Opioid Craving Research Articles

Randomised clinical trial of a 16 mg vs 24 mg maintenance daily dose of buprenorphine to increase retention in treatment among people with an opioid use disorder in Rhode Island: study protocol paper

IntroductionBuprenorphine is a highly effective treatment for opioid use disorder (OUD). However, provider observations and preliminary research suggest that the current standard maintenance dose may be insufficient for suppressing withdrawal...

Medial prefrontal neuroplasticity during extended-release naltrexone treatment of opioid use disorder – a longitudinal structural magnetic resonance imaging study

Opioid use disorder (OUD) has been linked to macroscopic structural alterations in the brain. The monthly injectable, extended-release formulation of μ-opioid antagonist naltrexone (XR-NTX) is highly effective in reducing opioid craving and preventing opioid relapse. Here, we investigated the neuroanatomical effects of XR-NTX by examining changes in cortical thickness during treatment for OUD. Forty-seven OUD patients underwent structural magnetic resonance imaging and subjectively rated their opioid craving ≤1 day before (pre-treatment) and 11 ± 3 days after (on-treatment) the first XR-NTX injection. A sample of fifty-six non-OUD individuals completed a single imaging session and served as the comparison group. A publicly available [¹¹C]carfentanil positron emission tomography dataset was used to assess the relationship between changes in cortical thickness and μ-opioid receptor (MOR) binding potential across brain regions. We found that the thickness of the medial prefrontal and anterior cingulate cortices (mPFC/aCC; regions with high MOR binding potential) was comparable between the non-OUD individuals and the OUD patients at pre-treatment. However, among the OUD patients, mPFC/aCC thickness significantly decreased from pre-treatment to on-treatment. A greater reduction in mPFC/aCC thickness was associated with a greater reduction in opioid craving. Taken together, our study suggests XR-NTX-induced cortical thickness reduction in the mPFC/aCC regions in OUD patients. The reduction in thickness does not appear to indicate a restoration to the non-OUD level but rather reflects XR-NTX’s distinct therapeutic impact on an MOR-rich brain structure. Our findings highlight the neuroplastic effects of XR-NTX that may inform the development of novel OUD interventions.

Collaborating to heal addiction and mental health in primary care (CHAMP): A protocol for a hybrid type 2a trial

BackgroundThe gold-standard treatment for opioid use disorder (OUD) is medication for OUD (MOUD). However, less than a quarter of people with OUD initiate MOUD. Expanding the Collaborative Care Model (CoCM) to include primary care patients with OUD could improve access to and initiation of MOUD. This paper presents the methods and baseline sample characteristics of a Hybrid Type 2a trial comparing the effectiveness of CoCM for OUD and co-occurring mental health symptoms (MHS) to CoCM for MHS only. Method42 primary care clinics were cluster randomized and 254 primary care patients with OUD and elevated MHS were enrolled. Recruitment was terminated early by the Data and Safety Monitoring Board for futility. Participants completed research assessments at baseline, 3 months, and 6 months. The multiple primary outcomes were past-month number of days of nonmedical opioid use and SF12 Mental Health Component Summary (MCS) scores. ResultsMCS scores were over a standard deviation below the national mean (M = 34.5). Nearly half (47.6 %) of participants had previously overdosed in their lifetimes. Three quarters (76.0 %) were already being prescribed MOUD at baseline, only 30.4 % reported non-medical use of opioids, and only 33.9 % reported being bothered by opioid cravings. ConclusionThe unexpectedly high proportion of enrollees already prescribed MOUD at baseline indicates that most patients were in the maintenance rather than acute phase of treatment. Challenges identifying and enrolling patients in the acute phase of OUD treatment implies that intervention effectiveness will depend on its success preventing the discontinuation of MOUD rather than initiating MOUD.

