102-488: A joint ( / dʒ ɔɪ n t / ) is a rolled cannabis cigarette . Unlike commercial tobacco cigarettes, the user ordinarily hand-rolls joints with rolling papers , though in some cases they are machine-rolled. Rolling papers are the most common rolling medium in industrialized countries ; however, brown paper, cigarettes or beedies with the tobacco removed, receipts and paper napkin can also be used, particularly in developing countries . Modern papers are manufactured in
204-499: A 5-HT 1A receptor agonist. CBD can interfere with the uptake of adenosine , which plays an important role in biochemical processes, such as energy transfer. It may play a role in promoting sleep and suppressing arousal. CBD shares a precursor with THC and is the main cannabinoid in CBD-dominant Cannabis strains. CBD has been shown to play a role in preventing the short-term memory loss associated with THC . There
306-576: A chemical substance used in religious, shamanic , or spiritual contexts – in the Indian subcontinent since the Vedic period . The earliest known reports regarding the sacred status of cannabis in the Indian subcontinent come from the Atharva Veda , estimated to have been composed sometime around 1400 BCE. The Hindu god Shiva is described as a cannabis user, known as the "Lord of bhang ". In modern culture,
408-524: A cigarette filter or a bit of rolled thin cardboard in one end to serve as a mouthpiece, commonly referred to as the crutch , filter , or roach . The term "spliff" is sometimes used to distinguish a joint prepared with both cannabis and tobacco, as is commonly done in European countries, where joints containing only cannabis are uncommon. In the West Indies where this term originated (especially Jamaica ),
510-466: 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. Researchers at John Jay College of Criminal Justice reported that dietary zinc supplements can mask the presence of THC and other drugs in urine. However, a 2013 study conducted by researchers at the University of Utah School of Medicine refute
612-479: A spliff is simply a marijuana cigarette, normally containing no tobacco. Special vaporizers , made to look like joints, have also been designed for use with cannabis extract. The word joint ultimately originated from French, where it is an adjective meaning 'joined' ( past participle of the verb joindre ), derived in turn from Latin iunctus , past participle of iungere ('join'/'bind'/'yoke'). By 1821, 'joint' had become an Anglo-Irish term for an annexe, or
714-451: A vaporizer , consuming THC in pill form, or consuming cannabis foods . There is concern that cannabis may contribute to cardiovascular disease, but as of 2018 , evidence of this relationship was unclear. Research in these events is complicated because cannabis is often used in conjunction with tobacco, and drugs such as alcohol and cocaine that are known to have cardiovascular risk factors. Smoking cannabis has also been shown to increase
816-579: A biogenetic origin. It was reported in 2020 that phytocannabinoids can be found in other plants such as rhododendron , licorice and liverwort , and earlier in Echinacea . Phytocannabinoids are multi-ring phenolic compounds structurally related to THC, but endocannabinoids are fatty acid derivatives. Nonclassical synthetic cannabinoids (cannabimimetics) include aminoalkylindoles , 1,5-diarylpyrazoles, quinolines , and arylsulfonamides as well as eicosanoids related to endocannabinoids. Medical uses include
918-415: A causal relationship between cannabis use and chronic obstructive pulmonary disease . Short-term use of cannabis is associated with bronchodilation . Other side effects of cannabis use include cannabinoid hyperemesis syndrome (CHS), a condition which involves recurrent nausea, cramping abdominal pain, and vomiting. Cannabis smoke contains thousands of organic and inorganic chemical compounds. This tar
1020-641: A conclusion. Cannabis use is associated with increased risk of anxiety disorders, although causality has not been established. A review in 2019 found that research was insufficient to determine the safety and efficacy of using cannabis to treat schizophrenia, psychosis, or other mental disorders . Another found that cannabis during adolescence was associated with an increased risk of developing depression and suicidal behavior later in life, while finding no effect on anxiety. Heavy, long-term exposure to marijuana may have physical, mental, behavioral and social health consequences. It may be "associated with diseases of
1122-426: A decrease in short-term memory, dry mouth, impaired motor skills, reddening of the eyes, dizziness, feeling tired and vomiting. Some users may experience an episode of acute psychosis , which usually abates after six hours, but in rare instances, heavy users may find the symptoms continuing for many days. Legalization has increased the rates at which children are exposed to cannabis, particularly from edibles. While
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#17329024372601224-458: 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
1326-611: A drug. Emergency room (ER) admissions associated with cannabis use rose significantly from 2012 to 2016; adolescents from age 12–17 had the highest risk. At one Colorado medical center following legalization, approximately two percent of ER admissions were classified as cannabis users. The symptoms of one quarter of these users were partially attributed to cannabis (a total of 2567 out of 449,031 patients); other drugs were sometimes involved. Of these cannabis admissions, one quarter were for acute psychiatric effects , primarily suicidal ideation , depression, and anxiety. An additional third of
