ming behavior, which is a stress-reduction behavior in rodents, increased in response to SR141716A administration. Mind and body medicine: acupuncture. Acupuncture reduced stress-related behavior and normalized HPA-induced corticosterone PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19632476 release. Electroacupunture reduced thermal hyperalgesia and Debio1347 chemical information mechanical allodynia induced by an injection of complete Freund’s adjuvant into rat paws. EA increased AEA levels in skin tissue. The antinociceptive effects of EA were attenuated by the CB2 antagonist AM630, but not by the CB1 antagonist AM251. Moreover, EA upregulated the expression of CB2 receptors in skin tissues. It appears likely that CB2 activation in the skin stimulates the release of b-endorphin, which then acts on peripheral m-opioid receptors to inhibit nociception. However, CB1 may play a role in the central effects of EA: rats treated with EA showed reduced GABA levels in the ventrolateral periaqueductal gray, an effect reversed by CB1 blockade with AM251. Enhanced activation of epsilon protein kinase C in rat brain by EA was reversed by CB1 blockade with AM251 and not by CB2 blockade with AM630. Mind and body medicine: body-based practices. Massage and osteopathic manipulation of asymptomatic participants increased serum AEA 168% over pretreatment levels; mean OEA levels decreased 27%, and no changes occurred in 2-AG. Participants receiving sham manipulation showed no changes. Osteopathic manipulation of participants with low back pain increased serum PEA 1.6-fold over pretreatment levels, with no change in AEA. Participants receiving sham manipulation showed no changes. Lifestyle modifications Diet and 
weight change. Dozens of animal studies and human cohort studies have shown that diets rich in fats and sugars alter levels of AEA, 2-AG, their metabolic enzymes, and CB1. The reverse causality is also true–many studies show that CB1 agonists stimulate the consumption of fat and sugar. The rewarding properties of palatable foods are attenuated by CB1 blockade and in CB12/2 knockouts. Stimulation of feeding behavior by CB1 agonists occurs across the phylogenetic scale, from humans to Hydra, although there is no molecular evidence for CB1 orthologs in invertebrates other than the boneless chordates Ciona intestinalis and Branchiostoma floridae. Reviews on this topic are available, which we do not intend to duplicate here. Upregulation of the eCB system in obese humans seems to be driven by excessive production of eCBs in several peripheral tissues such as visceral adipose tissue, liver, pancreas, and skeletal PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19632868 muscle. Differences arise between central adipocytes versus peripheral adipocytes, with additional variations due to gender, age, and genetic polymorphisms in metabolic enzymes. Visceral adiposity particularly correlates with elevated levels of 2-AG in blood plasma. Increases in circulating eCBs likely reflect spillover from adipose tissues and liver parenchyma, where CB1 activation promotes de novo lipogenesis and reduces insulin sensitivity, respectively. In mice with diet-induced obesity, CB1 mRNA and protein levels increased in the hippocampus, compared to lean controls. Furthermore, hippocampal slices from obese mice showed increased CB1 functionality, with no sign of CB1 desensitization. We find it surprising that sustained elevations of eCB ligands do not result in CB1 downregulation. This may be due to the fact that such elevations are not as dramatic as those caused, for example, by chronic MAGL inhibition. The lack of
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