87-591: The South Carolina Compassionate Care Act (S.150 / H.3361) is a 2022 bill in the South Carolina legislature to allow medical cannabis . The bill was prefiled December 9, 2020. Primary sponsors were Rep. Bill Herbkersman and Sen. Tom Davis , both Republicans. It was advanced by the Senate Medical Affairs Committee in March 2021, but failed to receive a vote in that year's session, and was scheduled by
174-499: 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
261-749: A 2006 advisory against smoked medical cannabis stating: "marijuana has a high potential for abuse, has no currently accepted medical use in treatment in the United States, and has a lack of accepted safety for use under medical supervision." Cannabis, called má 麻 (meaning "hemp; cannabis; numbness") or dàmá 大麻 (with "big; great") in Chinese, was used in Taiwan for fiber starting about 10,000 years ago. The botanist Hui-lin Li wrote that in China, "The use of Cannabis in medicine
348-579: 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
435-471: A condition known as cannabinoid hyperemesis syndrome (CHS). A 2016 Cochrane review said that cannabinoids were "probably effective" in treating chemotherapy-induced nausea in children, but with a high side-effect profile (mainly drowsiness, dizziness, altered moods, and increased appetite). Less common side effects were "ocular problems, orthostatic hypotension, muscle twitching, pruritus, vagueness, hallucinations, lightheadedness and dry mouth". Evidence
522-489: A higher risk of psychosis, particularly in individuals with a genetic predisposition to psychotic disorders like schizophrenia. Some studies have shown that cannabis can trigger a temporary psychotic episode, which may increase the risk of developing a psychotic disorder later. The impact of cannabis on depression is less clear. Some studies suggest a potential increase in depression risk among adolescents who use cannabis, though findings are inconsistent across studies. There
609-524: A lack of production controls. The potential for adverse effects from smoke inhalation makes smoking a less viable option than oral preparations. Cannabis vaporizers have gained popularity because of a perception among users that fewer harmful chemicals are ingested when components are inhaled via aerosol rather than smoke. Cannabinoid medicines are available in pill form ( dronabinol and nabilone ) and liquid extracts formulated into an oromucosal spray ( nabiximols ). Oral preparations are "problematic due to
696-400: 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
783-642: A majority of CBD is excreted in feces and some in the urine. The terminal half-life is approximately 18–32 hours. Smoking has been the means of administration of cannabis for many users, but it is not suitable for the use of cannabis as a medicine. It was the most common method of medical cannabis consumption in the US as of 2013 . It is difficult to predict the pharmacological response to cannabis because concentration of cannabinoids varies widely, as there are different ways of preparing it for consumption (smoked, applied as oils, eaten, infused into other foods, or drunk) and
870-518: 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
957-514: 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
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#17330854558731044-548: 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
1131-451: A period of days or weeks. The amount of cannabis normally used for medicinal purposes is not believed to cause any permanent cognitive impairment in adults, though long-term treatment in adolescents should be weighed carefully as they are more susceptible to these impairments. Withdrawal symptoms are rarely a problem with controlled medical administration of cannabinoids. The ability to drive vehicles or to operate machinery may be impaired until
1218-446: 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
1305-436: A reasonable option in those who do not improve following preferential treatment. Comparative studies have found cannabinoids to be more effective than some conventional antiemetics such as prochlorperazine , promethazine , and metoclopramide in controlling CINV, but these are used less frequently because of side effects including dizziness, dysphoria, and hallucinations. Long-term cannabis use may cause nausea and vomiting,
1392-486: A role in the overall effect of cannabis. The most studied are THC, CBD and CBN. CB1 and CB2 are the primary cannabinoid receptors responsible for several of the effects of cannabinoids, although other receptors may play a role as well. Both belong to a group of receptors called G protein-coupled receptors (GPCRs). CB1 receptors are found in very high levels in the brain and are thought to be responsible for psychoactive effects. CB2 receptors are found peripherally throughout
1479-602: A slower onset of effect than the inhalation of it because the THC travels to the liver first through the blood before it travels to the rest of the body. Inhaled cannabis can result in THC going directly to the brain, where it then travels from the brain back to the liver in recirculation for metabolism. Eventually, both routes of metabolism result in the metabolism of psychoactive THC to inactive 11-COOH-THC. Due to substantial metabolism of THC and CBD, their metabolites are excreted mostly via feces , rather than by urine. After delta-9-THC
1566-422: 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
1653-399: 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
1740-559: A tolerance is developed. Although supporters of medical cannabis say that it is safe, further research is required to assess the long-term safety of its use. Recreational use of cannabis is associated with cognitive deficits, especially for those who begin to use cannabis in adolescence. As of 2021 there is a lack of research into long-term cognitive effects of medical use of cannabis, but one 12-month observational study reported that "MC patients demonstrated significant improvements on measures of executive function and clinical state over
