Int. J. Pharm. Sci. Rev. Res., 49(2), March - April 2018; Article No. 20, Pages: 97-106 ISSN 0976 – 044X Review Article The Endocannabioids System and their Implications in Various Disorders Heena Khan, Rahul Sharma, Amarjot Kaur, Thakur Gurjeet Singh* Chitkara College of Pharmacy, Chandigarh-Patiala National Highway, Rajpura– 140401, Patiala, Punjab, India. *Corresponding author’s E-mail: [email protected] Received: 08-03-2018; Revised: 02-04-2018; Accepted: 13-04-2018. ABSTRACT With the increased use of cannabis, research on cannabis has become extremely important. Approximately 500 compounds have been isolated from Cannabis sativa with around 105 being cannabinoids. Of those 105 compounds, Δ9-tetrahydrocannabinol has been determined as the primary constituent, which is also responsible for the psychoactivity associated with Cannabis in the human. The endogenous cannabinoid system (ECS) has been described as “an ancient lipid signaling network, which in the mammals modulates neuronal functions, inflammatory processes, neurodegeneration, post traumic stress disorder, rheumatoid arthritis, AIDS and cancer. Cannabinoid receptors belong to the superfamily of G protein-coupled receptors. Receptors for cannabinoids are highly expressed in the hippocampus, which plays a key role in certain forms of memory and substance dependence. Improvements in the current therapy of cannabis can make it a safe and effective medicine. On the contrary to uses, the plant has some serious risks associated with it if consumed on a chronic basis like psychosis, schizophrenia, respiratory disorders, loss of libido, dependence etc. Therefore, the aim of this review is to study the role of cannabis in various disorders and the risks associated with it. Keywords: Cannabis, role of cannabis, cannabinoid signaling, neurodegeneration ,substance dependence, inflammation INTRODUCTION tetrahydrocannabinol. Tetrahydrocannabivarin has therapeutic potential both as an anti-inflammatory agent annabis is obtained from Cannabis sativa, Cannabis and for the relief of inflammatory, or indeed, neuropathic indica, Cannabis ruderalis belonging to the family pain. 2–arachidonyl glycerol is an agonist of CB1 and CB2 Cannabaceae. Cannabinoids are mainly collected C receptors. It plays important role in the regulation of the from the appendages of sepal and specialized leaves of a circulatory system via direct and/or indirect, through their female plant. There are 483 different chemical metabolites, effects on blood vessels and/or heart. 2- components out of which 66 are known. It comprises of arachidonyl glyceryl ether decreases intestinal mobility, nitrogenous compounds, amino acids, proteins, used in pain, hypothermia and causes sedation. glycoproteins, amino acids, enzymes, aldehydes, alcohols, Virodhamine is a CB2 agonist, a partial agonist of CB1 amino acids, hydrocarbons, ketones, flavonoids, receptors. Virodhamine lowers body temperature in mice, cannabinoid phenolic steroids, vitamins1. There are a total demonstrating cannabinoid activity in vivo. Dronabinol is of 13 phytocannabinoids discovered till date, namely used in the loss of appetite in HIV patients, nausea tetrahydrocannabinol, cannabidiol (CBD), cannabigerol, vomiting in cancer patients. Nabilone is an antiemetic2. cannabichromene, tetrahydrocannaivarin, Delta-9-THC and THC nearly possess the same effects. cannabigervarin, cannabigerol, virodhamine, 2– Medical marijuana named dronabinol and Nabilone has arachidonylglycerol, 2-arachidonyl glyceryl ether, been approved by FDA to be used as antiemetic in cancer Dronabinol, nabilone, delta-9-THC and out of these main therapy. Hashish oil, hashish, weed are the methods to components aretetrahydrocannabinol (THC), delta-9-THC. consume marijuana. On the contrary to uses, the plant All the constituents contribute to its medicinal value. has some serious risks associated with it if consumed on a Cannabichromene affects memory, increases neuronal chronic basis like psychosis, schizophrenia, respiratory growth and is used in Alzheimer's disease, autoimmune disorders, loss of libido, dependence etc3. diseases, pruritus, schizophrenia, depression, inflammation, fungal infections, viral diseases. It improves THC –(tetrahydrocannabinol) positive and negative symptoms of psychiatric illness. THCis a mind-altering ingredient which is found in the Cannabidiol is used in seizures, convulsions, anxiety. Cannabis plant. The main psychoactive component, which Cannabidiol is the major compound that is used in is responsible for the psychotogenic effect of cannabis, is epilepsy in convulsion. CBG is an alpha-2 adregeneric Δ9-tetrahydrocannabinol (Δ9-THC). It is an analgesic agonist, serotonin antagonist (5HT1A). Cannabigerol have which is used in psychiatric