations". Oncologist (Review). 12 (9): 1143–50. doi:10.1634/theoncologist.12-9-1143. PMID 17914084. 
  20. ^ Nicolson SE, Denysenko L, Mulcare JL, et al. (May–Jun 2012). "Cannabinoid hyperemesis syndrome: a case series and review of previous reports". Psychosomatics (Review, case series). 53 (3): 212–9. doi:10.1016/j.psym.2012.01.003. PMID 22480624. 
  21. ^ Phillips, RS; Friend, AJ; Gibson, F; Houghton, E; Gopaul, S; Craig, JV; Pizer, B (2 February 2016). "Antiemetic medication for prevention and treatment of chemotherapy-induced nausea and vomiting in childhood". The Cochrane database of systematic reviews. 2: CD007786. PMID 26836199. 
  22. ^ Lutge EE, Gray A, Siegfried N (2013). "The medical use of cannabis for reducing morbidity and mortality in patients with HIV/AIDS". Cochrane Database Syst Rev (Review). 4: CD005175. doi:10.1002/14651858.CD005175.pub3. PMID 23633327. 
  23. ^ Nugent, Shannon M.; Morasco, Benjamin J.; O'Neil, Maya E.; Freeman, Michele; Low, Allison; Kondo, Karli; Elven, Camille; Zakher, Bernadette; Motu'apuaka, Makalapua; Paynter, Robin; Kansagara, Devan (15 August 2017). "The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms". Annals of Internal Medicine. doi:10.7326/M17-0155. 
  24. ^ Martín-Sánchez E, Furukawa TA, Taylor J, Martin JL (November 2009). "Systematic review and meta-analysis of cannabis treatment for chronic pain". Pain Medicine (Review, meta-analysis). 10 (8): 1353–68. doi:10.1111/j.1526-4637.2009.00703.x. PMID 19732371. 
  25. ^ Lynch ME, Campbell F (November 2011). "Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials". British Journal of Clinical Pharmacology (Review). 72 (5): 735–44. doi:10.1111/j.1365-2125.2011.03970.x. PMC 3243008Freely accessible. PMID 21426373. 
  26. ^ Carter GT, Flanagan AM, Earleywine M, et al. (August 2011). "Cannabis in palliative medicine: improving care and reducing opioid-related morbidity". The American journal of hospice & palliative care (Review). 28 (5): 297–303. doi:10.1177/1049909111402318. PMID 21444324. 
  27. ^ Kahan, M; Srivastava, A; Spithoff, S; Bromley, L (December 2014). "Prescribing smoked cannabis for chronic noncancer pain: preliminary recommendations". Canadian Family Physician. 60 (12): 1083–90. PMC 4264803Freely accessible. PMID 25500598. 
  28. ^ Andreae, MH; Carter, GM; Shaparin, N; Suslov, K; Ellis, RJ; Ware, MA; Abrams, DI; Prasad, H; Wilsey, B; Indyk, D; Johnson, M; Sacks, HS (8 September 2015). "Inhaled cannabis for chronic neuropathic pain: an individual patient data meta-analysis". The Journal of Pain. 16: 1221–32. doi:10.1016/j.jpain.2015.07.009. PMC 4666747Freely accessible. PMID 26362106. 
  29. ^ Deshpande, A; Mailis-Gagnon, A; Zoheiry, N; Lakha, SF (August 2015). "Efficacy and adverse effects of medical marijuana for chronic noncancer pain: Systematic review of randomized controlled trials". Canadian Family Physician. 61 (8): e372–81. PMC 4541447Freely accessible. PMID 26505059. 
  30. ^ Koppel, BS; Brust, JC; Fife, T; Bronstein, J; Youssof, S; Gronseth, G; Gloss, D (29 April 2014). "Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology". Neurology. 82 (17): 1556–63. doi:10.1212/WNL.0000000000000363. PMC 4011465Freely accessible. PMID 24778283. 
  31. ^ a b Lakhan SE, Rowland M (2009). "Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review". BMC Neurology (Review). 9: 59. doi:10.1186/1471-2377-9-59. PMC 2793241Freely accessible. PMID 19961570. 
  32. ^ Koppel, BS; Brust, JC; Fife, T; Bronstein, J; Youssof, S; Gronseth, G; Gloss, D (29 April 2014). "Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology". Neurology. 82 (17): 1556–63. doi:10.1212/WNL.0000000000000363. PMC 4011465Freely accessible. PMID 24778283. 
  33. ^ [conflicted source?] Clark PA, Capuzzi K, Fick C (2011). "Medical marijuana: Medical necessity versus political agenda". Medical Science Monitor (Review). 17 (12): RA249–61. doi:10.12659/MSM.882116. PMC 3628147Freely accessible. PMID 22129912. 
  34. ^ Oreja-Guevara, C (2012). "Treatment of spasticity in multiple sclerosis: New perspectives regarding the use of cannabinoids". Revista de neurologia (Review) (in Spanish). 55 (7): 421–30. PMID 23011861. 
  35. ^ Yarnell S (2015). "The Use of Medicinal Marijuana for Posttraumatic Stress Disorder: A Review of the Current Literature". Prim Care Companion CNS Disord (Review). 17 (3). doi:10.4088/PCC.15r01786. PMC 4578915Freely accessible. PMID 26644963. 
