An Effective and Safe Novel Treatment of Opioid Use Disorder: Unilateral Transcranial Photobiomodulation

Fredric Schiffer, Alaptagin Khan, Elizabeth Bolger, Edward Flynn, William P Seltzer, Martin H Teicher, Fredric Schiffer, Alaptagin Khan, Elizabeth Bolger, Edward Flynn, William P Seltzer, Martin H Teicher

Abstract

Background: The opioid epidemic is a global tragedy even with current treatments, and a novel, safe, and effective treatment would be welcomed. We report here our findings from our second randomized controlled trial to evaluate unilateral transcranial photobiomodulation as a treatment for opioid use disorder. Methods: We enrolled 39 participants with active opioid cravings at 2 sites, 19 received the active treatment which consisted of a 4-min twice weekly (every 3 or 4 days) application of a light-emitting diode at 810 nm with an irradiance of 250 mW/cm2 and a fluence of 60 J/cm2 to the forehead over either the left or right dorsolateral prefrontal cortex with a fluence to the brain of 2.1 J/cm2. Twenty participants received a sham treatment with the same device with foil over the bulb. The side of the treatment was based on Dual-Brain Psychology, which posits that one hemisphere is more affected by past maltreatments and is more prone to anxiety and drug cravings that the other hemisphere. We treated the hemisphere with the more positive hemispheric emotional valence (HEV) by 2 tests for HEV. Results: Our primary outcome was changes in pre-treatment opioid craving scale (OCS) minus baseline, and we found using a mixed model that the active group had a highly significant treatment * time benefit over the sham group, p < 0.0001, effect size at the last follow-up of 1.5. The active treatment benefited those not on buprenorphine as well as those not on it. The TimeLine Follow Back measure of opioid use was significantly better in the actively treated group, p = 0.0001, with an effect size of 0.45. We observed no adverse effects. Conclusion: Active unilateral transcranial photobiomodulation to the brain hemisphere with the better HEV was better than sham in the reduction of opioid cravings and opioid use to a very significant degree in a RCT of 39 participants at 2 independent sites. In the active group those on buprenorphine and those not on it both had improvements in cravings over the study. No adverse responses were reported in either group. ClinicalTrials.gov Identifier: NCT04340622.

Keywords: hemispheric laterality; opioid cravings; opioid use; opioid use disorder; photobiomodulation.

Conflict of interest statement

FS is the Founder of MindLight, LLC, which intends further research and commercialization of the methods and device described in the paper. The author has been issued 2 US patents which cover the method of unilateral tPBM to a positive hemisphere as described in this study: U.S. Patent No. 8303636, Methods for treating psychiatric disorders using light energy. Issued 11/06/2012, and U.S. Patent No. 8574279, Methods for treating psychiatric disorders using light energy. Issued 11/05/2013. He has filed on December 5, 2019 a US patent application, #16/703,937, Method and Apparatus for Determining Hemispheric Emotional Valence, and on August 3, 2020, he filed a US provisional patent application #63060177, Enhanced Treatment of Brain Disorders Utilizing Coordinated Negative Suppressive Stimulation and Related Devices Designed to Achieve Treatment. EF and WS were employed by MindLight, LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Schiffer, Khan, Bolger, Flynn, Seltzer and Teicher.

Figures

Figure 1
Figure 1
Least square means for opioid craving scores minus baseline from mixed model comparing active vs. sham treatments across visits. Data are means ± 95% confidence intervals.
Figure 2
Figure 2
Scatter plots showing differences across visit in opioid craving scores in participants receiving active vs. sham treatment with unilateral transcranial photobiomodulation from mixed model analysis, N = 39 with 20 actives.
Figure 3
Figure 3
Least square means for opioid craving scores minus baseline from mixed model comparing active vs. sham treatments across visits at MindLight site vs. McLean site. Data are means ± 95% confidence intervals. Overall, there were no significant differences between sites or significant site by visit or treatment interactions.
Figure 4
Figure 4
Least square means for opioid craving scores minus baseline from mixed model comparing participants receiving buprenorphine/suboxone vs. participants not receiving medication management. Data are means ± 95% confidence intervals. A significant treatment:visit interaction was present in both groups of participants.
Figure 5
Figure 5
Least square means for Opioid Use (days * amount) minus baseline from TimeLine FollowBack across visits for active vs. sham treatment at MindLight and McLean sites.
Figure 6
Figure 6
Scatter plot showing individual results for participants on and not on medication management with buprenorphine/suboxone following active vs. sham treatment with unilateral transcranial photobiomodulation. Note unexpected reduction in Hamilton Depression Rating Scale scores in two participants on buprenorphine who received sham treatment.

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