The Best Medicine

Cannabis, also known as marijuana^[2] (sometimes spelled "marihuana"^[3]) among many other names,^a[›] refers to any number ofpreparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana.^[4] According to the United Nations, cannabis "is the most widely used illicit substance in the world."^[5]

The typical herbal form of cannabis consists of the flowers and subtending leaves and stalks of mature pistillate female plants. The resinousform of the drug is known as hashish (or merely as 'hash').^[6]

The major psychoactive chemical compound in cannabis is Δ⁹-tetrahydrocannabinol (commonly abbreviated as THC). Cannabis contains more than 400 different chemical compounds, including at least 66 other cannabinoids (cannabidiol (CBD), cannabinol (CBN) andtetrahydrocannabivarin (THCV), etc.) which can result in different effects from those of THC alone.^[7]

Documented instances of cannabis use go back as far as the 3rd millennium BC.^[8] In modern times, the drug has been used for recreational,religious or spiritual, and medicinal purposes. The UN estimated that in 2004 about 4% of the world's adult population (162 million people) use cannabis annually, and about 0.6% (22.5 million) use it on a daily basis.^[9] The possession, use, or sale of cannabis preparations containing psychoactive cannabinoids became illegal in most parts of the world in the early 20th century.^[10]

Effects

Main short-term physical effects of cannabis

Cannabis has psychoactive and physiological effects when consumed. The minimum amount of THC required to have a perceptible psychoactive effect is about 10 micrograms per kilogram of body weight.^[11] Aside from a subjective change in perception and, most notably, mood, the most common short-term physical and neurological effects include increased heart rate, lowered blood pressure, impairment of short-term and working memory,^[12] psychomotor coordination, and concentration. Long-term effects are less clear.^[13][14]

Classification

While many 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. Though 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.^[15][16][17]

Medical use

Cannabis used medically does have several well-documented beneficial effects. Among these are: the amelioration of nausea andvomiting, stimulation of hunger in chemotherapy and AIDS patients, lowered intraocular eye pressure (shown to be effective for treatingglaucoma), 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 frommultiple 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[›] In 2011, an oromucosal spray for Multiple Sclerosis patients became licensed for use as a medicine from the European regulatory body, allowing it to be routinely prescribed by doctors.^[18]

Currently, the U.S. Food and Drug Administration (FDA) has not approved smoked marijuana for any condition or disease in the United States, largely because good quality scientific evidence for its use from U.S. studies is lacking; however, a major barrier to acquiring the necessary evidence is the lack of federal funding for this kind of research.^[19] Regardless, fourteen states have legalized cannabis for medical use.^[20][21] The United States Supreme Court has ruled in United States v. Oakland Cannabis Buyers' Coop and Gonzales v. Raichthat it is the federal government that has the right to regulate and criminalize cannabis, even for medical purposes. Canada, Spain, The Netherlands and Austria have legalized some form of cannabis for medicinal use.^[22]

Long-term effects

Cannabis is ranked one of the least harmful drugs by a study published in the UK medical journal, The Lancet.^[23]

Though the long-term effects of cannabis have been studied, there remains much to be concluded. Debated aspects include the possibility of cannabis dependence, the potential of cannabis as a "gateway drug", its effects on intelligence and memory, and the relationship, if any, of cannabis use to mental disorders such as schizophrenia and depression.^[24][25][26] On some topics, such as the drug's effects on the lungs, relatively little research has been conducted, leading to division as to the severity of its impact.

While cannabis has been correlated with the development of various mental disorders in multiple studies, these studies differ widely as to whether cannabis use is the cause of the mental problems, whether the mental problems encourage cannabis use, or whether both the cannabis use and the mental problems are the effects of some other cause. Similarly, experiments regarding the "gateway drug" hypothesis that cannabis and alcohol make users more inclined to become addicted to "harder" drugs likecocaine and heroin have produced mixed results, with different studies finding varying degrees of correlation between the use of cannabis and other drugs, and some finding none.^{[citation needed]} Generally, no scientific consensus exists regarding many of cannabis's long-term effects, despite a large number of studies.

