On The Cover
Rachel Balick, Loren Bonner, and Leah Sera, PharmD, MA, BCPS
CBD & cannabis: The basics
What’s the difference between CBD and cannabis?
Cannabis is the scientific name of the plant, while CBD, or cannabidiol, is one of the most abundant of the hundreds of active chemicals contained in the cannabis plant.
What’s the difference between CBD and hemp?
Hemp is a variety of cannabis grown specifically for fiber that is used for industrial purposes. This variety of cannabis has very little THC, or tetrahydrocannabinol. THC is another common chemical found in cannabis and is the chemical responsible for the plant’s psychoactive effects. Hemp contains less than 0.3% THC.
How do CBD and cannabis interfere with other medications? What adverse events can they cause?
The safety profile of CBD comes largely from the FDA-approved, prescription-only cannabidiol, Epidiolex (GW Research) clinical data, in which use was associated with dose-related increases in liver function tests, specifically, elevations in AST, ALT and total bilirubin, and liver injury. CBD is also known to affect the metabolism of other drugs, as it is a substrate for hepatic isoenzymes CYP3A4 and 2C19. Concomitant use with moderate or strong inhibitors or strong inducers of these isoenzymes may result in increased risk of potentially serious adverse effects associated with CBD or reduced therapeutic response to CBD, respectively.
From a pharmacodynamic perspective, concomitant use of CBD with licit or illicit substances, such as alcohol or other prescription medications with central nervous system (CNS)–depressant effects, may increase the risk of sedation and drowsiness. Pharmacists should warn patients about these potential concerns, particularly use of CBD when completing tasks or activities requiring a high degree of mental acuity.
What are common disease contraindications for CBD and cannabis?
Currently, CBD and cannabis have an incomplete risk profile. From a medical perspective, individuals with hypersensitivity to CBD or formulation ingredients should not use these products. Consider use of cannabis contraindicated if you are younger than 25 years, have a personal or family history of psychosis or schizophrenia, have a current or past history of cannabis use disorder or another active substance use disorder, have significant cardiovascular or respiratory disease, or are pregnant or breastfeeding. If you meet any one of these criteria, the potential medical risks may outweigh any clinical benefits of use.
Pharmacists’ top 5 cannabis questions
How does cannabis work?
Although it’s still an area of evolving research, cannabinoids such as THC and CBD are known to have different effects on the body. THC binds to cannabinoid receptors in the body, while CBD may interact indirectly with cannabinoid receptors. THC is the chemical responsible for the psychoactive effects of cannabis but also has antinausea and analgesic effects. CBD, which has no psychoactive properties, may have anti-inflammatory properties and may mitigate some of the negative effects of THC. Other phytochemicals, such as the terpenes and flavonoids, may play a synergistic role in the therapeutic effects of cannabis. This is known as the “entourage effect.”
What conditions can cannabis be used for?
The medical cannabis program in each state has different regulations specifying the conditions for which patients can be certified to use medical cannabis. A report published in 2017 by the National Academies of Science, Engineering, and Medicine found substantial evidence supporting the use of cannabinoids to treat chronic pain. This report also found substantial evidence supporting use of cannabinoids for nausea and muscle spasms and summarized the available evidence for many other symptoms and conditions.
However, much more research is needed to help determine indications, optimal delivery systems, and adverse effects of medical cannabis use.
How should I counsel patients on medical cannabis?
Pharmacists can educate patients and other health professionals about the evidence supporting medical cannabis use for different symptoms and conditions. Pharmacists can also provide information on contraindications, adverse effects, and drug interactions, just like they would for other medications. If patients use medical cannabis, pharmacists should be able to perform a DUR just as they normally would for any medication, including determining whether therapy is appropriate and identifying any contraindications, as well as the potential for abuse.
How do patients obtain medical cannabis?
Typically, patients must see a provider practicing in their state in order to be certified to obtain medical cannabis, and then must register with the state’s regulatory organization. However, states differ widely on regulations related to medical cannabis processing, dispensing, and use. Pharmacists should become familiar with the medical cannabis program in their state, if one exists. In some states, pharmacists are required to be a part of the process of providing medical cannabis to patients.
What is the future of medical cannabis?
Despite regulatory challenges, research continues into the clinical effects of cannabis. States continue to develop medical cannabis programs, and if the federal regulatory status of cannabis changes, it could open many more opportunities for research.
Answers courtesy of Leah Sera, PharmD, MA, BCPS, program director, MS in Medical Cannabis Science and Therapeutics, University of Maryland School of Pharmacy, Rockville
Common questions patients ask pharmacists
Will CBD show on a drug test or get me high?
Full-spectrum CBD products contain all cannabinoids and other compounds of the cannabis plant, which includes up to 0.3% THC. Although this may not be enough to cause a “high,” a test could read positive for THC depending on the individual’s metabolism and the sensitivity of the test.
What is the best dosage form of CBD?