1827-512: A variety of illnesses and ailments, including insomnia, headaches, gastrointestinal disorders, and pain, including during childbirth. The Ancient Greeks used cannabis to dress wounds and sores on their horses, and in humans, dried leaves of cannabis were used to treat nose bleeds, and cannabis seeds were used to expel tapeworms. 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
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#17330854558731914-475: Is a lack of evidence that cannabinoids are effective in treating depressive or anxiety disorders , attention-deficit hyperactivity disorder (ADHD), Tourette syndrome , post-traumatic stress disorder , or psychosis . Research indicates that cannabis, particularly CBD, may have anxiolytic (anxiety-reducing) effects. A study found that CBD significantly reduced anxiety during a simulated public speaking test for individuals with social anxiety disorder. However,
2001-463: 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
2088-505: 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
2175-462: Is also dependent on route of administration. Smoking and inhalation of vaporized cannabis have better absorption than do other routes of administration, and therefore also have more predictable distribution. THC is highly protein bound once absorbed, with only 3% found unbound in the plasma. It distributes rapidly to highly vascularized organs such as the heart, lungs, liver, spleen, and kidneys, as well as to various glands. Low levels can be detected in
2262-583: 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
2349-787: 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
2436-414: 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
2523-447: Is deemed to be a reasonable option if other treatments have not been effective. Its use for MS is approved in ten countries. A 2012 review found no problems with tolerance, abuse, or addiction. In the United States, cannabidiol , one of the cannabinoids found in the marijuana plant, has been approved for treating two severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome . A 2019 systematic review found that there
2610-594: Is dose-related. A 2004 literature review on the subject concluded that cannabis use is associated with a two-fold increase in the risk of psychosis, but that cannabis use is "neither necessary nor sufficient" to cause psychosis. A French review from 2009 came to a conclusion that cannabis use, particularly that before age 15, was a factor in the development of schizophrenic disorders. The genus Cannabis contains two species which produce useful amounts of psychoactive cannabinoids: Cannabis indica and Cannabis sativa , which are listed as Schedule I medicinal plants in
2697-610: Is hydroxylated into 11-OH-THC via CYP2C9, CYP2C19, and CYP3A4, it undergoes phase II metabolism into more than 30 metabolites, a majority of which are products of glucuronidation . Approximately 65% of THC is excreted in feces and 25% in the urine, while the remaining 10% is excreted by other means. The terminal half-life of THC is 25 to 36 hours, whereas for CBD it is 18 to 32 hours. CBD is hydroxylated by P450 liver enzymes into 7-OH-CBD. Its metabolites are products of primarily CYP2C19 and CYP3A4 activity, with potential activity of CYP1A1, CYP1A2, CYP2C9, and CYP2D6. Similar to delta-9-THC,
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2784-439: Is insufficient data to draw strong conclusions about the safety of medical cannabis. Typically, adverse effects of medical cannabis use are not serious; they include tiredness, dizziness, increased appetite, and cardiovascular and psychoactive effects. Other effects can include impaired short-term memory; impaired motor coordination; altered judgment; and paranoia or psychosis at high doses. Tolerance to these effects develops over
2871-547: Is lacking for both efficacy and safety of cannabis and cannabinoids in treating patients with HIV/AIDS or for anorexia associated with AIDS. As of 2013, current studies suffer from the effects of bias, small sample size, and lack of long-term data. A 2021 review found little effect of using non-inhaled cannabis to relieve chronic pain. According to a 2019 systematic review, there have been inconsistent results of using cannabis for neuropathic pain, spasms associated with multiple sclerosis and pain from rheumatic disorders, but
2958-764: Is largely attributed to significant first-pass metabolism in the liver and erratic absorption from the gastrointestinal tract. However, oral administration of CBD has a faster time to peak concentrations (2 hours) than THC. Due to the poor bioavailability of oral preparations, alternative routes of administration have been studied, including sublingual and rectal. These alternative formulations maximize bioavailability and reduce first-pass metabolism. Sublingual administration in rabbits yielded bioavailability of 16% and time to peak concentration of 4 hours. Rectal administration in monkeys doubled bioavailability to 13.5% and achieved peak blood concentrations within 1 to 8 hours after administration. Like cannabinoid absorption, distribution
3045-619: Is not clear whether it is a useful treatment for any condition, or whether harms outweigh any benefit. There is no consistent evidence that it helps with chronic pain and muscle spasms . Low quality evidence suggests its use for reducing nausea during chemotherapy , improving appetite in HIV/AIDS , improving sleep, and improving tics in Tourette syndrome . When usual treatments are ineffective, cannabinoids have also been recommended for anorexia , arthritis , glaucoma , and migraine . It
3132-412: Is one of the 50 "fundamental" herbs in traditional Chinese medicine . The Ebers Papyrus ( c. 1550 BCE ) from Ancient Egypt describes medical cannabis. The ancient Egyptians used hemp (cannabis) in suppositories for relieving the pain of hemorrhoids . Surviving texts from ancient India confirm that cannabis' psychoactive properties were recognized, and doctors used it for treating
