As FDA Grapples With CBD Dosing, Definitions, ASA Issues Patient Guide

June 10, 2019 | Geoffrey Marshall

By Beth Wang for InsideHealthPolicy

Just days after FDA held a 10-hour meeting to discuss the science and regulation of cannabis-based products, Americans for Safe Access issued a resource guide for patients, health care providers, consumers and anyone interested in learning more about cannabidiol (CBD). The guide defines key terminology – including broad spectrum, full spectrum and isolate -- and discusses issues with dosing, two major issues on which FDA officials asked multiple stakeholders to submit more detailed information.

During the May 31 meeting, several representatives of the epilepsy community said patients are taking CBD off label to control their seizures but even for those taking it with their doctor’s help, figuring out dosage is mostly a guessing game. One speaker said, “They’re making it up as they go along.”

In response to the FDA meeting, ASA released a “Patient’s Guide to CBD” on Tuesday (June 4) that aims to clarify important factors patients and family members should know when considering CBD as a therapy.

The guide covers available forms for use, what to look for on package labels, how to read a certificate of analysis, how CBD interacts with the endocannabinoid system, current research, background on CBD’s legal status, and how to talk with a doctor about using CBD.

ASA lays out clear explanations for the terms broad spectrum, full spectrum and isolate, all of which were used by presenters at the meeting to describe CBD products but that lack consistent definitions within the CBD community.

On Friday, Josh Epstein, CEO of Socati, a company that processes broad-spectrum hemp extracts, explained to FDA officials that the terms can take on different meanings depending on who you talk to, but to him full spectrum means a product features all the compounds and cannabinoids that are in the cannabis plant; broad spectrum is basically full spectrum but without the tetrahydrocannabinol (THC); and isolate refers to CBD without any other component added to it.

Dana McMurchy, owner of CBD retailer Harvard Health Center in Tulsa, OK, took that one step further, saying full-spectrum hemp oil is not CBD. Rather, she said, it comprises cannabinoids, terpenes, flavonoids, fatty acids, and vitamins and minerals.

ASA’s definition seems to line up with Epstein’s but counters McMurchy’s view that full spectrum does not apply to CBD products.

“Full-spectrum products contain the full array of cannabinoids and terpenes present within the cannabis flower, including THC; this applies to CBD products derived from hemp as well as THC-rich cannabis since even hemp plants may have up to 0.3% THC,” the organization’s patient guide says.

ASA also says broad spectrum products do not contain THC and that CBD isolate is often marketed as being 99+% pure.

On Friday, when FDA officials asked Epstein what CBD levels he sees in the broad-spectrum products, he said it depends on the starting materials, but that once products go through the manufacturing process, the CBD content in the oil will typically be anywhere from 70% to 90%.

“You can understand the challenge in creating a standard around something that varies like that,” Douglas Throckmorton, deputy director for regulatory programs at FDA, said to Epstein. He then asked the Socati CEO to submit to the docket a list of terminology he feels could benefit from standardization.

ASA’s patient guide also connects the need for consistent terminology with choosing the correct dose, as knowing whether a product is full spectrum, broad spectrum or isolate can help doctors and patients understand how much product to use.

FDA officials also asked multiple stakeholders how they figure out dosing of CBD products. Many of them did not provide details in person but said they would do so on the comment docket.

However, Lucille Vega of Vega Medical Direct gave examples of specific CBD products her patients use for their conditions and told FDA officials she always starts patients with sublingual dosage forms at the lowest dose. “I always start with 1 milligram, and let’s see how you do. The lowest dose possible,” Vega said, later adding that for some she might even start with a half a milligram if needed.

Vega also emphasized she takes into account patients’ ages – especially as people over the age of 55 are typically on some form of medicines for hypertension or high cholesterol – and any other medications they may be taking.

When asked whether she screens patients for liver issues and other negative effects that have been linked to CBD, Vega said she always considers those factors.

“[Because I’m their primary care physician], I know what I’m prescribing them for their blood pressure, their cholesterol and such,” Vega said. “So it’s constantly in the back of my mind. Every person I see, I always want to know: What’s your kidney function? What’s your liver function? And, what’s your blood pressure. Absolutely.” Vega urged FDA to implement labeling standards for CBD products that include information on dosing, as well as clear definitions for full spectrum, broad spectrum and isolate, saying  doctors need that information to help their patients.

“My biggest pet peeve as a physician is seeing these CBD companies put out 1,000 milligrams in a bottle,” she said. “I want to know what’s the milligram per smallest dose unit per drop, per edible, etc. Also, definition – broad spectrum, full spectrum – we need to get consensus on the nomenclature, particularly how many cannabinoids are in a particular article. Are there one, two, three, four cannabinoids?”

ASA underscores its patient guide is not intended to provide concrete dosing information. Rather, the group says, patients must go through trial-and-error to find the correct dose for their condition and take into account that the correct dose may change over time due to factors such as age, tolerance, body fat percentage, genetics and metabolism.

Dosing, ASA says, will depend on whether the product used by a patient is full spectrum or CBD isolate. Purified CBD products, including isolate and distillate, seem to have a narrower therapeutic window than fullspectrum products, which tend to show a direct correlation between dose and response, with increased doses resulting in increased responses until a plateau is reached.

“[P]urified CBD exhibits a bell-shaped dose-response curve when administered; as one team of researchers noted, ‘Healing was only observed when CBD was given within a very limited dose range, whereas no beneficial effect was achieved at either lower or higher doses,’” ASA writes.

That means that those taking products made with purified forms of CBD need to be more precise and deliberate when finding the right dosage.

“[N]ot only will they find too little CBD ineffective, they will also find too much CBD ineffective,” the guide says. The organization suggests patients keep a journal to log product use with specific information about the date and time the CBD was taken, the amount, the cultivar, how it was consumed, the cannabinoid and terpene content, the negative and positive side effects, and how they felt before and after taking the CBD.



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