“The endocannabinoid CB2 receptor system has been implicated in the neuropathology of Alzheimer’s disease (AD)…
The results confirm the constitutive role of the CB2 receptor system both in reducing amyloid plaque pathology in AD and also support the potential of cannabinoid therapies targeting CB2 to reduce Aβ…”
“Emerging findings suggest the existence of a cross-talk between hypocretinergic and endocannabinoid systems…
The present review attempts to piece together what is known about this interesting interaction and describes its potential therapeutic implications.”
http://www.frontiersin.org/Neuropharmacology/10.3389/fnins.2013.00256/abstract
“Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder, associated with alterations of bowel function, abdominal pain and other symptoms related to the GI tract. Recently the endogenous cannabinoid system (ECS) was shown to be involved in the physiological and pathophysiological control of the GI function. The aim of this pilot study was to investigate whether IBS defining symptoms correlate with changes in endocannabinoids or cannabinoid like fatty acid levels in IBS patients.
IBS subtypes and their symptoms show distinct alterations of endocannabinoid and endocannabinoid-like fatty acid levels. These changes may partially result from reduced FAAH expression. The here reported changes support the notion that the ECS is involved in the pathophysiology of IBS and the development of IBS symptoms.”
“Sativex(®) (nabiximols, USAN name) oromucosal spray contains the two main active constituents of Cannabis sativa, tetrahydrocannabinol and cannabidiol in a 1:1 molecular ratio, and acts as an endocannabinoid system modulator. Randomized, controlled clinical trials of Sativex as add-on therapy provide conclusive evidence of its efficacy in the treatment of more than 1500 patients with multiple sclerosis (MS)-related resistant spasticity…
Sativex oromucosal spray appears to be a useful and welcomed option for the management of resistant spasticity in MS patients. Although the management of MS has been improved by the availability of disease-modifying agents that target the underlying pathophysiological processes of the disease, a clear need remains for more effective symptomatic treatments, especially as regards MS-related spasticity and pain.”
“Modulation of the endocannabinoid system has been shown to have therapeutic potential in a number of disease states.
Sativex(®) (nabiximols, USAN name) contains the two main phytocannabinoids from Cannabis sativa, tetrahydrocannabinol and cannabidiol in a 1:1 ratio, and it acts as an endocannabinoid system modulator.
In an experimental mouse model of MS-related spasticity, Sativex dose-dependently improved hind limb flexion/stiffness and a dosage of 10 mg/kg was shown to be as effective as the most widely established anti-spasticity treatment baclofen (5 mg/kg).
These findings with Sativex are very promising and offer encouragement for MS patients, the majority of whom will develop spasticity-related disabling and recalcitrant symptoms. Furthermore, research into the endocannabinoid system may offer potential in other neurodegenerative, inflammatory and pain disorders.”
“Extensive evidence indicates that endocannabinoids modulate cognitive processes in animal models and human subjects. However, the results of endocannabinoid system manipulations on cognition have been contradictory. As for anxiety behavior, a duality has indeed emerged with regard to cannabinoid effects on memory for emotional experiences. Here we summarize findings describing cannabinoid effects on memory acquisition, consolidation, retrieval and extinction. Additionally, we review findings showing how the endocannabinoid system modulates memory function differentially, depending on the level of stress and arousal associated with the experimental context. Based on the evidence reviewed here, we propose that the endocannabinoid system is an emotional buffer that moderates the effects of environmental context and stress on cognitive processes.”
“Accumulating evidence suggests involvement of the endocannabinoid system in the pathophysiology of schizophrenia, which signifies a potential application for this system in the treatment of this disorder.
…similarities in brain function between intoxicated healthy volunteers and schizophrenia patients provide an argument for a role of the endocannabinoid system in symptoms of schizophrenia, and further emphasise this system as a potential novel target for treatment of these symptoms.”
“Soon after the discovery of cannabis by western societies, its psychotropic effects overshadowed its medical benefits. However, investigation into the molecular action of the main constituents of cannabis has led to the discovery of an intercellular signalling system, called the endocannabinoid system (ECS).
The ECS comprises a set of molecular components, including enzymes, signalling lipids and G-protein coupled receptors, which has an outstanding role in modulating eating behaviour and energy homeostasis. Interestingly, evidence has shown that the ECS is present at the central and peripheral nervous system, modulating the function of the hypothalamus, the brain reward system and the brainstem, and coordinating the crosstalk between these brain structures and peripheral organs.
Indeed, the ECS is present and functional in metabolically relevant peripheral tissues, directly modulating their physiology. In the context of a global obesity pandemic, these discoveries are highly suggestive in order to design novel pharmaceutical tools to fight obesity and related morbidities.
In fact, a cannabinoid-based first generation of drugs was developed and marketed. Their failure, due to central side-effects, is leading to a second generation of these drugs unable to cross the blood-brain barrier, as well as other ECS-focused strategies that are still in the pipeline. In the next few years we will hopefully know whether such an important player in energy homeostasis can be successfully targeted without significantly affecting other vital processes related to mood and sense of well-being.”
“G protein-coupled receptor 55 (GPR55) is a putative cannabinoid receptor that is expressed in several tissues involved in regulating energy homeostasis, including the hypothalamus, gastrointestinal tract, pancreas, liver, white adipose and skeletal muscle.
GPR55 has been shown to have a role in cancer and gastrointestinal inflammation, as well as in obesity and type 2 diabetes mellitus (T2DM).
Despite this, the (patho)physiological role of GPR55 in cell dysfunction is still poorly understood, largely because of the limited identification of downstream signalling targets.
Nonetheless, research has suggested that GPR55 modulation would be a useful pharmacological target in metabolically active tissues to improve treatment of diseases such as obesity and T2DM.
Further research is essential to gain a better understanding of the role that this receptor might have in these and other pathophysiological conditions.”
“After 4 millennia of more or less documented history of cannabis use, the identification of cannabinoids, and of Δ(9)-tetrahydrocannabinol in particular, occurred only during the early 1960s, and the cloning of cannabinoid CB1 and CB2 receptors, as well as the discovery of endocannabinoids and their metabolic enzymes, in the 1990s.
Despite this initial relatively slow progress of cannabinoid research, the turn of the century marked an incredible acceleration in discoveries on the “endocannabinoid signaling system,” its role in physiological and pathological conditions, and pain in particular, its pharmacological targeting with selective agonists, antagonists, and inhibitors of metabolism, and its previously unsuspected complexity.
The way researchers look at this system has thus rapidly evolved towards the idea of the “endocannabinoidome,” that is, a complex system including also several endocannabinoid-like mediators and their often redundant metabolic enzymes and “promiscuous” molecular targets.
These peculiar complications of endocannabinoid signaling have not discouraged efforts aiming at its pharmacological manipulation, which, nevertheless, now seems to require the development of multitarget drugs, or the re-visitation of naturally occurring compounds with more than one mechanism of action.
In fact, these molecules, as compared to “magic bullets,” seem to offer the advantage of modulating the “endocannabinoidome” in a safer and more therapeutically efficacious way.
This approach has provided so far promising preclinical results potentially useful for the future efficacious and safe treatment of chronic pain and inflammation.”