Prescription grade versus over-the-counter Cannabidiol (CBD), medication education, and the future of the all natural “miracle” drug.

Introduction:

A family member recently informed us that she has been giving cannabidiol oil to her dog to help treat his anxiety.  She says, “It really helps”, and honestly, her dog, with a likely trauma history, did seem more at ease this past weekend. Anecdotally, many of my friends, family members, and patients have either experimented with CBD or are currently using it as part of their treatment regimen with varying results.  I hypothesized perhaps their metabolism, genetics, dosing, or even species may play a role in efficacy. Or, perhaps over-the-counter CBD is just good old fashioned “snake oil”. With all the buzz around CBD, is it a placebo or medical miracle? In short, it’s both, but to fully answer this question we need to discuss the differences between prescription and over-the-counter CBD.

What is the difference between prescription grade and over-the-counter CBD?

Cannabidiol, commonly referred to as CBD, is a cannabinoid derived from cannabis (marijuana, indica, sativa, hemp).  One prescription grade CBD, Epidiolex, recently obtained FDA approval, after a fast track process, for the treatment of two rare and severe forms of childhood epilepsy (seizure disorder), Lennox-Gastaut and Dravet syndromes.  There are no other indications for the medication, no other studies to indicate off label use, and it is a schedule V controlled substance; the lowest level of DEA regulation. But, you still need a prescription. According to the DEA website, any form of cannabidiol, not derived from hemp, that is not FDA approved, remains a schedule I controlled substance; the highest level of DEA regulation (on par with heroin and cocaine).  But, CBD oil is also available over-the-counter (OTC), and is legal in all 50 states (Aiken, 2019). What’s the deal?

Well, over-the-counter CBD oil purity seems, at best, inconsistent.  For example, in a 2017 study of 84 online products, only 30 percent contained the amount of CBD on the label, and notably, 21 percent contained THC.  Epidiolex is a purified extract of marijuana that is 99-100 percent CBD and less than 1 percent THC (Epidiolex, 2019). The difference is purity, plant derivation, and regulatory status.  OTC formulations of CBD oil are legal as long as the CBD is extracted from the hemp plant, a variety of cannabis that contains little tetrahydrocannabinol (THC), the cannabinoid associated with “getting high” and “the munchies”.  THC is a potentially harmful cannabinoid associated with cognitive impairment, anxiety, and less commonly, psychosis (Aiken, 2019).  

At this point, until there is an FDA approved, psychiatric indication for prescription CBD it will not be available for use in treating psychiatric conditions.  In terms of over-the-counter CBD oil, we don’t have much evidence to endorse or warn against its use. That being said, we want to guide patients to safer products if they are already getting them on their own.  We call this harm reduction; the same relative concept for prescribing suboxone or methadone to patients with opioid addiction or simply recommending drinking red wine versus beer or spirits.

Where are the most reputable places to purchase over-the-counter CBD?

Hemp is a bioaccumulator, which means the plant absorbs everything beneficial and toxic from the environment (air, water, soil, etc). Toxic substances like pesticides, herbicides, and heavy metals have been linked to multiple types of cancer including leukemia, non-hodgkin lymphoma, and multiple myeloma (Lexicorp, 2018).  If you decide to purchase hemp based CBD oil then buy organically grown, make sure it can be tracked to its source, and that it is grown in the United States. Other considerations to ensure CBD quality outside of FDA regulation are that its extracted using CO2 methods, tested in third party labs, and shows high concentrations of CBD and only trace levels of THC.  Make sure the companies involved are following the guidelines and laws associated with production and distribution – I know it’s old fashioned, but call them.

The FDA keeps a record of warning letters and test results for CBD products at this website – click here.

The Carlat Report: Psychiatry references the watchdog Consumer Labs which recommends elixinol.com and bluebirdbotanicals.com. 

How much does CBD cost?

A 300mg dose is $20-50/day over-the-counter and around $35/day for prescription when paying out of pocket.

What else can CBD be used to treat?

