THC raised endocannabinoid levels in healthy volunteers, but adding CBD made no difference
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- CBD at 10-30 mg had no effect on THC-induced endocannabinoid changes
- Evidence Grade:
- Well-designed double-blind crossover RCT with objective biomarker outcomes. Limited by relatively low CBD doses and acute-only assessment.
- Study Age:
- Published in 2024 in Cannabis and Cannabinoid Research.
- Original Title:
- Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on Plasma Endocannabinoid Levels in Healthy Volunteers: A Randomized Double-Blind Four-Arm Crossover Study.
- Published In:
- Cannabis and cannabinoid research, 9(1), 188-198 (2024)
- Authors:
- Chester, Lucy A(2), Englund, Amir(6), Chesney, Edward(13), 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
- Database ID:
- RTHC-05201
Evidence Hierarchy
Participants are randomly assigned to treatment or placebo groups to test cause and effect.
What do these levels mean? →Frequently Asked Questions
Does CBD change what THC does to the endocannabinoid system?
In this study, no. Adding 10 to 30 mg of CBD to a 10 mg THC dose did not alter the acute changes in plasma endocannabinoid levels, though higher CBD doses or chronic use might produce different results.
What did THC do to endocannabinoid levels?
Inhaling THC acutely increased plasma anandamide by 18% and boosted several related lipid signaling molecules, suggesting THC triggers the body to release its own endocannabinoids.
Read More on RethinkTHC
- CBD-oil-quality-guide
- anxiety-medication-after-quitting-weed
- cannabis-chemotherapy-nausea
- cannabis-chronic-pain-research
- cannabis-epilepsy-CBD-Epidiolex
- cbd-anxiety-research-evidence
- cbd-for-weed-withdrawal
- cbd-vs-thc-difference
- medical-benefits-of-cannabis
- quitting-weed-before-surgery
- quitting-weed-medication-interactions
- quitting-weed-pregnancy
- quitting-weed-pregnant
- seniors-older-adults-cannabis-risks-medications
- weed-breastfeeding-THC-breast-milk
Cite This Study
https://rethinkthc.com/research/RTHC-05201APA
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
MLA
Chester, Lucy A, et al. "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, 2024. https://doi.org/10.1089/can.2022.0174
RethinkTHC
RethinkTHC Research Database. "Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on P..." RTHC-05201. Retrieved from https://rethinkthc.com/research/chester-2024-effects-of-cannabidiol-and
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.