Jump to content

Cannabidiol

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by Vjiced (talk | contribs) at 16:15, 30 December 2012. The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Cannabidiol
Clinical data
AHFS/Drugs.comInternational Drug Names
ATC code
  • None
Legal status
Legal status
  • Schedule II (Can)
Identifiers
  • 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.215.986 Edit this at Wikidata
Chemical and physical data
FormulaC21H30O2
Molar mass314.4636 g·mol−1
3D model (JSmol)
Melting point66 °C (151 °F)
Boiling point180 °C (356 °F)
(Range: 160°C-180°C) [1]
  • Oc1c(c(O)cc(c1)CCCCC)[C@@H]2\C=C(/CC[C@H]2\C(=C)C)C
  • InChI=1S/C21H30O2/c1-5-6-7-8-16-12-19(22)21(20(23)13-16)18-11-15(4)9-10-17(18)14(2)3/h9,12-13,17-18,22-23H,2,5-8,10-11H2,1,3-4H3/t17-,18+/m0/s1 checkY
  • Key:ZTGXAWYVTLUPDT-ZWKOTPCHSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Cannabidiol (CBD) is a cannabinoid found in cannabis. It is a major constituent of the plant, representing up to 40% in its extracts.[2]

It has displayed sedative effects in animal tests.[3] Some research, however, indicates that CBD can increase alertness.[4] It may decrease the rate of THC clearance from the body, perhaps by interfering with the metabolism of THC in the liver.

Medically, it has been shown to relieve convulsion, inflammation, anxiety, and nausea, as well as inhibit cancer cell growth.[5] Recent studies have shown cannabidiol to be as effective as atypical antipsychotics in treating schizophrenia.[6] Studies have also shown that it may relieve symptoms of dystonia.[7][8]

In November 2007, it was reported that CBD reduces growth of aggressive human breast cancer cells in vitro and reduces their invasiveness.[9]

A 2008 study published in the British Journal of Psychiatry showed significant differences in the Oxford-Liverpool Inventory of Feelings and Experiences scores between three groups: the first consisted of non-cannabis users, the second consisted of users with THC detected, and the third consisted of users with both THC and CBD detected. The THC only group scored significantly higher for unusual experiences than the THC and CBD group, whereas the THC and CBD group had significantly lower introvertive anhedonia scores than the THC only group and non-cannabis user group. This research indicates that CBD acts as an anti-psychotic and may counteract the potential psychotomimetic effects of THC on individuals with latent schizophrenia.[10]


Medicinal use

The bud of a Cannabis sativa flower coated with trichomes, which contain more CBD than any other part of the plant. [citation needed]

Cannabidiol has shown to decrease activity of the limbic system[11] and to decrease social isolation induced by THC.[12] It's also shown that Cannabidiol reduces anxiety in social anxiety disorder. [13] [14] In April 2005, Canadian authorities approved the marketing of Sativex, a mouth spray for multiple sclerosis to alleviate pain. Sativex contains tetrahydrocannabinol together with cannabidiol. It is marketed in Canada by GW Pharmaceuticals.

In 1985 a single case study suggested that CBD may be effective in the management of levodopa-induced dyskinesia in a Parkinson's Disease patient.[15]

Studies have shown that CBD may reduce schizophrenic symptoms in patients, likely due to their apparent ability to stabilize disrupted or disabled NMDA receptor pathways in the brain, which are shared and sometimes contested by norepinephrine and GABA.[6][16] Leweke et al. performed a double blind, 4 week, explorative controlled clinical trial to compare the effects of purified cannabidiol and the atypical antipsychotic amisulpride on improving the symptoms of schizophrenia in 42 patients with acute paranoid schizophrenia. Both treatments were associated with a significant decrease of psychotic symptoms after 2 and 4 weeks as assessed by Brief Psychiatric Rating Scale and Positive and Negative Syndrome Scale. While there was no statistical difference between the two treatment groups, cannabidiol induced significantly fewer side effects (extrapyramidal symptoms, increase in prolactin, weight gain) when compared to amisulpride.[17]

Cannabidiol has also been shown as being effective treating an often drug-induced set of neurological movement disorders known as dystonia.[8] In one study, five out of five participants showed noted improvement in their dystonic symptoms by 20-50%.[7] CBD also appears to protect against 'binge' alcohol induced neurodegeneration.[18][19]

A 2010 study found that strains of cannabis which contained higher concentrations of Cannabidiol did not produce short-term memory impairment vs. strains which contained similar concentrations of THC, but lower concentrations of CBD. The researchers attributed this attenuation of memory effects to CBD's role as a CB1 antagonist.[20]

