Pea8.5

PEA Research

39 peer-reviewed studies · Evidence score: 8.5/10

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

Lang-Illievich K et al. • Nutrients (2023)

Further study is warranted to determine the optimal dosing and administration parameters of PEA for analgesic effects in the context of chronic pain.

PEA was found to reduce pain scores relative to comparators in a pooled estimate, with a standard mean difference of 1.68 (95% CI 1.05 to 2.31, p = 0.00001).
Several studies reported additional benefits of PEA for quality of life and functional status, and no major side effects were attributed to PEA in any study.
The results of this systematic review and meta-analysis suggest that PEA is an effective and well-tolerated treatment for chronic pain.

Meta-Analysisn=774

DOI

Navigating agitation in neurodevelopmental disorders: A comparative study of pharmacotherapies via network meta-analysis in children and adults with autism spectrum disorder or intellectual disabilities

Bahji A et al. • Journal of psychopharmacology (Oxford, England) (2025)

This study underscores the efficacy and tolerability of several pharmacotherapies in managing agitation among children and adults with ASD or ID.

Importantly, these treatments were generally well-tolerated, with no significant increase in all-cause dropouts compared to placebo, highlighting their suitability for clinical use in managing agitation in individuals with ASD or ID.
This study underscores the efficacy and tolerability of several pharmacotherapies in managing agitation among children and adults with ASD or ID.
Our findings provide robust evidence that specific treatments, such as arbaclofen, risperidone plus buspirone and omega-3 fatty acids, are both effective and well-tolerated, offering valuable therapeutic options for clinicians.

Meta-Analysisn=2,503

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Meta-Analysis of Palmitoylethanolamide in Pain Management: Addressing Literature Gaps and Enhancing Understanding

Viña I et al. • Nutrition reviews (2025)

This meta-analysis confirmed that PEA effectively reduces pain and enhances quality of life, with significant benefits observed within 4-6 weeks of treatment.

This meta-analysis confirmed that PEA effectively reduces pain and enhances quality of life, with significant benefits observed within 4-6 weeks of treatment.
Palmitoylethanolamide is a promising alternative to chronic opioid analgesics, potentially reducing the risk of opioid abuse and dependency.
Further research warranted to confirm findings

Meta-Analysisn=1,196

DOI

Comparative analysis of medical treatments for long-term control of normal tension glaucoma: A systematic review and model-based network meta-analysis

Yang TK et al. • Clinical & experimental ophthalmology (2025)

This study revealed PEA as a promising agent for long-term IOP control in NTG patients, suggesting potential use as primary or adjunctive therapy.

Both brimonidine and unoprostone isopropyl have SUCRA scores below 4.0%, indicating modest but limited efficacy.
Brovincamine has the lowest SUCRA score (1.32%), reflecting minimal effectiveness.
This study revealed PEA as a promising agent for long-term IOP control in NTG patients, suggesting potential use as primary or adjunctive therapy.

Meta-Analysisn=795

DOI

Extended Treatment with Micron-Size Oral Palmitoylethanolamide (PEA) in Chronic Pain: A Systematic Review and Meta-Analysis

Schweiger V et al. • Nutrients (2024)

Overall, these results confirm the clinically relevant and time-depended pain-relieving effect of micron-size PEA and therefore the advantage of an extended treatment, especially in patient with incomplete pain management.

These two obtained scores corresponded to a 35.1% pain intensity reduction within the first month, followed by a further 35.4% during the second month.
The meta-analysis showed a statistically and clinically significant pain intensity reduction after 60 days of micron-size PEA supplementation, compared to 30 days (1.36 points, p < 0.01).
The secondary analysis revealed a weighted NRS/VAS score decrease of 2.08 points within the first month of treatment.

Meta-Analysisn=742

DOI

Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis

Artukoglu BB et al. • Pain physician (2017)

PEA may be a useful treatment for pain and is generally well tolerated in research populations.

PEA was associated with significantly greater pain reduction compared to inactive control conditions (WMD = 2.03, 95% CI: 1.19 - 2.87, z = 4.75, P < 0.001).
All-cause dropout was non-significantly reduced in the PEA group compared to inactive control conditions (RR = 0.36, 95% CI: 0.10 - 1.26, z = -1.60, P = 0.11).
PEA may be a useful treatment for pain and is generally well tolerated in research populations.

