Cannabinoid receptor 1 (CB1R) expression in rat dental pulp

Oral Science International“Accumulating evidence supports the role of the cannabinoid system in providing an antinociceptive effect in various painful conditions.

This effect is mediated through the Cannabinoid receptor 1 (CB1R) expressed on nociceptive afferent nerve terminals.

To investigate whether this receptor plays a similar role in dental pain, we studied the presence and distribution of CB1R in rat dental pulp.

CB1R was present on nerve fibers in rat dental pulp and possibly plays a role in dental pain mechanisms.

Interestingly, CB1R has recently been demonstrated in human dental pulp.

This strongly suggests that CB1R could be a therapeutic target for dental pain management.”

https://www.sciencedirect.com/science/article/pii/S1348864312000031

Cannabis and cannabinoids on treatment of inflammation: a patent review

The inflammatory process is a physiological response to a vast number harmful stimulus that takes place in order to restore homeostasis. Many drugs used in pharmacotherapy are effective to control inflammatory responses, however there is a range of adverse effects attributed to steroidal and non-steroidal anti-inflammatory drugs (NSAIDs).

In this sense, herbal medicine and derivatives gain more adepts because of their effectiveness and safety, showing the importance of medicinal plants, especially the Cannabis genus and the cannabinoid derivatives.
The aim of this prospection was to identify data related to patents involving Cannabis and cannabinoids for the treatment of inflammation.
A total of 370 patents were found, of which 17 patents met the inclusion criteria.
Although reports show synergistic effects of the plant components, patents involving Cannabis and cannabinoids focus on isolated substances (CBD e THC). However, patents related to Cannabis and cannabinoids are promising for future use of the plant or its derivatives on the treatment of inflammation.”
“Cannabis-based drugs have been shown to be effective in inflammatory diseases.” https://www.ncbi.nlm.nih.gov/pubmed/29110674
“Cannabinoid-based drugs as anti-inflammatory therapeutics.” http://www.ncbi.nlm.nih.gov/pubmed/15864274

Chemical Characterization and Evaluation of the Antibacterial Activity of Essential Oils from Fibre-Type Cannabis sativa L. (Hemp).

molecules-logo“Volatile terpenes represent the largest group of Cannabis sativa L. components and they are responsible for its aromatic properties. Even if many studies on C. sativa have been focused on cannabinoids, which are terpenophenolics, little research has been carried out on its volatile terpenic compounds.

In the light of all the above, the present work was aimed at the chemical characterization of seventeen essential oils from different fibre-type varieties of C. sativa (industrial hemp or hemp) by means of GC-MS and GC-FID techniques.

In total, 71 compounds were identified, and the semi-quantitative analysis revealed that α- and β-pinene, β-myrcene and β-caryophyllene are the major components in all the essential oils analysed. In addition, a GC-MS method was developed here for the first time, and it was applied to quantify cannabinoids in the essential oils.

The antibacterial activity of hemp essential oils against some pathogenic and spoilage microorganisms isolated from food and food processing environment was also determined. The inhibitory effects of the essential oils were evaluated by both the agar well diffusion assay and the minimum inhibitory concentration (MIC) evaluation. By using the agar diffusion method and considering the zone of inhibition, it was possible to preliminarily verify the inhibitory activity on most of the examined strains.

The results showed a good antibacterial activity of six hemp essential oils against the Gram-positive bacteria, thus suggesting that hemp essential oil can inhibit or reduce bacterial proliferation and it can be a valid support to reduce microorganism contamination, especially in the food processing field.”

https://www.ncbi.nlm.nih.gov/pubmed/31234360

https://www.mdpi.com/1420-3049/24/12/2302

“Cannabis Found Effective in Fighting Drug-Resistant Bacteria”