However, cannabis has been consistently shown to induce depersonalization disorder.^[27] There are case reports in the literature where chronic depersonalization is induced by only short-term cannabis ingestion.^[28][29] In a series of 117 individuals with depersonalization disorder, about 13% reported the short-term triggering of chronic depersonalization by marijuana smoking.^[30]There are cases where individuals have gotten depersonalization disorder when trying cannabis for the first time. Chronic depersonalization disorder can last an entire lifetime, and to date there are no specific medical treatments (just medications which ameliorate the negative symptoms of depersonalization disorder, which are mainly depression and anxiety), although some research has been promising.^[31]

Forms

Unprocessed

Dried Cannabis flowers in natural herbal form

The terms cannabis or marijuana generally refer to the dried flowers and subtending leaves and stems of the female cannabis plant.^{[citation needed]} This is the most widely consumed form, containing 3% to 22% THC.^[32][33] In contrast, cannabis strains used to produce industrial hemp contain less than 1% THC and are thus not valued for recreational use.^[34]

Processed

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.^[35]

Hashish

Hashish

Hashish (also spelled hasheesh, hashisha, or simply hash) is a concentrated resin produced from the flowers of the female cannabis plant. Hash can often be more potent than marijuana and can be smoked or chewed.^[36] It varies in color from black to golden brown depending upon purity.

Hash oil

Hash oil, or "butane honey oil" (BHO), is a mix of essential oils and resins extracted from mature cannabis foliage through the use of various solvents. It has a high proportion of cannabinoids (ranging from 40 to 90%).^[37] and is used in a variety of cannabis foods.

Residue (resin)

Because of THC's adhesive properties, a sticky residue, most commonly known as "resin", builds up inside utensils used to smoke cannabis. It has tar-like properties but still contains THC as well as other cannabinoids. This buildup retains some of the psychoactive properties of cannabis but is more difficult to smoke without discomfort caused to the throat and lungs. This tar may also contain CBN, which is a breakdown product of THC. Cannabis users typically only smoke residue when cannabis is unavailable. Glass pipes may be water-steamed at a low temperature prior to scraping in order to make the residue easier to remove.^[38]

Routes of administration

A joint

A forced-air vaporizer. The detachable balloon (top) fills with vapors that are then inhaled.

A conductionvaporizer, with flexible extension tube ("whip"). A small serving of cannabis is heated on a metal platform (center).

Cannabis is consumed in many different ways, most of which involve inhaling vaporized cannabinoids ("smoke") from small pipes, bongs (portable version of hookahwith water chamber), paper-wrapped joints or tobacco-leaf-wrapped blunts.

A Vaporizer heats herbal cannabis to 365–410 °F (185–210 °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).^[39] A lower proportion of toxic chemicals is released than by smoking, depending on the design of the vaporizer and the temperature setting. This method of consuming cannabis produces markedly different effects than smoking due to the flash points of different cannabinoids; for example, CBN (usually considered undesirable) has a flash point of 212.7 °C (414.9 °F)^[40] and would normally be present in smoke but not in vapor.

Fresh, non-dried cannabis may be consumed orally. However, the cannabis or its extract must be sufficiently heated or dehydrated to cause decarboxylation of its most abundant cannabinoid, tetrahydrocannabinolic acid (THCA), into psychoactive THC.^[41]

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.

Cannabis can also be consumed as a tea. THC is lipophilic and only slightly water-soluble (with a solubility of 2.8 mg per liter),^[42] so tea is made by first adding asaturated fat to hot water (i.e. cream or any milk except skim) with a small amount of cannabis.

