Antiviral activities of hemp cannabinoids

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“Hemp is an understudied source of pharmacologically active compounds and many unique plant secondary metabolites including more than 100 cannabinoids.

After years of legal restriction, research on hemp has recently demonstrated antiviral activities in silico, in vitro, and in vivo for cannabidiol (CBD), Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), and several other cannabinoids against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), human immunodeficiency virus (HIV), and γ-herpes viruses.

Mechanisms of action include inhibition of viral cell entry, inhibition of viral proteases, and stimulation of cellular innate immune responses. The anti-inflammatory properties of cannabinoids are also under investigation for mitigating the cytokine storm of COVID-19 and controlling chronic inflammation in people living with HIV.

Retrospective clinical studies support antiviral activities of CBD, Δ9-THC, and cannabinoid mixtures as do some prospective clinical trials, but appropriately designed clinical trials of safety and efficacy of antiviral cannabinoids are urgently needed.”

https://pubmed.ncbi.nlm.nih.gov/37083031/

“Antiviral activities of some of the most abundant cannabinoids have been documented in silicoin vitro, and in vivo. Studies of the antiviral activities of the more than 100 less abundant cannabinoids are still needed as are carefully designed clinical trials. Based on the preclinical evidence of antiviral activity as well as oral bioavailability and long history of safe human use of cannabinoids individually or as mixtures, multiple clinical studies of antiviral cannabinoid safety and efficacy are in progress worldwide using CBD and Δ9-THC, and additional studies will certainly follow.”

https://portlandpress.com/clinsci/article/137/8/633/232928/Antiviral-activities-of-hemp-cannabinoids

Cannabis as antivirals

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“Cannabis is a plant notorious for its psychoactive effect, but when used correctly, it provides a plethora of medicinal benefits. With more than 400 active compounds that have therapeutic properties, cannabis has been accepted widely as a medical treatment and for recreational purposes in several countries.

The compounds exhibit various clinical benefits, which include, but are not limited to, anticancer, antimicrobial, and antioxidant properties.

Among the vast range of compounds, multiple research papers have shown that cannabinoids, such as cannabidiol and delta-9-tetrahydrocannabinol, have antiviral effects. Recently, scientists found that both compounds can reduce severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral infection by downregulating ACE2 transcript levels and by exerting anti-inflammatory properties. These compounds also act as the SARS-CoV-2 main protease inhibitors that block viral replication.

Apart from cannabinoids, terpenes in cannabis plants have also been widely explored for their antiviral properties. With particular emphasis on four different viruses, SARS-CoV-2, human immunodeficiency virus, hepatitis C virus, and herpes simplex virus-1, this review discussed the role of cannabis compounds in combating viral infections and the potential of both cannabinoids and terpenes as novel antiviral therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/36626776/

“Recently, scientists have discovered the potential medical roles of cannabis compounds in viral diseases. Cannabinoids such as CBD and Δ-9-THC, as well as essential oil such as terpenes extracted from the cannabis plants, were reported to have therapeutic effects in several virus infections such as SARS-CoV-2, HIV, HCV, and HSV.”

https://academic.oup.com/jambio/article/134/1/lxac036/6902073?login=false

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

ijms-logo“The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems.

In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development.

The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development.

The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases.

This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.”

https://pubmed.ncbi.nlm.nih.gov/34502379/

https://www.mdpi.com/1422-0067/22/17/9472

 

“Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830475/

Delta-9-tetrahydrocannabinol inhibits the splenocyte proliferative response to herpes simplex virus type 2.

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“The present investigation was undertaken to determine the effect of in vivo Delta-9-tetrahydrocannabinol (Delta-9-THC) treatment on immune responsiveness to secondary exposure to herpes simplex virus type 2 (HSV2) antigens in vitro.

Administration of 50 mg/kg or 100 mg/kg Delta-9-THC to B6C3F1 mice in concert with HSV2 infection resulted in suppression of the proliferative response to HSV2 cell-surface antigens expressed on virus-infected mouse embryo fibroblasts. Similarly, in vitro treatment of HSV2-infected cells with Delta-9-THC (10(-7) M to 10(-5) M) resulted in a dose-dependent suppression of proliferative responsiveness of splenocytes of non-drug-treated HSV2-sensitized mice.