Justin Redding, PharmD, RPh, owner of Mo City Apothecary in Missouri City, TX, said there are pros and cons to each dosage form. “For the quickest onset of action,” he said, “use the oil or tincture sublingually.” Inhalation—vaporization or smoking—is also a quick delivery method, but some people find the odor unpleasant, according to Redding. Patients with respiratory issues should avoid inhaling CBD. “Edibles taste good and the dose is already measured but must be digested first before experiencing effects. Topicals are best for those who don’t want to ingest CBD and just want some temporary relief,” he said.
It’s important for patients and pharmacists to recognize that they often don’t know what they are getting. Products vary widely and are often labeled incorrectly. FDA does not regulate these products.
What are some of the most common forms of CBD?
Oil and tinctures, edibles, teas, topicals, and vaporization liquid are some of the most common forms.
What evidence exists to support the use of CBD oil?
FDA has approved one CBD product—Epidiolex (CBD—GW Research). Epidiolex is indicated for the treatment of severe seizures due to Lennox–Gastaut syndrome or Dravet Syndrome in patients aged 2 years or older. Data from the trials is the only reliable evidence that exists currently.
Researchers continue to look into the safety and effectiveness of CBD for other ailments, such as pain and even PTSD. Pharmacists who sell CBD products report that their patients use the products to treat pain, anxiety, insomnia, arthritis, Crohn’s, and ADHD, but no scientific evidence exists to back up its effectiveness.
Cannabis, CBD, and the law
Are pharmacies that sell cbd oil and other products putting themselves at legal risk?
“It depends upon what CBD you sell. If you sell CBDs that meet the definition in the Agricultural Improvement Act, a.k.a the Farm Bill—hemp-derived CBD with less than 0.3% THC—it’s legal to sell them under federal law, period, full stop, as they are no longer considered a controlled substance,” said Karla L. Palmer, JD, director at the Washington, DC, law firm Hyman, Phelps, & McNamara, P.C. Palmer has several pharmacists, pharmacies, drug distributors, and manufacturers as clients.
Outside of those specifications, and depending on what health claims are made, pharmacies are in dangerous territory. “If your CBD has greater than 0.3% THC and it’s not derived from hemp, it’s no longer outside of the definition of marijuana, and therefore it’s a controlled substance that is illegal to sell without an appropriate registration.”
Although hemp-derived CBD that contains less than 0.3% THC is legal, FDA still hasn’t determined under what conditions it’s legal. “Those who are selling this need to be careful about what they say and how they say it. They need to be careful about how they advertise its use, how they promote its use, what they tell patients, what they communicate on social media about it, and more,” Palmer said.
FDA has specified that CBD is an inappropriate dietary supplement and can’t be considered thus, that it’s an unapproved new drug, and that it’s not appropriate for use in animals.
“The issue is that CBD is a product without an appropriate and well-defined regulatory ‘home’ right now. And until it has its appropriate home, anybody who is promoting its use for certain indications needs to be careful,” she said. “You can’t tell patients how to use it, and if you do, you have to be very, very circumspect concerning its use because right now, FDA seems to be saying through its various enforcement letters and other public communications on its website there’s just no appropriate use of the product.” FDA also has not described what would be an appropriate use or dose.
FDA has sent warning letters to entities that have made claims about CBD’s safety and efficacy.
“There are outrageous claims that CBD cures cancer, Alzheimer’s, autism—the list goes on and on. It’s just dangerous from a regulatory perspective to promote CBD for such uses without adequate studies,” Palmer said.
“FDA’s position on this is that there’s not enough information to know its safe and effective use. Until FDA has sufficiently gathered and reviewed available safety and efficacy data, pharmacies, suppliers, manufacturers, and distributors need to take a step back to ensure that these products, as used and promoted, aren’t causing more harm than good,” she continued.
Pharmacists should similarly be cautious about how they answer questions from patients.
“I can’t tell them to answer or not to answer, or to answer questions in a particular format, as the information sought by patients likely is subject to infinite variation,” Palmer said. “But using their pharmacist–patient relationship, it would be appropriate for a pharmacist to communicate the ways the pharmacist believes CBD may be appropriate for a particular patient. “Even then I would be very careful about doing it. The more recommendations you make about potential safety and efficacy, the riskier it is for the entity or individual making such claims.” Pharmacists’ responses to patient questions should also differ according to the needs of the individual patient.
As a lawyer, Palmer is more comfortable with those selling the products engaging in face-to-face communication with a patient than in writing, although sellers still need to exercise significant care in what they tell their patients about uses of CBD products.
For example, “if pharmacists were communicating in written promotional pieces, or via social media, about anecdotal experiences using CBD-type products and reporting efficacy claims like, ‘This treats this condition,’ and ‘Look how well it works on this condition,’ that’s more risky.” She advises pharmacists to review Federal Trade Commission guidance on the limitations of patient testimonials. “I believe that, until further reliable information about products is available, these entities are going to be held to that standard.”