Virtual reality-based Mindfulness-Oriented Recovery Enhancement (MORE-VR) as an adjunct to medications for opioid use disorder: a Phase 1 trial

Introduction Medications for opioid use disorder (MOUD) are the most effective interventions for this condition, yet many patients discontinue treatment. Though adjunct psychosocial treatments are recommended to increase retention and reduce relapse, the scarcity of trained providers hinders access to and utilization of evidence-based interventions. We conducted a Phase 1 study to assess the feasibility of a virtual reality-delivered Mindfulness-Oriented Recovery Enhancement (MORE-VR) intervention for patients receiving MOUD. Patients and Methods Patients receiving buprenorphine or methadone for OUD (N = 34) were scheduled for 8 weekly sessions of MORE-VR. Enrollment and retention rates were analyzed. Participants reported on the usability and acceptability of MORE-VR, opioid use, and craving and affect before and after each VR session. Heart rate was monitored during one session of MORE-VR. Results Twenty-three participants completed four or more MORE-VR sessions (minimum recommended intervention dose). Participants reported high usability and acceptability of MORE-VR, which had an excellent safety profile. Illicit opioid use decreased significantly from pre- to post-treatment (F = 4.44, p=.04). We observed a significant within-session decrease in opioid craving (F = 39.3, p<.001) and negative affect (F = 36.3, p<.001), and a significant within-session increase in positive affect (F = 23.6, p<.001). Heart rate shifted during cue-exposure and mindfulness practices (F = 6.79, p<.001). Conclusions High retention, usability and acceptability rates and low adverse events demonstrated that MORE-VR is a feasible, engaging, and safe intervention. Our findings show that MORE-VR can be delivered as an adjunctive intervention to MOUD and suggest that MORE-VR may improve OUD treatment outcomes and modulate autonomic responses. MORE-VR’s efficacy will be tested in a subsequent Phase 2 trial. Trial Registration ClinicalTrials.gov NCT05034276; https://classic.clinicaltrials.gov/ct2/show/NCT05034276

Protocol for a randomised trial of a self-directed digital pain management intervention (Empowered Relief) tailored to adults with chronic pain and prescription opioid misuse/disorder: the MOBILE Relief study

IntroductionChronic pain increases the risk of prescription opioid misuse or opioid use disorder (OUD). Non-pharmacological treatments are needed to dually address pain and opioid risks. The purpose of the Mobile...

Transcranial Photobiomodulation Therapy as an Intervention for Opioid Cravings and Depression: A Pilot Cohort Study.

Introduction: The opioid crisis, a declared national health emergency, has prompted the exploration of innovative treatments to address the pervasive issues of opioid cravings and associated depression. Aims: This pilot cohort study investigated the efficacy of transcranial Photobiomodulation (tPBM) therapy using the SunPowerLED helmet to alleviate these symptoms in individuals undergoing treatment for opioid addiction at a rehabilitation center in West Virginia. Methods: Employing a quasi-experimental design, this study enrolled participants into two groups: one receiving tPBM therapy alongside standard care and a control group receiving standard care alone. The helmet features include the following: total wavelength = 810 nm, total irradiance = 0.06 W/cm2 (60 m W/cm2), and total fluence = 172.8J/cm2. Results: The results of the Wilcoxon signed-rank tests for within-group analysis and Mann-Whitney U tests for between-group comparisons revealed statistically significant reductions in the intensity (W = 7.36, p = 0.012), time (W = 6.50, p = 0.015), frequency (W = 6.50, p = 0.010), and total scores of opioid cravings (W = 7.50, p = 0.009), as well as improvements in depression symptoms (W= 8.00, p = 0.005) within the PBM group compared to the non-PBM group. Discussion: These findings suggest that transcranial PBM therapy could be a promising noninvasive intervention for reducing opioid cravings and depressive symptoms in individuals with opioid use disorder, warranting further investigation through larger randomized controlled trials.

Yoga and Physical Therapy for Chronic Pain and Opioid Use Disorder Onsite in an Opioid Treatment Program: A Randomized Controlled Trial.

There is a lack of integrated treatment for chronic pain and opioid use disorder (OUD). Yoga and physical therapy (PT) may improve pain and physical function of people living with (PLW) chronic low back pain (CLBP) and may also reduce opioid craving and use, but PLW with OUD face barriers to accessing these interventions. We hypothesize that compared to treatment as usual (TAU), providing yoga and PT onsite at opioid treatment programs (OTPs) will be effective at improving pain, opioid use, and quality of life among people with CLBP and OUD, and will be cost-effective. In this hybrid type-1 effectiveness-implementation study, we will randomly assign 345 PLW CLBP and OUD from OTPs in the Bronx, NY, to 12 weeks of onsite yoga, onsite PT, or TAU. Primary outcomes are pain intensity, opioid use, and cost-effectiveness. Secondary outcomes include physical function and overall well-being. This trial tests an innovative, patient-centered approach to combined management for pain and OUD in real-world settings. We rigorously examine the efficacy of yoga and PT onsite at OTPs as nonpharmacologic, cost-effective treatments among people with CLBP and OUD who face barriers to integrated care.

