Can CBD fight COVID-19? A new study published in Science Advances reports evidence that cannabidiol, a product of the cannabis plant, can inhibit infection by SARS-CoV-2 in human cells and in UChicago Medicine study suggests high-purity CBD may help block virus from replicating Feasibility of Cannabidiol for the Treatment of Long COVID This is an open label, phase 2 clinical trial to assess the feasibility of a cannabidiol (CBD) dominant medicinal cannabis for the
Can CBD fight COVID-19?
A new study published in Science Advances reports evidence that cannabidiol, a product of the cannabis plant, can inhibit infection by SARS-CoV-2 in human cells and in mice. SARS-CoV-2 is the virus that causes COVID-19.
The study, co-authored by researchers from the University of Illinois Chicago and the University of Chicago, found that pharmaceutical-grade cannabidiol showed a significant negative association with SARS-CoV-2 replication.
A new study co-authored by UIC researchers reports evidence that pure, pharmaceutical-grade CBD can inhibit SARS-CoV-2 replication. (Photo: Elsa Olofsson/Unsplash).
To study the effect of cannabidiol, commonly called CBD, the researchers first treated human lung cells with a non-toxic dose of CBD for two hours. Then they exposed the cells to SARS-CoV-2 and monitored them for the virus and the viral spike protein, which binds to human cells. While CBD did not affect the ability of SARS-CoV-2 to enter cells, the researchers observed that when above a certain threshold concentration, CBD inhibited the virus’s ability to replicate early in the infection cycle — approximately six hours after the virus had already infected the cell. Further investigation found that CBD had the same effect in two other types of cells and for three variants of SARS-CoV-2 in addition to the original strain.
The researchers also studied the effect of CBD on viral replication in animals. The team showed that pretreatment with CBD for one week prior to infection suppressed infection both in the lung and the nasal passages of mice.
Guido Pauli, the Norman R. Farnsworth professor of pharmacognosy and director of the Pharmacognosy Institute at the UIC College of Pharmacy, and his team were responsible for ensuring the integrity and purity of CBD and related products, enabling them to determine the compounds with valid therapeutic potential and identify the lead compound tested in the experiments.
“To truly understand the medicinal potential of a natural product, we not only need to verify the active compound and how it is derived from the plant source but also that we can extract and prepare the compound in a reliable way,” Pauli said. “When it comes to something like CBD, this is even trickier because of the widespread availability of products whose quality is essentially unregulated and practically impossible to determine without knowledge of and access to reliable laboratory testing.”
Pauli and his team have extensive experience studying biologically active natural products and their therapeutic potential.
A recent study led by Pauli on the essential medicinal chemistry of cannabidiol provided evidence that the popularization of CBD-fortified or CBD-labeled health products and CBD-associated health claims generally lack a rigorous scientific foundation. In another previous publication, the UIC team reported a process to analyze, characterize and, if possible, prepare pure CBD compounds from the range of widely available products called CBD Oils, which Pauli points out may contain many other things than the declared cannabinoid.
“The products that are commercially or readily available with CBD labels or ingredients are not nearly regulated in the same way as medical drugs,” Pauli said. “Buyers can really have no idea what is in those products, which may or may not contain CBD, and if they do, CBD might be present in largely different amounts and along with many other ingredients.
“It’s critical to understand that the CBD materials evaluated in this study were high-quality, pharmaceutical-grade, high-purity CBD,” he said.
The success of CBD as published in the Science Advances publication wasn’t limited to the laboratory. A retrospective analysis of 1,212 patients from the National COVID Cohort Collaborative revealed that patients taking a medically prescribed oral solution of CBD for the treatment of epilepsy tested positive for COVID-19 at significantly lower rates than a sample of matched patients from similar demographic backgrounds who were not taking CBD.
The researchers reported that the COVID-blocking effects of CBD were confined strictly to high purity, high concentrations of CBD. Closely related cannabinoids such as CBDA, CBDV and THC, the psychoactive element enriched in marijuana (not hemp) plants, did not have the same power. Combining pure CBD with equal amounts of THC in fact drastically reduced the efficacy of CBD.
“While I believe strongly in the therapeutic potential of many natural products and am confident the results of this study provide a promising avenue for further research into CBD to mitigate the harm of COVID-19, the last thing I want to see is people running to a local dispensary. Until we have obtained clinical evidence, it is premature and will likely have no benefit, or could even potentially cause harm in some cases,” Pauli said.
