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

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

Pharmacological characterization of the cannabinoid receptor 2 agonist, β-caryophyllene on seizure models in mice.

Seizure - European Journal of Epilepsy Home

“Activation of CB1 receptors, produces anticonvulsant effect accompanied by memory disturbance both in animal seizure tests and in patients with epilepsy.

Few reports considered the role of CB2 receptor on seizure susceptibility and cognitive functions. The aim of the present study was to explore the effect of a selective CB2 receptor agonist β-caryophyllene (BCP) in models of seizures and cognition in mice.

CONCLUSION:

Our results suggest that the CB2 receptor agonists might be clinically useful as an adjunct treatment against seizure spread and status epilepticus and concomitant oxidative stress, neurotoxicity and cognitive impairments.”

https://www.ncbi.nlm.nih.gov/pubmed/29547827

http://www.seizure-journal.com/article/S1059-1311(17)30611-8/fulltext

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”  http://www.ncbi.nlm.nih.gov/pubmed/23138934

Pascal Biosciences Identifies Molecules in Cannabis That Stimulate the Immune System to Destroy Tumor Cells

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“Pascal Biosciences Inc. (TSX.V:PAS) (“Pascal” or the “Company”) announced the Company has discovered certain cannabinoids that enhance the immunogenicity of tumor cells, rendering them more susceptible to recognition by the immune system. This discovery is important because the leading class of new cancer fighting agents, termed “checkpoint inhibitors”, activates the immune system to destroy cancer cells. Enhancing recognition of cancer cells with cannabinoids may greatly improve the efficacy of this drug class. Cannabinoids are the chemical compounds which give the cannabis plant its medicinal properties with over 100 different cannabinoids identified. There is a growing body of research demonstrating the effectiveness of cannabinoids in the treatment of cancer symptoms, including nausea, appetite enhancement, and pain management. However, Pascal is the first to identify a mechanism in which cannabinoids may provide a direct benefit in immunotherapy.”

https://globenewswire.com/news-release/2018/02/21/1372706/0/en/Pascal-Biosciences-Identifies-Molecules-in-Cannabis-That-Stimulate-the-Immune-System-to-Destroy-Tumor-Cells.html

““We are very excited about this novel discovery,” commented Dr. Patrick Gray, CEO of Pascal Biosciences.” Cannabinoids typically have good pharmacological properties, as most have low toxicity and are easily absorbed into the blood, which are great advantages for drug development. In combination with immune checkpoint inhibitors, cannabinoids may significantly improve cancer care. ”We wish to highlight specifically the line “Pascal is the first to identify a mechanism in which cannabinoids may provide a direct benefit in immunotherapy”.” http://nasdaqnewsreports.blogspot.com/2018/02/pascal-biosciences-cannabis.html
“Pascal Biosciences Stock Soars on New Cannabinoids Discovery” https://smallcappower.com/news/market-news/pascal-biosciences-inc-stock/

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

Publication Cover

“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

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

Toxicity, Cannabinoids.

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/

Effect of marijuana on Essential Tremor: A case report

MDS Abstracts

“Objective: Examine the effectiveness of THC marijuana versus non-THC marijuana on handwriting in Essential Tremor.

Background: Essential tremor (ET) is a chronic movement disorder which can be quite debilitating. ET is often progressive, beginning as a mild visible tremor with little or no impact on activities of daily living (ADLs) but tends to increase in severity over the course of years, often to the extent that people with ET may have extreme difficulty with task such as writing, drinking, eating, shaving, or putting on make-up. Unfortunately, a certain portion of people with ET are either intolerant or unresponsive to the currently recommended treatments. Patients occasionally report improvement in ET after marijuana use. While reports exist of THC effect on tremor in patients with Multiple Sclerosis (MS) and Parkinson’s disease (PD), the same is not true for ET.

Methods: Case Report.

Results: Patient JB, a retired psychologist, had long-standing severe familial tremor significantly interfering with ADLs. Standard treatments were tried. Primidone was partially effective, but resulted in erectile dysfunction and anorgasmia. Propranolol was mildly effective, but was switched to metoprolol by his cardiologist. Gabapentin was ineffective and caused GI distress. Topiramate was ineffective. Diazepam and alcohol were effective but used only occasionally due to sedating effects. While on a family vacation in a state with legalized marijuana, JB recorded his handwriting at baseline, after using an oral non-THC marijuana derivative, after using standard marijuana (oral), and after using alcohol. Handwriting was moderately improved after taking the THC preparation, as well as after taking alcohol; the improvement was roughly equivalent with these two treatments. It did not improve with the non-THC preparation.

