PMC:3951193 / 7535-10785 JSONTXT

{"project":"2_test","denotations":[{"id":"24622769-19621070-95790172","span":{"begin":172,"end":174},"obj":"19621070"}],"text":"Methods\n\nData Sources and Search Parameters\nThis review followed the guidelines proposed by PRISMA, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses [24], see Checklist S1. PubMed (www.ncbi.nlm.nih.gov/pubmed/) was searched through March 2013 using three MeSH keywords: endocannabinoids, cannabinoids, cannabinoid receptors. Each keyword was entered in a boolean combination with each of the intervention groups listed in the previous paragraph. Titles and abstracts of identified articles in all languages were screened for inclusion and exclusion criteria. We included randomized clinical trials, observational studies, and preclinical research on model organisms and in vitro studies. We excluded redundant articles that used identical methods and reported parallel results, or review articles that presented duplicate information.\nBecause this review focuses upon clinical interventions affecting the eCB system, we deemed as irrelevant (and excluded) articles that described the reverse scenario, such as eCB ligands modulating opioid receptors, THC enhancing tobacco or alcohol abuse, etc. Retrieved articles were scanned for supporting citations, and antecedent sources were retrieved and screened for inclusion and exclusion criteria. In addition, we checked reference lists of relevant narrative reviews.\n\nData Selection, Abstraction, and Synthesis\nAll three authors selected studies for inclusion and exclusion; the first author abstracted all data, the second and third authors arbitrated uncertainties and disagreements. We undertook a qualitative synthesis across studies because there was substantial heterogeneity with respect to research methodologies amongst the identified articles—ranging from randomized clinical trials, observational studies, and preclinical research on model organisms and in vitro studies. The substantial heterogeneity amongst these methodologies precluded a single metric of quality assessment.\nMany studies utilized in vitro measures of receptor density and signal transduction, as differences in means before- and after-interventions. Briefly: assays for CB1/CB2 receptor density include autoradiography with tritiated ligands (usually [3H]CP55,940 or [3H]SR141716), Western blot or immunostaining with antibodies to CB1/CB2 proteins, and Northern blot with radio-labeled or fluorescent riboprobes for CB1/CB2 mRNA. Signal transduction studies measure cannabinoid-stimulated inhibition of adenylyl cyclase, cannabinoid-stimulated [35S]GTPγS binding, or electrophysiological assays of ex vivo brain slices. Electrophysiological studies include depolarization-induced suppression of excitation (DSE, via glutamatergic synapses), depolarization-induced suppression of inhibition (DSI, via GABAergic synapses), long-term depression of excitatory synaptic transmission (LTDE, via glutamatergic synapses), or long-term depression of inhibitory synaptic transmission (LTDI, via GABAergic synapsis).\nPublication bias was addressed by asking investigators to contribute unpublished studies. Clinical interventions (intervention groups) with five or more studies are provided with an interpretive summary at the end of the section (e.g., the sections on NSAIDs, glucocorticoids, opiates, etc.)."}