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

Trial Summary

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.

What evidence supports the effectiveness of the drug Palmitoylethanolamide (PEA) for chronic pain?

Research shows that Palmitoylethanolamide (PEA) can effectively reduce pain in people with chronic pain conditions, improving their quality of life and functional status without major side effects. ^{1 2 3 4 5}

Is Palmitoylethanolamide (PEA) safe for humans?

Palmitoylethanolamide (PEA) is generally well tolerated in humans and has been studied in several clinical trials without serious adverse effects for treatment durations up to 49 days. However, for treatments longer than 60 days, there isn't enough data to fully rule out less common side effects. ^{1 2 6 7 8}

How is the drug Palmitoylethanolamide (PEA) unique for treating chronic pain?

Palmitoylethanolamide (PEA) is unique for treating chronic pain because it is a naturally occurring fatty acid that reduces pain and inflammation by binding to a receptor in the cell nucleus, and it has shown effectiveness without major side effects or drug interactions. Additionally, the ultra-micronized form of PEA (um-PEA) offers better absorption and efficacy, especially in older patients who are at higher risk of side effects from traditional pain medications. ^{1 2 3 4 9}

What is the purpose of this trial?

The goal of this clinical trial is to evaluate if a supplement called palmitoylethanolamide (PEA) is effective in reducing the pain in patients with chronic inflammatory pain conditions. The main question the trial aims to answer is if PEA works better at treating a patients pain and improving their function better than a placebo. Participants will be divided into two equal groups and asked to take either PEA or a placebo for 8 weeks.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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) 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Palmitoylethanolamide in the treatment of chronic pain caused by different etiopathogenesis. [2020]

2. New Zealand pubmed.ncbi.nlm.nih.gov

N-of-1 Randomized Trials of Ultra-Micronized Palmitoylethanolamide in Older Patients with Chronic Pain. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Palmitoylethanolamide (PEA) on Nociceptive, Musculoskeletal and Neuropathic Pain: Systematic Review and Meta-Analysis of Clinical Evidence. [2023]

6. England pubmed.ncbi.nlm.nih.gov

The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

The Basal Pharmacology of Palmitoylethanolamide. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Oral Ultramicronized Palmitoylethanolamide: Plasma and Tissue Levels and Spinal Anti-hyperalgesic Effect. [2022]