“Introduction: Coronavirus Disease 2019 (COVID-19) causes a wide range of symptoms, including death. As persons recover, some continue to experience symptoms described as Post-Acute COVID-19 Syndrome (PACS). The objectives of this study were to measure the efficacy of Formula C™, a cannabidiol (CBD)-rich, whole-flower terpene-rich preparation in managing PACS symptoms. 

Materials and Methods: This randomized, placebo-controlled, single-blind, open-label crossover study was conducted in 2021. Informed consent was obtained from participants, and they were randomized to two treatment groups. Group 1 (n=15) received blinded active product for 28 days, and Group 2 (n=16) received blinded placebo for 28 days (Treatment Period 1). Both groups crossed over to open-label active product for 28 days (Treatment Period 2) with a safety assessment at day 70. Patient-Reported Outcomes Measurement Information System (PROMIS^®) scores and the Patient Global Impression of Change (PGIC) score were used to assess primary and secondary objectives. Safety assessments were also done at each visit. 

Results: Twenty-four participants completed study, with 8 withdrawals, none related to study product. PGIC and PROMIS scores improved across both groups at day 28. This raised questions about the placebo. A reanalysis of the placebo confirmed absence of CBD and unexpected medical concentration of terpenes. The study continued despite no longer having a true placebo. The improved scores on outcome measures were maintained across the open label treatment period. There were no safety events reported throughout the study. 

Discussion: For persons with PACS who are nonresponsive to conventional therapies, this study demonstrated symptom improvement for participants utilizing Formula C. In addition, the benefits seen in Group 2 suggest the possibility that non-CBD formulations rich in antioxidants, omega-3, and omega-6 fatty acids, gamma-linoleic acid, and terpenes may also have contributed to the overall improvement of the partial active group through the study. 

Conclusion: Given that both groups demonstrated improvement, both formulations may be contributing to these findings. Limitations include the small number of participants, the lack of a true placebo, and limited time on study products. Additional studies are warranted to explore both CBD-rich hemp products and hempseed oil as treatment options for PACS. Trial Registration ClinicalTrials.gov Identifier:NCT04828668.”

https://pubmed.ncbi.nlm.nih.gov/36252151/

“Formula C is an easy to use, commercially available product which appears to be safe and efficacious in people with PACS. There were no adverse events or safety concerns with utilizing Formula C in this patient population.

In summary, PACS has emerged as a patient population requiring extended periods of chronic care. The failure to identify an effective treatment with the use of traditional western medicinal products suggests the need to explore alternative and integrative approaches to improving the lives of those people affected with ongoing post-COVID conditions.”

https://www.liebertpub.com/doi/10.1089/can.2022.0135

“Cannabidiol (CBD) was formulated as a metered dose inhaler (CBD-MDI) and evaluated in vitro for its efficacy as an inhaled dosage form against inflammation caused by the SARS-CoV-2 virus, lipopolysaccharide (LPS) from Escherichia coli, silica particles, nicotine, and coal tar.

A CBD-MDI formulation was prepared with 50 mg of CBD in 10 mL for a CBD dose of 250 μg/puff. The formulation ingredients included CBD, absolute ethanol as a cosolvent, and HFA-134a as the propellant. High aerosol performance of CBD-MDI was obtained with mass median aerodynamic diameter of 1.25 ± 0.01 μm, geometric standard deviation of 1.75 ± 0.00, emitted dose of 244.7 ± 2.1 μg, and fine particle dose of 122.0 ± 1.6 μg. The cytotoxicity and anti-inflammatory effectiveness of CBD-MDI were performed in alveolar macrophage (NR8383) and co-culture of alveolar macrophage (NR8383) and human lung adenocarcinoma (A549) cell line.

CBD delivered from an MDI was safe on respiratory cells and did not trigger an immune response in alveolar macrophages. CBD-MDI effectively reduced the generation of cytokines in immune cells treated with viral antigen S-RBD, bacterial antigen LPS, silica particles, and coal tar. The efficacy of CBD-MDI was comparable to budesonide. Furthermore, the findings demonstrated that the use of CBD-MDI was more effective in treatment rather than prevention when inflammation was induced by either a viral or bacterial stimulant.”

https://pubmed.ncbi.nlm.nih.gov/36159727/

https://www.sciencedirect.com/science/article/pii/S177322472200716X?via%3Dihub

“Small molecule therapeutic agents are needed to treat or prevent infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is the cause of the COVID-19 pandemic.

To expedite the discovery of lead compounds for development, assays have been developed based on affinity selection-mass spectrometry (AS-MS), which enables the rapid screening of mixtures such as combinatorial libraries and extracts of botanicals or other sources of natural products. AS-MS assays have been used to find ligands to the SARS-CoV-2 spike protein for inhibition of cell entry as well as to the 3-chymotrypsin-like cysteine protease (3CLpro) and the RNA-dependent RNA polymerase complex constituent Nsp9, which are targets for inhibition of viral replication.

