Bioavailability of CBD can be over 50%, but as low as 4%

Bioavailability usually refers to how much of what you consume actually gets into your bloodstream. It's compared to a direct intravenous injection (IV), which is considered 100%.

This study examined the bioavailability via pharmacokinetic (PK) parameters of CBD when administered by several different methods using experimental data from 9 different previously published human studies. It was published online ahead of print in April 2024 in the journal Cannabis & Cannabinoid Research.

The primary purpose of this study was to develop an analytical model to estimate bioavailability of an FDA-approved CBD isolate in sesame oil. However, we are more interested in the collection of previously published data on actual CBD bioavailability, so we won't comment on their resulting model. 

6 of the reference studies used an ingested (oral) FDA-approved CBD isolate in sesame oil. 3 studies evaluated inhaled CBD in different forms, including flower.

While these results have been published previously, this study pulls the data together and presents it on a nice single chart. Here's the authors' simple graphic summary of the dose versus its bioavailability of the actual experimental data points and their model (solid blue line):

 

The red data points show the bioavailability of a few types of smoked or vaporized CBD. They range from roughly 10% to 30%. Of note, vaporized CBD isolate had a much lower bioavailability than did CBD hemp flower (9.8% vs. 25.9%). This demonstrates a significant bioavailability "Entourage, or Ensemble Effect" with full spectrum CBD versus CBD isolate when vaporized.

Inhaled CBD mostly bypasses liver metabolism, so the effects are shorter-lived and may be more or less effective than ingested CBD, depending on individual physiology.

One thing we can see from their model, and the actual (oral) data, is that the percentage bioavailability increases for a while (proportional to increasing dosage), then drops consistently as the dosage continues to increase. This type of relationship is called nonmonotonic*. In economics, they often call that "diminishing returns".

Just as significant as the increased bioavailability of inhaled flower versus isolate, is probably the vastly increased bioavailability of oral CBD when administered after meals, especially high-fat meals. After high-fat meals, the CBD bioavailability reached 57%! However, when CBD was ingested in a "fasted state" (empty stomach), the CBD bioavailability could be as low as 4%.

The main take-away for patients and consumers is that to maximize the amount of CBD in our bloodstream, ingest it after a meal, or smoke or vaporize full-spectrum flower instead of isolate. That means you can potentially save money by minimizing the amount of CBD that is wasted by never making it to the bloodstream.

Authors' observations and conclusions:

the oral bioavailability can significantly vary based on the food intake, with a high-fat meal increasing the maximum concentration (Cmax) by fivefold

 

Depending on the oral dose, the oral bioavailability ranges from 4.36% - 22.9% in fasted state and 36.5% - 57% in fed state.

 

inhalation-based delivery of CBD, while delivering a similar systemic delivered dose compared with oral dosing due to high device losses, bypasses first-pass metabolism and can be efficient.

 

CBD PKs vary across different doses due to nonmonotonic* oral bioavailability, and inhalation-based delivery could minimize such variability in humans.

 

* nonmonotonic in this case means the percentage bioavailabilty increases AND then decreases as the dose gets larger; monotonic functions only increase OR decrease as the dose gets larger.

 

The full text article is here at LiebertPub.com.

Source:

Kolli AR, Hoeng J. Cannabidiol Bioavailability Is Nonmonotonic with a Long Terminal Elimination Half-Life: A Pharmacokinetic Modeling-Based Analysis. Cannabis Cannabinoid Res. 2024 Apr 16. doi: 10.1089/can.2023.0214. Epub ahead of print. PMID: 38624257.