Tetrahydrocannabinol
Tetrahydrocannabinol (THC), or more precisely its main isomer (−)-trans-Δ9-tetrahydrocannabinol (Template:Hsp(6aR,10aR)-delta-9-tetrahydrocannabinol), is the principal psychoactive constituent (or cannabinoid) of cannabis. First isolated in 1964 by Israeli scientists Prof. Raphael Mechoulam and Dr. Yechiel Gaoni at the Weizmann Institute of Science<ref name="doi10.1021/ja01062a046">Template:Cite journal</ref><ref>Template:Cite web</ref><ref>Template:Cite journal</ref> it can be an amber or gold colored glassy solid when cold, which becomes viscous and sticky if warmed. A pharmaceutical formulation of (−)-trans-Δ9-tetrahydrocannabinol, known by its INN dronabinol, is available by prescription in the U.S. and Canada under the brand name Marinol. An aromatic terpenoid, THC has a very low solubility in water, but good solubility in most organic solvents, specifically lipids and alcohols.<ref name='Garrett1974'>Template:Cite journal</ref> THC, CBD, CBN, CBC, CBG and about 80 other molecules make up the phytocannabinoid family.
Like most pharmacologically-active secondary metabolites of plants, THC in Cannabis is assumed to be involved in self-defense, perhaps against herbivores.<ref name=Pate1994>Template:Cite journal</ref> THC also possesses high UV-B (280–315 nm) absorption properties, which, it has been speculated, could protect the plant from harmful UV radiation exposure.<ref name=Pate1983>Template:Cite journal</ref><ref name=Lydon1987a>Template:Cite journal</ref><ref name=Lydon1987b>Template:Cite journal</ref>
Tetrahydrocannabinol, along with its double bond isomers and their stereoisomers, is one of only three cannabinoids scheduled by the Convention on Psychotropic Substances (the other two are dimethylheptylpyran and parahexyl). Previously listed as a substance under Schedule I of the 1971 Convention on Psychotropic Substances, THC was reclassified to Schedule II in 1991 following a recommendation from the World Health Organization. Based on their subsequent studies, the WHO has recommended the reclassification of THC to the less-stringent Schedule III.<ref>A Primer on the UN Drug Control Conventions. Transnational Institute</ref> Cannabis as a plant is scheduled by the Single Convention on Narcotic Drugs (Schedule I and IV).
Effects
THC has mild to moderate analgesic effects, and cannabis can be used to treat pain by altering transmitter release on dorsal root ganglion of the spinal cord and in the periaqueductal gray.<ref name="pmid11316486" /> Other effects include relaxation, alteration of visual, auditory, and olfactory senses, fatigue, and appetite stimulation. THC has marked antiemetic properties. It may acutely reduce aggression.<ref>Template:Cite journal</ref>
Due to its partial agonistic activity, THC appears to result in greater downregulation of cannabinoid receptors than endocannabinoids, further limiting its efficacy over other cannabinoids. While tolerance may limit the maximal effects of certain drugs, evidence suggests that tolerance develops irregularly for different effects with greater resistance for primary over side-effects, and may actually serve to enhance the drug's the*****utic window.<ref name="pmid17828291" /> However, this form of tolerance appears to be irregular throughout mouse brain areas. THC, as well as other cannabinoids that contain a phenol group, possesses mild antioxidant activity sufficient to protect neurons against oxidative stress, such as that produced by glutamate-induced excitotoxicity.<ref name="pmid16570099" />
Appetite and taste
A study in mice suggested that based on the connection between palatable food and stimulation of dopamine (DA) transmission in the shell of the nucleus accumbens (NAc), cannabis may not only stimulate taste, but possibly the hedonic (pleasure) value of food as well. The study later demonstrates habitual use of THC lessening this heightened pleasure response, indicating a possible similarity in humans.<ref name="pmid22063718">Template:Cite journal</ref> The inconsistency between DA habituation and enduring appetite observed after THC application suggests that cannabis-induced appetite stimulation is not only mediated by enhanced pleasure from palatable food, but through THC stimulation of another appetitive response as well.Template:Citation needed
