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Friday, February 6, 2015

Cannabis (drug)


From Wikipedia, the free encyclopedia

Cannabis
Cannabis Plant.jpg
Flowering cannabis plant
Botanical Cannabis
Source plant(s) Cannabis sativa, Cannabis sativa forma indica, Cannabis ruderalis
Part(s) of plant flower
Geographic origin Central and South Asia.[1]
Active ingredients Tetrahydrocannabinol, cannabidiol, cannabinol, tetrahydrocannabivarin
Main producers Afghanistan,[2] Canada,[3] China,[4][not in citation given] Colombia,[5] India,[2] Jamaica,[2] Mexico,[6] Morocco,[2] Netherlands, Pakistan, Paraguay,[6] Spain,[2] Thailand, Turkey, United States[2]
Cannabis, commonly known as marijuana[7] and by numerous other names,a[›] is a preparation of the Cannabis plant intended for use as a psychoactive drug and as medicine.[8][9] Pharmacologically, the principal psychoactive constituent of cannabis is tetrahydrocannabinol (THC); it is one of 483 known compounds in the plant,[10] including at least 84 other cannabinoids, such as cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabivarin (THCV),[11][12] and cannabigerol (CBG).

Cannabis is often consumed for its psychoactive and physiological effects, which can include heightened mood or euphoria, relaxation,[13] and an increase in appetite.[14] Possible side-effects include a decrease in short-term memory, dry mouth, impaired motor skills, reddening of the eyes,[13] and feelings of paranoia or anxiety.[15]

Modern 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.[16] 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 deems it the most-used illicit drug in the world.[17][18] 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.[19] Medical marijuana refers to the use of the Cannabis plant as a physician-recommended herbal therapy, which is taking place in Canada, Belgium, Australia, the Netherlands, Spain, and several U.S. states.

Effects

Main short-term physical effects of cannabis

Cannabis has psychoactive and physiological effects when consumed.[20] 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.[21] 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,[22][23] 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".[24]

Cannabis has been used to reduce nausea and vomiting in chemotherapy and people with AIDS, and to treat pain and muscle spasticity.[25] 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."[25]

The medicinal value of cannabis is disputed. The American Society of Addiction Medicine dismisses the concept of medical cannabis because of concerns about its potential for dependence and adverse health effects. The US Food and Drug Administration (FDA) states 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 approves of the prescription of two products (not for smoking) that have pure THC in a small controlled dose as the active substance.[26][27]

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.[28] 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.[29] 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.[28][29]

Gateway drug

The Gateway Hypothesis states that cannabis use increases the probability of trying "harder" drugs. The hypothesis has been hotly debated as it is regarded by some as the primary rationale for the United States prohibition on cannabis use.[30][31] A Pew Research Center poll found that political opposition to marijuana use was significantly associated with concerns about health effects and whether legalization would increase marijuana use by children.[32]
Some studies state that while there is no proof for the gateway hypothesis,[33] young cannabis users should still be considered as a risk group for intervention programs.[34] 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.[35] Almost two-thirds of the poly drug users in the "2009/10 Scottish Crime and Justice Survey" used cannabis.[36]

The gateway effect may appear due to social factors involved in using any illegal drug. Because of the illegal status of cannabis, its consumers are likely to find themselves in situations allowing them to acquaint with individuals using or selling other illegal drugs.[37][38] Utilizing this argument some studies have shown that alcohol and tobacco may additionally be regarded as gateway drugs;[39] 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 since they are most likely to experiment with any drug offered.[30]

An alternative to the gateway hypothesis is the Common Liability to Addiction theory (CLA). It states that some individuals are, for various reasons, willing to try multiple recreational substances. The "gateway" drugs are merely those that are (usually) available at an earlier age than the harder drugs. Researchers have noted in an extensive review, Vanyukov et al., that it is dangerous to present the sequence of events described in gateway "theory" in causative terms as this hinders both research and intervention.[40]

Safety

Fatal overdoses associated with cannabis use have not been reported as of 2008.[41] 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.[41]
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,[42] and human deaths from overdose are extremely rare, usually following the injection of hashish oil.[43]

Evaluations of safety and tolerability of Sativex, a pharmacological preparation made from a low dose of cannabinoids, have concluded that it is indeed well-tolerated and, in one class of patients, useful.[44]

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,[45] and over fifty known carcinogens have been identified in cannabis smoke,[46] including; nitrosamines, reactive aldehydes, and polycylic hydrocarbons, including benz[a]pyrene.[47] Combustion products are not present when using a vaporizer, consuming THC in pill form, or consuming cannabis foods.

