CB1 also responds to allosteric modulators, which influence cannabinoid binding and efficacy.
To understand the mechanism of these compounds, we solved the crystal structure of CB1 with the negative allosteric modulator (NAM) ORG27569 and the agonist CP55940.
The structure reveals that the NAM binds to an extrahelical site within the inner leaflet of the membrane, which overlaps with a conserved site of cholesterol interaction in many G protein-coupled receptors (GPCRs).
The ternary structure with ORG27569 and CP55940 captures an intermediate state of the receptor, in which aromatic residues at the base of the agonist-binding pocket adopt an inactive conformation despite the large contraction of the orthosteric pocket.
The structure illustrates a potential strategy for drug modulation of CB1 and other class A GPCRs.”
“WIN55,212-2 (WIN) is a synthetic agonist of 
“Hepatic fibrosis is the consequence of an unresolved wound healing process in response to chronic liver injury and involves multiple cell types and molecular mechanisms. The hepatic endocannabinoid and apelin systems are two signalling pathways with a substantial role in the liver fibrosis pathophysiology-both are upregulated in patients with advanced liver disease. Endogenous 
“The symptomatic treatment of myotonia and myalgia in patients with dystrophic and non-dystrophic myotonias is often not satisfactory.
“Medical 
“We used mouse microglial cells in culture activated by lipopolysaccharide (LPS, 10 ng/ml) to study the anti-inflammatory potential of 
“Excessive daytime sleepiness and cataplexy are among the symptoms of narcolepsy, a sleep disorder caused by the loss of hypocretin/orexin (HCRT/OX) neurons placed into the hypothalamus (LH). Several treatments for managing narcolepsy include diverse drugs to induce alertness, such as antidepressants, amphetamine, or modafinil, etc.
“Although driving under the influence of cannabis is increasingly common among young adults, little is known about residual effects on driver behavior.
“Parkinson’s disease (PD) and L-DOPA-induced dyskinesia (LID) are motor disorders with significant impact on the patient’s quality of life. Unfortunately, pharmacological treatments that improve these disorders without causing severe side effects are not yet available. Delay in initiating L-DOPA is no longer recommended as LID development is a function of disease duration rather than cumulative L-DOPA exposure.