Distinct Functions of Endogenous Cannabinoid System in Alcohol Abuse Disorders.

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“Δ9-tetrahydrocannabinol (Δ9 -THC), the principal active component in Cannabis sativa extracts such as marijuana, participates in cell signaling by binding to cell surface receptors. CB1 receptors (CB1 s) are present in both inhibitory and excitatory presynaptic terminals. CB2 receptors (CB2 s) found in neuronal subpopulations in addition to microglial cells and astrocytes and are present in both pre- and postsynaptic terminals.

Subsequent to endocannabinoid (eCB) system discoveries, studies have suggested that alcohol alters the eCB system and that the eCB system plays a major role in the motivation to abuse alcohol.

Preclinical studies have provided evidence that chronic alcohol consumption modulates eCBs and CB1 expression in brain addiction circuits. In addition, studies have further established the distinct function of the eCB system in the development of fetal alcohol spectrum disorders. This review provides a recent and comprehensive assessment of the literature related to the function of the eCB system in alcohol abuse disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31265740

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14780

“Cannabis and Alcohol: From Basic Science to Public Policy.”  https://www.ncbi.nlm.nih.gov/pubmed/31265135

The heterogeneity and complexity of Cannabis extracts as antitumor agents

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“The Cannabis plant contains over 100 phytocannabinoids and hundreds of other components. The biological effects and interplay of these Cannabis compounds are not fully understood and yet influence the plant’s therapeutic effects.

Here we assessed the antitumor effects of whole Cannabis extracts, which contained significant amounts of differing phytocannabinoids, on different cancer lines from various tumor origins.

Our results show that specific Cannabis extracts impaired the survival and proliferation of cancer cell lines as well as induced apoptosis.

Our findings showed that pure (-)-Δ9–trans-tetrahydrocannabinol (Δ9-THC) did not produce the same effects on these cell lines as the whole Cannabis extracts. Furthermore, Cannabis extracts with similar amounts of Δ9-THC produced significantly different effects on the survival of specific cancer cells.

In addition, we demonstrated that specific Cannabis extracts may selectively and differentially affect cancer cells and differing cancer cell lines from the same organ origin. We also found that cannabimimetic receptors were differentially expressed among various cancer cell lines and suggest that this receptor diversity may contribute to the heterogeneous effects produced by the differing Cannabis extracts on each cell line.

Our overall findings indicate that the effect of a Cannabis extract on a specific cancer cell line relies on the extract’s composition as well as on certain characteristics of the targeted cells.”

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=26983

“Many previous reports highlight and demonstrate the anti-tumor effects of cannabinoids. In the last decade, accumulating evidence has indicated that phytocannabinoids might have antitumor properties. A number of in vitro and in vivo studies have demonstrated the effects of phytocannabinoids on tumor progression by interrupting several characteristic features of cancer. These studies suggest that specific cannabinoids such as Δ9-THC and CBD induce apoptosis and inhibit proliferation in various cancer cell lines.”

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=26983&path%5B%5D=85698

https://pubmed.ncbi.nlm.nih.gov/31289609/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609248/

Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral CB1 receptors.

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“Central antinociceptive effects of cannabinoids have been well documented.

Our results indicate that cannabinoids produce antihyperalgesia via interaction with a peripheral CB1 receptor.

This hypothesis is supported by the finding that anandamide inhibited capsaicin-evoked release of calcitonin gene-related peptide from isolated hindpaw skin.

Collectively, these results indicate that cannabinoids reduce inflammation via interaction with a peripheral CB1 receptor.”

“The Endocannabinoid System and Pain. Cannabis has been used for more than twelve thousand years and for many different purposes (i.e. fiber, medicinal, recreational). However, the endocannabinoid signaling system has only recently been the focus of medical research and considered a potential therapeutic target. Cannabinoid receptors and their endogenous ligands are present at supraspinal, spinal and peripheral levels. Cannabinoids suppress behavioral responses to noxious stimulation and suppress nociceptive processing through activation of cannabinoid CB1 and CB2 receptor subtypes. These studies suggest that manipulation of peripheral endocannabinoids may be promising strategy for the management of pain.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834283/

