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[Beneficial Effect of Medical Cannabis in the Treatment of a Pharmacoresistant Nausea Associated with a Somatoform Disorder in a Patient with Post-Polio Syndrome].

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“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

Extraction Method and Analysis of Cannabinoids in Cannabis Olive Oil Preparations.

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“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

β-Amyrin, the cannabinoid receptors agonist, abrogates mice brain microglial cells inflammation induced by lipopolysaccharide/interferon-γ and regulates Mφ1/Mφ2 balances.

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“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

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Nutritional Value of Commercial Protein-Rich Plant Products.

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 Plant Foods for Human Nutrition

“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

Role of cannabinoid receptor type 1 in rostral ventrolateral medulla in high-fat diet-induced hypertension in rats.

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“Stimulation of cannabinoid type 1 (CB1) receptor in the rostral ventrolateral medulla (RVLM) increases renal sympathetic activity (RSNA) and blood pressure (BP) in rats. Thus, we hypothesized that CB1 receptor in the RVLM may play a critical role in the development of obesity-induced hypertension.

METHODS:

To this end, we evaluated the levels of endocannabinoids and CB1 receptors in the RVLM in high-fat diet (HFD)-induced hypertensive rats. We then used pharmacological and molecular methods to examine the role of RVLM CB1 receptors in regulation of BP, heart rate (HR), and RSNA in obesity-induced hypertensive rats.

RESULTS:

We found that HFD-fed rats exhibited higher basal BP, HR, and RSNA than standard diet-fed rats, which were associated with increased levels of endocannabinoids and CB1 receptor expression in the RVLM. Furthermore, unilateral intra-RVLM microinjections of AM251 (0, 100, or 500 nM/0.5 μl/site) dose-dependently decreased BP, HR, and RSNA to a greater extent in HFD-fed rats than in standard diet-fed rats. Finally, siRNA-mediated knockdown of CB1 receptor expression in the RVLM robustly decreased BP, HR, and RSNA in HFD-fed rats.

CONCLUSION:

Taken together, our results suggested that enhanced CB1 receptor-mediated neurotransmissions in the RVLM may play a role in the development of obesity-induced hypertension.”

https://www.ncbi.nlm.nih.gov/pubmed/29493561

https://insights.ovid.com/crossref?an=00004872-201804000-00015

Toxicity, Cannabinoids.

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Cover of StatPearls

“Cannabinoids are a collective group of compounds that act on cannabinoid receptors. They include plant-derived phytocannabinoids, synthetic cannabinoids, and endogenously-derived endocannabinoids. The primary source of cannabinoid toxicity is from plant-derived cannabinoids and synthetic cannabinoids. These agents act as cannabinoid receptor agonists. More than 60 naturally occurring cannabinoids are found in the Sativa and Indica species of Cannabis, with delta-9 tetrahydrocannabinol (THC) being the main psychoactive compound. Other naturally occurring cannabinoids include cannabidiol and cannabinol. Marijuana is the most common colloquial name for crushed, dried leaves and flowers of the Cannabis plant. In recent years, there have been many reports of marijuana toxicity, primarily in the pediatric population, as medical and recreational marijuana has been legalized. The terms phytocannabinoids, marijuana and cannabis are used interchangeably. Synthetic cannabinoids were created for therapeutic and research purposes; however, despite legal efforts to limit their availability, synthetic cannabinoids have become an increasingly common drug of abuse, sold under various street names such as K2, Spice, and Black Mamba. Synthetic cannabinoids are associated with much more morbidity and mortality than the phytocannabinoids. Prescription preparations for medical usage include dronabinol, or pure THC, nabilone, a synthetic cannabinoid, and cannabidiol (CBD). Pharmaceutical use of cannabinoids is an ongoing field of research.”

https://www.ncbi.nlm.nih.gov/pubmed/29489164

https://www.ncbi.nlm.nih.gov/books/NBK482175/

Innovative Therapeutic Potential of Cannabinoid Receptors as Targets in Alzheimer’s disease and Less Well-Known Diseases.

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“The discovery of cannabinoid receptors at the beginning of the 1990s, CB1 being cloned in 1990 and CB2 cloned in 1993, and the availability of selective and potent cannabimimetics could only be justified by the existence of endogenous ligands that are capable of binding to them. Thus, the characterisation and cloning of the first cannabinoid receptor (CB1) led to the isolation and characterisation of the first endocannabinoid, arachidonoylethanolamide (AEA), two years later and the subsequent identification of a family of lipid transmitters known as the fatty acid ester 2-arachidonoylglycerol (2-AG). The endogenous cannabinoid system is a complex signalling system that comprises transmembrane endocannabinoid receptors, their endogenous ligands (the endocannabinoids), the specific uptake mechanisms and the enzymatic systems related to their biosynthesis and degradation. The endocannabinoid system has been implicated in a wide diversity of biological processes, in both the central and peripheral nervous systems, including memory, learning, neuronal development, stress and emotions, food intake, energy regulation, peripheral metabolism, and the regulation of hormonal balance through the endocrine system. In this context, this article will review the current knowledge of the therapeutic potential of cannabinoid receptor as a target in Alzheimer’s disease and other less well-known diseases that include, among others, multiple sclerosis, bone metabolism, and Fragile X syndrome. The therapeutic applications will be addressed through the study of cannabinoid agonists acting as single drugs and multi-target drugs highlighting the CB2 receptor agonist.”

https://www.ncbi.nlm.nih.gov/pubmed/29484980

http://www.eurekaselect.com/160083/article

2-AG limits Theiler’s virus induced acute neuroinflammation by modulating microglia and promoting MDSCs.

