Editing Cannabinoid (section)

=== Pharmacology ===
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]].<ref name=":1">{{cite journal | vauthors = Stout SM, Cimino NM | title = Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review | journal = Drug Metabolism Reviews | volume = 46 | issue = 1 | pages = 86–95 | date = February 2014 | pmid = 24160757 | doi = 10.3109/03602532.2013.849268 | s2cid = 29133059 | url = https://zenodo.org/record/1093138 | access-date = 2017-12-07 | archive-date = 2022-10-06 | archive-url = https://web.archive.org/web/20221006071438/https://zenodo.org/record/1093138 | url-status = live }}</ref> Thus supplementing with CYP 2C9 [[Enzyme inhibitor|inhibitors]] leads to extended intoxication.<ref name=":1" />

Some is also stored in [[adipose|fat]] in addition to being metabolized in the liver. Δ<sup>9</sup>-THC is metabolized to [[11-Hydroxy-THC|11-hydroxy-Δ<sup>9</sup>-THC]], which is then metabolized to [[11-nor-9-Carboxy-THC|9-carboxy-THC]].<ref>{{cite journal | vauthors = Aizpurua-Olaizola O, Zarandona I, Ortiz L, Navarro P, Etxebarria N, Usobiaga A | title = Simultaneous quantification of major cannabinoids and metabolites in human urine and plasma by HPLC-MS/MS and enzyme-alkaline hydrolysis | journal = Drug Testing and Analysis | volume = 9 | issue = 4 | pages = 626–633 | date = April 2017 | pmid = 27341312 | doi = 10.1002/dta.1998 | s2cid = 27488987 | url = https://figshare.com/articles/journal_contribution/5028359 | access-date = 2022-12-02 | archive-date = 2023-01-05 | archive-url = https://web.archive.org/web/20230105025824/https://figshare.com/articles/journal_contribution/Simultaneous_quantification_of_major_cannabinoids_and_metabolites_in_human_urine_and_plasma_by_HPLC-MS_MS_and_enzymealkaline_hydrolysis/5028359 | url-status = live }}</ref> Some cannabis [[metabolite]]s 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 level]]s), but an integration of past consumption over an approximately month-long window. This is because they are fat-soluble, [[lipophilic]] molecules that accumulate in fatty tissues.<ref>{{cite journal | vauthors = Ashton CH | title = Pharmacology and effects of cannabis: a brief review | journal = The British Journal of Psychiatry | volume = 178 | issue = 2 | pages = 101–106 | date = February 2001 | pmid = 11157422 | doi = 10.1192/bjp.178.2.101 | quote = Because they are extremely lipid soluble, cannabinoids accumulate in fatty tissues, reaching peak concentrations in 4-5 days. They are then slowly released back into other body compartments, including the brain. They are then slowly released back into other body compartments, including the brain. Because of the sequestration in fat, the tissue elimination half-life of THC is about 7 days, and complete elimination of a single dose may take up to 30 days. | doi-access = free }}</ref>

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]].<ref name="PMCentourage2011">{{cite journal | vauthors = Russo EB | title = Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects | journal = British Journal of Pharmacology | volume = 163 | issue = 7 | pages = 1344–1364 | date = August 2011 | pmid = 21749363 | pmc = 3165946 | doi = 10.1111/j.1476-5381.2011.01238.x }}</ref>

==== Modulation of mitochondrial activity ====
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 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.<ref>{{Cite journal |last1=Malheiro |first1=Rui Filipe |last2=Carmo |first2=Helena |last3=Carvalho |first3=Félix |last4=Silva |first4=João Pedro |date=January 2023 |title=Cannabinoid-mediated targeting of mitochondria on the modulation of mitochondrial function and dynamics |journal=Pharmacological Research |language=en |volume=187 |pages=106603 |doi=10.1016/j.phrs.2022.106603 |pmid=36516885 |s2cid=254581177 |doi-access=free }}</ref>

