Table 2.

Commonly Asked Questions from Clinicians and Patients

What is the difference between CBD, medical marijuana/cannabis, and hemp?	CBD is a cannabinoid found in cannabis and hemp plants in varying amounts. CBD is considered a primary, non-intoxicating constituent. The terms “medical cannabis” or “medical marijuana” generally refer to use of the cannabis plant or cannabinoids to treat medical conditions or alleviate symptoms. It is a broad term and does not refer to a specific dose or cultivar of cannabis, and it does not specifically refer to a cannabis-based product that is FDA-approved. Medical cannabis/marijuana has varying amounts of cannabinoids, including CBD. Hemp is a species of Cannabis Sativa L. plant that was originally cultivated for industrial use. By definition, hemp contains <0.3% THC by dry weight in the United States. Hemp often contains larger amounts of CBD than other cannabis plants. For this reason, hemp has more recently been cultivated specifically to make CBD products. CBD is extracted from hemp using several different processes to be used in a variety of product types (e.g., CBD oils, edibles, topicals). CBD can also be extracted from other varieties of the cannabis plant (those containing >0.3% THC). The total amount of CBD or THC in a product is also related to the extraction and manufacturing process.
Where are most CBD and hemp products obtained?	CBD products made from cannabis must be sold at a dispensary, while hemp-based products are sold in stores or online but may also be sold in dispensaries. Although it is possible to manufacture synthetic or non-plant derived versions of CBD, these products are generally not currently available to medical cannabis patients/consumers.
Is CBD approved by the FDA?	Currently, the only CBD-containing product approved by the FDA is Epidiolex; a plant-derived, highly purified form of CBD. Epidiolex is an unscheduled substance that has been approved for the treatment of two rare, intractable pediatric onset seizure disorders, Lennox Gastaut syndrome and Dravet Syndrome (Billakota et al., 2019).
Do you need a prescription for CBD products? What about medical cannabis?	Prescriptions are required for FDA-approved medications, and therefore are required for Epidiolex. Prescriptions cannot be written for commercial CBD products. Cannabis or any products derived from cannabis require a certification or recommendation (not a prescription) for use from a physician to access products from medical dispensaries. However, a certification or recommendation from a physician is not required to purchase CBD products that are derived from hemp (less than 0.3% THC by weight).
What conditions are people using commercially available CBD products to treat?	The most commonly reported conditions are chronic pain, arthritis/joint pain, anxiety, depression, insomnia/sleep disorders, headache, PTSD, ADHD, nausea, and skin care, among many others (Corroon and Phillips, 2018; Poll, 2020).
What are the most common ways that people use CBD?	The most common ways to use CBD include sublingual, vaping, capsule/pill, smoking, edibles, infused beverages, as well as topical lotions and ointments (Corroon and Phillips, 2018).
How did CBD become so popular?	There has been an evolving acceptance of cannabis and cannabis-related products. The last decade has seen an increase in interest in CBD particularly. The 2018 Farm Bill separated hemp from the definition of “marijuana”, which permitted the sale of hemp products and created an expansion of commercially available CBD products. The FDA approval of Epidiolex, a specific formulation of highly purified CBD for pediatric epilepsy, also sparked interest and underscored the possibility of treating other medical conditions.
Is CBD addictive?	CBD at moderate doses (200–800 mg) has not been shown to have significant addiction liability (Babalonis et al., 2017). One study showed that at very high doses (1500 mg and 4500 mg), CBD may have some subjective effects compared to placebo. This finding was much less than dronabinol (synthetic THC) and alprazolam (Schoedel et al., 2018), but more research is needed. Route of administration may also change the addiction potential of CBD, as vaporized CBD has been reported to confer subjective effects of “feeling stoned” (Solowij et al., 2019), pleasantness, or drug-liking (Spindle et al., 2020).
If a CBD product also contains THC, will the THC show up on a drug test?	This depends greatly on how much THC is in a CBD product, which is often unknown/not indicated or incorrectly indicated on a label (Bonn-Miller et al., 2017). Consistent, continued use of high-CBD, with even very low THC content, may lead to a positive drug test for THC. In a recent study, 50% of participants tested positive for THC on a drug test after four weeks of using a full-spectrum, high CBD product (1.04% CBD, 0.02% THC) (Dahlgren et al., 2021). This effect can depend on many variables such as patterns of use and individual pharmacokinetics. There is no way to be certain that the use of commercial CBD products will not affect a drug test.
Where are people getting information about CBD?	Many people are not accessing information that is evidence-driven and peer-reviewed, and most consumers (76%) of CBD report that they learned about it from their own internet research, family members, or friends (Corroon and Phillips, 2018).
