“The activity of a new, terpene-based formulation, code-named NT-VRL-1, against Human Coronavirus (HCoV) strain 229E was evaluated in human lung fibroblasts (MRC-5 cells), with and without the addition of cannabidiol (CBD). The main constituents in the terpene formulation used for the experiment were beta caryophyllene, eucalyptol, and citral. The tested formulation exhibited an antiviral effect when it was pre-incubated with the host cells prior to virus infection. The combination of NT-VRL-1 with CBD potentiated the antiviral effect better than the positive controls pyrazofurin and glycyrrhizin. There was a strong correlation between the quantitative results from a cell-viability assay and the cytopathic effect seen under the microscope after 72 h. To the best of our knowledge, this is the first report of activity of a combination of terpenes and CBD against a coronavirus.”
Category Archives: Uncategorized
Non-Cannabinoid Metabolites of Cannabis sativa L. with Therapeutic Potential
“The cannabis plant (Cannabis sativa L.) produces an estimated 545 chemical compounds of different biogenetic classes. In addition to economic value, many of these phytochemicals have medicinal and physiological activity. The plant is most popularly known for its two most-prominent and most-studied secondary metabolites-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Both Δ9-THC and CBD have a wide therapeutic window across many ailments and form part of a class of secondary metabolites called cannabinoids-of which approximately over 104 exist.
This review will focus on non-cannabinoid metabolites of Cannabis sativa that also have therapeutic potential, some of which share medicinal properties similar to those of cannabinoids. The most notable of these non-cannabinoid phytochemicals are flavonoids and terpenes. We will also discuss future directions in cannabis research and development of cannabis-based pharmaceuticals. Caflanone, a flavonoid molecule with selective activity against the human viruses including the coronavirus OC43 (HCov-OC43) that is responsible for COVID-19, and certain cancers, is one of the most promising non-cannabinoid molecules that is being advanced into clinical trials.
As validated by thousands of years of the use of cannabis for medicinal purposes, vast anecdotal evidence abounds on the medicinal benefits of the plant. These benefits are attributed to the many phytochemicals in this plant, including non-cannabinoids. The most promising non-cannabinoids with potential to alleviate global disease burdens are discussed.”
Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response
“The rapid spread of COVID-19 underscores the need for new treatments.
Here we report that cannabidiol (CBD), a compound produced by the cannabis plant, inhibits SARS-CoV-2 infection. CBD and its metabolite, 7-OH-CBD, but not congeneric cannabinoids, potently block SARS-CoV-2 replication in lung epithelial cells.
CBD acts after cellular infection, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD induces interferon expression and up-regulates its antiviral signaling pathway. A cohort of human patients previously taking CBD had significantly lower SARS-CoV-2 infection incidence of up to an order of magnitude relative to matched pairs or the general population.
This study highlights CBD, and its active metabolite, 7-OH-CBD, as potential preventative agents and therapeutic treatments for SARS-CoV-2 at early stages of infection.”
https://www.biorxiv.org/content/10.1101/2021.03.10.432967v1
“Cannabis compound inhibits SARS-CoV-2 replication in human lung cells” https://www.news-medical.net/news/20210314/Cannabis-compound-inhibits-SARS-CoV-2-replication-in-human-lung-cells.aspx
Fighting the storm: could novel anti-TNFα and anti-IL-6 C. sativa cultivars tame cytokine storm in COVID-19?
“The main aspects of severe COVID-19 disease pathogenesis include hyper-induction of proinflammatory cytokines, also known as ‘cytokine storm’, that precedes acute respiratory distress syndrome (ARDS) and often leads to death. COVID-19 patients often suffer from lung fibrosis, a serious and untreatable condition. There remains no effective treatment for these complications.
Out of all cytokines, TNFα and IL-6 play crucial roles in cytokine storm pathogenesis and are likely responsible for the escalation in disease severity. These cytokines also partake in the molecular pathogenesis of fibrosis. Therefore, new approaches are urgently needed, that can efficiently and swiftly downregulate TNFα, IL-6, and the inflammatory cytokine cascade, in order to curb inflammation and prevent fibrosis, and lead to disease remission.
Cannabis sativa has been proposed to modulate gene expression and inflammation and is under investigation for several potential therapeutic applications against autoinflammatory diseases and cancer. Here, we hypothesized that the extracts of novel C. sativa cultivars may be used to downregulate the expression of pro-inflammatory cytokines and pathways involved in inflammation and fibrosis.