3219-403: Is one reason why treatment with cannabis is difficult to classify and study. A 2014 review stated that the variations in ratio of CBD-to-THC in botanical and pharmaceutical preparations determines the therapeutic vs psychoactive effects (CBD attenuates THC's psychoactive effects ) of cannabis products. Overall, research into the health effects of medical cannabis has been of low quality and it
3306-484: 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
3393-404: Is the first metabolic product in this pathway. Both Delta-9-THC and 11-OH-THC are psychoactive. The metabolism of THC into 11-OH-THC plays a part in the heightened psychoactive effects of edible cannabis. Next, 11-OH-THC is metabolized in the liver into 11-COOH-THC, which is the second metabolic product of THC. 11-COOH-THC is not psychoactive. Ingestion of edible cannabis products lead to
3480-465: 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
3567-632: Is unclear whether American states might be able to mitigate the adverse effects of the opioid epidemic by prescribing medical cannabis as an alternative pain management drug. Cannabis should not be used in pregnancy . Research analyzing data from the National Health and Nutrition Examination Survey (NHANES) did not find significant differences in sleep duration between cannabis users and non-users. This suggests that while some individuals may perceive benefits from cannabis use in terms of sleep, it may not significantly change overall sleep patterns across
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3654-501: 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)
3741-490: 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
3828-459: 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
3915-699: 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
4002-580: 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
4089-478: 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 ,
4176-401: 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
4263-539: 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
4350-476: 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
4437-448: The Senate majority leader to be the first item debated in 2022. Senate floor debate began on January 26, 2022 – the first time cannabis legalization of any kind had been debated in South Carolina. As of February 9, 2022, the bill had survived seven days of debate and a vote to gut the bill. It received a 28–15 vote for a second reading in the senate on February 9, and final passage by
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#17330854558734524-565: 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×
4611-705: The US; a third species, Cannabis ruderalis , has few psychogenic properties. Cannabis contains more than 460 compounds; at least 80 of these are cannabinoids – chemical compounds that interact with cannabinoid receptors in the brain. As of 2012, more than 20 cannabinoids were being studied by the U.S. FDA. The most psychoactive cannabinoid found in the cannabis plant is tetrahydrocannabinol (or delta-9-tetrahydrocannabinol, commonly known as THC). Other cannabinoids include delta-8-tetrahydrocannabinol , cannabidiol (CBD), cannabinol (CBN), cannabicyclol (CBL), cannabichromene (CBC) and cannabigerol (CBG); they have less psychotropic effects than THC, but may play
4698-534: 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
4785-425: 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
4872-570: The body and are thought to modulate pain and inflammation. Cannabinoid absorption is dependent on its route of administration. Inhaled and vaporized THC have similar absorption profiles to smoked THC, with a bioavailability ranging from 10 to 35%. Oral administration has the lowest bioavailability of approximately 6%, variable absorption depending on the vehicle used, and the longest time to peak plasma levels (2 to 6 hours) compared to smoked or vaporized THC. Similar to THC, CBD has poor oral bioavailability, approximately 6%. The low bioavailability
4959-468: 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),
5046-443: The brain, testes, and unborn fetuses, all of which are protected from systemic circulation via barriers. THC further distributes into fatty tissues a few days after administration due to its high lipophilicity, and is found deposited in the spleen and fat after redistribution. Delta-9-THC is the primary molecule responsible for the effects of cannabis. Delta-9-THC is metabolized in the liver and turns into 11-OH-THC. 11-OH-THC
5133-478: 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
5220-522: 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
5307-476: 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
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#17330854558735394-450: 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
5481-400: The course of 12 months". Exposure to THC can cause acute transient psychotic symptoms in healthy individuals and people with schizophrenia. A 2007 meta analysis concluded that cannabis use reduced the average age of onset of psychosis by 2.7 years relative to non-cannabis use. A 2005 meta analysis concluded that adolescent use of cannabis increases the risk of psychosis, and that the risk
5568-415: 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
5655-447: 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
5742-793: The federal level, the Rohrabacher–Farr amendment was enacted in December 2014, limiting the ability of federal law to be enforced in states where medical cannabis has been legalized. In the U.S., the National Institute on Drug Abuse defines medical cannabis as "using the whole, unprocessed marijuana plant or its basic extracts to treat symptoms of illness and other conditions". A cannabis plant includes more than 400 different chemicals, of which about 70 are cannabinoids . In comparison, typical government-approved medications contain only one or two chemicals. The number of active chemicals in cannabis
