Cannabidiol (CBD) is an active ingredient in cannabis that is derived from the hemp plant, but it does not cause a high and is not addictive. CBD has been shown to be effective in treating conditions like pain, insomnia, and anxiety. The FDA is working to answer questions about the science, safety, and quality of products containing cannabis and cannabis-derived compounds, particularly CBD. A new study shows that an FDA-approved, pharmaceutical-grade formulation of CBD has an antiviral effect in human lung cells and mice, and shows a significant negative association with COVID infection in human patients.
Cannabidiol (CBD): What we know and what we don’t
Cannabidiol (CBD) is often covered in the media, and you may see it touted as an add-in booster to your post-workout smoothie or morning coffee. You can even buy a CBD-infused sports bra. But what exactly is CBD? And why is it so popular?
How is cannabidiol different from marijuana, cannabis and hemp?
CBD, or cannabidiol, is the second most prevalent active ingredient in cannabis (marijuana). While CBD is an essential component of medical marijuana, it is derived directly from the hemp plant, a cousin of marijuana, or manufactured in a laboratory. One of hundreds of components in marijuana, CBD does not cause a “high” by itself. According to a report from the World Health Organization, “In humans, CBD exhibits no effects indicative of any abuse or dependence potential…. To date, there is no evidence of public health related problems associated with the use of pure CBD.”
Is cannabidiol legal?
CBD is readily obtainable in most parts of the United States, though its exact legal status has been in flux. All 50 states have laws legalizing CBD with varying degrees of restriction. In December 2015, the FDA eased the regulatory requirements to allow researchers to conduct CBD trials. In 2018, the Farm Bill made hemp legal in the United States, making it virtually impossible to keep CBD illegal – that would be like making oranges legal, but keeping orange juice illegal.
The Farm Bill removed all hemp-derived products, including CBD, from the Controlled Substances Act, which criminalizes the possession of drugs. In essence, this means that CBD is legal if it comes from hemp, but not if it comes from cannabis (marijuana) – even though it is the exact same molecule. Currently, many people obtain CBD online without a medical marijuana license, which is legal in most states.
The evidence for cannabidiol health benefits
CBD has been touted for a wide variety of health issues, but the strongest scientific evidence is for its effectiveness in treating some of the cruelest childhood epilepsy syndromes, such as Dravet syndrome and Lennox-Gastaut syndrome (LGS), which typically don’t respond to antiseizure medications. In numerous studies, CBD was able to reduce the number of seizures, and, in some cases, stop them altogether. Epidiolex, which contains CBD, is the first cannabis-derived medicine approved by the FDA for these conditions.
Animal studies, and self-reports or research in humans, suggest CBD may also help with:
Studies and clinical trials are exploring the common report that CBD can reduce anxiety.
- Insomnia. Studies suggest that CBD may help with both falling asleep and staying asleep.
- Chronic pain. Further human studies are needed to substantiate claims that CBD helps control pain. One animal study from the European Journal of Pain suggests CBD could help lower pain and inflammation due to arthritis when applied to skin. Other research identifies how CBD may inhibit inflammatory and neuropathic pain, which are difficult treat.
- Addiction. CBD can help lower cravings for tobacco and heroin under certain conditions, according to some research in humans. Animal models of addiction suggest it may also help lessen cravings for alcohol, cannabis, opiates, and stimulants.
Is CBD safe?
Side effects of CBD include nausea, fatigue and irritability. CBD can increase the level of blood thinning and other medicines in your blood by competing for the liver enzymes that break down these drugs. Grapefruit has a similar effect with certain medicines.
People taking high doses of CBD may show abnormalities in liver related blood tests. Many non-prescription drugs, such as acetaminophen (Tylenol), have this same effect. So, you should let your doctor know if you are regularly using CBD.
A significant safety concern with CBD is that it is primarily marketed and sold as a supplement, not a medication. Currently, the FDA does not regulate the safety and purity of dietary supplements. So, you cannot be sure that the product you buy has active ingredients at the dose listed on the label. In addition, the product may contain other unknown elements. We also don’t know the most effective therapeutic dose of CBD for any particular medical condition.
How can CBD be taken?
CBD comes in many forms, including oils, extracts, capsules, patches, vapes, and topical preparations for use on skin. If you’re hoping to reduce inflammation and relieve muscle and joint pain, a topical CBD-infused oil, lotion or cream – or even a bath bomb — may be the best option. Alternatively, a CBC patch or a tincture or spray designed to be placed under the tongue allows CBD to directly enter the bloodstream.
