Cannabis, also known as marijuana

Cannabis, also known as marijuana[2] (from the Mexican Spanish marihuana), and by numerous other names,a[›] is a preparation of the Cannabis plant intended for use as a psychoactive drug and as medicine.[3][4][5] Pharmacologically, the principal psychoactive constituent of cannabis is tetrahydrocannabinol (THC); it is one of 483 known compounds in the plant,[6] including at least 84 other cannabinoids, such as cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabivarin (THCV).[7][8] and cannabigerol (CBG).
Cannabis is often consumed for its psychoactive and physiological effects which can include heightened mood or euphoria, relaxation,[9] and increase in appetite.[10] Unwanted side-effects can sometimes include decrease in short-term memory, dry mouth, impaired motor skills, reddening of the eyes,[9] and feelings of paranoia or anxiety.[11]
Contemporary uses of cannabis are as a recreational or medicinal drug, and as part of religious or spiritual rites; the earliest recorded uses date from the 3rd millennium BC.[12] Since the early 20th century cannabis has been subject to legal restrictions with the possession, use, and sale of cannabis preparations containing psychoactive cannabinoids currently illegal in most countries of the world; the United Nations has said that cannabis is the most-used illicit drug in the world.[13][14] In 2004, the United Nations estimated that global consumption of cannabis indicated that approximately 4% of the adult world population (162 million people) used cannabis annually, and
that approximately 0.6% (22.5 million) of people used cannabis daily.[15]
Contents  [hide]
1 Effects
1.1 Psychoactive classification
1.2 Medical use
1.3 Other effects
1.3.1 Addictiveness
1.3.2 Adolescent brain development
1.3.3 Gateway drug theory
1.3.4 Memory, learning, and intelligence
1.3.5 Obesity
1.3.6 Pulmonary function
1.3.7 Effect on lifespan
2 Varieties and strains
2.1 Concentration of psychoactive ingredients
3 Preparations
3.1 Whole flower and leaf
3.2 Kief
3.3 Hashish
3.4 Tincture
3.5 Hash oil
3.6 Infusions
3.7 Adulterated cannabis
4 Consumption
4.1 Methods of consumption
4.2 Mechanism of action
4.3 Detection of consumption
5 Production
5.1 Price
6 History
7 Legal status
7.1 Constraints on open research
8 See also
9 Footnotes
10 Citations
11 Further reading
12 External links
Effects

Main article: Effects of cannabis


Main short-term physical effects of cannabis
Cannabis has psychoactive and physiological effects when consumed.[16] The immediate desired effects from consuming cannabis include relaxation and mild euphoria (the "high" or "stoned" feeling), while some immediate undesired side-effects include a decrease in short-term memory, dry mouth, impaired motor skills and reddening of the eyes.[17] Aside from a subjective change in perception and, most notably, mood, the most common short-term physical and neurological effects include increased heart rate, increased appetite and consumption of food lowered blood pressure, impairment of short-term and working memory,[18][19] psychomotor coordination, and concentration. Long-term effects are less clear.[20] In humans aside from respiratory damage when smoked,[21] relatively few adverse clinical health effects have been documented from chronic cannabis use.[22][23]
Psychoactive classification
Main article: Psychoactive effects
While many psychoactive drugs clearly fall into the category of either stimulant, depressant, or hallucinogen, cannabis exhibits a mix of all properties, perhaps leaning the most towards hallucinogenic or psychedelic properties, though with other effects quite pronounced as well. THC is typically considered the primary active component of the cannabis plant; various scientific studies have suggested that certain other cannabinoids like CBD may also play a significant role in its psychoactive effects.[24][25][26]
Medical use


Medical cannabis
Main article: Medical cannabis
Cannabis used medically has several well-documented beneficial effects.[27] Among these are: the amelioration of nausea and vomiting, stimulation of hunger in chemotherapy and AIDS patients, lowered intraocular eye pressure (shown to be effective for treating glaucoma), as well as general analgesic effects (pain reliever).b[›] Less confirmed individual studies also have been conducted indicating cannabis to be beneficial to a gamut of conditions running from multiple sclerosis to depression. Synthesized cannabinoids are also sold as prescription drugs, including Marinol (dronabinol in the United States and Germany) and Cesamet (nabilone in Canada, Mexico, the United States and the United Kingdom).b[›]