1428-472: A limited number of territories, including Canada, Belgium , Australia, the Netherlands , New Zealand, Spain, and many U.S. states . This usage generally requires a prescription, and distribution is usually done within a framework defined by local laws. According to DEA Chief Administrative Law Judge, Francis Young, "cannabis is one of the safest therapeutically active substances known to man". Being under
1530-523: A longer period of abstinence was associated with smaller magnitudes of impairment, both retrospective and prospective memory were impaired in cannabis users. The authors concluded that some, but not all, of the deficits associated with cannabis use were reversible. A 2012 meta-analysis found that deficits in most domains of cognition persisted beyond the acute period of intoxication, but was not evident in studies where subjects were abstinent for more than 25 days. Few high quality studies have been performed on
1632-400: A lower affinity for CB1 receptors, meaning that much higher doses of CBN are required in order to experience physiologic effects (e.g., mild sedation) associated with CB1R agonism. Although scientific reports are conflicting, the majority of findings suggest that CBN has a slightly higher affinity for CB2 as compared to CB1. Although CBN has been marketed as a sleep aid in recent years, there
1734-518: A moderately psychoactive cannabinoid, has been isolated from different Radula varieties. Machaeriol A and related compounds are found in plants from the Machaerium family. Most of the phytocannabinoids are nearly insoluble in water but are soluble in lipids , alcohols , and other non-polar organic solvents . Cannabis plants can exhibit wide variation in the quantity and type of cannabinoids they produce. The mixture of cannabinoids produced by
1836-514: A near 1:1 ratio of CBD and THC. Also included are minor cannabinoids and terpenoids , ethanol and propylene glycol excipients , and peppermint flavoring. The drug, made by GW Pharmaceuticals , was first approved by Canadian authorities in 2005 to alleviate pain associated with multiple sclerosis , making it the first cannabis-based medicine. It is marketed by Bayer in Canada. Sativex has been approved in 25 countries; clinical trials are underway in
1938-548: A partial agonist at CB 1 , it behaves as a CB 1 antagonist in vivo . In rats, virodhamine was found to be present at comparable or slightly lower concentrations than anandamide in the brain , but 2- to 9-fold higher concentrations peripherally. Lysophosphatidylinositol is the endogenous ligand to novel endocannabinoid receptor GPR55 , making it a strong contender as the sixth endocannabinoid. Endocannabinoids serve as intercellular ' lipid messengers ', signaling molecules that are released from one cell and activating
2040-446: A plant is known as the plant's cannabinoid profile. Selective breeding has been used to control the genetics of plants and modify the cannabinoid profile. For example, strains that are used as fiber (commonly called hemp ) are bred such that they are low in psychoactive chemicals like THC. Strains used in medicine are often bred for high CBD content, and strains used for recreational purposes are usually bred for high THC content or for
2142-652: A range of sizes from a wide variety of materials including rice, hemp, and flax , and are also available in liquorice and other flavoured varieties. Joint size can vary, typically containing between 0.25 and 1 g ( 1 ⁄ 112 and 1 ⁄ 28 oz) net weight of cannabis. Tobacco is sometimes used in the rolling process. Although joints by definition contain cannabis, regional differences exist. In Europe, in certain Commonwealth nations , and more recently in North America, joints, or spliffs, typically include
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#17329024372602244-528: A record 44% of the US population has tried marijuana in their lifetime, an increase from 38% in 2013 and 33% in 1985. Marijuana use in the United States is three times above the global average, but in line with other Western democracies. Forty-four percent of American 12th graders have tried the drug at least once, and the typical age of first-use is 16, similar to the typical age of first-use for alcohol but lower than
2346-407: A side-room 'joined' to a main room. By 1877, this had developed into U.S. slang for a 'place, building, establishment,' and especially to an opium den . Its first usage in the sense of 'marijuana cigarette' is dated to 1938. Many slang terms are synonymous with the word joint . 'Spliff' is a West Indian word of Jamaican English origin which has spread to several western countries, particularly
2448-422: A specific chemical balance. Quantitative analysis of a plant's cannabinoid profile is often determined by gas chromatography (GC), or more reliably by gas chromatography combined with mass spectrometry (GC/MS). Liquid chromatography (LC) techniques are also possible and, unlike GC methods, can differentiate between the acid and neutral forms of the cannabinoids. There have been systematic attempts to monitor
2550-399: A subpopulation of microglia in the human cerebellum . CB 2 receptors appear to be responsible for immunomodulatory and possibly other therapeutic effects of cannabinoid as seen in vitro and in animal models. The classical cannabinoids are concentrated in a viscous resin produced in structures known as glandular trichomes . At least 113 different cannabinoids have been isolated from
2652-463: Is a lack of scientific evidence to support these claims, warranting skepticism on the part of consumers. Cannabinoid production starts when an enzyme causes geranyl pyrophosphate and olivetolic acid to combine and form CBGA . Next, CBGA is independently converted to either CBG , THCA , CBDA or CBCA by four separate synthase , FAD-dependent dehydrogenase enzymes. There is no evidence for enzymatic conversion of CBDA or CBD to THCA or THC. For
