No abstract

Cannabinoids, endocannabinoids and marijuana activate two well-characterized cannabinoid receptors (CB-Rs), CB1-Rs and CB2-Rs. The expression of CB1-Rs in the brain and periphery has been well studied, but neuronal CB2-Rs have received much less attention than CB1-Rs. Many studies have now identified and characterized functional glial and neuronal CB2-Rs in the central nervous system. However, many features of CB2-R gene structure, regulation and variation remain poorly characterized in comparison with the CB1-R. In this study, we report on the discovery of a novel human CB2 gene promoter transcribing testis (CB2A) isoform with starting exon located ca 45 kb upstream from the previously identified promoter transcribing the spleen isoform (CB2B). The 5 exons of both CB2 isoforms are untranslated 5 UTRs and alternatively spliced to the major protein coding exon of the CB2 gene. CB2A is expressed higher in testis and brain than CB2B that is expressed higher in other peripheral tissues than CB2A. Species comparison found that the CB2 gene of human, rat and mouse genomes deviated in their gene structures and isoform expression patterns. mCB2A expression was increased significantly in the cerebellum of mice treated with the CB-R mixed agonist, WIN55212-2. These results provide much improved information about CB2 gene structure and its human and rodent variants that should be considered in developing CB2-R-based therapeutic agents.

Clozapine-induced obsessive/compulsive symptoms (OCS) have been reported by many authors. This study investigated the incidence of these side effects, together with the relation between these side effects and the plasma concentration (Cps) of clozapine and its metabolites norclozapine and clozapine-N-oxide in schizophrenic patients. One hundred and two schizophrenic patients treated with clozapine were interviewed and screened with questionnaires testing for OCS during a 1-year study period. Cps of clozapine and the metabolites were monitored using reversed-phase high-performance liquid chromatography with ultraviolet detection. Thirty-nine patients (38.2%) presented with OCS, and, of these, 29 patients (28.4%) were classified as clozapine-induced, with an average latent period of 39.8+/-22.5 months. The Cps of clozapine and norclozapine were significantly higher in patients with OCS than in those without (595.1+/-364.9 vs. 433.5+/-252.8 ng/mL, P=0.001 and 266.4+/-144.4 vs. 203.1+/-119.8 ng/mL) OCS. Clozapine-induced OCS were not uncommon side effects. The authors suggest that the emergence of these side effects may be related to higher Cps of clozapine and clinicians should routinely check for and manage these side effects.

These results indicate that our alcohol-dependent individuals are vulnerable to excessive production of free radicals. Notably, the oxidative DNA damage persisted after 1-week detoxification. The AWS severity was correlated with the increase in oxidative stress, particularly the 8-OHdG levels. The impact of sustained abstinence in alcoholic patients needs to be investigated in future studies.