Palmitoylethanolamide for Chronic Pain

Overseen By Brian McLean Pain Physician, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Navy Medical Center San Diego

Disqualifiers: Severe food allergy

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 8 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the supplement palmitoylethanolamide (PEA) can reduce pain and improve function in individuals with chronic inflammatory pain. Participants will be divided into two groups: one will take PEA, and the other will take a placebo for 8 weeks. The trial aims to determine if PEA is more effective than a placebo in managing pain. Individuals with chronic pain lasting more than 3 months, unresponsive to treatments like rest or medication, may be suitable for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that palmitoylethanolamide is likely to be safe for humans?

Research has shown that palmitoylethanolamide (PEA) is generally safe for people. PEA, a natural fatty acid in the body, often helps with pain and swelling. Most people taking PEA experience only mild side effects, such as an upset stomach or diarrhea, if any. Serious side effects are rare. The presence of PEA in a mid-stage clinical trial indicates that earlier tests did not find major safety issues. If PEA were unsafe, it would not have reached this stage of testing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Palmitoylethanolamide (PEA) is unique because it's a naturally occurring fatty acid that works by reducing inflammation and modulating the body's pain response. Unlike traditional treatments for chronic pain, such as opioids or NSAIDs, which can have significant side effects or addiction potential, PEA offers a potentially safer alternative. Researchers are excited about PEA because it targets the endocannabinoid system differently, potentially providing effective pain relief with fewer side effects.

What evidence suggests that palmitoylethanolamide might be an effective treatment for chronic pain?

Research shows that palmitoylethanolamide (PEA), which participants in this trial may receive, can help reduce various types of pain. Studies have found that it possesses properties that lower inflammation, benefiting conditions like osteoarthritis and fibromyalgia. PEA is a natural substance in the body that helps manage pain and swelling. Some individuals have reported experiencing less chronic pain after taking PEA supplements. Although more research is needed to confirm its effectiveness, early findings are promising for those seeking alternative pain relief methods. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for people who have been dealing with chronic inflammatory pain for more than 3 months, which hasn't improved with basic treatments like rest or over-the-counter meds. The pain should be at least a 5 out of 10 in intensity. It's not suitable for those with severe food allergies, including nuts, eggs, or soy.

Inclusion Criteria

I have had chronic pain for over 3 months, with a pain level of at least 5/10, that hasn't improved with basic treatments.

Exclusion Criteria

Severe allergy to any specific food component such as nut, egg or soy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Palmitoylethanolamide (PEA) or a placebo for 8 weeks

8 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Palmitoylethanolamide

Trial Overview

The study is testing if taking palmitoylethanolamide (PEA), a supplement, can reduce chronic pain better than a sugar pill (placebo). Participants will randomly receive either PEA or placebo and use it twice daily for 8 weeks to compare the effects on their pain and function.

How Is the Trial Designed?

Group I: Palmitoylethanolamide Experimental Treatment 1 Intervention

Participants randomized to the experimental arm will receive the supplement Palmitoylethanolamide (PEA) at a dose of 600mg twice a day

Group II: Placebo Placebo Group 1 Intervention

Participants randomized to the placebo arm will receive a visually identical placebo capsule

Who Is Running the Clinical Trial?

Navy Medical Center San Diego

Lead Sponsor

Trials

4

Recruited

480+

Published Research Related to This Trial

In a study involving 11 older patients with chronic pain, ultra-micronized palmitoylethanolamide (um-PEA) showed a small but statistically significant effect on pain intensity in two patients, suggesting it may be beneficial for chronic pain management in this population.

The study utilized N-of-1 trials, which allowed for personalized treatment decisions, and resulted in changes to treatment plans for some patients, indicating that um-PEA could be a viable alternative to traditional analgesics for older adults at risk of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-of-1 Randomized Trials of Ultra-Micronized Palmitoylethanolamide in Older Patients with Chronic Pain. Germini, F., Coerezza, A., Andreinetti, L., et al.[2020]

Palmitoylethanolamide (PEA) has been shown to significantly reduce pain intensity in patients with chronic pain, based on a systematic review and meta-analysis of 11 studies involving 774 patients, with a strong effect size (standard mean difference of 1.68).

PEA is well-tolerated with no major side effects reported, and it may also improve quality of life and functional status, indicating its potential as a safe and effective treatment option for chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials. Lang-Illievich, K., Klivinyi, C., Lasser, C., et al.[2023]

Palmitoylethanolamide (PEA) appears to have analgesic properties with a low incidence of serious adverse drug reactions (ADRs) reported in clinical trials lasting up to 49 days, suggesting it is a safe option for pain management.

However, the evidence is limited for treatment durations over 60 days, and the quality of existing studies varies, indicating a need for further research, especially comparing different formulations of PEA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy. Gabrielsson, L., Mattsson, S., Fowler, CJ.[2021]

Palmitoylethanolamide (PEA) is a well-tolerated compound with anti-inflammatory and pain-relieving properties, primarily acting through the activation of the PPAR-α receptor, but also involving other receptors like TRPV1 and GPR55.

