Editing Cannabinoid (section)

=== Well known cannabinoids ===
{{also|Conversion of CBD to THC}}

The best studied cannabinoids include [[tetrahydrocannabinol]] (THC), [[cannabidiol]] (CBD) and [[cannabinol]] (CBN).

==== Tetrahydrocannabinol ====
{{Main|Tetrahydrocannabinol}}
Tetrahydrocannabinol (THC) is the primary psychoactive component of the Cannabis plant. ''Delta''-9-[[tetrahydrocannabinol]] (Δ<sup>9</sup>-THC, THC) and [[delta-8-tetrahydrocannabinol]] (Δ<sup>8</sup>-THC), through intracellular CB<sub>1</sub> activation, induce [[anandamide]] and [[2-arachidonoylglycerol]] synthesis produced naturally in the body and brain{{citation needed|date=February 2019}}{{dubious|date=July 2019}}. These cannabinoids produce the effects associated with [[Cannabis (drug)|cannabis]] by binding to the CB<sub>1</sub> cannabinoid receptors in the brain.<ref>{{cite report |date = July 2020 |title = Cannabis (Marijuana) Research Report |url = https://nida.nih.gov/publications/research-reports/marijuana/how-does-marijuana-produce-its-effects |access-date = 2023-05-28 |publisher = [[National Institute on Drug Abuse]] |chapter = How does marijuana produce its effects?|language=en|archive-date=2023-01-05|archive-url=https://web.archive.org/web/20230105025954/https://nida.nih.gov/publications/research-reports/marijuana/how-does-marijuana-produce-its-effects|url-status=live}}</ref>

==== Cannabidiol ====
{{Main|Cannabidiol}}
Cannabidiol (CBD) is mildly [[psychotropic]]. Evidence shows that the compound counteracts cognitive impairment associated with the use of cannabis.<ref name=2015CBDantipsychReview /> Cannabidiol has little affinity for [[Cannabinoid receptor#CB1|CB<sub>1</sub>]] and [[Cannabinoid receptor#CB2|CB<sub>2</sub>]] receptors but acts as an indirect antagonist of cannabinoid agonists.<ref name="recentadvances">{{cite journal | vauthors = Mechoulam R, Peters M, Murillo-Rodriguez E, Hanus LO | title = Cannabidiol--recent advances | journal = Chemistry & Biodiversity | volume = 4 | issue = 8 | pages = 1678–1692 | date = August 2007 | pmid = 17712814 | doi = 10.1002/cbdv.200790147 | s2cid = 3689072 }}</ref> It was found to be an antagonist at the putative new cannabinoid receptor, [[GPR55]], a [[GPCR]] expressed in the [[caudate nucleus]] and [[putamen]].<ref>{{cite journal | vauthors = Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ | display-authors = 6 | title = The orphan receptor GPR55 is a novel cannabinoid receptor | journal = British Journal of Pharmacology | volume = 152 | issue = 7 | pages = 1092–1101 | date = December 2007 | pmid = 17876302 | pmc = 2095107 | doi = 10.1038/sj.bjp.0707460 }}</ref> Cannabidiol has also been shown to act as a [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]] agonist.<ref name="pmid16258853">{{cite journal | vauthors = Russo EB, Burnett A, Hall B, Parker KK | title = Agonistic properties of cannabidiol at 5-HT1a receptors | journal = Neurochemical Research | volume = 30 | issue = 8 | pages = 1037–1043 | date = August 2005 | pmid = 16258853 | doi = 10.1007/s11064-005-6978-1 | s2cid = 207222631 }}</ref> 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.<ref>{{cite journal | vauthors = Campos AC, Moreira FA, Gomes FV, Del Bel EA, Guimarães FS | title = Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 367 | issue = 1607 | pages = 3364–3378 | date = December 2012 | pmid = 23108553 | pmc = 3481531 | doi = 10.1098/rstb.2011.0389 }}</ref>

CBD shares a [[wikt:Precursor|precursor]] with THC and is the main cannabinoid in CBD-dominant ''Cannabis'' strains. CBD has been shown to play a role in preventing [[cannabis and memory|the short-term memory loss associated with THC]].<ref name=NatureCBDMemory>{{Cite journal| vauthors = Frood A |title=Key ingredient staves off marijuana memory loss |journal=Nature |doi=10.1038/news.2010.508|year=2010}}</ref>