Cannabis as illustrated in Köhler's Medicinal Plants book from 1897
Currently, the U.S. Food and Drug Administration (FDA) has not approved smoked cannabis for any condition or disease in the United States, largely because the FDA claims good quality scientific evidence for its use from U.S. studies is lacking.[28] Others, for example American Society of Addiction Medicine, argue that there is no "Medical marijuana" because the plant parts in question fails to meet the standard requirements for approved medicines.[29]
Eighteen states and the District of Columbia have legalized cannabis for medical use in state laws.[30][31] The United States Supreme Court has ruled in United States v. Oakland Cannabis Buyers' Coop and Gonzales v. Raich that it is the federal government that has the right to regulate and criminalize cannabis, even for medical purposes and even if the state legalize it. Canada, Spain, The Netherlands, France,[32] Italy, Czech Republic[33] and Austria have legalized some form of cannabis or extract containing a low dose of THC for medicinal use.[34] Recently, Uruguay has taken steps towards legalising and regulating the production and sale of the drug.[35]
Other effects
Main article: Long-term effects of cannabis
Though the long-term effects of cannabis have been studied, there remains much to be concluded. Many studies have investigated whether long-term use of cannabis can cause or contribute to the development of illnesses such as heart disease, bipolar disorder, depression, mood swings or schizophrenia. Its effects on intelligence, memory, respiratory functions and the possible relationship of cannabis use to mental disorders[36] such as schizophrenia,[37] psychosis,[38] depersonalization disorder[39] and depression[40] are still under discussion.[41]
Both advocates and opponents of cannabis are able to call upon numerous scientific studies supporting their respective positions.[42] For instance, while cannabis has been implicated in the development of various mental disorders in some studies, these studies differ widely as to whether cannabis use is the cause of the mental problems displayed in heavy users, whether the mental problems are exacerbated by cannabis use, or whether both the cannabis use and the mental problems are the effects of some other cause.[42]
It has been pointed out that as cannabis use has risen, rates of schizophrenia have not risen in tandem. Lester Grinspoon argues that the cannabis-causes-psychosis argument is disproved by the lack of "even a blip in the incidence of schizophrenia in the US after millions of people started smoking marijuana in the 1960s". Worldwide prevalence of schizophrenia is about 1% in adults; the amount of cannabis use in any given country seems to have no effect on that rate.[43]
A medical study published in 2009 taken by the Medical Research Council in London, concluded recreational cannabis users do not release significant amounts of dopamine from an oral THC dose equivalent to a standard cannabis cigarette, and that therefore cannabis use could leave users vulnerable to psychosis.[44]
Positive effects of the drug have also been observed. For example, in a recent study researchers found that compared with those who did not smoke cannabis, long-term cannabis smokers were roughly 62% less likely to develop head and neck cancers.[45]
Addictiveness
Main article: Cannabis dependence
Dr. Jack E. Henningfield of NIDA ranked the relative addictiveness of 6 substances (cannabis, caffeine, cocaine, alcohol, heroin and nicotine). Cannabis ranked least addictive, with caffeine the second least addictive and nicotine the most addictive.[46]
Adolescent brain development
A 35-year cohort study published August 2012 in Proceedings of the National Academy of Sciences and funded partly by NIDA and other NIH institutes reported an association between long-term cannabis use and neuropsychological decline, even after controlling for education.[47] It was found that the persistent, dependent use of marijuana before age 18 was associated with lasting harm to a person's intelligence, attention and memory, and were suggestive of neurological harm from cannabis. Quitting cannabis did not appear to reverse the loss. However, individuals who started cannabis use after the age of 18 did not show similar declines.[48]
Results of the study came into question when in a new analysis, published January 2013 in Proceedings of the National Academy of Sciences, researchers from Oslo's Ragnar Frisch Center for Economic Research noted other differences among the study group including education, occupation and other socioeconomic factors that showed the same effect on IQ as cannabis use. From the abstract: "existing research suggests an alternative confounding model based on time-varying effects of socioeconomic status on IQ. A simulation of the confounding model reproduces the reported associations from the [August 2012 study], suggesting that the causal effects estimated in Meier et al. are likely to be overestimates, and that the true effect could be zero".[49][50] The researchers pointed to three other studies which showed cannabis did not cause a decline in IQ.[51] The studies showed that heavy smokers had clear reductions in IQ, but they were not permanent.[52][51]
A July 2012 article in Brain reported neural-connectivity impairment in some brain regions following prolonged heavy cannabis use initiated in adolescence or young adulthood.[53]
A 2012 study conducted by researchers at UC San Diego failed to show deleterious effects on the adolescent brain from cannabis use. Researchers looked at brain scans taken before-and-after of subjects aged 16–20 years who consumed alcohol and compared them to subjects of the same age who used cannabis instead. The 92 person study was conducted over an eighteen-month period. While teen alcohol use resulted in observable reduced white matter brain tissue health, cannabis use was not linked to any structural damage. The study did not measure the subjects' cognitive performance. Publication is scheduled for April 2013 in Alcoholism: Clinical and Experimental Research.[54]
Gateway drug theory
Further information: Gateway drug theory
Since the 1950s, United States drug policies have been guided by the assumption that trying cannabis increases the probability that users will eventually use "harder" drugs.[55] This hypothesis has been one of the central pillars of anti-cannabis drug policy in the United States,[56] though the validity and implications of this hypothesis are hotly debated.[55] Studies have shown that tobacco smoking is a better predictor of concurrent illicit hard drug use than smoking cannabis.[57]
No widely accepted study has ever demonstrated a cause-and-effect relationship between the use of cannabis and the later use of harder drugs like heroin and cocaine. However, the prevalence of tobacco cigarette advertising and the practice of mixing tobacco and cannabis together in a single large joint, common in Europe, are believed to be cofactors in promoting nicotine dependency among young people trying cannabis.[58]
A 2005 comprehensive review of the literature on the cannabis gateway hypothesis found that pre-existing traits may predispose users to addiction in general, the availability of multiple drugs in a given setting confounds predictive patterns in their usage, and drug sub-cultures are more influential than cannabis itself. The study called for further research on "social context, individual characteristics, and drug effects" to discover the actual relationships between cannabis and the use of other drugs.[59]
Some studies state that while there is no proof for this gateway hypothesis,[60] young cannabis users should still be considered as a risk group for intervention programs.[61] Other findings indicate that hard drug users are likely to be "poly-drug" users, and that interventions must address the use of multiple drugs instead of a single hard drug.[62]