Medical uses
Template:Cannabis sidebar In April 2014 the American Academy of Neurology published a systematic review of the efficacy and safety of medical marijuana and marijuana-derived products in certain neurological disorders.<ref name="AAN">Template:Cite journal</ref> The review identified 34 studies meeting inclusion criteria, of which 8 were rated as Class I quality.<ref name="AAN" /> The study found evidence supporting the effectiveness of cannabis extracts and THC in treating certain symptoms of multiple sclerosis, but found insufficient evidence to determine the effectiveness of cannabis products in treating several other neurological diseases.<ref name="AAN" />
Multiple sclerosis symptoms
- Spasticity. Based on the results of 3 high quality trials and 5 of lower quality, oral cannabis extract was rated as effective, and THC as probably effective, for improving patient's subjective experience of spasticity. Oral cannabis extract and THC both were rated as possibly effective for improving objective measures of spasticity.<ref name="AAN"/>
- Centrally mediated pain and painful spasms. Based on the results of 4 high quality trials and 4 low quality trials, oral cannabis extract was rated as effective, and THC as probably effective in treating central pain and painful spasms.<ref name="AAN"/>
- Bladder dysfunction. Based on a single high quality study, oral cannabis extract and THC were rated as probably ineffective for controlling bladder complaints in multiple sclerosis<ref name="AAN"/>
Neurodegenerative disorders
- Huntington disease. No reliable conclusions could be drawn regarding the effectiveness of THC or oral cannabis extract in treating the symptoms of Huntington disease as the available trials were too small to reliably detect any difference<ref name="AAN"/>
- Parkinson disease. Based on a single study, oral cannabis extract was rated probably ineffective in treating levodopa-induced dyskinesia in Parkinson disease.<ref name="AAN"/>
- Alzheimer's disease. A 2011 Cochrane Review found insufficient evidence to conclude whether cannabis products have any utility in the treatment of Alzheimer's disease.<ref>Template:Cite journal</ref>
Other neurological disorders
- Tourette syndrome. The available data was determined to be insufficient to allow reliable conclusions to be drawn regarding the effectiveness of oral cannabis extract or THC in controlling tics.<ref name="AAN"/>
- Cervical dystonia. Insufficient data was available to assess the effectiveness of oral cannabis extract of THC in treating cervical dystonia.<ref name="AAN"/>
- Epilepsy. Data was considered insufficient to judge the utility of cannabis products in reducing seizure frequency or severity.<ref name="AAN"/>
Other studies in humans
Evidence suggests that THC helps alleviate symptoms suffered both by AIDS patients, and by cancer patients undergoing chemotherapy, by increasing appetite and decreasing nausea.<ref>Template:Cite web</ref><ref name=Haney>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name="groten">Template:Cite book</ref> It has also been shown to assist some glaucoma patientsTemplate:Medical citation needed by reducing pressure within the eye, and is used in the form of cannabis by a number of multiple sclerosis patients, who use it to alleviate neuropathic pain and spasticity. The National Multiple Sclerosis Society is currently supporting further research into these uses.<ref name="MS society">Template:Cite web</ref> THC has also shown antitumor activity in animal studies where it killed cancer cells.<ref>https://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq/#link/_13</ref> Studies in humans have been limited by federal and state laws criminalizing marijuana.