Novel anti-TNFα and anti-IL-6 cannabis extracts can be useful additions to the current anti-inflammatory regimens to treat COVID-19, as well as various rheumatological diseases and conditions, and ‘inflammaging’ – the inflammatory underpinning of aging and frailty.”
Cannabinoids as Key Regulators of Inflammasome Signaling: A Current Perspective
“Inflammasomes are cytoplasmic inflammatory signaling protein complexes that detect microbial materials, sterile inflammatory insults, and certain host-derived elements. Inflammasomes, once activated, promote caspase-1-mediated maturation and secretion of pro-inflammatory cytokines, interleukin (IL)-1β and IL-18, leading to pyroptosis. Current advances in inflammasome research support their involvement in the development of chronic inflammatory disorders in contrast to their role in regulating innate immunity.
Cannabis (marijuana) is a natural product obtained from the Cannabis sativa plant, and pharmacologically active ingredients of the plant are referred to as cannabinoids. Cannabinoids and cannabis extracts have recently emerged as promising novel drugs for chronic medical conditions. Growing evidence indicates the potent anti-inflammatory potential of cannabinoids, especially Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), and synthetic cannabinoids; however, the mechanisms remain unclear. Several attempts have been made to decipher the role of cannabinoids in modulating inflammasome signaling in the etiology of chronic inflammatory diseases.
In this review, we discuss recently published evidence on the effect of cannabinoids on inflammasome signaling. We also discuss the contribution of various cannabinoids in human diseases concerning inflammasome regulation. Lastly, in the milieu of coronavirus disease-2019 (COVID-19) pandemic, we confer available evidence linking inflammasome activation to the pathophysiology of COVID-19 suggesting overall, the importance of cannabinoids as possible drugs to target inflammasome activation in or to support the treatment of a variety of human disorders including COVID-19.”
https://pubmed.ncbi.nlm.nih.gov/33584697/
“Cannabis has been shown to possess anti-inflammatory effects owing to its constituents, cannabinoids and terpenoids. Overall, cannabinoids hold a great promise as additional therapeutics to support the current treatment of chronic inflammatory diseases, along with COVID-19”
https://www.frontiersin.org/articles/10.3389/fimmu.2020.613613/full
Cannabinoids in Dermatologic Surgery
“Though known as a medicinal herb for centuries, the recent legalization of cannabinoids across many states has ushered in a new era where cannabinoids have become a popular treatment option amongst clinicians and patients alike. Cannabinoids have demonstrated efficacy in wound healing, reducing inflammation, ameliorating pain, and have shown potential as an anti-tumor agent. As a result, cannabinoids have been rapidly woven into the fabric of modern medicine. However, the utility of cannabinoids in dermatologic surgery has not been explored to date. In this paper, we review the current literature to discuss the potential impact of cannabinoid use in dermatologic surgery.”
Association Between Marijuana Use and Cardiovascular Disease in US Adults
“This study aims to add evidence regarding the impact marijuana use has on the prevalence of cardiovascular disease.
Our study lends support to the notion that marijuana use does not have an association with cardiovascular disease.
Although previous literature has shown that marijuana use has a negative impact on cardiovascular health, our study suggests that users and non-users of marijuana did not have an association with the prevalence of cardiovascular disease.”
https://pubmed.ncbi.nlm.nih.gov/33409101/
“The primary aim of this study was to evaluate the relationship between marijuana use and cardiovascular disease. After controlling for several confounding variables, we found that there was a decrease in the prevalence of cardiovascular events with marijuana use. In conclusion, our study found that there is no link to marijuana use and an increase in cardiovascular disease. Furthermore, there may be a link between marijuana use and lowered risk of cardiovascular disease”
Phytocannabinoid Pharmacology: Medicinal Properties of Cannabis sativa Constituents Aside from the “Big Two”
“Plant-based therapies date back centuries. Cannabis sativa is one such plant that was used medicinally up until the early part of the 20th century.
Although rich in diverse and interesting phytochemicals, cannabis was largely ignored by the modern scientific community due to its designation as a schedule 1 narcotic and restrictions on access for research purposes. There was renewed interest in the early 1990s when the endocannabinoid system (ECS) was discovered, a complex network of signaling pathways responsible for physiological homeostasis. Two key components of the ECS, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), were identified as the molecular targets of the phytocannabinoid Δ9-tetrahydrocannabinol (Δ9-THC).
Restrictions on access to cannabis have eased worldwide, leading to a resurgence in interest in the therapeutic potential of cannabis. Much of the focus has been on the two major constituents, Δ9-THC and cannabidiol (CBD). Cannabis contains over 140 phytocannabinoids, although only a handful have been tested for pharmacological activity. Many of these minor cannabinoids potently modulate receptors, ionotropic channels, and enzymes associated with the ECS and show therapeutic potential individually or synergistically with other phytocannabinoids.
