CBD did not reduce THC side effects and actually increased THC blood levels and psychoactive effects in a clinical trial | Research

The takeaway

In a rigorous crossover trial of 37 healthy volunteers, high-dose oral CBD (450 mg) did not reduce THC adverse effects but instead significantly increased THC plasma levels and psychotropic effects by over 60%, without improving analgesic properties.

Cannabis clinicians dosing THC:CBD combination products; regulators assessing CBD product safety claims.

CBD doubled THC blood levels and increased intoxication by 60%

What the researchers found

Co-administration of 450 mg CBD with 9 mg THC increased "Feeling High" by 60.5%, more than doubled THC blood levels (AUC ratio 2.18), and increased the active metabolite 11-OH-THC levels (AUC ratio 1.89). Lower CBD doses (10 and 30 mg) also affected pharmacokinetics. CBD did not counteract psychomotor, cognitive, or autonomic effects of THC, and did not improve THC's analgesic properties.

Why it matters

This is among the most rigorous tests of the widely held assumption that CBD counteracts THC. The finding that CBD increases rather than decreases THC effects has major implications for cannabis product labeling, dosing guidelines, and the marketing of CBD-containing products as "safer."

The numbers in context

37 healthy volunteers. CBD 450mg: Feeling High increased 60.5% (95% CI 12.7%-128.5%). THC AUC ratio: 2.18 (95% CI 1.54-3.08). 11-OH-THC AUC ratio: 1.89 (95% CI 1.30-2.77). CBD 30mg also increased THC AUC (ratio 1.44, 95% CI 1.01-2.04).

How the study worked

Randomized, double-blind, placebo-controlled, five-way crossover trial in 37 healthy volunteers. Each participant received double-placebo, THC 9mg alone, or THC 9mg with CBD 10, 30, or 450 mg orally. Standardized test batteries for psychoactive and analgesic effects. Pharmacokinetic sampling.

What this study cannot tell us

Oral administration only; inhaled cannabis may have different pharmacokinetic interactions. Single-dose study in healthy volunteers with no cannabis tolerance. THC dose (9 mg) is relatively low. Laboratory setting does not replicate real-world use conditions.

How to read the evidence

Gold-standard crossover RCT design with pharmacokinetic data. Single-dose, oral-only, and healthy volunteers limit generalizability.

When this study was published

2024 study

The bigger picture

CBD likely increases THC effects through pharmacokinetic interaction (inhibiting THC metabolism in the liver), not pharmacodynamic antagonism. This means CBD-containing cannabis products may actually be more potent, not less, challenging a widespread consumer assumption.

Questions still open

Does this CBD-THC interaction also occur with inhaled cannabis? At what CBD doses, if any, does the interaction become clinically negligible?

Common questions

Why does CBD increase THC effects?

CBD inhibits the liver enzymes (particularly CYP2C9 and CYP3A4) that metabolize THC, causing more THC to remain in the bloodstream for longer. This pharmacokinetic interaction means the body processes THC more slowly when CBD is present.

Does this mean high-CBD cannabis products are more dangerous?

Products containing both THC and CBD may produce stronger THC effects than expected. This does not apply to CBD-only products without THC. The clinical significance depends on the specific THC and CBD doses and the route of administration.

Read the original research

Cannabidiol Increases Psychotropic Effects and Plasma Concentrations of Δ9-Tetrahydrocannabinol Without Improving Its Analgesic Properties.

Clinical pharmacology and therapeutics, 116(5), 1289-1303

View on PubMed ↗Publisher’s paper ↗

Citation

Gorbenko, Andriy A; Heuberger, Jules A A C; Klumpers, Linda E; de Kam, Marieke L; Strugala, Pamela K; de Visser, Saco J; Groeneveld, Geert J. (2024). Cannabidiol Increases Psychotropic Effects and Plasma Concentrations of Δ9-Tetrahydrocannabinol Without Improving Its Analgesic Properties.. Clinical pharmacology and therapeutics, 116(5), 1289-1303. https://doi.org/10.1002/cpt.3381