There is serious suspicion among cardiologists, spurring research but falling short of definitive proof, that cannabis use has the potential to contribute to cardiovascular disease. 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.[48] 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.[49] 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.[50]

Varieties and strains


Types of cannabis

CBD is a 5-HT1A receptor agonist, which may also contribute to an anxiolytic effect.[51] This likely means the high concentrations of CBD found in Cannabis indica mitigate the anxiogenic effect of THC significantly.[51] 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.[51]

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."[52] 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."[52]

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".[53] 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,[54] for example THC levels in 1985 averaged 3.48% by 2006 this had increased to an average of 8.77%.[54]

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".[55] The UN states that leaves can contain ten times less THC than the buds, and the stalks one hundred times less THC.[52]

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[56] (despite the fact that skunk can sometimes be incorrectly mistaken for all types of herbal cannabis).[57][58] Extracts such as hashish and hash oil typically contain more THC than high potency cannabis flowers.[59]

Preparations

Marijuana

Marijuana consists of the dried flowers and subtending leaves and stems of the female Cannabis plant.[60][61] This is the most widely consumed form, containing 3% to 20% THC,[62] with reports of up-to 33% THC.[63] In contrast, cannabis varieties used to produce industrial hemp contain less than 1% THC and are thus not valued for recreational use.[64]

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.[65]

Kief

Kief is a powder, rich in trichomes,[66] 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.[67] The word "kif" derives from colloquial Arabic كيف kēf/kīf, meaning pleasure.[68]

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.[69] It varies in color from black to golden brown depending upon purity and variety of cultivar it was obtained from.[70] It can be consumed orally or smoked.[71]

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".[72] Nabiximols is a branded product name from a tincture manufacturing pharmaceutical company.[73]

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.[74] The solvents are evaporated to leave behind a very concentrated oil. Owing to its purity, hash oil is consumed by smoking, vaporizing, eating, or topical application. Hash oil is very different from both hemp seed oil and cannabis flower essential oil.[75]

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.[76]

Adulterated cannabis

Contaminants may be found in hashish obtained from "soap bar"-type sources.[77] The dried flowers of the plant may be contaminated by the plant taking up heavy metals and other toxins from its growing environment,[78] or by the addition of glass.[79] In the Netherlands, chalk has been used to make cannabis appear to be of a higher quality.[80] Increasing the weight of hashish products in Germany with lead caused lead intoxication in at least 29 users.[81]

Despite cannabis being generally perceived as a natural product,[82] in a recent Australian survey[83] 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

A joint prior to rolling, with a paper handmade filter on the left

Woman selling cannabis and bhang in Guwahati, Assam, India

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:[84]
  • vaporizer, which heats herbal cannabis to 165–190 °C (329–374 °F),[86] causing the active ingredients to evaporate into a vapor without burning the plant material (the boiling point of THC is 157 °C (315 °F) at 760 mmHg pressure).[87]
  • 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).[88] 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.[89]
  • 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.[90]

Mechanism of action

The high lipid-solubility of cannabinoids results in their persisting in the body for long periods of time.[91] 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).[91] 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.[92]
Not until the end of the 20th century was the specific mechanism 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.[93] 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.[94] 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.[95] However, due to the dysphoric effect of CB1 antagonists, this drug is often discontinued due to these side effects.[96]

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.[97] THC also potentiates the effects of the glycine receptors.[98] The role of these interactions in the "marijuana high" remains elusive.[citation needed]

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.[99] 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.[100] 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.[101] Urine contains predominantly THC-COOH, while hair, oral fluid and sweat contain primarily THC.[99] Blood may contain both substances, with the relative amounts dependent on the recency and extent of usage.[99]
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.[102] 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.[103]

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.[104]
"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%.[105]

Price

The price or street value of cannabis varies widely depending on geographic area and potency.[106]
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.[107][108] It is believed to generate an estimated $36 billion market.[109] 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 $40 to $400 per ounce, depending on quality.[110] In Washington and Colorado, however, the two states that have legalized marijuana for recreational use, illicit dealers have suffered now that their lucrative underground market has all but disappeared, and as a result, prices have fallen sharply (they cannot compete with the genuine, professionally grown and superior quality crop, the price of which they also cannot compete with). Buyers from nearby states have further damaged the illegal market, putting several thousands of illegal dealers out of business.

