View source for Tetrahydrocannabinol

{{Redirect|THC}}
<!-- Here is a table of data; skip past it to edit the text. -->
{{Drugbox
| Watchedfields = changed
| verifiedrevid = 307466872
| IUPAC_name        = (−)-(6a''R'',10a''R'')-6,6,9-trimethyl-<br />3-pentyl-6a,7,8,10a-tetrahydro-<br />6''H''-benzo[''c'']chromen-1-ol
| image             = Tetrahydrocannabinol.svg
| width             = 200px
| imagename         =
| image2 = Delta-9-tetrahydrocannabinol-from-tosylate-xtal-3D-balls.png
| drug_name         = Tetrahydrocannabinol (THC)
| CASNo_Ref = {{cascite}}
| CAS_number        = 1972-08-3
| ChemSpiderID      = 15266
| CAS_supplemental  =
| ATC_prefix        = A04
| ATC_suffix        = AD10
| ATC_supplemental  =
| PubChem           = 16078
| DrugBank          = DB00470
| chemical_formula  =
| C=21 | H=30 | O=2
| molecular_weight  = 314.45
| smiles            = C1=C(CC[C@@H]3[C@@H]1C2=C(C=C(C=C2OC3(C)C)CCCCC)O[H])C
| synonyms          = Dronabinol
| density           =
| melting_point     =
| melting_high      =
| melting_notes     =
| boiling_point     = 157
| boiling_notes     = <ref>{{cite web
|url=http://www.omma1998.org/McPartland-Russo-JCANT%201(3-4)-2001.pdf
|title=Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts?
|publisher=www.haworthpress.com
|accessdate=2009-10-22
|last=
|first=}}</ref>
| solubility        = 0.0028 <ref>
{{cite web
|url=http://chem.sis.nlm.nih.gov/chemidplus/ProxyServlet?objectHandle=Search&actionHandle=getAll3DMViewFiles&nextPage=jsp%2Fcommon%2FChemFull.jsp%3FcalledFrom%3Dlite&chemid=001972083&formatType=_3D
|title=ChemIDplus Lite
|publisher=chem.sis.nlm.nih.gov
|accessdate=2008-08-08
|last=
|first=
}}
{{Dead link|date=August 2009}}
{{Verify source|date=August 2009}}
</ref> (23 °C)
| specific_rotation = -152° (ethanol)
| sec_combustion    =
| bioavailability   = 10-35% (inhalation), 6-20% (oral)<ref name="pmid12648025">{{cite journal |author=Grotenhermen F |title=Pharmacokinetics and pharmacodynamics of cannabinoids |journal=Clin Pharmacokinet |volume=42 |issue=4 |pages=327–60 |year=2003 |pmid=12648025 | doi = 10.2165/00003088-200342040-00003}}</ref>
| protein_bound     = 95-99%<ref name="pmid12648025"/>
| metabolism        = mostly hepatic by CYP2C<ref name="pmid12648025"/>
| elimination_half-life = 1.6-59 hours <ref name="pmid12648025"/>, 25-36 hours (orally administered Dronabinol)
| excretion         = 65-80% (feces), 20-35% (urine) as acid metabolites<ref name="pmid12648025"/>
| licence_EU        =  <!-- EMEA requires brand name -->
| licence_US        =  <!-- FDA may use generic name --> 
| pregnancy_AU      =  <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US      =  <!-- A / B            / C / D / X -->
| pregnancy_category = C
| legal_AU          =  <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA          =  <!--             / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK          =  <!-- GSL         / P       / POM / CD / Class A, B, C -->
| legal_US =
| legal_status      = [[Controlled Substances Act|Schedule I and III]] ([[United States|US]])
| dependency_liability =
| routes_of_administration =
}}

'''Tetrahydrocannabinol''' ({{pron-en|ˌtɛtrəˌhaɪdrɵkəˈnæbɨnɒl}} {{Respell|tet-rə|HYE|drə-kə|NAB|i-nol}}) ('''THC'''), also known as '''delta-9-tetrahydrocannabinol''' (Δ<sup>9</sup>-THC), '''Δ<sup>1</sup>-THC''' (using an older [[International Union of Pure and Applied Chemistry nomenclature|chemical nomenclature]]), or '''dronabinol''', is the main [[psychoactive substance]] found in the [[cannabis]] plant.

It was first isolated by [[Yechiel Gaoni]] and [[Raphael Mechoulam]] from the [[Weizmann Institute of Science]] in [[Rehovot]], [[Israel]], in [[1964]].<ref name="doi10.1021/ja01062a046">{{cite journal
  | last = Gaoni | first = Yechiel
  | coauthors = Raphael Mechoulam
  | title = Isolation, structure and partial synthesis of an active constituent of hashish
  | journal = Journal of the American Chemical Society
  | volume = 86
  | issue = 8
  | pages = 1646–1647
  | year = 1964
  | url = http://pubs.acs.org/cgi-bin/searchRedirect.cgi/jacsat/1964/86/i08/pdf/ja01062a046.pdf
  | doi = 10.1021/ja01062a046
  | accessdate = 2008-05-31|format=PDF}}</ref><ref>[http://matters.ecnp.nl/number11/interview2.shtml Interview with the winner of the first ECNP Lifetime Achievement Award: Raphael Mechoulam, Israel] February 2007</ref><ref>Geller, Tom. (2007)."[http://chemicalheritage.org/pubs/ch-v25n2-articles/feature_cannabinoids.html Cannabinoids: A Secret History]",  ''Chemical Heritage Newsmagazine'', '''25''' (2)</ref> In pure form, it is a glassy solid when cold and becomes [[viscous]] and sticky if warmed. An [[aromatic]] [[terpenoid]], THC has a very low [[solubility]] in water, but good solubility in most organic [[solvent]]s.