1957: “[Hemp (Cannabis sativa); antibiotic drug. I. Hemp in the old & popular medicine].” https://www.ncbi.nlm.nih.gov/pubmed/13484424
1958: “[Hemp (Cannabis sativa)–antibiotic drugs. II. Method & results of bacteriological experiments & preliminary clinical experience].” https://www.ncbi.nlm.nih.gov/pubmed/13553773
1959: “[Hemp (Cannabis sativa)-an antibiotic drug. 3. Isolation and constitution of two acids from Cannabis sativa].” https://www.ncbi.nlm.nih.gov/pubmed/14411912
1962: “Antibiotic activity of various types of cannabis resin.” https://www.ncbi.nlm.nih.gov/pubmed/14489783
2008: “Antibacterial cannabinoids from Cannabis sativa: a structure-activity study.” https://www.ncbi.nlm.nih.gov/pubmed/18681481
“Cannabis plant extracts can effectively fight drug-resistant bacteria.” http://abcnews.go.com/Technology/story?id=5787866
“According to research, the five most common cannabinoid compounds in weed—tetrahydrocannabinol (THC), cannabidiol, cannabigerol, cannabinol and cannabichromene—can kill antibiotic-resistant bacteria.” https://blogs.scientificamerican.com/news-blog/whoa-the-stuff-in-pot-kills-germs-2008-08-27/
“All five cannabinoids (THC, CBD, CBG, CBC, and CBN) were potent against bacteria. Notably, they performed well against bacteria that were known to be multidrug resistant, like the strains of MRSA” http://arstechnica.com/science/2008/08/killing-bacteria-with-cannabis/
2014: “Better than antibiotics, cannabinoids kill antibiotic-resistant MRSA bacteria” http://usahealthresource.blogspot.com/2014/02/marijuana-extracts-and-compounds-kill.html
2019: “Cannabis Found Effective in Fighting Drug-Resistant Bacteria” https://www.courthousenews.com/cannabis-found-effective-in-fighting-drug-resistant-bacteria/
“Cannabis oil kills bacteria better than established antibiotics… providing a possible new weapon in the war on superbugs, according to new research. It offers hope of curing killer infections – including MRSA and pneumonia, say scientists.” https://www.thelondoneconomic.com/lifestyle/cannabis-oil-kills-bacteria-better-than-established-antibiotics/24/06/ 
“CANNABIS COMPOUND COULD BE LATEST WEAPON IN WAR AGAINST SUPERBUGS”
“Marijuana skin cream kills superbugs, says Botanix” https://stockhead.com.au/health/marijuana-skin-cream-kills-superbugs-says-botanix/
“Botanix’s CBD-based product destroys superbug skin infections in another ‘world first’” https://smallcaps.com.au/botanix-cbd-based-product-destroys-skin-superbug-infections/
“Compound in cannabis found to be ‘promising’ new antibiotic that does not lose its effectiveness with use” https://www.kelownanow.com/watercooler/news/news/Cannabis/Compound_in_cannabis_found_to_be_promising_new_antibiotic_that_does_not_lose_its_effectiveness_with_use/
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Repetitive high-frequency transcranial magnetic stimulation reverses depressive-like behaviors and protein expression at hippocampal synapses in chronic unpredictable stress-treated rats by enhancing endocannabinoid signaling.

Pharmacology Biochemistry and Behavior“The anti-depressant effect of repetitive transcranial magnetic stimulation (rTMS), a clinically-useful treatment for depression, is associated with changes to the endocannabinoid system (ECS).

However, it is currently unknown whether different frequencies of rTMS alter the ECS differently. To test this, rats exposed to chronic unpredictable stress (CUS) were treated with rTMS at two different frequencies (5 (high) or 1 Hz (low), 1.26 Tesla) for 7 consecutive days.