The idea to test CBD as a potential COVID-19 therapeutic was serendipitous, according to a news release on the study from the University of Chicago.
“CBD has anti-inflammatory effects, so we thought that maybe it would stop the second phase of COVID infection involving the immune system, the so-called ‘cytokine storm,’” said Marsha Rosner, professor of cancer research at the University of Chicago and a senior author of the study. “We just wanted to know if CBD would affect the immune system. No one in their right mind would have ever thought that it blocked viral replication, but that’s what it did.”
The study, “Cannabidiol Inhibits SARS-CoV-2 Replication through Induction of the Host ER Stress and Innate Immune Responses,” was supported by grants from the National Institutes of Health (R01 GM121735, R01 CA184494, R01 AI137514, R01 AI127518, R01 AI134980, R01 CA219815, R35 GM119840, P30 CA014599), the University of Chicago, and the Harry B. and Leona M Helmsley Charitable Trust.
Additional authors include Shao-Nong Chen, Takashi Ohtsuki and John Brent Friesen of UIC; Long Chi Nguyen, Dongbo Yang, Thomas Best, Nir Drayman, Adil Mohamed, Christopher Dann, Diane Silva, Lydia Robinson-Mailman, Andrea Valdespino, Letícia Stock, Eva Suárez, Krysten Jones, Saara-Anne Azizi, James Michael Millis, Bryan Dickinson, Savas Tay, Scott Oakes, and David Meltzer of the University of Chicago; Vlad Nicolaescu, Haley Gula, and Glenn Randall of the University of Chicago and Argonne National Laboratory; Divayasha Saxena, Jon Gabbard, Jennifer Demarco, William Severson, Charles Anderson, and Kenneth Palmer of the University of Louisville; and the National COVID Cohort Collaborative Consortium.
Researchers recommend clinical trials for CBD to prevent COVID-19 based on promising animal data
UChicago Medicine study suggests high-purity CBD may help block virus from replicating
An interdisciplinary team of researchers from the University of Chicago has found evidence that cannabidiol, or CBD, a product of the cannabis plant, can inhibit infection by the COVID-19 virus in human cells and in mice.
The study, published on Jan. 20 in Science Advances, found CBD showed a significant negative association with positive COVID tests in a national sample of medical records of patients taking the FDA-approved drug for treating epilepsy. The researchers now say that clinical trials should be done to determine whether CBD could eventually be used as a preventative or early treatment for COVID-19.
They caution, however, that the COVID-blocking effects of CBD come only from a high-purity, specially formulated dose taken in specific situations. The study’s findings do not suggest that consuming commercially available products with CBD additives that vary in potency and quality can prevent COVID-19.
An unexpected avenue
The idea to test CBD as a potential COVID-19 therapeutic was serendipitous. “CBD has anti-inflammatory effects, so we thought that maybe it would stop the second phase of COVID infection involving the immune system, the so-called ‘cytokine storm,’” said Marsha Rosner, Charles B. Huggins Professor in the Ben May Department of Cancer Research and a senior author of the study. “Surprisingly, it directly inhibited viral replication in lung cells.”
To see this effect, the researchers first treated human lung cells with a non-toxic dose of CBD for two hours before exposing the cells to the COVID virus and monitoring them for the virus and the viral spike protein. They found that, above a certain threshold concentration, CBD inhibited the virus’ ability to replicate. Further investigation found that CBD had the same effect in two other types of cells and for three variants of the COVID virus in addition to the original strain.
CBD did not affect the ability of the virus to enter the cell. Instead, CBD was effective at blocking replication early in the infection cycle and six hours after the virus had already infected the cell.
Like all viruses, the COVID virus affects the host cell by hijacking its gene expression machinery to produce more copies of itself and its viral proteins. This effect can be observed by tracking virus-induced changes in cellular RNAs. High concentrations of CBD almost completely eradicated the expression of viral RNAs. It was a completely unexpected result.
“We just wanted to know if CBD would affect the immune system,” Rosner said. “No one in their right mind would have ever thought that it blocked viral replication, but that’s what it did.”
The researchers showed that the mechanism by which CBD blocks the COVID virus replication involves CBD activation of one of the host cell stress responses and generation of interferons, an antiviral cell protein.