2754-835: Is a non-chemically uniform drug from the cannabis plant. Native to Central or South Asia, the cannabis plant has been used as a drug for both recreational and entheogenic purposes and in various traditional medicines for centuries. Tetrahydrocannabinol (THC) is the main psychoactive component of cannabis, which is one of the 483 known compounds in the plant, including at least 65 other cannabinoids , such as cannabidiol (CBD). Cannabis can be used by smoking , vaporizing , within food , or as an extract . Cannabis has various mental and physical effects , which include euphoria , altered states of mind and sense of time , difficulty concentrating, impaired short-term memory , impaired body movement (balance and fine psychomotor control), relaxation, and an increase in appetite . Onset of effects
2856-505: Is about as potent as THC at the CB 1 receptor. Anandamide is found in nearly all tissues in a wide range of animals. Anandamide has also been found in plants, including small amounts in chocolate. Two analogs of anandamide, 7,10,13,16-docosatetraenoylethanolamide and homo -γ-linolenoylethanolamine, have similar pharmacology . All of these compounds are members of a family of signalling lipids called N -acylethanolamines , which also includes
2958-583: Is also stored in fat in addition to being metabolized in the liver. Δ -THC is metabolized to 11-hydroxy-Δ -THC , which is then metabolized to 9-carboxy-THC . Some cannabis metabolites can be detected in the body several weeks after administration. These metabolites are the chemicals recognized by common antibody-based "drug tests"; in the case of THC or others, these loads do not represent intoxication (compare to ethanol breath tests that measure instantaneous blood alcohol levels ), but an integration of past consumption over an approximately month-long window. This
3060-457: Is associated with cumulative cannabis exposure, and is reversed after one month of abstinence. There is limited evidence that chronic cannabis use can reduce levels of glutamate metabolites in the human brain. About 9% of those who experiment with marijuana eventually become dependent according to DSM-IV (1994) criteria. A 2013 review estimates daily use is associated with a 10–20% rate of dependence. The highest risk of cannabis dependence
3162-526: Is associated with heavy cannabis use, although the relationship is inconsistent and weaker than for tobacco and other substances. The direction of cause and effect , however, is unclear. The long-term effects of cannabis are not clear. There are concerns surrounding memory and cognition problems , risk of addiction, and the risk of schizophrenia in young people. Although global abnormalities in white matter and grey matter are not consistently associated with cannabis use, reduced hippocampal volume
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3264-787: Is because they are fat-soluble, lipophilic molecules that accumulate in fatty tissues. Research shows the effect of cannabinoids might be modulated by aromatic compounds produced by the cannabis plant, called terpenes . This interaction would lead to the entourage effect . Recent evidence has shown that cannabinoids play a role in the modulation of various mitochondrial processes, including intracellular calcium regulation, activation of apoptosis, impairment of electron transport chain activity, disruption of mitochondrial respiration and ATP production, and regulation of mitochondrial dynamics. These processes contribute to various aspects of cellular biology and can be modified in response to external stimuli. The interaction between cannabinoids and mitochondria
3366-528: Is by far the most widely used illicit substance, with the highest use among adults (as of 2018 ) in Zambia , the United States , Canada , and Nigeria . Between 1973 and 1978, eleven states decriminalized marijuana. In 2001, Nevada reduced marijuana possession to a misdemeanor and since 2012, several other states have decriminalized and even legalized marijuana. In 2018, surveys indicated that almost half of
3468-459: 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 polycyclic aromatic hydrocarbons , including benz[a]pyrene. Cannabis smoke is also inhaled more deeply than tobacco smoke. As of 2015 , there is no consensus regarding whether cannabis smoking is associated with an increased risk of cancer. Light and moderate use of cannabis
3570-414: Is complex, and various molecular mechanisms have been proposed, including direct effects on mitochondrial membranes and receptor-mediated effects. However, an integrated hypothesis of cannabinoids' actions on these processes has yet to be formulated due to conflicting data and the complexity of the pathways involved. Nabiximols (brand name Sativex) is an aerosolized mist for oral administration containing
3672-436: Is consistently found. Amygdala abnormalities are sometimes reported, although findings are inconsistent. Cannabis use is associated with increased recruitment of task-related areas, such as the dorsolateral prefrontal cortex , which is thought to reflect compensatory activity due to reduced processing efficiency. Cannabis use is also associated with downregulation of CB 1 receptors. The magnitude of down regulation
3774-408: Is felt within minutes when smoked, but may take up to 90 minutes when eaten (as orally consumed drugs must be digested and absorbed). The effects last for two to six hours, depending on the amount used. At high doses, mental effects can include anxiety , delusions (including ideas of reference ), hallucinations , panic , paranoia , and psychosis . There is a strong relation between cannabis use and
3876-447: Is formally known as acute cannabis-associated psychotic symptoms (CAPS). At an epidemiological level, a dose–response relationship exists between cannabis use and increased risk of psychosis and earlier onset of psychosis. Although the epidemiological association is robust, evidence to prove a causal relationship is lacking. Cannabis may also increase the risk of depression, but insufficient research has been performed to draw