Outside of the US, the prescription drug Sativex, which uses CBD as an active ingredient, is approved for muscle spasticity associated with multiple sclerosis and for cancer pain. Within the US, Epidiolex is approved for certain types of epilepsy and tuberous sclerosis.
The bottom line on cannabidiol
Some CBD manufacturers have come under government scrutiny for wild, indefensible claims, such that CBD is a cure-all for cancer or COVID-19, which it is not. We need more research but CBD may prove to be a helpful, relatively non-toxic option for managing anxiety, insomnia, and chronic pain. Without sufficient high-quality evidence in human studies, we can’t pinpoint effective doses, and because CBD currently is typically available as an unregulated supplement, it’s hard to know exactly what you are getting.
If you decide to try CBD, make sure you are getting it from a reputable source. And talk with your doctor to make sure that it won’t affect any other medicines you take.
What You Need to Know (And What We’re Working to Find Out) About Products Containing Cannabis or Cannabis-derived Compounds, Including CBD
The FDA is working to answer questions about the science, safety, and quality of products containing cannabis and cannabis-derived compounds, particularly CBD.
- Cannabis is a plant of the Cannabaceae family and contains more than eighty biologically active chemical compounds. The most commonly known compounds are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the component that produces the “high” associated with marijuana use. Much interest has been seen around CBD and its potential related to health benefits.
- Marijuana is different from CBD. CBD is a single compound in the cannabis plant, and marijuana is a type of cannabis plant or plant material that contains many naturally occurring compounds, including CBD and THC.
- The FDA has approved only one CBD product, a prescription drug product to treat seizures associated with Lennox Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in people one year of age and older.
- It is currently illegal to market CBD by adding it to a food or labeling it as a dietary supplement.
- The FDA has seen only limited data about CBD safety and these data point to real risks that need to be considered before taking CBD for any reason.
- Some CBD products are being marketed with unproven medical claims and are of unknown quality.
- The FDA will continue to update the public as it learns more about CBD.
Potential harm, side effects and unknowns
- CBD has the potential to harm you, and harm can happen even before you become aware of it.
- CBD can cause liver injury.
- CBD can affect how other drugs you are taking work, potentially causing serious side effects.
- Use of CBD with alcohol or other drugs that slow brain activity, such as those used to treat anxiety, panic, stress, or sleep disorders, increases the risk of sedation and drowsiness, which can lead to injuries.
- Male reproductive toxicity, or damage to fertility in males or male offspring of women who have been exposed, has been reported in studies of animals exposed to CBD.
- CBD can cause side effects that you might notice. These side effects should improve when CBD is stopped or when the amount used is reduced.
- Changes in alertness, most commonly experienced as somnolence (drowsiness or sleepiness).
- Gastrointestinal distress, most commonly experienced as diarrhea and/or decreased appetite.
- Changes in mood, most commonly experienced as irritability and agitation.
- There are many important aspects about CBD that we just don’t know, such as:
- What happens if you take CBD daily for sustained periods of time?
- What level of intake triggers the known risks associated with CBD?
- How do different methods of consumption affect intake (e.g., oral consumption, topical , smoking or vaping)?
- What is the effect of CBD on the developing brain (such as on children who take CBD)?
- What are the effects of CBD on the developing fetus or breastfed newborn?
- How does CBD interact with herbs and other plant materials?
- Does CBD cause male reproductive toxicity in humans, as has been reported in studies of animals?
Unanswered questions about the science, safety, and quality
You may have noticed that cannabidiol (CBD) seems to be available almost everywhere, and marketed as a variety of products including drugs, food, dietary supplements, cosmetics, and animal health products. Other than one prescription drug product to treat seizures associated with Lennox Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in people one year of age and older, the U.S. Food and Drug Administration (FDA) has not approved any other CBD products, and there is very limited available information about CBD, including about its effects on the body.
The FDA recognizes the significant public interest in cannabis and cannabis-derived compounds, particularly CBD. However, there are many unanswered questions about the science, safety, and quality of products containing CBD. The agency is working on answering these questions through ongoing efforts including feedback from a recent FDA hearing and information and data gathering through a public docket.
Despite the 2018 Farm Bill removing hemp — defined as cannabis and cannabis derivatives with very low concentrations (no more than 0.3% on a dry weight basis) of THC — from the definition of marijuana in the Controlled Substances Act, CBD products are still subject to the same laws and requirements as FDA-regulated products that contain any other substance.