A case of severe opioid and methamphetamine use disorder in a 14 year old

We present the case of a 14-year-old who established care at our primary care clinic after hospitalization for unintentional fentanyl overdose. They were diagnosed with severe opioid use disorder (OUD) and stimulant use disorder (StUD) and initiated buprenorphine while inpatient. They were then transitioned to the only known outpatient primary care clinic in her county who was actively providing medications for opioid use disorder (MOUD) in adolescents.At the first visit, they reported a history of 20 overdoses, struggling with adherence to buprenorphine and continued opioid cravings. An overdose safety plan was reviewed with them and their parent including providing them naloxone kits, fentanyl test strips, and education handout sheets. Due to their significant overdose history and adherence challenges with sublingual buprenorphine, they were started on long-acting injectable buprenorphine (LAIB) with weekly provider visits and urine toxicology screening. In collaboration with the treatment team, they initiated behavioral treatment with contingency management (CM), with incentives for appointment completion, expected urine results, and successful medication administration. Over the next 19 months, and to date, they have increasingly engaged with care and have remained abstinent. LAIB may be an appealing alternative for adolescents with OUD to improve adherence and reduce risk of recurrent use and overdose. Adjunctive treatment with CM may improve retention in MOUD and have the benefit of treating StUD. There is a need for further research to explore innovative, community-based treatment for youth with OUD.

Predictive Relationship Between Different Timescales of Opioid Craving and Opioid Use

Predictive Relationship Between Different Timescales of Opioid Craving and Opioid Use

Effect of Acupuncture for Methadone Reduction : A Randomized Clinical Trial.

Methadone maintenance treatment (MMT) is effective for managing opioid use disorder, but adverse effects mean that optimal therapy occurs with the lowest dose that controls opioid craving. To assess the efficacy of acupuncture versus sham acupuncture on methadone dose reduction. Multicenter, 2-group, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR2200058123). 6 MMT clinics in China. Adults aged 65 years or younger with opioid use disorder who attended clinic daily and had been using MMT for at least 6 weeks. Acupuncture or sham acupuncture 3 times a week for 8 weeks. The 2 primary outcomes were the proportion of participants who achieved a reduction in methadone dose of 20% or more compared with baseline and opioid craving, which was measured by the change from baseline on a 100-mm visual analogue scale (VAS). Of 118 eligible participants, 60 were randomly assigned to acupuncture and 58 were randomly assigned to sham acupuncture (2 did not receive acupuncture). At week 8, more patients reduced their methadone dose 20% or more with acupuncture than with sham acupuncture (37 [62%] vs. 16 [29%]; risk difference, 32% [97.5% CI, 13% to 52%]; P < 0.001). In addition, acupuncture was more effective in decreasing opioid craving than sham acupuncture with a mean difference of -11.7 mm VAS (CI, -18.7 to -4.8 mm; P < 0.001). No serious adverse events occurred. There were no notable differences between study groups when participants were asked which type of acupuncture they received. Fixed acupuncture protocol limited personalization and only 12 weeks of follow-up after stopping acupuncture. Eight weeks of acupuncture were superior to sham acupuncture in reducing methadone dose and decreasing opioid craving. National Natural Science Foundation of China.

The Role of Repetitive Transcranial Magnetic Stimulation in Reduction of Opioid Craving; A Single Blinded Randomized Sham Controlled Clinical Trial

Abstract Background Opioid use disorder (OUD) poses a great concern due to problems associated with their abuse as well as fatal and non fatal overdose consequences. Craving has a complex relationship with opioid use and relapse. Developing new, effective treatments for substance use disorders (SUDs), including opioid use disorders is crucial. This study aimed to assess the effect of 18 sessions of high frequency (HF) repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) on opioid craving in early abstinence using brief substance craving scale (BSCS) for Tramadol and morphine and Heroin craving questionnaire (HCQ) for Heroin craving. Results There was a statistically significant reduction in craving scores in the group of OUD patients receiving real rTMS compared to those receiving sham rTMS for both BSCS( p value = 0.044) and HCQ (p value = 0.002). A statistically significant positive correlation was revealed between the number of hospital admissions and the mean scores of post rTMS HCQ scores (r = 0.05, p value = 0.040). Conclusion High frequency 10 Hz rTMS over the left DLPFC for 18 treatment sessions reduced craving OUD patients during early abstinence. These preliminary results suggest that 10 Hz rTMS of the left DLPFC may be used in treatment of OUD; so our study recommends that use of rTMS in reduction of opioid craving in early abstinence.

