ceptors. 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 PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19632594 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. Because this review focuses upon clinical interventions affecting the eCB system, we deemed as irrelevant 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. Data Selection, Abstraction, and Synthesis All three authors selected GSK1278863 chemical information 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 Systematic Review of eCB Modulation 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. Many studies utilized in 
vitro measures of receptor density and signal transduction, as differences in means before- and afterinterventions. Briefly: assays for CB1/CB2 receptor density include autoradiography with tritiated ligands, 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 GTPcS binding, or electrophysiological assays of ex vivo brain slices. Electrophysiological studies include depolarization-induced suppression of excitation, depolarization-induced suppression of inhibition, long-term depression of excitatory synaptic transmission, or long-term depression of inhibitory synaptic transmission. Publication bias was addressed by asking investigators to contribute unpublished studies. Clinical interventions with five or more studies are provided with an interpretive summary at the end of the section. Pharmaceutical drugs Non-steroidal anti-inflammatory agents. NSAIDs inhibit two cyclooxygenase enzymes, COX1 and COX2, and thereby block the conversion of arachidonic acid into inflammatory prostaglandins. Ibuprofen, ketorolac, and flurbiprofen also block the hydrolysis of AEA into arachidonic acid and ethanolamine. PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19630872 See Results and Discussion The search algorithm identified 6,353 potentially relevant articles. The majority of these were irrelevant. For example, combining the three MeSH keywords with “alcohol”generated 2450 hits, many of which concerned the relationship between alcohol and cannabis in motor vehicle accidents or suicides. Only 322 articles met the predefined selection criteria for relevance. See Systematic Review of eCB Modulation tration of acetaminophen in rats. A sub-effective dose of AEA in mice
