What Is Palmitoylethanolamide (PEA)? Other Names: Hydroxyethylpalmitamide, Impulsin, Palmidrol

What is Palmitoylethanolamide (PEA)?

This post was written with Consensus AI Academic Search Engine – please read our Disclaimer at the end of this article. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide that has garnered significant attention for its potential therapeutic properties. It is naturally produced in the body and is involved in various physiological processes, particularly those related to pain and inflammation. Other names include: Hydroxyethylpalmitamide, Impulsin, N-(2-Hydroxyethyl) hexadecanamide, N-(2-Hydroxyethyl)palmitamide, Palmidrol, Palmitamide MEA, Palmitic Acid Monoethanolamide, Palmitoylethanolamine, PEA.

Clinical Applications of Palmitoylethanolamide (PEA)

Pain Management

PEA has been extensively studied for its role in pain management. It has shown efficacy in reducing both peripheral and central sensitization, making it a promising candidate for treating various types of pain, including chronic pain conditions like fibromyalgia and neuropathic pain1 3 5 7. For instance, in fibromyalgia patients, the addition of PEA to standard treatments like pregabalin and duloxetine resulted in significant improvements in pain and overall disease severity1 9.

Inflammation and Neuroprotection

PEA also exhibits potent anti-inflammatory properties. Studies have demonstrated its ability to reduce inflammation markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) in conditions like COVID-192. Additionally, its neuroprotective effects make it a potential therapeutic agent for neuroinflammatory conditions and neurodegenerative diseases3.

Mental Health

Emerging research suggests that PEA may have antidepressant effects. In a study involving patients with major depressive disorder, PEA supplementation alongside citalopram significantly improved depressive symptoms compared to placebo4. This rapid-onset antidepressant effect highlights its potential as an adjunctive therapy in mental health treatment.

Autism

PEA has also been investigated as an adjunctive therapy for autism. In a randomized controlled trial, the combination of PEA and risperidone showed superior efficacy in reducing irritability and hyperactivity symptoms in children with autism compared to risperidone alone6.

Safety and Tolerability

PEA is generally well-tolerated with a favorable safety profile. In various clinical trials, it has not been associated with significant adverse effects, making it a safe option for long-term use4 6 7.

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Palmitoylethanolamide (PEA) Mechanisms of Action

PEA exerts its effects through multiple mechanisms. It is known to potentiate the action of endocannabinoids, which are compounds that play a crucial role in regulating pain and inflammation. PEA also interacts with several receptors, including cannabinoid receptors (CB1 and CB2), transient receptor potential vanilloid 1 (TRPV1), and peroxisome proliferator-activated receptors (PPARs)3 8. These interactions contribute to its broad-spectrum analgesic, anti-inflammatory, and neuroprotective effects.

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Adverse Effects of Palmitoylethanolamide (PEA)

General Tolerability: PEA has been shown to be well-tolerated in various studies, with no significant increase in adverse effects compared to placebo1 2 10.

Gastrointestinal Issues: In one study, a patient experienced diarrhea, but this occurred under placebo treatment, not PEA2.

No Major Adverse Effects: Studies on different populations, including those with spinal cord injury, chronic pain, and major depressive disorder, did not report significant adverse effects attributable to PEA1 2 10.

Specific Observations: In a study on postoperative pain in rats, PEA did not show adverse effects on body weight, liver, or kidneys6. Similarly, in a study on osteoarthritis in rats, no adverse effects on body weight or organ health were observed7.

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How has Palmitoylethanolamide (PEA) Improved Patient Outcomes?

Fibromyalgia

PEA, when combined with acetyl-L-carnitine (ALC), significantly improved outcomes in fibromyalgia patients already on pregabalin and duloxetine. Patients experienced reduced pain severity, better fibromyalgia impact scores, and improved overall disease status over a 24-week period1 3.

Major Depressive Disorder

In patients with major depressive disorder, PEA as an adjunct to citalopram led to a more significant reduction in depression scores compared to placebo. The PEA group showed rapid improvement in depressive symptoms and a higher response rate2.

COVID-19

In early-stage COVID-19 patients, ultramicronized PEA (um-PEA) reduced inflammation, oxidative stress, and coagulative cascade alterations. It also improved immune response, as evidenced by higher levels of IgG against SARS-CoV-24.

Neuropathic Pain

In patients with spinal cord injury, um-PEA did not significantly reduce neuropathic pain intensity compared to placebo. There were also no significant effects on spasticity, insomnia, or psychological functioning5.

Ocular Hypertension

PEA improved systemic endothelial function and reduced intraocular pressure (IOP) in ocular hypertensive patients. These benefits persisted beyond the treatment period, indicating a lasting positive effect on endothelial function6.

Chronic Pain in Older Adults

In older patients with chronic pain, um-PEA showed a small but statistically significant reduction in pain intensity and functional impairment in some individuals. This suggests that um-PEA can be a useful option for pain management in geriatric patients7.

Autism

PEA, when combined with risperidone, significantly improved irritability and hyperactivity symptoms in children with autism. The combination treatment was more effective than risperidone alone8.

Long COVID

In patients with long COVID, PEA combined with luteolin (PEA-LUT) improved olfactory dysfunction and mental clouding. Patients showed significant improvements in odor identification and a reduction in parosmia and mental clouding over three months9.

Normal-Tension Glaucoma

PEA reduced IOP and improved visual field indices in patients with normal-tension glaucoma. These improvements were significant and not influenced by demographic or clinical characteristics10.

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Common Complaints Associated with Palmitoylethanolamide (PEA) Use

General Tolerability

Overall Tolerability: PEA is generally well-tolerated with no significant differences in the frequency of side effects between PEA and placebo groups in studies on major depressive disorder and autism2 4.

Specific Side Effects

Gastrointestinal Issues: Some users may experience mild gastrointestinal discomfort, although this is not frequently reported in the studies reviewed2.

No Significant Adverse Effects: In studies involving geriatric patients with chronic pain and children with autism, no significant adverse effects were reported, indicating a favorable safety profile1 4.

Study-Specific Observations

Major Depressive Disorder: In a study on PEA as an adjunctive therapy for major depressive disorder, no significant differences in baseline parameters and frequency of side effects were observed between the PEA and placebo groups2.

Autism: In a trial involving children with autism, PEA combined with risperidone showed no significant differences in adverse effects compared to the placebo group, suggesting good tolerability4.

COVID-19: In a study on COVID-19 patients, PEA was well-tolerated with no specific complaints or adverse effects reported3.

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