==== Cannabinoid-based pharmaceuticals ====
[[Nabiximols]] (brand name Sativex) is an aerosolized mist for oral administration containing a near 1:1 ratio of CBD and THC.<ref>{{cite journal | vauthors = Keating GM | title = Delta-9-Tetrahydrocannabinol/Cannabidiol Oromucosal Spray (Sativex<sup>®</sup>): A Review in Multiple Sclerosis-Related Spasticity | journal = Drugs | volume = 77 | issue = 5 | pages = 563–574 | date = April 2017 | pmid = 28293911 | doi = 10.1007/s40265-017-0720-6 | s2cid = 2884550 }}</ref> Also included are minor cannabinoids and [[terpenoids]], [[ethanol]] and [[propylene glycol]] [[excipients]], and peppermint flavoring.<ref name="ReferenceA">{{cite journal | vauthors = Russo EB | title = Cannabinoids in the management of difficult to treat pain | journal = Therapeutics and Clinical Risk Management | volume = 4 | issue = 1 | pages = 245–259 | date = February 2008 | pmid = 18728714 | pmc = 2503660 | doi = 10.2147/TCRM.S1928 | doi-access = free }}</ref> 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.<ref>{{cite news |vauthors=Cooper R |title=GW Pharmaceuticals launches world's first prescription cannabis drug in Britain |url=https://www.telegraph.co.uk/finance/newsbysector/pharmaceuticalsandchemicals/7842794/GW-Pharmaceuticals-launches-worlds-first-prescription-cannabis-drug-in-Britain.html |access-date=29 November 2018 |date=21 June 2010 |archive-date=30 November 2018 |archive-url=https://web.archive.org/web/20181130030419/https://www.telegraph.co.uk/finance/newsbysector/pharmaceuticalsandchemicals/7842794/GW-Pharmaceuticals-launches-worlds-first-prescription-cannabis-drug-in-Britain.html |url-status=live }}</ref> Sativex has been approved in 25 countries; clinical trials are underway in the United States to gain FDA approval.<ref name="USATodaySativex">{{cite web |title=3 prescription drugs that come from marijuana |url=https://www.usatoday.com/story/money/personalfinance/2014/03/17/three-drugs-that-come-from-marijuana/6531291/ |website=USA Today |access-date=30 November 2018 |archive-date=20 April 2023 |archive-url=https://web.archive.org/web/20230420163531/https://www.usatoday.com/story/money/personalfinance/2014/03/17/three-drugs-that-come-from-marijuana/6531291/ |url-status=live }}</ref> In 2007, it was approved for treatment of cancer pain.<ref name="ReferenceA" /> 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.<ref name="Schubert">{{cite book | vauthors = Schubert-Zsilavecz M, Wurglics M | title = Neue Arzneimittel | date = 2011–2012 | language = de }}</ref>

[[Dronabinol]] (brand names Marinol and Syndros) is a delta-9-THC containing drug for treating [[HIV/AIDS]]-induced [[anorexia (symptom)|anorexia]] and [[chemotherapy-induced nausea and vomiting]].<ref name="fda">{{cite web |title=FDA and Cannabis: Research and Drug Approval Process |url=https://www.fda.gov/news-events/public-health-focus/fda-and-cannabis-research-and-drug-approval-process |archive-url=https://web.archive.org/web/20191212132738/https://www.fda.gov/news-events/public-health-focus/fda-and-cannabis-research-and-drug-approval-process |url-status=dead |archive-date=12 December 2019 |publisher=US Food and Drug Administration |access-date=23 May 2023 |date=24 February 2023}}</ref>

The [[Cannabidiol|CBD]] drug Epidiolex has been approved by the [[Food and Drug Administration]] for treatment of two rare and severe forms of [[epilepsy]],<ref name="fda18">{{cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm611046.htm|title=FDA approves first drug {{sic|comprised |hide=y|of}} an active ingredient derived from marijuana to treat rare, severe forms of epilepsy|publisher=US Food and Drug Administration|date=25 June 2018|access-date=25 June 2018|archive-date=23 April 2019|archive-url=https://web.archive.org/web/20190423071605/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm611046.htm|url-status=dead}}</ref> [[Dravet syndrome|Dravet]] and [[Lennox-Gastaut syndrome|Lennox-Gastaut]] syndromes.<ref name="CNNDravet">{{cite web|vauthors=Scutti S|url=https://www.cnn.com/2018/06/25/health/fda-approves-first-cannabis-drug-bn/index.html|title=FDA approves first cannabis-based drug|website=CNN|date=25 June 2018|access-date=1 December 2018|archive-date=2 December 2018|archive-url=https://web.archive.org/web/20181202070652/https://www.cnn.com/2018/06/25/health/fda-approves-first-cannabis-drug-bn/index.html|url-status=live}}</ref>

[[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.<ref name=fda/>