Are there any adverse side effects associated with using CBD?	There are potential adverse side effects when using high doses of CBD, but broadly, CBD has a favorable side effect profile (Iffland and Grotenhermen, 2017), particularly when compared to many psychiatric medications. In clinical trials, which have primarily used single, extracted CBD study products (thus requiring higher doses relative to commercially available CBD products), nearly half of all study subjects reported an adverse event associated with use, including transaminase elevations, sedation and fatigue, diarrhea, sleep disturbances, and weight loss (Brown and Winterstein, 2019). However, when pediatric epilepsy was removed from the reviewed studies, only diarrhea remained as an adverse event (Chesney et al., 2020). There is also the chance of drug-drug, herb, or other dietary supplement interactions. Importantly, some CBD products may contain THC which can lead to psychoactive effects.
How regulated are commercially available CBD products? Are they safe?	Commercially available CBD products are not regulated or overseen by the FDA and are not held to the same standards as Epidiolex. They lack the consistent dosing, safety, and therapeutic response studies required for FDA-approved treatments (Freeman et al., 2019b). Many products are mislabeled with regard to CBD content and may contain higher than expected amounts of THC (Bonn-Miller et al., 2017). Studies have indicated that purified CBD as Epidiolex is generally safe and well tolerated (Organization, 2018); however, there is less known about the safety of commercially available products due to the aforementioned reasons.
Should I recommend a patient to use whole plant cannabis products with a higher CBD: THC content?	Given the lack of randomized controlled clinical trials, clinicians treating patients with psychiatric disorders should recommend that patients abstain from cannabis use (particularly cannabis with significant THC content). For patients who plan to continue their use, the most important recommendation is that they use products with the lowest possible THC content as a harm reduction strategy to mitigate some of the psychomimetic effects of THC.
Is CBD safe with other psychiatric medications?	There are potential drug-drug interactions that can occur when using CBD with psychiatric medications due to the metabolism of CBD (and other cannabinoids) in the liver (Brown and Winterstein, 2019; Rong et al., 2018; Stout and Cimino, 2014). However, the extent of these interactions in humans remains unclear. Patients with underlying liver disease or who are using medications that affect the CYP450 enzyme system (e.g., CYP2C19 and CYP3A4 substrates) should be cautious when using CBD, and make sure to inform their healthcare providers. Those using sedating medications should be careful with CBD, as some individuals experience sedation with the use of CBD. While CBD and other cannabinoids can increase or decrease serum levels of other medications, the role cannabinoids play with regard to herbal or other dietary supplements remains unclear.
Can CBD be used while pregnant or breastfeeding?	As there are currently no studies assessing the impact of CBD on individuals who are pregnant or breastfeeding, and the use of CBD products while pregnant or breastfeeding is strongly discouraged.
What are some of the biggest concerns and unknowns about CBD right now?	Some of the greatest unknowns about CBD include the effects of chronic CBD use, and how CBD may affect the developing brain of a fetus or an infant during pregnancy and/or breastfeeding, or the effects on the developing adolescent brain. There is also very limited information on how CBD interacts with dietary/herbal supplements or prescription drugs in humans, particularly since there are many variables such as route of administration (sublingual, vaping, capsule/pill, infused beverages, smoking, edibles, topical lotions/ointments), as well as different formulations (single extracted compound, plant-derived products) which can have a significant difference in their constituents. Another concern from animal studies is that CBD affects fertility, however whether this effect occurs in humans is unclear (Carvalho et al., 2020).
Why is CBD so difficult to study?	CBD may become easier to study now the Epidiolex is an FDA approved medication, if Epidiolex is the CBD product being used. However, testing commercial, non-FDA approved, legal hemp-based CBD products remains a challenge. It is of note that commercially available products, including full and broad-spectrum products, are not able to be studied via standard clinical trials at this time. This creates a discrepancy between the type of CBD being clinically used and the type of CBD being most likely used by patients. Additionally, there is an unusually high regulatory burden involved in clinical research on any cannabinoid, including CBD, when they are derived from cannabis (and not industrial hemp) given the Drug Enforcement Agency Schedule I status of cannabis. Gaining approval for administering Schedule I substances can be challenging and using federally approved cannabis products (such as the cannabis grown at the National Institute of Drug Abuse) may not offer the representative array of THC, CBD, or other cannabinoids that parallel those that are present in commercially available products.
Should clinicians recommend CBD for their patients?	Currently, there is not enough high-quality evidence to support the use of CBD as a treatment for any psychiatric symptom or disorder. Pending clinical trials will hopefully clarify its utility in treating psychotic and anxiety disorders, where it shows the most promise as a viable treatment option.