In August 2009 a phase IV clinical trial by the Hadassah Medical Center in Jerusalem, Israel started to investigate the effects of THC on post-traumatic stress disorders.<ref name="urlAdd on Study on Δ9-THC Treatment for Posttraumatic Stress Disorders (PTSD) – Full Text View – ClinicalTrials.gov">Template:ClinicalTrialsGov</ref>
Studies have been conducted with spinal injury patients and THC.<ref name="Hanigan 1986">Template:Cite journal</ref>
Both THC and CBD phytocannabinoids have been shown to decrease intestinal permeability.<ref>SCLabs, Leaky Gut Syndrome: Cannabinoids and the Endocannabinoid System (ECS) as a the*****utic target</ref>
Adverse effects
Acute toxicity
There has never been a documented human fatality solely from overdosing on tetrahydrocannabinol.<ref name="Walker and Huang">Template:Cite journal</ref> However, numerous reports have suggested an association of cannabis smoking with an increased risk of myocardial infarction ,<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> also known as a heart attack but oral administration does not have this effect. Information about the toxicity of THC is primarily based on results from non-human studies. The toxicity depends on the route of administration and the laboratory animal.
The estimated lethal dose of intravenous dronabinol in humans is 30 mg/kg,<ref name="American Health Packaging">Template:Cite web</ref> meaning lethality is unlikely. The typical medicinal dosage administered is two 2.5 mg capsules daily; for an 80 kg man (~170 lb). A lethal dose for such a person would be 960 of those capsules infused intravenously. Non-fatal overdoses have occurred: "Significant CNS symptoms in antiemetic studies followed oral doses of 0.4 mg/kg (28 mg/70 kg) of dronabinol capsules."<ref name="American Health Packaging" />
- A meta analysis of cannabis and THC clinical trials conducted by the American Academy of Neurology found that of 1619 persons treated with cannabis products (including some treated with smoked cannabis and nabiximols), 6.9% discontinued due to side effects, compared to 2.2% of 1,118 treated with placebo. Detailed information regarding side effects was not available from all trials, but nausea, increased weakness, behavioral or mood changes, suicidal ideation, hallucinations, dizziness, and vasovagal symptoms, fatigue, and feelings of intoxication were each described as side effects in at least 2 trials. There was a single death rated by the investigator as "possibly related" to treatment. This person had a seizure followed by aspiration pneumonia. The paper does not describe whether this was one of the patients from the epilepsy trials.<ref name="AAN"/>
Cognitive effects
Its status as an illegal drug in most countries can make research difficult; for instance in the United States where the National Institute on Drug ***** was the only legal source of cannabis for researchers until it recently became legalized in Colorado, Washington state, Oregon, Alaska, and Washington D.C.<ref name="MAPS">Template:Cite web</ref>
A 2011 systematic review evaluated published studies of the acute and long-term cognitive effects of cannabis. THC intoxication is well established to impair cognitive functioning on an acute basis, including effects on the ability to plan, organize, solve problems, make decisions, and control impulses. The extent of this impact may be greater in novice users, and paradoxically, those habituated to high level ingestion may have reduced cognition during withdrawal. Studies of long-term effects on cognition have provided conflicting results, with some studies finding no difference between long-term abstainers and never-users and others finding long-term deficits. The discrepancies between studies may reflect greater long-term effects among heavier users relative to occasional users, and greater duration of effect among those with heavy use as adolescents compared to later in life.<ref>Template:Cite journal</ref> A second systematic review focused on neuroimaging studies found little evidence supporting an effect of cannabis use on brain structure and function.<ref>Template:Cite journal</ref> A 2003 meta analysis concluded that any long-term cognitive effects were relatively modest in magnitude and limited to certain aspects of learning and memory.<ref>Template:Cite journal</ref>
Impact on psychosis
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.<ref>Template:Cite journal</ref> A 2005 meta analysis concluded that adolescent use of cannabis increases the risk of psychosis, and that the risk is dose-related.<ref>Template:Cite journal</ref> 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.<ref name=Arseneault2004>Template:Cite journal</ref> 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.<ref name="Laqueille">Template:Cite journal</ref>
Some studies have suggested that cannabis users have a greater risk of developing psychosis than non-users. This risk is most pronounced in cases with an existing risk of psychotic disorder.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> A 2005 paper from the Dunedin study suggested an increased risk in the development of psychosis linked to polymorphisms in the COMT gene.<ref>Template:Cite journal</ref> However, a more recent study cast doubt on the proposed connection between this gene and the effects of cannabis on the development of psychosis.<ref name="pmid17978319">Template:Cite journal</ref>
A 2008 German review reported that cannabis was a causal factor in some cases of schizophrenia and stressed the need for better education among the public due to increasingly relaxed access to cannabis.<ref>Template:Cite journal</ref>
Other potential long-term effects
A 2008 National Institutes of Health study of 19 chronic heavy marijuana users with cardiac and cerebral abnormalities (averaging 28 g to 272 g (1 to 9+ oz) weekly) and 24 controls found elevated levels of apolipoprotein C-III (apoC-III) in the chronic smokers.<ref>Template:Cite journal</ref> An increase in apoC-III levels induces the development of hypertriglyceridemia.
