The Effect of Griffonia simplicifolia on Pain Intensity, Central and Peripheral Sensitization, and Pain Modulation in Healthy Volunteers-A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial.

2026-05-19
Nutrients 18(10)
- Anselm Johannes Schlemmer
- Sascha Hammer
- Simon Fandler-Höfler
- Kordula Lang-Illievich
- Helmar Bornemann-Cimenti

PubMed: 42197069
DOI: 10.3390/nu18101609

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 17
Population: 18 healthy volunteers
Methods: randomized, double-blind, placebo-controlled crossover trial; 100 mg Griffonia simplicifolia orally once daily for 28 days or matching placebo; 4-week washout period
Blinding: Double-blind
Duration: 28 days
Funding: Unclear

Rigorous Journal

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-brain 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 (β = -4.17; 95% CI -14.44 to 6.10; p = 0.401). The only significant difference was an increased distance of mechanical allodynia in the verum group (β = 0.82; 95% CI 0.05-1.59; 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.

Research Insights

Griffonia→Changed Mechanical Pain Sensitivity
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.
Effect
Neutral
Effect size
Small
Dose
100 mg once daily for 28 days
Griffonia→Changed Pressure Pain Threshold
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.
Effect
Neutral
Effect size
Small
Dose
100 mg once daily for 28 days
Griffonia→Changed Thermal Detection Threshold
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.
Effect
Neutral
Effect size
Small
Dose
100 mg once daily for 28 days
Griffonia→Changed Thermal Pain Threshold
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.
Effect
Neutral
Effect size
Small
Dose
100 mg once daily for 28 days
Griffonia→Changed Wind-Up Ratio
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.
Effect
Neutral
Effect size
Small
Dose
100 mg once daily for 28 days
Griffonia→Increased Mechanical Allodynia Distance
The only significant difference was an increased distance of mechanical allodynia in the verum group (β = 0.82; 95% CI 0.05-1.59; p = 0.038).
Effect
Harmful
Effect size
Small
Dose
100 mg once daily for 28 days
Griffonia→Reduced Conditioned Pain Modulation
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.
Effect
Neutral
Effect size
Small
Dose
100 mg once daily for 28 days
Griffonia→Reduced Flare Area
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.
Effect
Neutral
Effect size
Small
Dose
100 mg once daily for 28 days
Griffonia→Reduced Pain Intensity
Griffonia simplicifolia showed no significant effect on acute pain perception after RPHA (β = -4.17; 95% CI -14.44 to 6.10; p = 0.401).
Effect
Neutral
Effect size
Small
Dose
100 mg once daily for 28 days

Adverse Events Reported

Griffonia→mild, transient adverse events
Mild, transient adverse events occurred in two participants (11%) during Griffonia simplicifolia intake.
Finding
Reported
Grade
mild