If you buy or sell CBD, you could be breaking the law. These science lessons can explain why. Questions and answers about FDA regulation of cannabis and cannabis-derived products The explosive growth of consumer products containing hemp-derived cannabidiol (CBD) has increased exponentially in the past few years, as demand for the novel
Is CBD legal? Here’s what you need to know, according to science
I’ve come upon it in pharmacy chain stores and gas stations. My dog kennel sells CBD (cannabidiol) gummies for pets, and multiple massage spas in the D.C.-metro area offer “CBD-infused relaxation” through lotions, oils and sprays. There are at least four cafes within a 15-minute walk of the White House that sell CBD coffee.
Yet here’s a strange fact about the overnight ubiquity of these products: Selling them is illegal. That’s true even though the 2018 Farm Bill removed legal restrictions on CBD if it’s derived from hemp plants.
What’s equally strange: Buying CBD products is legal…at least sometimes.
This paradox is one of many in America’s long history of both utilizing and criminalizing cannabis. As marijuana, cannabis has been a tool for relaxation, as well as an element of mass incarceration — but also for medical benefits, like to fight the side effects of cancer chemotherapy.
That tension is something two professors and their students are trying to better understand at the University of Connecticut, which launched the nation’s only college course on growing weed earlier this year.
While “there are all sorts of classes to train lawyers to understand cannabis law and programs for medical practitioners to learn how to dispense medical marijuana,” said Gerry Berkowitz, a 20-year professor of plant science who co-runs UConn’s new course, this is the first in decades to focus on questions like: How exactly does this stuff grow and how can we use it?
They’re among many in the U.S. who are peering through the fog of the clinical claims, legal quagmires and social stigma around weed.
Cannabis, which has been cultivated by humans for at least 12,000 years, is “one of the oldest plants on record as having been used for human benefit,” said Shelley Durocher, a UConn research grower who manages the hemp greenhouse for the class. It’s a fascinating plant that occupies a unique space in the natural world, Durocher said, one that has helped shape the modern existence of Western countries like the U.S.
As hemp, its fiber made the sails that carried European colonists across much of the known world. It was so fundamental to America’s foundations that its image was printed on money. George Washington was notoriously bad at growing hemp, though.
“Began to separate the Male from the Female hemp…rather too late,” Washington penned in his diary in August 1765. (We’ll get to why that’s a problem later.)
A cheat guide to CBD
If you’re looking for the abridged version of this story so you can pass your “pot” quiz, here are the main takeaways.
- The 2018 Farm Bill legalized the production and sale of hemp and its extracts. Hemp, by federal law, cannot contain more than 0.3 percent THC (tetrahydrocannabinol). Anything with more THC is classified as marijuana, is considered a schedule 1 drug by the Drug Enforcement Administration and is federally illegal.
- A hemp crop can accidentally start growing marijuna packed with THC because of pollination and sexual reproduction. (Cannabis plants are typically either male or female). Unexpected pollination can easily happen in outdoor fields, given cannabis plants grow abundantly in the wild and their pollen can travel for miles. If your CBD comes from a marijuana plant, it’s illegal. If your CBD contains too much THC (more than 0.3 percent), it’s illegal.
- The extraction process for CBD and THC is essentially the same. As a consequence, CBD can be contaminated with THC, chemical solvents or pesticides if the extraction is done improperly.
- The only approved health use of CBD is the seizure drug Epidiolex, despite having many other suspected benefits. The FDA prohibits the sale of CBD in any unapproved health products, dietary supplements or food — which literally means everything except for this epilepsy drug.
- If CBD comes from a hemp plant with less than 0.3 percent THC, you can buy it under federal law — but some states still have legal restrictions on the possession of CBD.
Cannabis’ reputation has shifted significantly since then, from vital resource to societal ill to maybe something in between.
Berkowitz and professor Matthew DeBacco launched the class at UConn — called “Horticulture of Cannabis: from Seed to Harvest” — to fill a desperate need in the ever-budding cannabis industry, with U.S. sales expected to reach $80 billion by 2030. Three years ago, another of Berkowitz’s undergrad classes took a field trip to one of Connecticut’s medical marijuana producers.
“The owner said his head grower learned their trade by growing pot in their basement,” Berkowitz said. In pointing this out, he was not trying to throw shade on these employees, but rather emphasizing that many of the growing practices in the marijuana industry aren’t typically standardized nor backed by research.
Which brings us back to those CBD lotions and lattes — and how they can be both legal and illegal.
Due to the way cannabis plants naturally grow and breed, many CBD products in stores contain the same drug that makes marijuana federally illicit — THC or tetrahydrocannabinol.
And even if you make sure that your CBD is pure, some federal agencies and state laws still forbid it — even in places where medical or recreational weed is legal.
So before you add CBD to your routine, it might help us all to head back to school for a few science lessons that explain how cannabis is grown, how the compound is collected, and the ways it might benefit and harm your health.
What is cannabis?
Cannabis has many names, strains and varieties, including hemp and marijuana. But these days, they’re all considered one species: Cannabis sativa.
“Marijuana” is any cannabis plant with abundant amounts — technically, more than 0.3 percent — of the mind-altering drug THC. Though 11 states and Washington, D.C., have legalized recreational marijuna, this version of cannabis remains federally illegal and classified as a schedule 1 drug by the Drug Enforcement Administration.
“Hemp,” by contrast, cannot legally contain more than 0.3 percent THC. There are almost no restrictions on the hundreds of other compounds made by the plant, such as terpenes (which are responsible for weed’s “distinctive” aroma).
One noteworthy contradiction in weed law: Marijuana can also produce CBD. If your purified CBD comes from hemp plants, it is federally legal, but if it comes from a marijuana plant, it is illegal. That’s because marijuna plants themselves are prohibited by the DEA.
CBD versus THC
The most obvious hurdles to making pure and legal CBD arise from being unable to tell marijuana and hemp plants apart.
Just try it for yourself:
Hemp versus marijuana. Good luck spotting a difference. Image by Devin Pinckard
“So how do we make a distinction when … basically looking at the plant structure, you really can’t tell the difference?” DeBacco, one of the cannabis course professors, asked us on the campus quad after class (located in the university’s largest lecture hall, due to its popularity).
His answer: “You’ve got to go beyond what they look like to the chemical profiles.”
Scientists suspect cannabinoids protect the plant from UV rays, much like sunscreen does for human skin.
Both THC and CBD are members of a chemical family called cannabinoids. Cannabinoids are plants oils, and cannabis comes packed with more than 100 versions of them.
Scientists suspect cannabinoids protect the plant from UV rays, much like sunscreen does for human skin. They think that because up to a quarter of a cannabis plant’s weight can come from just cannabinoids — and cannabinoid levels change with light exposure. “At the top of the plant, you’ll get more cannabinoids, compared to flowers that are at the lower end of the plant,” graduate student Peter Apicella said.
Cannabis makes most of its cannabinoids in its flowers, which are more commonly called “buds.”
“If they don’t get pollinated, the buds will essentially just keep growing and keep producing cannabinoids,” Apicella said.
This is true of both CBD and THC. The only chemical difference between them comes down to a couple of chemical bonds.
CBD and THC are like the “fraternal twins” of plant chemistry. They are basically identical, aside from a couple bond. Image by Adam Sarraf
All cannabinoids start out as a bit of sugar, which hitchhikes around the plants’ enzymes, changing its identity, bit by bit, with each ride. In some cases, this wandering sugar reaches a crossroads, where it can either can bum a ride from one of two enzymes: THC-a synthase or CBD-a synthase. One route leads to becoming THC, the other to becoming CBD.
But in hemp, THC synthase is genetically dormant, Apicella said. As a result, some hemp plants can make loads of CBD because there is no internal competition for making THC.
