Pharmacist’s Guide to CBD Oil
Natalie M. Treese, MBA, PharmD
Department of Pharmacy Practice
Florida A&M University
College of Pharmacy and Pharmaceutical Sciences
Institute of Public Health
Mia Flowers, PharmD Candidate 2020
Florida A&M University
College of Pharmacy and Pharmaceutical Sciences
US Pharm. 2020;45(3):20-23.
ABSTRACT: Cannabidiol (CBD) is becoming more prevalent, and pharmacists must be knowledgeable about these products in order to counsel patients effectively. CBD laws and regulations are determined at the state level in the United States. Non–FDA-approved CBD products are not regulated and may contain harmful chemicals. Pharmacists must counsel patients on where and how to obtain products and to check the amount of CBD and delta-9-tetrahydrocannabinol in the product. CBD has numerous drug interactions that should be evaluated by a pharmacist. CBD is most promising for treatment-resistant seizures, and more research is necessary to evaluate its use for other indications. Sativex is currently being investigated in the U.S. for treatment of spasticity associated with multiple sclerosis and schizophrenia. In general, more studies of CBD are needed.
Cannabidiol (CBD) is gaining popularity across the United States. Pharmacists must be able to answer patients’ questions about CBD and make recommendations. This article will provide specific information about CBD, including laws, how to select a non–FDA-approved CBD product, indications for use, side effects and warnings, drug interactions, dosing and directions, pharmacokinetics, and the future of CBD oil. After reading this article, pharmacists should feel confident about counseling patients about CBD and recommending CBD products.
Laws Concerning CBD
CBD was first isolated from the Cannabis sativa plant in the 1930s. CBD is a nonpsychoactive part of the plant, whereas delta-9-tetrahydrocannabinol (THC) is the major psychoactive part of the plant. In the 1970s, researchers evaluated CBD as a pharmacologic agent. 1 Epidiolex, a 100 mg/mL oral solution with less than 0.01% THC, became the first FDA-approved CBD-containing drug in June 2018. 2 The drug is Schedule V and indicated only as an anticonvulsant for Lennox-Gastaut syndrome or Dravet syndrome in patients aged 2 years and older. 3
In December 2018, the Agriculture Improvement Act, which removed hemp from Drug Enforcement Administration (DEA) regulation as a controlled substance, was passed and signed into U.S. law. Hemp is defined as a cannabis plant that contains no more than 0.3% THC. (In contrast, marijuana has a higher THC.) Hemp is now regulated by the U.S. Department of Agriculture and is legal in all 50 states. Laws and restrictions regarding the selling of hemp products vary by state, making it questionable to travel with CBD products. 2
U.S. laws and regulations concerning CBD are determined at the state level. Currently, 33 states have legalized CBD use for medical purposes, and 10 states (Alaska, California, Colorado, Maine, Massachusetts, Michigan, Nevada, Oregon, Vermont, and Washington) and the District of Columbia have legalized marijuana for recreational use. In states such as New York, Minnesota, and Connecticut, pharmacists are required to dispense the products in authorized dispensaries. Marijuana-derived CBD oil is still considered illegal under the Controlled Substances Act in accordance with the DEA’s classification of marijuana as a Schedule I substance. 2
Selecting a Non–FDA-Approved CBD Product
Pharmacists must educate patients about how to select an appropriate non–FDA-approved CBD product. These products are not tested for safety, efficacy, or quality. 4 The main concerns in picking a non–FDA-approved CBD product are that it may contain harmful chemicals and may not accurately list the correct amounts of CBD and THC it contains. These products could contain harmful contaminants (e.g., pesticides, heavy metals) or have high levels of THC, which would result in a positive urine drug test. 5 The patient should be advised to obtain CBD products from a medical dispensary because these products are regulated. The patient should also consider ordering products from states where CBD is legal because more testing is done in those states. When selecting a product, the patient should check the label to see if it lists the amount of CBD in each dose. 5,6 The manufacturer should provide a Certificate of Analysis, which shows an independent laboratory’s assessment of the product’s potency and the presence of contaminants. 5 When assessing quality, the patient should look for the Hemp Authority seal, which means that the product is legal and the manufacturer is adhering to quality standards. 7