There is tentative evidence that CBD has an anti-psychotic effect, but research in this area is limited.<ref>{{cite journal | vauthors = Leweke FM, Mueller JK, Lange B, Rohleder C | title = Therapeutic Potential of Cannabinoids in Psychosis | journal = Biological Psychiatry | volume = 79 | issue = 7 | pages = 604–612 | date = April 2016 | pmid = 26852073 | doi = 10.1016/j.biopsych.2015.11.018 | s2cid = 24160677 }}</ref><ref name="2015CBDantipsychReview">{{cite journal | vauthors = Iseger TA, Bossong MG | title = A systematic review of the antipsychotic properties of cannabidiol in humans | journal = Schizophrenia Research | volume = 162 | issue = 1–3 | pages = 153–161 | date = March 2015 | pmid = 25667194 | doi = 10.1016/j.schres.2015.01.033 | s2cid = 3745655 }}<!--|access-date=9 October 2015--></ref>

==== Cannabinol ====
{{Main|Cannabinol}}
Cannabinol (CBN) is a mildly [[Psychoactive drug|psychoactive]] cannabinoid that acts as a low affinity [[partial agonist]] at both CB1 and CB2 receptors.'''<ref name="Rhee_1997">{{cite journal |display-authors=6 |vauthors=Rhee MH, Vogel Z, Barg J, Bayewitch M, Levy R, Hanus L, Breuer A, Mechoulam R |date=September 1997 |title=Cannabinol derivatives: binding to cannabinoid receptors and inhibition of adenylylcyclase |journal=Journal of Medicinal Chemistry |volume=40 |issue=20 |pages=3228–3233 |doi=10.1021/jm970126f |pmid=9379442}}</ref>'''<ref name=":02">{{Cite journal |last=Sampson |first=Peter B. |date=2021-01-22 |title=Phytocannabinoid Pharmacology: Medicinal Properties of Cannabis sativa Constituents Aside from the "Big Two" |url=https://pubmed.ncbi.nlm.nih.gov/33356248 |journal=Journal of Natural Products |volume=84 |issue=1 |pages=142–160 |doi=10.1021/acs.jnatprod.0c00965 |issn=1520-6025 |pmid=33356248 |s2cid=229694293 |access-date=2022-12-07 |archive-date=2022-11-19 |archive-url=https://web.archive.org/web/20221119033717/https://pubmed.ncbi.nlm.nih.gov/33356248/ |url-status=live }}</ref>'''<ref name="NCI_C84510">{{Cite web |title=Cannabinol (Code C84510) |url=https://ncithesaurus.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C84510 |work=NCI Thesaurus |publisher=National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services |access-date=2022-12-07 |archive-date=2022-11-19 |archive-url=https://web.archive.org/web/20221119033719/https://ncithesaurus.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C84510 |url-status=live }}</ref>''' 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 was the first cannabis compound to be isolated from [[cannabis]] extract in the late 1800s. Its structure and chemical synthesis were achieved by 1940'''<ref name=":3">{{cite journal |vauthors=Pertwee RG |date=January 2006 |title=Cannabinoid pharmacology: the first 66 years |journal=British Journal of Pharmacology |volume=147 |issue=Suppl 1 |pages=S163–S171 |doi=10.1038/sj.bjp.0706406 |pmc=1760722 |pmid=16402100 |quote=Cannabinol (CBN; Figure 1), much of which is thought to be formed from THC during the storage of harvested cannabis, was the first of the plant cannabinoids (phytocannabinoids) to be isolated, from a red oil extract of cannabis, at the end of the 19th century. Its structure was elucidated in the early 1930s by R.S. Cahn, and its chemical synthesis first achieved in 1940 in the laboratories of R. Adams in the U.S.A. and Lord Todd in the U.K.}}</ref>''', followed by some of the first pre-clinical research studies to determine the effects of individual cannabis-derived compounds [[in vivo]].<ref name=":4">{{Cite journal |last=Pertwee |first=Roger G |date=2006 |title=Cannabinoid pharmacology: the first 66 years: Cannabinoid pharmacology |journal=British Journal of Pharmacology |language=en |volume=147 |issue=S1 |pages=S163–S171 |doi=10.1038/sj.bjp.0706406 |pmc=1760722 |pmid=16402100}}</ref> Although CBN shares the same [[mechanism of action]] as other more well-known [[phytocannabinoids]] (e.g., delta-9 [[tetrahydrocannabinol]] or D9THC), it has a lower [[Affinity (pharmacology)|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.<ref name=":5">{{Cite journal |last=Corroon |first=Jamie |date=2021-08-31 |title=Cannabinol and Sleep: Separating Fact from Fiction |journal=Cannabis and Cannabinoid Research |volume=6 |issue=5 |language=en |pages=366–371 |doi=10.1089/can.2021.0006 |issn=2578-5125 |pmc=8612407 |pmid=34468204}}</ref><ref name=":4" /> 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 is a lack of scientific evidence to support these claims, warranting skepticism on the part of consumers.<ref name=":5" />