“With other highly valuable crops — like saffron or vanilla — you get a small percentage of the plant that’s actually usable yield,” Apicella explained. But with hemp, “it’s a huge amount.” Some strains have are upwards of 12 to 15 percent CBD by weight.
How a hemp crop can sometimes become marijuana
Thanks to the “miracle” of reproduction, a hemp crop can start off making only CBD and then unwittingly turn into a THC-laden field of marijuana.
Let’s just say that again because it is a bit mind-blowing. A hemp crop — that is federally legal and only makes CBD — can become marijunana. Studies have found that if two certifiable hemp plants hook up, most of their offspring will be able to make THC. In fact, some of these seedlings will ONLY make THC.
Cannabis is abundant in the wild — meaning an outdoor hemp field is one gust of pollen away from accidentally breeding marijuana.
The wild card for hemp growers is pollination. Most flowering plants boast both male and female parts. They’re hermaphrodites that can mate with themselves. But a cannabis plant is an exception, in that it is almost always either female OR male. And when the plants reproduce sexually, their traits mix and once dormant genes — like those behind THC production — can suddenly be replaced with active versions.
Any biological organism is going to fluctuate — a variable that farmers and growers are always really concerned about, Apicella said.
So to prevent sexual reproduction, UConn’s greenhouse smashes the (cannabis) patriarchy. You don’t want a male in your greenhouse, Apicella said: “If there’s a male, your whole crops can be destroyed.”
So UConn’s greenhouses only grows female hemp plants — all of them are clones. There’s even a small pistil — called a preflower — on young plants that allows horticulturists to identify females without a genetic test.
To grow an all-female group, “you snip a part of a plant off, and you put it in soil with a little rooting hormone and that cutting is actually genetically identical to that first mother plant that you took from,” Apicella explained, raising his arms and pointing to a long row of hemp plants. “So these are all genetically identical to one of the mother plants we have in here.”
Keeping a greenhouse all-female is easy, but it’s a different story growing hemp outdoors.
Cannabis is abundant in the wild — meaning an outdoor hemp field is one gust of pollen away from accidentally breeding marijuana.
The other way that THC can sneak into your CBD bottle
To collect CBD or THC from hemp, farmers harvest the plants and send them to an extractor, who collects the drugs and preps them for sale. The issue is that extracting CBD or THC is essentially the same process. If your supplier does it incorrectly, your CBD bottle might carry an illegal dose of THC.
“It happens all the time,” said Rino Ferrarese, COO of the medical marijuana extractor CT Pharma, who is frustrated by low-quality and tainted products flooding the CBD market. Under Connecticut law, Ferrarese’s company must ensure their products match the labels on their bottles — which they accomplish through pharmaceutical-grade extraction.
Ferrarese said many states across the country do not hold their CBD suppliers to the same standards and federal enforcement is lacking.
Cannabinoids are extracted as oils or resins, which can be gooey. Image by CT Pharma
“What a lot of consumers don’t realize is that the FDA, who’s charged with protecting our safety with respect to food and medicine in the U.S., are not on top of policing those CBD products that you see in the gas station or at the grocery store,” Ferrarese said. “A lot of these products are also not under the purview of departments of public health either.”
As a lark, he and others at the company keep tabs on the sloppy and sometimes illicit products flooding the CBD market. Ferrarese said the results vary widely, and rarely do these products ever meet the claims on their labels.
The math that’s fueling the CBD green rush
A little math can explain why farmers and suppliers are excited about CBD.
To make CBD, farmers can grow up to 4,000 hemp plants in an acre. A single hemp plant can make about a half kilogram of plant material for CBD extraction.
A half kilogram of this cannabis material can yield about 75 grams of CBD, according to Rino Ferrarese, COO of the medical marijuana extractor CT Pharma. That much CBD can make about 350 bottles of lotion, he said, which each typically hold about 200 milligrams of the compound.
That means a single acre of hemp can make about 1.4 million bottles of CBD lotion. If you sell each of those bottles for $30, that’s…a boatload of greenbacks.
“Whenever we see CBD at a gas station or in a retail location, we purchase it and we send it to our independent third-party laboratory,” Ferrarese said. “Sometimes it even contains THC in the bottle when it’s not supposed to. It’s really a crap shoot.”
Extractors can prevent THC from entering a CBD supply. To sap CBD or THC from plant material, all extractions use a chemical solvent. That sounds nefarious, but a solvent is any substance that can dissolve another. Water, for instance, is one of nature’s best solvents — but it wouldn’t be effective for something like this.
“In Connecticut, we’re limited to using only [liquid] carbon dioxide as a solvent for extraction or ethanol as a solvent, Ferrarese said. “In other states, such as Colorado and California, they’re allowed to use solvents like butane.”
Liquid carbon dioxide and ethanol come with distinct advantages. Carbon dioxide is very efficient at stripping cannabinoids from plants, but it must be kept at cold temperatures — -70 degrees Fahrenheit — to stay liquid.
Ethanol extraction, meanwhile, can be conducted at warmer temperatures in a process similar to making liquor, said Kimberly Provera, the operations manager at CT Pharma.
“There is a process called fractional distillation, where you can actually isolate different cannabinoids,” Provera said. “Each cannabinoid will separate based on a specific temperature…so you can isolate just CBD and THC.”
Once the gooey cannabinoids are separated, they add a little heat. The carbon dioxide and ethanol will eventually evaporate, leaving behind pure CBD or THC — but only if the extraction is done properly.
If your supplier makes a mistake, it might taint your CBD with THC — a consequence that can be problematic if your job randomly drug tests. Poor extractions can also leave behind the chemical solvents, which is hazardous in the case of butane, or even pesticides.
“There is a certain consumer expectation that we have here in America when we interact with our products, and cannabis should be no different,” Ferrarese said. “Cannabis, as a consumer packaged good, should have to meet those same standards for purity, identity and composition.”
Before you buy CBD, ask the store how its extracts were made and if they’re validated by a third-party tester.
Why you shouldn’t assume CBD is a cure-all
Raise your hand if you’ve heard someone state a version of the following:
“THC is psychoactive or mind-altering, hence it can make you high and why it is illegal. CBD, meanwhile, isn’t psychoactive.”
That’s not entirely accurate. CBD won’t intoxicate you, but from a neuroscience perspective, CBD is absolutely psychoactive, psychotropic or whatever adjective you want to use to say that it affects the mind and behavior. CBD just affects you differently than THC.
This lack of understanding has led to a lot of misconceptions about CBD, said Joseph Cheer, a neurobiologist at the University of Maryland School of Medicine who specializes in cannabinoids.
The first thing you need to know is that our bodies make their own natural versions of these compounds called endocannabinoids.
Akin to dopamine and serotonin, endocannabinoids can operate like neurotransmitters — the chemical messengers that activate or switch off our nerves. That, in turn, sparks or dampens the electric pulses that create our thoughts, behaviors and movements.
Why hemp seeds and their oils are typically legal
Cannabis pollination causes a plant’s flowers — its buds — to set seed and stop making cannabinoids. Hemp seeds and their oils have essentially zero cannabinoids and are only considered illegal if THC residue lands on them.
Cannabis pollination can also stunt the growth of female plants, which is problematic if you’re cultivating the plant for fibers. George Washington made the mistake of allowing his hemp crop to undergo pollination, and it ruined his harvest.
Our nerves receive those chemical messages through neurotransmitter receptors — think of them like radio antennas. Cannabinoids have two known receptors called CB1 and CB2.
This is where the mental effects of THC and CBD differ. THC makes us high because it has a strong affinity for the CB1 receptor, but CBD is the opposite. CBD does not typically interact with the CB1 receptor…at least not directly. Research shows CBD can elevate the body’s self-made endocannabinoids, and scientists are also hunting for a “hidden” brain receptor for the cannabis extract.
The other evidence that CBD is psychoactive? It can battle seizures.