These results suggest that Delta-9-THC inhibits immune responsiveness of B6C3F1 mice to homotypic challenge with HSV2. This inhibition may be resultant of drug action on both effector immunocytes and target HSV2 antigen-bearing cells.”

https://www.ncbi.nlm.nih.gov/pubmed/2830329

https://www.tandfonline.com/doi/abs/10.3109/08923978709035219

“Inhibition of cell-associated herpes simplex virus type 2 glycoproteins by delta 9-tetrahydrocannabinol. These results indicate that delta 9-THC inhibits the synthesis, maturation, and cellular transport of HSV2-specified glycoproteins.” https://www.ncbi.nlm.nih.gov/pubmed/3033681

ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

Image result for Curr Clin Pharmacol.

“Cannabis sativa is also popularly known as marijuana. It is being cultivated and used by man for recreational and medicinal purposes from many centuries.

Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries.

The research of drugs acting on endocannabinoid system has seen many ups and down in recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve “protective role” in many medical conditions.

Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid system.

Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008.

Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite of some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists.

One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that acts selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted.

Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids.

In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as “protective” and “disease inducing substance”, time-dependent changes in the expression of cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27086601

Marijuana Ingredient Kills Herpes Virus, Study Says

“Marijuana’s active ingredient killed herpes viruses in test-tube experiments…

University of South Florida microbiologist Gerald Lancz said his study may help scientists discover new anti-herpes medicines.

http://articles.orlandosentinel.com/1990-05-15/news/9005150630_1_herpes-virus-people-with-herpes-anti-herpes

 

THC in marijuana may block the spread of forms of cancer causing herpes viruses

Medical News

“The compound in marijuana that produces a high, delta-9 tetrahydrocannbinol or THC, may block the spread of several forms of cancer causing herpes viruses, University of South Florida College of Medicine scientists report.

The findings, published Sept. 15 in the online journal BMC Medicine, could lead to the creation of antiviral drugs based on nonpsychoactive derivatives of THC.”

http://www.news-medical.net/news/2004/09/22/4990.aspx

‘Achilles’ Heel’ of the Herpes Virus Possibly Found in Marijuana

“It’s one of the most common viruses in America, and one that causes the most guilt and shame. It can get inside almost any kind of human cell, reproduce in vast numbers, and linger for years in the body, causing everything from recurrent genital blisters to sores around the mouth. Its complications can kill, and it may increase susceptibility to many nerve and brain disorders.

But until now, scientists haven’t fully understood how the herpes simplex virus (HSV) manages to do all of this. And that has stood in the way of developing more targeted, effective treatments against it to help those infected.

New research from the University of Michigan Medical School may help change that.

An estimated 45 million Americans have genital herpes and millions more have the more visible oral variety. Once someone is infected, they’re infected for a lifetime. New medicines for herpes infection are badly needed; currently, antiviral drugs can quell symptoms of an outbreak, but not eliminate the virus. And, there’s increasing evidence that HSV may damage the nerve cells in which it hides between outbreaks, possibly contributing to neurological disease.

In a presentation Sunday at the International Congress of Virology and in two new papers in the Journal of Virology, U-M researchers are reporting the discovery of a receptor that appears to function as one “lock” that HSV opens to allow it to enter human cells. They’ve also found the gene that controls the production of that receptor, deciphered some aspects of the receptor’s structure, and developed a pig-cell system that could be used to test new anti-herpes drugs.

The findings may help explain why the oral and genital herpes virus has such a successful track record: The receptor, dubbed B5, is made by most cells for another purpose not yet understood. HSV appears to have evolved a way to latch onto it, and fool the cell into letting the virus in. And since most cells express the gene for the B5 receptor, this may be a reason HSV can get into most kinds of cells.

“This may be one central part of the Achilles’ heel in interactions of herpes virus with a cell to start infection. We can use the receptor molecule to try to understand the process and perhaps combat infection at this vulnerable site,” says A. Oveta Fuller, Ph.D. the leader of the U-M team, senior author on the two papers and an associate professor in the U-M Medical School’s Microbiology and Immunology Department. “While we’re still a few years away from being able to use this new knowledge to find effective drug candidates, this is a very exciting confluence of discoveries.”

The U-M holds a patent on the system and methods that the team used to make the discoveries.

Coincidentally, the U-M team’s findings about the B5 receptor are being published at about the same time as an Italian team’s reports about a possible ‘key’ on the herpes simplex virus surface that may match the ‘lock’ found by the U-M team. The Italian team has identified a region of a viral surface protein that matches the U-M team’s predictions of what the virus likely would use to bind and engage the B5 receptor.

