:
“Stressful conditions affect the brain’s neurotransmission and neural pathways that are involved in seizure susceptibility. Stress alters the intensity and/or frequency of seizures.
Although evidence indicates that chronic stress exerts proconvulsant effects and acute stress has anticonvulsant properties, the underlying mechanisms which mediate these effects are not well understood.
In the present study, we assessed the role of endogenous opioids, endocannabinoids, as well as functional interaction between opioid and cannabinoid systems in the anticonvulsant effects of acute foot-shock stress (FSS) against pentylenetetrazole (PTZ)-induced seizures in mice.
Gut microbiota, cannabinoid system and neuroimmune interactions: New perspectives in multiple sclerosis.
“The gut microbiota plays a fundamental role on the education and function of the host immune system.
Immunological dysregulation is the cause of numerous human disorders such as autoimmune diseases and metabolic disorders frequently associated with inflammatory processes therefore is critical to explore novel mechanisms involved in maintaining the immune system homeostasis.
The cannabinoid system and related bioactive lipids participate in multiple central and peripheral physiological processes that affect metabolic, gastrointestinal and neuroimmune regulatory mechanisms displaying a modulatory role and contributing to the maintenance of the organism’s homeostasis.
In this review, we gather the knowledge on the gut microbiota-endocannabinoids interactions and their impact on autoimmune disorders such as inflammatory bowel disease, rheumatoid arthritis and particularly, multiple sclerosis (MS) as the best example of a CNS autoimmune disorder.
Furthermore, we contribute to this field with new data on changes in many elements of the cannabinoid system in a viral model of MS after gut microbiota manipulation by both antibiotics and probiotics.
Finally, we highlight new therapeutic opportunities, under an integrative view, targeting the eCBS and the commensal microbiota in the context of neuroinflammation and MS.”
https://www.ncbi.nlm.nih.gov/pubmed/30171835
https://www.sciencedirect.com/science/article/abs/pii/S0006295218303630
When Orexins Meet Cannabinoids: Bidirectional Functional Interactions.
“A growing body of evidence suggests the existence of biochemical and functional interactions between the endocannabinoid and orexin systems. Cannabinoid and orexin receptors have been shown to form heterodimers in agreement with the overlapping distribution of both receptors in several brain areas, and the activation of common intracellular signaling pathways, such as the MAP kinase cascade. The activation of orexin receptors induces the synthesis of the endocannabinoid 2-arachidonoyl glycerol suggesting that the endocannabinoid system participates in some physiological functions of orexins. Indeed, functional interactions between these two systems have been demonstrated in several behavioral responses including nociception, reward and food intake. The present review is focused on the latest developments in cannabinoid-orexin cross-modulation and the implications of this interesting interaction.”
https://www.ncbi.nlm.nih.gov/pubmed/30171834
https://www.sciencedirect.com/science/article/abs/pii/S0006295218303666
“The recent legalization of recreational marijuana use in some parts of the world, the discovery of new indications for the clinical application of 
“Compounds extracted from the cannabis plant, including the psychoactive Δ9-tetrahydrocannabinol (THC) and related phytocannabinoids, evoke multiple diverse biological actions as ligands of the G protein-coupled 
“Anticonvulsant effects of cannabidiol (CBD), a nonpsychoactive 
“This meta-analysis paper describes the analysis of observational clinical studies on the treatment of refractory epilepsy with cannabidiol (CBD)-based products. Beyond attempting to establish the safety and efficacy of such products, we also investigated if there is enough evidence to assume any difference in efficacy between CBD-rich extracts compared to purified CBD products.
The systematic search took place in February/2017 and updated in December/2017 using the keywords “epilepsy” or “Dravet” or “Lennox-Gastaut” or “CDKL5” combined with “Cannabis”, “cannabinoid”, “cannabidiol” or “CBD” resulting in 199 papers. The qualitative assessment resulted in 11 valid references, with an average impact factor of 8.1 (ranging from 1.4 to 47.8). The categorical data of a total of 670 patients were analyzed by Fischer test. The average daily dose ranged between 1 and 50 mg/kg, with treatment length from 3 to 12 months (mean 6.2 months).
Two thirds of patients reported improvement in the frequency of convulsive crisis (399/622, 64%). There were more reports of improvement from patients treated with CBD-rich extracts (318/447, 71%) than patients treated with purified CBD (81/223, 36%), with statistical significance (p<0.0001).
Nevertheless, when the standard clinical threshold of a “50% reduction or more in the frequency of convulsive crisis” was applied, only 39% of the individuals were considered “responders”, and there was no difference (p=0.56) between treatments with CBD-rich extracts (97/255, 38%) and purified CBD (94/223, 42%).
Patients treated with CBD-rich extracts reported lower average dose (6.1 mg/kg/day) than those using purified CBD (27.1 mg/kg/day). The reports of mild (109/285 vs 291/346, p<0.0001) and severe (23/285 vs 77/346, p<0.0001) adverse effects were more frequent in products containing purified CBD than in CBD-rich extracts.
CBD-rich extracts seem to present a better therapeutic profile than purified CBD, at least in this population of patients with refractory epilepsy. The roots of this difference is likely due to synergistic effects of CBD with other phytocompounds (aka Entourage effect), but this remains to be confirmed in controlled clinical studies.”