Meta-Analysisn=786

DOI

Dietary interventions for multiple sclerosis-related outcomes

Parks NE et al. • The Cochrane database of systematic reviews (2020)

There are a variety of controlled trials addressing the effects of dietary interventions for MS with substantial variation in active treatment, comparator, and outcomes of interest.

Among four trials comparing PUFAs with MUFAs, there may be little to no difference in global impression of deterioration (RR 0.85, 95% CI 0.71 to 1.03; 4 studies, 542 participants; 40% in the PUFA group versus 47% in the MUFA group; low-certainty evidence).
In two trials comparing different PUFAs (omega-3 versus omega-6), there may be little to no difference in relapses (RR 1.02, 95% CI 0.62 to 1.66; 2 studies, 129 participants; 30% in the omega-3 versus 29% in the omega-6 group; low-certainty evidence).
Among three trials comparing omega-3 with omega-6, there may be little to no difference in change in disability progression, measured as mean change in Expanded Disability Status Scale (EDSS) (mean difference (MD) 0.00, 95% CI -0.30 to 0.30; 3 studies, 166 participants; low-certainty evidence).

Meta-Analysisn=217

DOI

Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction

O'Byrne L et al. • The Cochrane database of systematic reviews (2022)

There is very limited evidence available on the efficacy and harms of treatments for persistent olfactory dysfunction following COVID-19 infection.

There is very limited evidence available on the efficacy and harms of treatments for persistent olfactory dysfunction following COVID-19 infection.
However, we have identified a number of ongoing trials in this area.
As this is a living systematic review we will update the data regularly, as new results become available.

Systematic Reviewn=30

DOI

Treatment of COVID-19 Associated Olfactory Dysfunction: A Systematic Review

Bischoff S et al. • Current allergy and asthma reports (2024)

Treatments such as PRP and calcium chelators demonstrated significant improvements on OFS, whereas olfactory training and corticosteroids did not show notable efficacy for COVID-19 associated olfactory dysfunction.

Systematic review examining Luteolin efficacy
Further research warranted to confirm findings

Systematic Review

DOI

Effect of any form of steroids in comparison with that of other medications on the duration of olfactory dysfunction in patients with COVID-19: A systematic review of randomized trials and quasi-experimental studies

Winn PZ et al. • PloS one (2023)

Corticosteroid treatment is effective in reducing the duration of COVID-19-related smell loss and olfactory training, the basic, essential and effective intervention, should be used as a combination therapy.

Treatment with oral corticosteroid plus olfactory training significantly improved Threshold, Discrimination and Identification (TDI) scores compared with olfactory training alone.
Corticosteroid treatment is effective in reducing the duration of COVID-19-related smell loss and olfactory training, the basic, essential and effective intervention, should be used as a combination therapy.
Further research warranted to confirm findings

Systematic Review

DOI

Intervention modalities for brain fog caused by long-COVID: systematic review of the literature

Gorenshtein A et al. • Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology (2024)

This systematic-review examined the effects of Luteolin.

Noninvasive brain stimulation and hyperbaric oxygen therapy showed promising results in the treatment of brain fog symptoms caused by long-COVID, with improved perfusion and cortical excitability.
Furthermore, both rehabilitation strategies and PEA-LUT administration have been associated with improvements in symptoms of brain fog.
Future studies should explore combinations of interventions and include longer follow-up periods to assess the long-term effects of these treatments.

Systematic Reviewn=17

DOI

Interventions for Improving Long COVID-19 Symptomatology: A Systematic Review

Veronese N et al. • Viruses (2022)

Our systematic review found only two intervention studies focused on patients affected by long COVID-19.

Our systematic review found only two intervention studies focused on patients affected by long COVID-19.
More intervention studies are needed to investigate potentially positive interventions for long COVID-19 symptoms.
Further research warranted to confirm findings

Systematic Review

DOI

Investigational drugs for the treatment of olfactory dysfunction

Di Stadio A et al. • Expert opinion on investigational drugs (2022)

The authors believe these treatments might be an option also for treating olfactory disease related to neurodegeneration.

Systematic review examining Luteolin efficacy
Further research warranted to confirm findings

Systematic Review

DOI

Long-term and serious harms of medical cannabis and cannabinoids for chronic pain: a systematic review of non-randomised studies

Zeraatkar D et al. • BMJ open (2022)

There is very low certainty evidence that adverse events are common among people living with chronic pain who use medical cannabis or cannabinoids, but that few patients experience serious adverse events.

