Early research suggesting that a popular non-psychoactive compound derived from marijuana might help prevent or treat COVID-19 warrants further investigation in rigorous clinical trials, researchers say.
Several recent laboratory studies of cannabidiol, or CBD, have shown promising results, attracting media attention.
However, many other potential COVID treatments that showed promise in test tubes, from hydroxychloroquine to various drugs used to treat cancer and other diseases, ultimately failed to show benefit for COVID-19 patients once studied in clinical trials.
Marsha Rosner of the University of Chicago led a team that found CBD appeared to help curb SARS-CoV-2 in infected cells in laboratory experiments. “Our findings do not say this will work in patients. Our findings make a strong case for a clinical trial,” she said.
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Using small doses of highly purified CBD that approximate what patients receive in an oral drug already approved for severe epilepsy, Rosner and colleagues found that CBD did not keep the coronavirus from infecting cells in test tubes.
Rather, it acted soon after the virus entered the cells, blocking it from making copies of itself in part via effects on the inflammatory protein interferon. They found similar effects in infected mice, according to a report in Science Advances.
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Merck Canada announces its antiviral COVID-19 treatment will be manufactured in Ontario – Dec 6, 2021
When they looked at a group of adults with severe epilepsy, the researchers found those who were taking the approved CBD drug had lower rates of COVID-19. But a backward look at a small number of patients does not yield conclusive information. Only randomized clinical trials can do that, Rosner said.
“I know my message is not something people want to hear,” she said.
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Small doses of tetrahydrocannabinol (THC) – the marijuana ingredient that causes the high -cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabichromene (CBC), and cannabigerol (CBG) did not keep the virus out of cells or prevent it from replicating, her team found.
“Not only did THC not work, but combining it with CBD prevented CBD from working,” Rosner said.
NO COVID CURES AT CBD DISPENSARY
A separate team reported recently in the Journal of Natural Products that high doses of CBG and CBDA do prevent the coronavirus from breaking into cells.
Richard van Breemen from Oregon State University told Reuters that the doses his team tested were non-toxic to cells.
It is not clear yet that similarly high doses would be safe for humans, his team said.
“You want the lowest possible effective dose,” Rosner said, because of potential side effects as the drug is filtered through the liver.
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The CBD her team tested was more than 98% pure, while purity in commercial products is far lower. “People should not run out and get CBD from their favorite dispensary,” she said.
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Health Canada approves COVID-19 treatment drug Paxlovid – Jan 17, 2022
CBD products have become widely available in many forms and have been touted – often without proof from clinical trials – as treatments for pain and other ailments.
Small CBD trials in humans with COVID-19 are underway.
In one completed study, researchers in Brazil randomly assigned 105 patients with mild or moderate COVID-19 to receive CBD or a placebo for 14 days along with standard care. The CBD had no apparent effect, according to an October report in Cannabis and Cannabinoid Research.
In a proof-of-concept study at Sheba Medical Center in Israel, researchers are randomly assigning patients with mild COVID to receive CBD or a placebo.
An early-stage trial at Rabin Medical Center, also in Israel, aims to test the effect of CBD in severely or critically ill patients. However, study leader Dr. Moshe Yeshurun told Reuters that accruing participants has been difficult because the current Omicron-driven coronavirus wave “consists mostly of patients with mild to moderate disease.”
Rosner’s team is exploring the possibility of a clinical trial that would likely focus on asymptomatic or mild cases of COVID. Meanwhile, she is concerned that media reports overstating the potential of cannabinoids will lead people to self-medicate with CBD, stop using masks and avoid vaccines.
“We would love to be able to say specifically” that a certain dose of cannabinoids is helpful, she said, but at this point, “vaccine-induced antibodies and antibody drugs are much more effective at blocking infection.”
(Reporting by Nancy Lapid; Editing by Michele Gershberg and Bill Berkrot)
Where does the use of CBD stand legally in the US? What legal boundaries exist in the US of CBD?
The market for products containing hemp-derived cannabidiol (CBD) has risen sharply since the passage of the 2018 Farm Bill. Over the past several years, companies have continued to introduce new products containing CBD across consumer-packaged goods categories.
The FDA has publicly stated that the sale of food and beverage products containing CBD is unlawful at the federal level. (See here and here). Nonetheless, the FDA acknowledges that foods, dietary supplements and cosmetics (among other products) continue to be available “almost everywhere” despite FDA’s many unanswered questions about product quality and safety.
In the absence of a clear enforcement policy from FDA, states are leading the charge on regulation of products containing CBD. These state laws can vary widely, leading to conflicting mandates, and complicated situations for businesses.
