Medical cannabis

A dried bud of cannabis, which can be used for medical therapy

Medical cannabis, or medical marijuana, can refer to the use of cannabis and its cannabinoids to treat disease or improve symptoms; however, there is no single agreed upon definition.[1][2] The use of cannabis as a medicine has not been rigorously scientifically tested, often due to production restrictions and other governmental regulations.[3] There is limited evidence suggesting cannabis can be used to reduce nausea and vomiting during chemotherapy, to improve appetite in people with HIV/AIDS, and to treat chronic pain and muscle spasms.[4][5][6] Its use for other medical applications, however, is insufficient for conclusions about safety or efficacy.

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] Its current use is controversial. The American Medical Association, the Minnesota Medical Association, the American Society of Addiction Medicine, and other medical organizations have issued statements opposing its use for medicinal purposes.[8][9][10] The American Academy of Pediatrics states that while cannabinoids may have potential as therapy for a number of medical conditions, they do not recommend it until more research is done. They, along with the American Medical Association and the Minnesota Medical Association, call for moving cannabis out of DEA Schedule I to facilitate this research.[10][11][12]

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 certain countries, including Austria, Canada, Czech Republic, Finland, Germany, Israel, Italy, the Netherlands (where it is also legal recreationally), Portugal and Spain. Australia is currently in the process of passing a law which would allow the use of marijuana for medical and scientific purposes.[13][14] In the United States, federal law outlaws all cannabis use, while 25 states and the District of Columbia no longer prosecute individuals for the possession or sale of medical marijuana, as long as the individuals are in compliance with the state's medical marijuana sale regulations. However, an appeals court ruled in January 2014 that a 2007 Ninth Circuit ruling remains binding in relation to the ongoing illegality, in federal legislative terms, of Californian cannabis dispensaries, reaffirming the impact of the federal Controlled Substances Act.[15]

Classification

Many different cannabis strains are collectively called "medical cannabis." Since many varieties of 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.[16] In comparison, typical government-approved medications contain only 1 or 2 chemicals.[16] The number of active chemicals in cannabis is one reason why treatment with cannabis is difficult to classify and study.[16]

Using a THC-dominant strain/breed can show anecdotally that it may help people with insomnia (and other sleep disorders) get more rest, and that it could reduce the severity of tics in people with Tourette syndrome, yet the same strain could induce psychosis in a person with a psychiatric disorder.[17] 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 limits THC's psychoactive effects[18]) of cannabis products.[19]

Medical uses

Cannabis as illustrated in Köhler's book of medicinal plants from 1897

Medical cannabis has several potential beneficial effects.[5] Evidence is moderate that it helps in chronic pain and muscle spasms.[5] Lesser evidence supports its use for reducing nausea during chemotherapy, improving appetite in HIV/AIDS, improving sleep, and improving tics in Tourettes syndrome.[5] When usual treatments are ineffective, cannabinoids have also been recommended for anorexia, arthritis, migraine, and glaucoma.[20]

The National Institute on Drug Abuse (NIDA) states that "so far, researchers have not conducted enough large-scale clinical trials that show that the benefits of the marijuana plant (as opposed to its cannabinoid ingredients) outweigh its risks in patients it is meant to treat."[21] In 2015 American Society of Addiction Medicine wrote that "legalization of cannabis in some states but not others provides a unique opportunity for a thorough investigation into the societal and public health impact of broader cannabis use"[22] American Medical Association in 2015 stated that there is not enough large-scale studies on cannabis,[23] while Office of National Drug Control Policy "opposes legalization of marijuana and other drugs because legalization would increase the availability and use of illicit drugs, and pose significant health and safety risks to all Americans, particularly young people."[24] The FDA finds that cannabis does not meet the criteria for accepted medical use due to lack of evidence regarding safety and the high risk of abuse.[25]

It is recommended that cannabis use be stopped in pregnancy.[26]