The FDA has only approved one drug made from CBD: an epilepsy medication named Epidiolex. No one knows for sure how it works, but Cheer and other researchers suspect that Epidiolex tweaks how much calcium can get inside of our nerves.
Without going too far into the particulars, our nerve cells use calcium to carry those electrical pulses throughout the body. If a nerve cell has too much calcium, it will fire electric pulses at too fast a rate, which can cause a state of distress called excitotoxicity.
CBD appears to maintain a healthy balance of calcium in nerve cells, which wards off the electrical overloads and damage that happen during seizures.
Cheer said there is also strong support that CBD reduces anxiety and stymies addiction to opioids and marijuana. It may also offer sleep benefits to patients with multiple sclerosis, Parkinson’s disease and Huntington’s disease.
But FDA approval for these treatments, other medicines like lotions and foods may take years, and “the pace of discovery has already been significantly hindered by the scheduling of the plant,” Cheer said.
Most CBD products are illegal — but only if someone is checking
So if you buy CBD…and it came from a hemp plant…and it’s pure…then you’re in the clear…right? Not quite.
Yes, purchasing CBD is federally legal as long as it doesn’t contain more than 0.3 percent THC, but some state laws have put restrictions on buyers. For example, Virginians can only buy and possess CBD if they have a prescription.
Federal provisions have a blindspot whereby a store can sell as much CBD as it wants, as long it doesn’t make any health claims about its products…
It gets more complicated for sellers.
The FDA has prohibited the sale of CBD in any unapproved health products, dietary supplements or food — which literally means everything except for the drug Epidiolex.
The FDA can officially go after any companies selling or marketing items that make health claims about CBD, especially if those products involve interstate trade of the cannabis extract.
But the agency has limited staff for enforcement. As of this writing, the FDA has only issued warning letters to violators, though it has hinted at pursuing broader enforcement with federal and state partners if the CBD craze continues. Local law enforcement in states like Iowa, Ohio and Texas have also raided hemp and CBD stores this year.
These federal provisions, as written, also have a blindspot whereby a store can sell as much CBD as it wants, as long it doesn’t make any health claims about its products, put it in food nor add it to dietary supplements.
University of Connecticut grad student Peter Apicella works with a cannabis plant in a UConn greenhouse growing THC-free hemp. Photo by Mark Mirko/Hartford Courant/TNS via Getty Images
Connecticut’s road to a hemp industry
As PBS NewsHour science correspondent Miles O’Brien has detailed in past reports, marijuana research has been stymied by the plant’s designation as a federally illegal drug. And until recently, the same restrictions have applied to hemp and CBD.
The 2014 Farm Bill was the first piece of national legislation to permit hemp research, both for health and agriculture pilot programs. Last year’s updated law further loosened restrictions and expanded the grants available for such studies.
Connecticut is looking to capitalize. Legislation to start the state’s industrial hemp program was passed rapidly by state officials this spring.
“It solves a lot of issues for us in the state of Connecticut by creating an industry that can be quite lucrative,” said state senator Christine Cohen, who chairs the environmental committee that reviewed the bills. “The Connecticut Farm Bureau has been predicting $37,000 to $150,000 per acre and in gross value.”
Cohen said this green rush could help dairy farmers in Connecticut and across the nation. Nearly 3,000 U.S. dairy farms folded in 2018 alone.
A spokesperson for the Drug Enforcement Administration told the PBS NewsHour that their agency would have a limited role with these infractions. Since the Farm Bill said CBD with less than 0.3 percent THC was no longer a banned substance, it’s no longer under DEA’s purview, a spokesperson said in an email.
“It is now regulated by the FDA, so we refer you to them for this request,” the DEA spokesperson wrote. Another factor: “DEA does not pursue individual users – we focus on larger-scale operations and drug trafficking organizations,” the spokesperson added.
All of this is important for CBD sellers and consumers because the FDA has a mandate to verify the safest dosage for the chemicals that we consume or apply to our bodies — whether they be applied to drugs, food and dietary supplements — under the Food, Drug and Cosmetic Act.
The rapid legalization of hemp and CBD has put the FDA in a tough position. Under its mandate, the agency must validate the safety of foods, drugs and dietary supplements. But CBD products are already flooding American stores.
Cheer and the FDA caution “against all of the off-the-shelf CBD products” because the cannabis extract — like any compound you put in your body — can come with adverse side effects.
Human studies have shown that taking CBD can cause liver problems, diarrhea, vomiting and fatigue. Rodent research also suggests CBD can cause harm to male and female reproductive organs.
When it comes to CBD in the U.S., “whatever I tell you today may change significantly a week from today,” Cheer said.
Left: Even if your CBD is pure, some federal agencies and state laws still forbid it — even in places where medical or recreational cannabis is legal. The PBS NewsHour visited the nation’s only college course for growing weed — at the University of Connecticut — to explore the science and legality behind growing hemp to make CBD. Video by Nsikan Akpan and Jamie Leventhal. (Photo by AAron Ontiveroz/The Denver Post/Getty Images)
FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD)
There is a significant interest in the development of therapies and other consumer products derived from cannabis and its components, including cannabidiol (CBD). FDA recognizes the potential opportunities that cannabis or cannabis-derived compounds may offer and acknowledges the significant interest in these possibilities. However, FDA is aware that some companies are marketing products containing cannabis and cannabis-derived compounds in ways that violate the Federal Food, Drug and Cosmetic Act (FD&C Act) and that may put the health and safety of consumers at risk. The agency is committed to protecting the public health while also taking steps to improve the efficiency of regulatory pathways for the lawful marketing of appropriate cannabis and cannabis-derived products. FDA has a number of resources available that address cannabis and cannabis-derived products, such as CBD, and the agency wants to ensure that consumers and other stakeholders have access to these resources in a centralized location.
Questions and Answers
Below are a number of frequently asked questions and answers on this topic.
1. What are cannabis and marijuana?
A. 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). Parts of the Cannabis sativa plant have been controlled under the Controlled Substances Act (CSA) since 1970 under the drug class “Marihuana” (commonly referred to as “marijuana”) [21 U.S.C. 802(16)]. “Marihuana” is listed in Schedule I of the CSA due to its high potential for abuse, which is attributable in large part to the psychoactive effects of THC, and the absence of a currently accepted medical use of the plant in the United States.
2. How does the 2018 Farm Bill define hemp? What does it mean for FDA-regulated products?
A. At the federal level, the Agriculture Improvement Act of 2018, Pub. L. 115-334, (the 2018 Farm Bill) was signed into law on Dec. 20, 2018. Among other things, this new law changes certain federal authorities relating to the production and marketing of hemp, defined as “the plant Cannabis sativa L. and any part of that plant, including the seeds thereof and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing or not, with a delta-9 tetrahydrocannabinol concentration of not more than 0.3 percent on a dry weight basis.” These changes include removing hemp from the CSA, which means that cannabis plants and derivatives that contain no more than 0.3 percent THC on a dry weight basis are no longer controlled substances under federal law.
The 2018 Farm Bill, however, explicitly preserved FDA’s authority to regulate products containing cannabis or cannabis-derived compounds under the FD&C Act and section 351 of the Public Health Service Act (PHS Act). FDA treats products containing cannabis or cannabis-derived compounds as it does any other FDA-regulated products — meaning they’re subject to the same authorities and requirements as FDA-regulated products containing any other substance. This is true regardless of whether the cannabis or cannabis-derived compounds are classified as hemp under the 2018 Farm Bill.
3. Has FDA approved any medical products containing cannabis or cannabis-derived compounds such as CBD?
A. To date, the agency has not approved a marketing application for cannabis for the treatment of any disease or condition. FDA has, however, approved one cannabis-derived and three cannabis-related drug products. These approved products are only available with a prescription from a licensed healthcare provider.