In November 2012, a Medical Marijuana facility in Israel announced a new strain of the plant which only has Cannabidiol as an active ingredient, and virtually no THC. This new strain gives the benefits of Medical Marijuana with none of the side-effects associated with being "high".[21]

Pharmacology

Cannabidiol has no affinity for CB1 and CB2 receptors but acts as an indirect antagonist of cannabinoid agonists.[5] Recently it was found to be an antagonist at the putative new cannabinoid receptor, GPR55, a GPCR expressed in the caudate nucleus and putamen.[22] Cannabidiol has also been shown to act as a 5-HT1A receptor agonist,[23] an action which is involved in its antidepressant,[24][25] anxiolytic,[25][26] and neuroprotective[27][28] effects. Cannabidiol is also an allosteric modulator at the Mu and Delta opioid receptor sites.[29]

Cannabidiol has also been shown to inhibit cancer cell growth with low potency in non-cancer cells. Although the inhibitory mechanism is not yet fully understood, Ligresti et al. suggest that "cannabidiol exerts its effects on these cells through a combination of mechanisms that include either direct or indirect activation of CB2 and TRPV1 receptors, and induction of oxidative stress, all contributing to induce apoptosis."[30] In November 2007, researchers at the California Pacific Medical Center reported that CBD shows promise for controlling the spread of metastatic breast cancer. In vitro CBD downregulates the activity of the gene ID1 which is responsible for tumor metastasis.[9]

Chemistry

Cannabidiol is insoluble in water but soluble in organic solvents, such as pentane. At room temperature it is a colorless crystalline solid.[31] In strongly basic medium and the presence of air it is oxidized to a quinone.[32] Under acidic conditions it cyclizes to THC.[33] The synthesis of cannabidiol has been accomplished by several research groups.[34][35][36]

Biosynthesis

Cannabis produces CBD-carboxylic acid through the same metabolic pathway as THC, until the last step, where CBDA synthase performs catalysis instead of THCA synthase.[37]

Natural occurrence

Cannabis Indica may have a CBD:THC ratio 4–5 times that of Cannabis Sativa. Cannabis strains with relatively high CBD:THC ratios are less likely to induce anxiety than vice versa. This may be due to CBD's antagonistic effects at the cannabinoid receptors, compared to THC's partial agonist effect. CBD is also a 5-HT1A receptor agonist, which may also contribute to an anxiolytic effect.[38] This likely means the high concentrations of CBD found in Cannabis indica mitigate the anxiogenic effect of THC significantly.[38] The effects of sativa are well known for its cerebral high, hence used daytime as medical cannabis, while indica are well known for its sedative effects and preferred night time as medical cannabis.[38]

Cannabidiol (CBD) is unscheduled in the US. However tetrahydrocannabinols, both naturally and synthetically occurring, are currently classified under Schedule I of the US Controlled Substances Act.[39]

Cannabidiol is a Schedule 2 Drug in Canada.[40]