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.^[43]

Until recently, little was known about the specific mechanisms of action of THC at the neuronal level. However, researchers have now 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 exclusively in peripheral tissues.^[44]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 interestingly 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.^[45]

Potency

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."^[46] The three main forms of cannabis products are the herb (marijuana), resin (hashish), and oil (hash oil). The UNODC states that marijuana often contains 5% THC content, resin "can contain up to 20% THC content", and that "Cannabis oil may contain more than 60% THC content."^[46]

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".^[47] More recent research undertaken at the University of Mississippi's Potency Monitoring Project^[48] has found that average THC levels in cannabis samples between 1975 and 2007 have increased from 4% in 1983 to 9.6% in 2007.

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".^[49] The UN states that the leaves can contain ten times less THC than the buds, and the stalks one hundred times less THC.^[46]

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 ^[50] (despite the fact that skunk can sometimes be incorrectly mistaken for all types of herbal cannabis).^[51][52] Extracts such as hashish and hash oil typicality contain more THC than high potency cannabis flowers.

While commentators have warned that greater cannabis "strength" could represent a health risk, others have noted that users readily learn to compensate by reducing their dosage, thus benefiting from reductions in smoking side-hazards such as heat shock or carbon monoxide.

Adulterants

Chalk (in the Netherlands) and glass particles (in the UK) have been used to make cannabis appear to be higher quality.^[53][54][55] Increasing the weight of hashish products in Germany with lead caused lead intoxication in at least 29 users.^[56] In the Netherlands two chemical analogs of Sildenafil (Viagra) were found in adulterated marijuana.^[57]

According to both the "Talk to FRANK" website and the UKCIA website, Soap Bar, "perhaps the most common type of hash in the UK", was found "at worst" to contain turpentine, tranquilizers, boot polish, henna and animal feces—amongst several other things.^[58][59] One small study of five "soap-bar" samples seized by UK Customs in 2001 found huge adulteration by many toxic substances, including soil, glue, engine oil and animal feces.^[60]

Detection of use

THC and its major (inactive) metabolite, THC-COOH, can be quantitated 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, prescription use from illicit use, 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.^[61] 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.^{[61][62][63][64]}

The Duquenois-Levine test is commonly used as a screening test in the field, but it cannot definitively confirm the presence of marijuana, 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.^[65]

Gateway drug theory

Some^[who?] claim that trying cannabis increases the probability that users will eventually use "harder" drugs. This hypothesis has been one of the central pillars of anti-cannabis drug policy in the United States,^[66] though the validity and implications of these hypotheses are hotly debated.^[67] Studies have shown that tobacco smoking is a better predictor of concurrent illicit hard drug use than smoking cannabis.^[68]

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.^[69]

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.^[70]

A new user of cannabis who feels there is a difference between anti-drug information and their own experiences will apply this distrust to public information about other, more powerful drugs. Some studies state that while there is no proof for this gateway hypothesis, young cannabis users should still be considered as a risk group for intervention programs.^[71] 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.^[72]

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.^[73][74] By this argument, some studies have shown that alcohol and tobacco may be regarded as gateway drugs.^[68] 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.^[67]

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 found there is no "gateway theory" and that drug use is more closely tied to a person's life situation, although marijuana users are more likely to use other drugs.^[75]

History

The use of cannabis, at least as fiber, has been shown to go back at least 10,000 years in Taiwan.^[76] Má (麻), the Chinese expression for hemp, is a pictograph of two plants under a shelter.^[77]

Cannabis is indigenous to Central and South Asia.^[78] Evidence of the inhalation of cannabis smoke can be found in the 3rd millennium BC, as indicated by charred cannabis seeds found in a ritual brazier at an ancient burial site in present day Romania.^[8] 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.^[79][80] 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/গাঁজা ganja in modern Indic languages).^[81][82] The ancient drug soma, mentioned in the Vedas, was sometimes associated with cannabis.^[83]

