Homeostasis. That word is synesthetic for me. The sound of a system functioning in complete balance rings sweetly in my ears. Our bodies strive to achieve this equilibrium and, in fact, have numerous systems that function together in perfect harmony to maintain this constancy. One of those systems is the endocannabinoid system. And, yes, it pretty much means what you think it means, “the inside cannabis” system.
The endocannabinoid system was discovered in the mid-1990s by Israeli researcher Dr. Ralph Mechoulam who also identified THC as the main active ingredient in cannabis in the early 1960s  . This discovery followed earlier research in the late 80’s that identified receptor sites in the mammalian brain that respond pharmacologically to compounds in cannabis resin. So basically, your brain and your body is designed to work cohesively with the compounds found in cannabis. Lucky us.
The endocannabinoid system (ECS) effects all aspects of homeostasis including the endocrine system, the immune system, and the nervous system. Our bodies make endogenous cannabinoids that interact with the cannabinoid receptors. Three of the most heavily researched endocannabinoids are anandamide (AEA), 2-arachidonoylglycerol (2AG), and arachidonyl glyceryl ether (noladin ether). The two most heavily researched receptors are the CB1 receptors (which are primarily located on nerve cells in the brain, spinal cord, but they are also found in some peripheral organs and tissues such as the spleen, white blood cells, endocrine gland and parts of the reproductive, gastrointestinal and urinary tracts.) and the CB2 receptors (which are mainly found on white blood cells, in the tonsils and in the spleen.) These cannabinoids are produced on the cell membrane of the post synaptic cell and travel in retrograde across the synapse to interact with the receptor on the presynaptic nerve terminal. It helps to think of this as a “lock and key” mechanism. New research is also showing that non-CB receptor targets may exist for these receptor molecules such as transient receptor potential channels (TRPV1 and TRPM8), the peroxisome proliferator activated receptors (PPAR alpha and gamma), G protein-coupled orphan receptors (GRP55), certain ion channels (e.g. calcium channels), transmitter-gated ion channels (e.g. glycine receptors) and finally established non-cannabinoid G protein-coupled receptors (e.g. acetylcholine muscarinic receptors). These non-CB receptor targets implicate the endocannabinoids system’s role in the regulation of metabolism, cell differentiation, and inflammation.
The endocannabinoid system is so important to the proper functioning of the human body, that it is believed that many disorders and functional conditions could be due to an endocannabinoid deficiency.  These deficits are associated with a reduced ability to adapt to chronic stress resulting in autoimmune disease or an inflammatory disorder. An efficient ECS is vital to the very basics of life, beginning with reproduction. Blastocyst implantation into the endometrium requires suitable levels of anandamide. In other words, you need anandamide to begin life. Endocannabinoids are found in breast milk and it is believed that the transference of these cannabinoids from mother to baby is the reason why breastfeeding boosts the infant’s immune system and prevents colic. The ECS also regulates the activity of the immune system by suppressing the production of TH1 cytokines and increasing the production of TH2 cytokines. It also induces apoptosis in malignant cells of immune origin leading new approaches to treatment of certain cancers. Dr. Prakash Nagarkatti, the Vice President of Research at the University of South Carolina, believes that the endocannabinoid system’s regulation of the immune system is the reason why administration of Tetrahydrocannabinol is successful in the treatment of graft-versus-host disease (GVHD) in organ transplant recipients. The endocannabinoid system also plays a role in the regulation of connective tissues. Stimulation of the CB2 receptors leads to decreased osteoclast activity and increased osteoblast activity thus increasing bone formation. Cannabinoids prevent cartilage destruction and decrease connective tissue inflammation. The sympathetic and parasympathetic nervous systems are also effected by the endocannabinoid system. It dampens sympathetically mediated pain and, when activated by exogenous cannabinoids, it causes antinociceptive effects in acute pain, inflammatory pain, and neuropathic pain. In almost every system in the body, there is a direct impact by the functioning of the endocannabinoid system.
Exogenous cannabinoids effect the ECS in different ways unique to the individual compound found in the cannabis plant. Two of the most commonly researched phytocannabinoids are THC (Tetrahydrocannabinol) and CBD (Cannabidiol). THC mimics the activity of anadamide and 2-AG by acting as a partial agonist at the CB1 and CB2 receptor sites. While CBD shows a low affinity for these receptors, it does activiate 5-HT1A and TRPV-2 vanilloid receptors which is why it is effective at treating pain. CBD also inhibits uptake of dopamine, GABBA and AEA. Synthetic cannabinoids can also activate the endocannabinoid system; however, only THC is currently being synthesized resulting in the absence of the entourage effect when using whole plant therapies. In most cases, it is best to go real or go home.
Cannabis is still a Schedule One drug and is illegal on a federal level, however 26 states plus the District of Columbia have enacted legislation that provides for medical cannabis programs. Cannabis has been studied over the last few decades more so than most leading FDA-approved pharmaceutical drugs. More and more scientists, researchers, and physicians are calling for the rescheduling or descheduling of cannabis. The scientific revelations of the endocannabinoid system are the driving catalyst behind much of the reduction of stigma associated with cannabis use. Way to go, ENDO!
 The Discovery of the Endocannabinoid System, By Martin A. Lee
 The Emerging Role of the Endocannabinoid System in Endocrine Regulation and Energy Balance - See more at: http://press.endocrine.org/doi/full/10.1210/er.2005-0009#sthash.OwFGw0L0.dpuf
 Endocannabinoids and immune regulation, Rupal Pandey, Khalida Mousawy, Mitzi Nagarkatti, and Prakash Nagarkatti
 The role of the endocannabinoid system in the regulation of endocrine function and in the control of energy balance in humans, Komorowski J, Stepień H. https://www.ncbi.nlm.nih.gov/pubmed/17369778
 Cannabinoid Receptors By Dr Ananya Mandal, MD
 Cannabinoid Receptors By Dr. Ananya Mandal, MD
 Clinical Endocannabinoid Deficiency (CECD): Can this Concept Explain Therapeutic Benefits of Cannabis in Migraine, Fibromyalgia, Irritable Bowel Syndrome and other Treatment-Resistant Conditions? By Ethan B. Russo
 The endocannabinoid system during development: emphasis on perinatal events and delayed effects.
Fride E1, Gobshtis N, Dahan H, Weller A, Giuffrida A, Ben-Shabat S.
 The endocannabinoid system and cancer: therapeutic implication Josée Guindon and Andrea G Hohmann
 Targeting Cannabinoid Receptors as a Novel Approach in the Treatment of Graft-versus-Host Disease: Evidence from an Experimental Murine Model
Rupal Pandey, Venkatesh L. Hegde, Mitzi Nagarkatti, and Prakash S. Nagarkatti
 Cannabinoid Receptors as Target for Treatment of Osteoporosis: A Tale of Two Therapies Aymen I Idris
 Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes J Manzanares, MD Julian, and A Carrascosa
 Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes Luciano De Petrocellis, Alessia Ligresti, Aniello Schiano Moriello, Marco Allarà, Tiziana Bisogno, Stefania Petrosino, Colin G Stott, and Vincenzo Di Marzo