{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T10:06:26Z","timestamp":1779185186243,"version":"3.51.4"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: The plant Griffonia simplicifolia is marketed as a dietary supplement; it is said to have antidepressant and sleep-promoting properties. Its main ingredient, 5-hydroxytryptophan (5-HTP), is the immediate precursor of serotonin and crosses the blood\u2013brain barrier, thereby enhancing central serotonergic neurotransmission. Reduced serotonergic activity has been associated with affective disorders, sleep disturbances, and impaired central pain modulation. Despite this neurobiological rationale, evidence for analgesic efficacy remains limited. This study investigated the effects of Griffonia simplicifolia on peripheral and central sensitization and descending pain inhibition. Methods: In a randomized, double-blind, placebo-controlled crossover trial, 18 healthy volunteers underwent quantitative sensory testing (QST). Participants received 100 mg Griffonia simplicifolia orally once daily for 28 days or matching placebo. Sensory parameters were reassessed, followed by repetitive phasic heat application (RPHA) to induce short-term peripheral and central sensitization. After a 4-week washout period, participants crossed over to the alternate intervention. Results: A total of 17 participants completed the study. Griffonia simplicifolia showed no significant effect on acute pain perception after RPHA (\u03b2 = \u22124.17; 95% CI \u221214.44 to 6.10; p = 0.401). The only significant difference was an increased distance of mechanical allodynia in the verum group (\u03b2 = 0.82; 95% CI 0.05\u20131.59; p = 0.038). No differences were observed in thermal detection or pain thresholds, pressure pain thresholds, conditioned pain modulation, wind-up ratio, mechanical pain sensitivity, or flare area. Mild, transient adverse events occurred in two participants (11%) during Griffonia simplicifolia intake. Conclusions: Griffonia simplicifolia demonstrated limited effects on experimentally induced pain mechanisms compared with placebo and was well tolerated. Increased distance of allodynia may reflect serotonergic facilitation of pronociceptive pathways, suggesting an enhanced central and peripheral sensitization. Larger controlled trials are required to clarify its impact on pain perception.<\/jats:p>","DOI":"10.3390\/nu18101609","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T08:55:28Z","timestamp":1779180928000},"page":"1609","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of Griffonia simplicifolia on Pain Intensity, Central and Peripheral Sensitization, and Pain Modulation in Healthy Volunteers\u2014A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial"],"prefix":"10.3390","volume":"18","author":[{"given":"Anselm Johannes","family":"Schlemmer","sequence":"first","affiliation":[{"name":"Department of Radiology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4062-2572","authenticated-orcid":false,"given":"Sascha","family":"Hammer","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9043-0378","authenticated-orcid":false,"given":"Simon","family":"Fandler-H\u00f6fler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kordula","family":"Lang-Illievich","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, 8036 Graz, Austria"},{"name":"Department of Anaesthesiology and Intensive Care Medicine, State Hospital G\u00fcssing, 7540 G\u00fcssing, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1201-3752","authenticated-orcid":false,"given":"Helmar","family":"Bornemann-Cimenti","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.4137\/IJTR.S1022","article-title":"Production and Peripheral Roles of 5-HTP, a Precursor of Serotonin","volume":"2","author":"Nakamura","year":"2009","journal-title":"Int. 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