Interactions
The effects of the drug can be reduced by the CB1 receptor inverse agonist rimonabant (SR141716A) as well as opioid receptor antagonists (opioid blockers) naloxone and naloxonazine.<ref name="pmid22063718" /><ref name="Lupica 2004">Template:Cite journal</ref> The α7 nicotinic receptor antagonist methyllycaconitine can block self-administration of THC in rates comparable to the effects of varenicline on nicotine administration.<ref>Template:Cite journal</ref>
Cannabidiol, the second most abundant cannabinoid found in cannabis, is an indirect antagonist against cannabinoid agonists; thus reducing the effects of anandamide and THC agonism on the CB1 and CB2 receptors.
Pharmacology
Mechanism of action
Template:For The actions of THC result from its partial agonist activity at the cannabinoid receptor CB1 (Ki=10nM<ref name="PDSP Database">Template:Cite web</ref>), located mainly in the central nervous system, and the CB2 receptor (Ki=24nM<ref name="PDSP Database" />), mainly expressed in cells of the immune system.<ref name="pmid16570099">Template:Cite journal</ref> The psychoactive effects of THC are primarily mediated by its activation of CB1G-protein coupled receptors, which result in a decrease in the concentration of the second messenger molecule cAMP through inhibition of adenylate cyclase.<ref name="pmid11316486">Template:Cite journal</ref>
The presence of these specialized cannabinoid receptors in the brain led researchers to the discovery of endocannabinoids, such as anandamide and 2-arachidonoyl glyceride (2-AG). THC targets receptors in a manner far less selective than endocannabinoid molecules released during retrograde signaling, as the drug has a relatively low cannabinoid receptor efficacy and affinity. In populations of low cannabinoid receptor density, THC may act to antagonize endogenous agonists that possess greater receptor efficacy.<ref name="pmid17828291">Template:Cite journal</ref> THC is a lipophilic molecule<ref>Template:Cite journal</ref> and may bind non-specifically to a variety of entities in the brain and body, such as adipose tissue (fat).<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
THC, similarly to cannabidiol, albeit less potently, is an allosteric modulator of the μ- and δ-opioid receptors.<ref name="pmid16489449">Template:Cite journal</ref>
Pharmacokinetics
THC is metabolized mainly to 11-OH-THC by the body. This metabolite is still psychoactive and is further oxidized to 11-nor-9-carboxy-THC (THC-COOH). In humans and animals, more than 100 metabolites could be identified, but 11-OH-THC and THC-COOH are the dominating metabolites. Metabolism occurs mainly in the liver by cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP3A4.<ref>Template:Cite journal</ref> More than 55% of THC is excreted in the feces and ~20% in the urine. The main metabolite in urine is the ester of glucuronic acid and THC-COOH and free THC-COOH. In the feces, mainly 11-OH-THC was detected.<ref name="pmid16596792">Template:Cite journal</ref>
Physical and chemical properties
Discovery and structure identification
