“Regulators of G protein signaling (RGS) proteins provide timely termination of G protein-coupled receptor (GPCR) responses. Serving as a central control point in GPCR signaling cascades, RGS proteins are promising targets for drug development. In this review, we discuss the involvement of RGS proteins in the pathophysiology of the gastrointestinal inflammation and their potential to become a target for anti-inflammatory drugs. Specifically, we evaluate the emerging evidence for modulation of selected receptor families: opioid, cannabinoid and serotonin by RGS proteins. We discuss how the regulation of RGS protein level and activity may modulate immunological pathways involved in the development of intestinal inflammation. Finally, we propose that RGS proteins may serve as a prognostic factor for survival rate in colorectal cancer. The ideas introduced in this review set a novel conceptual framework for the utilization of RGS proteins in the treatment of gastrointestinal inflammation, a growing major concern worldwide.”
Tag Archives: Cannabinoids
Social defeat leads to changes in the endocannabinoid system; an overexpression of calreticulin and motor impairment in mice.
“Social defeat leads to changes in the endocannabinoid system; an overexpression of calreticulin and motor impairment in mice… the aim of this study was to investigate the long-lasting effects of chronic psychosocial stress on motor coordination and motor learning, CB1 receptor expression, endogenous cannabinoid ligands and gene expression in the cerebellum. After chronic psychosocial stress, motor coordination and motor learning were impaired… The present study provides evidence that chronic stress activates calreticulin and might be one of the pathological mechanisms underlying the motor coordination and motor learning dysfunctions seen in social defeat mice.” http://www.ncbi.nlm.nih.gov/pubmed/26815100
[Efficacy, tolerability, and safety of cannabinoids in gastroenterology : A systematic review].
“Cannabis may be useful for symptom relief in Crohn’s disease such as pain, nausea, and loss of appetite.”
Molecular Mechanisms of Cannabis Signaling in the Brain.
“Cannabis has been cultivated and used by humans for thousands of years. Research for decades was focused on understanding the mechanisms of an illegal/addictive drug. This led to the discovery of the vast endocannabinoid system.
Research has now shifted to understanding fundamental biological questions related to one of the most widespread signaling systems in both the brain and the body.
Our understanding of cannabinoid signaling has advanced significantly in the last two decades. In this review, we discuss the state of knowledge on mechanisms of Cannabis signaling in the brain and the modulation of key brain neurotransmitter systems involved in both brain reward/addiction and psychiatric disorders.
It is highly probable that various cannabinoids will be found to be efficacious in the treatment of a number of psychiatric disorders.
We are at crossroads for research on endocannabinoid function and therapeutics (including the use of exogenous treatments such as Cannabis).
With over 100 cannabinoid constituents, the majority of which have not been studied, there is much Cannabis research yet to be done. With more states legalizing both the medicinal and recreational use of marijuana the rigorous scientific investigation into cannabinoid signaling is imperative.”
Antidepressant-like effect of cannabidiol injection into the ventral medial prefrontal cortex – possible involvement of 5-HT1A and CB1 receptors.
“Systemic administration of Cannabidiol (CBD), the main non-psychotomimetic constituent of Cannabis sativa, induces antidepressant-like effects.
The mechanism of action of CBD is thought to involve the activation of 5-HT1A receptors and the modulation of endocannabinoid levels with subsequent CB1 activation…
Administration of CBD into the vmPFC induces antidepressant-like effects possibly through indirect activation of CB1 and 5-HT1A receptors.”
Impact of adolescent marijuana use on intelligence: Results from two longitudinal twin studies.
“The purpose of the present study was to examine the associations of marijuana use with changes in intellectual performance in two longitudinal studies of adolescent twins.
There was no evidence of a dose-response relationship between frequency of use and intelligence quotient (IQ) change. Furthermore, marijuana-using twins failed to show significantly greater IQ decline relative to their abstinent siblings.
Evidence from these two samples suggests that observed declines in measured IQ may not be a direct result of marijuana exposure but rather attributable to familial factors that underlie both marijuana initiation and low intellectual attainment.”