Another gateway hypothesis is that a gateway effect may be detected as a result of the "common factors" involved with using any illegal drug. Because of its illegal status, cannabis users are more likely to be in situations which allow them to become acquainted with people who use and sell other illegal drugs.[63][64] By this argument, some studies have shown that alcohol and tobacco may be regarded as gateway drugs.[57] However, a more parsimonious explanation could be that cannabis is simply more readily available (and at an earlier age) than illegal hard drugs, and alcohol/tobacco are in turn easier to obtain earlier than cannabis (though the reverse may be true in some areas), thus leading to the "gateway sequence" in those people who are most likely to experiment with any drug offered.[55]
A 2008 study at Karolinska Institute suggested that young rats treated with THC received an increased motivation for drug use, heroin in the study, under conditions of stress.[65][66]
A 2010 study published in the Journal of Health and Social Behavior found that the main factors in users moving on to other drugs were age, wealth, unemployment status, and psychological stress. The study concluded that there is no validity to the "gateway theory" and that drug use is more closely tied to a person's life situation, although cannabis users are more likely to use other drugs.[67]
Memory, learning, and intelligence
Researchers from the University of California, San Diego School of Medicine failed to show substantial, systemic neurological effects from long-term recreational use of cannabis. Their findings were published in the July 2003 issue of the Journal of the International Neuropsychological Society.[68] The research team, headed by Dr Igor Grant, found that cannabis use did affect perception, but did not cause permanent brain damage. Researchers looked at data from 15 previously published controlled studies involving 704 long-term cannabis users and 484 nonusers. The results showed long-term cannabis use was only marginally harmful on the memory and learning. Other functions such as reaction time, attention, language, reasoning ability, perceptual and motor skills were unaffected. The observed effects on memory and learning, they said, showed long-term cannabis use caused "selective memory defects", but that the impact was "of a very small magnitude".[69]
Obesity
According to a 2011 study published in the American Journal of Epidemiology, obesity is lower in cannabis users than in nonusers. Authors of the study looked at data from two representative epidemiological studies for US citizens aged 18 and over.[70] Obesity rates in those who didn't use cannabis were 22% and 25.3%. Study participants who smoked cannabis at least three times a week had obesity rates of 14.3% and 17.2%.[71] The association between cannabis smoking and lower risk of obesity remained strong after factors such as cigarette smoking, age and gender, which could have an impact on obesity, were taken into account.[72]
Cannabis is known for inducing hunger, but two cannabinoids, THCV and cannabidiol, were found to have an appetite suppressing effect. In animal tests, the drug also had an impact on the level of fat in the body as well as its response to insulin. Cannabis compounds were shown to raise metabolism in rats, leading to lower levels of fat in the liver and lower cholesterol. Human trials are being conducted to find a drug targeting obesity-related diseases.[73]
Pulmonary function
See also: Cannabis-associated respiratory disease
A 2012 study published in JAMA and funded by National Institutes of Health looked at a population of over 5,115 American men and women to see whether smoked cannabis has effects on the pulmonary system similar to those from smoking tobacco. The researchers found "Occasional and low cumulative marijuana use was not associated with adverse effects on pulmonary function." Smoking an average of one joint a day for seven years, they found, did not worsen pulmonary health.[74][75]
Dr. Donald Tashkin commented on the study, saying it confirmed findings from several other studies[76] showing "that essentially there is no significant relationship between marijuana exposure and impairment in lung function." He noted despite containing similar noxious ingredients, one reason cannabis smoke may not be as harmful as tobacco smoke may be due to the anti-inflammatory effects of THC. "We don't know for sure but a very reasonable possibility is that THC may actually interfere with the development of chronic obstructive pulmonary disease", Tashkin elaborated. In his own research, Tashkin unexpectedly found that smoking up to three joints a day appeared to have no decrease in lung function. Tashkin said, "I think that the bottom line is that there does not appear to be any negative impact on lung function of marijuana smoking."[77][78]
Effect on lifespan
Due to the low number of studies conducted on cannabis, there is not enough evidence to reach a conclusion regarding the effect of cannabis on overall risk of death or lifespan.[79] Cannabis has not been proven to have caused deaths but an association is currently being researched."[80][81] There are medical reports of occasional infarction, stroke and other cardiovascular side effects.[82] Marijuana's cardiovascular effects are not associated with serious health problems for most young, healthy users.[82]
According to a 2006 United Kingdom government report, using cannabis is much less dangerous than tobacco, prescription drugs, and alcohol in social harms, physical harm, and addiction.[83] Harvard's Dr. Lester Grinspoon, has stated in a newspaper editorial that "herbal marijuana is remarkably nontoxic".[84]
Dr. Stephen Ross, a professor of child psychiatry and addiction at New York University's Tish Hospital explains reports of some cannabis-related deaths: "deaths associated with the drug are the result of activities undertaken while on the drug, such as driving under the influence".[85] The US Substance Abuse and Mental Health Services Administration stated in its July 2001 report from the Drug Abuse Warning Network Mortality Data: "Marijuana is rarely the only drug involved in a drug abuse death. Thus, in most cases, the proportion of marijuana-involved cases labeled as 'One drug' (i.e., marijuana only) will be zero or nearly zero".[86][87]
THC, the principal psychoactive constituent of the cannabis plant, has an extremely low toxicity. A 1998 study published in The Lancet reports: "There are no confirmed published cases worldwide of human deaths from cannabis poisoning, and the dose of THC required to produce 50% mortality in rodents is extremely high compared with other commonly used drugs".[88] Cannabis researcher Dr. Paul Hornby said that "you have to smoke something like 15,000 joints in 20 minutes to get a toxic amount of delta-9 tetrahydrocannibinol".[89] Recorded fatalities resulting from cannabis overdose in animals are generally only after intravenous injection of hashish oil.[90]
Evaluations of safety and tolerability of Sativex, a pharmacological preparation made from cannabinoids, have concluded that it is indeed well-tolerated and useful.[91]
Many studies have looked at the effects of smoking cannabis on the respiratory system. Cannabis smoke contains thousands of organic and inorganic chemical compounds. This tar is chemically similar to that found in tobacco smoke or cigars.[92] Over fifty known carcinogens have been identified in cannabis smoke.[93] These include nitrosamines, reactive aldehydes, and polycylic hydrocarbons, including benz[a]pyrene.[94] Marijuana smoke was listed as a cancer agent in California in 2009.[95] A 2012 literature review by the British Lung Foundation identified cannabis smoke as a carcinogen and also found awareness of the danger was low compared with the high awareness of the dangers of smoking tobacco particularly among younger users. Other observations include increased risk from each marijuana cigarette due to drawing in large puffs of smoke and holding them; lack of research on the effect of cannabis smoke alone due to common mixing of cannabis and tobacco and frequent tobacco use by cannabis users; low rate of addiction compared to tobacco; and episodic nature of cannabis use compared to steady frequent smoking of tobacco.[96] The review has been criticized by David Nutt.[97] In contrast to the British Lung Foundation report, a large 2006 study found no lung cancer link to marijuana, even in heavy smokers, when adjusting for several confounders including cigarette smoking and alcohol use.[98]
Varieties and strains