The AS-MS approach of magnetic microbead affinity selection screening has been used to discover high-affinity peptide ligands to the spike protein as well as the hemp cannabinoids cannabidiolic acid and cannabigerolic acid, which can prevent cell infection by SARS-CoV-2.

Another AS-MS method, native mass spectrometry, has been used to discover that the flavonoids baicalein, scutellarein, and ganhuangenin, can inhibit the SARS-CoV-2 protease 3CLpro. Native mass spectrometry has also been used to find an ent-kaurane natural product, oridonin, that can bind to the viral protein Nsp9 and interfere with RNA replication.

These natural lead compounds are under investigation for the development of therapeutic agents to prevent or treat SARS-CoV-2 infection.”

https://pubmed.ncbi.nlm.nih.gov/35929396/

https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/mas.21800

“Background: While cannabis is known to have immunomodulatory properties, the clinical consequences of its use on outcomes in COVID-19 have not been extensively evaluated. We aimed to assess whether cannabis users hospitalized for COVID-19 had improved outcomes compared to non-users.

Methods: We conducted a retrospective analysis of 1831 patients admitted to two medical centers in Southern California with a diagnosis of COVID-19. We evaluated outcomes including NIH COVID-19 Severity Score, need for supplemental oxygen, ICU (intensive care unit) admission, mechanical ventilation, length of hospitalization, and in-hospital death for cannabis users and non-users. Cannabis use was reported in the patient’s social history. Propensity matching was used to account for differences in age, body-mass index, sex, race, tobacco smoking history, and comorbidities known to be risk factors for COVID-19 mortality between cannabis users and non-users.

Results: Of 1831 patients admitted with COVID-19, 69 patients reported active cannabis use (4% of the cohort). Active users were younger (44 years vs. 62 years, p < 0.001), less often diabetic (23.2% vs 37.2%, p < 0.021), and more frequently active tobacco smokers (20.3% vs. 4.1%, p < 0.001) compared to non-users. Notably, active users had lower levels of inflammatory markers upon admission than non-users-CRP (C-reactive protein) (3.7 mg/L vs 7.6 mg/L, p < 0.001), ferritin (282 μg/L vs 622 μg/L, p < 0.001), D-dimer (468 ng/mL vs 1140 ng/mL, p = 0.017), and procalcitonin (0.10 ng/mL vs 0.15 ng/mL, p = 0.001). Based on univariate analysis, cannabis users had significantly better outcomes compared to non-users as reflected in lower NIH scores (5.1 vs 6.0, p < 0.001), shorter hospitalization (4 days vs 6 days, p < 0.001), lower ICU admission rates (12% vs 31%, p < 0.001), and less need for mechanical ventilation (6% vs 17%, p = 0.027). Using propensity matching, differences in overall survival were not statistically significant between cannabis users and non-users, nevertheless ICU admission was 12 percentage points lower (p = 0.018) and intubation rates were 6 percentage points lower (p = 0.017) in cannabis users.

Conclusions: This retrospective cohort study suggests that active cannabis users hospitalized with COVID-19 had better clinical outcomes compared with non-users, including decreased need for ICU admission or mechanical ventilation. However, our results need to be interpreted with caution given the limitations of a retrospective analysis. Prospective and observational studies will better elucidate the effects cannabis use in COVID-19 patients.”

https://pubmed.ncbi.nlm.nih.gov/35932069/

“In this retrospective review of 1831 COVID-19 patients requiring hospital admission, current cannabis use was associated with decreased disease severity. This was demonstrated in lower NIH severity scores as well as less need for oxygen supplementation, ICU admission and mechanical ventilation. While there was a trend toward improved survival in cannabis users”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-022-00152-x

“This review presents information from several studies that have demonstrated the antiviral activity of extracts (Andrographis paniculata, Artemisia annua, Artemisia afra, Cannabis sativa, Curcuma longa, Echinacea purpurea, Olea europaea, Piper nigrum, and Punica granatum) and phytocompounds derived from medicinal plants (artemisinins, glycyrrhizin, and phenolic compounds) against SARS-CoV-2.

A brief background of the plant products studied, the methodology used to evaluate the antiviral activity, the main findings from the research, and the possible mechanisms of action are presented.

These plant products have been shown to impede the adsorption of SARS-CoV-2 to the host cell, and prevent multiplication of the virus post its entry into the host cell. In addition to antiviral activity, the plant products have also been demonstrated to exert an immunomodulatory effect by controlling the excessive release of cytokines, which is commonly associated with SARS-CoV-2 infections.”

https://pubmed.ncbi.nlm.nih.gov/35894129/

https://journals.sagepub.com/doi/10.1177/15353702221108915

“Antimicrobial and Antiviral (SARS-CoV-2) Potential of Cannabinoids and Cannabis sativa: A Comprehensive Review”

https://pubmed.ncbi.nlm.nih.gov/34885798/

“Anti-Inflammatory and Antiviral Effects of Cannabinoids in Inhibiting and Preventing SARS-CoV-2 Infection”

https://pubmed.ncbi.nlm.nih.gov/35456990/

“Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants”

https://pubmed.ncbi.nlm.nih.gov/35007072/