Regarding cosmetics, the FDA’s position is that products containing CBD must comply with federal regulations regarding cosmetic products, and no ingredient, including CBD, can be used in a cosmetic if it would cause the product to be adulterated or misbranded.
Further, if the cosmetic product containing CBD was marketed with claims regarding the product’s effect on the structure or function of the body or the product’s ability to cure or treat disease, the FDA might regulate the cosmetic as a drug.
In addition, the Federal Trade Commission (FTC) announced a focus on CBD products making unsubstantiated health claims. For example, they brought suit against a company manufacturing CBD skin creams and other products that claimed that CBD could treat or prevent cancer and Alzheimer’s Disease.
Cannabidiol (CBD), an active ingredient in cannabis, might help block infection with the virus that causes COVID-19.
But don’t go drop a bunch of cash on CBD oils at your local dispensary: The possible effect still needs to be tested in humans. (And definitely don’t smoke marijuana to prevent coronavirus infection.) Even if the findings do hold up, they apply to the kind of medical-grade, Food and Drug Administration (FDA)-approved CBD used to treat seizure disorders, not the low-potency stuff available to consumers.
CBD is also no substitute for weapons against COVID-19 that are known to work, such as vaccination and high-quality masks, said study leader Marsha Rosner, a cancer researcher at the University of Chicago who studies immune responses. But the researchers are hopeful that the compound could be an additional tool in the fight against the SARS-CoV-2 virus — and perhaps other viruses. So far, the team has shown that the compound can help mice fight off COVID-19, and they’ve turned up suggestive evidence that it might be helping humans, too.
„We don’t know yet if CBD can prevent COVID, but we think our results provide a strong case for conducting a clinical trial,” Rosner told Live Science. „That’s really our mantra: We want a clinical trial.”
CBD is derived from the cannabis plant. Unlike tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana, CBD doesn’t cause a high. But it does bind to more than a thousand different receptors in the human body, said Robin Duncan, a biochemist and nutritional scientist at the University of Waterloo in Ontario, who was not involved in the new research. This biological activity has given it a reputation as a health supplement — CBD oils, shakes and other products are available all over the place — but little about CBD’s impact on health has been tested or proven.
Rosner and her colleagues stumbled into studying CBD and COVID-19. They were screening compounds for cancer research, trying to trigger an immune response in cells called the host stress response. The host stress response is part of the innate immune response. It’s not targeted at any particular pathogen, but when a cell senses a threat, such as an invading virus, this response puts the cell into a defensive state, triggering the release of protective chemicals and helping prevent the cell’s machinery from being used to replicate the virus.
CBD seemed surprisingly good at triggering the host stress response, which is important for cells to fight back against viruses, Rosner said, so she and her colleagues decided to study the compound against the novel coronavirus.
They began by treating human lung cells in a lab dish with CBD and then exposing them to SARS-CoV-2, the virus that causes COVID-19. They found that compared with untreated cells, the CBD-dosed cells were much better at staving off infection. The same held true for monkey kidney cells, which are susceptible to the virus. It also held true for the alpha, beta and gamma variants of the coronavirus. (Delta and omicron weren’t available when the study was done, Rosner said.)
„We show that CBD can stop replication of SARS-COV2 in cells in a dish and that it acts at least up to 15 hours after infection, so that suggests it might be effective even at early times after viruses enter cells,” Rosner said.
Putting CBD to the test
Cells in a dish are one thing; living organisms are another. The researchers next tested the compound in mice, injecting pure CBD into the guts of the animals daily for seven days and then spraying live SARS-CoV-2 into their nasal passages — a surefire route to infection. They then continued the CBD injections for four more days.
Five days after the viral treatment, the researchers measured the viral load in the nasal passages and lungs of the mice. They found that with a low dose of CBD, the viral load was 4.8 times lower in the lungs and 3.7 times lower in the nasal passages compared with untreated mice. With a high dose, the viral load in CBD-treated mice was 4.8 times lower in the nose and a whopping 40 times lower in the lungs than in untreated mice. The infected mice also seemed to be fighting off the pathogen with relative ease: Lab-infected mice typically become ill and lose weight, but the CBD-treated mice showed no symptoms.