3978-641: Is found in those with a history of poor academic achievement, deviant behavior in childhood and adolescence, rebelliousness, poor parental relationships, or a parental history of drug and alcohol problems. Of daily users, about 50% experience withdrawal upon cessation of use (i.e. are dependent), characterized by sleep problems, irritability, dysphoria, and craving. Cannabis withdrawal is less severe than withdrawal from alcohol. According to DSM-V criteria, 9% of those who are exposed to cannabis develop cannabis use disorder, compared to 20% for cocaine , 23% for alcohol and 68% for nicotine . Cannabis use disorder in
4080-404: Is insufficient for drawing conclusions about safety or efficacy. There is evidence supporting the use of cannabis or its derivatives in the treatment of chemotherapy-induced nausea and vomiting, neuropathic pain, and multiple sclerosis. Lower levels of evidence support its use for AIDS wasting syndrome , epilepsy, rheumatoid arthritis, and glaucoma. The medical use of cannabis is legal only in
4182-527: Is legalized only in the Australian Capital Territory . Cannabis is a Scythian word. The ancient Greeks learned of the use of cannabis by observing Scythian funerals, during which cannabis was consumed. In Akkadian , cannabis was known as qunubu ( 𐎯𐎫𐎠𐎭𐏂 ). The word was adopted in to the Hebrew as qaneh bosem ( קָנֶה בֹּשׂם ). Medical cannabis, or medical marijuana, refers to
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4284-409: Is mostly used recreationally or as a medicinal drug, although it may also be used for spiritual purposes. In 2013, between 128 and 232 million people used cannabis (2.7% to 4.9% of the global population between the ages of 15 and 65). It is the most commonly used largely-illegal drug in the world, with the highest use among adults in Zambia , the United States , Canada , and Nigeria . Since the 1970s,
4386-585: Is not believed to increase risk of lung or upper airway cancer. Evidence for causing these cancers is mixed concerning heavy, long-term use. In general there are far lower risks of pulmonary complications for regular cannabis smokers when compared with those of tobacco. A 2015 review found an association between cannabis use and the development of testicular germ cell tumors (TGCTs), particularly non- seminoma TGCTs. Another 2015 meta-analysis found no association between lifetime cannabis use and risk of head or neck cancer. Combustion products are not present when using
4488-484: Is tentative evidence that CBD has an anti-psychotic effect, but research in this area is limited. Cannabinol (CBN) is a mildly psychoactive cannabinoid that acts as a low affinity partial agonist at both CB1 and CB2 receptors. Through its mechanism of partial agonism at the CB1R, CBN is thought to interact with other kinds of neurotransmission (e.g., dopaminergic, serotonergic, cholinergic, and noradrenergic). CBN
4590-465: Is the primary psychoactive component of the Cannabis plant. Delta -9- tetrahydrocannabinol (Δ -THC, THC) and delta-8-tetrahydrocannabinol (Δ -THC), through intracellular CB 1 activation, induce anandamide and 2-arachidonoylglycerol synthesis produced naturally in the body and brain . These cannabinoids produce the effects associated with cannabis by binding to the CB 1 cannabinoid receptors in
4692-501: The Cannabis plant. All classes derive from cannabigerol-type (CBG) compounds and differ mainly in the way this precursor is cyclized. The classical cannabinoids are derived from their respective 2- carboxylic acids (2-COOH) by decarboxylation (catalyzed by heat, light, or alkaline conditions). The best studied cannabinoids include tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN). Tetrahydrocannabinol (THC)
4794-490: The Anandamide -like alkylamides from Echinacea species, most notably the cis/trans isomers of dodeca-2E,4E,8Z,10E/Z-tetraenoic-acid-isobutylamide. At least 25 different alkylamides have been identified, and some of them have shown affinities to the CB 2 -receptor. In some Echinacea species, cannabinoids are found throughout the plant structure, but are most concentrated in the roots and flowers. Yangonin found in
4896-459: The Food and Drug Administration for treatment of two rare and severe forms of epilepsy , Dravet and Lennox-Gastaut syndromes. Nabilone (Cesamet) is an FDA approved synthetic analog of THC, prescribed for the treatment of nausea and vomiting induced by chemotherapy treatment in people who have failed to respond adequately to conventional antiemetic treatments. Cannabinoids can be separated from
4998-699: The aromatic ring. In THC, CBD, and CBN, this side-chain is a pentyl (5-carbon) chain. In the most common homologue, the pentyl chain is replaced with a propyl (3-carbon) chain. Cannabinoids with the propyl side chain are named using the suffix varin and are designated THCV, CBDV, or CBNV, while those with the heptyl side chain are named using the suffix phorol and are designated THCP and CBDP. Phytocannabinoids are known to occur in several plant species besides cannabis. These include Echinacea purpurea , Echinacea angustifolia , Acmella oleracea , Helichrysum umbraculigerum , and Radula marginata . The best-known cannabinoids that are not derived from Cannabis are
5100-580: The cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoactive compound in cannabis . Cannabidiol (CBD) is also a major constituent of temperate cannabis plants and a minor constituent in tropical varieties. At least 100 distinct phytocannabinoids have been isolated from cannabis, although only four (i.e., THCA, CBDA, CBCA and their common precursor CBGA) have been demonstrated to have