Like most pharmacologically-active [[secondary metabolite]]s of plants, THC in [[cannabis]] is assumed to be involved in [[self-defense]], perhaps against [[herbivore]]s.<ref name=Pate1994>{{Cite journal
 | last = Pate | first =  D.W.
 | year = 1994
 | title = Chemical ecology of Cannabis
 | journal = J. Int. Hemp Assoc
 | volume = 1
 | issue = 29
 | pages = 32–37
 | url = http://www.kew.org/kbd/detailedresult.do?id=91816
}}</ref> THC also possesses high [[Ultraviolet|UV-B]] (280-315&nbsp;nm) absorption properties, which, it has been speculated, could protect the plant from harmful UV radiation exposure.<ref name=Pate1983>{{Cite journal
 | last = Pate | first =  D.W.
 | year = 1983
|title =Possible role of ultraviolet radiation in evolution of  Cannabis  chemotypes

 | journal = Economic Botany
 | volume = 37
 | pages = 396–405
| doi =10.1007/BF02904200
 | doi_brokendate = 2009-12-04
}}</ref><ref name=Lydon1987a>{{Cite journal
 | last = Lydon | first =  J
 | coauthors = A.H. Teramura
 | year = 1987
 | journal = Phytochemistry
 | volume = 26
 | pages = 1216
 | doi = 10.1016/S0031-9422(00)82388-2
 | title = Photochemical decomposition of cannabidiol in its resin base
}}</ref><ref name=Lydon1987b>{{Cite journal
 | last = Lydon | first =  J
 | coauthors = A.H. Teramura, C.B. Coffman
 | year = 1987
 | journal = Photochem. Photobiol. A
 | volume = 46
 | pages = 201
 | doi = 10.1111/j.1751-1097.1987.tb04757.x
 | title = UV-B radiation effects on photosynthesis, growth and cannabinoid production of two Cannabis sativa chemotypes}}</ref>

Dronabinol is the [[International Nonproprietary Name]] (INN) for a pure [[isomer]] of THC, (-)-trans-Δ<sup>9</sup>-tetrahydrocannabinol, that is, the main isomer in cannabis.<ref>http://www.incb.org/pdf/e/list/green.pdf</ref> It is sold as '''Marinol''' (a registered trademark of [[Solvay (company)|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.

==Pharmacology==
The [[pharmacology|pharmacological]] actions of THC result from its binding to the [[cannabinoid receptor]] [[Cannabinoid receptor type 1|CB<sub>1</sub>]], located mainly in the [[central nervous system]], and the [[Cannabinoid receptor type 2|CB<sub>2</sub>]] receptor, mainly present in cells of the [[immune system]]. It acts as a partial [[agonist]] on both receptors, i.e., it activates them but not to their full extent. The psychoactive effects of THC are mediated by its activation of the [[Cannabinoid receptor type 1|CB<sub>1</sub>]] receptor, which is the most abundant [[G protein-coupled receptor]] in the [[brain]].

The presence of these specialized receptors in the [[brain]] implied to researchers that [[endogenous]] [[cannabinoids]] are manufactured by the body, so the search began for a substance normally manufactured in the brain that binds to these receptors, the so-called natural [[ligand]] or [[agonist]], leading to the eventual discovery of [[anandamide]], 2-arachidonyl glyceride ([[2-AG]]), and other related compounds known as [[endocannabinoid]]s. This is similar to the story of the discovery of endogenous [[opiates]] ([[endorphins]], [[enkephalins]], and [[dynorphin]]), after the realization that [[morphine]] and other opiates bind to specific receptors in the brain. In addition, it has been shown that cannabinoids, through an unknown mechanism, activate endogenous opioid pathways involving the μ<sub>1</sub> [[opioid receptor]], precipitating a [[dopamine]] release in the [[nucleus accumbens]]. The effects of the drug can be suppressed by the CB1 [[cannabinoid receptor]] antagonist [[rimonabant]] (SR141716A) as well as [[opioid receptor]] antagonists (opioid blockers) [[naloxone]] and [[naloxonazine]].<ref name="Lupica 2004">{{cite journal |author=Lupica CR, Riegel AC, Hoffman AF |title=Marijuana and cannabinoid regulation of brain reward circuits |journal=Br. J. Pharmacol. |volume=143 |issue=2 |pages=227–34 |year=2004 |month=September |pmid=15313883 |pmc=1575338 |doi=10.1038/sj.bjp.0705931}}</ref>

The mechanism of endocannabinoid synaptic transmission is thought to occur as follows: First, transmission of the excitatory neurotransmitter [[glutamate]] causes an influx of [[calcium]] ions into the [[post-synaptic]] neuron. Through a mechanism not yet fully understood, the presence of post-synaptic calcium induces the production of endocannabinoids in the post-synaptic neuron. These endocannabinoids (such as anandamide), then, are released into the synaptic cleft, where binding occurs at cannabinoid receptors present on pre-synaptic neurons, where they modulate neurotransmission. Thus, this form of neurotransmission is termed [[retrograde signaling|retrograde transmission]], as the signal is carried in the opposite direction of orthodox propagation, which previously was thought to be exclusively one way.

THC has mild to moderate [[analgesic]] effects, and [[cannabis]] can be used to treat pain. The mechanism for analgesic effects caused directly by THC or other cannabinoid agonists is not fully understood.  Other effects include relaxation; [[euphoria]]; altered space-time perception; alteration of visual, auditory, and olfactory senses; anxiety; disorientation; fatigue; and [[Health_issues_and_the_effects_of_cannabis#Appetite|appetite stimulation]] (colloquially known as "the munchies"). The mechanism for appetite stimulation in subjects is believed to result from activity in the gastro-hypothalamic axis. CB1 activity in the hunger centers in the hypothalamus increases the palatability of food when levels of a hunger hormone [[ghrelin]] increase as food enters the stomach. After chyme is passed into the [[duodenum]], signaling [[hormone]]s such as [[cholecystokinin]] and [[leptin]] are released, causing reduction in gastric emptying and transmission of satiety signals to the hypothalamus. Cannabinoid activity is reduced through the satiety signals induced by leptin release. It also has [[anti-emetic]] properties, and also may reduce aggression in certain subjects.

THC has an active [[metabolite]], [[11-Hydroxy-THC]], which may also play a role in the analgesic and recreational effects of [[cannabis]].