Indications for CBD
As consumer demand in the U.S. has risen, along with the number of dispensaries, the number of studies addressing the therapeutic effects of CBD has increased. The studies performed, however, are insufficient; large randomized, placebo-controlled trials need to be conducted. CBD seems most promising for treatment-resistant seizures. There is limited evidence concerning the use of CBD for psychotic symptoms in Parkinson’s disease and for anxiety related to public speaking. CBD has not been proven effective for pain, nausea, or depression. 4 THC, conversely, is thought to be effective for these conditions because it has a different mechanism of action. THC activates the CB1 and CB2 receptors in the brain, and CBD does not. As mentioned previously, CBD does not have psychotropic effects and THC does. These differences are believed to account for the different uses of CBD and THC. 7,8
Patients with early-onset epilepsy who are resistant to conventional therapy may benefit from CBD oil. A trial that investigated the effect of CBD on drop seizures of Lennox-Gastaut syndrome found that CBD 10 mg/kg/day or 20 mg/kg/day, when added to conventional therapy, led to a greater reduction of drop seizures compared with placebo. 9 The most common adverse reactions were somnolence, decreased appetite, and diarrhea. Specific adverse events from CBD included elevated liver aminotransferase concentrations. 9
Clinical findings on the use of CBD oil in Parkinson’s disease (PD) remain unclear. Past studies have evaluated CBD’s efficacy in minimizing nonmotor symptoms of PD, such as cognitive deficits, sleep disturbances, psychosis, depression, and anxiety. 10 The neuroprotective properties of CBD have been studied in animals with PD, with results indicating that CBD appears to reduce psychotic symptoms. 11 Although patients with PD have reported fewer sleep disturbances as well as improvements in quality of life, treatment in humans requires further investigation on a larger scale, with longer durations and more standardized dosing. 12 Most studies have used combinations of CBD and THC extracts, including nabilone, a synthetic CB1 receptor agonist. CBD dosages of 150 mg/day for 4 weeks and titrated by 140 mg/week were found to be safe and well tolerated and did not worsen motor function. 10
More evidence is needed to support the use of CBD for anxiety. Studies have found that CBD 300 mg may be effective for anxiety related to public speaking, and doses of 400 mg to 600 mg may help patients with social anxiety disorder and public speaking–related anxiety. Studies are inconclusive concerning the utility of CBD for anxiety. 13
Side Effects and Warnings
Studies have reported various properties and potential benefits of CBD. Some undesired side effects of CBD use are decreased appetite, dry mouth, diarrhea, dizziness, drowsiness, fatigue, lightheadedness, orthostatic hypotension, psychomotor slowing, sedation, somnolence, weight loss, and increased risk of liver injury with dosages of 20 mg/kg/day or the use of clobazam or valproate. Monitoring of liver enzymes, weight, and cognitive function may be warranted. CBD can pass through the placenta, so it is recommended that CBD be avoided during pregnancy and while breastfeeding. Because CBD oils may contain trace amounts of THC, operating heavy machinery and driving should be avoided when treatment is initiated. 1
CBD is metabolized in the liver, mainly by CYP2C19, CYP3A4, and UGT. This can lead to interactions with prescription drugs, OTC medications, and herbal supplements. 1,14
The inhibition of CYP2C19 by CBD can increase levels of carisoprodol, citalopram, clopidogrel, diazepam, phenytoin, proton pump inhibitors (PPIs), valproic acid, and warfarin. As a strong CYP3A4 inducer, CBD may lessen the efficacy of amlodipine, atorvastatin, buprenorphine, bupropion, diltiazem, eplerenone, fentanyl, loperamide, midazolam, paclitaxel, pioglitazone, sildenafil, solifenacin, tamsulosin, testosterone, topiramate, zolpidem, and other 3A4 substrates. 7
More serious effects may occur with concomitant use of central nervous system depressants, such as barbiturates, benzodiazepines, fentanyl, morphine, and propofol. These effects are the result of the synergistic effects of sedation and hypnotic effects at high doses. Increased sedative effects may also be seen with herbal supplements, including kava, melatonin, S-adenosylmethionine, and St. John’s wort. 13,14
Other interactions to be aware of are presented in TABLE 1.