Real-world data: Patients taking CBD test positive for COVID-19 at lower rates
The researchers wanted scientific data to show that CBD prevents viral replication in live animals. The team showed pretreatment with CBD for one week prior to infection with the virus suppressed infection both in the lung and the nasal passages of mice. “These results provide major support for a clinical trial of CBD in humans,” said Rosner.
And the success of CBD wasn’t limited to the laboratory: An analysis of 1,212 patients from the National COVID Cohort Collaborative revealed that patients taking a medically prescribed oral solution of CBD for the treatment of epilepsy tested positive for COVID-19 at significantly lower rates than a sample of matched patients from similar demographic backgrounds who were not taking CBD.
The potential for CBD to treat patients recently exposed to or infected by SARS-CoV-2—the virus that causes COVID—does not precede the first lines of defense against COVID-19, which are to get vaccinated and follow existing public health guidelines for masking in indoor spaces and social distancing. But the published results offer a potential new therapeutic, something still needed as the pandemic rages on.
“A clinical trial is necessary to determine whether CBD is really effective at preventing or suppressing SARS-CoV-2 infection, but we think this may have potential as a prophylactic treatment,” said Rosner. “Maybe you’re in a hot spot or you think you might have been exposed or you’ve just tested positive—that’s where we think CBD might have an effect.”
Not your dispensary’s CBD
The research team emphasized that the COVID-blocking effects of CBD were confined strictly to high purity, high concentrations of CBD. Closely related cannabinoids such as CBDA, CBDV and THC, the psychoactive element enriched in marijuana plants, did not have the same power. In fact, combining CBD with equal amounts of THC actually reduced the efficacy of CBD.
“Going to your corner bakery and buying some CBD muffins or gummy bears probably won’t do anything,” said Rosner. “The commercially available CBD powder we looked at, which was off the shelf and something you could order online, was sometimes surprisingly of high purity but also of inconsistent quality. It is also hard to get into an oral solution that can be absorbed without the special, FDA-approved formulation.”
Furthermore, CBD use is not without potential risks. It appears to be extremely safe when consumed in food or drink, but methods of use such as vaping can have negative side effects, including potential damage to the heart and lungs. It’s also not well studied in certain populations, such as pregnant people, and so should be used only under the supervision of a physician and with caution.
While the study’s results are exciting, additional study is needed to determine the precise dosing of CBD that is effective at preventing infection in humans as well as its safety profile and any potential side effects.
“We are very eager to see some clinical trials on this subject get off the ground,” Rosner said. “Especially as we are seeing that the pandemic is still nowhere near the end—determining whether this generally safe, well-tolerated and non-psychoactive cannabinoid might have anti-viral effects against COVID-19 is of critical importance.”
Rosner was also pleased that this research project was a case study in the power of scientific collaboration by bringing together a highly interdisciplinary group of researchers. Senior authors listed on the paper came from three different research universities and from departments as diverse as microbiology, molecular engineering, cancer biology and chemistry.
“This was truly a team-science effort, and that’s something that really excites me,” said Rosner. “From clinicians to David Meltzer’s group who did the patient analysis to virologists like Glenn Randall, and it goes on and on. This is the way science should be carried out.”
Additional authors include Long Chi Nguyen, Dongbo Yang, Thomas J. Best, Nir Drayman, Adil Mohamed, Christopher Dann, Diane Silva, Lydia Robinson-Mailman, Andrea Valdespino, Letícia Stock, Eva Suárez, Krysten A. Jones, Saara-Anne Azizi, James Michael Millis, Bryan C. Dickinson, Savaş Tay, Scott A. Oakes, and David O. Meltzer of the University of Chicago; Vlad Nicolaescu, Haley Gula, and Glenn Randall of UChicago and Argonne National Laboratory; Divayasha Saxena, Jon D. Gabbard, Jennifer K. Demarco, William E. Severson, Charles D. Anderson, and Kenneth E. Palmer of the University of Louisville; Shao-Nong Chen, Takashi Ohtsuki, John Brent Friesen, and Guido F. Pauli of the University of Illinois at Chicago; and the National COVID Cohort Collaborative Consortium.
Funding: BIG Vision grant from the University of Chicago, the National Institutes of Health, Harry B. and Leona M Helmsley Charitable Trust.