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.[111]

History

The Chinese character for hemp (麻 or ) depicts two plants under a shelter.[112] Cannabis cultivation dates back at least 3000 years in Taiwan.[113]

Cannabis is indigenous to Central and South Asia.[114] 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.[115] 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.[116][117] Evidence for the consumption of cannabis has also been found in Egyptian mummies dated about 950 BC.[118][119]
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).[120][121] Some scholars suggest that the ancient drug soma, mentioned in the Vedas, was cannabis, although this theory is disputed.[122]

Cannabis was also known to the ancient Assyrians, who discovered its psychoactive properties through the Aryans.[123] Using it in some religious ceremonies, they called it qunubu (meaning "way to produce smoke"), a probable origin of the modern word "cannabis".[124] 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.[125]

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.[126] It was used by Muslims in various Sufi orders as early as the Mamluk period, for example by the Qalandars.[127]

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."[128] 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.[129] 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".[130][131][132]

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).[133] 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.[134] 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".[135][136]

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,[137][138][139] with the primary involvement of businessmen Andrew Mellon, Randolph Hearst, and the Du Pont family.[137][139] 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.[137][140][141][142]The company DuPont and many industrial historians dispute a link between nylon and hemp. They argue that the purpose of developing the nylon was to produce a fiber that could be used in thin stockings for females and compete with silk.[143][144][145]

In New York City, more than 41,000 pounds of marijuana, which was growing like weeds throughout the boroughs until 1951, when the "White Wing Squad", headed by the Sanitation Department General Inspector John E. Gleason, was charged with destroying the many pot farms that had sprouted up across the city. The Brooklyn Public Library reports: this group was held to a high moral standard and was prohibited from "entering saloons, using foul language, and neglecting horses." The Squad found the most weed in Queens but even in Brooklyn dug up "millions of dollars" worth of the plants, many as "tall as Christmas trees". Gleason oversaw incineration of the plants in Woodside, Queens.[146]

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.[147]

Medical marijuana

Medical marijuana refers to the use of the Cannabis plant as a physician-recommended herbal therapy as well as synthetic THC and cannabinoids. So far, the medical use of cannabis is legal only in a limited number of territories, including Canada, Belgium, Australia, the Netherlands, Spain, and several U.S. states. This usage generally requires a prescription, and distribution is usually done within a framework defined by local laws.

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.[148] 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,[149] closing of coffee shops near secondary schools in the Netherlands and crackdowns on "Pusher Street" in Christiania, Copenhagen in 2004.[150][151]

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),[152] with the state of Colorado following close behind (Colorado Amendment 64).[153] 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.[154] 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.[155]

In December 2013, Uruguay became the first country to legalize growing, sale and use of cannabis.[156] However, as of August 2014, no cannabis has yet been sold legally in Uruguay. According to the law, the only cannabis that can be sold legally must be grown in the country by no more than five licensed growers, and these have yet to be selected; in fact the call for applications did not go out until August 1, 2014.[157] In the elections of October, 2014, there is a significant chance that lawmakers opposed to legal cannabis will come to control the legislature, and the law will be repealed before it has fully taken effect.[158][159][160]

Constraints on open research

Cannabis research is challenging since the plant is illegal in most countries.[161][162][163][164][165] Research-grade samples of the drug are difficult to obtain for research purposes, unless granted under authority of national governments.
There are also other difficulties in researching the effects of cannabis. Many people who smoke cannabis also smoke tobacco.[166] This causes confounding factors, where questions arise as to whether 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.[167]

However many universities in different countries outside the US have published hundreds of studies on effects of cannabis.[168]

Measles


From Wikipedia, the free encyclopedia
Measles
RougeoleDP.jpg
A child showing a classic 4-day measles rash.
Classification and external resources
ICD-10 B05
ICD-9 055
DiseasesDB 7890
MedlinePlus 001569
eMedicine derm/259 emerg/389 ped/1388
Patient UK Measles
MeSH D008457

Measles, also known as morbilli, or rubeola is a highly contagious infection caused by the measles virus.[1] Initial symptoms typically include fever, often greater than 40 °C (104.0 °F), cough, runny nose, and red eyes.[1][2] Two or three days after the start of symptoms small white spots may form inside the mouth, known as Koplik's spots. A red, flat rash which usually starts on the face and then spreads to the rest of the body typically begins three to five days after the start of symptoms.[2] Symptoms usually develop 10–12 days after exposure to an infected person and lasts 7–10 days.[3][4] Complications occur in about 30% and may include: diarrhea, blindness, inflammation of the brain, and pneumonia among others.[3][5] Rubella (German measles) and roseola are different diseases.[6]
Measles is an airborne disease which spreads easily through the coughs and sneezes of those infected. It may also be spread through contact with saliva or nasal secretions.[3] Nine out of ten people who are not immune who share living space with an infected person will catch it. People are infectious to others from four days before to four days after the start of the rash.[5] People usually only get the disease at most once.[3] Testing for the virus in suspected cases is important for public health efforts.[5]