Dosing and Directions
In unregulated dispensaries, CBD oil sold comes in a sublingual formulation known as CBD tincture and is generally available in 30-mL bottles with dropper caps. 15 A bottle costs approximately $20. The concentration of the tincture ranges from about 1,500 mg to 3,000 mg per bottle. If a drop equals 0.05 mL, one bottle contains approximately 600 drops of CBD oil. Drops are usually placed under the tongue, and the patient should let the oil absorb into the lining of the mouth, without swallowing, for 30 seconds to 1 minute. Capsules and gummies are also available. 15
As noted earlier, Epidiolex (CBD) is an FDA-approved oral solution for treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome. The cost of Epidiolex is approximately $2,708 per month. It is supplied as 100 mL of solution containing CBD 100 mg/mL. For both indications, the initial starting dosage is 2.5 mg/kg orally twice daily for 1 week. The dosage may be titrated weekly in increments of 2.5 mg/kg twice daily to a maintenance dosage of 5 mg/kg twice daily. The maximum dosage is 10 mg/kg twice daily or 20 mg/kg/day. Gradual tapering is recommended when Epidiolex is discontinued. 3
Starting at a low dosage is recommended for elderly patients and patients with moderate or severe hepatic impairment. The dosage should be 1.25 mg/kg to 5 mg/kg twice daily or 0.5 mg/kg to 2 mg/kg twice daily, respectively. 3
CBD reaches its maximum concentration in 2.5 to 5 hours. High-calorie and high-fat meals can increase the maximum concentration of drug fivefold and the AUC fourfold. 14 Owing to the first-pass effect, CBD is poorly absorbed, with a bioavailability of 13% to 19%. Better bioavailability has been reported with inhaled CBD (11% to 45%). CBD is 94% protein bound; therefore, interactions may occur with other highly protein bound drugs or in patients who have abnormal albumin levels. The volume of distribution is 20,963 L to 42,849 L, meaning that the drug is largely distributed into the tissues. CBD is metabolized by the gut and primarily by the liver. Epidiolex has an active metabolite, 7-OH-CBD, and is a 2C19 and 3A4 substrate and inhibitor of 2C19, 1A2, UGT1A9, and UGT2B7. Its elimination half-life is 56 to 61 hours. CBD is excreted primarily in the feces and urine. 3
Pharmacist’s Guide to CBD Oil Natalie M. Treese, MBA, PharmD Assistant Professor Department of Pharmacy Practice Florida A&M University College of Pharmacy and Pharmaceutical Sciences
What is CBD?
CBD is a cannabinoid that is extracted from the Hemp plant, cannabis sativa. There are over 100 cannabinoids found in the cannabis plant, THC and CBD are the most prevalent and the most well-understood. CBD is a non-psychoactive cannabinoid and has numerous potential health benefits, such as anti-inflammatory and neuroprotective properties.
What has been identified as potential uses for CBD?*
CBD has potential medicinal benefit due to it’s impact on the endocannabinoid system (ECS), which affects immune cells, the brain, the gastrointestinal tract, and the peripheral nervous system. The ECS helps to maintain optimal balance in the body – known as homeostasis. It also helps regulate sleep, appetite, digestion, hunger, mood, anxiety, motor control, immune function, reproduction and fertility, pleasure and reward, pain, memory and temperature regulation.
The most common reasons patients utilize CBD include:
Patients that have received benefit with CBD often are able to reduce or discontinue use of pain medications, anti-inflammatory medications, sleep aids, and/or anxiety medications.
* These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease.
Why you should buy your CBD Products from us:
We only stock Professional Grade CBD Products.
All our products are quality tested for not only ingredients but also to confirm unwanted additives (such as pesticides) are not present.
Drug interaction reviews provided by our pharmacists
Dosage form and dosing recommendations provided by our pharmacists.
Frequently Asked Questions-
Is it safe to use CBD with my other medications?
CBD Oil and products are fairly safe to use with most medications, however there is a potential for drug interactions with a select group of medications. Please check with one of our Pharmacists to review your medications for potential interaction issues.
What is the Endocannabinoid System?
