These drugs will help the scientists figure out how CBD and THC affect how participants’ bodies metabolize other commonly used medications and dietary supplements (in analyses that will be published separately).
Participants were also given a drug cocktail consisting of five cytochrome (CYP) probe drugs (100 mg caffeine, 25 mg losartan, 20 mg omeprazole, 30 mg dextromethorphan, and 2 mg midazolam) 30 minutes after eating each brownie. Neither the participants nor the investigators knew in advance what was in the brownie that participants ate on a given session. In each session, participants consumed a brownie containing either 20 mg of THC, 20 mg of THC and 640 mg of CBD, or no THC or CBD (placebo). Study volunteers took part in three sessions, each separated by at least one week. The researchers recruited 18 adult participants (11 men and 7 women) who had not used cannabis for at least 30 days prior to beginning the study. The new study, which tested each type of cannabis extract and a placebo within the same subjects rather than using different people for each drug type, was conducted from January 2021 to March 2022 at the Behavioral Pharmacology Research Unit at Johns Hopkins Bayview Medical Center. “Overall, we saw stronger subjective drug effects, greater impairment of cognitive and psychomotor ability and greater increase in heart rate when the same dose of THC was given in a high CBD cannabis extract, compared with a high THC extract with no CBD,” says Zamarripa.
For this reason, much of the existing data regarding interactions between THC and CBD may not apply to edible cannabis products such as baked goods, candies and gummies, which get metabolized in the intestine and liver. Prior controlled human studies evaluating these interactions have predominantly administered THC and CBD by inhalation or intravenously, or have not administered them at the same time. “The fact that THC and CBD were orally administered was very important for the study, and played a large role in the behavioral effects and drug interactions we saw,” says Austin Zamarripa, Ph.D., a postdoctoral research fellow at the Johns Hopkins University School of Medicine and the study’s lead author. The work examined the pharmacokinetics (absorption and elimination of a drug by the body) and pharmacodynamics (the body’s response to a drug) between cannabis extracts that varied with respect to THC and CBD concentrations. In addition, the maximum amount of 11-OH-THC (a metabolic byproduct of THC that produces drug effects similar to THC) was 10-fold greater after eating the brownie with the high CBD extract compared with the one containing high THC extract. 13 in JAMA Network Open, found that the maximum amount of THC measured in participants’ blood samples was almost twice as high after consuming a brownie containing THC with CBD than after eating a brownie with only THC, even though the dose of THC in each brownie (20 mg) was the same.
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