Cannabis consumption and non-alcoholic fatty liver disease. A three years longitudinal study in first episode non-affective psychosis patients.

Progress in Neuro-Psychopharmacology and Biological Psychiatry“Increased incidence of obesity and excess weight lead to an increased incidence of non-alcoholic fatty liver disease (NAFLD). Recent evidence indicates a protective effect of cannabis consumption on weight gain and related metabolic alterations in psychosis patients. Overall, patients are at greater risk of presenting fatty diseases, such as NAFLD, partly due to lipid and glycemic metabolic disturbances. However, there are no previous studies on the likely effect of cannabis on liver steatosis. We aimed to explore if cannabis consumption had an effect on hepatic steatosis, in a sample of first-episode (FEP) non-affective psychosis.

RESULTS:

At 3-year follow-up, cannabis users presented significantly lower FLI scores than non-users (F = 13.874; p < .001). Moreover, cannabis users less frequently met the criteria for liver steatosis than non-users (X2 = 7.97, p = .019). Longitudinally, patients maintaining cannabis consumption after 3 years presented the smallest increment in FLI over time, which was significantly smaller than the increment in FLI presented by discontinuers (p = .022) and never-users (p = .016). No differences were seen in fibrosis scores associated with cannabis.

CONCLUSIONS:

Cannabis consumption may produce a protective effect against liver steatosis in psychosis, probably through the modulation of antipsychotic-induced weight gain.”

https://www.ncbi.nlm.nih.gov/pubmed/31228640

“Cannabis consumption is associated with a lower risk of liver steatosis in psychosis. Cannabis use is not associated with liver fibrosis.”

https://www.sciencedirect.com/science/article/pii/S0278584619301393?via%3Dihub

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake.

Addiction Biology banner“The administration of cannabidiol has shown promising evidence in the treatment of some neuropsychiatric disorders, including cocaine addiction. However, little information is available as to the mechanisms by which cannabidiol reduces drug use and compulsive seeking.

We investigated the role of adult hippocampal neurogenesis in reducing cocaine voluntary intake produced by repeated cannabidiol treatment in mice.

Cannabidiol (20 mg/kg) reduced cocaine self-administration behaviour acquisition and total cocaine intake and enhanced adult hippocampal neurogenesis.

The present study confirms that adult hippocampal neurogenesis is one of the mechanisms by which cannabidiol lowers cocaine reinforcement and demonstrates the functional implication of adult hippocampal neurogenesis in cocaine voluntary consumption in mice.

Such findings highlight the possible use of cannabidiol for developing new pharmacotherapies to manage cocaine use disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31162770

https://onlinelibrary.wiley.com/doi/abs/10.1111/adb.12778

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Retrograde activation of CB1R by muscarinic receptors protects against central organophosphorus toxicity.

Neuropharmacology“The acute toxicity of organophosphorus-based compounds is primarily a result of acetylcholinesterase inhibition in the central and peripheral nervous systems. The resulting cholinergic crisis manifests as seizure, paralysis, respiratory failure and neurotoxicity. Though overstimulation of muscarinic receptors is the mechanistic basis of central organophosphorus (OP) toxicities, short-term changes in synapse physiology that precede OP-induced seizures have not been investigated in detail. To study acute effects of OP exposure on synaptic function, field excitatory postsynaptic potentials (fEPSPs) were recorded from Schaffer collateral synapses in the mouse hippocampus CA1 stratum radiatum during perfusion with various OP compounds. Administration of the OPs paraoxon, soman or VX rapidly and stably depressed fEPSPs via a presynaptic mechanism, while the non-OP proconvulsant tetramethylenedisulfotetramine had no effect on fEPSP amplitudes. OP-induced presynaptic long-term depression manifested prior to interictal spiking, occurred independent of recurrent firing, and did not require NMDA receptor currents, suggesting that it was not mediated by activity-dependent calcium uptake. Pharmacological dissection revealed that the presynaptic endocannabinoid type 1 receptor (CB1R) as well as postsynaptic M1 and M3 muscarinic acetylcholine receptors were necessary for OP-LTD. Administration of CB1R antagonists significantly reduced survival in mice after a soman challenge, revealing an acute protective role for endogenous CB1R signaling during OP exposure. Collectively these data demonstrate that the endocannabinoid system alters glutamatergic synaptic function during the acute response to OP acetylcholinesterase inhibitors.”

https://www.ncbi.nlm.nih.gov/pubmed/31132436

“CB1R activation represents a novel therapy to mitigate acute OP toxicity”

https://www.sciencedirect.com/science/article/pii/S002839081930190X?via%3Dihub

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Protective effects of specific cannabinoid receptor 2 agonist GW405833 on concanavalin A-induced acute liver injury in mice.