The following review will focus on the pharmacological developments of the next generation of phytocannabinoid therapeutics.”
https://pubmed.ncbi.nlm.nih.gov/33356248/
https://pubs.acs.org/doi/10.1021/acs.jnatprod.0c00965
In vivo and in vitro anti-inflammatory activity evaluation of Lebanese Cannabis sativa L. ssp. indica (Lam.)
“Cannabis sativa L. is an aromatic annual herb belonging to the family Cannabaceae and it is widely distributed worldwide. Cultivation, selling, and consumption of cannabis and cannabis related products, regardless of its use, was prohibited in Lebanon until April 22, 2020. Nevertheless, cannabis oil has been traditionally used unlawfully for many years in Lebanon to treat diseases such as arthritis, diabetes, cancer and few neurological disorders.
Aim of the study: The present study aims to evaluate the phytochemical and anti-inflammatory properties of a cannabis oil preparation that is analogous to the illegally used cannabis oil in Lebanon.
Results: Chemical analysis of COE revealed that cannabidiol (CBD; 59.1%) and tetrahydrocannabinol (THC; 20.2%) were found to be the most abundant cannabinoids.Various monoterpenes (α-Pinene, Camphene, β-Myrecene and D-Limonene) and sesquiterpenes (β-Caryophyllene, α-Bergamotene, α-Humelene, Humulene epoxide II, and Caryophyllene oxide) were identified in the extract. Results showed that COE markedly suppressed the release of TNF-α in LPS-stimulated rat monocytes. Western blot analysis revealed that COE significantly inhibited LPS-induced COX-2 and i-NOS protein expressions and blocked the phosphorylation of MAPKs, specifically that of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 MAPK. COE displayed a significant inhibition of paw edema in both rat models. Histopathological examination revealed that COE reduced inflammation and edema in chronic paw edema model.
Conclusion: The current findings demonstrate that COE possesses remarkable in vivo and in vitro anti-inflammatory activities which support the traditional use of the Lebanese cannabis oil extract in the treatment of various inflammatory diseases including arthritis.”
https://pubmed.ncbi.nlm.nih.gov/33359187/
https://www.sciencedirect.com/science/article/abs/pii/S037887412033631X?via%3Dihub
Role of marijuana components on the regenerative ability of stem cells
“Stem cell therapy promotes tissue regeneration and wound healing. Efforts have been made to prime stem cells to enhance their regenerative abilities.
Certain marijuana components, namely the non-psychoactive cannabidiol (CBD) and psychoactive tetrahydrocannabinol (THC), are defined as immunomodulators.9 We test whether two sources of stem cells, primed with CBD or THC, would demonstrate improved regenerative abilities.
Human adipose-derived stem cells (ASCs) and bone marrow-derived stem cells (BMDSCs), not obtained from the same individual, were treated with low (300 nM) or high (3 μM) concentration CBD. Porcine ASCs and BMDSCs were isolated from a single pig, and treated with either low or high concentrations of CBD or THC. Transwell migration and MTT proliferation assays were performed on the human ASCs and BMDSCs. Also, transwell migration assay was performed on the porcine ASCs and BMDSCs. Finally, a wound healing scratch assay in porcine primary fibroblasts (PFs) was performed, co-cultured with the cannabinoid-treated ASCs.
CBD priming at low concentration induces migration by 180% (P < .01) in porcine ASCs, and by only 93% (P < .02) in porcine BMDSCs. In porcine stem cells, THC priming at low concentration induces migration by 91.6% (P < .01) in ASCs but by only 44.3% (P < .03) in BMDSCs. Compared to PFs co-cultured with untreated ASCs, PFs co-cultured with low CBD-primed ASCs had 75% faster wound closure at 18 hours (P < .01).
CBD and THC priming of ASCs and BMDSCs, particularly at lower doses, enhances a number of regenerative parameters, suggesting that these major marijuana components may improve stem cell-based therapies.
SIGNIFICANCE OF THE STUDY: Our study demonstrates that cannabinoids can enhance the regenerative capacity of two major sources of stem cells, adipose- and bone marrow-derived, from human and porcine donors. Stem cell isolation and expansion is invasive, costly and time consuming. Stem cells with improved regenerative properties may be effective in the treatment of acute or chronic wounds. This is the first study to compare the priming potential of two sources of stem cells from the same animal, with the same genetic and epigenetic profile, as well as the first to prime with THC.”