Tag Archives: phytocannabinoids

Pharmacology of Medical Cannabis.

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 “The Cannabis plant has been used for many of years as a medicinal agent in the relief of pain and seizures. It contains approximately 540 natural compounds including more than 100 that have been identified as phytocannabinoids due to their shared chemical structure. The predominant psychotropic component is Δ9-tetrahydrocannabinol (Δ9-THC), while the major non-psychoactive ingredient is cannabidiol (CBD). These compounds have been shown to be partial agonists or antagonists at the prototypical cannabinoid receptors, CB1 and CB2. The therapeutic actions of Δ9-THC and CBD include an ability to act as analgesics, anti-emetics, anti-inflammatory agents, anti-seizure compounds and as protective agents in neurodegeneration. However, there is a lack of well-controlled, double blind, randomized clinical trials to provide clarity on the efficacy of either Δ9-THC or CBD as therapeutics. Moreover, the safety concerns regarding the unwanted side effects of Δ9-THC as a psychoactive agent preclude its widespread use in the clinic. The legalization of cannabis for medicinal purposes and for recreational use in some regions will allow for much needed research on the pharmacokinetics and pharmocology of medical cannabis. This brief review focuses on the use of cannabis as a medicinal agent in the treatment of pain, epilepsy and neurodegenerative diseases. Despite the paucity of information, attention is paid to the mechanisms by which medical cannabis may act to relieve pain and seizures.”

https://www.ncbi.nlm.nih.gov/pubmed/31332738

https://link.springer.com/chapter/10.1007%2F978-3-030-21737-2_8

Cannabinoid Interactions with Proteins: Insights from Structural Studies.

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 “Cannabinoids have been widely used for recreational and medicinal purposes. The increasing legalization of cannabinoid use and the growing success in Medicinal Chemistry of cannabinoids have fueled recent interest in cannabinoid-sensing sites in receptor proteins. Here, we review structural data from high-resolution cryo-EM and crystallography studies that depict phytocannabinoid, endocannabinoid, and synthetic cannabinoid molecules bound to various proteins. The latter include antigen-binding fragment (Fab), cellular retinol binding protein 2 (CRBP2), fatty acid-binding protein 5 (FABP5), peroxisome proliferator-activated receptor γ (PPAR γ), and cannabinoid receptor types 1 and 2 (CB1 and CB2). Cannabinoid-protein complexes reveal the complex design of cannabinoid binding sites that are usually presented by conventional ligand-binding pockets on respective proteins. However, subtle differences in cannabinoid interaction with amino acids within the binding pocket often result in diverse consequences for protein function. The rapid increase in available structural data on cannabinoid-protein interactions will ultimately direct drug design efforts toward rendering highly potent cannabinoid-related pharmacotherapies that are devoid of side effects.”

https://www.ncbi.nlm.nih.gov/pubmed/31332733

https://link.springer.com/chapter/10.1007%2F978-3-030-21737-2_3

Endocannabinoid System Components: Overview and Tissue Distribution.

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 “Marijuana/cannabinoid research has been transformed into mainstream science during the last half-century. Evidence based research and remarkable biotechnological advances demonstrate that phytocannabinoids and endocannabinoid (eCBs) acting on cannabinoid receptors (CBRs) regulate various aspects of human physiological, behavioral, immunological and metabolic functions. The distribution and function of the components of the endocannabinoid system (ECS) in the central nervous system (CNS) and immune processes have garnished significant research focus with major milestones. With these advances in biotechnology, rapid extension of the ECS research in the periphery has gained momentum. In this chapter, we review the components and tissue distribution of this previously unknown but ubiquitous and complex ECS that is involved in almost all aspects of mammalian physiology and pathology.”

https://www.ncbi.nlm.nih.gov/pubmed/31332731

https://link.springer.com/chapter/10.1007%2F978-3-030-21737-2_1

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/

“Cannabis Found Effective in Fighting Drug-Resistant Bacteria”

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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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http://www.thctotalhealthcare.com/tag/antibiotic/

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

Antitumor Cannabinoid Chemotypes: Structural Insights.

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Image result for frontiers in pharmacology“Cannabis has long been known to limit or prevent nausea and vomiting, lack of appetite, and pain. For this reason, cannabinoids have been successfully used in the treatment of some of the unwanted side effects caused by cancer chemotherapy.

Besides their palliative effects, research from the past two decades has demonstrated their promising potential as antitumor agents in a wide variety of tumors.

Cannabinoids of endogenous, phytogenic, and synthetic nature have been shown to impact the proliferation of cancer through the modulation of different proteins involved in the endocannabinoid system such as the G protein-coupled receptors CB1, CB2, and GRP55, the ionotropic receptor TRPV1, or the fatty acid amide hydrolase (FAAH).

In this article, we aim to structurally classify the antitumor cannabinoid chemotypes described so far according to their targets and types of cancer. In a drug discovery approach, their in silico pharmacokinetic profile has been evaluated in order to identify appropriate drug-like profiles, which should be taken into account for further progress toward the clinic.