The FDA is concerned that people may mistakenly believe that using CBD “can’t hurt.” The agency wants to be clear that we have seen only limited data about CBD’s safety and these data point to real risks that need to be considered. As part of the drug review and approval process for the prescription drug containing CBD, it was determined that the risks are outweighed by the benefits of the approved drug for the particular population for which it was intended. Consumer use of any CBD products should always be discussed with a healthcare provider. Consumers should be aware of the potential risks associated with using CBD products. Some of these can occur without your awareness, such as:
- Liver Injury: During its review of the marketing application for Epidiolex — a purified form of CBD that the FDA approved in 2018 for use in the treatment of two rare and severe seizure disorders — the FDA identified certain safety risks, including the potential for liver injury. This serious risk can be managed when an FDA-approved CBD drug product is taken under medical supervision, but it is less clear how it might be managed when CBD is used far more widely, without medical supervision, and not in accordance with FDA-approved labeling. Although this risk was increased when taken with other drugs that impact the liver, signs of liver injury were seen also in patients not on those drugs. The occurrence of this liver injury was identified through blood tests, as is often the case with early problems with the liver. Liver injury was also seen in other studies of CBD in published literature. We are concerned about potential liver injury associated with CBD use that could go undetected if not monitored by a healthcare provider.
- Drug Interactions: Information from studies of the FDA-approved CBD drug Epidiolex show that there is a risk of CBD impacting other medicines you take – or that other medicines you take could impact the dose of CBD that can safely be used. Taking CBD with other medications may increase or decrease the effects of the other medications. This may lead to an increased chance of adverse effects from, or decreased effectiveness of, the other medications. Drug interactions were also seen in other studies of CBD in published literature. We are concerned about the potential safety of taking other medicines with CBD when not being monitored by a healthcare provider. In addition, there is limited research on the interactions between CBD products and herbs or other plant-based products in dietary supplements. Consumers should use caution when combining CBD products with herbs or dietary supplements.
- Male Reproductive Toxicity: Studies in laboratory animals showed male reproductive toxicity, including in the male offspring of CBD-treated pregnant females. The changes seen include decrease in testicular size, inhibition of sperm growth and development, and decreased circulating testosterone, among others. Because these findings were only seen in animals, it is not yet clear what these findings mean for human patients and the impact it could have on men (or the male children of pregnant women) who take CBD. For instance, these findings raise the concern that CBD could negatively affect a man’s fertility. Further testing and evaluation are needed to better understand this potential risk.
In addition, CBD can be the cause of side effects that you might notice. These side effects should improve when CBD is stopped or when the amount used is reduced. This could include changes in alertness, most commonly experienced as somnolence (sleepiness), but this could also include insomnia; gastrointestinal distress, most commonly experienced as diarrhea and/or decreased appetite but could also include abdominal pain or upset stomach; and changes in mood, most commonly experienced as irritability and agitation.
The FDA is actively working to learn more about the safety of CBD and CBD products, including the risks identified above and other topics, such as:
- Cumulative Exposure: The cumulative exposure to CBD if people access it across a broad range of consumer products. For example, what happens if you eat food with CBD in it, use CBD-infused skin cream and take other CBD-based products on the same day? How much CBD is absorbed from your skin cream? What if you use these products daily for a week or a month?
- Special Populations: The effects of CBD on other special populations (e.g., the elderly, children, adolescents, pregnant and lactating women).
- CBD and Animals: The safety of CBD use in pets and other animals, including considerations of species, breed, or class and the safety of the resulting human food products (e.g., meat milk, or eggs) from food-producing species.
Unproven medical claims, unsafe manufacturing practices
Some CBD Products are Being Marketed with Unproven Medical Claims and Could be Produced with Unsafe Manufacturing Practices
Unlike the FDA-approved CBD drug product, unapproved CBD products, which could include cosmetics, foods, products marketed as dietary supplements, and any other product (other than Epidiolex) making therapeutic claims, have not been subject to FDA evaluation regarding whether they are effective to treat a particular disease or have other effects that may be claimed. In addition, they have not been evaluated by the FDA to determine what the proper dosage is, how they could interact with other drugs or foods, or whether they have dangerous side effects or other safety concerns.
Misleading, unproven, or false claims associated with CBD products may lead consumers to put off getting important medical care, such as proper diagnosis, treatment, and supportive care. For that reason, it’s important to talk to your doctor about the best way to treat diseases or conditions with available FDA-approved treatment options.