5829-488: 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
5916-453: The general population. A review of literature up to 2018 indicates that cannabidiol (CBD) may have therapeutic potential for the treatment of insomnia. CBD, a non-psychoactive component of cannabis, is of particular interest due to its potential to influence sleep without the psychoactive effects associated with tetrahydrocannabinol (THC). Medical cannabis is somewhat effective in chemotherapy-induced nausea and vomiting (CINV) and may be
6003-644: The list of Schedule I controlled substances maintained by the United States federal government, followed by regulatory and scientific review. Others oppose its legalization, such as the American Academy of Pediatrics . Medical cannabis can be administered through various methods, including capsules , lozenges , tinctures , dermal patches , oral or dermal sprays, cannabis edibles , and vaporizing or smoking dried buds . Synthetic cannabinoids are available for prescription use in some countries, such as synthetic delta-9-THC and nabilone . Countries that allow
6090-523: The medical use of whole-plant cannabis include Argentina, Australia, Canada, Chile, Colombia, Germany, Greece, Israel, Italy, the Netherlands, Peru, Poland, Portugal, Spain, and Uruguay. In the United States, 38 states and the District of Columbia have legalized cannabis for medical purposes, beginning with the passage of California's Proposition 215 in 1996. Although cannabis remains prohibited for any use at
6177-510: 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
6264-449: 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
6351-443: The pain relief experienced after using medical cannabis is due to the placebo effect , especially given widespread media attention that sets the expectation for pain relief. Cannabis' efficacy is not clear in treating neurological problems, including multiple sclerosis (MS) and movement problems. Evidence also suggests that oral cannabis extract is effective for reducing patient-centered measures of spasticity. A trial of cannabis
6438-491: 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
6525-432: 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
6612-459: 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
6699-415: 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
6786-410: The relationship between cannabis use and anxiety symptoms is complex, and while some users report relief, the overall evidence from observational studies and clinical trials remains inconclusive. Cannabis is often used by people to cope with anxiety, yet the efficacy and safety of cannabis for treating anxiety disorders is yet to be researched. Cannabis use, especially at high doses, is associated with
6873-490: The risk of minor and major adverse effects. Common side effects include dizziness , feeling tired, vomiting, and hallucinations . Long-term effects of cannabis are not clear. Concerns include memory and cognition problems, risk of addiction, schizophrenia in young people, and the risk of children taking it by accident. Many cultures have used cannabis for therapeutic purposes for thousands of years. Some American medical organizations have requested removal of cannabis from
6960-497: The safety and efficacy of using cannabis to treat diseases. Preliminary evidence has indicated that cannabis might reduce nausea and vomiting during chemotherapy and reduce chronic pain and muscle spasms . Regarding non-inhaled cannabis or cannabinoids, a 2021 review found that it provided little relief against chronic pain and sleep disturbance, and caused several transient adverse effects , such as cognitive impairment, nausea , and drowsiness . Short-term use increases
7047-568: The senate on February 10. It was reintroduced as Senate Bill 0423 in January, 2024. Medical cannabis Medical cannabis , medicinal cannabis or medical marijuana ( MMJ ) refers to cannabis products and cannabinoid molecules that are prescribed by physicians for their patients. The use of cannabis as medicine has a long history, but has not been as rigorously tested as other medicinal plants due to legal and governmental restrictions, resulting in limited clinical research to define
7134-431: 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
7221-418: The uptake of cannabinoids into fatty tissue, from which they are released slowly, and the significant first-pass liver metabolism, which breaks down Δ9THC and contributes further to the variability of plasma concentrations". The US Food and Drug Administration (FDA) has not approved smoked cannabis for any condition or disease, as it deems that evidence is lacking concerning safety and efficacy. The FDA issued
7308-508: 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
7395-537: Was not effective treating chronic cancer pain. The authors state that additional randomized controlled trials of different cannabis products are necessary to make conclusive recommendations. When cannabis is inhaled to relieve pain, blood levels of cannabinoids rise faster than when oral products are used, peaking within three minutes and attaining an analgesic effect in seven minutes. A 2011 review considered cannabis to be generally safe, and it appears safer than opioids in palliative care. A 2022 review concluded
7482-440: Was probably a very early development. Since ancient humans used hemp seed as food, it was quite natural for them to also discover the medicinal properties of the plant." Emperor Shen-Nung , who was also a pharmacologist, wrote a book on treatment methods in 2737 BCE that included the medical benefits of cannabis. He recommended the substance for many ailments, including constipation, gout, rheumatism, and absent-mindedness. Cannabis
7569-442: 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
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