Conference on Endocannabinoid and Autism
Endocannibinoid receptor expression in autism...
The inventive method relates to a method for the determination of susceptibility or diagnosis of autism or autism spectrum disorders. Diagnosis or determination of susceptibility determinations are predicated on quantitative analysis of endocannibinoid levels or endocannibinoid receptor expression.
The endocannabinoid system works to regulate and modulate almost all of the neurotransmitters in your entire body. This group of receptors and their transmitters (endocannabinoids) are involved in most functions of your body including appetite, mood, pain-sensation, thought, memory, and much more. Piomelli and Manzoni have discovered that people with fragile X syndrome (the most common known genetic cause of autism) have a limited amount of a natural endocannabinoid transmitter compound called 2-AG, which is found in the human brain. This compound is crucial for efficient transport of neural signals to receptors, and affects basic motor skills like walking and talking.
Stress, Anxiety, and Fear
Alzheimer's caused by loss of cannabinoids....
During high-frequency (tetanic) stimulation, somatic synaptic inhibition is suppressed by endocannabinoids. We find that Aβ prevents this endocannabinoid-mediated disinhibition, thus leaving synaptic inhibition more intact during tetanic stimulation. This intact inhibition opposes the normal depolarization of hippocampal pyramidal neurons that occurs during tetanus, thus opposing the induction of synaptic plasticity. Thus, a pathway through which Aβ can act to modulate neural activity is identified, relevant to learning and memory and how it may mediate aspects of the cognitive decline seen in Alzheimer’s disease.
The endocannabinoid system (ECS) regulates numerous cellular and physiological processes through the activation of receptors targeted by endogenously produced ligands called endocannabinoids. Importantly, this signalling system is known to play an important role in modulating energy balance and glucose homeostasis. For example, current evidence indicates that the ECS becomes overactive during obesity whereby its central and peripheral stimulation drives metabolic processes that mimic the metabolic syndrome. Herein, we examine the role of the ECS in modulating the function of mitochondria which play a pivotal role in maintaining cellular and systemic energy homeostasis, in large part due to their ability to tightly coordinate glucose and lipid utilisation. Because of this, mitochondrial dysfunction is often associated with peripheral insulin resistance and glucose intolerance, as well as the manifestation of excess lipid accumulation in the obese state. This review aims to highlight the different ways through which the ECS may impact upon mitochondrial abundance and/or oxidative capacity, and where possible, relate these findings to obesity-induced perturbations in metabolic function. Furthermore, we explore the potential implications of these findings in terms of the pathogenesis of metabolic disorders and how these may be used to strategically develop therapies targeting the ECS.
Treatment For Psychosis
Studies were selected if they described experiments with psychosis models, psychotic symptoms or psychotic disorders as outcome measure and involved the use of CBD as intervention. Evidence from several research domains suggests that CBD shows potential for antipsychotic treatment.
Now a researcher says that the drug has neuroprotective qualities as well, protecting the brain from long-term cognitive damage in the wake of injury from lack of oxygen, seizures, or toxic drugs.
Thus the endocannabinoid system, which has neuroprotective and immunomodulatory actions mediated by IL-1 signalling cascades in the brain, could assist the process of proliferation and differentiation of embryonic or adult NSCs, and this may be of therapeutic interest in the emerging field of brain repair.
Mutations found in individuals with autism block the action of molecules made by the brain that act on the same receptors that marijuana's active chemical acts on, according to new research. The findings implicate specific molecules, called endocannabinoids, in the development of some autism cases and point to potential treatment strategies.
Taken together, our results suggest that CBC raises the viability of NSPCs while inhibiting their differentiation into astroglia, possibly through up-regulation of ATP and adenosine signalling.
A new study shows that mutations associated with autism block the action of brain molecules that act on the same receptors that marijuana’s active chemical acts on. Endocannabinoids are molecules that affect memory, learning, pain, and other important processes. They share a similar chemical structure with THC, the primary psychoactive component of marijuana. Endocannabinoids naturally occur in the human brain, and are responsible for synaptic signaling within the brain.
Here we showed that Gp1a, a highly selective CB2 agonist, with a four log higher affinity for CB2 than CB1, reduced clinical scores and facilitated recovery in EAE in conjunction with long term reduction in demyelination and axonal loss. We also established that Gp1a affected EAE through at least two different mechanisms, i.e. an early effect on Th1/Th17 differentiation in peripheral immune organs, and a later effect on the accumulation of pathogenic immune cells in the CNS, associated with reductions in the expression of CNS and T cell chemokine receptors, chemokines and adhesion molecules. This is the first report on the in vivo CB2-mediated Gp1a inhibition of Th17/Th1 differentiation. We also confirmed the Gp1a-induced inhibition of Th17/Th1 differentiation in vitro, both in non-polarizing and polarizing conditions. The CB2-induced inhibition of Th17 differentiation is highly relevant in view of recent studies emphasizing the importance of pathogenic self-reactive Th17 cells in EAE/MS. In addition, the combined effect on Th17 differentiation and immune cell accumulation into the CNS, emphasize the relevance of CB2 selective ligands as potential therapeutic agents in neuroinflammation.
Cannabidiol and O-1602 showed anti-inflammatory effects in mice with AP and improved the expression of GPR55 in the pancreatic tissue as well.
We demonstrate that in addition to unique gain-of-function effects produced by the neuroligin-3 R451C-knockin but not the neuroligin-3 knockout mutation, both mutations dramatically impaired tonic but not phasic endocannabinoid signaling. Our data thus suggest that neuroligin-3 is specifically required for tonic endocannabinoid signaling, raising the possibility that alterations in endocannabinoid signaling may contribute to autism pathophysiology
Phytocannabinoids are useful therapeutics for multiple applications including treatments of constipation, malaria, rheumatism, alleviation of intraocular pressure, emesis, anxiety and some neurological and neurodegenerative disorders. Consistent with these medicinal properties, extracted cannabinoids have recently gained much interest in research, and some are currently in advanced stages of clinical testing. Other constituents of Cannabis sativa, the hemp plant, however, remain relatively unexplored in vivo. These include cannabidiol (CBD), cannabidivarine (CBDV), Δ(9)-tetrahydrocannabivarin (Δ(9)-THCV) and cannabigerol (CBG).
This review discusses recent studies suggesting that cannabidiol may have utility in treating a number of human diseases and disorders now known to involve activation of the immune system and associated oxidative stress, as a contributor to their etiology and progression. These include rheumatoid arthritis, types 1 and 2 diabetes, atherosclerosis, Alzheimer disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain.
Results showed that the blockade of PPARγ was able to significantly blunt CBD effects on reactive gliosis and subsequently on neuronal damage. Moreover, due to its interaction at PPARγ, CBD was observed to stimulate hippocampal neurogenesis. All these findings report the inescapable role of this receptor in mediating CBD actions, here reported.
Special emphasis is placed on novel mechanisms which may shed light on the pharmacological activity associated with CBD preclinically. These include a self-defence system against inflammation and neurodegeneration mediated by inhibition of equilibrative nucleoside transporter and activation of adenosine receptor by treatment with CBD.
This differentiates these cannabinoids from cyclooxygenase-2 inhibitors that suppress the synthesis of eicosanoids that promote the induction of the inflammatory process.
Chronic Pain Treatment
These cannabinoids may represent a novel class of therapeutic agents for the treatment of chronic pain and other diseases involving GlyR dysfunction.
Enteric glial cells (EGC) actively mediate acute and chronic inflammation in the gut; EGC proliferate and release neurotrophins, growth factors, and pro-inflammatory cytokines which, in turn, may amplify the immune response, representing a very important link between the nervous and immune systems in the intestine... Our results therefore indicate that CBD indeed unravels a new therapeutic strategy to treat inflammatory bowel diseases.