Kanabinoid

Kanabinoidi su klasa hemijskih jedinjenja koja obuhvata fitokanabinoide (kiseonik-sadržavajuće C₂₁ aromatične ugljovodonike prisutne u biljci kanabis), i hemijska jedinjenja koja oponašaju dejstvo fitokanabinoida, ili imaju sličnu strukturu (npr. endokanabinoidi, koji su nađeni u nervnom i imunskom sistemu životinja, koja aktiviraju kanabinoidne receptore).^[1] Najpoznatiji kanabinoid je ∆⁹-tetrahidrokanabinol (∆⁹-THC — primarno psihoaktivno jedinjenje kanabisa).^[2]^[3]

Sintetički kanabinoidi obuhvataju mnoštvo distinktnih hemijskih klasa: klasični kanabinoidi koji su strukturno srodni sa THC-om, ne-klasični kanabinoidi kao što su aminoalkilindoli, 1,5-diarilpirazoli, kvinolini i arilsulfonamidi, kao i eikosanoidi srodni sa endokanabinoidima.^[2]

Kanabinoidni receptori

Pre 1980-ih se pretpostavljalo da kanabinoidi proizvode njihove fiziološke i bihevioralne efekte kroz nespecifične interakcije sa ćelijskim membranama, umesto interakcija sa specifičnim za membranu vezanim receptorima. Otkriće prvih kanabinoidnih receptora tokom 1980-ih je doprinelo rezoluciji te debate. Ti receptori su široko zastupljeni kod životinja, i nađeni su kod sisara, ptica, riba, i reptila. Trenutno su poznata dva tipa kanabinoidnih receptora, nazvanih CB₁ i CB₂.^[1] Smatra se da postoje još nekoliko kanabinoidnih receptora.^[4]

Fitokanabinoidi

Tip	Skeleton	Ciklizacija
Kanabigerolni tip CBG
Kanabihromenski tip CBC
Kanabidiolni tip CBD
Tetrahidrokanabinolni- i kanabinolni tip THC, CBN
Kanabielsoinski tip CBE
iso- Tetrahidrokanabinolni- tip iso-THC
Kanabiciklolni tip CBL
Kanabicitranski tip CBT
Glavne klase prirodnih kanabinoida

Fitokanabinoidi, prirodni kanabinoidi, biljni kanabinoidi, i klasični kanabinoidi, su klasa kanabinoida za koju se poznato da se prirodno javlja u znatnim količinama u biljci kanabis. Oni su koncentrovani u viskoznom rezinu koji nastaje u glandularnim strukturama poznatim kao trihomi. Pored kanabinoida, rezin je bogat u terpenima, koji su u znatnoj meri odgovorni za miris biljke kanabisa.

Fitokanabinoidi su skoro nerastvorni u vodi, ali su rastvorni u lipidima, alkoholima, i drugim nepolarnim organskim rastvaračima. Međutim, poput fenola, oni formiraju u većoj meri u vodi rastvorne fenolatne soli u jako alkalinim uslovima.

Svi prirodni kanabinoidi su izvedeni dekarboksilacijom njihovih respektivnih 2-karboksilnih kiselina (2-COOH) (ovaj proces je katalizovan toplotom, svetlošću, ili alkalnom sredinom).

Tipovi

Više od 85 kanabinoida je izolovano iz biljke konoplje^[5] Glavne klase prirodnih kanabinoida su prikazana u tabeli sa desne strane. Sve klase su izvedene iz kanabigerolnog tipa jedinjenja i razlikuju se uglavnom u načinu ciklizacije tog prekursora.