Vulnerability Factors, Adjustment, and Opioid Misuse in Chronic Noncancer Pain Individuals

Several person variables predate injury or pain onset that increase the probability of maladjustment to pain and opioid misuse. The aim of this study was to evaluate the role of 2 diathesis variables (impulsiveness and anxiety sensitivity [AS]) in the adjustment of individuals with chronic noncancer pain and opioid misuse. The sample comprised 187 individuals with chronic noncancer pain. The hypothetical model was tested using correlation and structural equation modeling analyses. The results show a significant association between impulsiveness and AS and all the maladjustment variables, and between impulsiveness and AS and opioid misuse and craving. However, although the correlation analysis showed a significant association between adjustment to pain and opioid misuse, the structural equation modeling analysis showed a nonsignificant association between them (as latent variables). The findings support the hypothesis that both impulsiveness and AS are vulnerability factors for maladaptive adjustment to chronic pain and opioid misuse. PerspectiveThis article adds to the empirical literature by including AS and impulsiveness as antecedent variables in a model of dual vulnerability to chronic pain maladjustment and opioid misuse. The findings suggest the potential utility of assessing both factors in individuals in the first stages of chronic pain.

Endocannabinoid agonist 2-arachidonoylglycerol differentially alters diurnal activity and sleep during fentanyl withdrawal in male and female mice

Fentanyl has become the leading driver of opioid overdoses in the United States. Cessation of opioid use represents a challenge as the experience of withdrawal drives subsequent relapse. One of the most prominent withdrawal symptoms that can contribute to opioid craving and vulnerability to relapse is sleep disruption. The endocannabinoid agonist, 2-Arachidonoylglycerol (2-AG), may promote sleep and reduce withdrawal severity; however, the effects of 2-AG on sleep disruption during opioid withdrawal have yet to be assessed. Here, we investigated the effects of 2-AG administration on sleep-wake behavior and diurnal activity in mice during withdrawal from fentanyl. Sleep-wake activity measured via actigraphy was continuously recorded before and after chronic fentanyl administration in both male and female C57BL/6J mice. Immediately following cessation of fentanyl administration, 2-AG was administered intraperitoneally to investigate the impact of endocannabinoid agonism on opioid-induced sleep disruption. We found that female mice maintained higher activity levels in response to chronic fentanyl than male mice. Furthermore, fentanyl administration increased wake and decreased sleep during the light period and inversely increased sleep and decreased wake in the dark period in both sexes. 2-AG treatment increased arousal and decreased sleep in both sexes during first 24-h of withdrawal. On withdrawal day 2, only females showed increased wakefulness with no changes in males, but by withdrawal day 3 male mice displayed decreased rapid-eye movement sleep during the dark period with no changes in female mice. Overall, repeated administration of fentanyl altered sleep and diurnal activity and administration of the endocannabinoid agonist, 2-AG, had sex-specific effects on fentanyl-induced sleep and diurnal changes.

0911 Characterizing Sleep, Pain, and Opioid Craving in People with Chronic Low Back Pain on Long Term Opioid Therapy

0911 Characterizing Sleep, Pain, and Opioid Craving in People with Chronic Low Back Pain on Long Term Opioid Therapy

From taboo to treatment: The emergence of psychedelics in the management of pain and opioid use disorder.