The α<sub>7</sub> nicotinic receptor antagonist [[methyllycaconitine]] can block self-administration of THC in rats comparable to the effects of [[varenicline]] on nicotine administration.<ref>"Plant extract may block cannabis addiction" http://www.newscientist.com/article/dn11904-plant-extract-may-block-cannabis-addiction-.html</ref><ref>{{cite journal |author=Solinas M, Scherma M, Fattore L, ''et al.'' |title=Nicotinic alpha 7 receptors as a new target for treatment of cannabis abuse |journal=J. Neurosci. |volume=27 |issue=21 |pages=5615–20 |year=2007 |month=May |pmid=17522306 |doi=10.1523/JNEUROSCI.0027-07.2007}}</ref>

==Toxicity==
[[Image:Thc.pdb.gif|thumb|3D rendering of the THC molecule]]
[[Image:Kolkata-Kut.jpg|thumb|A ''Cannabis sativa'' flower coated with [[trichomes]], which contain more THC than any other part of the plant]]
{{See also|Health issues and effects of cannabis}}

There has never been a documented human fatality from overdosing on tetrahydrocannabinol or cannabis.<ref name="Walker and Huang">{{cite journal |author=Walker JM, Huang SM |title=Cannabinoid analgesia |journal=Pharmacol. Ther. |volume=95 |issue=2 |pages=127–35 |year=2002 |month=August |pmid=12182960 |quote=...to date, there are no deaths known to have resulted from overdose of cannabis. (p. 128) |doi=10.1016/S0163-7258(02)00252-8}}</ref>  Information about THC's [[toxicity]] is derived from animal studies. The toxicity depends on the route of administration and the laboratory animal.  Absorption is limited by [[serum lipids]], which can become saturated with THC, mitigating toxicity.<ref name="ErowidMSDS">[http://www.erowid.org/plants/cannabis/thc_data_sheet.shtml Erowid Cannabis Vault : THC Material Safety Data Sheet<!-- Bot generated title -->]</ref>  According to the [[Merck Index]], 12th edition, THC has a [[LD50|LD<sub>50</sub>]] (dose killing half of the research subjects) value of 1270&nbsp;[[Milligram|mg]]/[[Kilogram|kg]] (male rats) and 730&nbsp;mg/kg (female rats) administered orally dissolved in [[sesame oil]].<ref name="Erowid">{{cite web|url=http://www.erowid.org/plants/cannabis/cannabis_chemistry.shtml|title=Cannabis Chemistry|accessdate=2006-03-20|author=Erowid}}</ref>  The LD<sub>50</sub> value for rats by inhalation of THC is 42&nbsp;mg/kg of body weight.<ref name="Erowid">{{cite web|url=http://www.erowid.org/plants/cannab/cannabis_chemistry.shtml|title=Cannabis Chemistry|accessdate=2006-03-20|author=Erowid}}</ref>  One estimate of THC's LD<sub>50</sub> for humans indicates that about 1500 pounds (680 kilograms) of cannabis would have to be smoked within 14 minutes.<ref>{{cite journal |author=Annas GJ |title=Reefer madness--the federal response to California's medical-marijuana law |journal=N. Engl. J. Med. |volume=337 |issue=6 |pages=435–9 |year=1997 |month=August |pmid=9241134 |doi=10.1056/NEJM199708073370621}}</ref>  This estimate is supported by studies which indicate that the effective dose of THC is at least 1000 times lower than the estimated lethal dose (a "[[therapeutic ratio]]" of 1000:1).  This is much higher than [[alcoholic beverage|alcohol]] (therapeutic ratio 10:1), [[cocaine]] (15:1), or [[heroin]] (6:1).<ref name=Gable2004>{{Cite journal
 | last = Gable | first =  R.S.
 | year = 2004
 | title = Comparison of acute lethal toxicity of commonly abused psychoactive substances
 | journal = Addiction
 | volume = 99
 | issue = 6
 | pages = 686–696
 | doi = 10.1111/j.1360-0443.2004.00744.x
 | url = http://web.cgu.edu/faculty/gabler/toxicity%20Addiction%20offprint.pdf
|format=PDF
 | pmid = 15139867}}</ref>

{| class="wikitable"
|-
! Animal
! Administration
! LD<sub>50</sub> [mg/kg]
|-
| rat
| oral
| 666 <ref name="ErowidMSDS" />
|-
| rat (male)
| oral
| 1270 <ref name="Erowid" />
|-
| rat (female)
| oral
| 730 <ref name="Erowid" />
|-
| rat
| inhalation
| 42 <ref name="Erowid" />
|-
| rat
| intraperitoneal
| 373 <ref name="ErowidMSDS" />
|-
| rat
| intravenous
| 29 <ref name="ErowidMSDS" />
|-
| mouse
| intravenous
| 42 <ref name="ErowidMSDS" />
|-
| mouse
| oral
| 482 <ref name="ErowidMSDS" />
|-
| mouse
| intraperitoneal
| 168 <ref name="ErowidMSDS" />
|-
| monkey ([[LDLo]])
| intravenous
| 128 <ref name="ErowidMSDS" />
|-
| dog
| oral
| 525 <ref name="ErowidMSDS" />
|-
|}

==Research==
The discovery of THC 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 (journal)|Science]]'', with "Marihuana chemistry" by [[Raphael Mechoulam]] in June 1970,<ref>{{cite journal
  | last = Mechoulam | first = Raphael
  | title = Marijuana Chemistry
  | journal = Science
  | volume = 168
  | issue = 3936
  | pages = 1159–1165
  | date = 5 June 1970
  | url = http://www.sciencemag.org/cgi/content/citation/168/3936/1159
  | doi = 10.1126/science.168.3936.1159
  | accessdate = 2008-05-31
  | pmid = 4910003}}</ref> followed by "Chemical basis of hashish activity" in August 1970.<ref>{{cite journal
  | last = Mechoulam | first = Raphael
  | coauthors = Arnon Shani, Habib Edery, and Yona Grunfeld
  | title = Chemical Basis of Hashish Activity
  | journal = Science
  | volume = 169
  | issue = 3945
  | pages = 611–612
  | date = 7 August 1970
  | url = http://www.sciencemag.org/cgi/content/abstract/169/3945/611
  | doi = 10.1126/science.169.3945.611
  | accessdate = 2008-05-31
  | pmid = 4987683}}</ref>  In the latter, the team of researchers from [[Hebrew University of Jerusalem|Hebrew University]] Pharmacy School and [[Tel Aviv University]] Medical School experimented on monkeys to isolate the active compounds in [[hashish]].  Their results provided evidence that, except for tetrahydrocannabinol, no other major active compounds were present in hashish.

