Clinical Efficacy and Biological Regulations of ω-3 PUFA-Derived Endocannabinoids in Major Depressive Disorder
Abstract
BACKGROUND: Endocannabinoids (ECs) are one type of bioactive endogenous neuroinflammatory mediator derived from polyunsaturated fatty acids (PUFAs), which may regulate the emotional processes. Here, we assessed the effect of ω-3 PUFAs on EC levels, which may be the novel targets for the ω-3 PUFAs' antidepressive effects.
METHODS: We conducted a 12-week double-blind, nonplacebo, randomized controlled trial. Eighty-eight major depressive disorder (MDD) participants were randomly assigned to receive eicosapentaenoic acid (EPA, 3.0 g/day), docosahexaenoic acid (DHA, 1.4 g/day), or a combination of EPA (1.5 g/d) and DHA (0.7 g/day). Eighty-five participants completed the trial, and their clinical remission and plasma PUFA-derived EC levels (pmol/mL) were measured.
RESULTS: The cumulative rates of clinical remission were significantly higher in the EPA and EPA + DHA groups than the DHA group (51.85 and 53.84 vs. 34.37%; p =0.027 and p =0.024, respectively). EPA and EPA + DHA treatments increased the eicosapentaenoylethanolamide (EPEA) levels compared to DHA treatment (0.33 ± 0.18 and 0.35 ± 0.24 vs. 0.08 ± 0.12; p =0.002 and p =0.001, respectively), while EPA + DHA treatment increased the docosahexaenoylethanolamide levels more than EPA treatment (1.34 ± 2.09 vs. 0.01 ± 1.79; p =0.006). Plasma EPEA levels were positively correlated with rates of clinical remission (hazard ratio: 1.60, 95% confidence interval: 1.08-2.39).
CONCLUSIONS: Treatments enriched with EPA increased plasma…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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