Petyr Baelish
12-08-2005, 10:54 PM
Neuroprotective antioxidants from marijuana.
Hampson AJ, Grimaldi M, Lolic M, Wink D, Rosenthal R, Axelrod J.
Laboratory of Cellular and Molecular Regulation, NIMH, Bethesda, Maryland 20892, USA. aidan@codon.nih.gov
Cannabidiol and other cannabinoids were examined as neuroprotectants in rat cortical neuron cultures exposed to toxic levels of the neurotransmitter, glutamate. The psychotropic cannabinoid receptor agonist delta 9-tetrahydrocannabinol (THC) and cannabidiol, (a non-psychoactive constituent of marijuana), both reduced NMDA, AMPA and kainate receptor mediated neurotoxicities. Neuroprotection was not affected by cannabinoid receptor antagonist, indicating a (cannabinoid) receptor-independent mechanism of action. Glutamate toxicity can be reduced by antioxidants. Using cyclic voltametry and a fenton reaction based system, it was demonstrated that Cannabidiol, THC and other cannabinoids are potent antioxidants. As evidence that cannabinoids can act as an antioxidants in neuronal cultures, cannabidiol was demonstrated to reduce hydroperoxide toxicity in neurons. In a head to head trial of the abilities of various antioxidants to prevent glutamate toxicity, cannabidiol was superior to both alpha-tocopherol and ascorbate in protective capacity. Recent preliminary studies in a rat model of focal cerebral ischemia suggest that cannabidiol may be at least as effective in vivo as seen in these in vitro studies.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10863546&query_hl=10
Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation.
Ramirez BG, Blazquez C, Gomez del Pulgar T, Guzman M, de Ceballos ML.
Neurodegeneration Group, Cajal Institute, Consejo Superior de Investigaciones Cientificas, 28002 Madrid, Spain.
Alzheimer's disease (AD) is characterized by enhanced beta-amyloid peptide (betaA) deposition along with glial activation in senile plaques, selective neuronal loss, and cognitive deficits. Cannabinoids are neuroprotective agents against excitotoxicity in vitro and acute brain damage in vivo. This background prompted us to study the localization, expression, and function of cannabinoid receptors in AD and the possible protective role of cannabinoids after betaA treatment, both in vivo and in vitro. Here, we show that senile plaques in AD patients express cannabinoid receptors CB1 and CB2, together with markers of microglial activation, and that CB1-positive neurons, present in high numbers in control cases, are greatly reduced in areas of microglial activation. In pharmacological experiments, we found that G-protein coupling and CB1 receptor protein expression are markedly decreased in AD brains. Additionally, in AD brains, protein nitration is increased, and, more specifically, CB1 and CB2 proteins show enhanced nitration. Intracerebroventricular administration of the synthetic cannabinoid WIN55,212-2 to rats prevent betaA-induced microglial activation, cognitive impairment, and loss of neuronal markers. Cannabinoids (HU-210, WIN55,212-2, and JWH-133) block betaA-induced activation of cultured microglial cells, as judged by mitochondrial activity, cell morphology, and tumor necrosis factor-alpha release; these effects are independent of the antioxidant action of cannabinoid compounds and are also exerted by a CB2-selective agonist. Moreover, cannabinoids abrogate microglia-mediated neurotoxicity after betaA addition to rat cortical cocultures. Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.
PMID: 15728830 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15728830&query_hl=10
[Cannabis and cannabinoid receptors: from pathophysiology to therapeutic options]
[Article in French]
Derkinderen P, Valjent E, Darcel F, Damier P, Girault JA.
Service de Neurologie et Centre d'investigations cliniques, CHU de Nantes, Hopital Laennec, Nantes. spnepgd@iop.kcl.ac.uk
BACKGROUND: Although cannabis has been used as a medicine for several centuries, the therapeutic properties of cannabis preparations (essentially haschich and marijuana) make them far most popular as a recreational drugs. STATE OF THE ART: Scientific studies on the effects of cannabis were advanced considerably by the identification in 1964 of cannabinoid D9-tetrahydrocannadinol (THC), recognized as the major active constituent of cannabis. Cloning of the centrally located CB1 receptor in 1990 and the identification of the first endogenous ligand of the CB1 receptor, anandamide, in 1992 further advanced our knowledge. PERSPECTIVE AND CONCLUSIONS: Progress has incited further research on the biochemistry and pharmacology of the cannabinoids in numerous diseases of the central nervous system. In the laboratory animal, cannabinoids have demonstrated potential in motion disorders, demyelinizing disease, epilepsy, and as anti-tumor and neuroprotector agents. Several clinical studies are currently in progress, but therapeutic use of cannabinoids in humans couls be hindered by undesirable effects, particularly psychotropic effects. CB1 receptor antagonists also have interesting therapeutic potential.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15247852&query_hl=10
Hampson AJ, Grimaldi M, Lolic M, Wink D, Rosenthal R, Axelrod J.