  36. ^ a b Washington, Tabitha A.; Brown, Khalilah M.; Fanciullo, Gilbert J. (2012). "Chapter 31: Medical Cannabis". Pain. Oxford University Press. p. 165. ISBN 978-0-19-994274-9. Proponents of medical cannabis site its safety, but there studies in later years that support that smoking of marijuana is associated with risk for dependence and that THC alters the structures of cells in the brain 
  37. ^ Barceloux, Donald G (2012). "Chapter 60: Marijuana (Cannabis sativa L.) and synthetic cannabinoids". Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. pp. 886–931. ISBN 978-0-471-72760-6. 
  38. ^ a b c W. Hall; N. Solowij (14 November 1998). "Adverse effects of cannabis". Lancet. 352 (9140): 1611–16. doi:10.1016/S0140-6736(98)05021-1. PMID 9843121. 
  39. ^ "Sativex Oral Mucosal Spray Public Assessment Report. Decentralized Procedure" (PDF). United Kingdom Medicines and Healthcare Products Regulatory Agency. p. 93. Retrieved 7 May 2015. There is clear evidence that recreational cannabis can produce a transient toxic psychosis in larger doses or in susceptible individuals, which is said to characteristically resolve within a week or so of absence (Johns 2001). Transient psychotic episodes as a component of acute intoxication are well-documented (Hall et al 1994) 
  40. ^ D'Souza, DC; Sewell, RA; Ranganathan, M (October 2009). "Cannabis and psychosis/schizophrenia: human studies". European archives of psychiatry and clinical neuroscience. 259 (7): 413–31. doi:10.1007/s00406-009-0024-2. PMC 2864503Freely accessible. PMID 19609589. 
  41. ^ "Drug Abuse Warning Network, 2011. National Estimates of Drug-Related Emergency Department Visits" (PDF). U.S. Department of Health and Human Services. 2011. Retrieved 8 May 2015. 
  42. ^ "www.samhsa.gov". 
  43. ^ a b c Volkow ND, Baler RD, Compton WM, Weiss SR (2014). "Adverse health effects of marijuana use". N. Engl. J. Med. 370 (23): 2219–27. doi:10.1056/NEJMra1402309. PMC 4827335Freely accessible. PMID 24897085. 
  44. ^ van Holst, RJ; Schilt, T (March 2011). "Drug-related decrease in neuropsychological functions of abstinent drug users". Current drug abuse reviews. 4 (1): 42–56. doi:10.2174/1874473711104010042. PMID 21466500. 
  45. ^ Hall, W (January 2015). "What has research over the past two decades revealed about the adverse health effects of recreational cannabis use?". Addiction (Abingdon, England). 110 (1): 19–35. doi:10.1111/add.12703. PMID 25287883. 
  46. ^ Stephen Maisto; Mark Galizio; Gerard Connors (2014). Drug Use and Abuse. Cengage Learning. p. 278. ISBN 978-1-305-17759-8. 
  47. ^ a b Tashkin, DP (June 2013). "Effects of marijuana smoking on the lung". Annals of the American Thoracic Society. 10 (3): 239–47. doi:10.1513/annalsats.201212-127fr. PMID 23802821. 
  48. ^ Hashibe, Mia; Straif, Kurt; Tashkin, Donald P.; Morgenstern, Hal; Greenland, Sander; Zhang, Zuo-Feng (April 2005). "Epidemiologic review of marijuana use and cancer risk". Alcohol. 35 (3): 265–275. doi:10.1016/j.alcohol.2005.04.008. PMID 16054989. 
  49. ^ "Does smoking cannabis cause cancer?". Cancer Research UK. 20 September 2010. Retrieved 9 January 2013. 
  50. ^ Tashkin, Donald (March 1997). "Effects of marijuana on the lung and its immune defenses". UCLA School of Medicine. Retrieved 23 June 2012. 
  51. ^ A. Riecher-Rössler (2014). Comorbidity of Mental and Physical Disorders. Karger Medical and Scientific Publishers. p. 88. ISBN 978-3-318-02604-7. 
  52. ^ Cottencin O. (Dec 2010). "Cannabis arteritis: review of the literature". J Addict Med (Review). 4 (4): 191–6. doi:10.1097/ADM.0b013e3181beb022. PMID 21769037. 
  53. ^ Thomas G (1 January 2014). "Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: what cardiologists need to know". Am J Cardiol. 113 (1): 187–90. doi:10.1016/j.amjcard.2013.09.042. PMID 24176069. 
  54. ^ RT Jones (2002). "Cardiovascular system effects of marijuana". J Clin Pharmacol (Review). 42 (11 Suppl): 58S–63S. doi:10.1002/j.1552-4604.2002.tb06004.x. PMID 12412837. 
  55. ^ "Withdrawal Symptoms From Smoking Pot?". WebMD. 
  56. ^ Hall, W; Degenhardt, L (17 October 2009). "Adverse health effects of non-medical cannabis use". Lancet. 374 (9698): 1383–91. doi:10.1016/s0140-6736(09)61037-0. PMID 19837255. 
