The dopamine D3 receptor (D3R) is a target for developing medications to treat substance use disorders. D3R-selective compounds with high affinity and varying efficacies have been discovered, providing critical research tools for cell-based studies that have been translated to in vivo models of drug abuse. D3R antagonists and partial agonists have shown especially promising results in rodent models of relapse-like behavior, including stress-, drug-, and cue-induced reinstatement of drug seeking. However, to date, translation to human studies has been limited. Herein, we present an overview and illustrate some of the pitfalls and challenges of developing novel D3R-selective compounds toward clinical utility, especially for treatment of cocaine abuse. Future research and development of D3R-selective antagonists and partial agonists for substance abuse remains critically important but will also require further evaluation and development of translational animal models to determine the best time in the addiction cycle to target D3Rs for optimal therapeutic efficacy.

Background Recent epidemiological data suggest a resurgence in cocaine use (CU) and cocaine-related problems in the United States. Demographic trends and correlates of problem CU are needed to determine potential factors that may be influencing the increased trend and to inform targeted prevention and intervention strategies. Methods Trends in any past-year CU, weekly CU, and cocaine use disorder (CUD) were examined among persons aged ≥12 years using the National Survey on Drug Use and Health from 2011 to 2015. Logistic regression analyses were used to determine correlates of past-year and weekly CU and CUD among adolescents and adults. Results The prevalence of past-year CU from 2011 to 2015 increased among females, ages 18–25, ages ≥50, non-Hispanic Blacks, and persons reporting low income, past-year tobacco use, past-year alcohol use, and past-month binge and heavy alcohol use. The prevalence of weekly CU increased among persons aged ≥50 years and persons reporting past-month heavy alcohol use. A significant increase in the prevalence of CUD was only found among persons aged ≥50 years. Adjusted logistic regression showed that older age, large metropolitan residence, past-year tobacco, alcohol, cannabis, and heroin use, and major depressive episode were associated with increased odds of CU or CUD among both adolescents and adults; however, sex and race/ethnicity correlates differed among adolescents and adults. Conclusions Findings have implications for increased monitoring of CU-related indicators among some high-risk groups, such as females, older adults, Blacks, and polysubstance users. Targeted screening and intervention strategies among these population subgroups may be needed.

Background and aims Pharmacy administration and dispensing of methadone for methadone maintenance treatment (MMT) can expand treatment access for opioid use disorder (OUD). This study investigated the feasibility and acceptability of a novel model permitting an opioid treatment program (OTP) physician to prescribe methadone for OUD treatment through collaboration with a partnered pharmacy. Design Non‐randomized, single‐arm, open‐label feasibility trial. Setting One OTP and one community pharmacy in the United States. Participants One OTP physician, two pharmacists and 20 MMT patients receiving between six and 13 take‐home methadone doses at 5–160 mg/day. Intervention Patients’ methadone administration and dispensing of take‐home doses was transferred from the OTP to the pharmacy for 3 months. Measurements Primary outcome was medication adherence. Secondary outcomes were recruitment, treatment retention, substance use, counseling attendance at the OTP, pharmacist prescription drug monitoring program (PDMP) use, safety and satisfaction. Findings Of 29 patients eligible at pre‐screen, 20 patients (69%) enrolled into the study. Recruitment occurred from 6 August 2020 to 10 October 2020. Treatment retention rate at month 3 was 80% (16 of 20). Two participants returned early to the OTP because of a work/schedule change, one due to pregnancy and one following a non‐study‐related hospitalization. Medication adherence among 16 patients who were retained was 100%. Intervention fidelity was 100%. All participants attended random call‐back visits. None showed evidence of tampering/diversion of methadone. Pharmacists checked the PDMP at all visits. All participants attended psychosocial counseling as planned. There were no positive urine screens for illicit opioid use and no study‐related adverse events. All participants endorsed ‘pharmacy is the right location for receiving methadone for MMT’, 88% endorsed ‘convenient or very convenient to receive methadone at the pharmacy’ and 88% were satisfied or very satisfied with the quality of treatment offered. Conclusions This feasibility trial has found pharmacy administration and dispensing of physician‐prescribed methadone for methadone maintenance treatment to be feasible and acceptable.

Rationale The dopamine (DA) D2 and D3 receptors have been associated with cocaine abuse. A recent study with the D3 receptor (D3R) partial agonist PG619 found that it attenuated cocaine-induced reinstatement and the D2-like receptor antagonist buspirone has shown positive outcomes in two studies of cocaine abuse in monkeys. However, a recent clinical trial indicated that buspirone did not improve abstinence in treatment-seeking cocaine abusers. Objective The objective of the study was to examine PG619 and buspirone under a food-drug choice paradigm in order to better model the clinical findings. In addition, we extended the characterization of both compounds to include methamphetamine (MA) self-administration (SA). Methods Six adult male rhesus monkeys were trained to respond under a concurrent food (1.0-g pellets) and drug (0.01–0.3 mg/kg/injection cocaine or MA) choice paradigm in which complete SA dose-response curves were determined each session (N=3/group). Monkeys received 5 days of treatment with either PG619 (0.1–3.0 mg/kg, i.v.) or buspirone (0.01–1.0 mg/kg, i.m.). In a follow-up study, the SA doses were reduced (0.003–0.1 mg/kg/injection) to increase reinforcement frequency and buspirone was retested. Results PG619 did not affect cocaine or MA choice, while buspirone increased low-dose cocaine choice. Changing the SA doses increased the number of reinforcers received each session, but buspirone did not decrease drug choice. Conclusions Consistent with clinical findings, these results do not support the use of buspirone for psychostimulant abuse and suggest that food-drug choice paradigms may have greater predictive validity than the use of other schedules of reinforcement.