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

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.

Individual Differences in Hemispheric Emotional Valence by Computerized Test Correlate with Lateralized Differences in Nucleus Accumbens, Hippocampal and Amygdala Volumes

“…In subsequent studies we have used the CTHEV to guide a lateralized treatment using unilateral transcranial photobiomodulation (tPBM), near infrared mode in two double-blinded randomized controlled trials. 13 , 18 We have also reported that HEV, as assessed using lateralizing field glasses, predicted response to left-sided rTMS 12 , 19 and that CTHEV would likely work as well. The potential importance of guiding treatment based on HEV makes sense given the observation that individuals with more negative left hemisphere are as likely to have histories of MDD as individuals with more negative right hemisphere.…”

“…The evidence presented on the correlations of the CTHEV lends further support to the psychological hypothesis and therapeutic method articulated in Dual-Brain Psychology. 9 , 13 HEV is a more complex concept than established hypotheses which propose that the right hemisphere is superior for emotional processing or that the right hemisphere processes negative emotion or withdrawal emotions. The dual brain hypothesis suggests that each hemisphere is associated with broad mental processes or personalities that differ in health and maturity and at the side that is healthier is a trait for an individual but varies among individuals.…”

“…9 Further, this study identified an array of brain imaging findings that likely play an important role in establishing these hemispheric differences given the importance of these identified subcortical structures in positive and negative affect 69–71 and the corpus callosum in hemispheric integration. 73 There is potentially great value in the use of CTHEV to guide lateralized treatments such as unilateral tPBM, 13 , 18 direct current stimulation, and rTMS. 12 , 74 In particular, unilateral tPBM, based on DBP principals, has been shown to be effective in trials treating anxiety, 11 , 13 depression, 18 and opioid use disorder.…”

“… 73 There is potentially great value in the use of CTHEV to guide lateralized treatments such as unilateral tPBM, 13 , 18 direct current stimulation, and rTMS. 12 , 74 In particular, unilateral tPBM, based on DBP principals, has been shown to be effective in trials treating anxiety, 11 , 13 depression, 18 and opioid use disorder. 13 , 18 Case reports have shown DBP to be a very effective adjunct to in-depth psychotherapy for the treatment of anxiety, depression, PTSD, and addiction.…”

“… 12 , 74 In particular, unilateral tPBM, based on DBP principals, has been shown to be effective in trials treating anxiety, 11 , 13 depression, 18 and opioid use disorder. 13 , 18 Case reports have shown DBP to be a very effective adjunct to in-depth psychotherapy for the treatment of anxiety, depression, PTSD, and addiction. 8 , 25 , 75 The fact that we have used HEV clinically and experimentally for several years with consistent results hopefully will encourage other groups to become interested in this novel finding that raises many interesting questions worthy of deep exploration.…”