The measles vaccine is effective at preventing the disease. Vaccination has resulted in a 75% decrease in deaths from the disease since the year 2000 with about 85% of children globally being vaccinated. No specific treatment is available. Supportive care, however, may improve outcomes.[3] This may include giving oral rehydration solution (slightly sweet and salty fluids), healthy food, and medications to help with the fever.[3][4] Antibiotics may be used if a bacteria infection such as pneumonia occurs. Vitamin A supplementation is also recommended in the developing world.[3]

Measles affects about 20 million people a year,[1] primarily in the developing areas of Africa and Asia.[3] It resulted in about 96,000 deaths in 2013 down from 545,000 deaths in 1990.[7] In 1980, the disease is estimated to have caused 2.6 million deaths per year.[3] Before immunization in the United States between three and four million cases occurred a year.[5] Most of those who are infected and who die are less than five years old.[3] The risk of death among those infected is usually 0.2%,[5] but may be up to 10% in those who have malnutrition.[3] It is not believed to affect animals.[3]

Signs and symptoms


Skin of a person after 3 days of measles infection

“Koplik's spots” on the third pre-eruptive day

The classic signs and symptoms of measles include four-day fevers (the 4 D's) and the three C's—cough, coryza (head cold), and conjunctivitis (red eyes)—along with fever and rashes. The fever may reach up to 40 °C (104 °F). Koplik's spots seen inside the mouth are pathognomonic (diagnostic) for measles, but are temporary and therefore rarely seen. Their recognition, before the affected person reaches maximum infectivity, can be used to reduce spread of epidemics.[8]

The characteristic measles rash is classically described as a generalized red maculopapular rash that begins several days after the fever starts. It starts on the back of the ears and, after a few hours, spreads to the head and neck before spreading to cover most of the body, often causing itching. The measles rash appears two to four days after the initial symptoms and lasts for up to eight days. The rash is said to "stain", changing color from red to dark brown, before disappearing.[9]

Complications

Complications with measles are relatively common, ranging from mild complications such as diarrhea to serious complications such as pneumonia (either direct viral pneumonia or secondary bacterial pneumonia),[10] otitis media,[11] acute brain inflammation[12] (and very rarely SSPE—subacute sclerosing panencephalitis),[13] and corneal ulceration (leading to corneal scarring).[14] Complications are usually more severe in adults who catch the virus.[15] The death rate in the 1920s was around 30% for measles pneumonia.[16]

Between 1987 and 2000, the case fatality rate across the United States was three measles-attributable deaths per 1000 cases, or 0.3%.[17] In underdeveloped nations with high rates of malnutrition and poor healthcare, fatality rates have been as high as 28%.[17] In immunocompromised persons (e.g., people with AIDS) the fatality rate is approximately 30%.[18] Risk factors for severe measles and its complications include: malnutrition,[19][20] underlying immunodeficiency,[19] pregnancy,[19][21] and vitamin A deficiency.[19][22]

Cause


An electron micrograph of the measles virus.

Measles is caused by the measles virus, a single-stranded, negative-sense, enveloped RNA virus of the genus Morbillivirus within the family Paramyxoviridae. The virus was first isolated in 1954 by Nobel Laureate John F. Enders and Thomas Peebles, who were careful to point out that the isolations were made from patients who had Koplik's spots.[23] Humans are the natural hosts of the virus; no other animal reservoirs are known to exist. This highly contagious virus is spread by coughing and sneezing via close personal contact or direct contact with secretions. Risk factors for measles virus infection include: immunodeficiency caused by HIV or AIDS,[24] leukemia,[25] alkylating agents, or corticosteroid therapy, regardless of immunization status;[19] travel to areas where measles is endemic or contact with travelers to endemic areas;[19] and the loss of passive, inherited antibodies before the age of routine immunization.[19]

Diagnosis

Clinical diagnosis of measles requires a history of fever of at least three days, with at least one of the three C's (cough, coryza, conjunctivitis). Observation of Koplik's spots is also diagnostic of measles.[8][26][27]