“It appears that B5 is a new class of viral receptor. Unlike other viruses so far, HSV seems to have evolved to take advantage of a broadly present cellular protein that has properties like that of known cellular fusion machinery,” says Fuller. “No other virus has been shown to use a cellular fusion protein for entry into cells.”

She explains that the search for the mechanisms by which HSV enters cells has been hindered by the fact that the virus is very good at entering so many kinds of cells. The many possibilities for virus binding to cells make deciphering the entry process a difficult problem to solve.

The gene that encodes B5 had in fact been sequenced, but not characterized, as part of the Human Genome Project. Discovering its role and studying the HSV entry mechanism was tricky and near impossible until Fuller’s team discovered a type of pig kidney cell that isn’t vulnerable to infection by human herpes virus. They searched the genome library to find genes essential to HSV infection, isolated the B5-coding sequence, and figured out how to get pig cells to express the human B5 protein to allow the pig cells to be infected with human herpes virus.

For these studies, Fuller credits the persistence of research team members in working with the genomic library and culture of human and pig cells, especially U-M doctorate graduate Aleida Perez and postdoctoral fellows Qingxue Li and Pilar Perez-Romero. Perez-Romero is first author of one of the two new papers, and a co-author on the other.

The two new papers show that the B5 receptor has important features that could explain why it is important to HSV’s ability to fuse with the fluid membrane that encloses every human cell. The researchers were able to show that by placing only the DNA sequence that encodes B5 into HSV-resistant pig cells, they could make the pig cells susceptible to HSV. They were also able to block viral infection of both human cells and susceptible pig cells by adding to cell cultures a synthetic peptide made to mimic the structure of a smaller region of the B5 receptor. This peptide looks like a functional region of B5 and apparently interferes with virus engaging of the cell receptor.

The papers detail how the team isolated and characterized the gene that encodes B5, called hfl-B5, and used the DNA sequence to find out more about the protein structure of the B5 receptor. In the presentation at the International Congress for Virology, Fuller will describe recent findings that further confirm B5’s importance in HSV infection.

The virology team reports that the B5 molecule appears to form a shape called a coiled coil. This intricately wound structure, they believe, may be similar to the structure of some fusion proteins of viruses and also to cellular proteins called SNAREs. Typically, SNARE proteins help cells to manage the fusion of membranes of vesicles inside the cell with other specific vesicles. Vesicles are tiny membrane-encased packets that encapsulate neurotransmitters, enzymes or other important substances and allow them to be transported within and between cells.

The researchers were able to show that B5 sits in the cell membrane with one end of the protein exposed outside of the cell ready to link up with viruses — or to serve the receptor’s “real” function, which still remains to be discovered. They also showed that HSV does not enter into pig cells that have an altered human B5 protein that is changed by mutations that affect a functional region important to forming a coiled coil.

“If B5 is a SNARE-like cell fusion receptor”, Fuller says, “it may turn out to be useful for more than HSV drug treatment. It could act as a way to link vesicles containing drugs with cells, and deliver them inside”. She is currently collaborating with U-M nanotechnology researchers on this concept.

The findings suggest that B5 or its viral ligand could be a target for antiviral treatment, much like cell receptors for the entry of human immunodeficiency virus (HIV) into cells have become targets for new AIDS drugs.”

http://www.hightimes.com/read/achilles-heel-herpes-virus-possibly-found-marijuana

Common weed helps treat herpes, study finds

herpes

“Tansy, a flowering plant that has long been used as a folk remedy to treat fevers, rheumatism, and other conditions, may now have another known health benefit. According to a recent study published in the journal Phytotherapy Research, antiviral compounds naturally present in tansy show effectiveness in treating the herpes virus.”

http://www.naturalnews.com/031510_weed_herpes.html

The effect of delta-9-tetrahydrocannabinol on herpes simplex virus replication.

“Both herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) failed, in an identical fashion to replicate and produce extensive c.p.e. in human cell monolayer cultures which were exposed (8 h before infection, at infection, or 8 h p.i.) to various concentrations of delta-9-tetrahydrocannabinol. Similar results were obtained with a plaque assay utilizing confluent monkey cells. Possible mechanisms for this antiviral activity are discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/6255077