5202-478: The kava plant has significant affinity to the CB1 receptor. Tea ( Camellia sinensis ) catechins have an affinity for human cannabinoid receptors. A widespread dietary terpene, beta-caryophyllene , a component from the essential oil of cannabis and other medicinal plants, has also been identified as a selective agonist of peripheral CB 2 -receptors, in vivo . Black truffles contain anandamide. Perrottetinene ,
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#17329024372605304-401: The medulla oblongata , the part of the brain stem responsible for respiratory and cardiovascular functions. CB1 is also found in the human anterior eye and retina. CB 2 receptors are predominantly found in the immune system , or immune-derived cells with varying expression patterns. While found only in the peripheral nervous system, a report does indicate that CB 2 is expressed by
5406-539: The stereochemistry of CBD. The following year, in 1964, Mechoulam and his team identified the stereochemistry of Tetrahydrocannabinol (THC). Due to molecular similarity and ease of synthetic conversion, CBD was originally believed to be a natural precursor to THC. However, it is now known that CBD and THC are produced independently in the Cannabis plant from the precursor CBG. The Agriculture Improvement Act of 2018 has been interpreted as allowing any hemp-derived product not exceeding 0.3% Δ -THC to be sold legally in
5508-415: The μ- and δ-opioid receptors . THC also potentiates the effects of the glycine receptors . It is unknown if or how these actions contribute to the effects of cannabis. 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
5610-455: The 20th century. In 2013, Uruguay became the first country to legalize recreational use of cannabis. Other countries to do so are Canada, Georgia , Germany , Luxembourg , Malta , South Africa , and Thailand . In the U.S., the recreational use of cannabis is legalized in 24 states , 3 territories, and the District of Columbia , though the drug remains federally illegal . In Australia , it
5712-476: The CB 1 receptor, and only weakly to the CB 2 receptor. Discovered in 2000, NADA preferentially binds to the CB 1 receptor. Like anandamide, NADA is also an agonist for the vanilloid receptor subtype 1 (TRPV1), a member of the vanilloid receptor family. A fifth endocannabinoid, virodhamine, or O -arachidonoyl-ethanolamine (OAE), was discovered in June 2002. Although it is a full agonist at CB 2 and
5814-462: The CB 2 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 CB 1 receptors, which inhibit a secondary messenger system ( adenylate cyclase ) in a dose-dependent manner. Via CB 1 receptor activation, THC indirectly increases dopamine release and produces psychotropic effects. CBD also acts as an allosteric modulator of
5916-489: The DSM-V involves a combination of DSM-IV criteria for cannabis abuse and dependence, plus the addition of craving, without the criterion related to legal troubles. From a clinical perspective, two significant school of thought exists for psychiatric conditions associated with cannabis (or cannabinoids) use: transient, non-persistent psychotic reactions, and longer-lasting, persistent disorders that resemble schizophrenia. The former
6018-483: The UK and Europe. Its precise etymology is unknown, but it is attested as early as 1936. There is also a myth that, because it is smoked within joint circle of friends, it is known as a 'joint'. 'J' or 'jay' can be used as an abbreviation for a generic joint. Another frequently used term is 'doobie.' The end or butt of a mostly smoked joint is referred to as a " roach " in U.S. and Australian slang. Small metal clips to facilitate
6120-565: The US. Because the law limited only Δ -THC levels, many other cannabinoids are generally considered legal to sell and are widely available in stores and online, including Δ -THC , Δ -THC , HHC , and THCP , but have not had the same in-depth research that the Δ isomer has on the human body; carrying potential risks in the short- or long-term. Other concerns include difficulties for drug testing due to novel metabolites , or high potency/ binding affinity of isomers for cannabinoid receptors showing potential for abuse (i.e., THCP, which has 33×
6222-534: The United States to gain FDA approval. In 2007, it was approved for treatment of cancer pain. In Phase III trials, the most common adverse effects were dizziness, drowsiness and disorientation; 12% of subjects stopped taking the drug because of the side effects. Dronabinol (brand names Marinol and Syndros) is a delta-9-THC containing drug for treating HIV/AIDS -induced anorexia and chemotherapy-induced nausea and vomiting . The CBD drug Epidiolex has been approved by
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#17329024372606324-423: The amount administered and the sensitivity of the assessment method). 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. The main psychoactive component of cannabis is tetrahydrocannabinol (THC), which is formed via decarboxylation of tetrahydrocannabinolic acid (THCA) from
6426-406: The application of heat. Raw leaf is not psychoactive because the cannabinoids are in the form of carboxylic acids . THC is one of the 483 known compounds in the plant, including at least 65 other cannabinoids, such as cannabidiol (CBD). 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
6528-425: The binding affinity of Δ -THC) From 2021 to 2023, the Δ -THC market generated US$ 2 billion in revenue. Many substances are scheduled at the state level under various synonyms owing to the different dibenzopyran and monoterpenoid naming conventions. Delta-1, Delta-6, and Delta 3,4-Tetrahydrocannabinol are alternative names for Delta-9, Delta-8, and Delta-6a10a Tetrahydrocannabinol, respectively. A 2023 paper seeking
