Coronavirus Disease-2019 Treatment Strategies Targeting Interleukin-6 Signaling and Herbal Medicine

View details for OMICS: A Journal of Integrative Biology cover image“Coronavirus disease-2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is evolving across the world and new treatments are urgently needed as with vaccines to prevent the illness and stem the contagion. The virus affects not only the lungs but also other tissues, thus lending support to the idea that COVID-19 is a systemic disease. The current vaccine and treatment development strategies ought to consider such systems medicine perspectives rather than a narrower focus on the lung infection only.

COVID-19 is associated with elevated levels of the inflammatory cytokines such as interleukin-6 (IL-6), IL-10, and interferon-gamma (IFN-γ). Elevated levels of cytokines and the cytokine storm have been linked to fatal disease. This suggests new therapeutic strategies through blocking the cytokine storm. IL-6 is one of the major cytokines associated with the cytokine storm. IL-6 is also known to display pleiotropic/diverse pathophysiological effects. We suggest the blockage of IL-6 signaling and its downstream mediators such as Janus kinases (JAKs), and signal transducer and activators of transcription (STATs) offer potential hope for the treatment of severe cases of COVID-19. Thus, repurposing of already approved IL-6-JAK-STAT signaling inhibitors as well as other anti-inflammatory drugs, including dexamethasone, is under development for severe COVID-19 cases.

We conclude this expert review by highlighting the potential role of precision herbal medicines, for example, the Cannabis sativa, provided that omics technologies can be utilized to build a robust scientific evidence base on their clinical safety and efficacy. Precision herbal medicine buttressed by omics systems science would also help identify new molecular targets for drug discovery against COVID-19.”

https://pubmed.ncbi.nlm.nih.gov/32857671/

Cannabis sativa is a plant known to contain anti-inflammatory compounds such as cannabinoid cannabidiol. In addition to other compounds such as terpenes, these compounds have been suggested to have potential anticancer properties. Like other herbal plants, we suggest C. sativa warrants further mechanistic research in relationship to putative effects in COVID-19.”

https://www.liebertpub.com/doi/10.1089/omi.2020.0122

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Hemp in Veterinary Medicine: From Feed to Drug

 See the source image“Hemp (Cannabis sativa) is an angiosperm plant belonging to the Cannabaceae family. Its cultivation dates back to centuries. It has always been cultivated due to the possibility of exploiting almost all the parts of the plant: paper, fabrics, ropes, bio-compounds with excellent insulating capacity, fuel, biodegradable plastic, antibacterial detergents, and food products, such as flour, oils, seeds, herbal teas, and beer, are indeed obtained from hemp.

Hemp flowers have also always been used for their curative effects, as well as for recreational purposes due to their psychotropic effects. Cannabis contains almost 500 chemical compounds, such as phytocannabinoids, terpenes, flavonoids, amino acids, fatty acids, vitamins, and macro-, and micro-elements, among others.

When utilized as a food source, hemp shows excellent nutritional and health-promoting (nutraceutical) properties, mainly due to the high content in polyunsaturated fatty acids (especially those belonging to the ω-3 series), as well as in phenolic compounds, which seem effective in the prevention of common diseases such as gastrointestinal disorders, neurodegenerative diseases, cancer, and others.

Moreover, hemp oil and other oils (i.e., olive oil and medium-chain triglyceride-MCT-oil) enriched in CBD, as well as extracts from hemp dried flowers (Cannabis extracts), are authorized in some countries for therapeutic purposes as a second-choice approach (when conventional therapies have failed) for a certain number of clinical conditions such as pain and inflammation, epilepsy, anxiety disorders, nausea, emesis, and anorexia, among others.

The present review will synthetize the beneficial properties of hemp and hemp derivatives in animal nutrition and therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/32850997/

C. sativa has been an important source of food in the Old World, as hempseeds and seed meal are excellent sources of dietary oil, fiber, and protein. Many of the constituents of C. sativa can be classified as either nutrients, nutraceuticals, or pharmaceutical ingredients.”

https://www.frontiersin.org/articles/10.3389/fvets.2020.00387/full

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Medical cannabis for chronic pain: can it make a difference in pain management?