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 Glia

“The innate immune response is mediated by primary immune modulators such as cytokines and chemokines that together with immune cells and resident glia orchestrate CNS immunity and inflammation. Growing evidence supports that the endocannabinoid 2-arachidonoylglycerol (2-AG) exerts protective actions in CNS injury models. Here, we used the acute phase of Theiler’s virus induced demyelination disease (TMEV-IDD) as a model of acute neuroinflammation to investigate whether 2-AG modifies the brain innate immune responses to TMEV and CNS leukocyte trafficking. 2-AG or the inhibition of its hydrolysis diminished the reactivity and number of microglia at the TMEV injection site reducing their morphological complexity and modulating them towards an anti-inflammatory state via CB2 receptors. Indeed, 2-AG dampened the infiltration of immune cells into the CNS and inhibited their egress from the spleen, resulting in long-term beneficial effects at the chronic phase of the disease. Intriguingly, it is not a generalized action over leukocytes since 2-AG increased the presence and suppressive potency of myeloid derived suppressor cells (MDSCs) in the brain resulting in higher apoptotic CD4+ T cells at the injection site. Together, these data suggest a robust modulatory effect in the peripheral and central immunity by 2-AG and highlight the interest of modulating endogenous cannabinoids to regulate CNS inflammatory conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/29484707

http://onlinelibrary.wiley.com/doi/10.1002/glia.23317/abstract

Medical marijuana laws and adolescent marijuana use in the United States: A systematic review and meta-analysis.

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“To conduct a systematic review and meta-analysis of studies in order to estimate the effect of US medical marijuana laws (MMLs) on past-month marijuana use prevalence among adolescents.

METHODS:

A total of 2999 papers from 17 literature sources were screened systematically. Eleven studies, developed from four ongoing large national surveys, were meta-analyzed. Estimates of MML effects on any past-month marijuana use prevalence from included studies were obtained from comparisons of pre-post MML changes in MML states to changes in non-MML states over comparable time-periods. These estimates were standardized and entered into a meta-analysis model with fixed-effects for each study. Heterogeneity among the study estimates by national data survey was tested with an omnibus F-test. Estimates of effects on additional marijuana outcomes, of MML provisions (e.g. dispensaries) and among demographic subgroups were abstracted and summarized. Key methodological and modeling characteristics were also described. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed.

RESULTS:

None of the 11 studies found significant estimates of pre-post MML changes compared with contemporaneous changes in non-MML states for marijuana use prevalence among adolescents. The meta-analysis yielded a non-significant pooled estimate (standardized mean difference) of -0.003 (95% confidence interval = -0.012, +0.007). Four studies compared MML with non-MML states on pre-MML differences and all found higher rates of past-month marijuana use in MML states pre-MML passage. Additional tests of specific MML provisions, of MML effects on additional marijuana outcomes and among subgroups generally yielded non-significant results, although limited heterogeneity may warrant further study.

CONCLUSIONS:

Synthesis of the current evidence does not support the hypothesis that US medical marijuana laws (MMLs) until 2014 have led to increases in adolescent marijuana use prevalence. Limited heterogeneity exists among estimates of effects of MMLs on other patterns of marijuana use, of effects within particular population subgroups and of effects of specific MML provisions.”

https://www.ncbi.nlm.nih.gov/pubmed/29468763

Exogenous Cannabinoid Efficacy: Merely a Pharmacokinetic Interaction?

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Clinical Pharmacokinetics

“Endocannabinoid pharmacology is now relatively well understood with a number of endocannabinoids and endogenous cannabinoid neurotransmitters identified and the pharmacokinetics relatively well ascertained.

Further, the cannabinoid receptors are now molecularly and pharmacologically characterised and the cell processes involved in endocannabinoid transcription, synthesis, post-translational modification and protein expression are reported.

Endogenous cannabinoids have been shown to have key roles in immune and pain pathways and neuro-behavioural signalling including appetite regulation. Significant recent interest has thus been shown in understanding these pathways to guide the development of agents that inhibit the natural catabolism of endogenous cannabinoids to modify pain and appetite, and to synthesise antagonists for the treatment of disease such as obesity.

This research is concurrent with the renewed clinical interest in exogenous cannabinoids and their use in disease. However, the complex pharmacology and physiological effects of exogenous cannabinoids, either as individual components or in combination, as extracts or via administration of the whole plant in humans, are less well known.

Yet as with all other therapeutics, including those derived from plants, knowledge of the pharmacokinetics and dynamics of the complete plant, the individual chemical molecules and their synthetic versions, including formulations and excipients is a standard part of drug development.

This article covers the key pharmacological knowledge required to guide further exploration of the toxicity and efficacy of different cannabinoids and their formulations in blinded placebo-controlled studies.”

https://www.ncbi.nlm.nih.gov/pubmed/28921125

https://link.springer.com/article/10.1007%2Fs40262-017-0599-0