This analysis may provide structural insights into the selection of specific cannabinoid scaffolds for the development of antitumor drugs for the treatment of particular types of cancer.” https://www.ncbi.nlm.nih.gov/pubmed/31214034

“The first report on the antitumor activity of phytocannabinoids was published over four decades ago. During these last years, significant research has been focused on the therapeutic potential of cannabinoids to manage palliative effects in cancer patients. Besides such palliative applications, some cannabinoids have shown anticancer properties. Since inflammation is a common risk factor for cancer, and some cannabinoids have shown anti-inflammatory properties, they could play a role in chemoprevention.” https://www.frontiersin.org/articles/10.3389/fphar.2019.00621/full
“Antitumor effects of THC.” http://www.ncbi.nlm.nih.gov/pubmed/11097557
“Antitumor effects of cannabidiol” http://www.ncbi.nlm.nih.gov/pubmed/14617682
“Anti-tumour actions of cannabinoids.” https://www.ncbi.nlm.nih.gov/pubmed/30019449
“Extensive preclinical research has demonstrated that cannabinoids, the active ingredients of Cannabis sativa, trigger antitumor responses in different models of cancer.” https://www.ncbi.nlm.nih.gov/pubmed/29940172

Effect of cannabidiol on endocannabinoid, glutamatergic and GABAergic signalling markers in male offspring of a maternal immune activation (poly I:C) model relevant to schizophrenia.

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Progress in Neuro-Psychopharmacology and Biological Psychiatry

“The mainstay treatment for schizophrenia is antipsychotic drugs (APDs), which are mostly effective against the positive symptoms (e.g. hallucinations), but provide minimal benefits for the negative symptoms (e.g. social withdrawal) and cognitive deficits.

We have recently shown that treatment with the non-intoxicating phytocannabinoid, cannabidiol (CBD), can improve cognition and social interaction deficits in a maternal immune activation (MIA) model relevant to the aetiology of schizophrenia, however, the mechanisms underlying this effect are unknown.

An imbalance in the main excitatory (glutamate) and inhibitory (GABA) neurotransmitter systems in the brain plays a role in the pathophysiology of schizophrenia. Therefore, the endocannabinoid system could represent a therapeutic target for schizophrenia as a regulator of glutamate and GABA release via the CB1 receptor (CB1R).

Overall, these findings show that CBD can restore cannabinoid/GABAergic signalling deficits in regions of the brain implicated in schizophrenia pathophysiology following maternal poly I:C exposure. These findings provide novel evidence for the potential mechanisms underlying the therapeutic effects of CBD treatment in the poly I:C model.”

https://www.ncbi.nlm.nih.gov/pubmed/31202911

https://www.sciencedirect.com/science/article/pii/S027858461930106X?via%3Dihub

The Endocannabinoid System and its Modulation by Cannabidiol (CBD).

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Image result for Altern Ther Health Med. “The endocannabinoid system (ECS) is an extensive endogenous signaling system with multiple elements, the number of which may be increasing as scientists continue to elucidate its role in human health and disease. The ECS is seemingly ubiquitous in animal species and is modulated by diet, sleep, exercise, stress, and a multitude of other factors, including exposure to phytocannabinoids, like Cannabidiol (CBD). Modulating the activity of this system may offer tremendous therapeutic promise for a diverse scope of diseases, ranging from mental health disorders, neurological and movement disorders, pain, autoimmune disease, spinal cord injury, cancer, cardiometabolic disease, stroke, TBI, osteoporosis, and others.”

https://www.ncbi.nlm.nih.gov/pubmed/31202198

Bipolar disorder and the endocannabinoid system.

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 Image result for acta neuropsychiatrica“Bipolar disorder (BD) is a debilitating, lifelong neuropsychiatric illness characterised by unsteady mood states which vacillate from (hypo)mania to depression. Despite the availability of pharmaceutical agents which can be effective in ameliorating the acute affective symptoms and prevent episodic relapse, BD is inadequately treated in a subset of patients.

The endocannabinoid system (ECS) is known to exert neuromodulatory effects on other neurotransmitter systems critical in governing emotions. Several studies ranging from clinical to molecular, as well as anecdotal evidence, have placed a spotlight on the potential role of the ECS in the pathophysiology of BD. In this perspective, we present advantages and disadvantages of cannabis use in the management of illness course of BD and provide mechanistic insights into how this system might contribute to the pathophysiology of BD.

RESULTS:

We highlight the putative role of selective cannabinoid receptor 2 (CB2) agonists in BD and briefly discuss findings which provide a rationale for targeting the ECS to assuage the symptoms of BD. Further, data encourage basic and clinical studies to determine how cannabis and cannabinoids (CBs) can affect mood and to investigate emerging CB-based options as probable treatment approaches.

CONCLUSION:

The probable role of the ECS has been almost neglected in BD; however, from data available which suggest a role of ECS in mood control, it is justified to support conducting comprehensive studies to determine whether ECS manipulation could positively affect BD. Based on the limited available data, we suggest that activation of CB2 may stabilise mood in this disorder.”

https://www.ncbi.nlm.nih.gov/pubmed/31159897

https://www.cambridge.org/core/journals/acta-neuropsychiatrica/article/bipolar-disorder-and-the-endocannabinoid-system/0C3191AF7BECA6D5A6EBED3C94CAA57B