FDA has approved Epidiolex, which contains a purified form of the drug substance CBD for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 1 years of age and older. It has also approved Epidiolex for the treatment of seizures associated with tuberous sclerosis complex in patients 1 year of age or older. That means FDA has concluded that this particular drug product is safe and effective for its intended use.
The agency also has approved Marinol and Syndros for therapeutic uses in the United States, including for the treatment of anorexia associated with weight loss in AIDS patients. Marinol and Syndros include the active ingredient dronabinol, a synthetic delta-9- tetrahydrocannabinol (THC) which is considered the psychoactive component of cannabis. Another FDA-approved drug, Cesamet, contains the active ingredient nabilone, which has a chemical structure similar to THC and is synthetically derived.
4. Aside from Epidiolex, are there other CBD drug products that are FDA-approved? What about the products I’ve seen in stores or online?
A. No. There are no other FDA-approved drug products that contain CBD. We are aware that some firms are marketing CBD products to treat diseases or for other therapeutic uses , and we have issued several warning letters to such firms. Under the FD&C Act, any product intended to have a therapeutic or medical use, and any product (other than a food) that is intended to affect the structure or function of the body of humans or animals, is a drug. Drugs must generally either receive premarket approval by FDA through the New Drug Application (NDA) process or conform to a “monograph” for a particular drug category, as established by FDA’s Over-the-Counter (OTC) Drug Review. CBD was not an ingredient considered under the OTC drug review. An unapproved new drug cannot be distributed or sold in interstate commerce.
FDA continues to be concerned at the proliferation of products asserting to contain CBD that are marketed for therapeutic or medical uses although they have not been approved by FDA. Often such products are sold online and are therefore available throughout the country. Selling unapproved products with unsubstantiated therapeutic claims is not only a violation of the law, but also can put patients at risk, as these products have not been proven to be safe or effective. This deceptive marketing of unproven treatments also raises significant public health concerns, because patients and other consumers may be influenced not to use approved therapies to treat serious and even fatal diseases.
Unlike drugs approved by FDA, products that have not been subject to FDA review as part of the drug approval process have not been evaluated as to whether they work, what the proper dosage may be if they do work, how they could interact with other drugs, or whether they have dangerous side effects or other safety concerns.
The agency has and will continue to monitor the marketplace and take action as needed to protect the public health against companies illegally selling cannabis and cannabis-derived products that can put consumers at risk and that are being marketed for therapeutic uses for which they are not approved. At the same time, FDA recognizes the potential therapeutic opportunities that cannabis or cannabis-derived compounds could offer and acknowledges the significant interest in these possibilities. FDA continues to believe that the drug approval process represents the best way to help ensure that safe and effective new medicines, including any drugs derived from cannabis, are available to patients in need of appropriate medical therapy. The Center for Drug Evaluation and Research (CDER) is committed to supporting the development of new drugs, including cannabis and cannabis-derived drugs, through the investigational new drug (IND) and drug approval process (see Question #16).
5. Why hasn’t FDA approved more products containing cannabis or cannabis-derived compounds for medical uses?
A. FDA is aware that unapproved cannabis or cannabis-derived products are being used for the treatment of a number of medical conditions including, for example, AIDS wasting, epilepsy, neuropathic pain, spasticity associated with multiple sclerosis, and cancer and chemotherapy-induced nausea.
To date, FDA has not approved a marketing application for cannabis for the treatment of any disease or condition and thus has not determined that cannabis is safe and effective for any particular disease or condition. The agency has, however, approved one cannabis-derived and three cannabis-related drug products (see Question #2).
FDA relies on applicants and scientific investigators to conduct research. The agency’s role, as laid out in the FD&C Act, is to review data submitted to the FDA in an application for approval to ensure that the drug product meets the statutory standards for approval.
The study of cannabis and cannabis-derived compounds in clinical trial settings is needed to assess the safety and effectiveness of these substances for the treatment of any disease or condition. FDA’s December 2016 Guidance for Industry: Botanical Drug Development provides specific recommendations on submitting INDs for botanical drug products, such as those derived from cannabis, in support of future marketing applications for these products. The agency’s July 2020 draft guidance, Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research Guidance for Industry, highlights quality considerations for anyone wishing to conduct clinical research in this area, particularly those who are less familiar with the FDA.
The FDA will continue to facilitate the work of companies interested in appropriately bringing safe, effective, and quality products to market, including scientifically-based research concerning the medicinal uses of cannabis. Additional information concerning research on the medical use of cannabis is available from the National Institutes of Health, particularly the National Cancer Institute (NCI) and National Institute on Drug Abuse (NIDA).
6. What is FDA’s reaction to states that are allowing cannabis to be sold for medical uses without the FDA’s approval?
A. The FDA is aware that several states have either passed laws that remove state restrictions on the medical use of cannabis and its derivatives or are considering doing so. It is important to conduct medical research into the safety and effectiveness of cannabis products through adequate and well-controlled clinical trials. We welcome the opportunity to talk with states who are considering support for medical research of cannabis and its derivatives, so that we can provide information on Federal and scientific standards.
7. Has the agency received any adverse event reports associated with cannabis use for medical conditions?
A. The agency has received reports of adverse events in patients using cannabis or cannabis-derived products to treat medical conditions. The FDA reviews such reports and will continue to monitor adverse event reports for any safety signals, with a focus on serious adverse effects. Consumers and healthcare providers can report adverse events associated with cannabis or cannabis-derived products via the FDA’s MedWatch reporting system, either online or by phone at 1-800-FDA-1088. For more information, please see the FDA’s webpage on MedWatch.
Information from adverse event reports regarding cannabis use is extremely limited; the FDA primarily receives adverse event reports for approved products. General information on the potential adverse effects of using cannabis and its constituents can come from clinical trials that have been published, as well as from spontaneously reported adverse events sent to the FDA. Additional information about the safety and effectiveness of cannabis and its constituents is needed. Clinical trials of cannabis conducted under an IND application could collect this important information as a part of the drug development process.
8. Is it legal for me to sell CBD products?
A. It depends, among other things, on the intended use of the product and how it is labeled and marketed. Even if a CBD product meets the definition of “hemp” under the 2018 Farm Bill (see Question #2), it still must comply with all other applicable laws, including the FD&C Act. The below questions and answers explain some of the ways that specific parts of the FD&C Act can affect the legality of CBD products.
We are aware that state and local authorities are fielding numerous questions about the legality of CBD. There is ongoing communication with state and local officials to answer questions about requirements under the FD&C Act, to better understand the landscape at the state level, and to otherwise engage with state/local regulatory partners.
9. Can THC or CBD products be sold as dietary supplements?
A. No. Based on available evidence, FDA has concluded that THC and CBD products are excluded from the dietary supplement definition under section 201(ff)(3)(B) of the FD&C Act [21 U.S.C. § 321(ff)(3)(B)]. Under that provision, if a substance (such as THC or CBD) is an active ingredient in a drug product that has been approved under section 505 of the FD&C Act [21 U.S.C. § 355], or has been authorized for investigation as a new drug for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public, then products containing that substance are excluded from the definition of a dietary supplement. FDA considers a substance to be “authorized for investigation as a new drug” if it is the subject of an Investigational New Drug application (IND) that has gone into effect. Under FDA’s regulations (21 CFR 312.2), unless a clinical investigation meets the limited criteria in that regulation, an IND is required for all clinical investigations of products that are subject to section 505 of the FD&C Act.
There is an exception to section 201(ff)(3)(B) if the substance was “marketed as” a dietary supplement or as a conventional food before the drug was approved or before the new drug investigations were authorized, as applicable. However, based on available evidence, FDA has concluded that this is not the case for THC or CBD.
FDA is not aware of any evidence that would call into question its current conclusions that THC and CBD products are excluded from the dietary supplement definition under section 201(ff)(3)(B) of the FD&C Act. Interested parties may present the agency with any evidence that they think has bearing on this issue. Our continuing review of information that has been submitted thus far has not caused us to change our conclusions.