In the future, CBD may be used for multiple psychiatric disorders, including psychosis.  Five of seven controlled trials of CBD’s antipsychotic effects have shown positive effects on psychosis.  Another prescription CBD product, Arvisol, is currently undergoing phase I clinical trials for schizophrenia.   While CBD may be effective for treating psychosis, it has not shown neuroprotective efficacy in treating the cognitive impairments of schizophrenia.  Controlled trials for CBD have also shown efficacy for social anxiety disorder. However, unlike other antiepileptics, like depakote, tegretol, and lamictal, CBD has not yet shown any benefit for treating bipolar mania (Aiken, 2019).

What are the side effects of CBD?

The World Health Organization has concluded that CBD has “a good safety profile”.  Somnolence is the main side effect of CBD, but side effects have also included signs of infection like fever, decreased appetite, diarrhea, vomiting, and trouble sleeping.  Sleep studies have shown mixed results, and it seems tolerance can develop to its sedative effects. Additionally, at doses below 160mg CBD may have stimulating effects. Let your provider know if you have any allergies, especially an allergy to sesame oil, and be aware of allergic reactions like itching, redness, wheezing, and tightness in your chest (Lexicorp, 2019).  

CBD is metabolized by the liver, and if you plan to take over-the-counter cannabidiol let your provider know, as it may be a good idea to assess your baseline liver function prior to initiating treatment.  Depakote may enhance the potential hepatotoxic (liver toxicity) effects of cannabidiol, and if taking Celexa (citalopram) the max dose recommended is 20mg (versus 40mg without CBD) and should be monitored for toxicity which can lead to serotonin syndrome and QT prolongation.  Signs of liver problems include dark urine, feeling tired, minimal appetite, stomach pain, vomiting, light-colored stools, and yellowish skin or eyes (from bilirubin accumulation, a molecule typically excreted in urine) (Lexicorp, 2019).

An important note: According to the Epidiolex website, about 1 in 500 people may have suicidal thoughts or actions after taking Epidiolex, similar to antidepressants and other psychiatric medications (Epidiolex, 2018).  It is important to discuss and develop a safety plan with your therapist and medication provider. The risk may be greater in people who have had these thoughts or actions in the past.  Call your provider right away if signs like low mood, feelings of worthlessness or hopelessness, nervousness, restlessness, grouchiness, panic attacks, or changes in behavior develop or become worse.  As always, call 911 or go to the emergency department if having suicidal thoughts with the intent of harming yourself or any other safety concerns.

How does CBD work?

In short, the mechanism of action for CBD is unknown, but it does not appear to involve the medications effects on cannabinoid receptors.  The onset of action typical begins with four weeks, and the medication is best absorbed with high fat and high calorie meals as all cannabinoids are lipid (fat) soluble (Lexicorp, 2019).

What is a safe and effective dose of CBD?

The dosages used in psychiatric research range from 300mg/day for anxiety to 800-1200 mg/day for schizophrenia.  The epilepsy dosage, 10-20mg/kg/day, for most adults adds up to approximately the same amount used in schizophrenia (Aiken, 2019).  Keep in mind, these dosages are based off purified CBD that contain only trace amounts of THC. As discussed, over-the-counter CBD potency and THC content will vary from product to product.  Before taking CBD, discuss safe dosing with your provider.

Is CBD safe during pregnancy and breastfeeding?

In terms of pregnancy and breastfeeding, CBD is detectable in the umbilical cord serum and meconium following maternal use of inhaled, non-medical cannabis (marijuana, indica, sativa, hemp) during pregnancy, and adverse events have been observed in animal reproductive studies.  It is not known if CBD is present in breast milk following oral use of CBD (Lexicomp, 2019).  The decision to breastfeed while using CBD should take into consideration the likely risk of infant exposure, the benefits to breastfeeding the infant, and the benefits of treatment to the mother.  Let your OB/GYN, psychiatrist, and all of your other providers know if you plan to take over-the-counter CBD while pregnant or breastfeeding.

Patients exposed to cannabidiol during pregnancy are encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.

References:

AIken, C. (2019). Prescription CBD is available, but are we ready to use it?. The Carlat Report: Psychiatry. 17(1):1-3

Epidiolex (cannabidiol) [prescribing information]. Carlsbad, CA: Greenwich Biosciences, Inc; September 2018.

Lexicomp (2019). Cannabidiol: Patient drug information. Retrieved from  https://www.uptodate.com/contents/cannabidiol-patient-drug-information?source=history_widget