CBD is an FDA-approved treatment for some seizure disorders, so some people take regular oral doses of the pure compound, Rosner said. She and her team combed through the medical records of people with seizure disorders, comparing the rates of COVID cases in those taking CBD as a treatment to those with similar demographics and medical histories who weren’t using CBD, about 530 in each group. They found that the rate of COVID-positivity in those actively taking CBD was 4.9%, compared with 9% among those not taking it.(However, because it was based on medical records alone, the study couldn’t rule out that there might be some unknown differences between the two groups that might independently affect their risk of COVID exposure.)
An immune booster?
With these promising findings in hand, the team then turned to investigating other cannabis compounds, such as cannabidiolic acid (CBDA), cannabidivarin (CBDV), and THC. They found that CBD alone demonstrated antiviral action. In fact, combining CBD with THC, as one might find in recreational marijuana products, reduced CBD’s antiviral effect. In other words, smoking or vaping pot won’t protect you against COVID-19, Rosner and her colleagues wrote in their new study, which was published Jan. 20 in the journal Science Advances. In fact, smoking or vaping might cause lung damage that can put a person at more risk if they do catch the disease.
The team also investigated why CBD might be having an effect. They found that CBD activates a couple of different protective processes in infected cells. One, known as the „unfolded protein response,” works on the cell machinery that gets hijacked by the virus to make more copies of itself; this response helps maintain function in a cell that is under stress. The unfolded protein response is so named because it helps halt the cell’s production of proteins and clear misfolded or unfolded proteins that are gumming up the works. CBD also helped trigger the production of interferons, immune system compounds that mount a first-line defense against viral replication within the cell.
The SARS-CoV-2 virus has its own defenses that help it suppress a cell’s interferon production; some early research hints that the omicron variant is less severe than previous variantsbecause it doesn’t suppress its host’s interferon production as much. If CBD is capable of boosting interferon even as the virus tries to suppress it, CBD might help reduce disease severity.
Similar results have been seen in other labs, including Duncan’s. Duncan and her colleagues have studied the effect of CBD on specific genes within SARS-CoV-2 infected cells and found results that complement Rosner’s. In that research, which has not yet been peer-reviewed but has been posted onthe preprint database bioRxiv, Duncan and her team found that kidney cells infected with SARS-CoV-2 did a poor job of mounting a frontline antiviral defense. But cells treated with CBD and infected showed a marked increase in genes involved in antiviral action.
„Overall, we both saw similar things: us, when we were looking at specific genes; and them, when they were looking at the whole virus,” Duncan said.
In another recent study published in the Journal of Natural Products, researchers at Oregon State University reported that cannabigerolic acid (CBGA) and cannabidiolic acid (CBDA) could bind to the coronavirus spike protein and prevent the virus from entering cells. That’s a different mechanism of action than shown in Rosner or Duncan’s research, as well as different cannabis compounds. That study also focused solely on cells in a petri dish, not in animals or humans. It’s not yet clear whether the CBGA or CBDA used in that study could be metabolized effectively to work in a living organism, Rosner said. CBD metabolism is better understood from its use in seizure treatment.
To apply for clinical trials in humans, scientists have to show preclinical data suggesting that a drug might have an impact and must also show evidence of safety. Rosner and her team have provided that preclinical data, Duncan said, and CBD is already well-known to be safe and nontoxic in most people. The FDA-grade compound is approved for the treatment of seizures in anyone over the age of 1 in the United States.
A study testing whether CBD could prevent infection would require a huge sample size, on the scale of the studies used to prove the efficacy of vaccination, Rosner said. For that reason, it’s more likely that the researchers will first launch a clinical trial testing whether CBD could help reduce symptoms or severity if taken right after COVID infection. They hope to move forward with those trials in the near future.
„We need to find a sponsor and we need to find funding, so we’ve been in conversation with both companies and our government about how to do that most effectively,” Rosner said.
Researchers at Université de Montréal have published a sweeping review of studies exploring cannabis use and its effects on cognitive function.
Their analysis examines six different areas of cognitive function.
The review finds that cannabis intoxication affects all of these areas, to different degrees, for at least as long as the intoxication lasts.
Long-term effects of cannabis use are less clear.
The effects of cannabis intoxication on cognitive function have been unclear. Research so far has been largely cross-sectional, while longitudinal studies, by contrast, are often more illuminating. There is also insufficient standardization among studies, and their findings do not always agree.
A review of studies, or “meta-analysis,” now offers a way to detect patterns in such diverse data. Researchers from the Université de Montréal analyzed a collection of 10 cannabis meta-analyses, with a collective total of 43,761 participants. The aim was to learn what these investigations revealed about cannabis intoxication and cognitive function.
The new review finds overall agreement that cannabis intoxication leads to small-to-moderate cognitive impairment, depending on the type of cognition.