  57. ^ a b Gordon AJ, Conley JW, Gordon JM (December 2013). "Medical consequences of marijuana use: a review of current literature". Curr Psychiatry Rep (Review). 15 (12): 419. doi:10.1007/s11920-013-0419-7. PMID 24234874. 
  58. ^ Crean RD, Crane NA, Mason BJ (March 2011). "An evidence-based review of acute and long-term effects of cannabis use on executive cognitive functions". J Addict Med. 5 (1): 1–8. doi:10.1097/ADM.0b013e31820c23fa. PMC 3037578Freely accessible. PMID 21321675. 
  59. ^ Martín-Santos R, Fagundo AB, Crippa JA, Atakan Z, Bhattacharyya S, Allen P, Fusar-Poli P, Borgwardt S, Seal M, Busatto GF, McGuire P (March 2010). "Neuroimaging in cannabis use: a systematic review of the literature". Psychol Med. 40 (3): 383–98. doi:10.1017/S0033291709990729. PMID 19627647. 
  60. ^ Grant I, Gonzalez R, Carey CL, Natarajan L, Wolfson T (2003). "Non-acute (residual) neurocognitive effects of cannabis use: A meta-analytic study". Journal of the International Neuropsychological Society. 9 (5): 679–89. doi:10.1017/S1355617703950016. PMID 12901774. Lay summaryWebMD (1 July 2003). 
  61. ^ Large M, Sharma S, Compton MT, Slade T, Nielssen O (June 2011). "Cannabis use and earlier onset of psychosis: a systematic meta-analysis". Arch. Gen. Psychiatry. 68 (6): 555–61. doi:10.1001/archgenpsychiatry.2011.5. PMID 21300939. 
  62. ^ Semple DM, McIntosh AM, Lawrie SM (March 2005). "Cannabis as a risk factor for psychosis: systematic review". J. Psychopharmacol. (Oxford). 19 (2): 187–94. doi:10.1177/0269881105049040. PMID 15871146. 
  63. ^ Arseneault L, Cannon M, Witton J, Murray RM (2004). "Causal association between cannabis and psychosis: examination of the evidence". The British Journal of Psychiatry. 184 (2): 110–117. doi:10.1192/bjp.184.2.110. PMID 14754822. 
  64. ^ Laqueille X (2009). "Le cannabis est-il un facteur de vulnérabilité des troubles schizophrènes?" [Is cannabis is a vulnerability factor of schizophrenic disorders?]. Archives de Pédiatrie. 16 (9): 1302–5. doi:10.1016/j.arcped.2009.03.016. PMID 19640690. (Registration required (help)). 
  65. ^ Moore TH, Zammit S, Lingford-Hughes A, Barnes TR, Jones PB, Burke M, Lewis G (2007). "Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review". The Lancet. 370 (9584): 319–28. doi:10.1016/S0140-6736(07)61162-3. PMID 17662880. 
  66. ^ Henquet C, Krabbendam L, Spauwen J, Kaplan C, Lieb R, Wittchen HU, van Os J (2005). "Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people". BMJ. 330 (7481): 11–0. doi:10.1136/bmj.38267.664086.63. PMC 539839Freely accessible. PMID 15574485. 
  67. ^ Caspi A, Moffitt TE, Cannon M, McClay J, Murray R, Harrington H, Taylor A, Arseneault L, Williams B, Braithwaite A, Poulton R, Craig IW (2005). "Moderation of the Effect of Adolescent-Onset Cannabis Use on Adult Psychosis by a Functional Polymorphism in the Catechol-O-Methyltransferase Gene: Longitudinal Evidence of a Gene X Environment Interaction". Biological Psychiatry. 57 (10): 1117–27. doi:10.1016/j.biopsych.2005.01.026. PMID 15866551. 
  68. ^ S. Zammit; G. Spurlock; H. Williams; N. Norton; N. Williams; M.C. O'Donovan; M.J. Owen (2007). "Genotype effects of CHRNA7, CNR1 and COMT in schizophrenia: interactions with tobacco and cannabis use". The British Journal of Psychiatry. 191 (5): 402–7. doi:10.1192/bjp.bp.107.036129. PMID 17978319. Lay summaryMedWireNews. 
  69. ^ Kawohl W, Rössler W (2008). "Cannabis and Schizophrenia: new findings in an old debate". Neuropsychiatrie : Klinik, Diagnostik, Therapie und Rehabilitation : Organ der Gesellschaft Osterreichischer Nervenarzte und Psychiater. 22 (4): 223–9. PMID 19080993. 
  70. ^ Jayanthi S, Buie S, Moore S, Herning RI, Better W, Wilson NM, Contoreggi C, Cadet JL (2008). "Heavy marijuana users show increased serum apolipoprotein C-III levels: evidence from proteomic analyses". Molecular Psychiatry. 15 (1): 101–112. doi:10.1038/mp.2008.50. PMC 2797551Freely accessible. PMID 18475272. Lay summaryReuters (13 May 2008). 
  71. ^ Downer EJ, Campbell VA (January 2010). "Phytocannabinoids, CNS cells and development: a dead issue?". Drug Alcohol Rev (Review). 29 (1): 91–8. doi:10.1111/j.1465-3362.2009.00102.x. PMID 20078688. 