Types of Cannabis
Cannabis indica may have a CBD:THC ratio 4–5 times that of Cannabis sativa. Cannabis strains with relatively high CBD:THC ratios are less likely to induce anxiety than vice versa. This may be due to CBD's antagonistic effects at the cannabinoid receptors, compared to THC's partial agonist effect. CBD is also a 5-HT1A receptor agonist, which may also contribute to an anxiolytic effect.[99] This likely means the high concentrations of CBD found in Cannabis indica mitigate the anxiogenic effect of THC significantly.[99] The effects of sativa are well known for its cerebral high, hence used daytime as medical cannabis, while indica are well known for its sedative effects and preferred night time as medical cannabis.[99]
Concentration of psychoactive ingredients
According to the United Nations Office on Drugs and Crime (UNODC), "the amount of THC present in a cannabis sample is generally used as a measure of cannabis potency."[100] The three main forms of cannabis products are the flower, resin (hashish), and oil (hash oil). The UNODC states that cannabis often contains 5% THC content, resin "can contain up to 20% THC content", and that "Cannabis oil may contain more than 60% THC content."[100]
A scientific study published in 2000 in the Journal of Forensic Sciences (JFS) found that the potency (THC content) of confiscated cannabis in the United States (US) rose from "approximately 3.3% in 1983 and 1984", to "4.47% in 1997". It also concluded that "other major cannabinoids (i.e., CBD, CBN, and CBC)" (other chemicals in cannabis) "showed no significant change in their concentration over the years".[101] More recent research undertaken at the University of Mississippi's Potency Monitoring Project has found that average THC levels in cannabis samples between 1975 and 2007 have steadily increased.[102] From example THC levels in 1985 averaged 3.48% by 2006 this had increased to an average of 8.77%.[102]
Australia's National Cannabis Prevention and Information Centre (NCPIC) states that the buds (flowers) of the female cannabis plant contain the highest concentration of THC, followed by the leaves. The stalks and seeds have "much lower THC levels".[103] The UN states that the leaves can contain ten times less THC than the buds, and the stalks one hundred times less THC.[100]
After revisions to cannabis rescheduling in the UK, the government moved cannabis back from a class C to a class B drug. A purported reason was the appearance of high potency cannabis. They believe skunk accounts for between 70 and 80% of samples seized by police[104] (despite the fact that skunk can sometimes be incorrectly mistaken for all types of herbal cannabis).[105][106] Extracts such as hashish and hash oil typically contain more THC than high potency cannabis flowers.
Preparations


