Diabetic neuropathy is a frequent complication of diabetes mellitus with a tremendous impact on patients' quality of life, and it remains poorly treated. Cannabinoids relieve the signs of diabetic neuropathy in different experimental models, including streptozotocin- (STZ-) induced type 1 diabetic rodents, and they may also relieve neuropathic signs in type 2 diabetic animals. This study compar...

Clinical use of antineoplastic drugs is associated with the development of numerous adverse effects that many patients find intolerable, including peripheral neuropathy. Cannabinoids have relieved neuropathic pain in different animal models. But their therapeutic activities could be affected by their psychoactive properties. The aim of this work was to determine the effect of cannabinoids in ci...

A paper by Dr. G. Marsicano’s group [1] in this issue of Molecular Metabolism is clarifying and further elaborating on some of their previous results on the action of cannabinoid type 1 receptor (CB1) in neuronal mitochondria [2]. This new article was written, at least in part, in response to our finding that anti-CB1 serum used in this as well as in other studies also recognizes mitochondrial ...

The CB1 subtype of the cannabinoid receptor is present on neurons in the brain and mediates the perceptual effects of Delta9-tetrahydrocannabinol and other cannabinoids. We found that cat cerebral arterial smooth muscle cells (VSMC) contain the protein for the CB1 receptor and express a cDNA that has >98% amino acid homology to the CB1 cDNA expressed in rat and human neurons. Activation of the ...

Cannabinoids exert pleiotropic actions in the CNS, including the inhibition of inflammatory responses and the enhancement of neuronal survival after injury. Although cannabinoid receptors are distributed widely in brain, their presence has not been investigated previously in oligodendrocytes. This study examined the expression of cannabinoid type 1 (CB1) receptors in rat oligodendrocytes in viv...

The compound N-piperidinyl-[8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6-tetrahydrobenzo [6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide] (NESS 0327) was synthesized and evaluated for binding affinity toward cannabinoid CB1 and CB2 receptor. NESS 0327 exhibited a stronger selectivity for CB1 receptor compared with N-piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamid...

Cannabinoids have been shown to have anticonvulsant properties, but no studies have evaluated the effects of cannabinoids in the hippocampal neuronal culture models of acquired epilepsy (AE) and status epilepticus (SE). This study investigated the anticonvulsant properties of the cannabinoid receptor agonist R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolol[1,2,3 de]-1,4-benzoxazinyl]-...

We investigated the mechanisms by which activation of group I metabotropic glutamate receptors (mGluRs) and CB1 cannabinoid receptors (CB1Rs) leads to inhibition of synaptic currents at the calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB) of the rat auditory brainstem. In approximately 50% of the MNTB neurons tested, activation of group I mGluRs by the specific agonist (...

The memory-disruptive effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and the synthetic cannabinoid WIN 55,212-2 (WIN-2) were assessed in rats exposed to varying doses of each drug (Delta(9)-THC, 0.5-2.0 mg/kg; WIN-2, 0.25-0.75 mg/kg) during performance of a delayed nonmatch to sample (DNMS) task. Cannabinoids affected performance in a dose x delay-dependent manner, with WIN-2 showing a...