6630-468: The brain than anandamide, and there is some controversy over whether 2-AG rather than anandamide is chiefly responsible for endocannabinoid signalling in vivo . In particular, one in vitro study suggests that 2-AG is capable of stimulating higher G-protein activation than anandamide, although the physiological implications of this finding are not yet known. In 2001, a third, ether -type endocannabinoid, 2-arachidonyl glyceryl ether (noladin ether),
6732-478: The brain. Cannabidiol (CBD) is mildly psychotropic . Evidence shows that the compound counteracts cognitive impairment associated with the use of cannabis. Cannabidiol has little affinity for CB 1 and CB 2 receptors but acts as an indirect antagonist of cannabinoid agonists. It was found to be an antagonist at the putative new cannabinoid receptor, GPR55 , a GPCR expressed in the caudate nucleus and putamen . Cannabidiol has also been shown to act as
6834-522: The cannabinoid profile of cannabis over time, but their accuracy is impeded by the illegal status of the plant in many countries. Cannabinoids can be administered by smoking, vaporizing, oral ingestion, transdermal patch, intravenous injection, sublingual absorption, or rectal suppository. Once in the body, most cannabinoids are metabolized in the liver , especially by cytochrome P450 mixed-function oxidases, mainly CYP 2C9 . Thus supplementing with CYP 2C9 inhibitors leads to extended intoxication. Some
6936-476: The cannabinoid receptors present on other nearby cells. Although in this intercellular signaling role they are similar to the well-known monoamine neurotransmitters such as dopamine , endocannabinoids differ in numerous ways from them. For instance, they are used in retrograde signaling between neurons. Furthermore, endocannabinoids are lipophilic molecules that are not very soluble in water. They are not stored in vesicles and exist as integral constituents of
7038-473: The cases were for gastrointestinal issues including cannabinoid hyperemesis syndrome . According to the United States Department of Health and Human Services, there were 455,000 emergency room visits associated with cannabis use in 2011. These statistics include visits in which the patient was treated for a condition induced by or related to recent cannabis use. The drug use must be "implicated" in
7140-450: The control of movement and motor coordination, learning and memory, emotion and motivation, addictive-like behavior and pain modulation, among others. CB 1 receptors are found primarily in the brain , more specifically in the basal ganglia and in the limbic system , including the hippocampus and the striatum . They are also found in the cerebellum and in both male and female reproductive systems . CB 1 receptors are absent in
7242-415: The dibenzopyran numbering system widely used today, the major form of THC is called Δ -THC, while the minor form is called Δ -THC. Under the alternate terpene numbering system, these same compounds are called Δ -THC and Δ -THC, respectively. Most classical cannabinoids are 21-carbon compounds. However, some do not follow this rule, primarily because of variation in the length of the side-chain attached to
7344-423: The effects of cannabis is usually referred to as being "high". Cannabis consumption has both psychoactive and physiological effects. The "high" experience can vary widely, based (among other things) on the user's prior experience with cannabis, and the type of cannabis consumed. When smoking cannabis, a euphoriant effect can occur within minutes of smoking. Aside from a subjective change in perception and mood,
7446-418: The emergency department visit, but does not need to be the direct cause of the visit. Most of the illicit drug emergency room visits involved multiple drugs. In 129,000 cases, cannabis was the only implicated drug. THC is a weak partial agonist at CB 1 receptors , while CBD is a CB 1 receptor antagonist. The CB 1 receptor is found primarily in the brain as well as in some peripheral tissues, and
7548-447: The extraction of these compounds. The first discovery of an individual cannabinoid was made, when British chemist Robert S. Cahn reported the partial structure of Cannabinol (CBN), which he later identified as fully formed in 1940. Two years later, in 1942, American chemist, Roger Adams , made history when he discovered Cannabidiol (CBD). Progressing from Adams research, in 1963 Israeli professor Raphael Mechoulam later identified
7650-488: The first cannabinoid receptors in the 1980s helped to resolve this debate. These receptors are common in animals. Two known cannabinoid receptors are termed CB 1 and CB 2 , with mounting evidence of more. The human brain has more cannabinoid receptors than any other G protein-coupled receptor (GPCR) type. The Endocannabinoid System (ECS) regulates many functions of the human body. The ECS plays an important role in multiple aspects of neural functions, including
7752-404: The first-use age for other illicit drugs. A 2022 Gallup poll concluded Americans are smoking more marijuana than cigarettes for the first time. Acute negative effects may include anxiety and panic, impaired attention and memory, an increased risk of psychotic symptoms, the inability to think clearly, and an increased risk of accidents. Cannabis impairs a person's driving ability, and THC
7854-417: 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
7956-569: The latter substances. Cannabinoid hyperemesis syndrome (CHS) is a severe condition seen in some chronic cannabis users where they have repeated bouts of uncontrollable vomiting for 24–48 hours. Four cases of death have been reported as a result of CHS. A limited number of studies have examined the effects of cannabis smoking on the respiratory system. Chronic heavy marijuana smoking is associated with respiratory infections , coughing, production of sputum, wheezing, and other symptoms of chronic bronchitis. The available evidence does not support