Dried flower



Kief



Hashish



Tincture



Hash oil



Infusion (dairy butter)



Pipe resin

Whole flower and leaf
The terms cannabis or marijuana generally refer to the dried flowers and subtending leaves and stems of the female cannabis plant.[107] This is the most widely consumed form, containing 3% to 22% THC.[108][109] In contrast, cannabis varieties used to produce industrial hemp contain less than 1% THC and are thus not valued for recreational use.[110]
This is the stock material from which all other preparations are derived. It is noted that cannabis or its extracts must be sufficiently heated or dehydrated to cause decarboxylation of its most abundant cannabinoid, tetrahydrocannabinolic acid (THCA), into psychoactive THC.[111]
Kief
Main article: Kief
Kief is a powder, rich in trichomes,[112] which can be sifted from the leaves and flowers of cannabis plants and either consumed in powder form or compressed to produce cakes of hashish.[113] The word "kif" derives from Arabic: كيف kayf, meaning well-being or pleasure.[114]
Hashish
Main article: Hashish
Hashish (also spelled hasheesh, hashisha, or simply hash) is a concentrated resin cake or ball produced from pressed kief, the detached trichromes and fine material that fell off of Cannabis flowers and leaves.[115] It varies in color from black to golden brown depending upon purity and variety of cultivar it was obtained from.[116] It can be consumed orally or smoked.[117]
Tincture
Main article: Green dragon (tincture)
Cannabinoids can be extracted from cannabis plant matter using high-proof spirits (often grain alcohol) to create a tincture, often referred to as Green dragon.[118] Nabiximols is a branded product name from a tincture manufacturing pharmaceutical company.[119]
Hash oil
Main article: Hash oil
Hash oil is obtained from the cannabis plant by solvent extraction, and contains the cannabinoids present in the natural oils of cannabis flowers and leaves.[120] The solvents are evaporated to leave behind a very concentrated oil. Hemp oil is very different from both Hemp seed oil and Cannabis flower essential oil.[121] Owing to its purity, these products are consumed by smoking, vaporizing, eating, or applied topically.
Infusions
There are many varieties of cannabis infusions owing to the variety of non-volatile solvents used. The plant material is mixed with the solvent and then pressed and filtered to express the oils of the plant into the solvent. Examples of solvents used in this process are cocoa butter, dairy butter, cooking oil, glycerine, and skin moisturizers. Depending on the solvent, these may be used in cannabis foods or applied topically.[122]
Adulterated cannabis
Contaminants may be found in hashish obtained from "soap bar"-type sources.[123] The dried flowers of the plant may be contaminated by the plant taking up heavy metals and other toxins from its growing environment,[124] or by the addition of lead or glass beads, used to increase the weight or to make the cannabis appear as if it has more crystal-looking trichomes indicating a higher THC content.[125] Iin the Netherlands, chalk has been used to make cannabis appear to be higher quality.[126] Increasing the weight of hashish products in Germany with lead caused lead intoxication in at least 29 users.[127]
Despite cannabis being generally perceived as a natural or "chemical-free" product,[128] in a recent Australian survey[129] one in four Australians consider cannabis grown indoors under hydroponic conditions to be a greater health risk due to increased contamination, added to the plant during cultivation to enhance the plant growth and quality.
Consumption