Interestingly, we found that only high-frequency rTMS ameliorated depressive-like behaviors and normalized the expression of hippocampal synaptic proteins in CUS-treated rats;

Collectively, our results suggest that high-frequency rTMS exerts its anti-depressant effect by up-regulating diacylglycerol lipase alpha (DAGLα) and cannabinoid type 1 receptor (CB1R).”

https://www.ncbi.nlm.nih.gov/pubmed/31229467

https://www.sciencedirect.com/science/article/pii/S0091305719301376?via%3Dihub

Transcranial magnetic stimulation.jpg

“Transcranial magnetic stimulation (TMS), also known as repetitive transcranial magnetic stimulation (rTMS), is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. An electric pulse generator, or stimulator, is connected to a magnetic coil, which in turn is connected to the scalp. The stimulator generates a changing electric current within the coil which induces a magnetic field; this field then causes a second inductance of inverted electric charge within the brain itself. Adverse effects of TMS are rare, and include fainting and seizure. Other potential issues include discomfort, pain, hypomania, cognitive change, hearing loss, and inadvertent current induction in implanted devices such as pacemakers or defibrillators”  https://www.sciencedirect.com/science/article/pii/S0091305719301376?via%3Dihub

A systematic review of cannabidiol dosing in clinical populations.

British Journal of Clinical Pharmacology banner“Cannabidiol is a cannabis-derived medicinal product with potential application in a wide-variety of contexts, however its effective dose in different disease states remains unclear. This review aimed to investigate what doses have been applied in clinical populations, in order to understand the active range of cannabidiol in a variety of medical contexts.

RESULTS:

A total of 1038 articles were retrieved, of which 35 studies met inclusion criteria covering 13 medical contexts. 23 studies reported a significant improvement in primary outcomes (e.g. psychotic symptoms, anxiety, seizures), with doses ranging between <1 – 50 mg/Kg/day. Plasma concentrations were not provided in any publication. Cannabidiol was reported as well tolerated and epilepsy was the most frequently studied medical condition, with all 11 studies demonstrating positive effects of cannabidiol on reducing seizure frequency or severity (average 15 mg/Kg/day within randomised controlled trials). There was no signal of positive activity of CBD in small randomised controlled trials (range n=6-62) assessing diabetes, Crohn’s disease, ocular hypertension, fatty liver disease or chronic pain. However, low doses (average 2.4 mg/Kg/day) were used in these studies.

CONCLUSION:

This review highlights cannabidiol has a potential wide range of activity in several pathologies. Pharmacokinetic studies as well as conclusive phase III trials to elucidate effective plasma concentrations within medical contexts are severely lacking and highly encouraged.”

https://www.ncbi.nlm.nih.gov/pubmed/31222854

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.14038

Molecular docking analysis of phyto-constituents from Cannabis sativa with pfDHFR.

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“Available antimalarial drugs have been associated with numerous side effects, which include skin rashes and myelo-suppression. Therefore, it is of interest to explore compounds from natural source having drug-like properties without side effect.

This study focuses on the screening of compounds from Cannabis sativa against malaria Plasmodium falciparum dihydrofolate reductase for antimalarial properties using Glide (Schrodinger maestro 2018-1).

The result showed that phytochemicals from Cannabis sativa binds with a higher affinity and lower free energy than the standard ligand with isovitexin and vitexin having a glide score of -11.485 and -10.601 respectively, sophoroside has a glide score of -9.711 which is lower than the cycloguanil (co-crystallized ligand) having a glide score of -6.908.

This result gives new perception to the use of Cannabis sativa as antimicrobial agent.”

https://www.ncbi.nlm.nih.gov/pubmed/31223216

http://www.bioinformation.net/014/97320630014574.htm

Aplicaciones terapéuticas por acción de los cannabinoides.

“The interest on cannabinoids became evident between the 1940 and 1950 decades. Although the active substance of the plant was not known, a series of compounds with cannabinomimetic activity were synthesized, which were investigated in animals and clinically. The most widely tested was Δ6a, 10a-THC hexyl. Δ6a, 10a-THC dimethylheptyl (DMHP) antiepileptic effects were studied in several children, with positive results being obtained in some cases. DMHP differs from sinhexyl in that its side chain is DMHP instead of n-hexyl. The first cannabinoid isolated from Cannabis sativa was cannabinol, although its structure was correctly characterized several years later. Cannabidiol was isolated some years later and was subsequently characterized by Mechoulam and Shvo. In 2013, the National Academy of Medicine and the Faculty of Medicine of the National Autonomous University of Mexico, through the Seminar of Studies on Entirety, decided to carry out a systematic review on a subject that is both complex and controversial: the relationship between marijuana and health. In recent years, studies have been conducted with cannabis in several diseases: controlled clinical trials on spasticity in multiple sclerosis and spinal cord injury, chronic, essentially neuropathic, pain, movement disorders (Gilles de Latourette, dystonia, levodopa dyskinesia), asthma and glaucoma, as well as non-controlled clinical trials on Alzheimer’s disease, neuroprotection, intractable hiccups, epilepsy, alcohol and opioid dependence and inflammatory processes.”