When a substance is excluded from the dietary supplement definition under section 201(ff)(3)(B) of the FD&C Act, the exclusion applies unless FDA, in the agency’s discretion, has issued a regulation, after notice and comment, finding that the article would be lawful under the FD&C Act. To date, no such regulation has been issued for any substance.
Ingredients that are derived from parts of the cannabis plant that do not contain THC or CBD might fall outside the scope of this exclusion, and therefore might be able to be marketed as dietary supplements. However, all products marketed as dietary supplements must comply with all applicable laws and regulations governing dietary supplement products. For example, manufacturers and distributors who wish to market dietary supplements that contain “new dietary ingredients” (i.e., dietary ingredients that were not marketed in the United States in a dietary supplement before October 15, 1994) generally must notify FDA about these ingredients (see section 413(d) of the FD&C Act [21 U.S.C. § 350b(d)]). Generally, the notification must include information demonstrating that a dietary supplement containing the new dietary ingredient will reasonably be expected to be safe under the conditions of use recommended or suggested in the labeling. A dietary supplement is adulterated if it contains a new dietary ingredient for which there is inadequate information to provide reasonable assurance that the ingredient does not present a significant or unreasonable risk of illness or injury (see section 402(f)(1)(B) of the FD&C Act [21 U.S.C. 342(f)(1)(B)]).
Numerous other legal requirements apply to dietary supplement products, including requirements relating to Current Good Manufacturing Practices (CGMPs) and labeling. Information about these requirements, and about FDA requirements across all product areas, can be found on FDA’s website.
10. Is it legal, in interstate commerce, to sell a food (including any animal food or feed) to which THC or CBD has been added?
A. No. Under section 301(ll) of the FD&C Act [21 U.S.C. § 331(ll)], it is prohibited to introduce or deliver for introduction into interstate commerce any food (including any animal food or feed) to which has been added a substance which is an active ingredient in a drug product that has been approved under section 505 of the FD&C Act [21 U.S.C. § 355], or a drug for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public. There are exceptions, including when the drug was marketed in food before the drug was approved or before the substantial clinical investigations involving the drug had been instituted or, in the case of animal feed, that the drug is a new animal drug approved for use in feed and used according to the approved labeling. However, based on available evidence, FDA has concluded that none of these is the case for THC or CBD. FDA has therefore concluded that it is a prohibited act to introduce or deliver for introduction into interstate commerce any food (including any animal food or feed) to which THC or CBD has been added. FDA is not aware of any evidence that would call into question these conclusions. Interested parties may present the agency with any evidence that they think has bearing on this issue. Our continuing review of information that has been submitted thus far has not caused us to change our conclusions.
When this statutory prohibition applies to a substance, it prohibits the introduction into interstate commerce of any food to which the substance has been added unless FDA, in the agency’s discretion, has issued a regulation approving the use of the substance in the food (section 301(ll)(2) of the FD&C Act [21 U.S.C. § 331(ll)(2)]). To date, no such regulation has been issued for any substance.
Ingredients that are derived from parts of the cannabis plant that do not contain THC or CBD might fall outside the scope of 301(ll), and therefore might be able to be added to food. For example, as discussed in Question #12, certain hemp seed ingredients can be legally marketed in human food. However, all food ingredients must comply with all applicable laws and regulations. For example, by statute, any substance intentionally added to food is a food additive, and therefore subject to premarket review and approval by FDA, unless the substance is generally recognized as safe (GRAS) by qualified experts under the conditions of its intended use, or the use of the substance is otherwise excepted from the definition of a food additive (sections 201(s) and 409 of the FD&C Act [21 U.S.C. §§ 321(s) and 348]). Aside from the three hemp seed ingredients mentioned in Question #12, no other cannabis or cannabis-derived ingredients have been the subject of a food additive petition, an evaluated GRAS notification, or have otherwise been approved for use in food by FDA. Food companies that wish to use cannabis or cannabis-derived ingredients in their foods are subject to the relevant laws and regulations that govern all food products, including those that relate to the food additive and GRAS processes.
11. In making the two previous determinations about THC, why did FDA conclude that THC is an active ingredient in a drug product that has been approved under section 505 of the FD&C Act? In making the two previous determinations about CBD, why did FDA determine that substantial clinical investigations have been authorized for and/or instituted, and that the existence of such investigations has been made public?
A. THC (dronabinol) is the active ingredient in the approved drug products, Marinol capsules (and generics) and Syndros oral solution. CBD is the active ingredient in the approved drug product, Epidiolex.
The existence of substantial clinical investigations regarding THC and CBD have been made public. For example, two such substantial clinical investigations include GW Pharmaceuticals’ investigations regarding Sativex. (See Sativex Commences US Phase II/III Clinical Trial in Cancer Pain )
12. Can hulled hemp seed, hemp seed protein powder, and hemp seed oil be used in human food?
A. In December 2018, FDA completed its evaluation of three generally recognized as safe (GRAS) notices for the following hemp seed-derived food ingredients: hulled hemp seed, hemp seed protein powder, and hemp seed oil. FDA had no questions regarding the company’s conclusion that the use of such products as described in the notices is safe. Therefore, these products can be legally marketed in human foods for the uses described in the notices, provided they comply with all other requirements. These GRAS notices related only to the use of these ingredients in human food. To date, FDA has not received any GRAS notices for the use of hemp-derived ingredients in animal food (see Question #25).
Hemp seeds are the seeds of the Cannabis sativa plant. The seeds of the plant do not naturally contain THC or CBD. The hemp seed-derived ingredients that are the subject of these GRAS notices contain only trace amounts of THC and CBD, which the seeds may pick up during harvesting and processing when they are in contact with other parts of the plant. Consumption of these hemp seed-derived ingredients is not capable of making consumers “high.”
The GRAS conclusions can apply to ingredients for human food marketed by other companies, if they are manufactured in a way that is consistent with the notices and they meet the listed specifications. Some of the intended uses for these ingredients include adding them as source of protein, carbohydrates, oil, and other nutrients to beverages (juices, smoothies, protein drinks, plant-based alternatives to dairy products), soups, dips, spreads, sauces, dressings, plant-based alternatives to meat products, desserts, baked goods, cereals, snacks and nutrition bars. Products that contain any of these hemp seed-derived ingredients must declare them by name on the ingredient list.
These GRAS conclusions do not affect the FDA’s position on the addition of CBD and THC to food.
13. What is FDA’s position on cannabis and cannabis-derived ingredients in cosmetics?
A. A cosmetic is defined in 201(i) as “(1) articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance, and (2) articles intended for use as a component of any such articles; except that such term shall not include soap.”
Under the FD&C Act, cosmetic products and ingredients are not subject to premarket approval by FDA, except for most color additives. Certain cosmetic ingredients are prohibited or restricted by regulation, but currently that is not the case for any cannabis or cannabis-derived ingredients. Ingredients not specifically addressed by regulation must nonetheless comply with all applicable requirements, and no ingredient – including a cannabis or cannabis-derived ingredient – can be used in a cosmetic if it causes the product to be adulterated or misbranded in any way. A cosmetic generally is adulterated if it bears or contains any poisonous or deleterious substance which may render it injurious to users under the conditions of use prescribed in the labeling, or under such conditions of use as are customary or usual (section 601(a) of the FD&C Act [21 U.S.C. § 361(a)]).
If a product is intended to affect the structure or function of the body, or to diagnose, cure, mitigate, treat or prevent disease, it is a drug, or possibly both a cosmetic and a drug, even if it affects the appearance. (See Question #3 for more information about drugs.)