Tetrahidrokanabinol (THC), kanabidiol (CBD) i kanabinol (CBN) su najzastupljeniji prirodni kanabinoidi, i oni su najbolje istraženi. Drugi uobičajeni kanabinoidi su:

Tetrahidrokanabinol

Tetrahidrokanabinol (THC) je primarna psihoaktivna komponenta biljke. Ona olakšava umereni bol (analgetik) i poseduje neurozaštitna svojstva. THC ima aproksimativno jednak afinitet za CB₁ i CB₂ receptore.^[6]

Delta-9-tetrahidrokanabinol (Δ⁹-THC, THC) i delta-8-tetrahidrokanabinol (Δ⁸-THC), oponašaju dejstvo anandamida, neurotransmitera koji se prirodno proizvodi u telu. THC molekuli proizvode stanje za upotrebu kanabisa vezivanjem za CB₁ kanabinoidne receptore mozga.

Kanabidiol

Kanabidiol (CBD) nije veoma psihoaktivan sam po sebi, i smatralo se da nema uticaja na THC psihoaktivnost.^[7] Međutim, nedavne studije su pokazale da su pušači kanabisa sa visokim CBD/THC odnosom manje skloni da dožive šizofreniji slične simptome.^[8] Ti nalazi su podržani psihološkim testovima, u kojima participanti doživljavaju manje intenzivne psihozi slične efekte kad se THC intravenozno administrira sa CBD-om (mereno putem PANSS-ovog testa).^[9] Kanabidiol nema afiniteta za CB₁ i CB₂ receptore, ali deluje kao indirektni antagonist kanabinoidnih agonista.^[10] Nedavno je utvrđeno da on antagonist mogućeg novoog kanabinoidnog receptora, GPR55, GPCR koji je izražen u lat. nucleus caudatus i putamenu.^[11] Za kanabidiol je takođe pokazano da deluje kao agonist 5-HT_1A receptora,^[12] na koji način deluje kao antidepresant,^[13]^[14] anksiolitik,^[14]^[15] i neurozaštitnik.^[16]^[17]

Kanabinol

Kanabinol (CBN) je primarni proizvod THC degradacije, i obično ga ima malo u svežim biljkama. CBN sadržaj se povećava sa THC degradacijom tokom skladištenja, i sa izlaganjem svetlosti i vazduhu. On je veoma blago psihoaktivan. Njegov afinitet za CB₂ receptor veći nego za CB₁ receptor.^[18]

Endokanabinoidi

Anandamid, jedan od endogenih liganda CB₁ i CB₂ receptora

Endokanabinoidi su supstance proizvedene u telu koje aktiviraju kanabinoidne receptore. Nakon otkrića prvog kanabinoidnog receptora 1988, naučnici su započeli potragu za endogenim ligandima tog receptora.

Tipovi endokanabinoidnih liganda

Arahidonoil etanolamid (Anandamid ili AEA)
2-arahidonoil glicerol (2-AG)
2-arahidonil gliceril etar (noladin etar)
N-arahidonoil-dopamin (NADA)
Virodhamin (OAE)

