“Negative emotional states that are associated with excessive alcohol intake, particularly anxiety-like states, have been linked to opponent processes in the central nucleus of the amygdala (CeA), affecting stress-related transmitters and monoamines. This study extends these observations to include endocannabinoid signaling in alcohol-dependent animals. Rats and mice were exposed to chronic intermittent alcohol with vapor inhalation or liquid diet to induce dependence. In vivo microdialysis was used to estimate interstitial concentrations of endocannabinoids [N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG)] and amino acids (glutamate and GABA) in rat CeA. Additionally, we evaluated the inhibition of endocannabinoids clearance enzymes [monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase] on anxiety-like behavior and alcohol consumption in alcohol-dependent rats and mice. Results revealed that alcohol dependence produced decreases in baseline 2-AG dialysate levels and increases in baseline levels of glutamate and GABA. Acute alcohol abstinence induced an enhancement of these dependence-induced effects and the levels of 2-AG and GABA were restored upon alcohol re-exposure. Additional studies showed that the increased CeA 2-AG levels induced by restraint stress and alcohol self-administration were blunted in alcohol-dependent rats. Pharmacological studies in rats and mice showed that anxiety-like behavior and alcohol consumption were increased in alcohol-dependent animals, and these behavioral effects were attenuated mainly by MAGL inhibitors [MJN110 (10 and 20 mg/kg) in rats and JZL184 (1 and 3 mg/kg) in mice]. The present results suggest a key role for endocannabinoid signaling in motivational neuroadaptations during alcohol dependence, in which a deficiency in CeA 2-AG signaling in alcohol-dependent animals is linked to stress and excessive alcohol consumption.” https://www.ncbi.nlm.nih.gov/pubmed/29748627 https://www.nature.com/articles/s41386-018-0055-3]]>
Monthly Archives: May 2018
A Critical Systematic Review of Evidence for Cannabinoids in the Treatment of Schizophrenia
“Cannabinoids have an emerging evidence base as an effective treatment option in a number of medical conditions, including anorexia and intractable vomiting. It is well known that patients with schizophrenia are more likely to use cannabis; it has also been argued that this could be a way of self-treating adverse side effects (secondary to antipsychotics) in a group of people with schizophrenia. Therefore, studies have attempted to examine the use of cannabinoids in schizophrenia. Given the recent interest in the use of cannabinoids in general and the ensuing ethical debates, we systematically review the available literature on the use of four cannabinoids, namely delta-9-tetrahydrocannabinol, dronabinol, rimonabant, and cannabidiol, in the management of schizophrenia. We also offer suggestions for future research in this area.” https://www.healio.com/psychiatry/journals/psycann/2018-5-48-5/%7B04639e36-7fd1-4e31-aff2-7cea85ea3bc3%7D/a-critical-systematic-review-of-evidence-for-cannabinoids-in-the-treatment-of-schizophrenia]]>
Cannabinoids and gastrointestinal motility: Pharmacology, clinical effects, and potential therapeutics in humans.
“Cannabinoid agents and cannabis are frequently used for relief of diverse gastrointestinal symptoms.
PURPOSE:
The objective of this article is to increase the awareness of gastroenterologists to the effects of cannabinoids on gastrointestinal motility, as gastroenterologists are likely to encounter patients who are taking cannabinoids, or those with dysmotility that may be associated with cannabinoid mechanisms. The non-selective cannabinoid agonist, dronabinol, retards gastric emptying and inhibits colonic tone and phasic pressure activity. In summary, cannabinoid mechanisms and pharmacology are relevant to the current and future practice of clinical gastroenterology.” https://www.ncbi.nlm.nih.gov/pubmed/29745439 https://onlinelibrary.wiley.com/doi/abs/10.1111/nmo.13370]]>Emerging Role of (Endo)Cannabinoids in Migraine.
“In this mini-review, we summarize recent discoveries and present new hypotheses on the role of cannabinoids in controlling trigeminal nociceptive system underlying migraine pain.
Individual sections of this review cover key aspects of this topic, such as: (i) the current knowledge on the endocannabinoid system (ECS) with emphasis on expression of its components in migraine related structures; (ii) distinguishing peripheral from central site of action of cannabinoids, (iii) proposed mechanisms of migraine pain and control of nociceptive traffic by cannabinoids at the level of meninges and in brainstem, (iv) therapeutic targeting in migraine of monoacylglycerol lipase and fatty acid amide hydrolase, enzymes which control the level of endocannabinoids; (v) dual (possibly opposing) actions of cannabinoids via anti-nociceptive CB1 and CB2 and pro-nociceptive TRPV1 receptors.