Main article: Cannabis consumption


A joint


A forced-air vaporizer. The detachable balloon (top) fills with vapors that are then inhaled.
Methods of consumption
Cannabis is consumed in many different ways:[130]
smoking, most of which involve inhaling vaporized cannabinoids ("smoke") from small pipes, bongs (portable version of hookah with water chamber), paper-wrapped joints or tobacco-leaf-wrapped blunts, roach clips, and other items.[131]
vaporizer heats herbal cannabis to 330–375 °F (166–191 °C), causing the active ingredients to evaporate into a vapor without burning the plant material (the boiling point of THC is 390.4 °F (199.1 °C) at 760 mmHg pressure).[132]
Cannabis tea has relatively small concentrations of THC because THC is an oil (lipophilic) and is only slightly water-soluble (with a solubility of 2.8 mg per liter).[133] Cannabis tea is made by first adding a saturated fat to hot water (e.g. cream or any milk except skim) with a small amount of cannabis.[134]
Mechanism of action
The high lipid-solubility of cannabinoids results in their persisting in the body for long periods of time.[135] Even after a single administration of THC, detectable levels of THC can be found in the body for weeks or longer (depending on the amount administered and the sensitivity of the assessment method).[135] A number of investigators have suggested that this is an important factor in marijuana's effects, perhaps because cannabinoids may accumulate in the body, particularly in the lipid membranes of neurons.[136]
Not until the end of the 20th century was the specific mechanisms of action of THC at the neuronal level studied. Researchers have subsequently confirmed that THC exerts its most prominent effects via its actions on two types of cannabinoid receptors, the CB1 receptor and the CB2 receptor, both of which are G-Protein coupled receptors.[137] The CB1 receptor is found primarily in the brain as well as in some peripheral tissues, and the CB2 receptor is found primarily in peripheral tissues, but is also expressed in neuroglial cells as well.[138] THC appears to alter mood and cognition through its agonist actions on the CB1 receptors, which inhibit a secondary messenger system (adenylate cyclase) in a dose dependent manner. These actions can be blocked by the selective CB1 receptor antagonist SR141716A (rimonabant), which has been shown in clinical trials to be an effective treatment for smoking cessation, weight loss, and as a means of controlling or reducing metabolic syndrome risk factors.[139] However, due to the dysphoric effect of CB1 antagonists, this drug is often discontinued due to these side effects.[140]
Via CB1 activation, THC indirectly increases dopamine release and produces psychotropic effects. Cannabidiol also acts as an allosteric modulator of the mu and delta opioid receptors.[141] THC also potentiates the effects of the glycine receptors.[142] The role of these interactions in the "marijuana high" remains elusive.
Detection of consumption
Main article: Cannabis drug testing
THC and its major (inactive) metabolite, THC-COOH, can be measured in blood, urine, hair, oral fluid or sweat using chromatographic techniques as part of a drug use testing program or a forensic investigation of a traffic or other criminal offense.[143] The concentrations obtained from such analyses can often be helpful in distinguishing active use from passive exposure, elapsed time since use, and extent or duration of use. These tests cannot, however, distinguish authorized cannabis smoking for medical purposes from unauthorized recreational smoking.[144] Commercial cannabinoid immunoassays, often employed as the initial screening method when testing physiological specimens for marijuana presence, have different degrees of cross-reactivity with THC and its metabolites.[145] Urine contains predominantly THC-COOH, while hair, oral fluid and sweat contain primarily THC.[143] Blood may contain both substances, with the relative amounts dependent on the recency and extent of usage.[143]
The Duquenois-Levine test is commonly used as a screening test in the field, but it cannot definitively confirm the presence of cannabis, as a large range of substances have been shown to give false positives Despite this, it is common in the United States for prosecutors to seek plea bargains on the basis of positive D-L tests, claiming them definitive, or even to seek conviction without the use of gas chromatography confirmation, which can only be done in the lab.[146] In 2011, researchers at John Jay College of Criminal Justice reported that dietary zinc supplements can mask the presence of THC and other drugs in urine. Similar claims have been made in web forums on that topic.[147]
Production

Main article: Cannabis cultivation
It is often claimed by growers and breeders of herbal cannabis that advances in breeding and cultivation techniques have increased the potency of cannabis since the late 1960s and early '70s, when THC was first discovered and understood. However, potent seedless cannabis such as "Thai sticks" were already available at that time. Sinsemilla (Spanish for "without seed") is the dried, seedless inflorescences of female cannabis plants. Because THC production drops off once pollination occurs, the male plants (which produce little THC themselves) are eliminated before they shed pollen to prevent pollination. Advanced cultivation techniques such as hydroponics, cloning, high-intensity artificial lighting, and the sea of green method are frequently employed as a response (in part) to prohibition enforcement efforts that make outdoor cultivation more risky. It is often cited that the average levels of THC in cannabis sold in United States rose dramatically between the 1970s and 2000, but such statements are likely skewed because of undue weight given to much more expensive and potent, but less prevalent samples.[148]
"Skunk" refers to several named strains of potent cannabis, grown through selective breeding and sometimes hydroponics. It is a cross-breed of Cannabis sativa and C. indica (although other strains of this mix exist in abundance). Skunk cannabis potency ranges usually from 6% to 15% and rarely as high as 20%. The average THC level in coffee shops in the Netherlands is about 18–19%.[149]
Price
The price or street value of cannabis varies widely depending on geographic area and potency.[150]
In the United States, cannabis is overall the #4 value crop, and is #1 or #2 in many states including California, New York and Florida, averaging $3,000/lb.[151][152] It is believed to generate an estimated $36 billion market.[153] Most of the money is spent not on growing and producing but on smuggling the supply to buyers. The United Nations Office on Drugs and Crime claims in its 2008 World Drug Report that typical U.S. retail prices are $10–15 per gram (approximately $280–420 per ounce). Street prices in North America are known to range from about $150 to $400 per ounce, depending on quality.[154]
The European Monitoring Centre for Drugs and Drug Addiction reports that typical retail prices in Europe for cannabis varies from 2€ to 20€ per gram, with a majority of European countries reporting prices in the range 4–10€.[155] In the United Kingdom, a cannabis plant has an approximate street value of £300,[156] but retails to the end-user at about £160/oz.
History