  72. ^ Burns TL, Ineck JR (2006). "Cannabinoid analgesia as a potential new therapeutic option in the treatment of chronic pain". The Annals of Pharmacotherapy (Review). 40 (2): 251–260. doi:10.1345/aph.1G217. PMID 16449552. 
  73. ^ a b c d Svrakic DM, Lustman PJ, Mallya A, Lynn TA, Finney R, Svrakic NM (2012). "Legalization, decriminalization & medicinal use of cannabis: a scientific and public health perspective". Mo Med (Review). 109 (2): 90–8. PMID 22675784. 
  74. ^ Mackie, K. (May 2008). "Cannabinoid receptors: where they are and what they do". Journal of Neuroendocrinology. 20 Suppl 1: 10–14. doi:10.1111/j.1365-2826.2008.01671.x. ISSN 1365-2826. PMID 18426493. 
  75. ^ Whiteside, G. T.; Lee, G. P.; Valenzano, K. J. (2007). "The role of the cannabinoid CB2 receptor in pain transmission and therapeutic potential of small molecule CB2 receptor agonists". Current Medicinal Chemistry. 14 (8): 917–936. ISSN 0929-8673. PMID 17430144. 
  76. ^ a b c Huestis, Marilyn A. (August 2007). "Human Cannabinoid Pharmacokinetics". Chemistry & biodiversity. 4 (8): 1770–1804. doi:10.1002/cbdv.200790152. ISSN 1612-1872. PMC 2689518Freely accessible. PMID 17712819. 
  77. ^ a b c d e Gaston, Tyler E.; Friedman, Daniel (2017-05-01). "Pharmacology of cannabinoids in the treatment of epilepsy". Epilepsy & Behavior. Cannabinoids and Epilepsy. 70 (Part B): 313–318. doi:10.1016/j.yebeh.2016.11.016. 
  78. ^ Mannila, Janne; Järvinen, Tomi; Järvinen, Kristiina; Tervonen, Jussi; Jarho, Pekka (2006-03-20). "Sublingual administration of Δ9-tetrahydrocannabinol/β-cyclodextrin complex increases the bioavailability of Δ9-tetrahydrocannabinol in rabbits". Life Sciences. 78 (17): 1911–1914. doi:10.1016/j.lfs.2005.08.025. 
  79. ^ a b Badowski, Melissa E. (2017). "A review of oral cannabinoids and medical marijuana for the treatment of chemotherapy-induced nausea and vomiting: a focus on pharmacokinetic variability and pharmacodynamics". Cancer Chemotherapy and Pharmacology. 80 (3): 441–449. doi:10.1007/s00280-017-3387-5. ISSN 0344-5704. PMC 5573753Freely accessible. PMID 28780725. 
  80. ^ Nahas, Gabriel G. (2001-04-01). "The pharmacokinetics of THC in fat and brain: resulting functional responses to marihuana smoking". Human Psychopharmacology: Clinical and Experimental. 16 (3): 247–255. doi:10.1002/hup.258. ISSN 1099-1077. 
  81. ^ Bridgeman, Mary Barna; Abazia, Daniel T. (March 2017). "Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting". Pharmacy and Therapeutics. 42 (3): 180–188. ISSN 1052-1372. PMC 5312634Freely accessible. PMID 28250701. 
  82. ^ Nahas, Gabriel G.; Sutin, Kenneth M.; Harvey, David J.; Agurell, Stig (1999-04-05). Marihuana and Medicine. Springer Science & Business Media. ISBN 9781592597109. 
  83. ^ a b c "Human Metabolism of THC". Sapiensoup Blog. 2016-12-21. Retrieved 2017-11-01. 
  84. ^ "11-Hydroxy-THC - Increased Potency That Explains the Effect of Edibles? - Prof of Pot". profofpot.com. Retrieved 2017-11-01. 
  85. ^ "Toxicology Litigation Support: Marijuana". consultox.com. Retrieved 2017-11-01. 
  86. ^ Grotenhermen, Franjo (2003-04-01). "Pharmacokinetics and Pharmacodynamics of Cannabinoids". Clinical Pharmacokinetics. 42 (4): 327–360. doi:10.2165/00003088-200342040-00003. ISSN 0312-5963. 
  87. ^ Juřica, Ondřej Zendulka, Gabriela Dovrtělová, Kristýna Nosková, Miroslav Turjap, Alexandra Šulcová, Lumír Hanuš and Jan (2016-02-29). "Cannabinoids and Cytochrome P450 Interactions". Current Drug Metabolism. 17 (3). 
  88. ^ Ohlsson, Agneta; Lindgren, Jan-Erik; Andersson, Susanne; Agurell, Stig; Gillespie, Hampton; Hollister, Leo E. (1986-02-01). "Single-dose kinetics of deuterium-labelled cannabidiol in man after smoking and intravenous administration". Biological Mass Spectrometry. 13 (2): 77–83. doi:10.1002/bms.1200130206. ISSN 1096-9888. 
