Cannabinoids

Abstract

Since the discovery of an endogenous cannabinoid system, research into the pharmacology and therapeutic potential of cannabinoids has steadily increased. Two subtypes of G-protein coupled cannabinoid receptors, CB(1) and CB(1), have been cloned and several putative endogenous ligands (endocannabinoids) have been detected during the past 15 years. The main endocannabinoids are arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol (2-AG), derivatives of arachidonic acid, that are produced "on demand" by cleavage of membrane lipid precursors. Besides phytocannabinoids of the cannabis plant, modulators of the cannabinoid system comprise synthetic agonists and antagonists at the CB receptors and inhibitors of endocannabinoid degradation. Cannabinoid receptors are distributed in the central nervous system and many peripheral tissues, including immune system, reproductive and gastrointestinal tracts, sympathetic ganglia, endocrine glands, arteries, lung and heart. There is evidence for some non-receptor dependent mechanisms of cannabinoids and for endocannabinoid effects mediated by vanilloid receptors. Properties of CB receptor agonists that are of therapeutic interest include analgesia, muscle relaxation, immunosuppression, anti-inflammation, antiallergic effects, improvement of mood, stimulation of appetite, antiemesis, lowering of intraocular pressure, bronchodilation, neuroprotection and antineoplastic effects. The current main focus of clinical research is their efficacy in chronic pain and neurological disorders. CB receptor antagonists are under investigation for medical use in obesity and nicotine addiction. Additional potential was proposed for the treatment of alcohol and heroine dependency, schizophrenia, conditions with lowered blood pressure, Parkinson's disease and memory impairment in Alzheimer's disease.

Terpenóides com atividade sobre o Sistema Nervoso Central (SNC)

“…Os receptores CB1 e CB2 junto com os ligantes canabinóides endógenos (anandamida, 2-AG, noladin éter, virodamina e NADA) constituem o sistema endocanabinóide. Os endocanabinóides são derivados do ácido araquidônico, o que os diferencia estruturalmente dos fitocanabinóides (Grotenhermen, 2005). Leweke et al (2004) relataram que os receptores canabinóides e seus ligantes endógenos estão alterados em pacientes esquizofrênicos.…”

Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis

“…Cannabidiol (CBD), by contrast, is a cannabinoid with few if any psychoactive effects (Zhornitsky and Potvin, 2012), and a varied and complex pharmacology. CBD has low affinity for CB 1 and CB 2 receptors (Pertwee et al, 2010), binds to TRPV 1,2 , GPR55, and 5HT 1a receptors and inhibits anandamide hydrolysis via FAAH inhibition (Mechoulam et al, 2002;Grotenhermen, 2005;Ryberg et al, 2007). Hashish may contain equal parts CBD and THC (ElSohly et al, 2003;Hardwick and King, 2008;Potter et al, 2008), but CBD is typically present in low concentrations in recreational cannabis (o0.1%), based on samples seized by law enforcement.…”

Positron emission tomography imaging using an inverse agonist radioligand to assess cannabinoid CB1 receptors in rodents

“…The cannabinoid type 1 (CB 1 ) receptor is the most abundant G-coupled protein receptor in brain known to date and is involved in multiple neuromodulatory pathways (Grotenhermen, 2005, Pacher et al, 2006. In addition, the CB 1 receptor is associated with addictive behaviors (alcohol, drugs, and food) and is now an active target for medication development (Xie et al, 2007).…”