Laboratory of Cellular and Molecular Regulation, NIMH, Bethesda, Maryland 20892, USA. aidan@codon.nih.gov
Cannabidiol and other cannabinoids were examined as neuroprotectants in rat cortical neuron cultures exposed to toxic levels of the neurotransmitter, glutamate. The psychotropic cannabinoid receptor agonist delta 9-tetrahydrocannabinol (THC) and cannabidiol, (a non-psychoactive constituent of marijuana), both reduced NMDA, AMPA and kainate receptor mediated neurotoxicities. Neuroprotection was not affected by cannabinoid receptor antagonist, indicating a (cannabinoid) receptor-independent mechanism of action. Glutamate toxicity can be reduced by antioxidants. Using cyclic voltametry and a fenton reaction based system, it was demonstrated that Cannabidiol, THC and other cannabinoids are potent antioxidants. As evidence that cannabinoids can act as an antioxidants in neuronal cultures, cannabidiol was demonstrated to reduce hydroperoxide toxicity in neurons. In a head to head trial of the abilities of various antioxidants to prevent glutamate toxicity, cannabidiol was superior to both alpha-tocopherol and ascorbate in protective capacity. Recent preliminary studies in a rat model of focal cerebral ischemia suggest that cannabidiol may be at least as effective in vivo as seen in these in vitro studies.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10863546&query_hl=10
Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation.
Ramirez BG, Blazquez C, Gomez del Pulgar T, Guzman M, de Ceballos ML.
Neurodegeneration Group, Cajal Institute, Consejo Superior de Investigaciones Cientificas, 28002 Madrid, Spain.
Alzheimer's disease (AD) is characterized by enhanced beta-amyloid peptide (betaA) deposition along with glial activation in senile plaques, selective neuronal loss, and cognitive deficits. Cannabinoids are neuroprotective agents against excitotoxicity in vitro and acute brain damage in vivo. This background prompted us to study the localization, expression, and function of cannabinoid receptors in AD and the possible protective role of cannabinoids after betaA treatment, both in vivo and in vitro. Here, we show that senile plaques in AD patients express cannabinoid receptors CB1 and CB2, together with markers of microglial activation, and that CB1-positive neurons, present in high numbers in control cases, are greatly reduced in areas of microglial activation. In pharmacological experiments, we found that G-protein coupling and CB1 receptor protein expression are markedly decreased in AD brains. Additionally, in AD brains, protein nitration is increased, and, more specifically, CB1 and CB2 proteins show enhanced nitration. Intracerebroventricular administration of the synthetic cannabinoid WIN55,212-2 to rats prevent betaA-induced microglial activation, cognitive impairment, and loss of neuronal markers. Cannabinoids (HU-210, WIN55,212-2, and JWH-133) block betaA-induced activation of cultured microglial cells, as judged by mitochondrial activity, cell morphology, and tumor necrosis factor-alpha release; these effects are independent of the antioxidant action of cannabinoid compounds and are also exerted by a CB2-selective agonist. Moreover, cannabinoids abrogate microglia-mediated neurotoxicity after betaA addition to rat cortical cocultures. Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.
PMID: 15728830 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15728830&query_hl=10
[Cannabis and cannabinoid receptors: from pathophysiology to therapeutic options]
[Article in French]
Derkinderen P, Valjent E, Darcel F, Damier P, Girault JA.
Service de Neurologie et Centre d'investigations cliniques, CHU de Nantes, Hopital Laennec, Nantes. spnepgd@iop.kcl.ac.uk
BACKGROUND: Although cannabis has been used as a medicine for several centuries, the therapeutic properties of cannabis preparations (essentially haschich and marijuana) make them far most popular as a recreational drugs. STATE OF THE ART: Scientific studies on the effects of cannabis were advanced considerably by the identification in 1964 of cannabinoid D9-tetrahydrocannadinol (THC), recognized as the major active constituent of cannabis. Cloning of the centrally located CB1 receptor in 1990 and the identification of the first endogenous ligand of the CB1 receptor, anandamide, in 1992 further advanced our knowledge. PERSPECTIVE AND CONCLUSIONS: Progress has incited further research on the biochemistry and pharmacology of the cannabinoids in numerous diseases of the central nervous system. In the laboratory animal, cannabinoids have demonstrated potential in motion disorders, demyelinizing disease, epilepsy, and as anti-tumor and neuroprotector agents. Several clinical studies are currently in progress, but therapeutic use of cannabinoids in humans couls be hindered by undesirable effects, particularly psychotropic effects. CB1 receptor antagonists also have interesting therapeutic potential.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15247852&query_hl=10