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 (-)-Δ9trans-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

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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/
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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

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Cannabinoid receptor CB1-immunoreactive nerve fibres in painful and non-painful human tooth pulp.

Journal of Clinical Neuroscience Home“The cannabinoid receptor CB1 is involved in modulation of neuronal hypersensitivity and pain. The aim of this study was to evaluate CB1 receptor levels for the first time in dental pain. A total of 19 patients due for molar extraction were divided into two groups, those with existing dental pain (n=9), and those with no history of pain (n=10). Immunohistochemistry and computer image analysis was used to evaluate CB1-positive nerve fibres in tooth pulp, with neurofilament-immunostaining as a structural nerve marker. CB1-immunoreactive nerve fibres were scattered throughout the tooth pulp and often seen in nerve bundles, but the fibres did not penetrate the subodontoblastic layer. There was no statistically significant change in the CB1 nerve fibre percentage area in the painful group compared to the non-painful group (p=0.146); the neurofilament fibres were significantly reduced in the painful group compared to the controls (p=0.028), but there was no difference in the ratio of CB1 to neurofilaments between the two groups. Thus, CB1 expression is maintained by nerve fibres in painful human dental pulp, and peripherally-restricted CB1 agonists currently in development may advance the treatment of dental pain.”

https://www.ncbi.nlm.nih.gov/pubmed/20705472

https://www.jocn-journal.com/article/S0967-5868(10)00289-4/fulltext

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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
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Endocannabinoid system imbalance in the postmortem prefrontal cortex of subjects with schizophrenia.

Image result for Journal of Psychopharmacology“The present findings reveal an imbalance in the expression and function of different elements of the endocannabinoid system in schizophrenia.

This outcome highlights the relevance of the endocannabinoid system in the pathophysiology of schizophrenia and emphasises its elements as potential targets in the search for new therapeutic strategies.”

https://www.ncbi.nlm.nih.gov/pubmed/31237179

https://journals.sagepub.com/doi/abs/10.1177/0269881119857205?journalCode=jopa

“Therapeutic potential of cannabinoids in schizophrenia.”   https://www.ncbi.nlm.nih.gov/pubmed/24605939

Cannabinoids for the Treatment of Schizophrenia: An Overview. Cannabinoids are found to be very useful in psychiatry because of their antipsychotic properties suggesting a therapeutic use. Cannabinoids treatments are both able to reduce the typical symptoms of schizophrenia and to slow down the disease aggravation.”   https://www.ncbi.nlm.nih.gov/pubmed/26845552

http://www.thctotalhealthcare.com/category/schizophrenia/

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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
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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

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“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

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