The use of drugs other than alcohol is a leading cause of fatal injury in the United States, accounting for more than 40 000 deathsperyear.1 Increases intherateofdrug-attributabledeaths over the past 2 decades have beenfueledbyoverdosesof illicitlyusedprescriptiondrugs (such as opioids and sedatives, sometimes in combination with alcohol). In 2011, an estimated 1 280 134 hospitalizations were related to drug overdosesnationwide,ofwhich1 021 563 (80%) involveddrugsonly and258 571 (20%) involveddrugs incombinationwithalcohol.2 National roadside research surveys have detected more drivers on roads after using drugs than alcohol,3 and severalmetaanalyses indicate that fatal trafficcrashrisksofdriverswhohave simultaneously used drugs and alcohol exceed the fatal crash risk of driving after either alone.4,5 In addition, marijuana use has increased in the past decade,6,7 perhaps accelerated by legalizationofmedicalmarijuanain22statesandWashington,DC, and legalization of recreational use by Colorado andWashington State. These public health trends underscore the need for continuing research to develop effective interventions for unhealthy drug use, and the emphasis on primary care in health care system reforms suggests that approaches to identify and effectively intervenewith patients exhibiting risky patterns of drug use should be evaluated in a variety of clinical settings. A substantial number of experimental studies have indicated that screeningandbriefnegotiated intervention (BNI) are effective inadultprimarycare inreducingriskyalcoholmisuse.8 Other research, such as a study of illicit drug screening and intervention for adults in anurgent care setting9 andanobservational study of screening and interventions in a broad array of generalmedical settings,10havesuggested thatBNImayalsobe effective in helping patients reduce their use of illicit drugs. A large multicenter international study showed overall significanteffects inprimarycare,althoughnosignificanteffectswere identifiedwhentheUSsiteswereexaminedseparately.11 Buildingonthesestudies, this issueofJAMA includesreports12,13 from 2well-designedandimplementedrandomizedclinical trials that foundscreeningandbrief interventions ingeneralmedical settings were not effective for reducing drug use. In a 3-group randomized trial, Saitz et al12 tested the efficacyof2briefcounseling interventions for illicitdruguseorprescription drug misuse. Adult primary care patients with Alcohol,Smoking,andSubstanceInvolvementScreeningTestscores of 4 or greaterwere studied (N = 528). The authors compared a 15-minute BNI and a 30to 45-minute adaption of motivational interviewing (MOTIV) and a booster with no brief intervention. The BNI included motivational interviewing feedback, review of “pros” and “cons” of use, and development of plans forchange.TheMOTIVinterventionelicitedpossible links betweendruguseandhealth concerns, highlighteddiscrepanciesbetweennegativedruguseoutcomesandvaluedgoals, enhanced self-efficacy about behavior change, and provided options for change. At intake, the reported main drug use was marijuana (63%), cocaine (19%), andopioids (17%), andboth interventionsaddressedalcohol in the15%forwhomitwasaconcern. In addition, all patients received a written list of substance use disorder treatment andmutual help resources. At the6-month follow-up, therewereno significantdifferences between groups inmeanmain drug use days in the past month, inanydruguse,or in riskofdrugdependence.Norwere there significant differences in drug use consequences, injectiondruguse, unsafe sex, hospitalizations, emergencydepartmentvisits, ormutualhelp attendance. Lackof effectwas consistent regardless of drug used, severity, alcohol use, and substance-relatedhealthcondition.Theauthorsconcludedthat if other trials yield consistent results, widespread implementation of drug screening and brief interventionwith referral to treatment should be reconsidered. Of note, contrary to many studies on alcohol screening and brief intervention, there was notareduction inheavydrinking.This raises thepossibility that drugandalcohol-using, single, low-incomepatientswithhigh unemployment and comorbidities may benefit less from BNI. In another study in this issue, Roy-Byrne et al13 randomized 868 adult (age ≥18 years) primary care patients in 7 safetynet clinics to receive enhanced care as usual or a brief 30minute intervention and booster within 2 weeks providing feedback on drug use, discussing pros and cons of use, raising participant confidence in being able to change, and presenting options for change. Patients in both groups received a handout depicting their drug problem, severity score, and a list of substance abuse treatment resources. The authors identified and trackedpast30-dayuseof themost frequentlyuseddrug,aswell as chemicaldependence treatment records, statealcohol arrest records,andin-patienthospitalizationanddeathrecords. Inboth groups, follow-up at 3, 6, 9, and 12monthswasmore than87%. During follow-up, therewerenosignificantdifferencesbetween the2 studygroupsondaysofdruguse,AddictionSeverity Indexdruguse,oranysecondaryoutcomesoradmissions to chemicaldependency.Bothgroupsreduceddrugusefrequency Related articles pages 492 and 502 Opinion