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Cannabinoid-induced increase of quantal size and enhanced neuromuscular transmission.

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Scientific Reports

“Cannabinoids exert dynamic control over many physiological processes including memory formation, cognition and pain perception. In the central nervous system endocannabinoids mediate negative feedback of quantal transmitter release following postsynaptic depolarization. The influence of cannabinoids in the peripheral nervous system is less clear and might have broad implications for the therapeutic application of cannabinoids. We report a novel cannabinoid effect upon the mouse neuromuscular synapse: acutely increasing synaptic vesicle volume and raising the quantal amplitudes. In a mouse model of myasthenia gravis the cannabinoid receptor agonist WIN 55,212 reversed fatiguing failure of neuromuscular transmission, suggesting future therapeutic potential. Our data suggest an endogenous pathway by which cannabinoids might help to regulate transmitter release at the neuromuscular junction.”

https://www.ncbi.nlm.nih.gov/pubmed/29549349

“Here we reveal evidence of their involvement in regulating neuromuscular transmission, and a possible therapeutic potential for cannabinoid signaling in myasthenia gravis. Our results suggest that cannabinoids might play a role in sustaining neuromuscular transmission.”

https://www.nature.com/articles/s41598-018-22888-4

Reduced levels of the endocannabinoid arachidonylethanolamide (AEA) in hair in patients with borderline personality disorder – a pilot study.

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“Endocannabinoids are involved in depressive and anxious symptoms and might play a role in stress-associated psychiatric disorders.

While alterations in the endogenous cannabinoid system have been repeatedly found in patients with posttraumatic stress disorder (PTSD), this system has been mostly neglected in borderline personality disorder (BPD). However, there is first evidence for elevated serum levels of the endocannabinoids arachidonylethanolamide (AEA) and 2-arachidonyl-sn-glycerol (2-AG) in BPD patients compared to healthy controls and PTSD patients.

In this study, hair endocannabinoids were analyzed, reflecting long-term endocannabinoid concentrations. We assessed AEA concentrations as well as 2-AG and the 2-AG main isomer 1-AG (1-AG/2-AG) in hair in women with BPD (n = 15) and age- and education-matched healthy women (n = 16).

We found significantly reduced log AEA in BPD patients compared to healthy women (p = .03) but no differences in log 1-AG/2-AG concentrations. In addition, there was no association between 1-AG/2-AG and hair cortisol, but we found a non-significant correlation between hair concentrations of AEA and cortisol (p = .06).

Our data indicate altered long-term release of endogenous cannabinoids in women with BPD depending on type of endocannabinoid. AEA has been suggested to modulate the basal activity of the endocannabinoid system and seems to attenuate depressive and anxious symptoms. Thus, chronically reduced AEA might contribute to psychiatric symptoms in BPD.”

https://www.ncbi.nlm.nih.gov/pubmed/29546791

https://www.tandfonline.com/doi/abs/10.1080/10253890.2018.1451837?journalCode=ists20

Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System.

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“The biological effects of cannabinoids, the major constituents of the ancient medicinal plant Cannabis sativa (marijuana) are mediated by two members of the G-protein coupled receptor family, cannabinoid receptors 1 (CB1R) and 2. The CB1R is the prominent subtype in the central nervous system (CNS) and has drawn great attention as a potential therapeutic avenue in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Furthermore, cannabinoids also modulate signal transduction pathways and exert profound effects at peripheral sites. Although cannabinoids have therapeutic potential, their psychoactive effects have largely limited their use in clinical practice. In this review, we briefly summarized our knowledge of cannabinoids and the endocannabinoid system, focusing on the CB1R and the CNS, with emphasis on recent breakthroughs in the field. We aim to define several potential roles of cannabinoid receptors in the modulation of signaling pathways and in association with several pathophysiological conditions. We believe that the therapeutic significance of cannabinoids is masked by the adverse effects and here alternative strategies are discussed to take therapeutic advantage of cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/29533978

http://www.mdpi.com/1422-0067/19/3/833

Cannabis Vaporizer Combines Efficient Delivery of THC with Effective Suppression of Pyrolytic Compounds

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“Cannabis vaporization is a technology designed to deliver inhaled cannabinoids while avoiding the respiratory hazards of smoking by heating cannabis to a temperature where therapeutically active cannabinoid vapors are produced, but below the point of combustion where noxious pyrolytic byproducts are formed.

This study was designed to evaluate the efficacy of an herbal vaporizer known as the Volcano®, produced by Storz & Bickel GmbH&Co. KG, Tuttlingen, Germany. Three 200 mg samples of standard NIDA cannabis were vaporized at temperatures of 155°–218°C. For comparison, smoke from combusted samples was also tested.

The study consisted of two phases: (1) a quantitative analysis of the solid phase of the vapor using HPLC-DAD-MS (High Performance Liquid Chromatograph-Diode Array-Mass Spectrometry) to determine the amount of cannabinoids delivered; (2) a GC/MS (Gas Chromatograph/ Mass Spectrometer) analysis of the gas phase to analyze the vapor for a wide range of toxins, focusing on pyrene and other polynuculear aromatic hydrocarbons (PAHs).

The HPLC analysis of the vapor found that the Volcano delivered 36%–61% of the THC in the sample, a delivery efficiency that compares favorably to that of marijuana cigarettes.

The GC/MS analysis showed that the gas phase of the vapor consisted overwhelmingly of cannabinoids, with trace amounts of three other compounds. In contrast, over 111 compounds were identified in the combusted smoke, including several known PAHs.

The results indicate that vaporization can deliver therapeutic doses of cannabinoids with a drastic reduction in pyrolytic smoke compounds. Vaporization therefore appears to be an attractive alternative to smoked marijuana for future medical cannabis studies.”

https://www.tandfonline.com/doi/abs/10.1300/J175v04n01_02

[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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“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/