In addition to safety risks and unproven claims, the quality of many CBD products may also be in question. The FDA is also concerned that a lack of appropriate processing controls and practices can put consumers at additional risks. For example, the agency has tested the chemical content of cannabinoid compounds in some of the products, and many were found to not contain the levels of CBD they claimed. We are also investigating reports of CBD potentially containing unsafe levels of contaminants (e.g., pesticides, heavy metals, THC).
CBD products are also being marketed for pets and other animals. The FDA has not approved CBD for any use in animals and the concerns regarding CBD products with unproven medical claims and of unknown quality equally apply to CBD products marketed for animals. The FDA recommends pet owners talk with their veterinarians about appropriate treatment options for their pets.
The FDA’s top priority is to protect the public health. This priority includes making sure consumers know about products that put their health and safety at greatest risk, such as those claiming to prevent, diagnose, treat, mitigate, or cure serious diseases. For example, the agency has warned companies to stop selling CBD products they claim are intended to prevent, diagnose, treat, mitigate, or cure serious diseases such as cancer, Alzheimer’s disease, psychiatric disorders and diabetes. While we have focused on these types of products, we will continue to monitor the marketplace for any product that poses a risk to public health, including those with dangerous contaminants, those marketed to vulnerable populations, and products that otherwise put the public health at risk.
Evaluation of the regulatory frameworks
The FDA is Continuing to Evaluate the Regulatory Frameworks for Products Containing Cannabis and Cannabis-Derived Compounds
The FDA continues to believe the drug approval process represents the best way to ensure that safe and effective new medicines, including any drugs derived from cannabis, are available to patients in need of appropriate medical therapy. The agency is committed to supporting the development of new drugs, including cannabis and cannabis-derived drugs, through the investigational new drug and drug approval process.
We are aware that there may be some products on the market that add CBD to a food or label CBD as a dietary supplement. Under federal law, it is illegal to market CBD this way.
The FDA is evaluating the regulatory frameworks that apply to certain cannabis-derived products that are intended for non-drug uses, including whether and/or how the FDA might consider updating its regulations, as well as whether potential legislation might be appropriate. The information we have underscores the need for further study and high quality, scientific information about the safety and potential uses of CBD.
The FDA is committed to setting sound, science-based policy. The FDA is raising these safety, marketing, and labeling concerns because we want you to know what we know. We encourage consumers to think carefully before exposing themselves, their family, or their pets, to any product, especially products like CBD, which may have potential risks, be of unknown quality, and have unproven benefits.
Our Consumer Update includes a practical summary of what we know to date. As we learn more, our goal is to update you with the information you need to make informed choices about CBD products. Also, as the regulatory pathways are clarified we will take care to inform all stakeholders as quickly as possible.
Researchers recommend clinical trials for CBD to prevent COVID-19 based on promising animal data
An interdisciplinary team of researchers from the University of Chicago has found evidence that cannabidiol (CBD), a product of the cannabis plant, can inhibit infection by SARS-CoV-2 in human cells and in mice.
The study, published on January 20, 2022, in Science Advances, found CBD showed a significant negative association with SARS-CoV-2 positive 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.
Scientists have been looking for new therapies for people infected by the coronavirus and emerging variants, especially those who lack access to vaccines, as the pandemic continues across the country and world and as breakthrough infections become more common.
CBD: An unexpected avenue for fighting COVID-19
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.’ Surprisingly, it directly inhibited viral replication in lung cells,” said Marsha Rosner, PhD, Charles B. Huggins Professor in the Ben May Department of Cancer Research and a senior author of the study.
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 SARS-CoV-2 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 SARS-CoV-2 in addition to the original strain.
CBD did not affect the ability of SARS-CoV-2 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, SARS-CoV-2 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 SARS-CoV-2 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 SARS-CoV-2 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 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,” Rosner said.
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 SARS-CoV-2 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.”
The study, “Cannabidiol Inhibits SARS-CoV-2 Replication through Induction of the Host ER Stress and Innate Immune Responses,” was supported by a BIG Vision grant from the University of Chicago, the National Institutes of Health (R01 GM121735, R01 CA184494, R01 AI137514, R01 AI127518, R01 AI134980, R01 CA219815, R35 GM119840, P30 CA014599), and the Harry B. and Leona M Helmsley Charitable Trust. 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.