Conclusions: This case report suggests 1) handwriting in ET may be improved with the use of THC, 2) handwriting in ET may not be improved with non-THC derivatives of marijuana, and 3) the effect of THC in this case was similar to that of alcohol. While there have been several small studies and case reports addressing the efficacy of marijuana in controlling tremor in PD and MS, no such studies have been conducted regarding ET and the use of marijuana and its derivatives for control of ET is currently considered category U due to insufficient evidence. Further investigation of the potential efficacy of marijuana for ET is clearly warranted.” http://www.mdsabstracts.org/abstract/effect-of-marijuana-on-essential-tremor-a-case-report/

Effect of marijuana on Essential Tremor: A case report

Marijuana May Improve Essential Tremor and Parkinson’s”  http://parkinsonsclinic.com/1/post/2016/05/marijuana-may-improve-essential-tremor-and-parkinsons.html

 

Time-dependent effect of phytocannabinoid treatments in fat cells.

Image result for Phytother Res

“The objectives of this paper is to investigate, demonstrate, and compare the mechanism of action of phytocannabinoids as antidiabetic and anti-obesity agents in preadipocytes and adipocytes, relative to rosiglitazone and metformin.

Briefly, cannabis extract, Δ9 -tetrahydrocannabinol and cannabidiol (in very low dosages) were shown to promote glucose uptake higher or to equivalent levels, reduce fat accumulation, and reverse the insulin-resistant state of 3T3-L1 cells more effectively, relative to rosiglitazone and metformin. The phytocannabinoids had a more pronounced effect in preadipocytes undifferentiated model rather than the differentiated model. They induced a protective effect at the mitochondrial level by preventing overactivity of the succinate dehydrogenase pathway (p < .01), unlike rosiglitazone, through activation of the glycerol-3-phosphate dehydrogenase shuttling system. An increase in oxygen consumption and an increased expression of beta to alpha adrenoceptors (p < .05) in treated cells were noted.

These findings contribute toward understanding the mechanism of action of phytocannabinoids in fat cells and highlight the antidiabetic and anti-obesity properties of various phytocannabinoids that could potentially support the treatment of obesity-related insulin resistance.”

https://www.ncbi.nlm.nih.gov/pubmed/29464872

Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability.

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“Cannabinoids combined with opioids produce synergistic antinociceptive effects, decreasing the lowest effective antinociceptive opioid dose (i.e., opioid-sparing effects) in laboratory animals.

Although pain patients report greater analgesia when cannabis is used with opioids, no placebo-controlled studies have assessed the direct effects of opioids combined with cannabis in humans or the impact of the combination on abuse liability.

This double-blind, placebo-controlled, within-subject study determined if cannabis enhances the analgesic effects of low dose oxycodone using a validated experimental model of pain and its effects on abuse liability.

Cannabis enhances the analgesic effects of sub-threshold oxycodone, suggesting synergy, without increases in cannabis’s abuse liability. These findings support future research into the therapeutic use of opioid-cannabinoid combinations for pain.”

The Role of Cannabinoid Receptor 1 in the Immunopathology of Respiratory Syncytial Virus.

Mary Ann Liebert, Inc. publishers

“Endocannabinoid system plays an important role in pathophysiologic processes such as immune functions and impacts on disease severity.

Our previous study showed that cannabinoid receptor 2 (CB2) affects clinical course of respiratory syncytial virus (RSV) infection. In this study, we investigated the role of cannabinoid receptor 1 (CB1) in RSV immunopathology and its therapeutic potential in mice model.

This study and our previous finding indicated that endocannabinoid signaling regulates the inflammatory response to RSV infection, and is a potential therapeutic candidate for alleviation of RSV-associated immunopathology.”

https://www.ncbi.nlm.nih.gov/pubmed/29461930

http://online.liebertpub.com/doi/10.1089/vim.2017.0098