# Sex-specific association between low oral doses of cannabidiol (CBD) and plasma concentration of anandamide (AEA), N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA) in healthy occasional cannabis users

> **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637)
> **Publisher:** CED Clinic (https://cedclinic.com)
> **Canonical URL:** https://cedclinic.com/research/cbd-for-inflammation-randomized-controlled-trial/
> **Published:** 2026-10-22T13:08:30-04:00 | **Last Modified / Clinically Audited:** 2026-10-22T13:08:44-04:00
> **Clinical Summary:** Researchers studied healthy adults who use cannabis now and then. The results were mixed, and the effect was seen only in women.

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Background: Cannabidiol (CBD), a phytocannabinoid produced by Cannabis sativa, is widely consumed and interacts with components of the endocannabinoid system through indirect and complex mechanisms. How CBD influences endogenous cannabinoids such as anandamide (AEA), and related N-acylethanolamines like N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA), remains poorly understood. This study investigates the acute impact of marketed CBD doses on plasmatic levels of these signaling lipids in occasional cannabis users. Methods: In a triple-blind, placebo-controlled, randomized crossover trial, 70 healthy volunteers received ten sequences of four oral CBD doses (20, 50, 100, 200 mg) and placebo. Blood was sampled at baseline and five timepoints post-dose. Plasma AEA, PEA, and OEA were quantified by LC-MS, and dose-response assessed with linear mixed-effects models on plasma concentrations (model 1) and Area Under the Curve to increase (AUCi, model 2). Results: Model 2 revealed a significant effect of CBD dose on AUCi of PEA and OEA, but not AEA. Placebo was associated with significantly higher AUCi than the 50 mg dose (p < 0.05) and trended higher than the 200 mg dose (p < 0.10). Sex emerged as a significant factor: reductions in AUCi were driven by female participants, confirmed at 50 mg and 200 mg (only PEA) compared to placebo. No corresponding effects were observed in males. All plasma levels decreased overall throughout each visit, at every dose of CBD and placebo. Conclusions: Among healthy adults who consume cannabis occasionally, low-dose oral CBD formulations significantly decreased cumulative plasma levels of PEA and OEA in a female-specific fashion, confirming the importance of sex-differences in cannabinoid response.

 

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### Verification & Medical Governance

- **Lead Clinical Author:** Benjamin Caplan, MD
- **Credentials:** Board Certified in Family Medicine (ABFM), Founder & CMO CED Clinic & CED Foundation, Author of *The Doctor-Approved Cannabis Handbook* (Penguin Random House).
- **Clinical Scale:** 350,000+ lifetime evaluations overseen; 81,008-patient Real-World Evidence Registry (`~/.ced_rwe_vault.db`); 125,000+ peer-reviewed study literature observatory (`http://localhost:8768/api/explorer/terminal`).
- **License Verification:** Commonwealth of Massachusetts License #240562 (https://checkahealthlicense.mass.gov/).
- **NPI Registry:** 1962722637 (https://npiregistry.cms.hhs.gov/provider-view/1962722637).
- **Ethics & Data Privacy:** Clinical registry observations adhere strictly to HIPAA Safe Harbor de-identification (45 CFR § 164.514(b)) and criteria for secondary research exemption under 45 CFR § 46.104(d)(4).