illness, delta-9 THC mimics the neuroprotective properties and isused for the treatment action of endocannabinoids like anandamide. It exerts its of neurodegenerative diseases such as Huntington’s psychotogenic role by modulating the dopamine disease and multiple sclerosis. CBG has potential for neurotransmission, which is directly involved in the alleviating pain especially neuropathic pain. THCV development of psychotic symptoms4. THC’s chemical improves the psychoactive properties of structure is same as brain chemical anandamide. International Journal of Pharmaceutical Sciences Review and Research . International Journal of Pharmaceutical Sciences Review and Research Available online at www.globalresearchonline.net 97 . Available online at www.globalresearchonline.net © Copyright protected. Unauthorised republication, reproduction, distribution, dissemination and copying of this document in whole or in part is strictly prohibited. Int. J. Pharm. Sci. Rev. Res., 49(2), March - April 2018; Article No. 20, Pages: 97-106 ISSN 0976 – 044X Similarity in its structure allows the body to recognize THC change within the receptor, which triggers the and alter the normal brain communication5. THC is one of subsequent signaling cascade11. The effects of cannabis the most important compounds found in the resin mainly depend on cannabis receptors (CB1 and CB2) secreted by the glands of the marijuana plant. According which are the endocannabinoid system located in the to Wu et al in 2011 the brain releases dopamine when brain and the periphery, regulate neuromodulation THC stimulates the astrocytes in the brain, creating through neuromodulatory lipids12. CB1 and CB2 receptors euphoria. It also interferes with how information is get bound with two endocannabinoids that act as ligands processed in the hippocampus, which is part of the brain namely arachidonylethanolamide and 2- responsible for forming new memories. Information arachidonylglycerol and out of the two receptors; ligands process also gets interrupted in the hippocampus, which have a greater expression towards CB1 receptors. The is part of the brain responsible for forming new CB1 receptors are present in the synaptic bouton(end memories. Various NIDA reports showed that THC foot),when endoligands bind to it , release of classical exposure before birth, after birth and during adolescence neurotransmitters is inhibited. Amide hydrolase shown to have problems in rats with specific learning and inactivates the endocannabinoids and this enzyme is memory tasks later in life6. targeted towards the cell body and dendritic sites excluding axon. Arachidonylethanolamide is synthesized Cannabidiol by postsynaptic neuron cells and messages in an inferior Till now CBD is the only non–∆9-THC phytocannabinoid to direction to attune the release of neurotransmitters from have been assessed in preclinical and clinical studies for presynaptic terminals. This endocannabinoid signaling anticonvulsant effects. In mice, CBD blocked MES-induced control memory pain and smooth muscle contractility13. seizures in one study but had no effect on The retrograde signaling of synaptic transmission is pentylenetetrazol (PTZ)–induced or MES-induced seizures modulated by the calcium release or calcium signaling. in another7.More recently, CBD has been shown to have The endocannabinoids like arachidonylethanolamide are antiepileptiform and anticonvulsant effects in invitro and released by the increased levels of calcium at the invivo models. In two different models of spontaneous postsynaptic compartment or by the activation of G- epileptiform local field potentials (LFPs), CBD decreased protein coupled receptors that causes the retrograde epileptiform LFP burst amplitude and duration. CBD also signaling from postsynaptic to presynaptic transmission exerted anticonvulsant effects against PTZ-induced acute and causes the Modulation of neurotransmitters. The generalized seizures, pilocarpine-induced temporal lobe GPCR pathway requires phospholipase Cβ and the calcium convulsions, and penicillin-induced partial seizures in pathway is independent of phospholipase Cβ14. As we Wistar-Kyoto rats8. The mechanisms by which CBD and know cannabis is involved in retrograde signaling from CBDV exert their antiseizure effects are not fully known, postsynaptic to presynaptic terminals thus affecting the although several of the potential targets of cannabidiols release of neurotransmitters. Parira et al. in 2017 shows described earlier may be involved Via modulation of that chronic exposure to ethanol decreases the intracellular calcium through interactions with targets expression of CB1 receptors by an increase in activity such as TRP channels, G-coupled protein receptor protein caused by endocannabinoids like