The endocannabinoid system (ECS) is made up of a collection of cell receptors and corresponding molecules. You can think of cell receptors like little locks on the surface of your cells. The keys to these locks are called endocannabinoids.
Endocannabinoids are the chemical messengers that tell your body when to get processes moving and when to stop. Each time an endocannabinoid binds to a cell, it relays a message, giving your cell specific direction.
Certain receptors are more concentrated in specific regions. CB1 receptors are abundant in the central nervous system. CB2 receptors are more often found on immune cells, in the gastrointestinal tract and in the peripheral nervous system. The diversity of receptor locations shows just how important endocannabinoids are for day-to-day bodily function.
The ECS helps to maintain optimal balance in the body – known as homeostasis. It also helps regulate sleep, appetite, digestion, hunger, mood, motor control, immune function, reproduction and fertility, pleasure and reward, pain, memory and temperature regulation.
When the ECS is disrupted, any one of these things can fall out of balance. When the body does not produce enough endocannabinoids or cannot regulate them properly, you are more susceptible to illnesses that affect one or several of the functions mentioned above.
The endocannabinoid system is extremely complex and plays important roles in many vital processes, and it holds promise as a treatment target for many debilitating conditions.
What is the Entourage Effect?
Cannabinoids, terpenes and other chemical compounds found in cannabis achieve limited success when working in isolation or as individual components. Research suggests that when these individual components of the cannabis plant support one another, therapeutic benefits are magnified. Together, they produce an effect that is greater than the sum of their parts. This phenomenon is known as the “entourage effect.” The entourage effect supports the idea that whole plant medicine is superior to pure extracts.
What is the difference between Hemp & Marijuana?
Hemp and marijuana are both plants that belong to the cannabis family. Hemp is completely different from marijuana in its function, cultivation and application. Hemp is used in a variety of other applications that marijuana can’t be used in. These include healthy dietary supplements, skin products, clothing and accessories.
Marijuana has high levels of THC, the molecule that causes intoxication or a “high.” Hemp has 0.3% THC or less. Ananda Professional’s hemp plants are tested by the Department of Agriculture to ensure they are below this threshold. Also, marijuana is highly regulated and not federally legal. Hemp is federally legal when grown in compliance with section 7606 of the 2014 Farm Bill.
Will I get “high” from Hemp?
The answer is no. Here’s why:
While there are at least 113 known cannabinoids produced by the hemp plant, cannabis is identified by its two active ingredients: THC and CBD. THC is the only molecule in the cannabis family with a psychoactive component. It’s the only one that will get you “high.” CBD, even at extremely high doses, will not make you feel “high.”
There are hundreds of other cannabinoids, terpenes and phytonutrients present in the cannabis plant that are beneficial to overall health and wellness. Unfortunately, they are improperly associated with the properties of one molecule, THC.
Can I fail a drug screen when using Ananda Professional Full Spectrum Products?
All of Ananda Professional’s products are derived from hemp, which means they have a naturally low level of THC: less than 0.3%. This also means they are perfectly permissible under federal law. Still, it is possible that someone could fail a drug screen when using these products. There is no “magic number” to stay below the threshold of a urine drug screen, as metabolism is individualized and depends on body composition, activity level, dose, duration of use, etc. Essentially, there are two reasons why someone could have a positive THC on their urine drug when using Ananda Professional. The first is that there is a very small amount of THC in our products. That amount is usually negligible and not enough to be above the threshold for a Urine Drug Screen, but obviously that depends on test sensitivity. Also, THC is stored in fat tissue, so body composition plays a major role. Some patients simply store more of it and for longer than others do. Additionally, and what is more likely the case, the immunoassay tests can give a false positive for THC when the molecule present is in fact CBD.
What about drug screens with THC free products?
Ananda Professional guarantees that the THC free products are 100% THC-free. This is reflected by the certificate of analysis, which is completed by an objective, third party-lab and made available on the company’s website. The THC Free product includes full-spectrum hemp oil with all traces of THC eliminated. Still, on rare occasions, the immunoassay drug screen may confuse CBD for THC, resulting in a false positive.
Cbd pharmacy What is CBD? CBD is a cannabinoid that is extracted from the Hemp plant, cannabis sativa. There are over 100 cannabinoids found in the cannabis plant, THC and CBD are the most