Alternatively, laboratory diagnosis of measles can be done with confirmation of positive measles IgM antibodies[28] or isolation of measles virus RNA from respiratory specimens.[29] For people unable to undergo phlebotomy, saliva can be collected for salivary measles-specific IgA testing.[30] Positive contact with other patients known to have measles adds strong epidemiological evidence to the diagnosis. The contact with any infected person in any way, including semen through sex, saliva, or mucus, can cause infection.[27]

Prevention


Rates of measles vaccination worldwide

In developed countries, children are immunized against measles at 12 months, generally as part of a three-part MMR vaccine (measles, mumps, and rubella). The vaccination is generally not given earlier than this because sufficient antimeasles immunoglobulins (antibodies) are acquired via the placenta from the mother during pregnancy may persist to prevent the vaccine viruses from being effective.[citation needed] A second dose is usually given to children between the ages of four and five, to increase rates of immunity. Vaccination rates have been high enough to make measles relatively uncommon. Adverse reactions to vaccination are rare, with fever and pain at the injection site being the most common. Life-threatening adverse reactions occur in less than one per million vaccinations (<0 .0001="" class="reference" id="cite_ref-cubavac_31-0" sup="">[31]

In developing countries where measles is highly endemic, WHO doctors recommend two doses of vaccine be given at six and nine months of age. The vaccine should be given whether the child is HIV-infected or not.[32] The vaccine is less effective in HIV-infected infants than in the general population, but early treatment with antiretroviral drugs can increase its effectiveness.[33] Measles vaccination programs are often used to deliver other child health interventions, as well, such as bed nets to protect against malaria, antiparasite medicine and vitamin A supplements, and so contribute to the reduction of child deaths from other causes.[34]

Treatment

There is no specific treatment for measles. Most patients with uncomplicated measles will recover with rest and supportive treatment. It is, however, important to seek medical advice if the patient becomes sicker, as they may be developing complications.

Some patients will develop pneumonia as a sequel to the measles. Other complications include ear infections, bronchitis (either viral bronchitis or secondary bacterial bronchitis), and brain inflammation.[35] Brain inflammation from measles has a mortality rate of 15%. While there is no specific treatment for brain inflammation from measles, antibiotics are required for bacterial pneumonia, sinusitis, and bronchitis that can follow measles.

All other treatment addresses symptoms, with ibuprofen or paracetamol to reduce fever and pain and, if required, a fast-acting bronchodilator for cough. As for aspirin, some research has suggested a correlation between children who take aspirin and the development of Reye syndrome.[36] Some research has shown aspirin may not be the only medication associated with Reye, and even antiemetics have been implicated,[37] with the point being the link between aspirin use in children and Reye's syndrome development is weak at best, if not actually nonexistent.[36][38] Nevertheless, most health authorities still caution against the use of aspirin for any fevers in children under 16.[39][40][41][42]

The use of vitamin A in treatment has been investigated. A systematic review of trials into its use found no significant reduction in overall mortality, but it did reduce mortality in children aged under two years.[43][44][45] A specific drug treatment for measles ERDRP-0519 has shown promising results in animal studies, but has not yet been tested in humans.[46][47][48]

Prognosis

The majority of patients survive measles, though in some cases, complications may occur, which may include bronchitis, and—in about 1 in 100,000 cases[49]panencephalitis, which is usually fatal.[50]
Acute measles encephalitis is another serious risk of measles virus infection. It typically occurs two days to one week after the breakout of the measles exanthem and begins with very high fever, severe headache, convulsions and altered mentation. A patient may become comatose, and death or brain injury may occur.[51]

Epidemiology

Disability-adjusted life year for measles per 100,000 inhabitants in 2002.
  no data
  ≤ 10
  10–25
  25–50
  50–75
  75–100
  100–250
  250–500
  500–750
  750–1000
  1000–1500
  1500–2000
  ≥ 2000