Doctoral candidate Emese Kroon, of the University of Amsterdam’s Social and Behavioural Sciences Programme group, is the lead author of a study titled, “The short-term and long-term effects of cannabis on cognition: Recent advances in the field.”
While she was not involved in the current review, she shared her impressions of it with Medical News Today:
“It is an interesting approach, to systematically evaluate meta-analyses, which makes this study unique in our field.”
“All included meta-analyses focus on part of the broader picture [of] cognitive functioning, and by combining them, you can draw broader conclusions. However, it must be noted that when the literature is inherently limited or methods among studies inconsistent for a certain cognitive domain, you cannot solve these problems by combining meta-analyses about these domains.”
Dr. Alexandre Dumais, the review’s senior author and an assistant clinical professor of psychiatry and addiction, told MNT:
“Our review enabled [us] to highlight that cannabis intoxication leads to small-to-moderate deficits in several cognitive domains, mainly verbal learning and memory, as well as executive function. These acute impairments accord with documented residual effects, suggesting that the detrimental effects of cannabis persist beyond acute intake.”
“Although most of the evidence on the cognitive effects of cannabis use has been provided by cross-sectional data associated with evidence ranging from low-to-moderate quality,” Dr. Dumais said, “a growing number of longitudinal studies, which are better to address causal inferences, as well as neuroimaging studies, have observed similar findings.”
Kroon noted, “I do believe that we should interpret the conclusions with caution, which the authors also do by evaluating the limitations of their study in great length. But low-to-moderate quality of included meta-analyses does not necessarily rule the conclusions invalid.”
Of the 10 meta-studies analyzed, seven explored executive function, five memory and learning, five processing speed, four complex attention, two perceptual and motor function, and two of them explored language.
For the purposes of the studies, the effects of cannabis were “acute,” during intoxication, or “residual,” lingering after abstinence.
Acute impairment was most frequently seen in learning and memory, followed by executive function. Complex attention and processing speed deficits were a little less than half as common, with processing speed about half as common as that. The least affected area was language.
Of residual effects, Dr. Dumais said that they are “still debated, particularly after abstinence periods.”
“Research has revealed that THC [the active ingredient in cannabis] is a fat-soluble compound that may be stored in body fat and, thus, gradually released into the bloodstream for months. Some literature has suggested that effects may persist for at least 1 week when cannabis use is chronic — [and] definitions of chronic use varied between individual studies — though these deficits are often resolved with long abstinence periods,” he said, adding that “long” might refer to 25 days without cannabis use, for example.
“One hypothesis that has received mixed evidence specifies that cannabis use leads to persistent cognitive impairments.”
“These neurotoxic effects last,” Dr. Dumais explained, “although cannabis users reduce their intake or quit altogether. While some longitudinal studies suggest that cognitive deficits resolve following abstinence (e.g., within the last 12 months), other studies have confirmed that cannabis use frequency led to subsequent long-term cognitive decline, regardless of prolonged cannabis intake. Currently, more research is needed on the matter.”
“I believe,” said Kroon, “the uneven quality of the research is partially inherent to the substance: There is high variability in quality of marijuana, which is also highly variable in different regions, and even within regions between users.”
Efforts to standardize research are underway.
“However,” she noted, “the varying legislation between countries, [and] the varying potency of marijuana and method by which marijuana is used makes this a very challenging task.”
Kroon suggested improving the quality of cannabis research by replicating research to confirm or refute results, standardizing ways of measuring and reporting cannabis use, and systematically tracking the recovery of cognitive function after periods of abstinence.
In addition, the researcher proposed “longitudinal studies to assess the causality between marijuana use and cognition.” Finally, Kroon suggested that researchers ”assess how cognitive functioning related to the development of cannabis use disorder and potentially affects treatment outcomes.”
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Biotech pharmaceutical firm Ananda Scientific has announced that the US Food and Drug Administration (FDA) has approved the Investigational New Drug (IND) application for a clinical study evaluating Nantheia ATL5. The candidate uses cannabidiol (CBD) with the company’s proprietary delivery technology as an adjunctive treatment for opioid use disorder.
According to Ananda Scientific representatives, the study is planned to take place at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at the University of California-Los Angeles (UCLA).
Sohail Zaidi, CEO of Ananda Scientific, said the IND approval is the latest in a line of promising developments for the company’s offerings.
