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Background: Opioid use disorder (OUD) continues to be major public health problem in the US and innovative medication strategies are needed. The extended-release injectable formulation of naltrexone (ER-NTX), an opioid receptor antagonist, is an effective treatment for OUD, but the need for an opioid-free period during the induction phase of treatment is a barrier to treatment success, particularly in the outpatient setting. Lofexidine, an alpha-2-adrenergic agonist, is an effective treatment for opioid withdrawal. Objectives: To evaluate the feasibility, safety, and tolerability of lofexidine for facilitating induction onto ER-NTX in the management of OUD. Methods: In an open-label, uncontrolled, 10-week outpatient clinical trial, 20 adults (four women) with OUD were treated with a fixed-flexible dosing strategy (maximum 0.54 mg 4×/daily) of lofexidine for up to 10 days to manage opioid withdrawal prior to receiving ER-NTX. The COVID-19 pandemic resulted in a modification of the study methods after enrolling 10 participants who attended all visits in person. The second group of 10 participants attended most induction period visits remotely. Results: Overall, 10 of the 20 participants (50%) achieved the primary outcome by receiving the first ER-NTX injection. Rates of induction success did not differ by the presence of fentanyl or remote visit attendance, although the small sample size provided limited statistical power. Six out of 20 participants (30%) initiated on lofexidine required dose adjustments. There were no study-related serious adverse events. Conclusions: This study provides preliminary evidence supporting the feasibility of inducting individuals with OUD onto ER-NTX using lofexidine.

Background : There is a need for alcohol use disorder (AUD) pharmacotherapy that can be administered to actively drinking outpatients. Pregabalin, a gabapentoid anticonvulsant, has preliminary evidence supporting effects on alcohol withdrawal and AUD. Objectives : To evaluate the safety, tolerability, and optimal dosing of pregabalin for treating AUD. Methods : In an open-label, 8-week, outpatient trial of eighteen adults (nine women) with AUD, participants were titrated to 600 mg/day (or the maximum tolerated dose) over 3 weeks and then maintained for 5 weeks. Results : The majority (11/14, 78.6%) of participants with at least one-week of medication exposure achieved a maximum dose of 600 mg/day. Mean retention was 6.8 weeks (SD = 2.6). Eighty percent (12/15) of participants with post-enrollment data reported any adverse effects during the trial; and for those reporting adverse effects the most common were drowsiness (33.3%, 4/12), and fogginess (25%, 3/12), dizziness (25%, 3/12), and insomnia (25%, 3/12). Two participants discontinued study medication due to adverse effects and one had a dose reduction. Mean Heavy Drinking Days (HDD)/week decreased significantly by 3.43 days (SD = 2.47; median (IQR) = 4.00 (1.00 to 5.50)); Wilcoxon signed rank test statistic ((S) = 49.5, p = .0006). Mean proportion of HDD significantly decreased on average by 48.7% (SD = 35.1%; median (IQR) = 57.1% (14.3% to 78.6%)). The proportion of abstinent days increased significantly on average by 36.1% (SD = 35.0%; median (IQR) = 17.9% (14.3% to 75.0%); S = 49.5, p = .0005). Conclusions : Pregabalin treatment of AUD appears to be safe and well tolerated in doses up to 600 mg per day. Trial Registration : clinicaltrials.gov identifier: NCT03256253.

Background : Cocaine use disorder (CUD) is a substantial public health problem with no FDA-approved medication treatments. Psychostimulants have shown promise as pharmacotherapy for CUD. Lisdexamfetamine, a novel prodrug psychostimulant, is roughly 40-50% as potent as dextroamphetamine. Objectives : To evaluate the safety, tolerability, and optimal dosing of lisdexamfetamine for treating CUD. Methods : Open-label, 8-week trial of 17 CUD adults. Participants were titrated to the maximum tolerated dose of 140 mg over 2-week period and maintained for 4 weeks, followed by a two-week taper period. The primary outcome measures were the maximum daily dose achieved during the study period and tolerability as measured by medication-related study drop-out. Results : Among the 16 participants with post-enrollment data, the mean dose of lisdexamfetamine achieved was 118.1 mg (standard deviation (SD) = 40.4), mean retention was 6.5 weeks (SD = 2.0), and no participants discontinued study medication due to adverse effects. Four participants had dose reductions due to adverse effects and continued in the trial. Six participants (37.5%) were abstinent for the last 3 weeks of their study participation. Mean dollars of cocaine spent per day significantly decreased from $19.72 at baseline to $7.57 during the last 3 weeks of study participation ( t 15  = 3.60, p = .003). The mean percent of using days significantly decreased from 25% at baseline to 12% during the last 3 weeks of study participation ( t 15  = 3.33, p = .005). Conclusion : The use of lisdexamfetamine for CUD in doses ranging to 140 mg daily was safe and generally well tolerated.

Background: There are no FDA-approved pharmacotherapies for cannabis use disorders (CUD), despite the evaluation of numerous medications. Notably, chronic dosing of oral naltrexone decreases self-administration of cannabis in human laboratory studies., Objectives: To test the feasibility of long-acting injectable naltrexone for the treatment of CUD, while obtaining preliminary safety and efficacy data., Methods: Twelve adult participants (seven male) meeting DSM-IV-TR criteria for cannabis dependence enrolled into an 8-week, open-label pilot study conducted at an academic treatment research clinic. They received 380 mg intramuscular injections of long-acting naltrexone on study day 1 and at the start of study week 5. Outcome measures included percentages of study completers and participants who received the second injection, frequency of adverse events (AEs), and cannabis consumption measured by average daily grams, dollars, and using days per week as measured by timeline follow-back and urine oral delta-9-tetrahydrocannabinol (THC) concentrations., Results: Of the 12 participants enrolled in the study, 9 completed the study and 6 received the second injection. There were no severe AEs but an unexpected AE led to the addition of supportive medications to the protocol. Number of cannabis use days per week significantly decreased over the course of the study (p = .001). Creatinine-corrected urine THC concentrations and average daily cannabis use per study week in grams and in dollars did not decrease over the course of the study., Conclusions: Long-acting injectable naltrexone is a feasible intervention for CUD worthy of further study in a placebo-controlled, double-blinded randomized clinical trial.