https://www.ncbi.nlm.nih.gov/pubmed/31219471

http://gacetamedicademexico.com/frame_esp.php?id=310

The Impact of Cannabis Consumption on Mortality, Morbidity, and Cost in Acute Pancreatitis Patients in the United States: A 10-Year Analysis of the National Inpatient Sample.

Image result for Pancreas journal

“The aim of this study was to identify the prevalence of cannabis use among all patients admitted with acute pancreatitis (AP) in the United States and to investigate the impact of cannabis use on AP mortality, morbidity, and cost of care.

RESULTS:

More than 2.8 million patients with AP patients were analyzed. Cannabis-exposed (CE) patients’ prevalence was 0.3%. Patients exposed to cannabis were younger and mostly males compared with non-cannabis-exposed patients. After adjusting for these factors, the CE group had significantly lower inpatient mortality compared with the noncannabis group (odds ratio, 0.17; 95% confidence interval, 0.06-0.53). Cannabis-exposed patients also had decreased length of stay, inflation-adjusted charges, acute kidney injury, ileus, shock, acute respiratory distress syndrome, and parenteral nutrition requirement.

CONCLUSIONS:

Cannabis-exposed hospitalized patients with AP had lower age-adjusted, mortality, morbidity, and hospitalization-cost than non-cannabis-exposed patients.”

The origins of cannabis smoking: Chemical residue evidence from the first millennium BCE in the Pamirs.

 Science Advances: 5 (6)“Cannabis is one of the oldest cultivated plants in East Asia, grown for grain and fiber as well as for recreational, medical, and ritual purposes. It is one of the most widely used psychoactive drugs in the world today, but little is known about its early psychoactive use or when plants under cultivation evolved the phenotypical trait of increased specialized compound production. The archaeological evidence for ritualized consumption of cannabis is limited and contentious. Here, we present some of the earliest directly dated and scientifically verified evidence for ritual cannabis smoking. This phytochemical analysis indicates that cannabis plants were burned in wooden braziers during mortuary ceremonies at the Jirzankal Cemetery (ca. 500 BCE) in the eastern Pamirs region. This suggests cannabis was smoked as part of ritual and/or religious activities in western China by at least 2500 years ago and that the cannabis plants produced high levels of psychoactive compounds.”

https://www.ncbi.nlm.nih.gov/pubmed/31206023

https://advances.sciencemag.org/content/5/6/eaaw1391

“Earliest evidence for cannabis smoking discovered in ancient tombs”  https://www.nationalgeographic.com/culture/2019/06/earliest-evidence-cannabis-marijuana-smoking-china-tombs/

“The First Evidence of Smoking Pot Was Found in a 2,500-Year-Old Pot”  https://www.smithsonianmag.com/smart-news/2500-year-old-chinese-cemetery-offers-earliest-physical-evidence-cannabis-smoking-180972410/

“Earliest Evidence of People “Smoking” Weed Found in 2,500-Year-Old Chinese Pots”  https://www.sciencealert.com/ancient-pots-from-china-reveal-humans-smoking-cannabis-2-500-years-ago

“Oldest evidence of marijuana use discovered in 2500-year-old cemetery in peaks of western China” https://www.sciencemag.org/news/2019/06/oldest-evidence-marijuana-use-discovered-2500-year-old-cemetery-peaks-western-china

“Cannabis use for medicinal purposes dates back at least 3,000 years.”  https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#section/_7

“Cannabis has been used for medicinal purposes for thousands of years.” https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq

“The use of Cannabis for medicinal purposes dates back to ancient times.” http://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq#section/all