Feasibility of Cannabidiol for the Treatment of Long COVID
This is an open label, phase 2 clinical trial to assess the feasibility of a cannabidiol (CBD) dominant medicinal cannabis for the treatment of Long COVID. The primary aim is to assess the feasibility of recruiting and retaining individuals diagnosed with Long COVID into a treatment trial of medicinal cannabis, as well as assessing the safety and tolerability of a dominant medicinal cannabis in this population. The secondary aim is to determine the effect of a CBD dominant medicinal cannabis on symptoms associated with Long COVID.
|Condition or disease||Intervention/treatment||Phase|
|Long COVID||Drug: MediCabilis Cannabis sativa 50||Phase 2|
Long COVID, also defined as post-COVID-19 syndrome, is a common outcome after infection with the SARS-COV-2 virus. The need for treatment and ongoing support for people experiencing Long COVID has been increasingly recognised, including through the establishment of dedicated treatment units within the NHS. While symptoms and their severity may vary greatly between individuals, some of the common symptoms associated with Long COVID include fatigue, breathlessness, pain, sleep disturbances and dysautonomia. In this study, we will test the feasibility of a broad spectrum cannabidiol (CBD) dominant formulation, MediCabilis Cannabis sativa 50, for treating these symptoms in people with a diagnosis of Long COVID. CBD is the primary non-psychoactive ingredient in cannabis, and it is being increasingly used in the treatment of symptoms which are similar to those associated with Long COVID. Additionally, there is some evidence that CBD may be effective in reducing inflammation associated with COVID infection. Together, this evidence suggests that it is possible that CBD may be an effective treatment for people diagnosed with Long COVID. We will therefore conduct a feasibility trial in which 30 people are prescribed CBD dominant medical cannabis. Patients will take this medication daily for a total of 21 weeks (2-week titration period, 18-weeks steady dose, 1-week dose reduction), followed by 3-weeks with no medication. We will collect monthly self-report assessments of common symptoms including breathlessness, fatigue, mood, cognition and pain via a smartphone app, as well as real-time data on heart rate, physical activity and sleep using wearable technology. We will also collect daily self-report assessments of key symptoms (mood, pain, fatigue and breathlessness) via a smartphone app for 7 days per 28 days. Our study will establish whether it is feasible to recruit and retain patients with a diagnosis of Long COVID into a trial of a CBD dominant medical cannabis. We will also monitor whether there are any side effects to assess the safety and tolerability of a CBD dominant medical cannabis. Our results will determine the feasibility of medicinal cannabis in the treatment of Long COVID and whether it is safe to use.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Safety and Tolerability of Full Spectrum Cannabidiol Dominant Medicinal Cannabis in Treating Symptoms Associated With Long COVID: A Feasibility Study|
|Actual Study Start Date :||April 14, 2022|
|Estimated Primary Completion Date :||April 2023|
|Estimated Study Completion Date :||April 2023|
The medicinal cannabis used for this study is MediCabilis Cannabis sativa 50, a full spectrum CBD dominant plant based medicinal cannabis containing 50 mg/ml CBD and 2 mg/ml THC.
On commencing the oral medication, it will be titrated over a 2 week period to a dose of 1 ml twice a day (total dose 2 ml = 100 mg CBD and 4 mg THC). Participants will be given a written titration schedule at the initial clinic visit. There will be the potential for a further dose increase to a total dose of 3 ml per day (150 mg CBD and 6 mg THC) at the 1-month follow-up visit.
Recruitment rate [ Time Frame: 12 months (48 weeks) ]
Retaining participants in a six month trial of medicinal cannabis using the proposed battery of assessments. Retention rate (%) of participants enrolled into the trial who complete the six-month protocol.
Long COVID symptoms [ Time Frame: 5 months (20 weeks) ]
Assessed by the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS, Sivan et al., 2021). This scale includes: breathlessness, cough/ voice, swallowing/ nutrition, fatigue, continence, cognition, pain/discomfort, anxiety, depression, post-traumatic stress disorder, communication, mobility, personal care, activities of daily living, social role, perceived health status and family/carers views. The C19-YRS provides an overview of 3 outcomes: symptoms severity score, functional disability score and global health score.
Fatigue will be assessed using the nine item Fatigue Severity Scale (Krupp et al., 1989). This scale, which was initially designed for use in multiple sclerosis and systemic lupus erythematosus has been used extensively across multiple disorders and has bene demonstrated to have good reliability and validity. Each of the nine items in this scale is assessed on a seven-point scale from 1 (strongly disagree) to 7 (strongly agree). Thus, the composite scale ranges from 9 to 63 with higher ratings representing more severe fatigue.
