Journal Article

Care and Feeding of the Endocannabinoid System: A Systematic Review of Potential Clinical Interventions that Upregulate the Endocannabinoid System

Di Marzo, Vincenzo, McPartland, John M., Guy, Geoffrey W.

2014

Overview

The \"classic\" endocannabinoid (eCB) system includes the cannabinoid receptors CB1 and CB2, the eCB ligands anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their metabolic enzymes. An emerging literature documents the \"eCB deficiency syndrome\" as an etiology in migraine, fibromyalgia, irritable bowel syndrome, psychological disorders, and other conditions. We performed a systematic review of clinical interventions that enhance the eCB system--ways to upregulate cannabinoid receptors, increase ligand synthesis, or inhibit ligand degradation. We searched PubMed for clinical trials, observational studies, and preclinical research. Data synthesis was qualitative. Exclusion criteria limited the results to 184 in vitro studies, 102 in vivo animal studies, and 36 human studies. Evidence indicates that several classes of pharmaceuticals upregulate the eCB system, including analgesics (acetaminophen, non-steroidal anti-inflammatory drugs, opioids, glucocorticoids), antidepressants, antipsychotics, anxiolytics, and anticonvulsants. Clinical interventions characterized as \"complementary and alternative medicine\" also upregulate the eCB system: massage and manipulation, acupuncture, dietary supplements, and herbal medicines. Lifestyle modification (diet, weight control, exercise, and the use of psychoactive substances--alcohol, tobacco, coffee, cannabis) also modulate the eCB system. Few clinical trials have assessed interventions that upregulate the eCB system. Many preclinical studies point to other potential approaches; human trials are needed to explore these promising interventions.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 2-Arachidonoylglycerol / Acetaminophen / Acupuncture / Alcohol / Alcohols / Alternative medicine / Analgesics / Anandamide / Animals / Anti-inflammatory agents / Anticonvulsants / Antidepressants / Antipsychotic agents / Antipsychotics / Anxiolytics / Biology / Brain research / Cannabinoid CB1 receptors / Cannabinoid CB2 receptors / Cannabis / Clinical trials / Coffee / Diet / Dietary supplements / Drug abuse / Drugs / Endocannabinoid system / Endocannabinoids - metabolism / Enzymes / Ethanol / Etiology / Fibromyalgia / Glucocorticoids / Herbal medicine / Humans / In vivo methods and tests / Inflammation / Intestine / Irritable bowel syndrome / Ligands / Marijuana / Medical research / Medicine / Mental disorders / Metabolism / Migraine / Narcotics / Neurochemistry / Neurosciences / Nonsteroidal anti-inflammatory drugs / Observational studies / Opioids / Pharmaceuticals / Qualitative analysis / Receptors / Receptors, Cannabinoid - metabolism / Rodents / Steroidal anti-inflammatory agents / Synthesis / Systematic review / Tobacco / Up-Regulation - drug effects / Weight control