Despite its potential as a treatment for pain, there is limited knowledge about PEA's bioavailability, tissue distribution, and excretion, indicating a need for further research to fully understand its pharmacokinetic properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Basal Pharmacology of Palmitoylethanolamide. Rankin, L., Fowler, CJ.[2021]

Ultramicronized palmitoylethanolamide (PEA-um) is more absorbable than non-micronized PEA, leading to higher plasma levels in both healthy and inflamed conditions, as shown in a study with rats.

PEA-um effectively reduces inflammation and pain in carrageenan-injected rats, demonstrating its ability to down-regulate spinal inflammatory pathways, which contributes to its anti-hyperalgesic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Ultramicronized Palmitoylethanolamide: Plasma and Tissue Levels and Spinal Anti-hyperalgesic Effect. Petrosino, S., Cordaro, M., Verde, R., et al.[2022]

Palmitoylethanolamide (PEA) is a naturally occurring compound with neuroprotective, anti-inflammatory, and analgesic properties, making it a promising nutraceutical for treating neurodegenerative disorders and pain.

New formulations of PEA, particularly micronized and ultra-micronized versions, may enhance its efficacy, especially when combined with antioxidant compounds like luteolin and polydatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations. Petrosino, S., Di Marzo, V.[2021]

In a study involving 610 patients with chronic pain, palmitoylethanolamide (PEA) significantly reduced pain severity over a treatment period of 7 weeks, regardless of the underlying condition.

PEA was found to be safe, with no reported adverse effects, and was effective even in patients not receiving additional analgesic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palmitoylethanolamide in the treatment of chronic pain caused by different etiopathogenesis. Gatti, A., Lazzari, M., Gianfelice, V., et al.[2020]

Palmitoylethanolamide (PEA) has shown potential in treating various chronic pain conditions, including diabetic neuropathy and osteoarthritis, by binding to the peroxisome proliferator-activated receptor, which may help reduce pain and inflammation.

PEA is considered safe with no serious side effects reported, likely due to its natural occurrence in food and its role as an endogenous modulator, making it a promising option for patients with chronic pain that doesn't respond well to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series. Hesselink, JM., Hekker, TA.[2023]

Palmitoylethanolamide (PEA) has shown significant efficacy in reducing chronic pain in a systematic review of 933 patients, outperforming control treatments, particularly in nociceptive musculoskeletal and neuropathic pain.

Despite promising results, the high variability among studies and potential publication bias indicate a need for more robust randomized, double-blind clinical trials to confirm PEA's effectiveness and explore its role as an add-on therapy for chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Palmitoylethanolamide (PEA) on Nociceptive, Musculoskeletal and Neuropathic Pain: Systematic Review and Meta-Analysis of Clinical Evidence. Scuteri, D., Guida, F., Boccella, S., et al.[2023]

Citations

1.

en.wikipedia.org

en.wikipedia.org/wiki/Palmitoylethanolamide

Palmitoylethanolamide

Palmitoylethanolamide (PEA) is an endogenous fatty acid amide, and lipid modulator. ... N-(2-Hydroxyethyl)hexadecanamide. Other names. Hydroxyethylpalmitamide ...

2.

webmd.com

webmd.com/vitamins/ai/ingredientmono-1596/palmitoylethanolamide-pea

Palmitoylethanolamide (Pea) - Uses, Side Effects, and More

PEA is used for different types of pain, fibromyalgia, osteoarthritis, multiple sclerosis (MS), carpal tunnel syndrome, autism, and many other conditions

3.

pubchem.ncbi.nlm.nih.gov

pubchem.ncbi.nlm.nih.gov/compound/Palmitoylethanolamide

Palmitoylethanolamide | C18H37NO2 | CID 4671 - PubChem

Palmitoyl ethanolamide is an N-(long-chain-acyl)ethanolamine that is the ethanolamide of palmitic (hexadecanoic) acid. It has a role as an anti-inflammatory ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3771453/

A Natural Body-Own Anti-Inflammatory Agent, Effective and ...

Palmitoylethanolamide (PEA) is a food component with anti-inflammatory properties, effective and safe against influenza and common cold, and has been studied ...

5.

precision.fda.gov

precision.fda.gov/uniisearch/srs/unii/6r8t1udm3v

UNII - 6R8T1UDM3V

PALMIDROL ; UNII: 6R8T1UDM3V ; Formula: C18H37NO2 ; Preferred Substance Name: PALMIDROL ; InChIKey: HXYVTAGFYLMHSO-UHFFFAOYSA-N ...

6.

webbook.nist.gov

webbook.nist.gov/cgi/cbook.cgi?InChI=1/C18H37NO2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-18(21)19-16-17-20/h20H,2-17H2,1H3,(H,19,21)

Palmidrol - the NIST WebBook

Palmidrol · Formula: C18H37NO · Molecular weight: 299.4919 · IUPAC Standard InChI: InChI=1S/C18H37NO2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-18(21)19-16-17-20/h20H,2 ...