See also: Cannabis, Hemp, War on Drugs, and Legal history of cannabis in the United States


The Chinese character for hemp (麻 or má) depicts two plants under a shelter.[157] Cannabis cultivation dates back at least 10,000 years in Taiwan.[158]
Cannabis is indigenous to Central and South Asia.[159] Evidence of the inhalation of cannabis smoke can be found in the 3rd millennium BCE, as indicated by charred cannabis seeds found in a ritual brazier at an ancient burial site in present day Romania.[160] In 2003, a leather basket filled with cannabis leaf fragments and seeds was found next to a 2,500- to 2,800-year-old mummified shaman in the northwestern Xinjiang Uygur Autonomous Region of China.[161][162]
Cannabis is also known to have been used by the ancient Hindus of India and Nepal thousands of years ago. The herb was called ganjika in Sanskrit (गांजा,ganja in modern Indo-Aryan languages).[163][164] The ancient drug soma, mentioned in the Vedas, was sometimes associated with cannabis.[165]
Cannabis was also known to the ancient Assyrians, who discovered its psychoactive properties through the Aryans.[166] Using it in some religious ceremonies, they called it qunubu (meaning "way to produce smoke"), a probable origin of the modern word "cannabis".[167] Cannabis was also introduced by the Aryans to the Scythians, Thracians and Dacians, whose shamans (the kapnobatai—"those who walk on smoke/clouds") burned cannabis flowers to induce a state of trance.[168]


Cannabis sativa from Vienna Dioscurides, 512 AD
Cannabis has an ancient history of ritual use and is found in pharmacological cults around the world. Hemp seeds discovered by archaeologists at Pazyryk suggest early ceremonial practices like eating by the Scythians occurred during the 5th to 2nd century BCE, confirming previous historical reports by Herodotus.[169] One writer has claimed that cannabis was used as a religious sacrament by ancient Jews and early Christians[170][171] due to the similarity between the Hebrew word "qannabbos" ("cannabis") and the Hebrew phrase "qené bósem" ("aromatic cane"). It was used by Muslims in various Sufi orders as early as the Mamluk period, for example by the Qalandars.[172]
A study published in the South African Journal of Science showed that "pipes dug up from the garden of Shakespeare's home in Stratford-upon-Avon contain traces of cannabis."[173] The chemical analysis was carried out after researchers hypothesized that the "noted weed" mentioned in Sonnet 76 and the "journey in my head" from Sonnet 27 could be references to cannabis and the use thereof.[174] Examples of classic literature featuring cannabis include Les paradis artificiels by Charles Baudelaire and The Hasheesh Eater by Fitz Hugh Ludlow.
John Gregory Bourke described use of "mariguan", which he identifies as Cannabis indica or Indian hemp, by Mexican residents of the Rio Grande region of Texas in 1894. He described its uses for treatment of asthma, to expedite delivery, to keep away witches, and as a love-philtre. He also wrote that many Mexicans added the herb to their cigarritos or mescal, often taking a bite of sugar afterward to intensify the effect. Bourke wrote that because it was often used in a mixture with toloachi (which he inaccurately describes as Datura stramonium), mariguan was one of several plants known as "loco weed". Bourke compared mariguan to hasheesh, which he called "one of the greatest curses of the East", citing reports that users "become maniacs and are apt to commit all sorts of acts of violence and murder", causing degeneration of the body and an idiotic appearance, and mentioned laws against sale of hasheesh "in most Eastern countries".[175][176][177]