FDA can take action if it has information that an ingredient or cosmetic product is unsafe to consumers. Consumers can report adverse events associated with cosmetic products via the FDA’s MedWatch reporting system, either online or by phone at 1-800-FDA-1088, or by contacting your nearest FDA district office consumer complaint coordinator. For more information, please see the FDA’s webpage on how to report a cosmetic-related complaint.
14. Will FDA take action against cannabis or cannabis-related products that are in violation of the FD&C Act?
A. The FDA has sent warning letters in the past to companies illegally selling CBD products that claimed to prevent, diagnose, treat, or cure serious diseases, such as cancer. Some of these products were in further violation of the FD&C Act because they were marketed as dietary supplements or because they involved the addition of CBD to food.
When a product is in violation of the FD&C Act, FDA considers many factors in deciding whether or not to initiate an enforcement action. Those factors include, among other things, agency resources and the threat to the public health. FDA also may consult with its federal and state partners in making decisions about whether to initiate a federal enforcement action.
15. Can I import or export cannabis-containing or cannabis-derived products?
A. General information about the import/export of drug products regulated by FDA can be found online here. The Drug Enforcement Administration (DEA) is the federal agency responsible for enforcing the controlled substance laws and regulations in the U.S. and, as such, should be consulted with respect to any regulations/requirements they may have regarding the import or export of products containing cannabis. Please see here for information about importing or exporting food ingredients.
Regarding imports, if it appears that an article is adulterated, misbranded, in violation of section 505 of the FD&C Act, or prohibited from introduction or delivery for introduction into interstate commerce under section 301(ll) of the FD&C Act, such article will be refused admission (see section 801(a)(3) of the FD&C Act [21 U.S.C. § 381(a)(3)]).
Research and Expanded Access
16. What is FDA’s role when it comes to the investigation of cannabis and cannabis-derived products for medical use?
A. To conduct clinical research that can lead to an approved new drug, including research using materials from plants such as cannabis, researchers need to work with the FDA and submit an IND application to the Center for Drug Evaluation and Research (CDER). The IND application process gives researchers a path to follow that includes regular interactions with the FDA to support efficient drug development while protecting the patients who are enrolled in the trials. For research for use as an animal drug product, researchers would establish an investigational new animal drug (INAD) file with the Center for Veterinary Medicine to conduct their research, rather than an IND with CDER.
As discussed above (see Question #2), the 2018 Farm Bill removed hemp from the CSA. This change may streamline the process for researchers to study cannabis and its derivatives, including CBD, that fall under the definition of hemp, which could speed the development of new drugs.
As also discussed above (see Question #5) the agency also issued a draft guidance in July 2020, Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research Guidance for Industry, for individuals considering clinical research in this area.
Conducting clinical research using cannabis-related substances that are scheduled by the DEA often involves interactions with several federal agencies. This includes: a registration administered by the DEA; obtaining the cannabis for research from NIDA, within the National Institutes of Health, or another DEA-registered source; and review by the FDA of the IND or INAD application and research protocol. Additionally:
- For a Schedule I controlled substance under the CSA, DEA provides researchers with investigator and protocol registrations and has Schedule I-level security requirements at the site cannabis will be studied.
- NIDA provides research-grade cannabis for scientific study. The agency is responsible for overseeing the cultivation of cannabis for medical research and has contracted with the University of Mississippi to grow cannabis for research at a secure facility. Cannabis of varying potencies and compositions is available. DEA also may allow additional growers to register with the DEA to produce and distribute cannabis for research purposes.
- Researchers work with the FDA and submit an IND application to the appropriate division in the Office of New Drugs in CDER depending on the therapeutic indication. Based on the results obtained in studies conducted at the IND stage, sponsors may submit a marketing application for formal approval of the drug.
17. Does the FDA object to the clinical investigation of cannabis for medical use?
A. No. The FDA believes that scientifically valid research conducted under an IND application is the best way to determine what patients could benefit from the use of drugs derived from cannabis. The FDA supports the conduct of that research by:
- Providing information on the process needed to conduct clinical research using cannabis.
- Providing information on the specific requirements needed to develop a drug that is derived from a plant such as cannabis. In December 2016, the FDA updated its Guidance for Industry: Botanical Drug Development, which provides sponsors with guidance on submitting IND applications for botanical drug products.
- Providing specific support for investigators interested in conducting clinical research using cannabis and its constituents as a part of the IND process through meetings and regular interactions throughout the drug development process.
- Providing general support to investigators to help them understand and follow the procedures to conduct clinical research through the FDA Center for Drug Evaluation and Research’s Small Business and Industry Assistance group.
18. How can patients gain access to cannabis or cannabis-derived products for medical use through expanded access?
A. Expanded access is a potential pathway for a patient with a serious or life-threatening disease or condition to try an investigational medical product (drug, biologic, or medical device) for treatment outside of clinical trials when there are no comparable or satisfactory therapies available. Manufacturers may be able to make investigational drugs available to individual patients in certain circumstances through expanded access, as described in the FD&C Act and implementing regulations.
19. Can patients gain access to cannabis or cannabis-derived products for medical use through Right to Try?
A. Information for patients on Right to Try (RTT) is available on our website. RTT is designed to facilitate access to certain investigational drugs through direct interactions between patients, their physicians and drug sponsors – FDA is not involved in these decisions. Sponsors developing drugs for life-threatening conditions are responsible for determining whether to make their products available to patients who qualify for access under RTT. If you are interested in RTT, you should discuss this pathway with your licensed physician. Companies who develop drugs and biologics, also known as sponsors, can provide information about whether their drug/biologic is considered an eligible investigational drug under RTT and if they are able to provide the drug/biologic under the RTT Act.
Children and Pregnant/Lactating Women
20. Does the FDA have concerns about administering a cannabis product to children?
A. We understand that parents are trying to find treatments for their children’s medical conditions. However, the use of untested drugs can have unpredictable and unintended consequences. Caregivers and patients can be confident that FDA-approved drugs have been carefully evaluated for safety, efficacy, and quality, and are monitored by the FDA once they are on the market. The FDA continues to support sound, scientifically-based research into the medicinal uses of drug products containing cannabis or cannabis-derived compounds, and will continue to work with companies interested in bringing safe, effective, and quality products to market. With the exception of Epidiolex, Marinol, and Syndros, no product containing cannabis or cannabis-derived compounds (either plant-based or synthetic) has been approved as safe and effective for use in any patient population, whether pediatric or adult.
21. Does the FDA have concerns about administering a cannabis product to pregnant and lactating women?
A. The FDA is aware that there are potential adverse health effects with use of cannabis products containing THC in pregnant or lactating women. Published scientific literature reports potential adverse effects of cannabis use in pregnant women, including fetal growth restriction, low birth weight, preterm birth, small-for-gestational age, neonatal intensive care unit (NICU) admission, and stillbirth. [1, 2, 3] Based on published animal research, there are also concerns that use of cannabis during pregnancy may negatively impact fetal brain development. [4, 5, 6 ] The American College of Obstetricians and Gynecologists (ACOG) recommends that women who are pregnant or contemplating pregnancy should be encouraged to discontinue cannabis use. In addition, ACOG notes that there are insufficient data to evaluate the effects of cannabis use on breastfed infants; therefore, cannabis use is discouraged when breastfeeding.  Pregnant and lactating women should talk with a health care provider about the potential adverse health effects of cannabis use.
22. What does the FDA think about making CBD available to children with epilepsy?
A. The FDA has approved Epidiolex, which contains a purified form of the drug substance CBD, for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 1 years of age and older. It has also approved Epidiolex for the treatment of seizures associated with tuberous sclerosis complex in patients 1 year of age or older. That means the FDA has concluded that this particular drug product is safe and effective for its intended use. Controlled clinical trials testing the safety and efficacy of a drug, along with careful review through the FDA’s drug approval process, is the most appropriate way to bring cannabis-derived treatments to patients. Because of the adequate and well-controlled clinical studies that supported this approval, and the assurance of manufacturing quality standards, prescribers can have confidence in the drug’s uniform strength and consistent delivery that support appropriate dosing needed for treating patients with these complex and serious epilepsy syndromes.
