Cannabis (drug)

Cannabis, also known as marijuana, and by numerous other names, is a preparation of the cannabis plant intended for use as a psychoactive drug and as medicine. Pharmacologically, the principal psychoactive constituent of cannabis is tetrahydrocannabinol (THC); it is one of 483 known compounds in the plant, including at least 84 other cannabinoids, such as cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabivarin (THCV), and cannabigerol (CBG).

Cannabis is often consumed for its psychoactive and physiological effects, which can include heightened mood or euphoria, relaxation, and an increase in appetite. Unwanted side-effects can sometimes include a decrease in short-term memory, dry mouth, impaired motor skills, reddening of the eyes, and feelings of paranoia or anxiety.

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. 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. 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.

Effects
Cannabis has psychoactive and physiological effects when consumed. 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. Aside from a subjective change in perception and 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, psychomotor coordination, and concentration.

A 2013 literature review said 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".

Cannabis has been used to reduce nausea and vomiting in chemotherapy and people with AIDS, and to treat pain and muscle spasticity. According to a 2013 review, "Safety concerns regarding cannabis include the increased risk of developing schizophrenia with adolescent use, impairments in memory and cognition, accidental pediatric ingestions, and lack of safety packaging for medical cannabis formulations."

The medicinal value of cannabis is disputed. The American Society of Addiction Medicine dismisses the concept of medical cannabis because the plant fails to meet its standard requirements for approved medicines. The US Food and Drug Administration (FDA) maintains that the herb cannabis is associated with numerous harmful health effects, and that significant aspects such as content, production, and supply are unregulated. The FDA approve of the prescription of two products (not for smoking) that have pure THC in a small controlled dose as the active substance.

Neurological
A 2013 review comparing different structural and functional imaging studies showed morphological brain alterations in long-term cannabis users which were found to possibly correlate to cannabis exposure. A 2010 review found resting blood flow to be lower globally and in prefrontal areas of the brain in cannabis users, when compared to non-users. It was also shown that giving THC or cannabis correlated with increased bloodflow in these areas, and facilitated activation of the anterior cingulate cortex and frontal cortex when participants were presented with assignments demanding use of cognitive capacity. Both reviews noted that some of the studies that they examined had methodological limitations, for example small sample sizes or not distinguishing adequately between cannabis and alcohol consumption.

Gateway drug
Since the 1950s, United States drug policy has been guided by the assertion that cannabis use increases the probability of trying "harder" drugs. The hypothesis has endured as one of the central pillars of anti-cannabis drug policy in the United States, and as such the validity and implications of the hypothesis are hotly debated. Almost two-thirds of the poly drug users in the "2009/10 Scottish Crime and Justice Survey" used cannabis.

Some studies state that while there is no proof for the gateway hypothesis, young cannabis users should still be considered as a risk group for intervention programs, while 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.

Another gateway hypothesis covers that a gateway effect may result of the "common factors" involved in using any illegal drug. Through the illegal status of cannabis, users are more likely to be subjected to situations allowing them to acquaint with individuals using or selling various illegal drugs. Utilizing this argument some studies have shown that alcohol and tobacco may additionally be regarded as gateway drugs, however, a more parsimonious explanation could be that cannabis is simply more readily available (and at an earlier age) than illegal hard drugs. In turn alcohol and tobacco are easier to obtain at an earlier point than is cannabis (though the reverse may be true in some areas), thus leading to the "gateway sequence" in those individuals; who are most likely to experiment with any drug offered.

Safety
Fatal overdoses associated with cannabis use have not been reported as of 2008. There has been too little research to determine whether cannabis users die at a higher rate as compared to the general population, though some studies suggest that fatal motor vehicle accidents and death from respiratory and brain cancers may be more frequent among heavy cannabis users. It is not clear whether cannabis use affects the rate of suicide.

THC, the principal psychoactive constituent of the cannabis plant, has low toxicity, the dose of THC needed to kill 50% of tested rodents is very high, and human deaths from overdose are extremely rare.

Evaluations of safety and tolerability of Sativex, a pharmacological preparation made from cannabinoids, have concluded that it is indeed well-tolerated and, in one class of patients, useful.

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, and over fifty known carcinogens have been identified in cannabis smoke, including; nitrosamines, reactive aldehydes, and polycylic hydrocarbons, including benz[a]pyrene.

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. 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. 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. 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.

Varieties and strains


Cannabis indica may have a CBD:THC ratio four to five times that of Cannabis sativa. Cannabis strains with relatively high CBD:THC ratios are less likely to induce anxiety than those with a lower ratio. 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. This likely means the high concentrations of CBD found in Cannabis indica mitigate the anxiogenic effect of THC significantly. The effects of sativa are well known for their cerebral high, hence its daytime use as medical cannabis, while indica is well known for its sedative effects and preferred night time use as medical cannabis.

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." 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."

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". The study 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". More recent research undertaken at the University of Mississippi's Potency Monitoring Project found that average THC levels in cannabis samples between 1975 and 2007 steadily increased, for example THC levels in 1985 averaged 3.48% by 2006 this had increased to an average of 8.77%.

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". The UN states that leaves can contain ten times less THC than the buds, and the stalks one hundred times less THC.

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 (despite the fact that skunk can sometimes be incorrectly mistaken for all types of herbal cannabis). Extracts such as hashish and hash oil typically contain more THC than high potency cannabis flowers.