See also

References

  1. ^ McPartland, JM; Russo, EB (2001). "Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts?" (PDF). Journal of Cannabis Therapeutics. 1 (3/4): 103–132.
  2. ^ Grlić, Ljubiša (1962). "A comparative study on some chemical and biological characteristics of various samples of cannabis resin". Bulletin on Narcotics (3). UNODC: 37–46. {{cite journal}}: Cite has empty unknown parameter: |coauthors= (help)
  3. ^ Pickens JT (1981). "Sedative activity of cannabis in relation to its delta'-trans-tetrahydrocannabinol and cannabidiol content". Br. J. Pharmacol. 72 (4): 649–56. PMC 2071638. PMID 6269680.
  4. ^ Nicholson, AN (2004). "Effect of Delta-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults" (fee required). J Clin Psychopharmacol. 24 (3): 305–13. doi:10.1097/01.jcp.0000125688.05091.8f. ISSN 0271-0749. PMID 15118485. Retrieved 2007-05-03. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  5. ^ a b Mechoulam, R. (21 Aug 2007). "Cannabidiol - recent advances". Chemistry & Biodiversity. 4 (8): 1678–1692. doi:10.1002/cbdv.200790147. PMID 17712814. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  6. ^ a b Zuardi, A.W (2006). "Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug" (PDF). Braz. J. Med. Biol. Res. 39 (4): 421–429. doi:10.1590/S0100-879X2006000400001. PMID 16612464. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  7. ^ a b Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 3793381, please use {{cite journal}} with |pmid=3793381 instead.
  8. ^ a b Snider, Stuart R.; Consroe, Paul (1985). "Beneficial and Adverse Effects of Cannabidiol in a Parkinson Patient with Sinemet-Induced Dystonic Dyskinesia". Neurology (Suppl 1): 201.
  9. ^ a b McAllister SD, Christian RT, Horowitz MP, Garcia A, Desprez PY (2007). "Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells". Mol. Cancer Ther. 6 (11): 2921–7. doi:10.1158/1535-7163.MCT-07-0371. PMID 18025276.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1192/bjp.bp.107.046649, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1192/bjp.bp.107.046649 instead.
  11. ^ José Alexandre de Souza Crippa, Antonio Waldo Zuardi, Griselda E J Garrido, Lauro Wichert-Ana, Ricardo Guarnieri, Lucas Ferrari, Paulo M Azevedo-Marques, Jaime Eduardo Cecílio Hallak, Philip K McGuire and Geraldo Filho Busatto (2003). "Effects of Cannabidiol (CBD) on Regional Cerebral Blood Flow". Neuropsychopharmacology. 29 (2): 417–426. doi:10.1038/sj.npp.1300340. PMID 14583744. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ Daniel Thomas Malone, Dennis Jongejana and David Alan Taylora (2009). "Cannabidiol reverses the reduction in social interaction produced by low dose Δ9-tetrahydrocannabinol in rats". Pharmacology Biochemistry and Behavior. 93 (2): 91–96. doi:10.1016/j.pbb.2009.04.010. PMID 19393686. {{cite journal}}: Unknown parameter |month= ignored (help)
  13. ^ Mateus M Bergamaschi, Regina Helena Costa Queiroz, Marcos Hortes Nisihara Chagas, Danielle Chaves Gomes de Oliveira, Bruno Spinosa De Martinis, Flávio Kapczinski, João Quevedo, Rafael Roesler, Nadja Schröder, Antonio E Nardi, Rocio Martín-Santos, Jaime Eduardo Cecílio (2011). "Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients". Neuropsychopharmacology. 36 (6): 1219–1226. doi:10.1038/npp.2011.6. PMC 3079847. PMID 21307846. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  14. ^ Crippa JA, Derenusson GN, Ferrari TB, Wichert-Ana L, Duran FL, Martin-Santos R, Simões MV, Bhattacharyya S, Fusar-Poli P, Atakan Z, Santos Filho A, Freitas-Ferrari MC, McGuire PK, Zuardi AW, Busatto GF, Hallak JE. (2011). "Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report". J Psychopharmacol. 25 (1): 121–130. doi:10.1177/0269881110379283. PMID 20829306. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  15. ^ Snider, SR (1985). "Beneficial and adverse effects of cannabidiol in a Parkinson patient with sinemet-induced dystonic dyskinesia". Neurology. 35: 201. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  16. ^ http://www.nature.com/npp/journal/v31/n4/abs/1300838a.html
  17. ^ Leweke, FM (2009). "Antipsychotic effects of cannabidiol". European Psychiatry 17th EPA Congress. 24 (1): s207. doi:10.1016/S0924-9338(09)70440-7. {{cite journal}}: |format= requires |url= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  18. ^ http://dx.doi.org/10.1124/jpet.105.085779 Comparison of Cannabidiol, Antioxidants, and Diuretics in Reversing Binge Ethanol-Induced Neurotoxicity
  19. ^ http://www.ncbi.nlm.nih.gov/pubmed/19631736 White matter integrity in adolescents with histories of marijuana use and binge drinking.
  20. ^ Morgan, C. J. (2010). "Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study: naturalistic study [corrected]". British Journal of Psychiatry. 197 (4): 285–90. doi:10.1192/bjp.bp.110.077503. {{cite journal}}: Check |doi= value (help); Unknown parameter |month= ignored (help)