===Studies in humans===
A number of studies show that THC provides medical benefits for [[cancer]] and [[AIDS]] patients by increasing appetite and decreasing nausea. It has also been shown to assist some [[glaucoma]] patients 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">{{cite web|url=http://www.nationalmssociety.org/about-multiple-sclerosis/treatments/complementary--alternative-medicine/marijuana/index.aspx|title=Marijuana (Cannabis)|publisher=National Multiple Sclerosis Society|accessdate=2009-09-05}}</ref><br>
In August 2009 a [[Clinical_study#Phase_IV|phase IV clinical trial]] by the [[Hadassah Medical Center]] in Jerusalem, Israel was started to investigate the effects of THC on [[post-traumatic stress disorder]]s.<ref name="urlAdd on Study on Δ9-THC Treatment for Posttraumatic Stress Disorders (PTSD) - Full Text View - ClinicalTrials.gov">{{cite web |url=http://clinicaltrials.gov/ct2/show/NCT00965809 |title=Add on Study on Δ9-THC Treatment for Posttraumatic Stress Disorders (PTSD) - Full Text View - ClinicalTrials.gov |format= |work= |accessdate=}}</ref> THC and other cannabinoid agonist have been shown to be beneficial both in [[Open-label trial|open label studies]], as well as in laboratory experiments with animals to ameliorate post-traumatic stress disorders.<br>
Preliminary research on synthetic THC has been conducted on patients with [[Tourette syndrome]], with results suggesting that it may help in reducing nervous tics and urges by a significant degree. Research on twelve patients showed that Marinol reduced tics with no significant adverse effects. A six-week controlled study on 24 patients showed that the patients taking [[dronabinol]] had a significant reduction in tic severity without serious adverse effects. More significant reduction in tic severity was reported with longer treatment. No detrimental effects on cognitive functioning and a trend towards improvement in cognitive functioning were reported during and after treatment. [[Dronabinol|Dronabinol's]] usefulness as a treatment for TS cannot be determined until/unless longer controlled studies on larger samples are undertaken.<ref>{{cite journal | author = Müller-Vahl,K.R.  Schneider,U.  Koblenz,A.  Jöbges,M.  Kolbe,H.  Daldrup,T.  Emrich,H.M. | title =Treatment of Tourette's Syndrome with Δ9-Tetrahydrocannabinol (THC): A Randomized Crossover Trial | journal =Pharmacopsychiatry | volume =35 | issue =2 | pages =57–61 | pmid =11951146 | doi =10.1055/s-2002-25028 | year =2002}}</ref><ref>{{cite journal | doi =10.4088/JCP.v64n0417 | author =Müller-Vahl KR, Schneider U, Prevedel H, Theloe K, Kolbe H, Daldrup T, Emrich HM.  | title =Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial  | journal= J Clin Psychiatry | month = April | year = 2003 | volume =64 | issue =4 | pages =459–65 | pmid =12716250}}</ref><ref>{{cite journal | author = Muller-Vahl KR, Prevedel H, Theloe K, Kolbe H, Emrich HM, Schneider U.  | title =Treatment of Tourette syndrome with delta-9-tetrahydrocannabinol (delta 9-THC): no influence on neuropsychological performance  | journal = Neuropsychopharmacology | month = February | year = 2003 | volume =28 | issue =2 | pages =384–388 | pmid =12589392  | doi =10.1038/sj.npp.1300047 }}</ref>

[[Dronabinol]] (Marinol®) is now a Schedule III medication which allows doctors to prescribe it for off label uses. It is now being prescribed to a small population of patients for ADHD and depression.<ref>{{cite doi|10.1080/10550490701861177}}/</ref>

===Studies in animals and in vitro===
New scientific evidence is showing that THC can prevent [[Alzheimer's Disease]] in an [[animal model]] by preventing the inflammation caused by [[microglia]] cells which are activated by binding of [[amyloid]] protein.<ref name="pmid15728830">{{cite journal
|author=Ramírez BG, Blázquez C, Gómez del Pulgar T, Guzmán M, de Ceballos ML
|title=Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation
|journal=J. Neurosci.
|volume=25
|issue=8
|pages=1904–13
|year=2005
|pmid=15728830
|doi=10.1523/JNEUROSCI.4540-04.2005
}}</ref><br>
In ''[[in-vitro]]'' experiments, THC at extremely high concentrations, which could not be reached with commonly-consumed doses, caused inhibition of plaque formation (which are associated with [[Alzheimer's disease]]) better than currently-approved drugs.<ref>{{cite journal |author=Eubanks LM, Rogers CJ, Beuscher AE, ''et al.'' |title=A molecular link between the active component of marijuana and Alzheimer's disease pathology |journal=Mol. Pharm. |volume=3 |issue=6 |pages=773–7 |year=2006 |pmid=17140265 |doi=10.1021/mp060066m |pmc=2562334}}</ref>

THC may also be an effective anti-cancer treatment, with studies showing tumor size reduction in mice conducted in 1975<ref>Munson AE, Harris LS, Friedman MA, Dewey WL, Carchman RA. [http://www.drugpolicycentral.com/bot/pg/cancer/THC_cancer_sep_1975.htm "Anticancer activity of cannabinoids."] Journal of the National Cancer Institute. September 1975;'''55'''(3):597-602. Accessed 2007-10-27.</ref> and 2007<ref>{{cite journal |author=Preet A, Ganju RK, Groopman JE |title=Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo |journal=Oncogene |volume=27 |issue=3 |pages=339–46 |year=2008 |month=January |pmid=17621270 |doi=10.1038/sj.onc.1210641}}</ref>, as well as in a pilot study in humans with [[glioblastoma multiforme]] (a type of brain cancer).<ref>{{cite journal |author=Guzmán M, Duarte MJ, Blázquez C, ''et al.'' |title=A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme |journal=Br. J. Cancer |volume=95 |issue=2 |pages=197–203 |year=2006 |month=July |pmid=16804518 |pmc=2360617 |doi=10.1038/sj.bjc.6603236}}</ref>

A two-year study in which rats and mice were force-fed tetrahydrocannabinol dissolved in corn oil showed reduced body mass, enhanced survival rates, and decreased tumor incidences in several sites, mainly organs under hormonal control.  It also caused [[testicular atrophy]] and uterine and ovarian [[hypoplasia]], as well as hyperactivity and convulsions immediately after administration, of which the onset and frequency were dose related.<ref>{{cite journal |author=Chan PC, Sills RC, Braun AG, Haseman JK, Bucher JR |title=Toxicity and carcinogenicity of delta 9-tetrahydrocannabinol in Fischer rats and B6C3F1 mice |journal=Fundamental and applied toxicology : official journal of the Society of Toxicology |volume=30 |issue=1 |pages=109–17 |year=1996 |pmid=8812248 |doi=10.1006/faat.1996.0048}}</ref>

