The pain of IC/BPS has been rated equivalent to cancer pain. It can be agonizing, difficult to ignore and make it impossible for patients to sleep and/or function. Yet, pain care remains a significant challenge. Most urologists simply refuse to provide pain medication, such as Norco. Today, we have a new alternative, a simple, affordable OTC supplement that carries no risk of addiction.

PEA Popularity Soars As New Research Shows Yet More Success.

The research behind the use of palmitoylethanolamide (PEA) continues to show great promise in reducing discomfort for patients with interstitial cystitis, chronic prostatitis, pelvic pain, vulvodynia, fibromyalgia and, most recently, menstrual cramps. Known for its anti-inflammatory and analgesic effects, it has become one of the most popular supplements for patients struggling with chronic pain. Loredana Nästa, head of Associazione Italiana Cistite Interstiziale, said “PEA has became a crucial therapy for IC patients in Italy, when mast cell degranulation, neuropathic pain and central sensitization are present. PEA has become a consolidated therapy due to the good results in term of pain, urgency, frequency….”

Interstitial Cystitis – A 2019 pilot study from Italy studied 32 IC/BPS patients who used PEA for six months  They shared that a “significant and progressive  reduction in pain intensity was observed during PEA treatment”, with addition improvements in urinary frequency and, to a lesser extent, bladder capacity. No adverse events were reported (1) PEAORA® and PEAlief® are two products now used by thousands of ICer’s, myself included, to reduce pain and discomfort. 

Newest Studies With Pain & Menstrual Cramps

This year, we’ve had two more papers/studies released that are very encouraging.

Chronic Pain – Researchers in Spain reviewed 18 PEA studies for effectiveness. Collectively, pain was significantly reduced in the PEA groups at 6 weeks, 8 weeks and 24-26 weeks. Patients using PEA experienced significantly higher improvements in their quality of life. Most importantly, PEA was found to be effective for ALL pain types, including pain from injuries (nociceptive), pain from nerves (neuropathic) and persistent pain (nociplastic). These researchers concluded that “PEA effectively reduces pain and enhances quality of life with significant benefits observed within 4 to 6 weeks of treatment. PEA is a promising alternative to chronic opioid analgesics, potentially reducing the risk of opioid abuse and dependency.” (2)

Menstrual Cramps – Researchers released the results of a study of 73 women who tried PEA (Levagen – Australia) for mild to moderate menstrual cramp pain.(3) Participants took one 300 mg capsule of PEA when the pain of their menstrual cycle hit 5 out of 10 and then monitored their symptoms for two hours. The results showed that PEA significantly reduced menstrual pain at 1.0, 1.5 and 2 hours post treatment when compared to placebo. At the 2 hour mark, about 50% of menstrual pain events remained unresolved and required a second dose. After the second dose, a further reduction in pain was seen at 2.5 hours.

While many studies have found a significant reduction of pain over time, this study found that PEA could be effective for acute pain, even with just one or two doses. Pain reduction occurred at roughly an hour after treatment, which coincides with increasing plasma levels at the 45 minute mark. Maximum PEA levels in plasma occurred at 90 minutes post consumption.

The majority of previously published PEA studies showed no significant side effects and that PEA was well tolerated, including the IC study. In an unusual first, this study found that six women did experience mild side effects, including: lower back pain, brain fog/sleepiness, dry mouth and 2 × increased menstrual bleeding. Yet three patients who did not receive PEA also experienced some adverse events, including hot flashes, headache, fatigue and increased menstrual bleeding. Baffling.

A larger clinical study of painful menstrual cramping showed 400 mg of PEA plus 40 mg transpolydatin reduced pelvic pain in 98.18 percent of participants compared to 56 percent in the control group (4)

Endometriosis – Prior studies have found that PEA reduced the pain of endometriosis. One study utilized 400mg of PEA with 40mg of polydatin twice daily for 90 days with significant pain reduction in as little as one month.(5) Another showed success with menstrual cramping, painful sex and pelvic pain. (6) Yet another showed 600 mg of PEA twice daily improved pelvic pain, deep dyspareunia, dysmenorrhea as well as quality of life and psychological well-being. (7)

Chronic Prostatitis/Chronic Pelvic Pain Syndrome in Men – Twelve weeks of treatment with PEA and Alpha-lipoic acid improved urinary symptoms.(8)

Laboratory Studies of PEA – Many laboratory studies have been done to understand the mechanism of action of PEA with various pelvic pain conditions. Each show promise though they all suggest additional research.(9-17)

PEA Makes A Great Addition To Your Self-Help Routine

The plentiful research behind PEA is remarkably encouraging. These studies are just a small subset of the dozens of studies with PEA in major medical journals. A comprehensive review of PEA randomized clinical trials found 47 clinical trials(18). It found:

  • Palmitoylethanolamide (PEA) is a safe anti-neuroinflammatory dietary supplement.
  • 47 randomized controlled trials (RCTs) so far have studied PEA in clinical samples.
  • Most RCTs show PEA efficacy on pain management and measures of general wellbeing.
  • PEA ultramicronized/micronized formulations are among the most used and effective.
  • Symptom improvement was often accompanied by the modulation of immune biomarkers.