SpringerLink “Globally, chronic pain is a major therapeutic challenge and affects more than 15% of the population. As patients with painful terminal diseases may face unbearable pain, there is a need for more potent analgesics.

Although opioid-based therapeutic agents received attention to manage severe pain, their adverse drug effects and mortality rate associated with opioids overdose are the major concerns. Evidences from clinical trials showed therapeutic benefits of cannabis, especially delta-9-tetrahydrocannabinol and cannabinoids reduced neuropathic pain intensity in various conditions. Also, there are reports on using combination cannabinoid therapies for chronic pain management.

The association of cannabis dependence and addiction has been discussed much and the reports mentioned that it can be comparatively lower than other substances such as nicotine and alcohol. More countries have decided to legalise the medicinal use of cannabis and marijuana. Healthcare professionals should keep themselves updated with the changing state of medical cannabis and its applications.

The pharmacokinetics and safety of medical cannabis need to be studied by conducting clinical research. The complex and variable chemically active contents of herbal cannabis and methodological limitations in the administration of cannabis to study participants, make the clinical research difficult.”

https://pubmed.ncbi.nlm.nih.gov/31535218/

https://link.springer.com/article/10.1007%2Fs00540-019-02680-y

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Pharmacological Analysis of Cannabis Sativa: A Potent Herbal Plant

“Genus Cannabis belong to family Cannabaceae and is traditionally used as medicinal plant against many diseases notably asthma, malaria, treatment of skin diseases, diabetes and headache. The plant Cannabis sativa L. is flowering and an annual herbaceous plant located to eastern Asia but now of cosmopolitan distribution due to extensive cultivation.

Aim of the study: The aim of review is to provide a complete evaluation of the botanical, ethnological and chemical aspects of Cannabis sativa L., and its importance in pharmacological studies.

Results and discussions: This article briefly reviews the botany, traditional knowledge, pharmacological and therapeutic application of the plant C. sativa. This is an attempt to compile and document information about the chemical constituent, pharmacological and therapeutic effects of C. sativa as important herbal drug due to its safety and effectiveness. Studies have revealed its use as anti-bacterial, anti-fungal, anti-cancer, anti-inflammatory and improving testicular function in rats. Consumption of C. sativa is greater in all over the world among all other drugs of abuse in its various forms such as marijuana, hashish and cannabis oil. The study of herbal medicine spans the knowledge of biology, history, source, physical and chemical nature, and mechanism of action, traditional, medicinal and therapeutic use of drug. This article also provide knowledge about macroscopically and microscopically characters of Cannabis sativa with geographical sources. The wellknown cannabinoids are Tetrahydrocannabinol (THC), Cannabidiol (CBD) and Cannabichromene (CBC) and their pharmacological properties and importance have been extensively studied. Hence, efforts are required to establish and validate evidence regarding safety and practices of Ayurveda medicines.

Conclusion: Thes studies will help in expanding the current therapeutic potential of C. sativa and it also provide a strong support to its future clinical use as herbal medicines having safe in use with no side effects.”

https://pubmed.ncbi.nlm.nih.gov/32600228/

https://www.eurekaselect.com/183226/article

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Cannabis for Pediatric Epilepsy.

 Related image“Epilepsy is a chronic disease characterized by recurrent unprovoked seizures. Up to 30% of children with epilepsy will be refractory to standard anticonvulsant therapy, and those with epileptic encephalopathy can be particularly challenging to treat.

The endocannabinoid system can modulate the physiologic processes underlying epileptogenesis. The anticonvulsant properties of several cannabinoids, namely Δ-tetrahydrocannabinol and cannabidiol (CBD), have been demonstrated in both in vitro and in vivo studies.

Cannabis-based therapies have been used for millennia to treat a variety of diseases including epilepsy. Several studies have shown that CBD, both in isolation as a pharmaceutical-grade preparation or as part of a CBD-enriched cannabis herbal extract, is beneficial in decreasing seizure frequency in children with treatment-resistant epilepsy.