Research in rats indicates that THC prevents [[hydroperoxide]]-induced [[oxidative damage]] as well as or better than other [[antioxidant]]s in a chemical ([[Fenton reaction]]) system and [[neuron]]al cultures.<ref name="pmid9653176">{{cite journal |author=Hampson AJ, Grimaldi M, Axelrod J, Wink D |title=Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=95 |issue=14 |pages=8268–73 |year=1998 |month=July |pmid=9653176 |pmc=20965 |doi= 10.1073/pnas.95.14.8268|url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=9653176}}</ref>  In [[mice]] low doses of Δ<sup>9</sup>-THC reduces the progression of [[atherosclerosis]].<ref name="pmid15815632">{{cite journal
|author=Steffens S, Veillard NR, Arnaud C, ''et al.''
|title=Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice
|journal=Nature
|volume=434
|issue=7034
|pages=782–6
|year=2005
|pmid=15815632
|doi=10.1038/nature03389
}}</ref>

Research has also shown that past claims of brain damage from cannabis use fail to hold up to the scientific method.<ref>{{cite web
|title=Heavy Marijuana Use Doesn't Damage Brain
|url=http://www.webmd.com/mental-health/news/20030701/heavy-marijuana-use-doesnt-damage-brain
|publisher=[[WebMD]] Medical News
|author=Sid Kirchheimer
|date=July 1, 2003
}}</ref>  Instead, recent studies with synthetic cannabinoids show that activation of CB1 receptors can facilitate [[neurogenesis]],<ref name=Jiang2005>{{Cite journal
 | author = Jiang, W.; Zhang, Y.; Xiao, L.; Van Cleemput, J.; Ji, S.P.; Bai, G.; Zhang, X.
 | year = 2005
 | title = Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic-and  …
 | journal = Journal of Clinical Investigation
 | volume = 115
 | issue = 11
 | pages = 3104
 | url = http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1253627
 | publisher = American Society for Clinical Investigation
 | doi = 10.1172/JCI25509
 | pmid = 16224541
 | pmc = 1253627
}}</ref> as well as neuroprotection<ref name=Sarne2005>{{Cite journal
 | author = Sarne, Y.; Mechoulam, R.
 | year = 2005
 | title = Cannabinoids: Between Neuroprotection and Neurotoxicity
 | journal = Current Drug Targets-Cns and Neurological Disorders-
 | volume = 4
 | issue = 6
 | pages = 677
 | doi = 10.2174/156800705774933005
 | url = http://www.ingentaconnect.com/content/ben/cdtcnsnd/2005/00000004/00000006/art00008
 | pmid = 16375685
}}</ref>, and can even help prevent natural neural degradation from neurodegenerative diseases such as MS, Parkinson's, and Alzheimer's. This, along with research into the CB2 receptor (throughout the immune system), has given the case for medical marijuana more support.<ref name=Correa2005>{{Cite journal
 | author = Correa, F.; Mestre, L.; Molina-holgado, E.; Arevalo-martin, A.; Docagne, F.; Romero, E.; Molina-holgado, F.; Borrell, J.; Guaza, C.
 | year = 2005
 | title = The Role of Cannabinoid System on Immune Modulation: Therapeutic Implications on CNS Inflammation
 | journal = Mini Rev Med Chem
 | volume = 5
 | issue = 7
 | pages = 671–5
 | doi = 10.2174/1389557054368790
 | url = http://www.ingentaconnect.com/content/ben/mrmc/2005/00000005/00000007/art00008
 | pmid = 16026313
}}</ref><ref name=Fernández-ruiz2007>{{Cite journal
 | author = Fernández-ruiz, J.; Romero, J.; Velasco, G.; Tolón, R.M.; Ramos, J.A.; Guzmán, M.
 | year = 2007
 | title = Cannabinoid CB2 receptor: A new target for controlling neural cell survival?
 | journal = Trends in Pharmacological Sciences
 | volume = 28
 | issue = 1
 | pages = 39–45
 | doi = 10.1016/j.tips.2006.11.001
 | url = http://linkinghub.elsevier.com/retrieve/pii/S0165614706002677
 | pmid = 17141334
}}</ref> THC is both a CB1 and CB2 agonist.<ref>http://www.tocris.com/pdfs/cannabinoid_receptor_review/page_003.html</ref>

===Research indicating negative side-effects===
Conceivable long-term ill effects of THC on humans are disputed, yet its status as an illegal drug in most countries makes research difficult.

Some studies claim a variety of negative effects associated with constant, long-term use, including short-term memory loss.<ref name="pmid19825904">{{cite journal |author=Bartholomew J, Holroyd S, Heffernan TM |title=Does cannabis use affect prospective memory in young adults? |journal=J. Psychopharmacol. (Oxford) |volume= 24|issue= 2|pages= 241–6|year=2009 |month=October |pmid=19825904 |doi=10.1177/0269881109106909 |url=}}</ref><ref name="pmid18635709">{{cite journal |author=Indlekofer F, Piechatzek M, Daamen M, ''et al.'' |title=Reduced memory and attention performance in a population-based sample of young adults with a moderate lifetime use of cannabis, ecstasy and alcohol |journal=J. Psychopharmacol. (Oxford) |volume=23 |issue=5 |pages=495–509 |year=2009 |month=July |pmid=18635709 |doi=10.1177/0269881108091076 |url=}}</ref> Other studies have refuted this by evidence of MRIs of long-term users, showing little or no difference to MRIs of the non-using control group. Using [[positron emission tomography]] (PET), one study reports altered memory-related brain function in chronic daily marijuana users.<ref name="Block2002">{{cite journal |author=Block RI, O'Leary DS, Hichwa RD, ''et al.'' |title=Effects of frequent marijuana use on memory-related regional cerebral blood flow |journal=Pharmacol. Biochem. Behav. |volume=72 |issue=1-2 |pages=237–50 |year=2002 |month=May |pmid=11900794 |doi=10.1016/S0091-3057(01)00771-7}}</ref>

