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Repeated treatment with cannabidiol but not Delta9-tetrahydrocannabinol has a neuroprotective effect without the development of tolerance.
Neuropharmacology 2007; 52(4):1079-87N

Abstract

Both Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and cannabidiol are known to have a neuroprotective effect against cerebral ischemia. We examined whether repeated treatment with both drugs led to tolerance of their neuroprotective effects in mice subjected to 4h-middle cerebral artery (MCA) occlusion. The neuroprotective effect of Delta(9)-THC but not cannabidiol was inhibited by SR141716, cannabinoid CB(1) receptor antagonist. Fourteen-day repeated treatment with Delta(9)-THC, but not cannabidiol, led to tolerance of the neuroprotective and hypothermic effects. In addition, repeated treatment with Delta(9)-THC reversed the increase in cerebral blood flow (CBF), while cannabidiol did not reverse that effect. Repeated treatment with Delta(9)-THC caused CB(1) receptor desensitization and down-regulation in MCA occluded mice. On the contrary, cannabidiol did not influence these effects. Moreover, the neuroprotective effect and an increase in CBF induced by repeated treatment with cannabidiol were in part inhibited by WAY100135, serotonin 5-HT(1A) receptor antagonist. Cannabidiol exhibited stronger antioxidative power than Delta(9)-THC in an in vitro study using the 1,1-diphenyl-2-picryhydrazyl (DPPH) radical. Thus, cannabidiol is a potent antioxidant agent without developing tolerance to its neuroprotective effect, acting through a CB(1) receptor-independent mechanism. It is to be hoped that cannabidiol will have a palliative action and open new therapeutic possibilities for treating cerebrovascular disorders.

Authors+Show Affiliations

Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma 8-19-1, Fukuoka City, Fukuoka 814-0180, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17320118

Citation

Hayakawa, Kazuhide, et al. "Repeated Treatment With Cannabidiol but Not Delta9-tetrahydrocannabinol Has a Neuroprotective Effect Without the Development of Tolerance." Neuropharmacology, vol. 52, no. 4, 2007, pp. 1079-87.
Hayakawa K, Mishima K, Nozako M, et al. Repeated treatment with cannabidiol but not Delta9-tetrahydrocannabinol has a neuroprotective effect without the development of tolerance. Neuropharmacology. 2007;52(4):1079-87.
Hayakawa, K., Mishima, K., Nozako, M., Ogata, A., Hazekawa, M., Liu, A. X., ... Fujiwara, M. (2007). Repeated treatment with cannabidiol but not Delta9-tetrahydrocannabinol has a neuroprotective effect without the development of tolerance. Neuropharmacology, 52(4), pp. 1079-87.
Hayakawa K, et al. Repeated Treatment With Cannabidiol but Not Delta9-tetrahydrocannabinol Has a Neuroprotective Effect Without the Development of Tolerance. Neuropharmacology. 2007;52(4):1079-87. PubMed PMID: 17320118.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Repeated treatment with cannabidiol but not Delta9-tetrahydrocannabinol has a neuroprotective effect without the development of tolerance. AU - Hayakawa,Kazuhide, AU - Mishima,Kenichi, AU - Nozako,Masanori, AU - Ogata,Ayumi, AU - Hazekawa,Mai, AU - Liu,An-Xin, AU - Fujioka,Masayuki, AU - Abe,Kohji, AU - Hasebe,Nobuyoshi, AU - Egashira,Nobuaki, AU - Iwasaki,Katsunori, AU - Fujiwara,Michihiro, Y1 - 2007/02/21/ PY - 2006/09/26/received PY - 2006/11/15/revised PY - 2006/11/16/accepted PY - 2007/2/27/pubmed PY - 2007/6/2/medline PY - 2007/2/27/entrez SP - 1079 EP - 87 JF - Neuropharmacology JO - Neuropharmacology VL - 52 IS - 4 N2 - Both Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and cannabidiol are known to have a neuroprotective effect against cerebral ischemia. We examined whether repeated treatment with both drugs led to tolerance of their neuroprotective effects in mice subjected to 4h-middle cerebral artery (MCA) occlusion. The neuroprotective effect of Delta(9)-THC but not cannabidiol was inhibited by SR141716, cannabinoid CB(1) receptor antagonist. Fourteen-day repeated treatment with Delta(9)-THC, but not cannabidiol, led to tolerance of the neuroprotective and hypothermic effects. In addition, repeated treatment with Delta(9)-THC reversed the increase in cerebral blood flow (CBF), while cannabidiol did not reverse that effect. Repeated treatment with Delta(9)-THC caused CB(1) receptor desensitization and down-regulation in MCA occluded mice. On the contrary, cannabidiol did not influence these effects. Moreover, the neuroprotective effect and an increase in CBF induced by repeated treatment with cannabidiol were in part inhibited by WAY100135, serotonin 5-HT(1A) receptor antagonist. Cannabidiol exhibited stronger antioxidative power than Delta(9)-THC in an in vitro study using the 1,1-diphenyl-2-picryhydrazyl (DPPH) radical. Thus, cannabidiol is a potent antioxidant agent without developing tolerance to its neuroprotective effect, acting through a CB(1) receptor-independent mechanism. It is to be hoped that cannabidiol will have a palliative action and open new therapeutic possibilities for treating cerebrovascular disorders. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/17320118/Repeated_treatment_with_cannabidiol_but_not_Delta9_tetrahydrocannabinol_has_a_neuroprotective_effect_without_the_development_of_tolerance_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(06)00392-3 DB - PRIME DP - Unbound Medicine ER -