Still, she supports pharmacies selling CBD, as long as it falls within federal and state legal limits. “I’ve seen struggling independents make a lot of money selling CBD.”
What states prohibit or limit the sale of CBD products?
In 47 states and the District of Columbia, it is legal to sell CBD oil that meets the federal standards. Idaho, Nebraska, and South Dakota have different rules.
In Idaho, just as in federal law, only hemp-derived CBD may be sold. Unlike federal law, the products must have 0% THC—not the 0.3% limit permitted at the federal level. CBD must also qualify as “not marijuana” according to state code—in other words, allowable CBD products can only come from certain parts of the hemp plant.
Nebraska decriminalized hemp-derived CBD in 2019, but it is still technically illegal. However, hemp and hemp-derived products were removed from the state’s controlled substances list as long as they contain less than 0.3% THC and meet certain delivery, testing, and manufacturing requirements.
It is not legal to sell or possess CBD products in South Dakota, although some counties have said they will not prosecute sellers or users.
How can pharmacists determine that the products they sell comply with the law?
Pharmacists should ensure they’re relying on a good supplier that will verify that their product is compliant with the limitations set forth in the Farm Bill.
“You need to ensure that you trust your supplier and that the supplier represents that its product, through a certificate of analysis or similar verifiable documentation, meets the appropriate specifications,” Palmer said. The supplier should provide information about the products it sells, including a detailed certificate of analysis.
“Legitimate suppliers have studied the product and run testing for potency and other measures to ensure that the product is within the specifications permitted by the Farm Bill,” she said.
One of Palmer’s clients was eager to get into the CBD business but was nervous to do so, lest he inadvertently sell a Schedule I controlled substance.
“We started inquiring about different suppliers and how they test to ensure that their product is appropriate—you have to do your due diligence with respect to those who are providing it to you,” she said. You also must ensure you are acting in compliance with differing state laws, some of which do not permit the sale of CBD.
“I was impressed with the availability of information concerning the analysis of CBD products. Several suppliers to pharmacies had QR codes on their products, so you could easily access the certificate of analysis, lot number, and expiration date on your phone or your computer. It was pretty ingenious technology.”
How will FDA approval of Epidiolex affect the scheduling of CBD and other cannabis products?
“Epidiolex was approved, and DEA scheduled it as a Schedule V controlled substance prior to the passage of the Farm Bill, which is interesting,” Palmer said. DEA’s scheduling of Epidiolex and the Farm Bill seem to contradict each other. “Notwithstanding international drug treaty requirements that likely affected the scheduling of Epidiolex, things might have been different had the federal definition of CBD changed prior to the scheduling of Epidiolex.” The Farm Bill made a distinction between marijuana and CBD that is hemp-derived and contains less than 0.3% THC.
Even with the passage of the Farm Bill, “the DEA still needs to comply with international treaty requirements, which require that the United States schedule that product because it contains CBD. The U.S. likely cannot have an unscheduled approved drug if the drug is subject to scheduling internationally according to a treaty to which the U.S. is a signatory, and according to DEA’s Federal Register notice scheduling Epidiolex,” Palmer said. Until the international schedule is changed and CBD is removed from that international schedule, it likely is going to remain scheduled federally.
“And if you read the Federal Register notice scheduling Epidiolex, it’s really all about those treaty requirements,” Palmer said. “It’s a complicated situation.”
How can I tell if a CBD product is credible?
Making sure a CBD product is credible is complicated. Most pharmacists who sell CBD know that the products they order should have a certificate of analysis from a third-party lab that tests the level of CBD and other cannabinoids in the product.
Kelly Hunt, RPh, an independent pharmacy owner in South Carolina, took it upon himself and his staff to test several CBD products they were interested in selling. They wanted to make sure the purity and claims were accurate and partnered with a well-established lab to carry this out. They found that many brands, especially those that are less expensive, strayed far from their label contents. For instance, they found out that a 15-mg labeled CBD gummy actually contained only 1.8 mg of CBD. They discovered that some well-known popular brands were way off, too.
“As we continue to analyze and discover more truths about CBD purity and transparency, we are finding more and more that it is indeed the wild west in terms of who is doing what,” said Hunt.
Although they expected lots of products to not hold true to their CBD labeling claims, Hunt said what they didn’t consider at first is that some testing sites may also be lacking in consistency and quality.
“It seems there is no regulation there either. We found this out by sending the same sample to two different testing sites only to get back two different results,” he said. “It’s an interesting time in the infancy of CBD and medical cannabis. You truly have to know who you are dealing with all the way from the seed to the bottle and then to the testing facility.”
Redding from Mo City Apothecary advises pharmacists to research the CBD companies as much as possible, “everything from the farm where the hemp was sourced, to the lab where it was tested,” he said. This should be in addition to having the certificate of analysis available. He said for the CBD products he sells in his pharmacy, he has met with each company personally.
“Hopefully, more guidelines and regulation will help clarify and verify these products so patients can be assured of what they are purchasing,” said Hunt.
Cannabis resources