The ASAM Weekly for June 16, 2026

This systematic review of publications (2000-2023) concerning tapering benzodiazepines (BZDs) was used to inform the Joint Clinical Practice Guideline on Benzodiazepine Tapering, published in 2025. Rates of taper were often faster than recommended, such as 25%-50% reduction in the initial 1-2 weeks. There was little information on long-term outcomes such as protracted withdrawal and quality of life, and some studies had high rates of attrition. Patients were often switched from short- to long-acting BZDs; however, there are no data on the effect on withdrawal severity or outcomes. There is little information about adverse events such as mortality and suicidality, despite insurance data associating discontinuing BZDs and mortality. The authors conclude the evidence base for tapering BZDs is deficient and list 10 areas for future research.

This meta-analysis of 12 randomized controlled trials assessed if pharmacotherapies for stimulant use disorder show evidence of benefit when reduced use is evaluated as an outcome. Researchers found that no medication demonstrated a significant benefit over placebo for abstinence. When reduced use was evaluated, pooled treatment effects remained nonsignificant; however, effect size estimates were consistently larger in magnitude than those observed for abstinence, and a positive signal for reduced cocaine use was observed for cabergoline in medication-specific analyses. Evaluating reduced stimulant use alongside abstinence may provide additional clinically relevant information for interpreting treatment effects in pharmacotherapy trials for stimulant use disorder.

Alpha-2 agonists (xylazine) as adulterants in the fentanyl drug supply may complicate overdose treatment and have other health effects. While the pharmacokinetics (PK) of xylazine among animals is established, the PK in humans is less well understood. Researchers conducted a PK study including 13 patients after overdose and who were positive for both fentanyl and xylazine. The researchers found that the half-life of xylazine was 345±145 minutes, which is much longer than found in animals (about 30 minutes). The researchers also noted potential side effects of xylazine and found about half of patients had hypotension (46.2%) and bradycardia (53.8%), while 84.6% had hyperglycemia. The authors note these findings help support clinical management of patients exposed to xylazine and also suggest future studies examining xylazine-related hyperglycemia.

While treatment guidelines recommend long-term use of medication for opioid use disorder (MOUD), some individuals wish to taper off treatment. Researchers conducted a retrospective observational study emulating a target trial to compare taper completion and all-cause mortality based on the timeframe of starting taper after MOUD induction (<3 months, 3-6 months, and 6-12 months vs 12-48 months). Initiation of a taper for buprenorphine or methadone in any timeframe <12 months was associated with greater likelihood of completing the taper, but also with an increased all-cause mortality. The authors note that while individuals may desire to taper off MOUD, these findings do support guidelines that recommend at least 12 months of stability on MOUD.

For this review paper, researchers included 16 peer-reviewed studies (9 quantitative, 3 qualitative, 4 mixed methods) and 6 grey literature studies (1 quantitative, 1 qualitative, 4 mixed methods) to synthesize the evidence on safer inhalation equipment provision for people who use crack. The studies found that safer inhalation interventions were highly acceptable and led to reduced pipe sharing, decreased injecting, and improved engagement with health and social services. Studies highlighted several implementation challenges, including limited resources, political barriers, and logistical constraints. The authors found that accessible, integrated, and peer-supported delivery models facilitated effective, safer crack use interventions.

Methamphetamine (METH) and MDMA are structurally similar amphetamines with markedly different clinical effects and addictive profiles, potentially mediated through tryptophan (TRY) metabolic pathways. This study compared serum TRY-related metabolites in chronic MDMA users, METH users, and healthy controls using ultra–high performance liquid chromatography–mass spectrometry. Results showed distinct alterations between groups, with METH use associated with reduced TRY and serotonin levels and increased activation of kynurenine pathways. In contrast, MDMA use was linked to selective activation of the hydroxylated kynurenine branch. These metabolite changes correlated with depression and psychosis severity, suggesting that differential TRY pathway alterations may underlie substance-specific neuropsychiatric effects and represent potential therapeutic targets.