  89. ^ a b c d e f g h i j Curtis A, Clarke CE, Rickards HE (2009). "Cannabinoids for Tourette's Syndrome". Cochrane Database Syst Rev (Review) (4): CD006565. doi:10.1002/14651858.CD006565.pub2. PMID 19821373. (Subscription required (help)). 
  90. ^ a b "Inter-agency advisory regarding claims that smoked marijuana is a medicine" (Press release). fda.gov. 20 April 2006. Retrieved 24 December 2012. 
  91. ^ Abel, Ernest L. (1980). "Cannabis in the Ancient World". Marihuana: the first twelve thousand years. New York City: Plenum Publishers. ISBN 978-0-306-40496-2. Retrieved 18 December 2013. [page needed]
  92. ^ Li, Hui-Lin (1974). "An Archaeological and Historical Account of Cannabis in China", Economic Botany 28.4:437–448, p. 444.
  93. ^ Bloomquist, Edward (1971). Marijuana: The Second Trip. California: Glencoe Press. 
  94. ^ Wong, Ming (1976). La Médecine chinoise par les plantes. Paris: Tchou. OCLC 2646789. [page needed]
  95. ^ [unreliable source?] "The Ebers Papyrus The Oldest (confirmed) Written Prescriptions For Medical Marihuana era 1,550 BC". onlinepot.org. Retrieved 10 June 2008. 
  96. ^ Pain, Stephanie (15 December 2007). "The Pharaoh's pharmacists". New Scientist. Reed Business Information Ltd. 
  97. ^ Touw, Mia (1981). "The Religious and Medicinal Uses ofCannabisin China, India and Tibet". Journal of Psychoactive Drugs. 13 (1): 23–34. doi:10.1080/02791072.1981.10471447. PMID 7024492. 
  98. ^ a b Butrica, James L. (2002). "The Medical Use of Cannabis Among the Greeks and Romans" (PDF). Journal of Cannabis Therapeutics. 2 (2): 51–70. doi:10.1300/J175v02n02_04. Retrieved 8 November 2014. 
  99. ^ Lozano, Indalecio (2001). "The Therapeutic Use of Cannabis sativa (L.) in Arabic Medicine". Journal of Cannabis Therapeutics. 1: 63–70. doi:10.1300/J175v01n01_05. 
  100. ^ Alison Mack; Janet Joy (7 December 2000). Marijuana As Medicine?: The Science Beyond the Controversy. National Academies Press. pp. 15–. ISBN 978-0-309-06531-3. 
  101. ^ a b Booth, Martin (June 2005). Cannabis: A History. New York: St. Martin's Press. ISBN 978-0-312-42494-7. 
  102. ^ a b c d Grinspoon, Lester; Bakalar, James (1997). Marihuana, the Forbidden Medicine (Revised and expanded ed.). Yale University Press. ISBN 978-0-300-07086-6. 
  103. ^ Pacula, Rosalie Piccardo (February 2002). "State Medical Marijuana Laws: Understanding the Laws and Their Limitations" (PDF). Journal of Public Health Policy. doi:10.2307/3343240. 
  104. ^ Joy, Janet E.; Watson, Stanley J.; Benson, John A. (1999). "Marijuana and Medicine -- Assessing the Science Base" (PDF). Washington, D.C.: National Academy Press. 
  105. ^ "History of Marijuana as Medicine – 2900 BC to Present". ProCon.org. Retrieved 27 July 2017. 
  106. ^ "Marijuana's journey to legal health treatment: the Canadian experience". CBC News. 17 August 2009. Retrieved 27 July 2017. 
  107. ^ a b c d e f g h i Williams, Sean (15 May 2016). "10 Countries (Aside From the U.S.) Where Some Form of Medical Marijuana Is Legal". The Motley Fool. Retrieved 5 November 2017. 
  108. ^ Veselica, Lajla (15 October 2015). "Croatia legalises marijuana for medical use". Yahoo News. AFP. Retrieved 4 November 2017. 
  109. ^ "Cyprus begins to distribute medical cannabis". InCyprus. 22 May 2017. Retrieved 11 November 2017. 
  110. ^ "Legal status of cannabis in Finland – An overview". Sensi Seeds. Retrieved 4 November 2017. 
  111. ^ Senthilingam, Meera (6 March 2017). "Germany joins the global experiment on marijuana legalization". CNN. Retrieved 4 November 2017. 
  112. ^ Revesz, Rachael (3 July 2017). "Greece legalises marijuana for medical purposes". The Independent. Retrieved 4 November 2017. 
  113. ^ Schwartz, Yardena (24 August 2017). "How the Booming Israeli Weed Industry Is Changing American Pot". Rolling Stone. Retrieved 4 November 2017. 
  114. ^ Samuels, Gabriel (26 July 2016). "Italian army aims to produce 'the best-quality' medical marijuana after finding current batches deficient". The Independent. Retrieved 4 November 2017. 
  115. ^ Marusic, Sinisa Jakov (1 June 2016). "Macedonia Allows Medical Marijuana in Pharmacies". Balkan Insight. Retrieved 4 November 2017. 
  116. ^ "Medical use of cannabis officially legal in Poland". Radio Poland. PAP. 11 February 2017. Retrieved 4 November 2017. 