The rise of psychedelics in contemporary medicine has sparked interest in their potential therapeutic applications. While traditionally associated with countercultural movements and recreational use, recent research has shed light on the potential benefits of psychedelics in various mental health conditions. In this review, we explore the possible role of psychedelics in the management of chronic pain and opioid use disorder (OUD), 2 critical areas in need of innovative treatment options. Pain control remains a significant clinical challenge, particularly for individuals with OUD and those who receive long-term opioid therapy who develop marked tolerance to opioid-induced analgesia. Despite the magnitude of this problem, there is a scarcity of controlled studies investigating pain management alternatives for these populations. Drawing from preclinical and human evidence, we highlight the potential of psychedelics to act on shared neurobiological substrates of chronic pain and OUD, potentially reversing pain- and opioid-induced neuroadaptations, such as central sensitization. We elaborate on the multifaceted dimensions of the pain experience (sensory, affective and cognitive) and their intersections that overlap with opioid-related phenomena (opioid craving and withdrawal), hypothesizing how these processes can be modulated by psychedelics. After summarizing the available clinical research, we propose mechanistic insights and methodological considerations for the design of future translational studies and clinical trials, building on a shared clinical and neurobiological understanding of chronic pain and OUD. Our intention is to provide timely perspectives that accelerate the development and exploration of novel therapeutics for chronic pain and OUD amidst the escalating opioid crisis.

‘I crave not to feel uncomfortable’ – investigating craving for opioids and cannabis among individuals with chronic pain

Background The assessment of drug craving is common in survey studies, including those using real-time data collection methods, such as Ecological Momentary Assessment (EMA). However, few studies investigate how participants with chronic pain interpret the word ‘craving’ and how interpretations impact survey responses. Methods We conducted a mixed-methods study among 12 individuals with chronic pain who were using prescription opioids and cannabis. Participants completed baseline surveys, cognitive interviews, and 14-day smartphone-based EMA data collection. Analyses included deductive and inductive coding of interviews and t-tests of EMA self-reports of opioid and cannabis craving. Results Four participants had negative reactions to the word ‘craving’, including mentions that these questions offended them. The remaining eight participants mentioned no negative connotation. EMA data showed that participants without negative reactions reported a greater range (opioids), higher standard deviation (opioids), and higher maximum (opioids, cannabis) on Likert-type EMA craving items, compared to those with a negative reaction. Conclusions Some individuals with chronic pain may have a negative reaction to the word ‘craving’ related to opioid and cannabis use and this reaction may impact survey responses. Alternative wording of survey items is recommended, for example focused on ‘wanting’ or ‘needing’.

Mediating effect of craving on the impact of buprenorphine/naloxone and methadone treatment on opioid use: Results from a randomized controlled trial

BackgroundThe relationship between opioid craving and opioid use is unclear. We sought to determine to what extent craving mediated the relationship between opioid agonist therapy and changes in opioid use. MethodsData came from a pragmatic, 24-week, pan-Canadian, multi-centric, open-label, randomized controlled trial comparing flexible buprenorphine/naloxone take-home doses to standard supervised methadone models of care for the treatment of prescription-type opioid use disorder. Participants were randomly allocated to buprenorphine/naloxone or methadone models of care. 270 people with prescription-type opioid use disorder were included in analyses. There were 93 women (34.4%) and 2 transgender (0.7%) participants. Most participants were white (67.4%), 45.9% reported unstable living conditions, and 44.8% had psychiatric comorbidities. Generalized linear mixed models followed by mediation analysis estimated the direct effect of treatment group on Timeline Followback-reported next-week opioid use and the indirect effect through past 24-hour opioid craving measured using the Brief Substance Craving Scale at week 2, 6, 10, 14, 18 and 22. ResultsUpon mediation analysis, the average direct effect of treatment on opioid use was 0.465 (95 % CI = 0.183 to 0.751, p < 0.001). The average causal mediated effect was 0.144 (95 % CI = 0.021 to 0.110; p < 0.001). Craving accounted for 23.6 % of the effect of treatment on opioid use (p < 0.001). ConclusionsPast 24-hour craving was associated with increased next-week opioid use; however, craving only partially mediated the effect of buprenorphine/naloxone and methadone on next-week opioid use. Research is needed to develop a comprehensive understanding of factors mediating opioid use during opioid agonist therapy.

The relationship of pain intensity and opioid craving with delayed methadone dose: A preliminary study of individuals with opioid use disorder.