8058-535: The liver (particularly with co-existing hepatitis C ), lungs, heart, and vasculature". A 2014 review found that while cannabis use may be less harmful than alcohol use, the recommendation to substitute it for problematic drinking was premature without further study. Various surveys conducted between 2015 and 2019 found that many users of cannabis substitute it for prescription drugs (including opioids), alcohol, and tobacco; most of those who used it in place of alcohol or tobacco either reduced or stopped their intake of
8160-579: The long-term effects of cannabis on cognition, and the results were generally inconsistent. Furthermore, effect sizes of significant findings were generally small. One review concluded that, although most cognitive faculties were unimpaired by cannabis use, residual deficits occurred in executive functions . Impairments in executive functioning are most consistently found in older populations, which may reflect heavier cannabis exposure, or developmental effects associated with adolescent cannabis use. One review found three prospective cohort studies that examined
8262-510: The membrane bilayers that make up cells. They are believed to be synthesized 'on-demand' rather than made and stored for later use. As hydrophobic molecules, endocannabinoids cannot travel unaided for long distances in the aqueous medium surrounding the cells from which they are released and therefore act locally on nearby target cells. Hence, although emanating diffusely from their source cells, they have much more restricted spheres of influence than do hormones , which can affect cells throughout
8364-817: The most common short-term physical and neurological effects include increased heart rate, increased appetite, impairment of short-term and working memory, and impairment of psychomotor coordination . Additional desired effects from consuming cannabis include relaxation, a general alteration of conscious perception , increased awareness of sensation, increased libido and distortions in the perception of time and space. At higher doses, effects can include altered body image , auditory or visual illusions , pseudohallucinations and ataxia from selective impairment of polysynaptic reflexes . In some cases, cannabis can lead to dissociative states such as depersonalization and derealization . Cannabis has held sacred status in several religions and has served as an entheogen –
8466-449: The noncannabimimetic palmitoylethanolamide and oleoylethanolamide , which possess anti-inflammatory and anorexigenic effects, respectively. Many N -acylethanolamines have also been identified in plant seeds and in molluscs. Another endocannabinoid, 2-arachidonoylglycerol, binds to both the CB 1 and CB 2 receptors with similar affinity, acting as a full agonist at both. 2-AG is present at significantly higher concentrations in
8568-490: The people in the United States had tried marijuana, 16% had used it in the past year, and 11% had used it in the past month. In 2014, surveys said daily marijuana use amongst US college students had reached its highest level since records began in 1980, rising from 3.5% in 2007 to 5.9% in 2014 and had surpassed daily cigarette use. In the US, men are over twice as likely to use marijuana as women, and 18–29-year-olds are six times more likely to use as over-65-year-olds. In 2015,
8670-491: The plant by extraction with organic solvents . Hydrocarbons and alcohols are often used as solvents. However, these solvents are flammable and many are toxic. Butane may be used, which evaporates extremely quickly. Supercritical solvent extraction with carbon dioxide is an alternative technique. Once extracted, isolated components can be separated using wiped film vacuum distillation or other distillation techniques. Also, techniques such as SPE or SPME are found useful in
8772-570: The possibility of self-administered zinc producing false-negative urine drug tests. CBD is a 5-HT 1A receptor agonist, which is under laboratory research to determine if it has an anxiolytic effect. It is often claimed that sativa strains provide a more stimulating psychoactive high while indica strains are more sedating with a body high. However, this is disputed by researchers. Cannabinoid Cannabinoids ( / k ə ˈ n æ b ə n ɔɪ d z ˌ ˈ k æ n ə b ə n ɔɪ d z / ) are several structural classes of compounds found in
8874-513: The potency of illicit cannabis has increased, with THC levels rising and CBD levels dropping. Cannabis plants have been grown since at least the 3rd millennium BCE and there is evidence of it being smoked for its psychoactive effects around 500 BCE in the Pamir Mountains , Central Asia. Since the 14th century, cannabis has been subject to legal restrictions. The possession, use, and cultivation of cannabis has been illegal in most countries since
8976-432: The propyl homologues (THCVA, CBDVA and CBCVA), there is an analogous pathway that is based on CBGVA from divarinolic acid instead of olivetolic acid. In addition, each of the compounds above may be in different forms depending on the position of the double bond in the alicyclic carbon ring. There is potential for confusion because there are different numbering systems used to describe the position of this double bond. Under
9078-459: The receptors. Anandamide was the first such compound identified as arachidonoyl ethanolamine. The name is derived from ananda , the Sanskrit word for bliss. It has a pharmacology similar to THC , although its structure is quite different. Anandamide binds to the central (CB 1 ) and, to a lesser extent, peripheral (CB 2 ) cannabinoid receptors, where it acts as a partial agonist. Anandamide
9180-415: The regulation of cannabinoid terminology coined the term "derived psychoactive cannabis products" to accurately and usefully distinguish said products whilst excluding unrelated substances. Endocannabinoids are substances produced from within the body that activate cannabinoid receptors . After the discovery of the first cannabinoid receptor in 1988, scientists began searching for endogenous ligands for
