Dronabinol

Interviews were conducted by trained research staff in a private setting and data were recorded anonymously, unaccompanied by any unique identifiers. Subjects were first asked the single screening question, “How many times in the past year have you used an illegal drug or used a prescription medication for non-medical reasons?” (where a response of ≥1 is considered positive). If asked to clarify the meaning of “non-medical reasons”, the research associate added "for instance because of the experience or feeling it caused”. After subjects responded to the single screening question, they were asked if they had ever experienced any of a list of problems related to drug use. For this we modified the previously described Short Inventory of Problems-Alcohol and Drug (SIP-AD) questionnaire, which asks about problems ever experienced in the subject’s lifetime related to alcohol or drug use8 (link). We modified this by eliminating the word alcohol from the questions, a modification we hereafter refer to as the Short Inventory of Problems- Drug Use (SIP-DU). In a separate analysis (but in these subjects) we determined the reliability and validity of the SIP-DU as a measure of drug use consequences 9 . The computerized version of the Composite International Diagnostic Interview (CIDI) Substance Abuse Module was used for the assessment of current (12-month) drug use disorders 10 . This structured interview yields a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of drug abuse or dependence. In addition, as part of the CIDI, subjects were asked detailed questions about current (past year) use of illicit drugs (marijuana, cocaine, heroin, stimulants or hallucinogens) and non-medical use of prescription drugs. Following the interview subjects were asked to undergo oral fluid testing for the presence of common drugs of abuse (opiates, benzodiazepines, cocaine, methamphetamines, tetrahydrocannabinol (THC). Once collected, oral fluid was sent to an outside laboratory for analysis using methodology that yields results comparable to urine drug screening (Intercept™ immunoassay, OraSure Technologies, Bethlehem, PA)11 (link)–14 (link). In order to aid in the interpretation of drug test results subjects had been asked, as part of the interview, if they had recently been prescribed any drugs from a list of opiates or benzodiazepines. Because this question was added to the questionnaire during the study, responses were missing from 23 subjects who underwent oral fluid testing. Subjects were not told that they would be asked to undergo drug testing until the interview was complete. After completing the interview, they were compensated and thanked for their participation. They were then asked to undergo oral fluid testing and a second informed consent process was completed. Following the single drug screening question, but before the other assessments, the 10-item Drug Abuse Screening Test (DAST-10) was administered for comparison 4 (link). As part of a parallel study on screening for unhealthy alcohol use, subjects were also asked a single alcohol screening question (preceding the drug screening question), two other brief alcohol screening questionnaires and a calendar based assessment of past-month alcohol consumption (all after the drug screen and prior to the CIDI) 7 (link).

Data were derived from 897 participants (513 women, mean age 19.62±1.24) who had successfully completed the ongoing Duke Neurogenetics Study (DNS) as of as of December 31, 2013. The DNS assesses a range of behavioral and biological traits among young adult, university students. The study was approved by the Duke University School of Medicine Institutional Review Board. All participants provided informed consent in accord with Duke University guidelines, and were in good general health. All participants were free of the following exclusionary criteria: (1) medical diagnoses of cancer, stroke, diabetes requiring insulin treatment, chronic kidney or liver disease, or lifetime history of psychotic symptoms; (2) use of psychotropic, glucocorticoid, or hypolipidemic medication; and (3) conditions affecting cerebral blood flow and metabolism (e.g., hypertension).
Our analyses focused on a subset of 759 participants (426 women, mean age 19.65±1.24) with BOLD fMRI data surviving a stringent multi-level quality control procedure (Supplementary Table 1). Of these 759 participants, 127 (55 women; mean age 19.79±1.21) met criteria for at least one current Axis I or select Axis II (borderline or antisocial personality disorder) diagnosis according to DSM-IV. The majority of these individuals (n=86; 35 women, mean age 19.94±1.15) were diagnosed with AUD (Supplementary Table 2). Since our study focuses on inter-individual variability in problem drinking, we did not exclude individuals with categorical disorders from analyses. Furthermore, we used presence of a current alcohol-related disorder (alcohol abuse or dependence) as a dependent variable in a subset of analyses. Notably, participants were required to pass a breathalyzer test before scanning to ensure they were not acutely intoxicated at the time of data collection. In addition, participants were asked to refrain from using any psychoactive substances while participating in the study and notified that they would be subject to a random drug screen on the day of their scan. Immediately preceding neuroimaging data collection, every 10^th male participant was asked to provide a urine sample, which was tested on a QuickScreen Pro Drug Screening test (Phamatech Inc, San Diego, CA) for the presence of amphetamine, methamphetamine, opiates, cocaine and tetrahydrocannabinol (THC). Due to the pharmacokinetics of THC,^{33 (link)} the presence of the chemical in urine was not deemed exclusionary unless the participant was acutely intoxicated. No participant was excluded for acute THC intoxication or tested positive for any other substance.