Overall, cannabis herbal extracts appear to provide greater efficacy in decreasing seizure frequency, but the studies assessing cannabis herbal extract are either retrospective or small-scale observational studies. The two large randomized controlled studies assessing the efficacy of pharmaceutical-grade CBD in children with Dravet and Lennox-Gastaut syndromes showed similar efficacy to other anticonvulsants. Lack of data regarding appropriate dosing and pediatric pharmacokinetics continues to make authorization of cannabis-based therapies to children with treatment-resistant epilepsy challenging.”

https://www.ncbi.nlm.nih.gov/pubmed/31895184

https://insights.ovid.com/crossref?an=00004691-202001000-00002

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Medical Cannabis Use in Palliative Care: Review of Clinical Effectiveness and Guidelines – An Update [Internet].

Cover of Medical Cannabis Use in Palliative Care: Review of Clinical Effectiveness and Guidelines – An Update“Palliative care is defined by the World Health Organization as “an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness…”. The last days and hours of a person’s life can be associated with immense physical as well as emotional suffering Relief of pain and other distressing symptoms, and enhancement of quality of life, are among the essential elements of good palliative care. Palliative care could benefit an estimated 69% to 82% of dying individuals in Canada. As Canada’s population ages, with increasing prevalence of chronic conditions and treatments resulting in prolonged life, it is expected that there will be an increased need for palliative care services.

Approximately 9% of Canadians (or 2.7 million) reported using cannabis for medical purposes in the first half of 2019. Herbal cannabis (cannabis sativa) contains hundreds of pharmacological components, many of which are not well-characterized. Tetrahydrocannabinol (THC) is the most prevalent pharmacologically active compound and is primarily responsible for the psychoactive and physical effects of cannabis. Cannabidiol (also commonly referred to as CBD) is the second most prevalent. It has very little if any psychotropic effects. Quantity and ratio of these and other components can vary considerably between plants and even within the same plant.

Two prescription cannabinoids are currently marketed in Canada: Nabiximols (Sativex) which contains THC and cannabidiol, and Nabilone (Cesamet) which is a synthetic cannabinoid. Dronabinol (Marinol), synthetic THC, was withdrawn from the Canadian market however it is available in other jurisdictions. For the purposes of this report, medical cannabis refers to use of the cannabis plant or its extracts or synthetic cannabinoids for medical purposes.

Medical cannabis may be of value for a number of conditions, including but not limited to pain, nausea and vomiting, depression, anxiety and appetite stimulation. Adverse effects of cannabis are very common, developing in 80% to 90% of patients. These include but are not limited to psychiatric disturbances, sedation, speech disorders, impaired memory, dizziness, ataxia, addiction, irritability, and driving impairment. Risk of adverse effects is likely lower with cannabidiol alone as compared to THC. The potential for drug interactions is also an important concern. These risks must be considered along with the an apparent lack of evidence surrounding effectiveness of medical cannabis in many conditions for which its use is promoted.

This report updates and expands on a previous summary of abstracts report.9 The objective of the report is to review evidence and guidelines for use of medical cannabis in the palliative care setting.”

https://www.ncbi.nlm.nih.gov/pubmed/31873991

https://www.ncbi.nlm.nih.gov/books/NBK551867/

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Medical cannabis for chronic pain: can it make a difference in pain management?

 “Globally, chronic pain is a major therapeutic challenge and affects more than 15% of the population. As patients with painful terminal diseases may face unbearable pain, there is a need for more potent analgesics.

Although opioid-based therapeutic agents received attention to manage severe pain, their adverse drug effects and mortality rate associated with opioids overdose are the major concerns.

Evidences from clinical trials showed therapeutic benefits of cannabis, especially delta-9-tetrahydrocannabinol and cannabinoids reduced neuropathic pain intensity in various conditions. Also, there are reports on using combination cannabinoid therapies for chronic pain management.

The association of cannabis dependence and addiction has been discussed much and the reports mentioned that it can be comparatively lower than other substances such as nicotine and alcohol.

More countries have decided to legalise the medicinal use of cannabis and marijuana.

