Objectives Since 70's, scientific research has analyzed how many acute and chronic issues can affect body systems. In case of depression, chronic pain and overtraining, centrals and peripherals systems act to manage and maintain body adaptations. The aim of this study is to evaluate if the osteopathic treatment can increase the release of Cannabinoid receptor (CB) and promote the linkage with their receptors. Content Documents research is based on PubMed and Google Scholar databases. Keywords used were "osteopathic treatment", "manual therapy", "endocannabinoid", "beta endorphin (BE)", and " CB1" "massage". From 70 articles collected (published in the last 10 years) 52 were excluded as non-relevant to the study aim. Summary The Key points have been the similar results found by different authors during different treatment periods and with different doses. From 22 articles examined, 13 have established positive effects on CB increasing post osteopathic treatment, three articles have indicated the most targeted tissues in which the substances are most expressed, two articles indicate how physical activities produce antalgic effects by increasing CB's values. Outlook As a result of this review, osteopathic manipulation treatment seems to be a valid and effective instrument for the treatment of a series of pathologies such as chronic low back pain, fibromyalgia, spinal cord lesions, myofascial graft point, migraine, GI tract dysfunctions, and depression.