The discovery of THC by a team of researchers from Hebrew University Pharmacy School was first described in "Isolation, structure and partial synthesis of an active constituent of hashish", published in the Journal of the American Chemical Society in 1964.<ref name="doi10.1021/ja01062a046"/> Research was also published in the academic journal Science, with "Marijuana chemistry" by Raphael Mechoulam in June 1970.<ref name="pmid4910003">Template:Cite journal</ref>
Isomerism
| 7 double bond isomers and their 30 stereoisomers | ||||||||
|---|---|---|---|---|---|---|---|---|
| Dibenzopyran numbering | Monoterpenoid numbering | Number of stereoisomers | Natural occurrence | Convention on Psychotropic Substances Schedule | Structure | |||
| Short name | Chiral centers | Full name | Short name | Chiral centers | ||||
| Δ6a,7-tetrahydrocannabinol | 9 and 10a | 8,9,10,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol | Δ4-tetrahydrocannabinol | 1 and 3 | 4 | No | Schedule I | File:Delta6a,7-Tetrahydrocannabinol.png |
| Δ7-tetrahydrocannabinol | 6a, 9 and 10a | 6a,9,10,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol | Δ5-tetrahydrocannabinol | 1, 3 and 4 | 8 | No | Schedule I | File:Delta7-Tetrahydrocannabinol.png |
| Δ8-tetrahydrocannabinol | 6a and 10a | 6a,7,10,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol | Δ6-tetrahydrocannabinol | 3 and 4 | 4 | Yes | Schedule I | File:Delta8-Tetrahydrocannabinol.png |
| Δ9,11-tetrahydrocannabinol | 6a and 10a | 6a,7,8,9,10,10a-hexahydro-6,6-dimethyl-9-methylene-3-pentyl-6H-dibenzo[b,d]pyran-1-ol | Δ1,7-tetrahydrocannabinol | 3 and 4 | 4 | No | Schedule I | File:Delta9,11-Tetrahydrocannabinol.png |
| Δ9-tetrahydrocannabinol | 6a and 10a | 6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol | Δ1-tetrahydrocannabinol | 3 and 4 | 4 | Yes | Schedule II | File:Delta9-Tetrahydrocannabinol.png |
| Δ10-tetrahydrocannabinol | 6a and 9 | 6a,7,8,9-tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol | Δ2-tetrahydrocannabinol | 1 and 4 | 4 | No | Schedule I | File:Delta10-Tetrahydrocannabinol.png |
| Δ6a,10a-tetrahydrocannabinol | 9 | 7,8,9,10-tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol | Δ3-tetrahydrocannabinol | 1 | 2 | No | Schedule I | File:Delta6a,10a-Tetrahydrocannabinol.png |
| 4 stereoisomers of Δ9-tetrahydrocannabinol | ||||
|---|---|---|---|---|
| Names | Description | Natural occurrence | Structure | |
| (−)-trans-Δ9-tetrahydrocannabinol | (6aR,10aR)-Δ9-tetrahydrocannabinol | levorotary trans | Yes | File:(−)-(6aR,10aR)-Δ9-Tetrahydrocannabinol (with hydrogen atoms shown).svg |
| (−)-cis-Δ9-tetrahydrocannabinol | (6aS,10aR)-Δ9-tetrahydrocannabinol | levorotary cis | Yes | File:(−)-(6aS,10aR)-Δ9-Tetrahydrocannabinol (with hydrogen atoms shown).svg |
| (+)-trans-Δ9-tetrahydrocannabinol | (6aS,10aS)-Δ9-tetrahydrocannabinol | dextrorotary trans | No | File:(+)-(6aS,10aS)-Δ9-Tetrahydrocannabinol (with hydrogen atoms shown).svg |
| (+)-cis-Δ9-tetrahydrocannabinol | (6aR,10aS)-Δ9-tetrahydrocannabinol | dextrorotary cis | No | File:(+)-(6aR,10aS)-Δ9-Tetrahydrocannabinol (with hydrogen atoms shown).svg |
Note that 6H-dibenzo[b,d]pyran-1-ol is the same as 6H-benzo[c]chromen-1-ol.
