Inhaling cannabis containing THC acutely increased plasma anandamide and related lipids in healthy volunteers, but co-administering 10-30 mg of CBD did not influence these endocannabinoid changes.
People interested in how THC and CBD interact biologically and what happens in the endocannabinoid system after cannabis use.
CBD at 10-30 mg had no effect on THC-induced endocannabinoid changes
What the researchers found
Cannabis inhalation induced acute increases in anandamide (+18%), DEA (+35.8%), oleoylethanolamide (+16.1%), and N-arachidonoyl-L-serine (+25.1%). Co-administration of 10, 20, or 30 mg CBD alongside 10 mg THC did not alter these endocannabinoid changes. An unexpected finding was progressive reduction in pre-treatment anandamide levels across repeated sessions.
Why it matters
A common claim is that CBD modulates THC effects through the endocannabinoid system. This rigorous RCT found no evidence that CBD (up to 30 mg) altered THC-induced endocannabinoid changes, challenging one proposed mechanism for CBD-THC interaction.
The numbers in context
46 healthy volunteers. 10 mg THC per session. CBD doses: 0, 10, 20, 30 mg. Anandamide increased 18%. DEA increased 35.8%. Median 14 days between sessions. No CBD dose influenced endocannabinoid responses.
How the study worked
Randomized, double-blind, four-arm crossover study with 46 healthy volunteers. Each participant inhaled cannabis vapor containing 10 mg THC with 0, 10, 20, or 30 mg CBD across four sessions (median 14 days apart). Blood samples taken pre-inhalation and at 0, 5, 15, and 90 minutes post-inhalation. Plasma endocannabinoids measured via LC-MS.
What this study cannot tell us
CBD doses (10-30 mg) were relatively low; higher doses might show effects. Acute, single-dose design; chronic co-administration could differ. Only plasma endocannabinoids measured; brain levels may differ. The progressive decline in baseline anandamide across sessions is unexplained.
How to read the evidence
Well-designed double-blind crossover RCT with objective biomarker outcomes. Limited by relatively low CBD doses and acute-only assessment.
When this study was published
Published in 2024 in Cannabis and Cannabinoid Research.
The bigger picture
The idea that CBD "balances" THC is widely believed but poorly supported by mechanistic evidence. This study adds to data suggesting that at commonly consumed doses, CBD may not meaningfully alter THC pharmacology through the endocannabinoid system, though other mechanisms remain possible.
Questions still open
- Would higher CBD doses (100+ mg) alter THC-induced endocannabinoid changes? Does CBD modulate THC through mechanisms other than the endocannabinoid system? Why did baseline anandamide levels decline across sessions?
Common questions
Does CBD change what THC does to the endocannabinoid system?
What did THC do to endocannabinoid levels?
Read the original research
Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on Plasma Endocannabinoid Levels in Healthy Volunteers: A Randomized Double-Blind Four-Arm Crossover Study.
Cannabis and cannabinoid research, 9(1), 188-198
Citation
Chester, Lucy A; Englund, Amir; Chesney, Edward; Oliver, Dominic; Wilson, Jack; Sovi, Simina; Dickens, Alex M; Oresic, Matej; Linderman, Tuomas; Hodsoll, John; Minichino, Amedeo; Strang, John; Murray, Robin M; Freeman, Tom P; McGuire, Philip. (2024). Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on Plasma Endocannabinoid Levels in Healthy Volunteers: A Randomized Double-Blind Four-Arm Crossover Study.. Cannabis and cannabinoid research, 9(1), 188-198. https://doi.org/10.1089/can.2022.0174
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