Cannabis indica fluid extract, American Druggists Syndicate, pre-1937
Cannabis was criminalized in various countries beginning in the early 20th century. In the United States, the first restrictions for sale of cannabis came in 1906 (in District of Columbia).[178] It was outlawed in South Africa in 1911, in Jamaica (then a British colony) in 1913, and in the United Kingdom and New Zealand in the 1920s.[179] Canada criminalized cannabis in the Opium and Drug Act of 1923, before any reports of use of the drug in Canada. In 1925 a compromise was made at an international conference in The Hague about the International Opium Convention that banned exportation of "Indian hemp" to countries that had prohibited its use, and requiring importing countries to issue certificates approving the importation and stating that the shipment was required "exclusively for medical or scientific purposes". It also required parties to "exercise an effective control of such a nature as to prevent the illicit international traffic in Indian hemp and especially in the resin".[180][181]
In the United States in 1937, the Marihuana Tax Act was passed, and prohibited the production of hemp in addition to cannabis. The reasons that hemp was also included in this law are disputed—several scholars have claimed that the Act was passed in order to destroy the US hemp industry,[182][183][184] with the primary involvement of businessmen Andrew Mellon, Randolph Hearst, and the Du Pont family.[182][184] With the invention of the decorticator, hemp became a very cheap substitute for the paper pulp that was used in the newspaper industry[182][185] and Hearst consequently believed that his extensive timber holdings were at threat. Mellon, Secretary of the Treasury and the wealthiest man in America at that time, had invested heavily in DuPont's new synthetic fiber, nylon, and believed that the replacement of the traditional resource, hemp, was integral to the new product's success.[182][186][187][188][189][190][191][192]
The United Nations' 2012 "Global Drug Report" stated that cannabis "was the world's most widely produced, trafficked, and consumed drug in the world in 2010", identifying that between 119 million and 224 million users existed in the world's adult (18 or older) population.[193]
Legal status

Main article: Legality of cannabis
See also: Prohibition of drugs and Drug liberalization


Cannabis propaganda sheet from 1935
Since the beginning of the 20th century, most countries have enacted laws against the cultivation, possession or transfer of cannabis.[194] These laws have impacted adversely on the cannabis plant's cultivation for non-recreational purposes, but there are many regions where, under certain circumstances, handling of cannabis is legal or licensed. Many jurisdictions have lessened the penalties for possession of small quantities of cannabis, so that it is punished by confiscation and sometimes a fine, rather than imprisonment, focusing more on those who traffic the drug on the black market.
In some areas where cannabis use has been historically tolerated, some new restrictions have been put in place, such as the closing of cannabis coffee shops near the borders of the Netherlands,[195] closing of coffee shops near secondary schools in the Netherlands and crackdowns on "Pusher Street" in Christiania, Copenhagen in 2004.[196][197]
Some jurisdictions use free voluntary treatment programs and/or mandatory treatment programs for frequent known users. Simple possession can carry long prison terms in some countries, particularly in East Asia, where the sale of cannabis may lead to a sentence of life in prison or even execution. More recently however, many political parties, non-profit organizations and causes based on the legalization of medical cannabis and/or legalizing the plant entirely (with some restrictions) have emerged.
On December 6, 2012, the U.S. state of Washington became the first state to officially legalize cannabis in a state law ( but still illegal by federal law),[198][199] with the state of Colorado following close behind.[200] On January 1, 2013, the first marijuana "club" for private marijuana smoking (no buying or selling, however) was allowed for the first time in Colorado.[201] The California Supreme Court decided in May 2013 that local governments can ban medical marijuana dispensaries despite a state law in California that permits the use of cannabis for medical purposes. At least 180 cities across California and the Bay Area have enacted bans in recent years.[202]
Constraints on open research
Cannabis research is challenging since the plant is illegal in most countries.[203][204][205][206][207] Research-grade samples of the drug are difficult to obtain for research purposes, unless granted under authority of national governments.
This issue was highlighted in the United States by the clash between Multidisciplinary Association for Psychedelic Studies (MAPS), an independent research group, and the National Institute on Drug Abuse (NIDA), a federal agency charged with the application of science to the study of drug abuse. The NIDA largely operates under the general control of the Office of National Drug Control Policy (ONDCP), a White House office responsible for the direct coordination of all legal, legislative, scientific, social and political aspects of federal drug control policy.[citation needed]
The cannabis that is available for research studies in the United States is grown at the University of Mississippi and solely controlled by the NIDA, which has veto power over the Food and Drug Administration (FDA) to define accepted protocols. Since 1942, when cannabis was removed from the U.S. Pharmacopoeia and its medical use was prohibited, there have been no legal (under federal law) privately funded cannabis production projects. This has resulted in a limited amount of research being done and possibly in NIDA producing cannabis which has been alleged to be of very low potency and inferior quality.[208]
MAPS, in conjunction with Professor Lyle Craker, PhD, the director of the Medicinal Plant Program at the University of Massachusetts Amherst, sought to provide independently grown cannabis of more appropriate research quality for FDA-approved research studies, and encountered opposition by NIDA, the ONDCP, and the U.S. Drug Enforcement Administration (DEA).[209]
See also

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Cannabis
Cannabinoids
Cannabinoid receptors
Effects of cannabis
Medical marijuana
Hemp
Footnotes

^ a: Weed,[210] pot,[211] grass,[212] and herb[213] are among the many other nicknames for marijuana or cannabis as a drug.[214][215]
^ b: Sources for this section and more information can be found in the Medical cannabis article
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