  117. ^ Collyns, Dan (20 October 2017). "Peru legalises medical marijuana in move spurred by mother's home lab". The Guardian. Retrieved 4 November 2017. 
  118. ^ Gates, Sara (15 October 2013). "Romania To Allow Medicinal Use Of Marijuana Derivatives, But Drug Remains Illegal". HuffPost. Retrieved 4 November 2017. 
  119. ^ "Sativex (delta-9-tetrahydrocannabinol and cannabidiol)". GW Pharmaceuticals. Retrieved 5 November 2017. 
  120. ^ Cedar, Ali (25 August 2015). "Exploring the Cannabis Clubs of Southern Spain, Europe's New Weed Destination". Vice. Retrieved 5 November 2017. 
  121. ^ Janikian, Michelle (14 September 2017). "Legal Pot In Mexico: Everything You Need to Know". Rolling Stone. Retrieved 5 November 2017. 
  122. ^ Depetris, Marina; Miller, John (21 March 2017). "Swiss cannabis entrepreneurs develop craving for low-potency pot". Reuters. Retrieved 5 November 2017. 
  123. ^ a b "State Medical Marijuana Laws". National Conference of State Legislatures. Retrieved 9 July 2017. 
  124. ^ Collett, Michael (22 February 2017). "Who can get medicinal marijuana?". ABC News. Retrieved 6 November 2017. 
  125. ^ a b "Single Convention on Narcotic Drugs, 1961 As amended by the 1972 Protocol" (PDF). International Narcotics Control Board. United Nations. 13 March 1961. pp. 2–3. Retrieved 17 August 2009. 
  126. ^ Ingraham, Christopher (13 June 2017). "Jeff Sessions personally asked Congress to let him prosecute medical-marijuana providers". The Washington Post. Retrieved 9 July 2017. 
  127. ^ Timothy B. Wheeler (11 October 2014). "Medical marijuana fees stir debate in Maryland". The Baltimore Sun. Retrieved 12 October 2014. 
  128. ^ Blackwell, Tom (16 October 2013). "The pot vending machine's first foreign market? Canada, of course, 'a seed for the rest of the world'". National Post. Retrieved 4 December 2013. 
  129. ^ "Uber-For-Weed Startup Meadow Lights Up In San Francisco". TechCrunch. AOL. 14 October 2014. Retrieved 22 January 2016. 
  130. ^ Clark, Tonya Body (10 February 2015). "The Medical Marijuana Debate". Compliance Corner. Wolters Kluwer Financial Services. Retrieved 26 February 2015. 
  131. ^ Peters, Joey (29 June 2015). "Court: Employer can't block workers' comp for medical marijuana". NM Political Report. Retrieved 30 June 2015. 
  132. ^ "Resolution on Medical Marijuana". druglibrary.org. Retrieved 30 July 2017. 
  133. ^ "House of Delegates 2017, Resolution: A8" (PDF). amsa.org. American Medical Student Association. Retrieved 30 July 2017. 
  134. ^ "Medical Marijuana (Cannabis) FAQs". National Multiple Sclerosis Society. Retrieved 30 July 2017. 
  135. ^ Gattone, Philip M.; Lammert, Warreb (20 February 2014). "Epilepsy Foundation Calls for Increased Medical Marijuana Access and Research" (Press release). Washington, D.C.: Epilepsy Foundation. Retrieved 30 July 2017. 
  136. ^ "Medical Marijuana Use and Research" (PDF). maps.org. Leukemia & Lymphoma Society. Retrieved 30 July 2017. 
  137. ^ "Position Statement on Marijuana as Medicine" (PDF). American Psychiatric Association. Retrieved 30 July 2017. 
  138. ^ "Public Policy Statement on Marijuana, Cannabinoids and Legalization" (PDF). American Society of Addiction Medicine. 21 September 2015. 
  139. ^ Use of Cannabis for Medicinal Purposes (PDF), American Medical Association, 2009 
  140. ^ Supporting Research into the Therapeutic Role of Marijuana (PDF), American College of Physicians, February 2016 
  141. ^ a b "Marijuana and Cancer". American Cancer Society. Retrieved 12 July 2017. 
  142. ^ a b c "Marijuana research: Overcoming the barriers". American Psychological Association. 14 September 2017. Retrieved 9 October 2017. 
  143. ^ a b Reinarman C, Nunberg H, Lanthier F, Heddleston T (2011). "Who are medical marijuana patients? Population characteristics from nine California assessment clinics". J Psychoactive Drugs (Review). 43 (2): 128–35. doi:10.1080/02791072.2011.587700. PMID 21858958. 
  144. ^ Clark, Amy (16 May 2006). "'New' Pot Pill For Chemo Patients". CBS News. Associated Press. Retrieved 26 July 2017. 
  145. ^ "Produkt – FASS Allmänhet". fass.se. 
  146. ^ Dr Farid F. Youssef. "Cannabis Unmasked: What it is and why it does what it does". UWIToday: June 2010. http://sta.uwi.edu/uwitoday/archive/june_2010/article9.asp
  147. ^ Fasinu PS, Phillips S, ElSohly MA, Walker LA (2016). "Current Status and Prospects for Cannabidiol Preparations as New Therapeutic Agents". Pharmacotherapy. 36: 781–96. doi:10.1002/phar.1780. PMID 27285147. 
