Tags

Type your tag names separated by a space and hit enter

Peripheral, but not central effects of cannabidiol derivatives: mediation by CB(1) and unidentified receptors.
Neuropharmacology. 2005 Jun; 48(8):1117-29.N

Abstract

Delta-9 tetrahydrocannabinol (Delta(9)-THC) and (-)-cannabidiol ((-)-CBD) are major constituents of the Cannabis sativa plant with different pharmacological profiles: (Delta(9)-THC activates cannabinoid CB(1) and CB(2) receptors and induces psychoactive and peripheral effects. (-)-CBD possesses no, or very weak affinity for these receptors. We tested a series of (+)- and (-)-CBD derivatives for central and peripheral effects in mice. None of the (-)-CBD derivatives were centrally active, yet most inhibited intestinal motility. Of the five (+)-CBD derivatives, all with CB(1) receptor affinity, only (+)-7-OH-CBD-DMH (DMH=1,1-dimethylheptyl), acted centrally, while all five arrested defecation. The effects of (+)-CBD-DMH and (+)-7-OH-CBD-DMH were inhibited by the CB(1) receptor antagonist SR141716. The CB(2) receptor antagonist SR144528, and the vanilloid TRPV1 receptor antagonist capsazepine, had no influence. Further, the (-)-CBD derivatives (-)-7-COOH-CBD and (-)-7-COOH-CBD-DMH, displayed antiinflammatory activity. We suggest that (+)-CBD analogues have mixed agonist/antagonist activity in the brain. Second, (-)-CBD analogues which are devoid of cannabinoid receptor affinity but which inhibit intestinal motility, suggest the existence of a non-CB(1), non-CB(2) receptor. Therefore, such analogues should be further developed as antidiarrheal and/or antiinflammatory drugs. We propose to study the therapeutic potential of (-)- and (+)-CBD derivatives for complex conditions such as inflammatory bowel disease and cystic fibrosis.

Authors+Show Affiliations

Department of Behavioral Sciences, College of Judea and Samaria, Ariel 44837, Israel; Department of Molecular Biology, College of Judea and Samaria, Ariel 44837, Israel. fride@research.yosh.ac.ilNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15910887

Citation

Fride, Ester, et al. "Peripheral, but Not Central Effects of Cannabidiol Derivatives: Mediation By CB(1) and Unidentified Receptors." Neuropharmacology, vol. 48, no. 8, 2005, pp. 1117-29.
Fride E, Ponde D, Breuer A, et al. Peripheral, but not central effects of cannabidiol derivatives: mediation by CB(1) and unidentified receptors. Neuropharmacology. 2005;48(8):1117-29.
Fride, E., Ponde, D., Breuer, A., & Hanus, L. (2005). Peripheral, but not central effects of cannabidiol derivatives: mediation by CB(1) and unidentified receptors. Neuropharmacology, 48(8), 1117-29.
Fride E, et al. Peripheral, but Not Central Effects of Cannabidiol Derivatives: Mediation By CB(1) and Unidentified Receptors. Neuropharmacology. 2005;48(8):1117-29. PubMed PMID: 15910887.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Peripheral, but not central effects of cannabidiol derivatives: mediation by CB(1) and unidentified receptors. AU - Fride,Ester, AU - Ponde,Datta, AU - Breuer,Aviva, AU - Hanus,Lumir, Y1 - 2005/04/26/ PY - 2004/09/07/received PY - 2005/01/17/revised PY - 2005/01/26/accepted PY - 2005/5/25/pubmed PY - 2009/7/18/medline PY - 2005/5/25/entrez SP - 1117 EP - 29 JF - Neuropharmacology JO - Neuropharmacology VL - 48 IS - 8 N2 - Delta-9 tetrahydrocannabinol (Delta(9)-THC) and (-)-cannabidiol ((-)-CBD) are major constituents of the Cannabis sativa plant with different pharmacological profiles: (Delta(9)-THC activates cannabinoid CB(1) and CB(2) receptors and induces psychoactive and peripheral effects. (-)-CBD possesses no, or very weak affinity for these receptors. We tested a series of (+)- and (-)-CBD derivatives for central and peripheral effects in mice. None of the (-)-CBD derivatives were centrally active, yet most inhibited intestinal motility. Of the five (+)-CBD derivatives, all with CB(1) receptor affinity, only (+)-7-OH-CBD-DMH (DMH=1,1-dimethylheptyl), acted centrally, while all five arrested defecation. The effects of (+)-CBD-DMH and (+)-7-OH-CBD-DMH were inhibited by the CB(1) receptor antagonist SR141716. The CB(2) receptor antagonist SR144528, and the vanilloid TRPV1 receptor antagonist capsazepine, had no influence. Further, the (-)-CBD derivatives (-)-7-COOH-CBD and (-)-7-COOH-CBD-DMH, displayed antiinflammatory activity. We suggest that (+)-CBD analogues have mixed agonist/antagonist activity in the brain. Second, (-)-CBD analogues which are devoid of cannabinoid receptor affinity but which inhibit intestinal motility, suggest the existence of a non-CB(1), non-CB(2) receptor. Therefore, such analogues should be further developed as antidiarrheal and/or antiinflammatory drugs. We propose to study the therapeutic potential of (-)- and (+)-CBD derivatives for complex conditions such as inflammatory bowel disease and cystic fibrosis. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/15910887/Peripheral_but_not_central_effects_of_cannabidiol_derivatives:_mediation_by_CB_1__and_unidentified_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(05)00063-8 DB - PRIME DP - Unbound Medicine ER -