- Further reading on cannabanoid isomerism: Template:Cite web
Biosynthesis
In the Cannabis plant, THC occurs mainly as tetrahydrocannabinolic acid (THCA, 2-COOH-THC). Geranyl pyrophosphate and olivetolic acid react, catalysed by an enzyme to produce cannabigerolic acid,<ref name="pmid9607329">Template:Cite journal</ref> which is cyclized by the enzyme THC acid synthase to give THCA. Over time, or when heated, THCA is decarboxylated, producing THC. The pathway for THCA biosynthesis is similar to that which produces the bitter acid humulone in hops.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
Detection in body fluids
Template:Main THC, 11-OH-THC and THC-COOH can be detected and quantified in blood, urine, hair, oral fluid or sweat using a combination of immunoassay and chromatographic techniques as part of a drug use testing program or in a forensic investigation of a traffic or other criminal offense or suspicious death.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite book</ref>
History
Template:Details Since at least 1986, the trend has been for THC in general, and especially the Marinol preparation, to be downgraded to less and less stringently-controlled schedules of controlled substances, in the U.S. and throughout the rest of the world.Template:Citation needed
On May 13, 1986, the Drug Enforcement Administration (DEA) issued a Final Rule and Statement of Policy authorizing the "Rescheduling of Synthetic Dronabinol in Sesame Oil and Encapsulated in Soft Gelatin Capsules From Schedule I to Schedule II" (DEA 51 FR 17476-78). This permitted medical use of Marinol, albeit with the severe restrictions associated with Schedule II status.<ref>51 Fed. Reg. 17476 (1986), Tuesday, May 13, 1986, pages 17476-17478</ref> For instance, refills of Marinol prescriptions were not permitted. At its 1045th meeting, on April 29, 1991, the Commission on Narcotic Drugs, in accordance with article 2, paragraphs 5 and 6, of the Convention on Psychotropic Substances, decided that Δ9-tetrahydrocannabinol (also referred to as Δ9-THC) and its stereochemical variants should be transferred from Schedule I to Schedule II of that Convention. This released Marinol from the restrictions imposed by Article 7 of the Convention (See also United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances).Template:Citation needed
An article published in the April–June 1998 issue of the Journal of Psychoactive Drugs found that "Healthcare professionals have detected no indication of scrip-chasing or doctor-shopping among the patients for whom they have prescribed dronabinol". The authors state that Marinol has a low potential for *****.<ref name="pmid9692381">Template:Cite journalTemplate:Better source</ref>
In 1999, Marinol was rescheduled from Schedule II to III of the Controlled Substances Act, reflecting a finding that THC had a potential for ***** less than that of cocaine and heroin. This rescheduling constituted part of the argument for a 2002 petition for removal of cannabis from Schedule I of the Controlled Substances Act, in which petitioner Jon Gettman noted, "Cannabis is a natural source of dronabinol (THC), the ingredient of Marinol, a Schedule III drug. There are no grounds to schedule cannabis in a more restrictive schedule than Marinol".<ref>Template:Cite webTemplate:Better source</ref>
At its 33rd meeting, in 2003, the World Health Organization Expert Committee on Drug Dependence recommended transferring THC to Schedule IV of the Convention, citing its medical uses and low ***** potential.<ref>Template:Cite web</ref>
Society and culture
Brand names
Template:Anchor Template:Distinguish Dronabinol is the INN for a pure isomer of THC, (–)-trans-Δ9-tetrahydrocannabinol,<ref>Template:Cite web</ref> which is the main isomer found in cannabis. Synthesized dronabinol is marketed as Marinol<ref>EMCDDA, ELDD Comparative Study, May 2002.</ref> (a registered trademark of Solvay Pharmaceuticals). Dronabinol is also marketed, sold, and distributed by PAR Pharmaceutical Companies under the terms of a license and distribution agreement with SVC pharma LP, an affiliate of Rhodes Technologies. Synthesized THC may be generally referred to as dronabinol. It is available as a prescription drug (under Marinol<ref>Template:Cite web</ref>) in several countries including the United States, Germany, South Africa and Australia.