Researchers found that Δ9-tetrahydrocannabinol (THC) completely prevented death in a mouse model of acute respiratory distress syndrome (ARDS) triggered by staphylococcal enterotoxin B. The untreated condition produced 100% mortality, while THC-treated mice showed 100% survival.
THC also reduced severe lung inflammation and suppressed the cytokine storm associated with the lethal immune response. The researchers linked this protection to the induction of apoptosis in activated immune cells and changes in mitochondrial pathways involved in inflammatory damage.
The findings suggest that THC was able to interrupt an otherwise fatal inflammatory cascade in this experimental model, leading the authors to conclude that THC may have therapeutic potential for ARDS and other conditions involving cytokine storm.
“Acute Respiratory Distress Syndrome (ARDS) causes up to 40% mortality in humans and is difficult to treat. ARDS is also one of the major triggers of mortality associated with coronavirus-induced disease (COVID-19). We used a mouse model of ARDS induced by Staphylococcal enterotoxin B (SEB), which triggers 100% mortality, to investigate the mechanisms through which Δ9-tetrahydrocannabinol (THC) attenuates ARDS.
SEB was used to trigger ARDS in C3H mice. These mice were treated with THC and analyzed for survival, ARDS, cytokine storm, and metabolome. Additionally, cells isolated from the lungs were used to perform single-cell RNA sequencing and transcriptome analysis. A database analysis of human COVID-19 patients was also performed to compare the signaling pathways with SEB-mediated ARDS.
The treatment of SEB-mediated ARDS mice with THC led to a 100% survival, decreased lung inflammation, and the suppression of cytokine storm. This was associated with immune cell apoptosis involving the mitochondrial pathway, as suggested by single-cell RNA sequencing. A transcriptomic analysis of immune cells from the lungs revealed an increase in mitochondrial respiratory chain enzymes following THC treatment. In addition, metabolomic analysis revealed elevated serum concentrations of amino acids, lysine, n-acetyl methionine, carnitine, and propionyl L-carnitine in THC-treated mice. THC caused the downregulation of miR-185, which correlated with an increase in the pro-apoptotic gene targets. Interestingly, the gene expression datasets from the bronchoalveolar lavage fluid (BALF) of human COVID-19 patients showed some similarities between cytokine and apoptotic genes with SEB-induced ARDS.
Collectively, this study suggests that the activation of cannabinoid receptors may serve as a therapeutic modality to treat ARDS associated with COVID-19.”
https://pubmed.ncbi.nlm.nih.gov/32872332
“Δ9-tetrahydrocannabinol (THC) is a psychoactive cannabinoid derived from Cannabis sativa that has potential therapeutic value for pain relief, control of nausea and vomiting, appetite stimulation, and its anti-inflammatory properties [7]. Indeed, a previous report from our laboratory showed that exposure to THC prior to the administration of SEB can prevent SEB-induced ARDS and associated mortality through the miRNA (miR) regulation of regulatory T cells [8]. In the current study, we tested whether THC administration after exposure to SEB would prevent SEB-mediated ARDS; to further understand the mechanisms, we used single-cell RNA sequencing (scRNA-seq) of cells isolated from the lungs.”
“The current study concludes that the treatment of mice with THC post-SEB challenge protects mice from SEB-mediated toxicity by inhibiting inflammation and ARDS through the modulation of miRs targeting mitochondria-related apoptotic genes. Because SEB is a superantigen that drives cytokine storm, our studies revealed that THC is a potent anti-inflammatory agent that has the potential to be used as a therapeutic modality to treat SEB-induced ARDS. Importantly, the metabolomic and metabolic profiling indicates profound effects on mitochondrial functions that may be responsible for the anti-inflammatory activity of THC. This study also concludes that THC may mediate its effects through downregulating the expression of miR-185-3p and the consequent upregulation of apoptotic genes and pathways; thus, targeting miR-185-3p may constitute another therapeutic modality for the alleviation of ARDS. Using gene expression datasets from the BALF of human COVID-19 patients, we found similarities between the cytokine and apoptotic genes with SEB-induced ARDS. Thus, our data suggests that THC may be useful in treating ARDS and cytokine storm seen in COVID-19 patients.”
https://www.mdpi.com/1422-0067/21/17/6244
Need this THC study explained? thcXplained.com
“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.
“Cannflavins are a group of prenylflavonoids derived from Cannabis sativa L.. Cannflavin A (CFL-A), B (CFL-B) and C (CFL-C) have been heralded for their anti-inflammatory properties in pre-clinical evaluations.
“Keratinocytes, the major cell type of the epidermis, are particularly sensitive to environmental factors including exposure to sunlight and chemical agents. Since oxidative stress may arise as a result of these factors, compounds are actively sought that can act as protective agents.
“Coronavirus disease 2019 (COVID-19) is spreading fast all around the world with more than fourteen millions of detected infected cases and more than 600.000 deaths by 20th July 2020. While scientist are working to find a vaccine, current epidemiological data shows that the most common comorbidities for patients with the worst prognosis, hypertension and diabetes, are often treated with angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).
“Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder linked to various converging toxic mechanisms. Evidence suggests that hyperglycemia induces oxidative stress, mitochondrial dysfunction, inflammation and excitotoxicity, all of which play important roles in the onset and progression of AD pathogenesis.
“Cannabis has been used for its medicinal purposes since ancient times. Its consumption leads to the activation of Cannabis receptors CB1 and CB2 that, through specific mechanisms can lead to modulation and progression of inflammation or repair. The novel findings are linked to the medical use of Cannabis in gastrointestinal (GI) system.
“Purpose of review: To evaluate the impact of flavonoids and cannabinoids as anti-inflammatory and antiallergic treatments on the anterior surface of the eye.
“Alcohol is a psychoactive substance highly used worldwide, whose harmful use might cause a broad range of mental and behavioural disorders. Underlying brain impact, the neuroinflammatory response induced by alcohol is recognised as a key contributing factor in the progression of other neuropathological processes, such as neurodegeneration. These sequels are determined by multiple factors, including age of exposure.
“Neurological disorders such as neurodegenerative diseases or traumatic brain injury are associated with cognitive, motor and behavioural changes that influence the quality of life of the patients. Although different therapeutic strategies have been developed and tried until now to decrease the neurological decline, no treatment has been found to cure these pathologies.