“Autophagy is a catabolic process involved in homeostatic and regulated cellular protein recycling and degradation via the lysosomal degradation pathway. Emerging data associates impaired autophagy, increased activity in the endocannabinoid system and upregulation of suppressor of cytokine signaling (SOCS)-3 protein expression during intestinal inflammatory states. We have investigated whether these three processes are linked. By assessing the impact of phyto-cannabinoid cannabidiol (CBD), synthetic cannabinoid (ACEA) and endocannabinoid (AEA) on autophagosome formation, we explored whether these actions were responsible for cyclic SOCS3 protein levels. Our findings show that all three cannabinoids induce autophagy in a dose-dependent manner in fully differentiated CaCo2 cells, a model of mature intestinal epithelium. ACEA and AEA induced canonical autophagy, which was cannabinoid receptor (CB)-1 mediated. In contrast, CBD was able to bypass both the CB1 receptor and the canonical pathway to induce autophagy, albeit to a lesser extent. Functionally, all three cannabinoids reduced SOCS3 protein expression, which was reversed by blocking both early and late autophagy. In conclusion, the regulatory protein, SOCS3, is itself regulated by autophagy and cannabinoids play a role in this process, which could be important when considering therapeutic applications for the cannabinoids in inflammatory conditions.”
New insights into the molecular pathophysiology of fragile X syndrome and therapeutic perspectives from the animal model.
“Fragile X syndrome is the most common monogenetic form of intellectual disability and is a leading cause of autism. This syndrome is produced by the reduced transcription of the fragile X mental retardation (FMR1) gene, and it is characterized by a range of symptoms heterogeneously expressed in patients such as cognitive impairment, seizure susceptibility, altered pain sensitivity and anxiety.
The recent advances in the understanding of the pathophysiological mechanisms involved have opened novel potential therapeutic approaches identified in preclinical rodent models as a necessary preliminary step for the subsequent evaluation in patients… New findings in the animal models open other possible therapeutic approaches such as the mammalian target of rapamycin signaling pathway or the endocannabinoid system… emerging data recently obtained in preclinical models of fragile X syndrome supporting these new therapeutic perspectives.”
http://www.ncbi.nlm.nih.gov/pubmed/24831882
http://www.thctotalhealthcare.com/category/fragile-x-syndrome-fxs/
Functionalization of β-Caryophyllene Generates Novel Polypharmacology in the Endocannabinoid System.
“The widespread dietary plant sesquiterpene hydrocarbon β-caryophyllene is a CB2 cannabinoid receptor-specific agonist showing anti-inflammatory and analgesic effects in vivo…
Our study shows that by removing the conformational constraints induced by the medium-sized ring and by introducing functional groups in the sesquiterpene hydrocarbon 1, a new scaffold with pronounced polypharmacological features within the endocannabinoid system could be generated.
The structural and functional repertoire of cannabimimetics and their yet poorly understood intrinsic promiscuity may be exploited to generate novel probes and ultimately more effective drugs.”
http://www.ncbi.nlm.nih.gov/pubmed/24831513
“Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception…β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis… The combined injection of morphine and BCP may be an alternative in treating chemogenic pain.” http://www.ncbi.nlm.nih.gov/pubmed/23138934
PTSD symptom reports of patients evaluated for the New Mexico Medical Cannabis Program.
“New Mexico was the first state to list post-traumatic stress disorder (PTSD) as a condition for the use of medical cannabis. There are no published studies, other than case reports, of the effects of cannabis on PTSD symptoms. The purpose of the study was to report and statistically analyze psychometric data on PTSD symptoms collected during 80 psychiatric evaluations of patients applying to the New Mexico Medical Cannabis Program from 2009 to 2011…
RESULTS:
Greater than 75% reduction in CAPS (Clinician Administered Posttraumatic Scale) symptom scores were reported when patients were using cannabis compared to when they were not.
CONCLUSIONS:
Cannabis is associated with reductions in PTSD symptoms in some patients, and prospective, placebo-controlled study is needed to determine efficacy of cannabis and its constituents in treating PTSD.”
http://www.ncbi.nlm.nih.gov/pubmed/24830188
http://www.thctotalhealthcare.com/category/post-traumatic-stress-disorder-ptsd/
CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier.
“Our data identify CB2 as a potential target in reducing the number of brain metastastes originating from melanoma.”
Intrahypothalamic injection of cannabidiol increases the extracellular levels of adenosine in nucleus accumbens in rats.
“Cannabidiol (CBD) is a constituent of Cannabis sativa that promotes wakefulness as well as enhances endogenous levels of wake-related neurotransmitters, including dopamine. However, at this date, the effects of CBD on the sleep-inducing molecules, such as adenosine (AD), are unknown. Here, we report that intrahypothalamic injection of CBD (10μg/1μL) increases the extracellular levels of AD collected from nucleus accumbens. Furthermore, the pharmacodynamic of this drug shows that effects on the contents of AD last 2h post-injection. These preliminary findings suggest that CBD promotes the endogenous accumulation of AD.”
http://www.ncbi.nlm.nih.gov/pubmed/24800644
“Cannabidiol, a constituent of Cannabis sativa, modulates sleep in rats…Since CBD induces alertness, it might be of therapeutic value in sleep disorders such as excessive somnolence.” http://www.ncbi.nlm.nih.gov/pubmed/16844117
“The nonpsychoactive Cannabis constituent cannabidiol is a wake-inducing agent.” http://www.ncbi.nlm.nih.gov/pubmed/19045957
Novel approaches to the development of anti-sepsis drugs.
“Sepsis is the dysregulated systemic immune response to an infection…
The authors discuss specific pharmacological approaches with a focus on immune modulation, for example, Toll-like receptor 4 inhibition and modulation of the endocannabinoid system.”
CB2 cannabinoid receptors contribute to bacterial invasion and mortality in polymicrobial sepsis.
“Sepsis is a major healthcare problem and current estimates suggest that the incidence of sepsis is approximately 750,000 annually. Sepsis is caused by an inability of the immune system to eliminate invading pathogens.
Here we examined the role of CB(2) receptors in regulating the host’s response to sepsis…
Taken together, our results establish for the first time that CB(2) receptors are important contributors to septic immune dysfunction and mortality, indicating that CB(2) receptors may be therapeutically targeted for the benefit of patients suffering from sepsis.”
Cannabinoid receptor 1 inhibition improves the intestinal microcirculation.
“The data supports the involvement of the CB1R signaling in leukocyte activation during sepsis. Drugs targeting the CB1R may have therapeutic potential in systemic inflammation, such as sepsis.”
http://www.ncbi.nlm.nih.gov/pubmed/23334604
“Cannabinoid receptor 1 inhibition causes seizures during anesthesia induction in experimental sepsis… The data suggest that CB1R inhibition in combination with pentobarbital may increase the incidence of anesthetic-induced seizures in the case of sepsis.”
http://www.ncbi.nlm.nih.gov/pubmed/22504215
The cannabinoid receptor 2 is critical for the host response to sepsis.
“These data suggest that CB2R is a critical regulator of the immune response to sepsis and may be a novel therapeutic target.”