Helali H. et al. - Transcranial photobiomodulation to reduce anxiety and depression in patients on methadone treatment

Share this article:

This randomized, double-blind trial compared transcranial photobiomodulation at 810 nm to a sham device in patients receiving methadone maintenance therapy. The treatment group showed a statistically significant reduction in anxiety, depression, and opioid cravings, which was sustained at one and three months.

What this study measured

This is a randomized, controlled, double-blind clinical trial, not a meta-analysis: its conclusions are based on a single population at a single center. Opioid-dependent patients receiving methadone maintenance therapy were randomly assigned to either active transcranial photobiomodulation or sham photobiomodulation. The intervention involved the use of light-emitting diodes applied to two frontal areas, with four minutes of exposure at 810 nm. Anxiety, depression, and opioid cravings were measured before the intervention, immediately afterward, and then at one month and three months.

Key Findings

The two groups were comparable at the start, with no significant differences on the three scales. Differences emerged after the intervention.

Each group consisted of 32 men (91.4%) and 3 women (8.6%).
Mean age: 37.97 ± 10.58 years in the active group versus 39.66 ± 9.94 years in the control group (p = 0.495).
There were no significant differences between groups before the intervention in terms of depression, anxiety, and craving scores (p > 0.05).
After the intervention, the active group showed statistically significant decreases in these scores compared with the control group (p < 0.05).
The improvements are reported to have persisted at one-month and three-month follow-up.
Irradiation parameters: 810 nm, 250 mW/cm² at a skin depth of 4 mm, for a total of 60 J/cm², applied for four minutes to two areas of the forehead.
Trial registration: IRCT20210502051162N1.

How Transcranial Photobiomodulation Works

The authors attribute the observed effect to a presumed stimulation of ATP biosynthesis and neurogenesis. The most commonly proposed mechanism—which remains hypothetical—involves cytochrome c oxidase, a near-infrared-sensitive mitochondrial enzyme whose activation is thought to increase cellular energy production. Also mentioned are changes in cerebral blood flow, a reduction in oxidative stress, and a reduction in neuroinflammation. None of these mechanisms was directly measured in this trial, which relies on clinical scales.

Limits You Should Know

The sample size is small, with 35 participants per group, and the participants are overwhelmingly male, which limits the generalizability of the findings to women. This is a single, single-center trial: its results require independent replication before any generalizations can be made. The abstract reports significance thresholds but not effect sizes or confidence intervals, so the clinical magnitude of the benefit remains undetermined. The study population is specific—those undergoing methadone maintenance treatment—and the results cannot be directly applied to isolated depression or anxiety.

What This Means in Practice

These findings are encouraging but preliminary: a single trial is not enough to establish a standard of care. Photobiomodulation is not a substitute for psychiatric follow-up or ongoing treatment, and a mood disorder requires professional care. As part of opioid substitution therapy, continued addiction monitoring and prescribed treatment remain essential. Any complementary approach must be discussed with the healthcare team providing care.

Frequently Asked Questions

Does transcranial photobiomodulation help with opioid withdrawal?

In this trial conducted among patients on methadone, the treatment group showed a significant reduction in craving, anxiety, and depression compared with the placebo group. This was a single trial with a limited sample size. Further confirmation by other research teams is still needed.

What lighting settings were used in this test?

Light-emitting diodes emitting at 810 nm, at 250 mW/cm² to a skin depth of 4 mm, for a total of 60 J/cm². The exposure lasted four minutes on two areas of the forehead. These values describe the published protocol and do not constitute a recommendation.

Did the effects last after the sessions ended?

The authors report that the improvements persisted at one month and three months of follow-up. The observation period ends there. Nothing beyond three months is documented in this publication.

Reference

Helali H, Samani N, Tabeie F, Eiliaei S, Kheradmand A. The effectiveness of transcranial photobiomodulation (tPBM) therapy in reducing anxiety, depression, and opioid craving in patients undergoing methadone maintenance treatment: a double-blind, randomized, controlled trial. BMC Psychiatry, 2025; 25 (1): 94. PMID 39901090. DOI 10.1186/s12888-025-06555-3. https://doi.org/10.1186/s12888-025-06555-3

This summary is provided for informational purposes only and does not constitute medical advice. Photobiomodulation is not a substitute for prescribed treatment or psychiatric care. Please consult a healthcare professional.