Measles is extremely infectious and its continued circulation in a community depends on the generation of susceptible hosts by birth of children. In communities which generate insufficient new hosts the disease will die out. This concept was first recognized in measles by Bartlett in 1957, who referred to the minimum number supporting measles as the critical community size (CCS).[52]
Analysis of outbreaks in island communities suggested that the CCS for measles is c. 250,000.[53]
In 2011, the WHO estimated that there were about 158,000 deaths caused by measles. This is down from 630,000 deaths in 1990.[54] In developed countries, death occurs in 1 to 2 cases out of every 1,000 (0.1% - 0.2%).[55] In populations with high levels of malnutrition and a lack of adequate healthcare, mortality can be as high as 10%. In cases with complications, the rate may rise to 20–30%.[56] Increased immunization has led to an estimated 78% drop in measles deaths among UN member states.[57][58] This reduction made up 25% of the decline in mortality in children under five during this period.[citation needed]
Reported cases[59][60][61][62]
WHO-Region 1980 1990 2000 2005 2014
African Region 1,240,993 481,204 520,102 316,224 12,125
Region of the Americas 257,790 218,579 1,755 19 3,100
Eastern Mediterranean Region 341,624 59,058 38,592 15,069 2,214
European Region 851,849 234,827 37,421 37,332 2,430
South-East Asia Region 199,535 224,925 61,975 83,627 1,540
Western Pacific Region 1,319,640 155,490 176,493 128,016 34,310
Worldwide 4,211,431 1,374,083 836,338 580,287 55,719

Even in countries where vaccination has been introduced, rates may remain high. In Ireland, vaccination was introduced in 1985. There were 99,903 cases that year. Within two years, the number of cases had fallen to 201, but this fall was not sustained. Measles is a leading cause of vaccine-preventable childhood mortality. Worldwide, the fatality rate has been significantly reduced by a vaccination campaign led by partners in the Measles Initiative: the American Red Cross, the United States Centers for Disease Control and Prevention (CDC), the United Nations Foundation, UNICEF and the WHO. Globally, measles fell 60% from an estimated 873,000 deaths in 1999 to 345,000 in 2005.[34] Estimates for 2008 indicate deaths fell further to 164,000 globally, with 77% of the remaining measles deaths in 2008 occurring within the Southeast Asian region.[63]

In 2006–07 there were 12,132 cases in 32 European countries: 85% occurred in five countries: Germany, Italy, Romania, Switzerland and the UK. 80% occurred in children and there were 7 deaths.[64]

Five out of six WHO regions have set goals to eliminate measles, and at the 63rd World Health Assembly in May 2010, delegates agreed a global target of a 95% reduction in measles mortality by 2015 from the level seen in 2000, as well as to move towards eventual eradication. However, no specific global target date for eradication has yet been agreed to as of May 2010.[65][66]

History


16th century Aztec drawing of someone with measles

The Antonine Plague,[67] 165–180 AD, also known as the Plague of Galen, who described it, was probably smallpox or measles. The epidemic may have claimed the life of Roman emperor Lucius Verus. Total deaths have been estimated at five million.[68] Estimates of the timing of evolution of measles seem to suggest this plague was something other than measles. The first scientific description of measles and its distinction from smallpox and chickenpox is credited to the Persian physician Rhazes (860–932), who published The Book of Smallpox and Measles.[69] Given what is now known about the evolution of measles, this account is remarkably timely, as recent work that examined the mutation rate of the virus indicates the measles virus emerged from rinderpest (Cattle Plague) as a zoonotic disease between 1100 and 1200 AD, a period that may have been preceded by limited outbreaks involving a virus not yet fully acclimated to humans.[70] This agrees with the observation that measles requires a susceptible population of >500,000 to sustain an epidemic, a situation that occurred in historic times following the growth of medieval European cities.[71]

Maurice Hilleman's measles vaccine is estimated to prevent 1 million deaths every year.[72]

Measles is an endemic disease, meaning it has been continually present in a community, and many people develop resistance. In populations not exposed to measles, exposure to the new disease can be devastating. In 1529, a measles outbreak in Cuba killed two-thirds of the natives who had previously survived smallpox. Two years later, measles was responsible for the deaths of half the population of Honduras, and had ravaged Mexico, Central America, and the Inca civilization.[73]

Between roughly 1855 to 2005 measles has been estimated to have killed about 200 million people worldwide.[74] Measles killed 20 percent of Hawaii's population in the 1850s.[75] In 1875, measles killed over 40,000 Fijians, approximately one-third of the population.[76] In the 19th century, the disease killed 50% of the Andamanese population.[77] In 1954, the virus causing the disease was isolated from an 13-year-old boy from the United States, David Edmonston, and adapted and propagated on chick embryo tissue culture.[78] To date, 21 strains of the measles virus have been identified.[79] While at Merck, Maurice Hilleman developed the first successful vaccine.[80] Licensed vaccines to prevent the disease became available in 1963.[81] An improved measles vaccine became available in 1968.[82]

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