Highlights
- Safe at different settings: People tolerated all transcranial PBM settings well.
- Side effects like placebo: Reported side effects were about the same as the “fake” session.
- No changes in vitals: Blood pressure and body weight stayed normal.
- What this means: A gentle, non-invasive option worth exploring
Safety is a fundamental prerequisite for any emerging therapy, particularly those applied to the human brain. The study “Dose-dependent tolerability and safety of transcranial photobiomodulation: a randomized controlled trial”, conducted by Coelho et al. (2025) and published in Lasers in Medical Science, represents an important advance by systematically assessing the dose-dependent safety and tolerability of transcranial photobiomodulation (t-PBM) in individuals with major depressive disorder (MDD).
The single-blind crossover trial included 31 adults aged 18–65 years diagnosed with MDD who were not treatment-resistant and met standard inclusion criteria. Each participant completed four weekly sessions—one sham condition and three active t-PBM sessions at low, medium, and high doses. The treatment order was randomized by an independent statistician to preserve blinding. The target area for stimulation was the bilateral dorsolateral prefrontal cortex (dlPFC), corresponding to electrode positions F3 and F4 in the EEG system. The stimulation parameters were as follows:
| Condition | Peak Irradiance (mW) | Mean Irradiance (mW) | Time (s) | Mean Fluence (J/cm²) | Total Energy (kJ) | Wave Mode | Frequency (Hz) |
| Sham | 0 | 0 | 0 | 0 | 0 | — | — |
| Low dose | ~50 | ~50 | 1200 | 60 | ~1.4 | Continuous | — |
| Medium dose | ~300 | ~300 | 333 | 100 | ~2.4 | Continuous | — |
| High dose | ~850 | ~300 | 600 | 180 | ~4.3 | Pulsed | ~40 |
Adverse events were assessed using the SAFTEE-SI scale, widely used in psychiatric research. The results showed that t-PBM was well tolerated across all dose conditions, with no statistically significant increase in adverse events compared to baseline or sham. Physiological parameters, including body weight and blood pressure, remained stable, confirming a favorable safety profile even at higher doses. These findings align with previous reports (Cassano et al., 2019) that also observed no relevant adverse effects, reinforcing the benign safety profile of t-PBM.
Among the strengths of this study are the dose-comparison design, the crossover structure, which minimizes interindividual variability, and the systematic evaluation of safety. However, several limitations must be considered: the small sample size limits statistical power; each dose was applied only once, preventing assessment of cumulative or long-term effects; and the limited demographic diversity restricts generalizability.
In summary, Coelho et al. (2025) provide consistent evidence that t-PBM is a safe, well-tolerated, and non-invasive intervention for depression. Although larger and more diverse trials with extended follow-up are needed to confirm long-term safety and refine optimal parameters, this study reinforces the potential of transcranial photobiomodulation as a low-risk, promising therapeutic tool in mental health care.
Reference:
Coelho, D. R. A., Fernando Vieira, W., Hurtado Puerto, A. M., B Gersten, M., Anne Collins, K., Peterson, A., Siu, K., Tural, Ü., Vlad Iosifescu, D., & Cassano, P. (2025). Dose-dependent tolerability and safety of transcranial photobiomodulation: a randomized controlled trial. Lasers in medical science, 40(1), 248. https://doi.org/10.1007/s10103-025-04501-z
Cassano P, Caldieraro MA, Norton R, Mischoulon D, Trinh N-H, Nyer M, Dording C, Hamblin MR, Campbell B, Iosifescu DV (2019) Reported side effects, weight and blood pressure, after repeated sessions of transcranial photobiomodulation. Photobiomodulation Photomed Laser Surg 37(10):651–656. https://doi.org/10.1089/photob.2019.4678