Image result for nature communications

“Cannabinoid receptor 2 (CB2R) is highly expressed in immune cells and plays an important role in regulating immune responses. In the current study, we investigated the effects of GW405833 (GW), a specific CB2R agonist, on acute liver injury induced by concanavalin A (Con A).

In animal experiments, acute liver injury was induced in mice by injection of Con A (20 mg/kg, i.v.). The mice were treated with GW (20 mg/kg, i.p., 30 min after Con A injection) or GW plus the selective CB2R antagonist AM630 (2 mg/kg, i.p., 15 min after Con A injection).

We found that Con A caused severe acute liver injury evidenced by significantly increased serum aminotransferase levels, massive hepatocyte apoptosis, and necrosis, as well as lymphocyte infiltration in liver tissues. Treatment with GW significantly ameliorated Con A-induced pathological injury in liver tissue, decreased serum aminotransferase levels, and decreased hepatocyte apoptosis.

Our results suggest that GW protects against Con A-induced acute liver injury in mice by inhibiting Jurkat T-cell proliferation through the CB2Rs.”

https://www.ncbi.nlm.nih.gov/pubmed/30918343

https://www.nature.com/articles/s41401-019-0213-0

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Lung alveolar tissue destruction and protein citrullination in diesel exhaust exposed mouse lungs.

Basic &amp; Clinical Pharmacology &amp; Toxicology banner

“Humanity faces an increasing impact of air pollution worldwide, including threats to human health. Air pollutants prompt and promote chronic inflammation, tumourigenesis, autoimmune and other destructive processes in the human body.

Post-translational modification of proteins, e.g. citrullination, results from damaging attacks of pollutants, including smoking, air pollution and others, rendering host tissues immunogenic. Citrullinated proteins and citrullinating enzymes, deiminases, are more prevalent in patients with COPD and correlate with ongoing inflammation and oxidative stress.

In this study, we installed an in-house-designed diesel exhaust delivery and cannabidiol vaporization system where mice were exposed to relevant, urban traffic-related levels of diesel exhaust for 14 days and assessed integrity of alveolar tissue, gene expression shifts and changes in protein content in the lungs and other tissues of exposed mice. Systemic presence of modified proteins was also tested.

The protective effect of phytocannabinoids was investigated as well.

Data obtained in our study show subacute effects of diesel exhaust on mouse lung integrity and protein content. Emphysematous changes are documented in exposed mouse lungs. In parallel, increased levels of citrulline were detected in the alveolar lung tissue and peripheral blood of exposed mice.

Pretreatment with vaporized cannabidiol ameliorated some damaging effects.

Results reported hereby provide new insights into subacute lung tissue changes that follow diesel exhaust exposure and suggest possible dietary and/or other therapeutic interventions for maintaining lung health and healthy ageing.”

https://www.ncbi.nlm.nih.gov/pubmed/30801928

https://onlinelibrary.wiley.com/doi/abs/10.1111/bcpt.13213

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Effect of cannabis on weight and metabolism in first-episode non-affective psychosis: Results from a three-year longitudinal study.

Image result for sage journals

“Recent evidence indicates a protective effect of cannabis on weight gain and related metabolic alterations. However, there are no previous studies on the long-term longitudinal effects of cannabis on first-episode drug-naïve patients, which would thereby avoid the confounding effects of chronicity and previous treatment exposure.

We aimed to explore the effect of cannabis smoking on weight and lipid/glycaemic metabolic measures in a sample of first-episode non-affective psychosis patients.

RESULTS::

Cannabis users at baseline presented a lower weight ( F=14.85, p<0.001), body mass index ( F=13.14, p<0.001), total cholesterol ( F=4.85, p=0.028) and low-density lipoprotein-cholesterol ( F=6.26, p=0.013) compared to non-users. These differences were also observed after three years: weight ( F=8.07, p=0.005), body mass index ( F=4.66, p=0.032) and low-density lipoprotein-cholesterol ( F=3.91, p=0.049). Moreover, those patients discontinuing cannabis use presented a higher increase in weight ( F=2.98, p=0.052), body mass index ( F=2.73, p=0.067) and triglyceride-high-density lipoprotein ratio ( F=2.72, p=0.067) than the ‘non-users’ and ‘continuers’.

CONCLUSIONS::

The study suggests that cannabis use may produce a protective effect against weight gain and related metabolic alterations in psychosis.”

https://www.ncbi.nlm.nih.gov/pubmed/30702972

https://doi.org/10.1177/0269881118822173

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Activation of ATP-sensitive K-channel promotes the anticonvulsant properties of cannabinoid receptor agonist through mitochondrial ATP level reduction.

“Cannabinoid receptor (CBR) agonist could act as a protective agent against seizure susceptibility in animal models of epilepsy.

Studies have shown that potassium channels could play a key role in ameliorating neuronal excitability.