“Short-term cannabis use in adolescence does not appear to cause IQ decline or impair executive functions, even when cannabis use reaches the level of dependence. Family background factors explain why adolescent cannabis users perform worse on IQ and executive function tests.”
https://www.ncbi.nlm.nih.gov/pubmed/28734078
https://www.ncbi.nlm.nih.gov/pubmed/28734078
CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Israeli experience.
“To describe the experience of five Israeli pediatric epilepsy clinics treating children and adolescents diagnosed as having intractable epilepsy with a regimen of medical cannabis oil.
A retrospective study describing the effect of cannabidiol (CBD)-enriched medical cannabis on children with epilepsy.
The cohort included 74 patients (age range 1-18 years) with intractable epilepsy resistant to >7 antiepileptic drugs. Forty-nine (66%) also failed a ketogenic diet, vagal nerve stimulator implantation, or both.
They all started medical cannabis oil treatment between 2-11/2014 and were treated for at least 3 months (average 6 months).
The selected formula contained CBD and tetrahydrocannabinol at a ratio of 20:1 dissolved in olive oil. The CBD dose ranged from 1 to 20mg/kg/d. Seizure frequency was assessed by parental report during clinical visits.
CBD treatment yielded a significant positive effect on seizure load.
Most of the children (66/74, 89%) reported reduction in seizure frequency: 13 (18%) reported 75-100% reduction, 25 (34%) reported 50-75% reduction, 9 (12%) reported 25-50% reduction, and 19 (26%) reported <25% reduction. Five (7%) patients reported aggravation of seizures which led to CBD withdrawal.
In addition, we observed improvement in behavior and alertness, language, communication, motor skills and sleep. Adverse reactions included somnolence, fatigue, gastrointestinal disturbances and irritability leading to withdrawal of cannabis use in 5 patients.
CONCLUSIONS:
The results of this multicenter study on CBD treatment for intractable epilepsy in a population of children and adolescents are highly promising. Further prospective, well-designed clinical trials using enriched CBD medical cannabis are warranted.”
Involvement of the orexin/hypocretin system in the pharmacological effects induced by Δ9-tetrahydrocannabinol.
“Anatomical, biochemical and pharmacological evidences suggest the existence of a cross-talk between the orexinergic and the endocannabinoid system.
The hypothermia, supraspinal antinociception and anxiolytic-like effects induced by THC were modulated by orexins through OX2 signalling.
OX1 did not seem to be involved in these THC responses. No differences in CB1 receptor levels were found between wild-type and PPO KO mice…
Our results provide new findings to further clarify the interaction between orexins and cannabinoids. OX1 and OX2 are differently implicated in the pharmacological effects of cannabinoids.”
Rescue of Impaired mGluR5-Driven Endocannabinoid Signaling Restores Prefrontal Cortical Output to Inhibit Pain in Arthritic Rats.
“Rescue of Impaired metabotropic glutamate receptor 5 (mGluR5)-Driven Endocannabinoid Signaling Restores Prefrontal Cortical Output to Inhibit Pain in Arthritic Rats…
Restoring endocannabinoid signaling allows mGluR5 activation to increase infralimbic output hence inhibit pain behaviors and mitigate pain-related cognitive deficits.”
The selective monoacylglycerol lipase inhibitor MJN110 produces opioid sparing effects in a mouse neuropathic pain model.
“Serious clinical liabilities associated with the prescription of opiates for pain control include constipation, respiratory depression, pruritus, tolerance, abuse, and addiction.
A recognized strategy to circumvent these side effects is to combine opioids with other antinociceptive agents.
The combination of opiates with the primary active constituent of cannabis, Δ9-tetrahydrocannabinol, produces enhanced antinociceptive actions, suggesting that cannabinoid receptor agonists can be opioid sparing…
Here, we tested whether elevating the endogenous cannabinoid 2-arachidonylglycerol (2-AG) through the inhibition of its primary hydrolytic enzyme monoacylglycerol lipase (MAGL), will produce opioid sparing effects…
These findings, taken together, suggest that MAGL inhibition produces opiate sparing events with diminished tolerance, constipation, and cannabimemetic side effects.”