9282-526: The relationship between self-reported cannabis use and intelligence quotient (IQ). The study following the largest number of heavy cannabis users reported that IQ declined between ages 7–13 and age 38. Poorer school performance and increased incidence of leaving school early were both associated with cannabis use, although a causal relationship was not established. Cannabis users demonstrated increased activity in task-related brain regions, consistent with reduced processing efficiency. A reduced quality of life
9384-459: The risk of myocardial infarction by 4.8 times for the 60 minutes after consumption. There is preliminary evidence that cannabis interferes with the anticoagulant properties of prescription drugs used for treating blood clots . As of 2019 , the mechanisms for the anti-inflammatory and possible pain relieving effects of cannabis were not defined, and there were no governmental regulatory approvals or clinical practices for use of cannabis as
9486-537: The risk of psychosis, though the direction of causality is debated. Physical effects include increased heart rate, difficulty breathing, nausea, and behavioral problems in children whose mothers used cannabis during pregnancy; short-term side effects may also include dry mouth and red eyes. Long-term adverse effects may include addiction, decreased mental ability in those who started regular use as adolescents, chronic coughing, susceptibility to respiratory infections , and cannabinoid hyperemesis syndrome . Cannabis
9588-480: The smoking of a "roach" are called "roach clips". In the UK the term roach is commonly used to describe the cardboard mouthpiece. Roach clips cover a wide variety of paraphernalia including alligator clips, forceps, needle nose pliers, ceramic pieces with holes through them, and tweezers. Cannabis (drug) Cannabis ( / ˈ k æ n ə b ɪ s / ), commonly known as marijuana ( / ˌ m æ r ə ˈ w ɑː n ə / ), weed , and pot , among other names ,
9690-461: The spiritual use of cannabis has been spread by the disciples of the Rastafari movement who use cannabis as a sacrament and as an aid to meditation. Many different ways to consume cannabis involve heat to decarboxylate THCA into THC; common modes include: In 2013, between 128 and 232 million people used cannabis (2.7% to 4.9% of the global population between the ages of 15 and 65). Cannabis
9792-422: The strain it can place on the cardiovascular system . Some deaths have also been attributed to cannabinoid hyperemesis syndrome . There is an association between cannabis use and suicide, particularly in younger users. A 16-month survey of Oregon and Alaska emergency departments found a report of the death of an adult who had been admitted for acute cannabis toxicity. A 2015 meta-analysis found that, although
9894-423: The toxicity and lethality of THC in children is not known, they are at risk for encephalopathy, hypotension, respiratory depression severe enough to require ventilation, somnolence and coma. There is no clear evidence for a link between cannabis use and deaths from cardiovascular disease, but a 2019 review noted that it may be an under-reported, contributory factor or direct cause in cases of sudden death , due to
9996-431: The treatment of nausea due to chemotherapy , spasticity , and possibly neuropathic pain . Common side effects include dizziness, sedation, confusion, dissociation, and "feeling high". Before the 1980s, cannabinoids were speculated to produce their physiological and behavioral effects via nonspecific interaction with cell membranes , instead of interacting with specific membrane-bound receptors . The discovery of
10098-635: The use of cannabis to treat disease or improve symptoms; however, there is no single agreed-upon definition (e.g., cannabinoids derived from cannabis and synthetic cannabinoids are also used). The rigorous scientific study of cannabis as a medicine has been hampered by production restrictions and by the fact that it is classified as an illegal drug by many governments. There is some evidence suggesting cannabis can be used to reduce nausea and vomiting during chemotherapy , to improve appetite in people with HIV/AIDS , or to treat chronic pain and muscle spasms . Evidence for its use for other medical applications
10200-508: Was isolated from porcine brain. Prior to this discovery, it had been synthesized as a stable analog of 2-AG; indeed, some controversy remains over its classification as an endocannabinoid, as another group failed to detect the substance at "any appreciable amount" in the brains of several different mammalian species. It binds to the CB 1 cannabinoid receptor ( K i = 21.2 nmol /L) and causes sedation, hypothermia, intestinal immobility, and mild antinociception in mice. It binds primarily to
10302-442: Was the first cannabis compound to be isolated from cannabis extract in the late 1800s. Its structure and chemical synthesis were achieved by 1940 , followed by some of the first pre-clinical research studies to determine the effects of individual cannabis-derived compounds in vivo . Although CBN shares the same mechanism of action as other more well-known phytocannabinoids (e.g., delta-9 tetrahydrocannabinol or D9THC), it has
10404-440: Was the illicit drug most frequently found in the blood of drivers who have been involved in vehicle crashes. Those with THC in their system are from three to seven times more likely to be the cause of the accident than those who had not used either cannabis or alcohol, although its role is not necessarily causal because THC stays in the bloodstream for days to weeks after intoxication. Some immediate undesired side effects include
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