We explore the cannabinoid-mediated mechanisms in the frame of the Clinical Endocannabinoid Deficiency (CECD) hypothesis, which implies reduced tone of endocannabinoids in migraine patients. We further discuss the control of cortical excitability by cannabinoids via inhibition of cortical spreading depression (CSD) underlying the migraine aura.
Finally, we present our view on perspectives of Cannabis-derived (extracted or synthetized marijuana components) or novel endocannabinoid therapeutics in migraine treatment.”
https://www.ncbi.nlm.nih.gov/pubmed/29740328
Marijuana Use Is Not Associated With Progression to Advanced Liver Fibrosis in HIV/Hepatitis C Virus-coinfected Women.
“Marijuana (hereafter “tetrahydrocannabinol [THC]”) use has been associated with liver fibrosis progression in retrospective analyses of patients with chronic hepatitis C (HCV). We studied long-term effects of THC on fibrosis progression in women coinfected with human immunodeficiency virus (HIV)/HCV enrolled in the Women’s Interagency HIV Study (WIHS).
CONCLUSIONS:
In this large cohort of HIV/HCV-coinfected women, THC was not associated with progression to significant liver fibrosis. Alcohol use was independently associated with liver fibrosis, and may better predict fibrosis progression in HIV/HCV-coinfected women.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967608/ https://academic.oup.com/cid/article/63/4/512/2595097]]>Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling
“Progress in research on endocannabinoid signaling has greatly advanced our understanding of how it controls neural circuit excitability in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses seizures by inhibiting glutamate release. In contrast, endocannabinoid signaling promotes seizures by inhibiting GABA release at inhibitory synapses. The physiological distribution of endocannabinoid signaling molecules becomes disrupted with the development of epileptic focus in patients with mesial temporal lobe epilepsy and in animal models of experimentally induced epilepsy. Augmentation of endocannabinoid signaling can promote the development of epileptic focus at initial stages. However, at later stages, increased endocannabinoid signaling delays it and suppresses spontaneous seizures. Thus, the regulation of endocannabinoid signaling at specific synapses that cause hyperexcitability during particular stages of disease development may be effective for treating epilepsy and epileptogenesis.” https://link.springer.com/article/10.1007/s00018-018-2834-8 http://www.x-mol.com/paper/661834]]>
Marijuana smoking does not accelerate progression of liver disease in HIV-hepatitis C coinfection: a longitudinal cohort analysis.
“Marijuana smoking is common and believed to relieve many symptoms, but daily use has been associated with liver fibrosis in cross-sectional studies. We aimed to estimate the effect of marijuana smoking on liver disease progression in a Canadian prospective multicenter cohort of human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfected persons. In this prospective analysis we found no evidence for an association between marijuana smoking and significant liver fibrosis progression in HIV/HCV coinfection.” https://www.ncbi.nlm.nih.gov/pubmed/23811492 “To conclude, in this first prospective evaluation of liver disease progression among HIV-HCV infected persons, we could not demonstrate any important effect of marijuana on liver disease outcomes. A causal association is unlikely: hazard ratios were weak and most importantly were attenuated when accounting for temporality in the exposure-disease relationship and there was no dose-response relationship. It is likely that previous studies have been biased by reverse causality as patients use more marijuana to relieve symptoms as liver disease progresses.” https://academic.oup.com/cid/article/57/5/663/312934]]>
Activation of the Cannabinoid Type 2 Receptor by a Novel Indazole Derivative Normalizes the Survival Pattern of Lymphoblasts from Patients with Late-Onset Alzheimer's Disease.
“Alzheimer’s disease is a multifactorial disorder for which there is no disease-modifying treatment yet.
CB2 receptors have emerged as a promising therapeutic target for Alzheimer’s disease because they are expressed in neuronal and glial cells and their activation has no psychoactive effects.
“Patients with obesity are susceptible to hypertension and diabetes. Over-activation of 
“Δ9-Tetrahydrocannabinol (Δ9-THC) is the active compound of