Prirodni kanabinoidi

Kanabigerolni tip (CBG)
Kanabigerol (E)-CBG-C₅	Kanabigerol monometil etar (E)-CBGM-C₅ A	Kanabinerolna kiselina A (Z)-CBGA-C₅ A	Kanabigerovarin (E)-CBGV-C₃
Kanabigerolna kiselina A (E)-CBGA-C₅ A	Kanabigerolna kiselina A monomethyl ether (E)-CBGAM-C₅ A	Kanabigerovarinska kiselina A (E)-CBGVA-C₃ A
Kanabihromenski tip (CBC)
(±)-Kanabihromen CBC-C₅	(±)-Kanabihromenska kiselina A CBCA-C₅ A	(±)-Kanabivarihromen, (±)-Kanabihromevarin CBCV-C₃	(±)-Kanabihromevarinska kiselina A CBCVA-C₃ A
Kanabidiolni tip (CBD)
(−)-Kanabidiol CBD-C₅	Kanabidiol monometil etar CBDM-C₅	Kanabidiol-C₄ CBD-C₄	(−)-Kanabidivarin CBDV-C₃	Kanabidiorkol CBD-C₁
Kanabidiolna kiselina CBDA-C₅	Kanabidivarinska kiselina CBDVA-C₃
Kanabinodiolni tip (CBND)
Kanabinodiol CBND-C₅	Kanabinodivarin CBND-C₃
Tetrahidrokanabinolni tip (THC)
Δ⁹-Tetrahidrokanabinol Δ⁹-THC-C₅	Δ⁹-Tetrahidrokanabinol-C₄ Δ⁹-THC-C₄	Δ⁹-Tetrahidrokanabivarin Δ⁹-THCV-C₃	Δ⁹-Tetrahidrokanabiorkol Δ⁹-THCO-C₁
Δ⁹-Tetrahidro- kanabinolna kiselina A Δ⁹-THCA-C₅ A	Δ⁹-Tetrahidro- kanabinolna kiselina B Δ⁹-THCA-C₅ B	Δ⁹-Tetrahidro- kanabinolna kiselina C₄ A i/ili B Δ⁹-THCA-C₄ A and/or B	Δ⁹-Tetrahidro- kanabivarinska kiselina A Δ⁹-THCVA-C₃ A	Δ⁹-Tetrahidro- kanabiorkolna kiselina A i/ili B Δ⁹-THCOA-C₁ A i/ili B
(−)-Δ⁸-trans-(6aR,10aR)- Δ⁸-Tetrahidrokanabinol Δ⁸-THC-C₅	(−)-Δ⁸-trans-(6aR,10aR)- Tetrahidrokanabinolna kiselina A Δ⁸-THCA-C₅ A	(−)-(6aS,10aR)-Δ⁹- Tetrahidrokanabinol *(−)-cis-Δ⁹-THC-C₅*
Kanabinolni tip (CBN)
Kanabinol CBN-C₅	Kanabinol-C₄ CBN-C₄	Kanabivarin CBN-C₃	Kanabinol-C₂ CBN-C₂	Kanabiorkol CBN-C₁
Kanabinolna kiselina A CBNA-C₅ A	Kanabinol metil etar CBNM-C₅
Kanabitriolni tip (CBT)
(−)-(9R,10R)-trans- Kanabitriol *(−)-trans-CBT-C₅*	( )-(9S,10S)-Kanabitriol *( )-trans-CBT-C₅*	(±)-(9R,10S/9S,10R)- Kanabitriol *(±)-cis-CBT-C₅*	(−)-(9R,10R)-trans- 10-O-Etil-kanabitriol *(−)-trans-CBT-OEt-C₅*	(±)-(9R,10R/9S,10S)- Kanabitriol-C₃ *(±)-trans-CBT-C₃*
8,9-Dihydroxy-Δ^6a(10a)- tetrahidrokanabinol 8,9-Di-OH-CBT-C₅	Kanabidiolna kiselina A kanabitriolni estar CBDA-C₅ 9-OH-CBT-C₅ estar	(−)-(6aR,9S,10S,10aR)- 9,10-Dihidroksi- heksahidrokanabinol, Kanabiripsol Kanabiripsol-C₅	(−)-6a,7,10a-Trihidroksi- Δ⁹-tetrahidrokanabinol (−)-Kanabitetrol	10-Okso-Δ^6a(10a)- tetrahidrokanabinol OTHC
Kanabielsoinski tip (CBE)
(5aS,6S,9R,9aR)- Kanabielsoin CBE-C₅	(5aS,6S,9R,9aR)- C₃-Kanabielsoin CBE-C₃	(5aS,6S,9R,9aR)- Kanabielsoinska kiselina A CBEA-C₅ A	(5aS,6S,9R,9aR)- Kanabielsoinska kiselina B CBEA-C₅ B	(5aS,6S,9R,9aR)- C₃-Kanabielsoinska kiselina B CBEA-C₃ B
Kanabiglendol-C₃ OH-izo-HHCV-C₃	Dehidrokanabifuran DCBF-C₅	Kanabifuran CBF-C₅
Izokanabinoidi
(−)-Δ⁷-trans-(1R,3R,6R)- Isotetrahydrocannabinol	(±)-Δ⁷-1,2-cis- (1R,3R,6S/1S,3S,6R)- Isotetrahydro- cannabivarin	(−)-Δ⁷-trans-(1R,3R,6R)- Isotetrahydrocannabivarin
Kanabiciklolni tip (CBL)
(±)-(1aS,3aR,8bR,8cR)- Kanabiciklol CBL-C₅	(±)-(1aS,3aR,8bR,8cR)- Kanabiciklolna kiselina A CBLA-C₅ A	(±)-(1aS,3aR,8bR,8cR)- Kanabiciklovarin CBLV-C₃
Kanabicitranski tip (CBT)
Kanabicitran CBT-C₅
Kanabihromanonski tip (CBCN)
Kanabihromanon CBCN-C₅	Kanabihromanon-C3 CBCN-C₃	Kanabikoumaronon CBCON-C₅

Reference

↑ ^1,0 ^1,1 Pacher P, Batkai S, Kunos G (2006). „The endocannabinoid system as an emerging target of pharmacotherapy.”. Pharmacol Rev. 58(3): 389-462. DOI:10.1124/pr.58.3.2. PMC 2241751. PMID 16968947.
↑ ^2,0 ^2,1 Lambert DM, Fowler CJ (2005). „The endocannabinoid system: drug targets, lead compounds, and potential therapeutic applications”. J. Med. Chem. 48 (16): 5059–87. DOI:10.1021/jm058183t. PMID 16078824.
↑ Roger Pertwee, ur. (2005). Cannabinoids. Springer-Verlag. str. 2. ISBN 3-540-22565-X.
↑ Begg M, Pacher P, Bátkai S, Osei-Hyiaman D, Offertáler L, Mo FM, Liu J, Kunos G (2005). „Evidence for novel cannabinoid receptors”. Pharmacol. Ther. 106 (2): 133–45. DOI:10.1016/j.pharmthera.2004.11.005. PMID 15866316.
↑ El-Alfy, Abir T. et. al. "Antidepressant-like effect of [Delta]9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L." Pharmacology Biochemistry and Behavior. 2010 Jun;95(4). ISSN 0091-3057
↑ Huffman JW (2000). „The search for selective ligands for the CB₂ receptor”. Curr. Pharm. Des. 6 (13): 1323–37. DOI:10.2174/1381612003399347. PMID 10903395.
↑ „Behavioural Pharmacology - Abstract: Volume 16(5-6) September 2005 p 487-496 Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids.”. Pristupljeno 24. 6. 2007.
↑ Morgan CJ, Curran HV (April 2008). „Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis”. The British journal of psychiatry : the journal of mental science 192 (4): 306–7. DOI:10.1192/bjp.bp.107.046649. PMID 18378995.
↑ „Should I Smoke Dope?”. Pristupljeno 24. 5. 2008.
↑ Mechoulam, R.; M. Peters, Murillo-Rodriguez (21 Aug 2007). „Cannabidiol - recent advances”. Chemistry & Biodiversity 4 (8): 1678–1692. DOI:10.1002/cbdv.200790147. PMID 17712814. ^{[mrtav link]}
↑ 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.
↑ Russo EB, Burnett A, Hall B, Parker KK (August 2005). „Agonistic properties of cannabidiol at 5-HT1a receptors”. Neurochemical Research 30 (8): 1037–43. DOI:10.1007/s11064-005-6978-1. PMID 16258853.
↑ Zanelati T, Biojone C, Moreira F, Guimarães F, Joca S (December 2009). „Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT receptors”. British Journal of Pharmacology 159 (1): 122–8. DOI:10.1111/j.1476-5381.2009.00521.x. PMC 2823358. PMID 20002102.
↑ ^14,0 ^14,1 Resstel LB, Tavares RF, Lisboa SF, Joca SR, Corrêa FM, Guimarães FS (January 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.
↑ Campos AC, Guimarães FS (August 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.
↑ Mishima K, Hayakawa K, Abe K, et al. (May 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. ^{[mrtav link]}
↑ Hayakawa K, Mishima K, Nozako M, et al. (March 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.
↑ Mahadevan A, Siegel C, Martin BR, Abood ME, Beletskaya I, Razdan RK (October 2000). „Novel cannabinol probes for CB₁ and CB₂ cannabinoid receptors”. Journal of medicinal chemistry 43 (20): 3778–85. DOI:10.1021/jm0001572. PMID 11020293.

Literatura

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Elsohly MA, Slade D (2005). „Chemical constituents of marijuana: the complex mixture of natural cannabinoids”. Life Sci. 78 (5): 539–48. DOI:10.1016/j.lfs.2005.09.011. PMID 16199061.
Hanuš L, Gopher A, Almog S, Mechoulam R (1993). „Two new unsaturated fatty acid ethanolamides in brain that bind to the cannabinoid receptor”. J. Med. Chem. 36 (20): 3032–4. DOI:10.1021/jm00072a026. PMID 8411021.
Hanuš L (1987). „Biogenesis of cannabinoid substances in the plant”. Acta Universitatis Palackianae Olomucensis Facultatis Medicae 116: 47–53. PMID 2962461.
Hanuš L., Krejčí Z. (1975). „Isolation of two new cannabinoid acids from Cannabis sativa L. of Czechoslovak origin”. Acta Univ. Olomuc., Fac. Med 74: 161–166.
Hanuš L., Krejčí Z., Hruban L. (1975). „Isolation of cannabidiolic acid from Turkish variety of cannabis cultivated for fibre”. Acta Univ. Olomuc., Fac. Med 74: 167–172.
Attila Köfalvi, ur. (2010). Cannabinoids and the Brain. Springer. DOI:10.1007/978-0-387-74349-3. ISBN 1-4419-4493-1.
Mechoulam R, Ben-Shabat S, Hanuš L, et al. (1995). „Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors”. Biochem. Pharmacol. 50 (1): 83–90. DOI:10.1016/0006-2952(95)00109-D. PMID 7605349.
Racz I, Nadal X, Alferink J, Baños JE, Rehnelt J, Martín M, Pintado B, Gutierrez-Adan A, Sanguino E, Bellora N, Manzanares J, Zimmer A, Maldonado R (November 2008). „Interferon-gamma is a critical modulator of CB(2) cannabinoid receptor signaling during neuropathic pain”. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience 28 (46): 12136–45. DOI:10.1523/JNEUROSCI.3402-08.2008. PMID 19005078. Pristupljeno 2011-04-05.
Racz I, Nadal X, Alferink J, Baños JE, Rehnelt J, Martín M, Pintado B, Gutierrez-Adan A, Sanguino E, Manzanares J, Zimmer A, Maldonado R (November 2008). „Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain”. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience 28 (46): 12125–35. DOI:10.1523/JNEUROSCI.3400-08.2008. PMID 19005077. Pristupljeno 2011-04-05.
Turner C. E., Mole M. L., Hanuš L., ElSohly H. N. (1981). „Constituents of Cannabis sativa L. XIX. Isolation and structure elucidation of cannabiglendol. A novel cannabinoid from an Indian variant”. J. Nat. Prod 44 (1): 27–33. DOI:10.1021/np50013a005.
Roger Pertwee, ur. (2005). Cannabinoids. Springer-Verlag. str. 2. ISBN 3-540-22565-X.