Healthcare professionals should keep themselves updated with the changing state of medical cannabis and its applications.”

https://www.ncbi.nlm.nih.gov/pubmed/31535218

https://link.springer.com/article/10.1007%2Fs00540-019-02680-y

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Olivia Newton John says medicinal cannabis is key to her cancer recovery

“Olivia Newton-John says medicinal marijuana is a key part of her treatment for stage four cancer. In an exclusive interview with 60 Minutes reporter Liz Hayes, Newton-John says that not only has cannabis assisted with her pain management, sleep and anxiety – but it’s having affects on her physical health too. “I’m incredibly pro cannabis,” she told Liz Hayes. “If I don’t take the cannabis, I can feel the pain so I know it’s working.”

 “Newton-John is maintaining her health with a combination of conventional and alternative medicines and remedies. But her husband of ten years, John Easterling, says he’s confident medicinal cannabis is contributing significantly to maintaining her health.
Easterling, who spent years cultivating herbs from the Amazon, has long held a strong belief in the medicinal power of plants. In a greenhouse at the Santa Barbara ranch the couple share in California, he grows various strains of cannabis that he uses to help treat his wife. “Cannabis can be used for so many things,” he told Hayes. “I don’t use the word cure…. but I’m confident. We had MRIs showing a lesser number of tumours, and the majority of the other ones are shrinking.”
 “Now a cannabis convert, Newton-John is joining the fight for medicinal cannabis to be legalised. She and Easterling want Australians to have greater access to the plant, like they do in their home state of California – where both medicinal and recreational cannabis is legal.  She’s also hoping to break down the stigma surrounding cannabis use.
“It’s not a drug, it’s a herb and a plant,” she told Hayes. “I think when people use the word drug, it’s a misconception as to what it is and it gets people thinking, ‘oh it’s just another drug’, but it’s not.” Doctors at the Olivia Newton-John Research Institute will conduct a clinical trial to determine the effectiveness of medicinal cannabis later this year.”
 
 “EXCLUSIVE: Olivia Newton-John and Chloe Lattanzi emotional interview | 60 Minutes Australia” https://www.youtube.com/watch?v=rJtPgpedcFo&feature=share

“Olivia Newton-John: ‘Medicinal cannabis enhanced my quality of life’.  For this special 60 Minutes report, Olivia Newton-John tells Liz Hayes that despite her latest diagnosis she was “getting strong again” and that her quality of life had been greatly enhanced by medicinal cannabis, grown for her by her husband John. Olivia and John are strong believers in the power of plants particularly cannabis. “I really believe the cannabis has made a huge difference,” says Olivia. “I’m confident,” John concurs. Olivia, John and Chloe are now cannabis converts, and now want medicinal cannabis legalised as an alternative treatment in Australia.” https://www.9news.com.au/national/olivia-newton-john-60-minutes-medical-cannabis-advocate-after-cancer-treatment-news/da315271-7387-47e0-a14e-c7fbb9a4b18b

“I have to credit again my wonderful husband because he gives me Cannabis oil that he makes for me, grows the plants here. We’re so lucky in California that we can grow our own, and so he’s made me these incredible tinctures that help with my pain and with sleep, and everything.” https://www.today.com/video/watch-olivia-newton-john-s-full-interview-with-natalie-morales-1455610947796