Some studies have suggested that marijuana 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>{{cite journal |author=Moore TH, Zammit S, Lingford-Hughes A, ''et al.'' |title=Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review |journal=Lancet |volume=370 |issue=9584 |pages=319–28 |year=2007 |month=July |pmid=17662880 |doi=10.1016/S0140-6736(07)61162-3}}</ref> Other studies have made similar associations, especially in individuals predisposed to psychosis prior to cannabis use.<ref>{{cite journal |author=Henquet C, Krabbendam L, Spauwen J, ''et al.'' |title=Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people |journal=BMJ |volume=330 |issue=7481 |pages=11 |year=2005 |month=January |pmid=15574485 |pmc=539839 |doi=10.1136/bmj.38267.664086.63}}</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>{{cite journal |author=Caspi A, Moffitt TE, Cannon M, ''et al.'' |title=Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction |journal=Biol. Psychiatry |volume=57 |issue=10 |pages=1117–27 |year=2005 |month=May |pmid=15866551 |doi=10.1016/j.biopsych.2005.01.026}}</ref>   A literature review on the subject concluded that "Cannabis  use appears to be neither a sufficient nor a necessary cause for psychosis. It  is a component cause, part of a complex constellation of factors leading to  psychosis."<ref name=Arseneault2004>{{Cite journal
 | author = Arseneault, Louise; Cannon, Mary; Witton, John; Murray, Robin M.
 | year = 2004
 | title = Causal association between cannabis and psychosis: examination of the evidence
 | journal = The British Journal of Psychiatry
 | volume = 184
 | issue = 2
 | pages = 110–117
 | doi = 10.1192/bjp.184.2.110
 | url = http://bjp.rcpsych.org/cgi/content/full/184/2/110
 | pmid = 14754822
}}</ref>  Contrastingly, 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">{{cite journal|author=Laqueille, X.|date=September 2009|title=Is cannabis a vulnerability factor in schizophrenic disorders|journal=Arch Pediatr.|volume=16|issue=9|pages=1302–5|pmid= 19640690|publisher=Elsevier|language=French|doi=10.1016/j.arcped.2009.03.016}}</ref>
A 2008 German review reported that cannabis was supposedly 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>{{cite journal|author=Kawohl W, Rössler W.|date=2008|title=[Cannabis and Schizophrenia: new findings in an old debate]|journal=Neuropsychiatr|volume=22|issue=4|pages=223–9|pmid= 19080993|language=German}}</ref> Interestingly, however, though cannabis use has increased dramatically in several countries over the past few decades, the rates of psychosis and schizophrenia have generally ''not'' increased, casting some doubt over whether the drug can cause cases that would not otherwise have occurred.<ref>{{cite paper|author=Degenhardt L, Hall W, Lynskey M |title=Comorbidity between cannabis use and psychosis: Modelling some possible relationships.| version = Technical Report No. 121. |publisher=Sydney: National Drug and Alcohol Research Centre.|year=2001 |url=http://ndarc.med.unsw.edu.au/NDARCWeb.nsf/resources/TR_18/$file/TR.121.PDF|format=[[PDF]]|accessdate=2006-08-19 }}</ref>

Research from 2007 reported a correlation between cannabis use and ''increased'' cognitive function in schizophrenic patients.<ref>{{cite journal |author=Coulston CM, Perdices M, Tennant CC |title=The neuropsychological correlates of cannabis use in schizophrenia: lifetime abuse/dependence, frequency of use, and recency of use |journal=Schizophr. Res. |volume=96 |issue=1-3 |pages=169–84 |year=2007 |month=November |pmid=17826035 |doi=10.1016/j.schres.2007.08.006}}</ref>

A 2008 [[National Institutes of Health]] study of 18 chronic heavy marijuana users with cardiac and cerebral abnormalities  (averaging 78 to 350 marijuana cigarettes per week, or 30 g to 270 g (1 to 9.5 ounces)) and 24 controls found elevated levels of [[Apolipoprotein C3|apolipoprotein C-III]] (apoC-III) in the chronic smokers.<ref>{{cite journal |author=Jayanthi S, Buie S, Moore S, ''et al.'' |title=Heavy marijuana users show increased serum apolipoprotein C-III levels: evidence from proteomic analyses |journal=Mol. Psychiatry |volume= 15|issue= 1|pages= 101–12|year=2008 |month=May |pmid=18475272 |doi=10.1038/mp.2008.50 |pmc=2797551}}</ref><ref>{{cite news|url=http://www.reuters.com/article/healthNews/idUSN1231013620080513|title=Marijuana may up heart attack, stroke risk: study|last=Dunham|first=Will|date=May 13, 2008|publisher=Reuters|accessdate=2009-09-05}}</ref> An increase in apoC-III levels induces the development of [[hypertriglyceridemia]].

A 2008 study by the [[University of Melbourne]] of 15 heavy marijuana users (consuming at least 5 marijuana cigarettes daily for on average 20 years) and 16 controls found an average size difference for the smokers in the [[hippocampus]] (12 percent smaller) and the [[amygdala]] (7 percent smaller).<ref>{{cite journal|author=Yücel M|coauthors=''et al.''|date=2008|title=Regional brain abnormalities associated with long-term heavy cannabis use|journal=Arch Gen Psychiatry|volume=65|issue=6|pages=694–701|pmid=18519827|doi=10.1001/archpsyc.65.6.694}}</ref> It has been suggested that such effects can be reversed with long term abstinence.<ref name=Chang2006>{{Cite journal
 | author = Chang, L.; Yakupov, R.; Cloak, C.; Ernst, T.
 | year = 2006
 | title = Marijuana use is associated with a reorganized visual-attention network and cerebellar hypoactivation.
 | journal = Brain
 | pmid = 16585053
 | volume = 129
 | issue = 5
 | pages = 1096
 | doi = 10.1093/brain/awl064
 | url = http://brain.oxfordjournals.org/cgi/content/full/129/5/1096
}}</ref> However, the study indicates that they are unsure that the problems were caused by marijuana alone. Furthermore, this correlation might suggest self-medication by individuals with these brain features.