“This is the fourth IND approval for our investigational drug Nantheia product line, and it further re-enforces our vision of developing CBD as a therapeutic for a number of key indications,” Zaidi said. “This clinical study at UCLA is an important component of our clinical development efforts focused on opioid addiction, where a non-addictive therapy is a significant unmet need; we are excited to be working with the UCLA team and look forward to this trial advancing.”
This particular trial is being led by principal investigators (PIs)
; and Richard De La Garza, Professor of Psychiatry and Biobehavioral Sciences at the Jane and Terry Semel Institute at David Geffen School of Medicine UCLA. Additionally, funding for the trial reportedly is coming from the National Institute on Drug Abuse (NIDA).
There is much confusion around CBD and the staff at Greenleaf Farms at 48 Franklin St. in Norwich educates about 12 people daily on the subject, said owner Brian Vertefeuille during a telephone interview.
The Army veteran said that even though marijuana is legal, it is illegal to sell it unless one is a licensed dispensary. “So people come into my store and they see these big jars full of buds. And they’re like, ‘Oh, this is marijuana.’ No, it’s not. It’s CBD or CBG or CBM, some sort of CBD compound that helps with ailments and inflammation and asthma and cognitive abilities for your frontal lobe. It’s amazing what these products do.”
He said that CBD and marijuana plants are two different plants that look exactly the same.
“They grow exactly the same. They take the same nutrients, sunlight and flower,” he said. “But it’s not the same because CBD is genetically modified to not produce the amount of THC (tetrahydrocannabinol) that a normal marijuana plant produces.”
CBD includes over 100 different cannabinoids, which can alleviate aches and pains on an individual basis, Vertefeuille said. “When the CBD compounds are isolated and given to patients, they tend to single out and treat ailments. For example, CBG is strictly for anti-anxiety. CBM is helpful in treating metabolic/eating disorders and regulating diabetes and gastrointestinal issues such as celiac disease and gluten problems. CBN serves as a sleep aid. It acts as a sedative and helps relieve pain and inflammation, especially from conditions of arthritis and Crohn’s disease. All of these are on a patient-by-patient basis.”
Vertefeuille opened Greenleaf Farms in the Sunlight Building in downtown Norwich in September. He also owns a store at 74.5 North Main St. in Jewett City and has affiliate stores at 613 Bank St. in New London and 870 Noble Ave. in Bridgeport.
Jan Tormay, a longtime resident of Norwich, now lives in Westerly.
MADISON, Wis. — A new study from the UW School of Medicine and Public Health shows that recreational cannabis companies use marketing that appeals to children and teens.
Laws in multiple states prohibit such advertising.
Dr. Megan Moreno led the study, which looked at one year of social media posts from marijuana companies in Alaska, Colorado, Oregon, and Washington, where recreational use of the drug is legal.
Moreno said the advertisements can be easily viewed by everybody, including kids.
“As a pediatrician, I know that marketing and advertisements have a strong influence on kids and teens,” Moreno said. “Previous studies have shown how alcohol and tobacco companies’ marketing is associated with youth using these products.”
The study looked at 2,660 posts from 14 different companies and found that 35% of posts advertised discounts or promotions. These types of advertisements are illegal.
Less than half of the posts contained the required safety warnings for products being advertised.
“Some cannabis companies generated dozens of social media posts per day,” Moreno said. “No current system in place to monitor or enforce these regulations on this scale.”
According to Moreno, the observed companies used content to appeal to young people, such as young models and cartoon characters. The companies also marketed to people with budgetary constraints, despite state regulations.
“It is important for parents to know that cannabis companies are actively sharing youth-friendly and restricted content,” Moreno said. “Parents should talk with their kids about how cannabis companies seek to influence them.”
Moreno recommends policymakers increase enforcement of rules and regulations regarding social media advertising, which could include banning cannabis companies from using social media altogether because of the ease of access for children.
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CONCORD (BCN) — The Concord City Council will decide Tuesday whether to allow a cannabis storefront retail operation to move into the Park & Shop strip mall.
Santa Barbara-based Coastal Retail wants to occupy 1847 Willow Pass Road, becoming the third retail cannabis storefront operation in Concord. The city adopted an ordinance in 2020 to allow three such adult-use only establishments in the city, along with manufacturers, non-storefront retail, distributors and microbusinesses.
The planning commission officially recommended the project in December, forwarding it to the council for final approval. The commission said the council should clarify a few things, such as healthcare benefits, labor agreements and change of ownership issues.
The Concord City Council meets at 6:30 p.m. and the session can be streamed on the city’s website. People can also take part via Zoom, at https://bit.ly/3AtFf6B (webinar ID: 852 0909 3884, passcode 286725).