Synopsis

Source of validity: Scientific
Rating (out of 5): 2

Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide that has been studied for its anti-inflammatory, neuroprotective, and analgesic properties. Its use in supporting or treating depression is based on preliminary scientific investigation rather than traditional use or widespread clinical adoption. Several small-scale studies and preclinical investigations suggest that PEA may exert antidepressant-like effects, possibly by modulating neuroinflammation, endocannabinoid signaling, and neurotrophic factors such as BDNF (brain-derived neurotrophic factor).

For example, a randomized, controlled pilot study published in 2013 (Crupi et al., CNS & Neurological Disorders - Drug Targets) found that adjunctive PEA (1.2g/day) with citalopram led to greater improvements in depressive symptoms than citalopram alone in patients with major depressive disorder over a 6-week period. Animal studies echo these findings, showing that PEA can reduce depressive-like behaviors in rodent models, likely via reductions in neuroinflammation and support of neuroplasticity.

However, the evidence base is still limited: clinical studies are few, sample sizes are small, and there is a lack of replication. Thus, while early data are promising and provide a mechanistic rationale, PEA cannot currently be considered an evidence-based treatment for depression. More large-scale randomized controlled trials are needed to confirm efficacy and safety.

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