<ref>Alchimia Blog, Marijuana and Medicine: Cesamet, Marinol, Sativex</ref> In the United States, Marinol is a Schedule III drug, available by prescription, considered to be non-narcotic and to have a low risk of physical or mental dependence. Efforts to get cannabis rescheduled as analogous to Marinol have not succeeded thus far, though a 2002 petition has been accepted by the DEA. As a result of the rescheduling of Marinol from Schedule II to Schedule III, refills are now permitted for this substance. Marinol has been approved by the U.S. Food and Drug Administration (FDA) in the treatment of anorexia in HIV/AIDS patients, as well as for refractory nausea and vomiting of patients undergoing chemotherapy, which has raised much controversy<ref>Template:Cite web</ref> as to why natural THC is considered a schedule I drug.<ref>Template:Cite web</ref>
An overdose usually presents with lethargy, decreased motor coordination, slurred speech, and postural hypotension. The FDA estimates the lethal human dose of intravenous dronabinol to be 30 mg/kg (2100 mg/ 70 kg).<ref name=FDAMarinolAdverse>Template:Cite web</ref>
An analog of dronabinol, nabilone, is available commercially in Canada under the trade name Cesamet, manufactured by Valeant Pharmaceuticals. Cesamet has also received FDA approval and began marketing in the U.S. in 2006. Nabilone is a Schedule II drug.<ref>Template:Cite web With changes through Template:USFR (January 27, 2012).</ref>
Comparisons with medical cannabis
Female cannabis plants contain more than 60 cannabinoids, including cannabidiol (CBD), thought to be the major anticonvulsant that helps multiple sclerosis patients;<ref name="pmid6269680">Template:Cite journal</ref> and cannabichromene (CBC), an anti-inflammatory which may contribute to the pain-killing effect of cannabis.<ref name=Burns2006>Template:Cite journal</ref>
It takes over one hour for Marinol to reach full systemic effect,<ref>Template:DailyMed</ref> compared to seconds or minutes for smoked or vaporized cannabis.<ref name="mckim">Template:Cite book</ref> Some patients accustomed to inhaling just enough cannabis smoke to manage symptoms have complained of too-intense intoxication from Marinol's predetermined dosagesTemplate:Citation needed. Many patients have said that Marinol produces a more acute psychedelic effect than cannabis, and it has been speculated that this disparity can be explained by the moderating effect of the many non-THC cannabinoids present in cannabis.Template:Citation needed For that reason, alternative THC-containing medications based on botanical extracts of the cannabis plant such as nabiximols are being developed. Mark Kleiman, director of the Drug Policy Analysis Program at UCLA's School of Public Affairs said of Marinol, "It wasn't any fun and made the user feel bad, so it could be approved without any fear that it would penetrate the recreational market, and then used as a club with which to beat back the advocates of whole cannabis as a medicine."<ref name="Respectable Reefer">*****o</ref> Mr. Kleiman's opinion notwithstanding, clinical trials comparing the use of cannabis extracts with Marinol in the treatment of cancer cachexia have demonstrated equal efficacy and well-being among patients in the two treatment arms.<ref name="urlCannabis and Cannabinoids (PDQ®) – National Cancer Institute">Template:Cite web</ref> United States federal law currently registers dronabinol as a Schedule III controlled substance, but all other cannabinoids remain Schedule I, except synthetics like nabilone.<ref>Template:Cite web</ref>
See also
- Cannabinoids
- 11-Hydroxy-THC, metabolite of THC
- Anandamide, 2-Arachidonoylglycerol, endogenous cannabinoid agonists
- Cannabidiol (CBD), an isomer of THC
- Cannabinol (CBN), a metabolite of THC
- Dimethylheptylpyran
- Parahexyl
- Tetrahydrocannabinolic acid, the biosynthetic precursor for THC
- HU-210, WIN 55,212-2, JWH-133, synthetic cannabinoid agonists
- Medical cannabis
- War on Drugs
- Effects of cannabis
References
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<references group=""></references>External links
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