 Olivia Newton-John: “The choices of your treatment is a very personal thing. I can’t tell anyone else what they should do. I’d like to tell you all something that I did that people should know about. I’ve mixed traditional medicine and herbal medicine and homoeopathic medicine and a lot of mind-body spiritual focus. Staying positive and believing I can get well is really important. I’m very fortunate that I have a husband who’s a plant medicine man who helps me with herbs and medicinal cannabis, it’s been a huge part of my journey. I weaned myself off morphine with cannabis and I just want people to know that that is possible and it’s not going to kill you. If we can start teaching people that cannabis can help keep the pain away and not kill you, that’s an important message to get out there. I want to see an end to cancer in my lifetime. I’ve had three bouts with cancer. I am living with it well, and I think I’m going to see an end of it. And that’s my dream, that it will be gone.” https://www.image.ie/life/olivia-newton-john-shares-her-advice-for-women-with-cancer-154470
 “”I want to see an end to cancer in my lifetime. And if it could be through cannabis, or helping people with cannabis, the patients, particularly who are in pain, that’s my goal. I want everyone to have access to this amazing plant”” https://www.facebook.com/watch/?v=269501097009373
 ““I truly believe medicinal cannabis will play a huge part in defeating cancer.”“I absolutely believe all patients should have the right to try. It is a matter of common-sense and it is a compassionate thing to do for people,” she said,” https://starinvesting.com.au/medicinal-cannabis-to-play-huge-role-in-beating-cancer-olivia-newton-john/
Olivia Newton-John reveals she’s using marijuana grown by her husband to fight cancer – and says reports she was on death’s door hurt her deeply. Australian singing sensation Olivia Newton-John says she has been using marijuana grown by her husband to help her through her cancer battle. ‘I really believe the cannabis has made a huge difference,'”
“‘It Has Helped Incredibly’. It’s an amazing plant, a maligned plant, but it’s helping so many people.”” https://www.inquisitr.com/5330159/home-grown-cannabis-is-helping-olivia-newton-john-amid-cancer-battle-it-has-helped-incredibly/
“Olivia Newton-John says she uses cannabis to treat her stage 4 breast cancer… and her husband grows it at home” https://www.dailymail.co.uk/tvshowbiz/article-6782847/Olivia-Newton-John-uses-cannabis-treat-stage-4-breast-cancer.html
““I’m Living With Cancer and It’s Going Away!” Olivia Newton John Declares That Her Body is “Winning” Against Stage 4 Cancer” https://www.survivornet.com/articles/im-living-with-cancer-and-its-going-away-olivia-newton-john-declares-that-her-body-is-winning-against-stage-4-cancer/
“Mainstream media has reported that the cannabis tincture she takes helps with pain, but Amazon John Easterling eagerly expounds on its many healing properties, including the potential to cause cancer cell death. “Cannabis initiates a number of healing responses that can result in apoptosis, cancer cell death—while healing and strengthening the body,” he detailed. His focus is on the plant as chemovar, a more scientific approach to looking at the many compounds, via terpene and cannabinoid extraction from the whole plant to treat the cancer and the entire body, building the immune system so it can aid in fighting the disease.“ https://culturemagazine.com/olivia-newton-john-and-john-easterling/
“Medicinal cannabis is a big part of my recovery. I’m living proof that it works. It’s a healing herb.” https://www.facebook.com/watch/?v=1580591005362546
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Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study.

 Image result for frontiers in neurology“There is uncertainty regarding the appropriate dose of Cannabidiol (CBD) for childhood epilepsy.

We present the preliminary data of seven participants from the Cannabidiol in Children with Refractory Epileptic Encephalopathy (CARE-E) study.

Methods: The study is an open-label, prospective, dose-escalation trial. Participants received escalating doses of a Cannabis Herbal Extract (CHE) preparation of 1:20 Δ9-tetrahydrocannabinol (THC): CBD up to 10-12 mg CBD/kg/day. Seizure frequency was monitored in daily logs, participants underwent regular electroencephalograms, and parents filled out modified Quality of Life in Childhood Epilepsy (QOLCE) and Side Effect rating scale questionnaires. Steady-state trough levels (Css, Min) of selected cannabinoids were quantified.

Results: All seven participants tolerated the CHE up to 10-12 mg CBD/kg/day and had improvements in seizure frequency and QOLCE scores. CSS, Min plasma levels for CBD, THC, and cannabichromene (CBC) showed dose-independent pharmacokinetics in all but one participant. CSS, Min CBD levels associated with a >50% reduction in seizures and seizure freedom were lower than those reported previously with purified CBD. In most patients, CSS, Min levels of THC remained lower than what would be expected to cause intoxication.

Conclusion: The preliminary data suggest an initial CBD target dose of 5-6 mg/kg/day when a 1:20 THC:CBD CHE is used. Possible non-linear pharmacokinetics of CBD and CBC needs investigation. The reduction in seizure frequency seen suggests improved seizure control when a whole plant CHE is used. Plasma THC levels suggest a low risk of THC intoxication when a 1:20 THC:CBD CHE is used in doses up to 12 mg/kg CBD/kg/day.”

https://www.ncbi.nlm.nih.gov/pubmed/31333569

https://www.frontiersin.org/articles/10.3389/fneur.2019.00716/full

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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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