  21. ^ http://edition.cnn.com/video/?hpt=wo_mid#/video/world/2012/11/08/pkg-sidner-israel-medical-marijuana.cnn
  22. ^ Ryberg E, Larsson N, Sjögren S; et al. (2007). "The orphan receptor GPR55 is a novel cannabinoid receptor". British Journal of Pharmacology. 152 (7): 1092–101. doi:10.1038/sj.bjp.0707460. PMC 2095107. PMID 17876302. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  23. ^ Russo EB, Burnett A, Hall B, Parker KK (2005). "Agonistic properties of cannabidiol at 5-HT1a receptors". Neurochemical Research. 30 (8): 1037–43. doi:10.1007/s11064-005-6978-1. PMID 16258853. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  24. ^ Zanelati T, Biojone C, Moreira F, Guimarães F, Joca S (2009). "Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors". British Journal of Pharmacology. 159 (1): 122–8. doi:10.1111/j.1476-5381.2009.00521.x. PMC 2823358. PMID 20002102. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  25. ^ a b Resstel LB, Tavares RF, Lisboa SF, Joca SR, Corrêa FM, Guimarães FS (2009). "5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats". British Journal of Pharmacology. 156 (1): 181–8. doi:10.1111/j.1476-5381.2008.00046.x. PMC 2697769. PMID 19133999. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  26. ^ Campos AC, Guimarães FS (2008). "Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats". Psychopharmacology. 199 (2): 223–30. doi:10.1007/s00213-008-1168-x. PMID 18446323. {{cite journal}}: Unknown parameter |month= ignored (help)
  27. ^ Mishima K, Hayakawa K, Abe K; et al. (2005). "Cannabidiol prevents cerebral infarction via a serotonergic 5-hydroxytryptamine1A receptor-dependent mechanism". Stroke; a Journal of Cerebral Circulation. 36 (5): 1077–82. doi:10.1161/01.STR.0000163083.59201.34. PMID 15845890. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  28. ^ Hayakawa K, Mishima K, Nozako M; et al. (2007). "Repeated treatment with cannabidiol but not Delta9-tetrahydrocannabinol has a neuroprotective effect without the development of tolerance". Neuropharmacology. 52 (4): 1079–87. doi:10.1016/j.neuropharm.2006.11.005. PMID 17320118. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  29. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 16489449, please use {{cite journal}} with |pmid=16489449 instead.
  30. ^ Ligresti A, Moriello AS, Starowicz K; et al. (2006). "Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma". J. Pharmacol. Exp. Ther. 318 (3): 1375–87. doi:10.1124/jpet.106.105247. PMID 16728591. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  31. ^ Jones PG, Falvello L, Kennard O, Sheldrick GM Mechoulam R (1977). "Cannabidiol". Acta Cryst. B33 (10): 3211–3214. doi:10.1107/S0567740877010577.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  32. ^ Mechoulam R, Ben-Zvi Z (1968). "Hashish—XIII On the nature of the beam test". Tetrahedron. 24 (16): 5615–5624. doi:10.1016/0040-4020(68)88159-1. PMID 5732891.
  33. ^ Gaoni Y, Mechoulam R (1966). "Hashish—VII The isomerization of cannabidiol to tetrahydrocannabinols". Tetrahedron. 22 (4): 1481–1488. doi:10.1016/S0040-4020(01)99446-3.
  34. ^ Petrzilka T, Haefliger W, Sikemeier C, Ohloff G, Eschenmoser A (1967). "Synthese und Chiralität des (-)-Cannabidiols". Helv. Chim. Acta. 50 (2): 719–723. doi:10.1002/hlca.19670500235. PMID 5587099.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  35. ^ Gaoni Y, Mechoulam R (1985). "Boron trifluoride etherate on alumuna - a modified Lewis acid reagent. An improved synthesis of cannabidiol". Tetrahedron Letters. 26 (8): 1083–1086. doi:10.1016/S0040-4039(00)98518-6.
  36. ^ Kobayashi Y, Takeuchi A, Wang YG (2006). "Synthesis of cannabidiols via alkenylation of cyclohexenyl monoacetate". Org. Lett. 8 (13): 2699–2702. doi:10.1021/ol060692h. PMID 16774235.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  37. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1093/jxb/erp210, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1093/jxb/erp210 instead.
  38. ^ a b c J. E. Joy, S. J. Watson, Jr., and J. A. Benson, Jr. (1999). Marijuana and Medicine: Assessing The Science Base. Washington, D.C.: National Academy of Sciences Press. ISBN 0-585-05800-8.{{cite book}}: CS1 maint: multiple names: authors list (link) Cite error: The named reference "joy" was defined multiple times with different content (see the help page).
  39. ^ http://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_11.htm#d27
  40. ^ http://laws.justice.gc.ca/en/showdoc/cs/C-38.8//20090606/en?command=search&caller=SI&fragment=schedule%201&search_type=all&day=6&month=6&year=2009&search_domain=cs&showall=L&statuteyear=all&lengthannual=50&length=50&offset=2
  • Erowid Compounds found in Cannabis sativa
  • Project CBD Non-profit educational service dedicated to promoting and publicizing research into the medical utility of cannabidiol.
Retrieved from "http://en.wiki.x.io/w/index.php?title=Cannabidiol&oldid=530467580"