PEA as a simple, affordable option for patients with IC/BPS and pelvic pain with a remarkable safety profile. It’s not an opiate. Provides no risk of addiction. If you are struggling with pain and discomfort, it might be worth trying! Check out the research below and, of course, talk with your doctor.

References:

  1. Cervigni M, et al. Micronized Palmitoylethanolamide-Polydatin Reduces the Painful Symptomatology in Patients with IC/BPS. Biomed Res Int. 2019 Nov 11
  2. Vina I, et al.  Meta-Analysis of Palmitoylethanolamide in Pain Management: Addressing Literature Gaps and Enhancing Understanding, Nutrition Reviews 2025
  3. Rao A, et al. Palmitoylethanolamide (Levagen+) for acute menstrual pain: a randomized, crossover, double-blind, placebo-controlled trial. Women & Health 2025 1–9.
  4. Tartaglia E, et al. Effectiveness of the Association N-Palmitoylethanolamine and Transpolydatin in the Treatment of Primary Dysmenorrhea. Journal of Pediatric and Adolescent Gynecology 2015 28 (6): 447–450
  5. Indraccolo U, et al.  Effect of Palmitoylethanolamide–Polydatin Combination on Chronic Pelvic Pain Associated with Endometriosis: Preliminary Observations. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2010 150 (1): 76–79
  6. Cobellis L, et al. Effectiveness of the Association Micronized N-Palmitoylethanolamine (PEA)–Transpolydatin in the Treatment of Chronic Pelvic Pain Related to Endometriosis After Laparoscopic Assessment: A Pilot Study. European Journal of Obstetrics, Gynecology, and Reproductive Biology 158 (1): 82–86. 2011
  7. Stochino E, et al.  Effect of Ultramicronized-Palmitoylethanolamide and Co-Micronized Palmitoylethanolamide/Polydatin on Chronic Pelvic Pain and Quality of Life in Endometriosis Patients: An Open-Label Pilot Study. International Journal of Women’s Health 2019 1:443–449. .
  8. Giammusso B, et al. The efficacy of an association of palmitoylethanolamide and alpha-lipoic acid in patients with chronic prostatitis/chronic pelvic pain syndrome: A randomized clinical trial Arch Ital Urol Androl. 2017 Mar 31;89(1):17-21.
  9. Kuret T, et al. A Systematic Review of Therapeutic Approaches Used in Experimental Models of Interstitial Cystitis/Bladder Pain Syndrome. Biomedicines 2021, 9(8), 865;  
  10. Miyamoto H, et al. Micronized Palmitoylethanolamide, Hempseed Oil, and Maritime Pine Bark Dry Extract (Pelvipea®) for Pelvic Pain: An In Vitro Study for Urothelial Inflammation Treatment. Cells. 2023 Feb; 12(4): 616. 
  11. Noce A, et al. Ultramicronized Palmitoylethanolamide (um-PEA): A New Possible Adjuvant Treatment in COVID-19 patients. Pharmaceuticals 2021, 14(4), 336 (This paper provides an excellent review of PEA mechanisms of actions.
  12. Capasso R, et al. Palmitoylethanolamide normalizes intestinal motility in a model of post-inflammatory accelerated transit: involvement of CB1 receptors and TRPV1 channels. Br J Pharmacol. 2014 Sep; 171(17): 4026–4037. –
  13. Hesselink JMK et al. New topical treatment of vulvodynia based on the pathogenetic role of cross talk between nociceptors, immunocompetent cells, and epithelial cells. J Pain Res. 2016 Oct 3:9:757-762.  –
  14. Kuret T, et al. A Systematic Review of Therapeutic Approaches Used in Experimental Models of Interstitial Cystitis/Bladder Pain Syndrome Biomedicines. 2021 Aug; 9(8): 865.  Published online 2021 Jul 22.
  15. Ugo Indraccolo et al. Looking for Responders among Women with Chronic Pelvic Pain Treated with a Comicronized Formulation of Micronized Palmitoylethanolamide and Polydatin Biomed Res Int. 2022; 2022: 8620077.  Published online 2022 May 7.-
  16. Scuteri D, et al. Effects of Palmitoylethanolamide (PEA) on Nociceptive, Musculoskeletal and Neuropathic Pain: Systematic Review and Meta-Analysis of Clinical Evidence – Pharmaceutics. 2022 Aug; 14(8): 1672.  –
  17. Anupam A, et al. Mast Cell-Mediated Mechanisms of Nociception. Int J Mol Sci. 2015 Dec; 16(12): 29069–29092.  –
  18. Bortoletto R, Comacchio C, Garzitto M, Piscitelli F, Balestrieri M, Colizzi M. Palmitoylethanolamide supplementation for human health: A state-of-the-art systematic review of Randomized Controlled Trials in patient populations. Brain Behav Immun Health. 2024 Dec 23;43:100927.