Very low certainty evidence suggests that adverse events are common (prevalence: 26.0%; 95% CI 13.2% to 41.2%) among users of medical cannabis for chronic pain, particularly any psychiatric adverse events (prevalence: 13.5%; 95% CI 2.6% to 30.6%).
There is very low certainty evidence that adverse events are common among people living with chronic pain who use medical cannabis or cannabinoids, but that few patients experience serious adverse events.
Further research warranted to confirm findings

Systematic Reviewn=20

DOI

Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal Evidence

Colizzi M et al. • Nutrients (2021)

Potential neurobiological underpinnings include modulation of immune response, neuroinflammation, neurotrophy, apoptosis, neurogenesis, neuroplasticity, neurodegeneration, mitochondrial function, and microbiota activity, possibly through peroxisome proliferator-activated receptor-α (PPAR-α) activation.

Stress and exposure to exogenous cannabinoids may modulate ECBs/AEs levels and expression of candidate genes for neuropsychiatric disorders, with implications for ASD.
Limited research suggests that PEA supplementation reduces overall autism severity by improving language and social and nonsocial behaviors.
Further research warranted to confirm findings

Systematic Review

DOI

Efficacy of mast cell directed therapies in irritable bowel syndrome: a systematic review

Coppens D et al. • Acta gastro-enterologica Belgica (2024)

Mast cell modulating therapies could be of significant value in therapy for IBS patients.

Mast cell modulating therapies could be of significant value in therapy for IBS patients.
Further high-quality research is needed to establish the therapeutic efficacy of mast cell targeted therapies in order to draw robust conclusions and improve the clinical management of irritable bowel syndrome.
Further research warranted to confirm findings

Systematic Reviewn=11

DOI

Medical Cannabis for Gynecologic Pain Conditions: A Systematic Review

Liang AL et al. • Obstetrics and gynecology (2022)

Survey data showed that most women reported that cannabis improved pain from numerous gynecologic conditions.

Prevalence of cannabis use ranged from 13% to 27%.
Sixty-one to 95.5% reported pain relief.
Survey data showed that most women reported that cannabis improved pain from numerous gynecologic conditions.

Systematic Review

DOI

Effectiveness of Nonpharmacologic Treatments of Burning Mouth Syndrome: A Systematic Review

Cabras M et al. • Journal of oral & facial pain and headache (2021)

Evidence was collected from highly biased, short-term, heterogenous studies mainly focused on BMS-related pain, with scarce data on quality of life, psychologic status, dysgeusia, and xerostomia.

Evidence was collected from highly biased, short-term, heterogenous studies mainly focused on BMS-related pain, with scarce data on quality of life, psychologic status, dysgeusia, and xerostomia.
Long-term effectiveness of nonpharmacologic treatments should be further investigated, with a more rigorous, bias-proof study design.
Further research warranted to confirm findings

Systematic Review

DOI

Palmitoylethanolamide: A Nutritional Approach to Keep Neuroinflammation within Physiological Boundaries-A Systematic Review

Petrosino S et al. • International journal of molecular sciences (2020)

In this review the large number of studies on the benefits derived from oral administration of micronized and highly bioavailable forms of Palmitoylethanolamide is discussed, with special reference to neuroinflammatory disorders.

It has been shown that the regulation of non-neuronal cells-and therefore the control of neuroinflammation-depends on the local "on demand" synthesis of the endogenous lipid amide Palmitoylethanolamide and related endocannabinoids.
When the balance between synthesis and degradation of this bioactive lipid mediator is disrupted in favor of reduced synthesis and/or increased degradation, the behavior of non-neuronal cells may not be appropriately regulated and neuroinflammation exceeds the physiological boundaries.
In this review the large number of studies on the benefits derived from oral administration of micronized and highly bioavailable forms of Palmitoylethanolamide is discussed, with special reference to neuroinflammatory disorders.

Systematic Review

DOI

The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review

Davis MP et al. • The American journal of hospice & palliative care (2019)

Further research is needed to define the palliative benefits to PEA.

There are a significant number of prospective and randomized trials demonstrating the pain-relieving effects of PEA.
There is lesser evidence of benefit in patients with nonpain symptoms related to depression, Parkinson disease, strokes, and autism.
There are no reported drug-drug interactions and very few reported adverse effects from PEA.

Systematic Review

DOI

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