A 2008 study at [[Karolinska Institute]] suggested  that young rats treated with [[THC]] received an increased motivation for drug use, heroin in the study, under conditions of stress.<ref>{{cite book|last=Ellgren, Maria|title=Neurobiological effects of early life cannabis exposure in relation to the gateway hypothesis |date=9 Feb 2007|isbn=978-91-7357-064-0  |url=http://diss.kib.ki.se/2007/978-91-7357-064-0/|language=English and Swedish|location=Stockholm}}</ref><ref>{{cite journal|author=Ellgren M, Spano SM, Hurd YL|date=2007|title=Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats|journal=Neuropsychopharmacology|volume=32|issue=3|pages=607–15 |pmid=16823391|doi=10.1038/sj.npp.1301127}}</ref>

A 2009 study found that there was a high prevalence of cannabis in the toxicologic analysis of homicide (22%) and suicide victims (11%) in Australia.<ref>{{cite journal|author=Darke S, Duflou J, Torok M|date=2009|title=Drugs and violent death: comparative toxicology of homicide and non-substance toxicity suicide victims.|journal=Addiction|volume=104|issue=6|pages=1000–5|pmid=19466923|doi=10.1111/j.1360-0443.2009.02565.x}}</ref> In a similar study from Sweden it was also found that suicide victims had a significant higher use of cannabis, but the authors found that "this was explained by markers of psychological and behavioural problems".<ref name="pmid19949196">{{cite journal |author=Price C, Hemmingsson T, Lewis G, Zammit S, Allebeck P |title=Cannabis and suicide: longitudinal study |journal=Br J Psychiatry |volume=195 |issue=6 |pages=492–7 |year=2009 |month=December |pmid=19949196 |doi=10.1192/bjp.bp.109.065227 |url=}}</ref>

==Biosynthesis==
[[Image:THC biosynthesis.png|thumb|Biosynthesis of THC]]
In the [[cannabis]] plant, THC occurs mainly as tetrahydrocannabinol [[carboxylic acid]] (THC-COOH). [[Geranyl pyrophosphate]] and [[olivetol]]ic acid react, catalysed by an [[enzyme]] to produce [[cannabigerol|cannabigerolic acid]],<ref name="pmid9607329">{{cite journal |author=Fellermeier M, Zenk MH |title=Prenylation of olivetolate by a hemp transferase yields cannabigerolic acid, the precursor of tetrahydrocannabinol |journal=FEBS Lett. |volume=427 |issue=2 |pages=283–5 |year=1998 |month=May |pmid=9607329 |doi= 10.1016/S0014-5793(98)00450-5|url=}}</ref> which is cyclized by the enzyme THC acid [[synthase]] to give THC-COOH. Over time, or when heated, THC-COOH is [[decarboxylation|decarboxylated]] producing THC. The pathway for THC-COOH biosynthesis is similar to that which produces the bitter acid, [[humulone]] in [[hops]].<ref>{{cite doi|10.1093/jxb/erp210}}</ref>

==Metabolism==
THC is metabolized mainly to [[11-Hydroxy-THC|11-OH-THC]] (11-hydroxy-THC) by the human 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]]. 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">{{cite journal
|author=Huestis MA
|title=Pharmacokinetics and metabolism of the plant cannabinoids, Δ<sup>9</sup>-tetrahydrocannabinol, cannabidiol and cannabinol
|journal=Handb Exp Pharmacol
|volume=168
|issue=168
|pages=657–90
|year=2005
|pmid=16596792
|doi=10.1007/3-540-26573-2_23
}}</ref>

===Detection in body fluids===
THC and THC-COOH can be quantitated in blood or urine using [[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. The concentrations obtained from such an analysis can often be helpful in distinguishing active from passive use or prescription from illicit use, elapsed time since use and extent or duration of use.<ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp 1513-1518.</ref>

==Dronabinol==
Synthetic THC is known as ''dronabinol''.  It is available as a prescription drug (under  Marinol<ref>http://www.usdoj.gov/dea/ongoing/marinol.html</ref>) in several countries including the [[United States]] and [[Germany]]. In the United States, Marinol is a [[Controlled Substances Act#Schedule III drugs|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 [[Removal of cannabis from Schedule I of the Controlled Substances Act#2002 Coalition for Rescheduling Cannabis petition|2002 petition]] has been accepted by the [[Drug Enforcement Administration|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 (symptom)|anorexia]] in [[AIDS]] patients, as well as for refractory [[nausea]] and [[vomiting]] of patients undergoing [[chemotherapy]], which has raised much controversy as to why natural THC is still a [[Controlled Substances Act#Schedule I controlled substances|schedule I]] drug.<ref>http://arthritis.about.com/cs/medmarijuana/a/marijuanadebate.htm</ref>

An analog of dronabinol, [[nabilone]], is available commercially in Canada under the trade name Cesamet, manufactured by Valeant. Cesamet has also received FDA approval and began marketing in the U.S. in 2006; it is a [[Controlled Substances Act#Schedule II drugs|Schedule II]] drug.

In April 2005, [[Canada|Canadian]] authorities approved the marketing of [[Sativex]], a mouth spray for [[multiple sclerosis]] patients, who can use it to alleviate [[neuropathic pain]] and [[spasticity]]. Sativex contains tetrahydrocannabinol together with [[cannabidiol]]. It is marketed in [[Canada]] by GW Pharmaceuticals, being the first cannabis-based prescription drug in the world (in modern times). In addition, [[Sativex]] received European regulatory approval in 2010.

===Comparisons to medical marijuana===
{{Main|Medical marijuana}}
Dronabinol is known to produce mild side effects similar to cannabis.{{Citation needed|date=April 2010}}  Many scientists{{Who|date=April 2010}} believe that dronabinol lacks the beneficial properties of cannabis, which contains more than 60 cannabinoids, including [[cannabidiol]] (CBD), thought to be the major [[anticonvulsant]] that helps [[multiple sclerosis]] patients;<ref name="pmid6269680">{{cite journal
|author=Pickens JT
|title=Sedative activity of cannabis in relation to its delta'-trans-tetrahydrocannabinol and cannabidiol content
|journal=Br. J. Pharmacol.
|volume=72
|issue=4
|pages=649–56
|year=1981
|pmid=6269680
|doi=
|pmc=2071638
}}</ref> and [[cannabichromene]] (CBC), an [[anti-inflammatory]] which may contribute to the [[Analgesic|pain-killing]] effect of cannabis.<ref name=Burns2006>{{Cite journal
 | last1 = Burns | first1 = Tammy L.
 | last2 = Ineck | first2 = Joseph R.
 | year = 2006
 | title = Cannabinoid Analgesia as a Potential New Therapeutic Option in the Treatment of Chronic Pain
 | journal = The Annals of Pharmacotherapy
 | volume = 40
 | issue = 2
 | pages = 251–260
 | doi = 10.1345/aph.1G217
 | url = http://www.theannals.com/cgi/content/abstract/40/2/251
 | pmid = 16449552
}}</ref>  Others have countered that the effects of all of cannabis's cannabinoids have not been completely studied and are not fully understood.{{Citation needed|date=November 2008}}