Nausea and vomiting

Medical cannabis is somewhat effective in chemotherapy-induced nausea and vomiting (CINV)[4][20] and may be a reasonable option in those who do not improve following preferential treatment.[27] Comparative studies have found cannabinoids to be more effective than some conventional antiemetics such as prochlorperazine, promethazine, and metoclopramide in controlling CINV,[28] but these are used less frequently because of side effects including dizziness, dysphoria, and hallucinations.[29][30] Long-term cannabis use may cause nausea and vomiting, a condition known as cannabinoid hyperemesis syndrome.[31]

A 2010 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".[32]

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.[33]

Pain

Cannabis appears to be somewhat effective for the treatment of chronic pain, including pain caused by neuropathy and possibly that due to fibromyalgia and rheumatoid arthritis.[34][35] A 2009 review states it was unclear if the benefits were greater than the risks,[34] while a 2011 review considered it generally safe for this use.[35] In palliative care the use appears safer than that of opioids.[36] 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.[37] 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.[38] Another 2015 systematic review and meta-analysis found limited evidence that medical cannabis was effective for neuropathic pain when combined with traditional analgesics.[39]

Neurological problems

The efficacy of cannabis in treating neurological problems, including multiple sclerosis, epilepsy, and movement problems, is not clear.[40] 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.[41] Evidence also suggests that oral cannabis extract is effective for reducing patient-centered measures of spasticity.[42] A trial of cannabis is deemed to be a reasonable option if other treatments have not been effective.[4] Its use for MS is approved in ten countries.[4][43] A 2012 review found no problems with tolerance, abuse or addiction.[44]

Posttraumatic stress disorder

There is tentative evidence that medical cannabis is effective at reducing posttraumatic stress disorder symptoms, but, as of as of 2015, there is insufficient evidence to confirm its effectiveness for this condition.[45]

Adverse effects

American medical hashish

Medical use

There is insufficient data to draw strong conclusions about the safety of medical cannabis.[46] Typically, adverse effects of medical cannabis use are not serious.[4] These include: tiredness, dizziness, cardiovascular and psychoactive effects. 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 vehicle or operating machinery may be impaired until a tolerance is developed.[27] Although supporters of medical cannabis say that it is safe,[46] further research is required to assess the long-term safety of its use.[29][47]

Recreational use

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.[48] Psychotic episodes are well-documented and typically resolve within minutes or hours. There have been few reports of symptoms lasting longer.[49][50]

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.[51] In 129,000 cases, cannabis was the only implicated drug.[52][53]

Effects of chronic use may include bronchitis, a cannabis dependence syndrome, and subtle impairments of attention and memory. These deficits persist while chronically intoxicated.[48] There is little evidence that cognitive impairments persist in adult abstinent cannabis users.[54] 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.[53] 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.[55]

There has been a limited amount of studies that have looked at the effects of smoking cannabis on the respiratory system.[56] Chronic heavy marijuana smoking is associated with coughing, production of sputum, wheezing, coughing, and other symptoms of chronic bronchitis.[48] Regular cannabis use has not been shown to cause significant abnormalities in lung function.[57]

Cannabis smoke contains thousands of organic and inorganic chemical compounds. This tar is chemically similar to that found in tobacco smoke,[58] and over fifty known carcinogens have been identified in cannabis smoke,[59] including; nitrosamines, reactive aldehydes, and polycylic hydrocarbons, including benz[a]pyrene.[60] 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.[57] Combustion products are not present when using a vaporizer, consuming THC in pill form, or consuming cannabis foods.

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.[61] 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.[62] 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.[63] 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.[64]

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.[65] About 9% of those who experiment with marijuana eventually become dependent. The rate goes up to 1 in 6 among those who begin use as adolescents, and one-quarter to one-half of those who use it daily according to a NIDA review.[53] 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.[66]

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".[67]

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.[68] A second systematic review focused on neuroimaging studies found little evidence supporting an effect of cannabis use on brain structure and function.[69] 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.[70]

Impact on psychosis

Exposure to THC can cause acute transient psychotic symptoms in healthy individuals and people with schizophrenia.[18]

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.[71] A 2005 meta analysis concluded that adolescent use of cannabis increases the risk of psychosis, and that the risk is dose-related.[72] 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.[73] 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.[74]

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.[75][76] A 2005 paper from the Dunedin study suggested an increased risk in the development of psychosis linked to polymorphisms in the COMT gene.[77] However, a more recent study cast doubt on the proposed connection between this gene and the effects of cannabis on the development of psychosis.[78]

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.[79]

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.[80] 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[81][82] – 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.[83]

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.[67]

Physical and chemical properties

Some forms of medicinal cannabis.