Cannabis was also known to the ancient Assyrians, who discovered its psychoactive properties through the Aryans.^[84] Using it in some religious ceremonies, they called it qunubu (meaning "way to produce smoke"), a probable origin of the modern word "cannabis".^[85] 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 oftrance.^[86] Members of the cult of Dionysus, believed to have originated in Thrace (Bulgaria, Greece and Turkey), are also thought to have inhaled cannabis smoke.^{[citation needed]}

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 BC, confirming previous historical reports by Herodotus.^[87] One writer has claimed that cannabis was used as a religious sacrament by ancient Jews and early Christians^[6][88] 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 Sufiorders as early as the Mamluk period, for example by the Qalandars.^[89]

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-Avoncontain traces of cannabis."^[90] The chemical analysis was carried out after researchers hypothesized that the "noted weed" mentioned in Sonnet 76and the "journey in my head" from Sonnet 27 could be references to cannabis and the use thereof.^[91]

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).^[92] 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.^[93] Canada criminalized marijuana 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".^[94][95]

In 1937 in the United States, the Marijuana Transfer Tax Act was passed, and prohibited the production of hemp in addition to marijuana. 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 hemp industry,^[96][97][98] largely as an effort of businessmen Andrew Mellon, Randolph Hearst, and the Du Pont family.^[96][98] With the invention of the decorticator, hemp became a very cheap substitute for the paper pulp that was used in the newspaper industry.^[96][99]Hearst felt that this was a threat to his extensive timber holdings. Mellon, Secretary of the Treasury and the wealthiest man in America, had invested heavily in the DuPont's new synthetic fiber, nylon, and considered its success to depend on its replacement of the traditional resource, hemp.^{[96][100][101][102][103][104][105][106]} The claims that hemp could have been a successful substitute for wood pulp have been based on an incorrect government report of 1916 which concluded that hemp hurds, broken parts of the inner core of the hemp stem, were a suitable source for paper production. This has not been confirmed by later research, as hemp hurds are not reported to be a good enough substitute. In 2003, 95 % of the hemp hurds in EU were used for animal bedding, almost 5 % were used as building material.^{[107][108][109][110]} See also Hemp.

Legal status

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. 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,^[111] closing of coffee shops near secondary schools in the Netherlands and crackdowns on "Pusher Street" in Christiania, Copenhagen in 2004.^[112][113]

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.

Price

The price or street value of cannabis varies strongly by region and area. In addition, some dealers may sell potent buds at a higher price.^[114]

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.^[115][116] It is believed to generate an estimated $36 billion market.^[117] 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.^[118]

The European Monitoring Centre for Drugs and Drug Addiction reports that typical retail prices in Europe for cannabis varies from 2€ to 14€ per gram, with a majority of European countries reporting prices in the range 4–10€.^[119] In the United Kingdom, a cannabis plant has an approximate street value of £300,^[120] but retails to the end-user at about £160/oz.

Truth serum

Cannabis was used as a truth serum by the Office of Strategic Services (OSS), a US government intelligence agency formed during World War II. In the early 1940s, it was the most effective truth drug developed at the OSS labs at St. Elizabeths Hospital; it caused a subject "to be loquacious and free in his impartation of information."^[121]

In May 1943, Major George Hunter White, head of OSS counter-intelligence operations in the US, arranged a meeting with Augusto Del Gracio, an enforcer for gangster Lucky Luciano. Del Gracio was given cigarettes spiked with THC concentrate from cannabis, and subsequently talked openly about Luciano's heroin operation. On a second occasion the dosage was increased such that Del Gracio passed out for two hours.^[121]

Breeding and cultivation

Maturing female Cannabis plant

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 marijuana 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 methodare frequently employed as a response (in part) to prohibition enforcement efforts that make outdoor cultivation more risky. These intensive horticultural techniques have made it possible to grow strains with fewer seeds and higher potency.^{[citation needed]} 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.^[122] The average THC level in coffee shops in the Netherlands is about 18–19%.^[123]

In arts and literature

• Les paradis artificiels by Charles Baudelaire
• The Hasheesh Eater by Fitz Hugh Ludlow