“Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy.
Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL).
Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5-55 years).
Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17).
CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs.
Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed.”
https://www.ncbi.nlm.nih.gov/pubmed/29511052
http://jnnp.bmj.com/content/early/2018/02/05/jnnp-2017-317168
Evaluation of Marijuana Compounds on Neuroimmune Endpoints in Experimental Autoimmune Encephalomyelitis.
“Cannabinoid compounds refer to a group of more than 60 plant-derived compounds in Cannabis sativa, more commonly known as marijuana. Exposure to marijuana and cannabinoid compounds has been increasing due to increased societal acceptance for both recreational and possible medical use. Cannabinoid compounds suppress immune function, and while this could compromise one’s ability to fight infections, immune suppression is the desired effect for therapies for autoimmune diseases. It is critical, therefore, to understand the effects and mechanisms by which cannabinoid compounds alter immune function, especially immune responses induced in autoimmune disease. Therefore, this unit will describe induction and assessment of the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and its potential alteration by cannabinoid compounds. The unit includes three approaches to induce EAE, two of which provide correlations to two forms of MS, and the third specifically addresses the role of autoreactive T cells in EAE.” https://www.ncbi.nlm.nih.gov/pubmed/29512125 http://onlinelibrary.wiley.com/doi/10.1002/cptx.43/abstract]]>
Marijuana Use and Renal Function Among US Adults.
“In recent years, the number of states that have legalized medical marijuana or retail sales has increased, bringing potential changes of marijuana use pattern among the general population. However, health effects of acute and chronic marijuana use on many relevant health outcomes, including renal function, remain largely unexamined. In this study, we aimed to assess the association between recent and past marijuana use and renal function.
CONCLUSIONS:
We did not observe any clinically significant association between current or past self-reported marijuana use and measures of kidney function.” https://www.ncbi.nlm.nih.gov/pubmed/29291894 http://www.amjmed.com/article/S0002-9343(17)31193-2/fulltext“No link between current or previous marijuana use and kidney disease, say researchers” https://www.sciencedaily.com/releases/2018/03/180301125051.htm
“Marijuana Doesn’t Seem to Harm the Kidneys” https://www.webmd.com/mental-health/addiction/news/20180306/marijuana-doesnt-seem-to-harm-the-kidneys
“”Our research provides some reassuring evidence suggesting that there is no detrimental effect of infrequent, relatively light use of marijuana on kidney function among healthy adults under age 60,”” https://consumer.healthday.com/general-health-information-16/illicit-drugs-news-217/marijuana-doesn-t-seem-to-harm-the-kidneys-731632.html“Pot Won’t Harm Healthy Young People’s Kidneys, Study Suggests” https://www.medicinenet.com/script/main/art.asp?articlekey=206375
]]>The anxiolytic effects of cannabidiol in chronically stressed mice are mediated by the endocannabinoid system: Role of neurogenesis and dendritic remodeling.
“Repeated injections of cannabidiol (CBD), the major non-psychotomimetic compound present in the Cannabis sativa plant, attenuate the anxiogenic effects induced by Chronic Unpredictable Stress (CUS). The specific mechanisms remain to be fully understood but seem to involve adult hippocampal neurogenesis and recruitment of endocannabinoids.
Here we investigated for the first time if the behavioral and pro-neurogenic effects of CBD administered concomitant the CUS procedure (14 days) are mediated by CB1, CB2 or 5HT1A receptors, as well as CBD effects on dendritic remodeling and on intracellular/synaptic signaling (fatty acid amide hydrolase – FAAH, Akt, GSK3β and the synaptic proteins Synapsin Ia/b, mGluR1 and PSD95).
After 14 days, CBD injections (30 mg/kg) induced anxiolytic responses in stressed animals in the elevated plus-maze and novelty suppressed feeding tests, that were blocked by pre-treatment with a CB1 (AM251, 0.3 mg/kg) or CB2 (AM630, 0.3 mg/kg), but not by a 5HT1A (WAY100635, 0.05 mg/kg) receptor antagonist. Golgi staining and immunofluorescence revealed that these effects were associated with an increase in hippocampal neurogenesis and spine density in the dentate gyrus of the hippocampus. AM251 and AM630 abolished the effects of CBD on spines density. However, AM630 was more effective in attenuating the pro-neurogenic effects of CBD. CBD decreased FAAH and increased p-GSK3β expression in stressed animals, which was also attenuated by AM630.
