A Project to Test the Efficacy and Safety of An Innovative Treatment for Opiate Use Disorders.

Approach. Investigators have had a and productive Pre-submission meeting with the FDA on April 21, 2022, and are following their guidance in our approach. The goal of this Phase II study is to test further the efficacy and safety of a new and innovative, patented application of transcranial photobiomodulation for the treatment of opioid use disorder (defined by DSM-5 criteria) with the possibility of achieving FDA clearance. The Opioid Addiction Therapy System is a photobiomodulation device platform intended to be used alone or as an aid to psychotherapy and medical-assisted treatments to treat opioid use disorder. It is intended to be used by trained psychotherapists in clinical environments on patients with opioid use disorder.

Specific Aim1:

1. Following FDA's preliminary guidance, Investigators aim first to assess whether active Rx with UtPBM administered to the more positive hemisphere helps participants taper and abstain from use of opioids as indicated by an increase in the percent of weekly visits in which there was no self-reported use of opioids on TimeLine Follow Back and urine screens for opioids were negative. This will be assessed from weeks 10 through 26, to give participants sufficient time to taper off opioids. An additional primary outcome will be the reduction in frequency of use (days per week) as assessed using timeline feedback from baseline to week 26. Secondary outcome measures will include the following: retention in treatment, opioid craving, withdrawal symptoms, clinical global impression ratings of severity and improvement, quality of life metrics and Treatment Success, as at least 80% opioid abstinence during weeks 10-26. An assessment will also be made of adverse events during the treatment period.

Milestones: a. Investigators predict based on our Phase I findings that active treatment will increase weekly abstinence rates by 20% or more over sham treatment (e.g., 30% vs 10% weekly opioid-negative visits). Investigators expect each of the secondary outcomes to be significantly better in the active group with a p value of less than 0.05. 2. Investigators wish to see if actively treated participants age more slowly over the 26-week course of the study than those who receive the sham treatments. Investigators will measure this by using epigenetic techniques. Investigators will use state-of-the-art epigenetic measures of Intrinsic Epigenetic Age Acceleration to assess subtype differences in DNA m. Investigators feel this is superior focusing on candidate genes. Peripheral lymphocytes are the most appropriate cell type for assessing Intrinsic Epigenetic Age Acceleration.

Sequence of Visits. Interested individuals will call to receive information and will complete a brief screen for age and key exclusion criteria. Those who appear eligible will be invited to interview. Visit 1 will consist of full study informed consent, structured interviews to assess inclusion and exclusion criteria, TimeLine Followback to assess current degree of substance use, urine drug screen and computerized assessment of hemispheric emotional valence. Those who meet entrance criteria and agree to participate will be randomized into active or sham groups. Treatment sessions will start with visit 1 and will occur twice weekly for 6 weeks, then weekly until week 25 with one untreated follow-up session on week 26.