Whole flower and leaf
The terms cannabis and marijuana generally refer to the dried flowers and subtending leaves and stems of the female cannabis plant. This is the most widely consumed form, containing 3% to 22% THC. In contrast, cannabis varieties used to produce industrial hemp contain less than 1% THC and are thus not valued for recreational use.

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.

Kief
Kief is a powder, rich in trichomes, 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. The word "kif" derives from Arabic: كيف kayf, meaning well-being or pleasure.

Hashish
Hashish (also spelled hasheesh, hashisha, or simply hash) is a concentrated resin cake or ball produced from pressed kief, the detached trichomes and fine material that falls off of cannabis flowers and leaves. It varies in color from black to golden brown depending upon purity and variety of cultivar it was obtained from. It can be consumed orally or smoked.

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". Nabiximols is a branded product name from a tincture manufacturing pharmaceutical company.

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. 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. Owing to its purity, these products are consumed by smoking, vaporizing, eating, or topical application.

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.

Adulterated cannabis
Contaminants may be found in hashish obtained from "soap bar"-type sources. The dried flowers of the plant may be contaminated by the plant taking up heavy metals and other toxins from its growing environment, or by the addition of glass. In the Netherlands, chalk has been used to make cannabis appear to be of a higher quality. Increasing the weight of hashish products in Germany with lead caused lead intoxication in at least 29 users.

Despite cannabis being generally perceived as a natural or chemical-free product, in a recent Australian survey 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.

Methods of consumption
Cannabis is consumed in many different ways:


 * smoking, which typically involves inhaling vaporized cannabinoids ("smoke") from small pipes, bongs (portable versions of hookahs with water chamber), paper-wrapped joints or tobacco-leaf-wrapped blunts, roach clips, and other items.


 * vaporizer, which heats herbal cannabis to 330 –, causing the active ingredients to evaporate into a vapor without burning the plant material (the boiling point of THC is 390.4 °F at 760 mmHg pressure).


 * cannabis tea, which contains 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). 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.


 * edibles, where cannabis is added as an ingredient to one of a variety of foods.

Marijuana vending machines for selling or dispensing cannabis are in use in the United States and are planned to be used in Canada.

Mechanism of action
The high lipid-solubility of cannabinoids results in their persisting in the body for long periods of time. 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). 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.

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. 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. 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. However, due to the dysphoric effect of CB1 antagonists, this drug is often discontinued due to these side effects.

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. THC also potentiates the effects of the glycine receptors. The role of these interactions in the "marijuana high" remains elusive.

Detection of consumption
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. 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. 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. Urine contains predominantly THC-COOH, while hair, oral fluid and sweat contain primarily THC. Blood may contain both substances, with the relative amounts dependent on the recency and extent of usage.

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. 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.

Production
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.

"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%.

Price
The price or street value of cannabis varies widely depending on geographic area and potency.

In the United States, cannabis is overall the number four value crop, and is number one or two in many states including California, New York and Florida, averaging $3,000/lb. It is believed to generate an estimated $36 billion market. 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.

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.

History


Cannabis is indigenous to Central and South Asia. 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. 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. Evidence for the consumption of cannabis has also been found in Egyptian mummies dated about 950 BC.

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). The ancient drug soma, mentioned in the Vedas, was sometimes associated with cannabis.

Cannabis was also known to the ancient Assyrians, who discovered its psychoactive properties through the Aryans. Using it in some religious ceremonies, they called it qunubu (meaning "way to produce smoke"), a probable origin of the modern word "cannabis". 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.



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. One writer has claimed that cannabis was used as a religious sacrament by ancient Jews and early Christians 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.

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." 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. 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".



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). 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. 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".

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, with the primary involvement of businessmen Andrew Mellon, Randolph Hearst, and the Du Pont family. But the improvements of the decorticators, machines that separate the fibers from the hemp stem, could not make hemp fiber a very cheap substitute for fibers from other sources because it could not change that basic fact that strong fibers are only found in the bast, the outer part of the stem. Only about 1/3 of the stem are long and strong fibers.

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.

Legal status


Since the beginning of the 20th century, most countries have enacted laws against the cultivation, possession or transfer of cannabis. 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, closing of coffee shops near secondary schools in the Netherlands and crackdowns on "Pusher Street" in Christiania, Copenhagen in 2004.

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.

In December 2012, the U.S. state of Washington became the first state to officially legalize cannabis in a state law (Washington Initiative 502) (but still illegal by federal law), with the state of Colorado following close behind (Colorado Amendment 64). 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. 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 have enacted bans in recent years.

In December 2013, Uruguay became the first country to legalize growing, sale and use of cannabis.

Constraints on open research
Cannabis research is challenging since the plant is illegal in most countries. 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.

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.

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).

There are also other difficulties in researching the effects of cannabis. Many people who smoke cannabis also smoke tobacco, and users of cannabis often mix it with tobacco. This can make it difficult to know whether it is the tobacco, the cannabis, or both that have caused a cancer. Another difficulty researchers have is in recruiting people who smoke cannabis into studies. Because cannabis is an illegal drug in many countries, people may be reluctant to take part in research, and if they do agree to take part, they may not say how much cannabis they actually smoke.

However, a large number of studies about cannabis have after year 2000 been published from a number of countries.