These results indicate that CBD prevents the behavioral effects caused by CUS probably due to a facilitation of endocannabinoid neurotransmission and consequent CB1/CB2receptors activation, which could recruit intracellular/synaptic proteins involved in neurogenesis and dendritic remodeling.”
https://www.ncbi.nlm.nih.gov/pubmed/29510186
https://www.sciencedirect.com/science/article/pii/S0028390818301023
[Beneficial Effect of Medical Cannabis in the Treatment of a Pharmacoresistant Nausea Associated with a Somatoform Disorder in a Patient with Post-Polio Syndrome].
“We report a 79-year-old patient with post-polio syndrome (PPS). In the course of this disease, recurrent upper abdominal pain and a therapy-resistant nausea developed without vomiting. In addition, the patient was limited by the combination of muscular weakness, obesity, dietary-treated diabetes and a degenerative spinal cord injury significantly in its mobility and physical capacity.
INVESTIGATIONS AND DIAGNOSIS:
Despite extensive diagnostics, no somatic cause could be found neither for the nausea nor for the upper abdominal pain. Due to the psychological stress within the scope of the PPS, the development of a somatoform autonomic function disorder of the upper gastrointestinal tract may have occurred.TREATMENT AND COURSE:
Even under combination therapy of antiemetic and pain-modulating drugs, no adequate symptom control could be achieved. In the absence of therapy alternatives and increasing psychological strain the patient was prescribed medical cannabis. Under the therapy there was a relief of the nausea symptoms and decreased pain.CONCLUSION:
Cannabis is a treatment option for treatment-resistant symptoms as part of a PPS.” https://www.ncbi.nlm.nih.gov/pubmed/29506301 https://www.thieme-connect.de/DOI/DOI?10.1055/s-0043-123897]]>Impact of Chronic Cannabis Use on Auditory Mismatch Negativity Generation in Schizophrenia Patients.
“Cannabis use disorders (CUD) are highly prevalent among patients with schizophrenia (SCZ). Deficient mismatch negativity (MMN) generation is a characteristic finding in SCZ patients and cannabis users. This study therefore examined the effects of CUD on MMN generation in SCZ patients.
These results demonstrate that comorbid cannabis use in SCZ patients might be associated with superior cognitive functioning. It can be assumed that the association between cannabis use and better cognitive performance may be due to a subgroup of cognitively less impaired SCZ patients characterized by lower genetic vulnerability for psychosis.”
https://www.ncbi.nlm.nih.gov/pubmed/29506304 https://www.thieme-connect.de/DOI/DOI?10.1055/a-0573-9866]]>Extraction Method and Analysis of Cannabinoids in Cannabis Olive Oil Preparations.
“Recently, an increasing number of pharmacists had to supply medicinal products based on Cannabis sativa L. (Cannabaceae), prescribed by physicians to individual patients.
Cannabis olive oil preparation is the first choice as a concentrated extract of cannabinoids, even though standardized operative conditions for obtaining it are still not available.
In this work, the impact of temperature and extraction time on the concentration of active principles was studied to harmonize the different compounding methods, optimize the extraction process, and reduce the variability among preparations.“
https://www.ncbi.nlm.nih.gov/pubmed/29202510
https://www.thieme-connect.de/DOI/DOI?10.1055/s-0043-123074
“Therapeutic Use of Δ9-THC and Cannabidiol: Evaluation of a New Extraction Procedure for the Preparation of Cannabis-based Olive Oil.” https://www.ncbi.nlm.nih.gov/pubmed/29189144
]]>The inhibition of CB1 receptor accelerates the onset and development of EAE possibly by regulating microglia/macrophages polarization.