23. What should I do if my child eats something containing cannabis?
A. With the exception of products such as the hemp seed ingredients discussed in Question #12, which have been evaluated for safety, it is important to protect children from accidental ingestion of cannabis and cannabis-containing products. FDA recommends that these products are kept out of reach of children to reduce the risk of accidental ingestion. If the parent or caregiver has a reasonable suspicion that the child accidentally ingested products containing cannabis, the child should be taken to a physician or emergency department, especially if the child acts in an unusual way or is/feels sick.
Pets and other Animals
24. I’ve seen cannabis products being marketed for pets. Are they safe?
A. FDA is aware of some cannabis products being marketed as animal health products. We want to stress that FDA has not approved cannabis for any use in animals, and the agency cannot ensure the safety or effectiveness of these products. For these reasons, FDA cautions pet-owners against the use of such products and recommends that you talk with your veterinarian about appropriate treatment options for your pet.
Signs that your pet may be suffering adverse effects from ingesting cannabis may include lethargy, depression, heavy drooling, vomiting, agitation, tremors, and convulsions.
If you have concerns that your pet is suffering adverse effects from ingesting cannabis or any substance containing cannabis, consult your veterinarian, local animal emergency hospital or an animal poison control center immediately.
While the agency is aware of reports of pets consuming various forms of cannabis, to date, FDA has not directly received any reports of adverse events associated with animals given cannabis products. However, adverse events from accidental ingestion are well-documented in scientific literature. If you feel your animal has suffered from ingesting cannabis, we encourage you to report the adverse event to the FDA. Please visit Reporting Information about Animal Drugs and Devices to learn more about how to report an adverse event related to an animal drug or for how to report an adverse event or problem with a pet food.
25. Can hemp be added to animal food?
A. All ingredients in animal food must be the subject of an approved food additive petition or generally recognized as safe (GRAS) for their intended use in the intended species. If an animal food contains an ingredient that is not the subject of an approved food additive petition or GRAS for its intended use in the intended species, that animal food would be adulterated under section 402(a)(2)(C)(i) of the FD&C Act [21 U.S.C. § 342(a)(2)(C)(i)]. In coordination with state feed control officials, CVM also recognizes ingredients listed in the Official Publication (OP) of the Association of American Feed Control Officials (AAFCO) as being acceptable for use in animal food. At this time, there are no approved food additive petitions or ingredient definitions listed in the AAFCO OP for any substances derived from hemp, and we are unaware of any GRAS conclusions regarding the use of any substances derived from hemp in animal food. Learn more about animal food ingredient submissions here.
With respect to products labeled to contain “hemp” that may also contain THC or CBD, as mentioned above it is a prohibited act under section 301(ll) of the FD&C Act to introduce or deliver for introduction into interstate commerce any animal food to which THC or CBD has been added.
26. Can approved human drugs containing CBD or synthetic THC be used extralabel in animals?
A. The Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA), permits veterinarians to prescribe extralabel uses of approved human and animal drugs for animals under certain conditions. Extralabel use must comply with all the provisions of AMDUCA and its implementing regulation at 21 CFR § 530. Among other limitations, these provisions allow extralabel use of a drug only on the lawful order of a licensed veterinarian in the context of a valid veterinarian-client-patient relationship and only in circumstances when the health of an animal is threatened or suffering, or death may result from failure to treat.
In addition, under 21 CFR 530.20, extralabel use of an approved human drug in a food-producing animal is not permitted if an animal drug approved for use in food-producing animals can be used in an extralabel manner for the use. In addition, under 21 CFR 530.20(b)(2), if scientific information on the human food safety aspect of the use of the approved human drug in food-producing animals is not available, the veterinarian must take appropriate measures to ensure that the animal and its food products will not enter the human food supply.
For more information on extralabel use of FDA approved drugs in animals, see Extralabel Use of FDA Approved Drugs In Animals.
 Gray, et al. Identifying Prenatal Cannabis Exposure and Effects of Concurrent Tobacco Exposure on Neonatal Growth. Clinical Chemistry. 2010; 56(9): 1442-1450.
 Gunn, et al. Prenatal Exposure to cannabis and maternal and child health outcomes: a systematic review and meta-analysis. BMJ Open. 2016; 6:e009986.
 Hayatbakhsh, et al. Birth Outcomes associated with cannabis use before and during pregnancy. Pediatric Research. 2012; 71 (2): 215-219.
 Silva, et al. Prenatal tetrahydrocannabinol (THC) alters cognitive function and amphetamine response from weaning to adulthood in the rat. Neurotoxicol and Teratol 2012; 34(1): 63-71.
 Trezza, et al. Effects of perinatal exposure to delta-9-tetrahydrocannabinol on the emotional reactivity of the offspring: a longitudinal behavioral study in Wistar rats. Psychopharmacology (Berl) 2008; 198(4): 529-537.
 Campolongo, et al. Perinatal exposure to delta-9-tetrahydrocannabinol causes enduring cognitive deficits associated with alteration of cortical gene expression and neurotransmission in rats. Addict Biol 2007; 12(3-4): 485–495.
The ‘State’ of CBD when Added to FDA-Regulated Products
The explosive growth of consumer products containing hemp-derived cannabidiol (CBD) has increased exponentially in the past few years, as demand for the novel ingredient continues to stoke interest from those ranging from the ‘merely curious’ to the ‘loyal believers.’ To many, CBD offers a variety of benefits when ingested, inhaled, or applied topically – with product marketing and advertising claims similarly ranging from calming effects to pain relief. Not surprisingly, therefore, the number of CBD-containing products that appear on store shelves has increased rapidly, presenting both opportunity and risk. Federal regulation has struggled to keep up, and in the absence of action and enforcement, states and localities have rapidly filled the void. Retailers, manufacturers, and consumers alike, therefore, need to be knowledgeable about requirements for the production, marketing, retail sale, and consumption of CBD-containing products – even where such requirements seemingly conflict across state lines.
Federal Regulation of CBD
Prior to 2014, it was illegal under federal law to grow, market, or distribute any part of the Cannabis sativa L. plant in the United States – including marijuana and hemp. Marijuana and hemp are both members of the Cannabis sativa family, and CBD can be derived (extracted) from both. The primary difference between the two varieties of the plant pertains to the amount of delta-9 tetrahydrocannabinol (THC) content present during growth and at cultivation. THC is a psychoactive agent, found at varying concentrations in Cannabis sativa L. The level of THC is influenced by a variety of factors, including the genetic profile of the plant, and the specific growing conditions that the plant is subjected to. Generally speaking, hemp typically contains significantly lower levels of THC and, depending on the variety, substantially higher levels of CBD than marijuana.
Marijuana is a Schedule I substance under the Controlled Substances Act (CSA), the most restrictive category of controlled substances. The CSA prohibits the possession and distribution of Schedule I-controlled substances without prior registration with, and approval by the Drug Enforcement Administration (DEA), including Cannabis sativa L. that contains more than 0.3% THC content. Prior to 2014, hemp and marijuana were regulated together under the common definition of marijuana.
Beginning in 2014, Congress granted special authority to the states to permit the growth and cultivation of “industrial hemp” under agricultural pilot programs. Industrial hemp was specifically defined under the 2014 Farm Bill to include Cannabis sativa L. containing less than 0.3% THC on a dry weight basis, thereby creating a distinction between hemp and marijuana under the purview of certain federal regulations, including those administered by the US Department of Agriculture (USDA). It wasn’t until the passage of the 2018 Farm Bill, however, when Congress effectively removed hemp from the statutory definition of marijuana, thereby exempting hemp from being included as a Schedule I-controlled substance under applicable DEA regulations. 1 The 2018 Farm Bill further loosened restrictions pertaining to the growth, cultivation, and distribution of hemp, permitting the individual states to implement licensing programs (consistent with USDA regulatory requirements) for individuals to grow, process, and distribute hemp and hemp-derived products. Following implementation of the 2018 Farm Bill, and subject to applicable federal and state requirements, therefore, hemp containing less than 0.3% THC is legal in all 50 states. Notably, the 2018 Farm Bill represents a floor, and not a ceiling – states are permitted to implement more restrictive requirements pertaining to the production, sale, and labeling of hemp and hemp-derived products, including those containing CBD.