Smoking is the means of administration of cannabis for many consumers,[84] 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.[84]

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".[84]

The U.S. 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.[85] 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."[85]

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.[86] 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."[87] 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.[88] Cannabis is one of the 50 "fundamental" herbs in traditional Chinese medicine.[89]

The Ebers Papyrus (ca. 1550 BCE) from Ancient Egypt describes medical cannabis.[90] The ancient Egyptians used hemp (cannabis) in suppositories for relieving the pain of hemorrhoids.[91]

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.[92]

The Ancient Greeks used cannabis to dress wounds and sores on their horses,[93] and in humans, dried leaves of cannabis were used to treat nose bleeds, and cannabis seeds were used to expel tapeworms.[93]

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.[94]

Modern

An Irish physician, William Brooke O'Shaughnessy, is credited with introducing the therapeutic use of cannabis to Western medicine, to help treat muscle spasms, stomach cramps and general pain.[95]

Albert Lockhart and Manley West began studying in 1964 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.[96]

In the 1970s, a synthetic version of THC was produced and approved for use in the United States as the drug Marinol.[97]

Voters in eight US states showed their support for cannabis prescriptions or recommendations given by physicians between 1996 and 1999, going against policies of the federal government.[98] As of mid-2014, 23 states plus the District of Columbia have passed medical marijuana laws,[99] and in the November elections three more states (total 26) joined the burgeoning group, many of which are as yet in conflict with conditions set forth by the federal government.

On 15 June 2015, the Colorado Supreme Court ruled that even though medical marijuana is legal in Colorado, employers can fire workers who use marijuana for medical reasons because it violates federal law. The case involved a quadriplegic who had a doctor’s authorization to smoke medical marijuana, but who was fired by Dish Network in 2010 after failing a company drug test.[100]

Society and culture

Legal status

Worldwide laws on cannabis possession for medical purposes as of 2016
  Legal or essentially legal
  Decriminalized
  Illegal but often unenforced
  Illegal
  No information

Medical use of cannabis or preparation containing THC as the active substance is legalized in Austria, Belgium, Canada, Chile, Colombia Czech Republic, Finland, Israel, Netherlands, Spain, the UK and some states in the US, although it is illegal under US federal law.

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:[101]

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

The convention thus allows countries to outlaw cannabis for all non-research purposes but lets nations choose to allow medical and scientific purposes if they believe total prohibition is not the most appropriate means of protecting health and welfare. The convention requires that states that permit the production or use of medical cannabis must operate a licensing system for all cultivators, manufacturers, and distributors and ensure that the total cannabis market of the state shall not exceed that required "for medical and scientific purposes."[101]

Programs

As of 2014, 23 states plus the District of Columbia have passed medical cannabis laws,[99] but its use remains illegal by federal law.[43] In 1978 the US government created a program called the Compassionate Investigational New Drug program which dispenses cannabis cigarettes to 20 people with debilitating conditions[7] including glaucoma and a rare bone disease. The program was "closed to new candidates in 1991",[7] but as of 2013, allowed four people previously in the program to continue receiving medical cannabis.

Economics

Distribution

Medical marijuana dispensary

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 23 states and the District of Columbia that permit the use of medical cannabis.[4][102] Marijuana vending machines for selling or dispensing cannabis are in use in the United States and are planned to be used in Canada.[103] In 2014, the startup Meadow began offering on-demand delivery of medical marijuana in the San Francisco Bay Area, through their mobile app.[104]

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.[105] However, the New Mexico Court of Appeals has ruled that workers' compensation insurance must pay for marijuana prescribed as part of the state's Medical Cannabis Program.[106]

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.[107] The report authors suggested rather that medical cannabis users occupied a "continuum" between medical and nonmedical use.[107]

Brand names

In the U.S., 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, and nabilone, a synthetic cannabinoid, is Schedule II, indicating high potential for side effects and addiction.[83] Nabiximols, an oromucosal spray derived from two strains of Cannabis sativa and containing THC and CBD,[83] is not approved in the U.S., 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 U.S. are underway.[4] It is also approved in several European countries for overactive bladder and vomiting.[83] 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.[108]

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]

Research

"Victoria", the United States' first legal medical marijuana plant grown by The Wo/Men's Alliance for Medical Marijuana.