Despite a strong theoretical link between opioid craving and pain, little is known about the temporal relationship between pain and craving and the acute experience of pain in the context of methadone treatment. Using a cross-over design, the current study evaluated the time course of pain and craving and objective experience of pain as a function of the last methadone dose. Participants (n = 20) presented for the study in the morning and either received methadone dose as scheduled or delayed dose until the afternoon. During the 4-h study visit, participants completed a series of tasks, including repeated assessment of pain and craving at 0, +40, +70, +130, +160 and +240 min and a cold pressor test (CPT) at +15 and +220 min. Separate mixed model results demonstrated no effect of dosing condition on craving; however, there was a significant dosing condition by time interaction (F(5,209) = 3.38, P = .006) such that pain increased over time in the delayed methadone condition but decreased in time in the scheduled methadone condition. A mixed model predicting self-reported pain revealed a three-way interaction between dosing condition, craving and time (F(5,197) = 2.39, P = .039) explained by a positive association between craving and pain at each time point (except 240 min) in delayed condition (P-range = .004-.0001). A separate mixed model on CPT data indicated a significant condition by time interaction such that pain threshold decreased in the delayed, but not scheduled, condition (F(1,57) = 4.01, P = .050). These preliminary findings highlight the potential for increased risks after even a short delay in receiving a methadone dose.

Psychedelic Therapy: A Primer for Primary Care Clinicians-Ibogaine.

Ibogaine is a plant-derived alkaloid that has been used for thousands of years in rites of passage and spiritual ceremonies in West-Central Africa. In the West, it has primarily been used and studied for its anti-addictive properties and more recently for other neuropsychiatric indications, including post-traumatic stress disorder, depression, anxiety, and traumatic brain injury. Ibogaine requires careful patient screening and monitoring because of significant safety issues. There is potential for cardiotoxicity (prolonged QT interval); without rigorous screening, fatal arrhythmias may occur. However, preliminary research suggests that co-administration of ibogaine with magnesium may mitigate cardiotoxicity. Additionally, ibogaine may have dangerous interactions with opiates, so patients who receive ibogaine treatment for opioid use disorder must withdraw from long-acting opioids. Other potential concerning effects of ibogaine include rare incidences of mania or psychosis. Anticipated transient effects during ibogaine treatment can include ataxia, tremors, and gastrointestinal symptoms. Robust effects after a single treatment with ibogaine have been reported. In open-label and randomized controlled trials (RCTs), ibogaine reduces heroin and opioid cravings by upwards of 50%, up to 24 weeks after the treatment. An observational study of 30 Special Operations Forces veterans with mild traumatic brain injury reported that 86% were in remission from post-traumatic stress disorder, 83% from depression, and 83% from anxiety, one month after a single-dose ibogaine treatment. Although there are several observational and open-label studies, there is only a single double-blind, placebo-controlled RCT on ibogaine. More RCTs with large sample sizes must be conducted to support ibogaine's safety and efficacy. Given the promising preliminary findings, ibogaine could potentially fill a much-needed gap in treatments for challenging conditions, including opioid dependence. Ibogaine's remarkable effects in traditionally treatment-resistant, combat-exposed individuals hints at its potential in broader populations with physical and psychological trauma.

The association of pain impact and sleep disruption with opioid withdrawal during opioid-use disorder treatment.

Persons with opioid-use disorder (OUD) often experience opioid withdrawal and opioid craving, which can drive continued opioid use and treatment discontinuation. In addition, hyperalgesia is common among persons with OUD, yet few studies have examined the role of pain impact during OUD treatment. The purpose of the present study was to test whether opioid withdrawal and craving were elevated in the context of greater pain impact (i.e. greater pain intensity and interference), and whether these associations changed throughout treatment. Participants in residential OUD treatment (n= 24) wore wrist actigraphy to measure sleep and completed daily measures of pain impact, opioid withdrawal and opioid craving for up to 28 days. Mixed effects models were used to examine whether daily elevations in pain impact and sleep continuity were associated with withdrawal severity and opioid craving. Elevations in withdrawal, but not craving, occurred on days when individuals reported higher scores on the pain impact scale. Associations between pain impact and withdrawal were present throughout treatment, but stronger during early treatment. In contrast, both withdrawal and opioid craving were elevated following nights of greater wake after sleep onset and awakenings, but these findings were often more pronounced in early treatment. Pain impact and sleep disturbance are 2 factors associated with opioid withdrawal and opioid craving. Novel pharmacotherapies and scalable adjunctive interventions targeting sleep and pain impact should be tested in future work to improve OUD treatment outcomes.