Food and Drug Administration Authority
The Food and Drug Administration (FDA) regulates cannabis and cannabis-derived compounds under the Federal Food, Drug, and Cosmetic (FD&C) Act (21 U.S.C. § 301, et seq.) as it would any other compound present in any otherwise FDA-regulated product. On this basis, biologics, cosmetics, drugs, food, animal feed, medical devices, and tobacco products containing CBD or any other hemp-derived component fall under FDA jurisdiction and are subject to applicable laws and regulations administered by the agency, without regard to individual state laws.
Consistent with the FD&C Act, and subject to limited exceptions or exemptions, substances added to drugs and food are subject to premarket approval by the agency. In practice, and to-date, FDA has taken a cautious and restrictive approach to the regulation of CBD. For example, only one CBD-containing drug – Epidiolex® – is presently authorized for use as a drug; similarly, only three hemp seed-derived substances have been affirmed by FDA as Generally Recognized as Safe (GRAS) for direct addition to food. 2 GRAS substances are exempted from the definition of the term “food additive” under the FD&C Act, and therefore, are not subject to premarket approval by FDA. For reasons not discussed in detail in this article, and subject to a provision of the FD&C Act, the approval of Epidiolex® effectively prohibits industry from making self-GRAS determinations for the addition of other CBD-based ingredients when added to food. 3 Similar provisions prevent industry from marketing CBD as a dietary supplement without premarket approval by FDA.
Unlike the other categories described above, however, cosmetics (and most ingredients used in the manufacture of cosmetics) are generally not subject to premarket approval by FDA. For this reason, a cosmetic containing hemp-derived CBD may be manufactured, marketed, and sold to consumers without prior explicit “clearance” or “approval” from FDA, provided that the use of CBD, and other ingredients used in the manufacture of cosmetics, is safe. FDA retains the authority to prohibit or restrict the use of certain ingredients in the manufacture of cosmetics (a so-called “negative list”) by way of regulation, but, as of the date of this article, cannabis, hemp, and CBD do not currently appear on this list.
In view of the regulatory landscape discussed above, a significant portion of any legal analysis regarding the suitable status of a hemp-derived CBD product – particularly consumer products sold at retail – necessarily relies on the scope and breadth of claims made on product advertising and labeling. Products that are intended to be sold at retail as cosmetics may contain certain claims that cause the product to become an unapproved drug, dietary supplement, or a misbranded food for purposes of FDA’s existing regulatory authority. Even where product labeling and advertising otherwise complies with FDA requirements for cosmetics, risks remain with labeling that purposefully or inadvertently results in consumer deception (i.e., CBD content claims). For this reason, FDA works in close coordination with the Federal Trade Commission (FTC) to ensure that product labeling and advertising is not unfair or deceptive, under Sections 5 and 12 of the Federal Trade Commission Act. 4 FDA and FTC have issued a number of combined agency warning letters to industry over the past few years, specifically targeting companies that made unsubstantiated claims targeting sensitive or vulnerable subpopulations. 5 For this reason, manufacturers and retailers should pay careful attention to not only the nature of the claim(s) (e.g., whether the product is intended for use as a cosmetic or a drug), but also whether the otherwise-authorized claim(s) are properly substantiated.
The States Step In
The 2018 Farm Bill provides states with authority to exercise “primary regulatory authority over the production of hemp,” provided that the state either submits a plan to monitor and regulate such production and receives approval from USDA, or otherwise adopts an equivalent plan as outlined by the USDA. 6 While the 2018 Farm Bill is silent with regard to the retail sale of such products, states have effectively stepped in to fill this void through explicit regulation or informal guidance – often through each state’s Department of Agriculture or equivalent regulatory agency.
In the perceived absence of action at the federal level – particularly with regard to the enforcement of FDA-regulated products – states have imposed additional regulatory requirements that range from expressly permitting the addition and retail sale of CBD-containing products sold at retail (without regard to the FDA considerations discussed above), to expressly prohibiting the sale of products not otherwise authorized at the federal level. Beyond federal regulations, certain states have implemented further requirements pertaining to the labeling of CBD-containing products, as well as the registration and licensing of facilities that market or sell products to consumers. Approaches vary significantly across state lines, as evidenced by the examples below:
- West Virginia takes a generally-permissive approach to the retail sale of products containing CBD, as evidenced by a publication issued by the West Virginia Department of Agriculture, entitled: West Virginia Hemp Products Guide. 7 Examples of permitted hemp-derived products include: concentrates or extracts, edibles and drinks, topicals and lotions, hemp seed pressed or otherwise processed into oil, aerosols, vaping products, and smokable hemp products. Notably, manufacturers and retailers of hemp products available for distribution within the state are required to register annually with the West Virginia Department of Agriculture (regardless of whether such products are manufactured inside or outside the state).
- Indiana does not explicitly regulate consumer products by category, instead addressing CBD-containing consumer products under the definition of “low THC hemp extract.” 8 A person may distribute low THC hemp extract in Indiana if: (1) the product has been approved by FDA or DEA as a prescription or over-the-counter drug; or (2) otherwise meets the requirements of the FD&C Act. Such products must, however, be labeled with a scannable bar code or QR code linked to a document or website that contains “information with respect to the manufacture of the low THC hemp extract,” including requirements that go well-beyond those specified under federal law. For this reason, retailers must ensure that cosmetics that may otherwise be authorized for retail sale under applicable federal requirements explicitly comply with provisions set forth by the state of Indiana. To satisfy Indiana requirements, retailers often must work closely with manufacturers and distributors to obtain relevant quality control information.
- Maryland generally permits the retail sale of cosmetics containing hemp-derived CBD, consistent with federal law. However, the state makes clear that products for which CBD has not yet been authorized for addition – such as food, remains expressly illegal for sale or distribution in the state. 9 On this basis, food to which hemp-derived CBD has been added (other than the three GRAS substances discussed above) is not yet authorized for retail sale in Maryland.
As the federal government continues to evaluate the safety and efficacy of hemp-derived CBD when added to products where premarket approval is required – such as drugs, dietary supplements, and food – states continue to move forward with implementing regulatory policies and approaches that serve to either: (1) promote the development and growth of the state’s CBD industry; and/or (2) align with federal requirements. As evidenced by the three examples provided above, state regulation does not always neatly comport with existing federal regulation of CBD, creating substantial confusion and a rapidly-changing landscape in the marketplace.
Companies would be well-served by evaluating and understanding the specific regulatory requirements applicable to the growth, processing, distribution, and consumption of hemp-derived CBD and CBD-containing products in each state where the company intends to do business or distribute product. Similarly, individuals should exercise caution when purchasing and consuming CBD-containing products that may be widely available – but may not yet be authorized at the federal or state level. While FDA continues to focus its limited resources on addressing the most egregious examples of products placed on the market without premarket approval (i.e., those directed toward children and other sensitive subpopulations), the agency will necessarily continue to move forward with considering novel uses of CBD in drugs, dietary supplements, foods, and tobacco products in time – when presented with appropriate safety data needed to support such use. In the meantime, companies that market cosmetics containing hemp-derived CBD to consumers should exercise caution and continue to ensure that both the CBD and the finished product containing CBD meets all applicable federal, state, and local regulatory requirements.