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.[109]

United States

The Schedule I classification of cannabis in the US makes the study of medical cannabis difficult there.[4] As of 2016, most cannabis-related research in the United States is on components chemicals in the cannabis plant, and not on the whole plant.[16] To do research on the effects of the whole plant, a medical research organization would need to propose a project then submit their proposal for United States government review.[16] For the research to proceed, the Food and Drug Administration would need to approve the plan for that project, then the Drug Enforcement Administration would need to grant a Schedule I Controlled Substances permit for research, then the National Institute on Drug Abuse would need to provide the actual cannabis which would be studied.[16] Any of the involved government agencies could halt a cannabis research project at any time, and consequently, medical research on cannabis has not advanced in the United States for many years.[16]

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.[110][111] Laboratory experiments have suggested that cannabis and cannabinoids have anticarcinogenic and antitumor effects,[112] including a potential effect on breast- and lung-cancer cells.[113] 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.[114] 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.[115]

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".[116]

There is no good evidence that cannabis use helps reduce the risk of getting cancer.[116] Whether smoking cannabis increases the risk is difficult to establish, since it is usually smoked mixed with tobacco – a known carcinogen – and this complicates research.[116]

Dementia

Cannabinoids have been proposed to have the potential for lessening the effects of Alzheimer's disease.[117] 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".[118] 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".[119]

Diabetes

There is emerging evidence that cannabidiol may help slow cell damage in diabetes mellitus type 1.[120] 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".[121] GW is studying tetrahydrocannabivarin for type 2 diabetes.[122]

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".[123] The mechanisms by which cannabis may be effective in the treatment of epilepsy remain unclear.[124]

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[125] - 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).[126]

Epidiolex, a cannabis-based product developed by GW Pharmaceuticals for experimental treatment of epilepsy, underwent stage-two trials in the US in 2014.[127] Pairs of phase 3 trials for Dravet syndrome and Lennox-Gastaut syndrome have begun and should be completed in 2015.[128][129] They are also running a phase 2 study of non-psychoactive cannabidivarin.[130]

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".[131] As of 2008 relatively little research had been done concerning therapeutic effects of cannabinoids on the eyes.[132]

Tourette syndrome

A 2007 review of the history of medical cannabis said cannabinoids showed potential therapeutic value in treating Tourette syndrome (TS).[133] 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;[134] a 2000 review said other studies had shown that cannabis "has no effects on tics and increases the individuals inner tension".[135]

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).[84] 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".[84] The sample size was small and a high number of individuals either dropped out of the study or were excluded.[84] 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.[84] The authors of the original studies acknowledged few significant results after Bonferroni correction.[84]

Cannabinoid medication might be useful in the treatment of the symptoms in patients with TS,[84] 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".[84]

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.[136] 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.[137]

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.[138]

Cannabinoids have been proposed for the treatment of primary anorexia nervosa, but have no measurable beneficial effect.[139] The authors of a 2003 paper argued that cannabinoids might have useful future clinical applications in treating digestive diseases.[140] Laboratory experiments have shown that cannabinoids found in marijuana may have analgesic and anti-inflammatory effects.[113]

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.[141]

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.[142]

A 2007 review said cannabidiol had shown potential to relieve convulsion, inflammation, cough, congestion and nausea, and to inhibit cancer cell growth.[143] Preliminary studies have also shown potential over psychiatric conditions such as anxiety, depression, and psychosis.[144] Because cannabidiol relieves the aforementioned symptoms, cannabis strains with a high amount of CBD may benefit people with multiple sclerosis or frequent anxiety attacks.[41][143]

See also

References

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