CBD did not change how the body absorbs or processes THC at therapeutic doses | Research

The takeaway

In 9 cannabis smokers, Sativex and equivalent oral THC doses produced nearly identical THC blood levels, indicating CBD's effects on THC are not due to changing THC absorption or metabolism.

Read this if you want to understand the science behind how CBD and THC interact in pharmaceutical products.

THC bioavailability was 93-99% equivalent between Sativex and pure oral THC

What the researchers found

Researchers measured plasma levels of cannabinoids after administering Sativex (THC+CBD) and pure oral THC to determine whether CBD alters THC pharmacokinetics.

Nine cannabis smokers received five treatments in randomized, double-blind sessions: placebo, low and high oral THC, and low and high Sativex doses. Blood was drawn at multiple time points over 10.5 hours.

There were no significant differences in peak plasma THC concentration, time to peak, or total THC exposure between equivalent oral THC and Sativex doses. Relative bioavailability calculations showed oral THC at 5 and 15 mg was 92.6% and 98.8% of Sativex, respectively, nearly identical.

These data demonstrated that whatever effects CBD has on THC are not due to pharmacokinetic interactions (changing absorption or metabolism) at therapeutic doses.

Why it matters

Ruling out pharmacokinetic interaction meant that any CBD modulation of THC effects would have to be pharmacodynamic (at the receptor level), which informed the design of future combination products.

The numbers in context

9 completers. THC bioavailability: 92.6% (5 mg) and 98.8% (15 mg) of equivalent Sativex doses. No significant differences in Cmax, Tmax, or AUC between oral THC and Sativex.

How the study worked

Randomized, double-blind, placebo-controlled, five-session crossover study. 9 cannabis smokers. CBD, THC, 11-OH-THC, and THC-COOH quantified in plasma by 2D GC-MS. Lower limits of quantification at 0.25 mcg/L or below.

What this study cannot tell us

Very small sample (9 participants). Only therapeutic doses tested. Cannabis smokers may metabolize cannabinoids differently than naive users. Single-dose pharmacokinetics may differ from steady-state with chronic dosing.

How to read the evidence

Well-designed pharmacokinetic study with rigorous analytical methods but very small sample.

When this study was published

Published in 2011. CBD-THC pharmacokinetic interaction research has continued.

The bigger picture

This pharmacokinetic study was important for understanding how CBD and THC interact in pharmaceutical products, establishing that CBD did not act as a metabolic modifier of THC at the doses tested.

Questions still open

Does CBD affect THC pharmacokinetics at higher doses or with chronic use? If CBD's interaction is pharmacodynamic, what receptors mediate the modulation?

Common questions

Does CBD change how the body processes THC?

At the doses tested in this study, no. THC blood levels were nearly identical whether given alone or with CBD in Sativex, indicating CBD does not affect THC absorption or metabolism at therapeutic doses.

Then how might CBD modify THC effects?

If CBD modifies THC effects (which was not clearly shown at these doses), it would have to be through pharmacodynamic interactions, meaning at the receptor level in the brain, rather than by changing THC blood levels.

Read the original research

Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration.

Clinical chemistry, 57(1), 66-75

View on PubMed ↗Publisher’s paper ↗

Citation

Karschner, Erin L; Darwin, W David; Goodwin, Robert S; Wright, Stephen; Huestis, Marilyn A. (2011). Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration.. Clinical chemistry, 57(1), 66-75. https://doi.org/10.1373/clinchem.2010.152439