In this study, we attempted to evaluate how CBRs and Adenosine Tri-Phosphate (ATP)-sensitive potassium channels collaborate to affect seizure susceptibility by changing the clonic seizure threshold (CST).

In conclusion, CB1 agonist accomplishes at least a part of its anticonvulsant actions through ATP-sensitive potassium channels, probably by decreasing the mitochondrial ATP level to open the potassium channel to induce its anticonvulsant effect.”

https://www.ncbi.nlm.nih.gov/pubmed/30776677

https://linkinghub.elsevier.com/retrieve/pii/S1525505018308503

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Modulation of the Endocannabinoid System Following Central Nervous System Injury.

ijms-logo

“Central nervous system (CNS) injury, such as stroke or trauma, is known to increase susceptibility to various infections that adversely affect patient outcomes (CNS injury-induced immunodepression-CIDS).

The endocannabinoid system (ECS) has been shown to have immunoregulatory properties. Therefore, the ECS might represent a druggable target to overcome CIDS.

Evidence suggests that cannabinoid type 2 receptor (CB₂R) activation can be protective during the early pro-inflammatory phase after CNS injury, as it limits neuro-inflammation and, therefore, attenuates CIDS severity. In the later phase post CNS injury, CB₂R inhibition is suggested as a promising pharmacologic strategy to restore immune function in order to prevent infection.”

https://www.ncbi.nlm.nih.gov/pubmed/30658442

https://www.mdpi.com/1422-0067/20/2/388

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

The protective effects of β-caryophyllene on LPS-induced primary microglia M1/M2 imbalance: A mechanistic evaluation.

Life Sciences

“Neuroinflammation is observed as a routine characterization of neurodegenerative disorders such as dementia, multiple sclerosis (MS) and Alzheimer’s diseases (AD). Scientific evidence propounds both of the neuromodulatory and immunomodulatory effects of CB2 in the immune system. β-Caryophyllene (BCP) is a dietary selective CB2 agonist, which deserves the anti-inflammatory and antioxidant effects at both low and high doses through activation of the CB2 receptor.

METHODS:

In this study, we investigated the protective effects of a broad range concentration of BCP against LPS-induced primary microglia cells inflammation and M1/M2 imbalance and identifying the portion of the involvement of related signaling pathways on BCP effects using pharmacological antagonists of CB2, PPAR-γ, and sphingomyelinase (SMase).

KEY FINDINGS:

The protective effects of BCP on LPS-induced microglia imbalance is provided by the M2 healing phenotype of microglia, releasing the anti-inflammatory (IL-10, Arg-1, and urea) and anti-oxidant (GSH) parameters and reducing the inflammatory (IL-1β, TNF-α, PGE2, iNOS and NO) and oxidative (ROS) biomarkers. Moreover, we showed that BCP exerts its effects through CB2receptors which overproduction of ceramides by SMase at middle to higher concentrations of BCP reduce the protective activity of BCP and results in the activation of the PPAR-γ pathway.

SIGNIFICANCE:

In conclusion, the low concentration of BCP has higher selective anti-inflammatory effects rather than high levels. On this occasion, BCP by modulating the microglia is able to have potential therapeutic effects in neuro-inflammation conditions and microglia cells such as MS and AD.”

https://www.ncbi.nlm.nih.gov/pubmed/30620895

https://www.sciencedirect.com/science/article/abs/pii/S0024320518308610?via%3Dihub

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”  https://www.ncbi.nlm.nih.gov/pubmed/18574142

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Peripubertal cannabidiol treatment rescued behavioral and neurochemical abnormalities in MAM model of schizophrenia.

 Neuropharmacology

“In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produced long-lasting behavioral alterations such as social withdrawal and cognitive impairment in the social interaction test and in the novel object recognition test, respectively. At molecular level, an increased cannabinoid receptor type-1 (CB1) mRNA and protein expression which might be due to a reduction in DNA methylation at gene promoter in the prefrontal cortex (PFC), coincided with deficits in the social interaction test and in the novel object recognition test in MAM rats. Both schizophrenia-like phenotype and altered transcriptional regulation of CB1 receptors were reversed by peripubertal treatment (from PND 19 to PND 39) with the non-psychotropic phytocannabinoid cannabidiol (30 mg/kg/day), or, in part, by treatment with the cannabinoid CB1 receptor antagonist/inverse agonist AM251 (0.5 mg/kg/day), but not with haloperidol (0.6 mg/kg/day). These results suggest that early treatment with cannabidiol may prevent both the appearance of schizophrenia-like deficits as well as CB1 alterations in the PFC at adulthood, supporting that peripubertal cannabidiol treatment might be protective against MAM insult.”

https://www.ncbi.nlm.nih.gov/pubmed/30496751

https://www.sciencedirect.com/science/article/pii/S0028390818308761?via%3Dihub

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous