Jie Yang,1 Nazifa Rahman,1 Thi Nguyen,1 Monica Jung,1 Dereje Assefa,1 Rhiannon Dowla,2 Lisa J Fyfield,3 Zoe Bertenshaw,1 Suzanne Nielsen,1 Louisa Picco11Monash Addiction Centre, Eastern Health Clinical School, Monash University, Melbourne, VIC, Australia; 2Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; 3Hamilton Centre, Turning Point, Melbourne, VIC, AustraliaCorrespondence: Suzanne Nielsen, Monash Addiction Centre, Eastern Health Clinical School, Monash University, 47 - 49 Moorooduc Hwy, Frankston, VIC, 3199, Australia, Tel +61 3 9904 4641, Email suzanne.nielsen@monash.eduBackground: Almost half (44%) of people receiving pharmacotherapy for opioid use disorder (OUD) have comorbid chronic non-cancer pain (CNCP). Non-pharmacological treatments for pain management are recommended alongside pharmacotherapy, yet evidence regarding their effectiveness, feasibility, acceptability, and affordability remains limited, warranting an updated review of current evidence.Methods: A scoping review was conducted following JBI methodology and PRISMA-ScR guidelines. Four databases were searched in November 2025, while a grey literature search was conducted in Google Scholar in December 2025 for publications on non-pharmacological interventions for adults with concurrent CNCP and OUD. Eligible publications were screened independently, data were extracted using a standardised form, and findings were synthesised narratively.Results: 35 publications were included, representing 15 publications from 13 primary studies and 20 protocols. Findings from the 13 primary studies primarily examined psychosocial, physical activity, and multimodal interventions, with psychosocial interventions being the most frequently studied. Overall, non-pharmacological interventions showed potential benefits in reducing pain, opioid craving, and substance use. Feasibility varied across intervention modalities, while acceptability was generally favourable among the 7 primary studies that assessed it.Conclusion: This scoping review mapped the available evidence on psychosocial, physical, and multimodal approaches for managing co-occurring CNCP and OUD. However, current evidence remains limited and insufficient to determine comparative effectiveness. The growing number of recently completed and ongoing trials indicates an expanding evidence base that will support more robust future evaluation and inform clinical practice.Keywords: chronic non-cancer pain, opioid use disorder, non-pharmacological treatment, scoping review
Hannah N Carlson,1,* Rachel M Carlson2,*1Lake Forest College, Lake Forest, IL, 60045, USA; 2Fellowship Hall, Greensboro, NC, 27405, USA*These authors contributed equally to this workCorrespondence: Hannah N Carlson, Lake Forest College, 555 N Sheridan Road, Lake Forest, IL, 60045, USA, Email hcarlson@lakeforest.eduAbstract: Despite substantial evidence of its efficacy, contingency management as a treatment for substance use disorder remains widely underutilized. Lack of long-term efficacy, inability to address the cause of addiction, and lack of identifiable mechanism feature prominently among the concerns reported by both clinicians and the public. In this narrative review, we consider the possible mechanisms of change involved in treatment and recovery for substance use disorders, including intrinsic motivation, decision making, neural plasticity, and abstinence, with a particular focus on how contingency management may act as a vehicle for facilitating long-term change in people with a substance use disorder, employing our combined expertise as a preclinical behavioral neuroscientist and a licensed clinical social worker specializing in the translational behavioral science and treatment of substance use disorders respectively. We present a theoretical model that combines the behaviorist foundations of contingency management with recent preclinical and clinical data to explain how the use of external reinforcers might facilitate long lasting, intrinsic change in behavior that addresses the pathology of addiction. Ultimately, we suggest that the use of extrinsic reinforcers during the application of contingency management might reinforce immediate behaviors that permit the development of longer-term mechanisms of change, such as abstinence, inhibitory control, or self-efficacy, and that when extrinsic reinforcement is removed at the conclusion of a contingency management program, recovery-related behaviors might still be maintained by these mechanisms.Keywords: contingency management, substance use disorder, addiction, learning theory, treatment, motivation
Background:Prenatal alcohol exposure can cause neurodevelopmental injury, but the cellular events linking altered inhibitory signalling to apoptotic changes in the developing spinal dorsal horn remain incompletely understood. Methods:C57BL/6J mice received two subcutaneous ethanol injections (2.5 g/kg each, 2 h apart) on postnatal day 7 (PD7). Dorsal horn injury and GABAergic changes were assessed by histology, immunostaining, and whole-cell patch-clamp recording. Intracellular Ca2+ signalling, CaMKII and GSK-3β regulation, mitochondrial apoptosis-related markers, oxidative stress, and cell viability were examined using calcium imaging, flow cytometry, Western blotting, and co-immunoprecipitation. Tetraethylammonium chloride (TEAC) and Bay K8644 were used to explore the contribution of membrane excitability and voltage-gated Ca2+ entry. Results:Ethanol exposure was associated with altered dorsal horn neuronal morphology, increased cleaved caspase-3, and prominent involvement of GAD67-positive neurons. It was also associated with increased GABA staining and mIPSC frequency, without a clear change in mIPSC amplitude; reduced intracellular Ca2+ signals; lower CaMKII Thr286 phosphorylation and CaMKII-GSK-3β association; decreased inhibitory GSK-3β Ser9 phosphorylation; and mitochondrial apoptosis-related changes, increased ROS, reduced cell viability, and caspase-3 activation. TEAC attenuated several ethanol-associated molecular and cellular injury markers, whereas Bay K8644 moderated selected Ca2+- and mitochondrial/oxidative stress-related outcomes. Conclusion:Acute PD7 ethanol exposure was associated with neuronal injury in the developing mouse spinal dorsal horn and with coordinated changes in GABAergic signalling, Ca2+-CaMKII regulation, GSK-3β activity, and apoptosis-related markers. These findings support a candidate membrane-potential/Ca2+-sensitive GABAergic and Ca2+-CaMKII-GSK-3β/BAX signalling framework, but do not establish a fixed causal sequence or behavioural consequence.
Yuting Wang,1,2,* Zhaoyang Cheng,1,2,* Zizhuo Wang,3 Xihui Ding,3 Xiaoxiang Xu,3 Shuaichen Sun,3 Yingying Zheng,3 Min Liu,3 Jianguang Xu,4 Xiang Nan,3 Jinyong Xu,3,5 Xiaohui Li,3,5 Zhenhua Ren,1,2,4 Kai Zhang1,2,5,61Department of Psychiatry, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Department of Anatomy, Anhui Medical University, Hefei, People’s Republic of China; 4College and Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, People’s Republic of China; 5Anhui Provincial Key Laboratory for Brain Bank Construction and Resource Utilization, Hefei, People’s Republic of China; 6Anhui Psychiatric Center, Hefei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenhua Ren, College and Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, 81 Meishan Road, Hefei, 238000, People’s Republic of China, Tel/Fax +86-0551-65161053, People’s Republic of China, Email renzhenhua@ahmu.edu.cn Kai Zhang, Department of Psychiatry, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, 238000, People’s Republic of China, Tel/Fax +86-551-82324114, Email zhangkai@ahmu.edu.cnBackground: Prenatal alcohol exposure can cause neurodevelopmental injury, but the cellular events linking altered inhibitory signalling to apoptotic changes in the developing spinal dorsal horn remain incompletely understood.Methods: C57BL/6J mice received two subcutaneous ethanol injections (2.5 g/kg each, 2 h apart) on postnatal day 7 (PD7). Dorsal horn injury and GABAergic changes were assessed by histology, immunostaining, and whole-cell patch-clamp recording. Intracellular Ca2+ signalling, CaMKII and GSK-3β regulation, mitochondrial apoptosis-related markers, oxidative stress, and cell viability were examined using calcium imaging, flow cytometry, Western blotting, and co-immunoprecipitation. Tetraethylammonium chloride (TEAC) and Bay K8644 were used to explore the contribution of membrane excitability and voltage-gated Ca2+ entry.Results: Ethanol exposure was associated with altered dorsal horn neuronal morphology, increased cleaved caspase-3, and prominent involvement of GAD67-positive neurons. It was also associated with increased GABA staining and mIPSC frequency, without a clear change in mIPSC amplitude; reduced intracellular Ca2+ signals; lower CaMKII Thr286 phosphorylation and CaMKII-GSK-3β association; decreased inhibitory GSK-3β Ser9 phosphorylation; and mitochondrial apoptosis-related changes, increased ROS, reduced cell viability, and caspase-3 activation. TEAC attenuated several ethanol-associated molecular and cellular injury markers, whereas Bay K8644 moderated selected Ca2+- and mitochondrial/oxidative stress-related outcomes.Conclusion: Acute PD7 ethanol exposure was associated with neuronal injury in the developing mouse spinal dorsal horn and with coordinated changes in GABAergic signalling, Ca2+-CaMKII regulation, GSK-3β activity, and apoptosis-related markers. These findings support a candidate membrane-potential/Ca2+-sensitive GABAergic and Ca2+-CaMKII-GSK-3β/BAX signalling framework, but do not establish a fixed causal sequence or behavioural consequence.Keywords: fetal alcohol spectrum disorders, developmental ethanol exposure, spinal dorsal horn, apoptosis, CaMKII, GSK-3β
Background:Sleep-related symptoms are common among people receiving medications for opioid use disorder (OUD), including buprenorphine. In outpatient addiction treatment, nighttime sleep complaints are often evaluated alongside active medication lists and recent substance exposures. This short report described patient-reported nighttime sleep symptoms and sleep-relevant medication class documentation among adults receiving buprenorphine for OUD. Methods:This cross-sectional study used survey data and medical-record abstraction from adults receiving buprenorphine for OUD at an academic addiction clinic from February 2022 to September 2023. Nighttime sleep symptoms were characterized using Insomnia Severity Index items 1-3: difficulty falling asleep, difficulty staying asleep, and waking too early. Participants were categorized as No-Sx, Single-Sx, or Multi-Sx. Sleep-relevant medications documented on the active outpatient medication list were grouped into eight classes. Sample characteristics, nighttime symptom groups, medication class documentation, and urine drug testing results within 30 days were summarized descriptively. Results:Among study participants (n = 136), 72.1% endorsed at least one nighttime sleep symptom. Symptom group distribution was No-Sx (27.9%), Single-Sx (11.0%), and Multi-Sx (61.0%). In the Multi-Sx group, gabapentinoids were most frequently documented (34.9%), followed by sedating antidepressants (26.5%), sedating antihistamines (22.9%), and adrenergic agents (22.9%). Cannabinoids were detected in 46.2% of participants with available urine drug testing results. Conclusion:Nighttime sleep symptoms and sleep-relevant medication documentation were common in this outpatient buprenorphine-treated OUD sample. Findings support routine nighttime sleep symptom assessment, together with medication review and consideration of recent substance exposure, to help identify clinically relevant sleep concerns and inform safer outpatient buprenorphine care.