It takes over one hour for Marinol to reach full systemic effect,<ref>http://www.druglibrary.org/schaffer/hemp/medical/marinol1.htm</ref> compared to minutes for [[Cannabis smoking|smoked]] or [[Vaporizer|vaporized]] cannabis.<ref name="mckim">{{cite book | author=McKim, William A | title=Drugs and Behavior: An Introduction to Behavioral Pharmacology (5th Edition)| publisher=Prentice Hall| year=2002| pages=400| isbn=0-13-048118-1 }}</ref>  Some patients accustomed to inhaling just enough cannabis smoke to manage symptoms have complained of too-intense intoxication from Marinol's predetermined dosages. 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. [[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">{{cite news|last=Greenberg|first=Gary|title=Respectable Reefer|publisher=Mother Jones|date=2005-11-01|url=http://motherjones.com/politics/2005/11/respectable-reefer?page=3|accessdate = 8 April 2010}}</ref> United States federal law currently registers dronabinol as a [[Schedule III controlled substance]], but all other cannabinoids remain [[Controlled Substances Act#Schedule I controlled substances|Schedule I]], except [[nabilone]].

==Regulatory history==
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.

On July 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. 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 Δ<sup>9</sup>-tetrahydrocannabinol (also referred to as Δ<sup>9</sup>-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 [http://www.ukcia.org/pollaw/lawlibrary/conventiononpsychotropicsubstances1971.html].

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 abuse<ref name="pmid9692381">{{cite journal |author=Calhoun SR, Galloway GP, Smith DE |title=Abuse potential of dronabinol (Marinol) |journal=Journal of psychoactive drugs |volume=30 |issue=2 |pages=187–96 |year=1998 |pmid=9692381 |doi= |url=}}</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 abuse less than that of [[cocaine]], and [[heroin]]. This rescheduling comprised 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>[http://www.drugscience.org/pt/b.htm]</ref>{{Citation broken|date=September 2009}}.

At its 33rd meeting, the [[World Health Organization]] Expert Committee on Drug Dependence recommended transferring THC to [[Convention on Psychotropic Substances#Schedules of Controlled Substances|Schedule IV]] of the Convention, citing its medical uses and low abuse potential. This would put THC in the Convention's least stringently-controlled Schedule.{{Citation needed|date=November 2009}}

== See also ==
* [[Cannabis (drug)]]
* [[Psychoactive drug]]
* [[Cannabinoids]]
** [[Anandamide]], [[2-Arachidonoylglycerol]], endogenous cannabinoid agonists
** [[Cannabidiol]] (CBD), an [[isomer]] of THC
** [[Cannabinol]] (CBN), a [[metabolite]] of THC
** [[HU-210]], [[WIN 55,212-2]], [[JWH-133]], synthetic cannabinoid agonists
* [[Medical cannabis]]
* [[War on Drugs]]
* [[Cannabis rescheduling in the United States]]
* [[Health issues and the effects of cannabis]]

== References ==
{{Reflist}}

== Further reading ==
{{Refbegin}}
* {{cite journal |author=Calhoun SR, Galloway GP, Smith DE |title=Abuse potential of dronabinol (Marinol) |journal=J Psychoactive Drugs |volume=30 |issue=2 |pages=187–96 |year=1998 |pmid=9692381}}
* [http://www.marijuananews.com/marijuananews/cowan/dea_moves_marinol_to_schedule_th.htm DEA Moves Marinol To Schedule Three, But Leaves Marijuana in Schedule One. The Magic of Sesame Oil], [[Richard Cowan]], MarijuanaNews.Com.
* [http://www.drugscience.org/pt/b.htm Petition to Reschedule Cannabis (Marijuana) per 21 CFR §1308.44(b)], Filed October 9, 2002 with the DEA by the [[Coalition for Rescheduling Cannabis]].
{{Refend}}

== External links ==
* [http://druginfo.nlm.nih.gov/drugportal/dpdirect.jsp?name=Tetrahydrocannabinol U.S. National Library of Medicine: Drug Information Portal - Tetrahydrocannabinol]

{{Drug use}}
{{Cannabinoids}}
{{Hallucinogens}}
{{Antiemetics and antinauseants}}
{{Ancient anaesthesia-footer}}

[[Category:Amorphous solids]]
[[Category:Antiemetics]]
[[Category:Entheogens]]
[[Category:Cannabinoids]]
[[Category:Euphoriants]]
[[Category:Phenols]]
[[Category:Benzochromenes]]

[[bs:Tetrahidrokanabinol]]
[[bg:Тетрахидроканабинол]]
[[ca:Tetrahidrocannabinol]]
[[cs:Tetrahydrocannabinol]]
[[cy:Tetrahydrocannabinol]]
[[da:Tetrahydrocannabinol]]
[[de:Tetrahydrocannabinol]]
[[es:Tetrahidrocannabinol]]
[[fa:تتراهیدروکانابینول]]
[[fr:Tétrahydrocannabinol]]
[[gl:Tetrahidrocannabinol]]
[[hr:Tetrahidrokanabinol]]
[[it:Delta-9-Tetraidrocannabinolo]]
[[he:THC]]
[[la:Tetrahydrocannabinol]]
[[lt:Tetrahidrokanabinolis]]
[[hu:Tetrahidrokannabinol]]
[[nl:Tetrahydrocannabinol]]
[[ja:テトラヒドロカンナビノール]]
[[no:Tetrahydrocannabinol]]
[[pl:Tetrahydrokannabinol]]
[[pt:Tetraidrocanabinol]]
[[ro:Tetrahidrocannabinol]]
[[ru:Тетрагидроканнабинол]]
[[simple:Tetrahydrocannabinol]]
[[sk:Tetrahydrokanabinol]]
[[sl:Tetrahidrokanabinol]]
[[sr:Tetrahidrokanabinol]]
[[sh:Tetrahidrokanabinol]]
[[fi:Tetrahydrokannabinoli]]
[[sv:Tetrahydrocannabinol]]
[[th:เตตร้าไฮโดรแคนนาบินอล]]
[[tr:THC]]
[[uk:Тетрагідроканнабінол]]
[[zh:四氢大麻酚]]
[[Category:2Fix]]