Vanjske veze

Medicinski kanabinoidi Arhivirano 2016-03-05 na Wayback Machine-u
Farmakologija kanabinoidnih receptora Arhivirano 2011-09-10 na Wayback Machine-u
Međunarodno društvo za kanabinoidna istraživanja

[pmid16968947-1] 1,0 ^1,1 Pacher P, Batkai S, Kunos G (2006). „The endocannabinoid system as an emerging target of pharmacotherapy.”. Pharmacol Rev. 58(3): 389-462. DOI:10.1124/pr.58.3.2. PMC 2241751. PMID 16968947.

[lambert-2] 2,0 ^2,1 Lambert DM, Fowler CJ (2005). „The endocannabinoid system: drug targets, lead compounds, and potential therapeutic applications”. J. Med. Chem. 48 (16): 5059–87. DOI:10.1021/jm058183t. PMID 16078824.

[3] Roger Pertwee, ur. (2005). Cannabinoids. Springer-Verlag. str. 2. ISBN 3-540-22565-X.

[pmid15866316-4] Begg M, Pacher P, Bátkai S, Osei-Hyiaman D, Offertáler L, Mo FM, Liu J, Kunos G (2005). „Evidence for novel cannabinoid receptors”. Pharmacol. Ther. 106 (2): 133–45. DOI:10.1016/j.pharmthera.2004.11.005. PMID 15866316.

[5] El-Alfy, Abir T. et. al. "Antidepressant-like effect of [Delta]9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L." Pharmacology Biochemistry and Behavior. 2010 Jun;95(4). ISSN 0091-3057

[6] Huffman JW (2000). „The search for selective ligands for the CB₂ receptor”. Curr. Pharm. Des. 6 (13): 1323–37. DOI:10.2174/1381612003399347. PMID 10903395.

[behaviouralpharm-7] „Behavioural Pharmacology - Abstract: Volume 16(5-6) September 2005 p 487-496 Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids.”. Pristupljeno 24. 6. 2007.

[pmid18378995-8] Morgan CJ, Curran HV (April 2008). „Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis”. The British journal of psychiatry : the journal of mental science 192 (4): 306–7. DOI:10.1192/bjp.bp.107.046649. PMID 18378995.

[televisionexperiment-9] „Should I Smoke Dope?”. Pristupljeno 24. 5. 2008.

[recentadvances-10] Mechoulam, R.; M. Peters, Murillo-Rodriguez (21 Aug 2007). „Cannabidiol - recent advances”. Chemistry & Biodiversity 4 (8): 1678–1692. DOI:10.1002/cbdv.200790147. PMID 17712814. ^{[mrtav link]}

[11] 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.

[pmid16258853-12] Russo EB, Burnett A, Hall B, Parker KK (August 2005). „Agonistic properties of cannabidiol at 5-HT1a receptors”. Neurochemical Research 30 (8): 1037–43. DOI:10.1007/s11064-005-6978-1. PMID 16258853.

[pmid20002102-13] Zanelati T, Biojone C, Moreira F, Guimarães F, Joca S (December 2009). „Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT receptors”. British Journal of Pharmacology 159 (1): 122–8. DOI:10.1111/j.1476-5381.2009.00521.x. PMC 2823358. PMID 20002102.

[pmid19133999-14] 14,0 ^14,1 Resstel LB, Tavares RF, Lisboa SF, Joca SR, Corrêa FM, Guimarães FS (January 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.

[pmid18446323-15] Campos AC, Guimarães FS (August 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.

[pmid15845890-16] Mishima K, Hayakawa K, Abe K, et al. (May 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. ^{[mrtav link]}

[pmid17320118-17] Hayakawa K, Mishima K, Nozako M, et al. (March 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.

[pmid11020293-18] Mahadevan A, Siegel C, Martin BR, Abood ME, Beletskaya I, Razdan RK (October 2000). „Novel cannabinol probes for CB₁ and CB₂ cannabinoid receptors”. Journal of medicinal chemistry 43 (20): 3778–85. DOI:10.1021/jm0001572. PMID 11020293.

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