  148. ^ a b Hudak, John; Wallack, Grace (October 2015), "Ending the U.S. government's war on medical marijuana research" (PDF), Center for Effective Public Management at Brookings, The Brookings Institution 
  149. ^ a b c The Obstruction Of Medical Cannabis Research In The U.S. (PDF), Americans for Safe Access, April 2009 
  150. ^ Zielinski, Alex (17 August 2016). "The DEA Hasn't Made Marijuana Research Any Easier". ThinkProgress. Retrieved 1 July 2017. 
  151. ^ a b c The DEA: Four Decades of Impeding And Rejecting Science (PDF), Drug Policy Alliance / Multidisciplinary Associations for Psychedelic Studies, June 2014 
  152. ^ a b Nelson, Steven (22 June 2015). "Major Pot Research Barrier Goes Up in Smoke". U.S. News & World Report. Retrieved 29 June 2017. 
  153. ^ Ferro, Shaunacy (13 April 2013). "Why It's So Hard For Scientists To Study Medical Marijuana". Popular Science. Retrieved 9 October 2017. 
  154. ^ Hellerman, Caleb (8 March 2017). "Scientists say the government's only pot farm has moldy samples — and no federal testing standards". PBS. Retrieved 9 October 2017. 
  155. ^ Hudak, John (11 August 2016). "The DEA's marijuana decision is more important than rescheduling". The Brookings Institution. Retrieved 9 October 2017. 
  156. ^ Bowles, DW; O'Bryant, CL; Camidge, DR; Jimeno, A (July 2012). "The intersection between cannabis and cancer in the United States". Critical reviews in oncology/hematology (Review). 83 (1): 1–10. doi:10.1016/j.critrevonc.2011.09.008. PMID 22019199. 
  157. ^ Chakravarti, Bandana; Ravi, Janani; Ganju, Ramesh K. (17 July 2014). "Cannabinoids as therapeutic agents in cancer: current status and future implications". Oncotarget. 5 (15): 5852–5872. doi:10.18632/oncotarget.2233. ISSN 1949-2553. PMC 4171598Freely accessible. PMID 25115386. 
  158. ^ "Cannabis (marihuana, marijuana) and the cannabinoids". Health Canada. February 2013. Retrieved 2 December 2013. 
  159. ^ a b "Cannabis and Cannabinoids (PDQ®)". National Cancer Institute at the National Institutes of Health. National Cancer Institute. 2 August 2013. Retrieved 24 August 2013. 
  160. ^ "Cannabis and Cannabinoids: Human/Clinical Studies". National Cancer Institute. 21 November 2013. Retrieved 2 December 2013. 
  161. ^ Wilkie, Gianna; Sakr, Bachir; Rizack, Tina (17 March 2016). "Medical Marijuana Use in Oncology". JAMA Oncology. doi:10.1001/jamaoncol.2016.0155. PMID 26986677. 
  162. ^ a b c Arney, Kat (25 July 2012). "Cannabis, cannabinoids and cancer – the evidence so far". Cancer Research UK. Retrieved 8 December 2013. 
  163. ^ Gurney J, Shaw C, Stanley J, Signal V, Sarfati D (2015). "Cannabis exposure and risk of testicular cancer: a systematic review and meta-analysis". BMC Cancer (Systematic review). 15: 897. doi:10.1186/s12885-015-1905-6. PMC 4642772Freely accessible. PMID 26560314. 
  164. ^ Madras, Bertha (11 December 2015). "Update of Cannabis and its medical use" (PDF). World Health Organization. Retrieved 18 December 2016. 
  165. ^ Campbell VA, Gowran A (2007). "Alzheimer's disease; taking the edge off with cannabinoids?". British Journal of Pharmacology (Review). 152 (5): 655–62. doi:10.1038/sj.bjp.0707446. PMC 2190031Freely accessible. PMID 17828287. 
  166. ^ Bilkei-Gorzo A (2012). "The endocannabinoid system in normal and pathological brain ageing". Philosophical Transactions of the Royal Society of London B: Biological Sciences (Review). 367 (1607): 3326–41. doi:10.1098/rstb.2011.0388. PMC 3481530Freely accessible. PMID 23108550. 
  167. ^ Krishnan S, Cairns R, Howard R (2009). "Cannabinoids for the treatment of dementia". Cochrane Database Syst Rev (Review) (2): CD007204. doi:10.1002/14651858.CD007204.pub2. PMID 19370677. (Subscription required (help)). 
  168. ^ Di Marzo V, Piscitelli F, Mechoulam R (2011). "Cannabinoids and endocannabinoids in metabolic disorders with focus on diabetes". Handb Exp Pharmacol. (Review). Handbook of Experimental Pharmacology. 203 (75): 75–104. doi:10.1007/978-3-642-17214-4_4. ISBN 978-3-642-17213-7. PMID 21484568. 
  169. ^ Fisher M, White S, Varbiro G, et al. (2010). "The role of cannabis and cannabinoids in diabetes". The British Journal of Diabetes & Vascular Disease. 10 (6): 267–273. doi:10.1177/1474651410385860. 
