According to a study published Feb. 13 in JAMA Network Open, when THC was combined with CBD in edibles, they produced significantly stronger subjective drug effects, greater impairment of cognitive and psychomotor ability.
The study supports what Harvard Professor Dr. Lester Grinspoon and many others have said all along: that CBD combined with THC produces stronger effects, part of what’s often called the entourage or ensemble effect.
The findings indicate that CBD in edibles inhibit the metabolism, or breakdown, of THC, which may result in stronger and longer effects. In the study, impairment was considered an adverse effect.
Researchers observed 18 adults, 11 male and 7 female from January 2021 to March 2022 at the Behavioral Pharmacology Research Unit at Johns Hopkins Bayview Medical Center in Baltimore, Maryland.
Study volunteers took part in three sessions eating infused brownies, separated for a week or more. In each session, participants ate a brownie with either 20 mg of THC, 20 mg of THC and 640 mg of CBD, or no THC or CBD as placebo. Neither the participants nor the investigators knew in advance what was in the brownie that participants ate as a double blind study.
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.
Researchers noted that the maximum amount of THC measured in participants’ blood samples was almost twice as high after consuming a brownie containing a CBD-dominant extract (with 640 mg of CBD) than after eating a brownie with only THC, even though the dose of THC in each brownie—20 mg—was the same.
Researchers acknowledged that edibles are metabolized very differently than other delivery methods.
“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,” study author Austin Zamarripa, Ph.D. said, as quoted by News Medical.
“Overall, we saw stronger subjective drug effects, greater impairment of cognitive [thinking] and psychomotor [moving] 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,” said Zamarripa.
To allow for comparison, blood samples were collected from study participants before each session, along with their vital signs, and their cognitive and psychomotor performance were measured. Participants provided blood and urine samples at timed intervals for 12 hours and then again about 24 hours after eating a dose.
Self-reported effects were measured using the Drug Effect Questionnaire (DEQ), a standardized tool used to measure aspects of subjective experiences after being given a psychoactive drug (in this case, cannabis).
Using the DEQ system, participants rated subjective effects from the edibles with a scale from 0 to 100, with 0 being “not at all affected” and 100 being “extremely affected.”
Participants reported greater increases in overall drug effects when they took the high oral dose of CBD.
“We have demonstrated that with a relatively high oral dose of CBD [640 mg] there can be significant metabolic interactions between THC and CBD, such that the THC effects are stronger, longer-lasting, and tend to reflect an increase in unwanted adverse effects,” says Ryan Vandrey, Ph.D., professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and the study’s senior author.
The study differs from previous findings. A study published in November 2022 in the journal Neuropsychology attempted to determine if CBD reduces the adverse effects of THC, which could be considered as including impairment. But they found that CBD doesn’t necessarily show evidence of reducing adverse side effects.
Researchers said that future studies are needed to better understand the impact of CBD and THC doses.