The health-related quality of life instrument that will be used in this study is the EuroQol 5 Dimensions (EQ-5D; Devlin et al., 2017). It is a widely used, validated, and reliable tool that assesses the quality of life of patients in many disease areas through assessment of the severity of each of 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). Each dimension has 5 levels (1-5): no problems, slight problems, moderate problems, severe problems and extreme problems. The digits for the five dimensions can be numerically summed into a single number, varying from 5 to 25 with higher numbers representing a lower quality of life. In addition, this measure contains a 100-point visual analogue which asks respondents to rate their current health with higher numbers representing better health.
The Brief Pain Inventory Short Form (BPI-SF; Cleeland, 1989; Cleeland & Ryan, 1994), a 9 item self-administered questionnaire, will be used to evaluate the severity of a patient’s pain and the interference of this pain on the patient’s daily feeling and functioning. The patient rates their worst, least, average, and current pain intensity, list current treatments and their perceived effectiveness, and rate the degree that pain interferes with general activity, mood, walking ability, normal work, relations with other persons, sleep, and enjoyment of life on a 10-point scale. The BPI scale defines pain as follows: 1-4=Mild Pain, 5-6=Moderate Pain, 7-10=Severe Pain. Thus, a mean of the items can be presented with higher ratings representing more severe pain. In addition, the mean of the 7 items assessing interference, each rated on a scale from 0 to 10, will be used as a measure of mean pain interference with higher numbers representing more interference.
The Generalised Anxiety Disorder Assessment (GAD-7; Spitzer et al., 2006) will be used to measure depression. The GAD-7 is a seven-item instrument that is used to measure or assess the severity of generalised anxiety disorder (GAD). Each item asks the individual to rate the severity of their symptoms over the past two weeks. Response options include “not at all”, “several days”, “more than half the days” and “nearly every day”. The GAD-7 score is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of “not at all,” “several days,” “more than half the days,” and “nearly every day,” respectively, and then adding together the scores for the seven questions. GAD-7 total score for the seven items ranges from 0 to 21.
The Patient Health Questionnaire (PHQ-9; Kroneke et al., 2001) will be used to measure mood/ depression. It is a reliable and valid measure of depression severity and is comprised of a 9-item self-rated instrument that has been validated in general populations, medical populations and psychiatric samples.
It is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of not at all, several days, more than half the days, and nearly every day, respectively. PHQ-9 total score for the nine items ranges from 0 to 27.
Assessed using Pittsburgh self-report questionnaires and wearable technology. The Pittsburgh Sleep Quality Index (PSQI) includes a scoring key for calculating a patient’s seven subscores, each of which can range from 0 to 3. The subscores are tallied, yielding a “global” score that can range from 0 to 21. A global score of 5 or more indicates poor sleep quality; the higher the score, the worse the quality. Mean ratings on this global score will be used in our analyses. Furthermore, the wearable technology (i.e. Fitbit) will provide the patients’ total time in sleep and time in sleep stages (light, deep and REM sleep), as well as a daily Sleep Score accessed via the Fitbit app. Seven day averages (means) of the Fitbit measures will be calculated for each participant across the duration of the study.
The wearable technology will provide 24/7 heart rate tracking and heart rate variability. We will have access to the daily resting heart rate and averages across discrete periods. We will analyse mean resting heart rate (beats per minute). Variation in the time between each heartbeat (heart rate variability) will be accessed via the Fitbit app. Seven day averages (means) of the Fitbit measures will be calculated for each participant across the duration of the study.
Activity levels assessed via wearable technology. The wearable technology (i.e. Fitbit) tracks all-day activity including number of steps walked, distance walked (expressed in kilometres), floors climbed, active minutes and calories burned. We will analyse the seven-day mean number of daily steps, distance walked, stairs climbed, active minutes and calories burned. Seven day averages (means) of the Fitbit measures will be calculated for each participant across the duration of the study.
Oxygen saturation expressed as percentage saturation, with typical numbers being in the region of 95% will also be assessed via the Fitbit. Seven day averages (means) of the Fitbit measures will be calculated for each participant across the duration of the study.
Assessed using daily reports of key symptoms (breathlessness, fatigue, mood and pain) adapted from the COVID-19 Yorkshire Rehabilitation Scale. Each symptom will be scored out of 10 for a period of 7 days per 28 days, to produce an average score for each symptom.