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The molecular logic of endocannabinoid signalling
- D. Piomelli
- BiologyNature Reviews Neuroscience
- 1 November 2003
The endocannabinoids are a family of lipid messengers that engage the cell surface receptors that are targeted by Δ9-tetrahydrocannabinol, the active principle in marijuana (Cannabis). They are made…
Role of endogenous cannabinoids in synaptic signaling.
The synthetic pathways of endocannabinoids are discussed, along with the putative mechanisms of their release, uptake, and degradation, and the fine-grain anatomical distribution of the neuronal cannabinoid receptor CB1 is described in most brain areas, emphasizing its general presynaptic localization and role in controlling neurotransmitter release.
Modulation of anxiety through blockade of anandamide hydrolysis
The results indicate that anandamide participates in the modulation of emotional states and point to fatty acid amide hydrolase inhibition as an innovative approach to anti-anxiety therapy.
Brain monoglyceride lipase participating in endocannabinoid inactivation
- T. Dinh, D. Carpenter, D. Piomelli
- BiologyProceedings of the National Academy of Sciences…
- 22 July 2002
The results suggest that hydrolysis by means of MGL is a primary mechanism for 2-AG inactivation in intact neurons, and not on the accumulation of anandamide, another endocannabinoid lipid.
A second endogenous cannabinoid that modulates long-term potentiation
2-AG activates neuronal cannabinoid receptors as a full agonist, and prevents the induction of long-term potentiation at CA3–CA1 synapses, indicating that 2-AG is a second endogenous cannabinoid ligand in the central nervous system.
Identification and Functional Characterization of Brainstem Cannabinoid CB2 Receptors
These functional CB2 receptors in the brainstem were activated by a CB2 receptor agonist, 2-arachidonoylglycerol, and by elevated endogenous levels of endocannabinoids, which also act at CB1 receptors.
Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-α
The results, which show that OEA induces satiety by activating PPAR-α, identify an unexpected role for this nuclear receptor in regulating behaviour, and raise possibilities for the treatment of eating disorders, are identified.
Control of pain initiation by endogenous cannabinoids
It is shown that anandamide attenuates the pain behaviour produced by chemical damage to cutaneous tissue by interacting with CB1-like cannabinoid receptors located outside the CNS, and that locally generated an andamide and PEA may mediate this effect.
Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia
It is suggested that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia.
An endocannabinoid mechanism for stress-induced analgesia
The results indicate that the coordinated release of 2-AG and anandamide in the periaqueductal grey matter might mediate opioid-independent stress-induced analgesia, and identify monoacylglycerol lipase as a previously unrecognized therapeutic target.