“Cannabinoid 1 receptor (CB1R) regulates the neuro-inflammatory and neurodegenerative damages of experimental autoimmune encephalomyelitis (EAE) and of multiple sclerosis (MS). The mechanism by which CB1R inhibition exerts inflammatory effects is still unclear. Here, we explored the cellular and molecular mechanisms of CB1R in the treatment of EAE by using a specific and selective CB1R antagonist SR141716A. Our study demonstrated that SR141716A accelerated the clinical onset and development of EAE, accompanied by body weight loss. SR141716A significantly up-regulated the expression of toll like receptor-4 (TLR-4) and nuclear factor-kappaB/p65 (NF-κB/p65) on microglia/macrophages of EAE mice as well as levels of inflammatory factors (TNF-α, IL-1β, IL-6) and chemokines (MCP-1, CX3CL1), accompanied by the shifts of cytokines from Th2 (IL-4, IL-10) to Th1 (IFN-γ)/Th17 (IL-17) in the spinal cords of EAE mice. Similar changes happened on splenic mononuclear cells (MNCs) except chemokine CX3CL1. Consistently, SR141716A promoted BV-2 microglia to release inflammatory factors (TNF-α, IL-1β, IL-6) while inhibited the production of IL-10 and chemokines (MCP-1, CX3CL1). Furthermore, when splenic CD4+ T cells co-cultured with SR141716A-administered BV-2 microglia, the levels of IL-4 and IL-10 were decreased while production of IL-17 and IFN-γ increased significantly. Our research indicated that inhibition of CB1R induced M1 phenotype-Th17 axis changed of microglia/macrophages through TLR-4 and NF-κB/p65 which accelerated the onset and development of EAE. Therefore, CB1R may be a promising target for the treatment of MS/EAE, but its complexity remains to be carefully considered and studied in further clinical application.” https://www.ncbi.nlm.nih.gov/pubmed/29501084 http://www.jni-journal.com/article/S0165-5728(17)30467-8/fulltext]]>
β-Amyrin, the cannabinoid receptors agonist, abrogates mice brain microglial cells inflammation induced by lipopolysaccharide/interferon-γ and regulates Mφ1/Mφ2 balances.
“Inflammation is a primary response to infection that can pathologically lead to various diseases including neurodegenerative diseases. The purpose of this study was to evaluate the effect of β-Amyrin, a naturally occurring pentacyclic triterpenoid compound, on inflammation induced by lipopolysaccharide (LPS) and interferone-γ (IFN-γ) in rat microglial cells.
CONCLUSION:
β-Amyrin reduces inflammation in microglial cells and can be used as a potential anti-inflammatory agent in central nervous system neurodegenerative diseases such as Alzheimer and multiple sclerosis, by affecting the inflammatory cytokine and differentiation of microglia as resident CNS macrophages.” https://www.ncbi.nlm.nih.gov/pubmed/29501766 “Amyrin and the endocannabinoid system. The canonical triterpene amyrin was recently suggested to bind to CB1 receptors and to significantly mediate cannabimimetic effects in animal models of pain.” http://gertschgroup.com/blog/entry/3188293/amyrin-and-the-endocannabinoid-system“The antinociceptive triterpene β-amyrin inhibits 2-arachidonoylglycerol (2-AG) hydrolysis without directly targeting CB receptors” https://www.researchgate.net/publication/225079976_The_antinociceptive_triterpene_b-amyrin_inhibits_2-arachidonoylglycerol_2-AG_hydrolysis_without_directly_targeting_CB_receptors
“Finally, pentacyclic triterpenes such as β-amyrin and cycloartenol have been shown to possess numerous biological activities including anti-bacterial, anti-fungal, anti-inflammatory and anti-cancer properties.” https://www.linkedin.com/pulse/cannabis-has-terpenes-say-what-pure-hempnotics
]]>
Nutritional Value of Commercial Protein-Rich Plant Products.
“The goal of this work was to analyze nutritional value of various minimally processed commercial products of plant protein sources such as faba bean (Vicia faba), lupin (Lupinus angustifolius), rapeseed press cake (Brassica rapa/napus subsp. Oleifera), flaxseed (Linum usitatissimum), oil hemp seed (Cannabis sativa), buckwheat (Fagopyrum esculentum), and quinoa (Chenopodium quinoa). Basic composition and various nutritional components like amino acids, sugars, minerals, and dietary fiber were determined. Nearly all the samples studied could be considered as good sources of essential amino acids, minerals and dietary fiber. The highest content of crude protein (over 30 g/100 g DW) was found in faba bean, blue lupin and rapeseed press cake. The total amount of essential amino acids (EAA) ranged from 25.8 g/16 g N in oil hemp hulls to 41.5 g/16 g N in pearled quinoa. All the samples studied have a nutritionally favorable composition with significant health benefit potential. Processing (dehulling or pearling) affected greatly to the contents of analyzed nutrients.”
https://www.ncbi.nlm.nih.gov/pubmed/29500810
https://link.springer.com/article/10.1007%2Fs11130-018-0660-7