“The Analgesic Potential of Cannabinoids. Historically and anecdotally cannabinoids have been used as analgesic agents. Moreover, cannabinoids act synergistically with opioids and act as opioid sparing agents, allowing lower doses and fewer side effects from chronic opioid therapy. Thus, rational use of cannabis based medications deserves serious consideration to alleviate the suffering of patients due to severe pain.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728280/

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

Nabilone administration in refractory chronic diarrhea: a case series

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“Through the years, the endocannabinoid system has been recognized in the homeostatic mechanisms of the gut, as well as in the physiological control of intestinal motility and secretion. Accordingly, cannabinoids may be a promising therapy against several gastrointestinal conditions, such as abdominal pain and motility-related disorders. After three months of therapy, oral nabilone improved the health of nearly all patients, with visible improvements in reducing diarrheal symptoms and weight gain. These findings encourage the study of cannabinoids acting on CB1 receptors in chronic gastrointestinal disorders, especially in refractory chronic diarrhea, offering a chance for a substantial improvement in the quality of life of selected patients, with a reasonable safety profile.” https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-019-1024-y
“Nabilone is a drug used to treat severe nausea and vomiting. It is in a family of drugs called cannabinoids (eg. marijuana).” https://hivclinic.ca/main/drugs_fact_files/nabilone.pdf

“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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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

Therapeutic impact of orally administered cannabinoid oil extracts in an experimental autoimmune encephalomyelitis animal model of multiple sclerosis.

Biochemical and Biophysical Research Communications“There is a growing surge of investigative research involving the beneficial use of cannabinoids as novel interventional alternatives for multiple sclerosis (MS) and associated neuropathic pain (NPP).

Using an experimental autoimmune encephalomyelitis (EAE) animal model of MS, we demonstrate the therapeutic effectiveness of two cannabinoid oil extract formulations (10:10 & 1:20 – tetrahydrocannabinol/cannabidiol) treatment.

Our research findings confirm that cannabinoid treatment produces significant improvements in neurological disability scoring and behavioral assessments of NPP that directly result from their ability to reduce tumor necrosis factor alpha (TNF-α) production and enhance brain derived neurotrophic factor (BDNF) production.

Henceforth, this research represents a critical step in advancing the literature by scientifically validating the merit for medical cannabinoid use and sets the foundation for future clinical trials.”

https://www.ncbi.nlm.nih.gov/pubmed/31213295

“Cannabinoid treatment produces improvements in neurological disability scoring. Cannabinoid treatment also improves behavioral assessments of neuropathic pain.”

https://www.sciencedirect.com/science/article/pii/S0006291X19311568?via%3Dihub

Safety and effectiveness of cannabinoids for the treatment of neuropsychiatric symptoms in dementia: a systematic review.

SAGE Journals“Neuropsychiatric symptoms (NPS) in dementia impact profoundly on the quality of life of people living with dementia and their care givers. Evidence for the effectiveness and safety of current therapeutic options is varied.

Cannabinoids have been proposed as an alternative therapy, mainly due to their activity on CB1 receptors in the central nervous system. However, little is known regarding the safety and effectiveness of cannabinoid therapy in people with dementia.

A literature review was undertaken to identify, describe and critically appraise studies investigating cannabinoid use in treating NPS in dementia.

RESULTS:

Twelve studies met the inclusion criteria. There was considerable variability across the studies with respect to study design (50% randomized controlled trials), intervention [dronabinol (33%), nabilone (25%) or delta-9 tetrahydrocannabinol (THC; 42%)] and outcome measures.

Dronabinol (three studies) and THC (one study) were associated with significant improvements in a range of neuropsychiatric scores.

The most common adverse drug event (ADE) reported was sedation. A high risk of bias was found in eight studies. The highest-quality trial found no significant improvement in symptoms or difference in ADE rate between treatment arms. Included studies used low doses of oral cannabinoids and this may have contributed to the lack of demonstrated efficacy.

CONCLUSION:

While the efficacy of cannabinoids was not proven in a robust randomized control trial, observational studies showed promising results, especially for patients whose symptoms were refractory. In addition, the safety profile is favourable as most of the ADEs reported were mild. Future trials may want to consider dose escalation and formulations with improved bioavailability.”

https://www.ncbi.nlm.nih.gov/pubmed/31205674

https://journals.sagepub.com/doi/10.1177/2042098619846993