  170. ^ Friedman D, Devinsky O (2015). "Cannabinoids in the Treatment of Epilepsy". N. Engl. J. Med. (Review). 373 (11): 1048–58. doi:10.1056/NEJMra1407304. PMID 26352816. 
  171. ^ Reddy, DS; Golub, V (19 January 2016). "The Pharmacological Basis of Cannabis Therapy for Epilepsy". The Journal of Pharmacology and Experimental Therapeutics. 357: 45–55. doi:10.1124/jpet.115.230151. PMID 26787773. 
  172. ^ Pertwee RG (2012). "Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities". Philosophical Transactions of the Royal Society B: Biological Sciences (Review). 367 (1607): 3353–63. doi:10.1098/rstb.2011.0381. PMC 3481523Freely accessible. PMID 23108552. 
  173. ^ "DEA.gov / Headquarters News Releases, 12/23/15". 
  174. ^ Ward, Andrew (9 January 2014). "GW raises nearly $90m to develop childhood epilepsy treatment". Financial Times. Retrieved 20 January 2014. 
  175. ^ Devinsky, Orrin; Cross, J. Helen; Laux, Linda; Marsh, Eric; Miller, Ian; Nabbout, Rima; Scheffer, Ingrid E.; Thiele, Elizabeth A.; Wright, Stephen (25 May 2017). "Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome". New England Journal of Medicine. 376 (21): 2011–2020. doi:10.1056/NEJMoa1611618. ISSN 0028-4793. PMID 28538134. 
  176. ^ Jampel, Henry (10 August 2009). "Position statement on marijuana and the treatment of glaucoma". American Glaucoma Society. Retrieved 30 November 2013. 
  177. ^ Yazulla S (Sep 2008). "Endocannabinoids in the retina: from marijuana to neuroprotection". Progress in retinal and eye research (Review). 27 (5): 501–26. doi:10.1016/j.preteyeres.2008.07.002. PMC 2584875Freely accessible. PMID 18725316. 
  178. ^ [needs update] Kogan NM, Mechoulam R (2007). "Cannabinoids in health and disease". Dialogues Clin Neurosci. 9 (4): 413–30. PMC 3202504Freely accessible. PMID 18286801. 
  179. ^ [needs update] Singer HS (2005). "Tourette's syndrome: from behaviour to biology". Lancet Neurol (Review). 4 (3): 149–59. doi:10.1016/S1474-4422(05)01012-4. PMID 15721825. 
  180. ^ [needs update] Robertson MM (2000). "Tourette syndrome, associated conditions and the complexities of treatment". Brain (Review). 123 (3): 425–62. doi:10.1093/brain/123.3.425Freely accessible. PMID 10686169. 
  181. ^ Iuvone T, Esposito G, De Filippis D, et al. (2009). "Cannabidiol: A promising drug for neurodegenerative disorders?". CNS neuroscience & therapeutics (Review). 15 (1): 65–75. doi:10.1111/j.1755-5949.2008.00065.x. PMID 19228180. 
  182. ^ [needs update] Carter GT, Rosen BS (2001). "Marijuana in the management of amyotrophic lateral sclerosis". The American journal of hospice & palliative care (Review). 18 (4): 264–70. doi:10.1177/104990910101800411. PMID 11467101. 
  183. ^ [needs update] Ashton CH, Moore PB, Gallagher P, Young AH (2005). "Cannabinoids in bipolar affective disorder: A review and discussion of their therapeutic potential". Journal of psychopharmacology (Review, meta-analysis). 19 (3): 293–300. doi:10.1177/0269881105051541. PMID 15888515. 
  184. ^ Ethan B Russo (5 September 2013). Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. Routledge. p. 191. ISBN 978-1-136-61493-4. 
  185. ^ [needs update] Di Carlo G, Izzo AA (2003). "Cannabinoids for gastrointestinal diseases: potential therapeutic applications". Expert Opinion on Investigational Drugs (Review). 12 (1): 39–49. doi:10.1517/13543784.12.1.39. PMID 12517253. 
  186. ^ Koppel, Barbara S., MD; et al. (29 April 2014). "Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders". Neurology. 82 (17): 1556–1563. doi:10.1212/wnl.0000000000000363. PMC 4011465Freely accessible. PMID 24778283. 
  187. ^ Naftali T, Mechulam R, Lev LB, Konikoff FM (2014). "Cannabis for inflammatory bowel disease". Dig Dis (Review). 32 (4): 468–74. doi:10.1159/000358155. PMID 24969296. 
  188. ^ a b Mechoulam R, Peters M, Murillo-Rodriguez E, Hanus LO (August 2007). "Cannabidiol--recent advances". Chem. Biodivers. (Review). 4 (8): 1678–92. doi:10.1002/cbdv.200790147. PMID 17712814. 
  189. ^ Campos AC, Moreira FA, Gomes FV, Del Bel EA, Guimarães FS (December 2012). "Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders". Philos. Trans. R. Soc. Lond., B, Biol. Sci. (Review). 367 (1607): 3364–78. doi:10.1098/rstb.2011.0389. PMC 3481531Freely accessible. PMID 23108553. 

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