Initiating buprenorphine maintenance for opiate-dependent hospitalized patients: A randomized trial

s / Drug and Alcohol Dependence 140 (2014) e86–e168 e123 with superior side-effect profiles. The present study involved the synthesis of new selective GABABR PAMs, and the assessment of their effects in animal models of nicotine dependence. Methods: New derivatives of BHF177, a selective and potent GABABR PAM with efficacy in animal models of nicotine dependence, were synthesized. In vitro pharmacology using a CHO-K1 cell line expressing the heterodimeric GABABR comprised of human GABAB(1b) and rat GABAB2 subunits; in vivo drugmetabolism and pharmacokinetics (DMPK) of these compoundswere characterized to prioritize the candidates. One of the high priority compounds, KK-92A,was assessed in thenicotine self-administrationprocedure in rats. Results: Nine active molecules were selected from 240 analogues of BHF-177 based on in vitro microsomal stability and efficacy in multiple cell-based functional assays, including cAMP accumulation, Ca2+ mobilization, ERK activation and a cellular impedance-based (CellKey) assay. Among these compounds, KK92A showed improved efficacy in the cAMP and Cellkey assays compared to BHF177, and had a similar in vivo DMPK profile. KK-92A (2, 5, 10, 20mg/kg, intraperitoneal) significantly decreased intravenous nicotine self-administration under fixedand progressive-ratio schedules of reinforcement in rats, indicating that this compound inhibited both the primary reinforcing and incentive motivational effects of nicotine. Conclusions: KK-92A, a novel selective GABABR PAM, attenuates the rewarding effects of nicotine in rats. The present results further confirm that GABABR PAMs may be useful antismoking medications. Financial support: 2U19DA026838. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.350 Initiating buprenorphine maintenance for opiate-dependent hospitalized patients: A randomized trial Jane M. Liebschutz1, M. Stein2, D. Crooks1, D. Herman2, B. Anderson2, L. Meshesha1, S. Dossabhoy1 1 Boston Medical Center, Boston, MA, United States 2 Butler Hospital, Providence, RI, United States Aims: To determine whether offering opiate-dependent persons hospitalized for medical conditions initiation and linkage to opioid agonist treatment (OAT) with buprenorphine/naloxone (Bupe) would increase engagement in Bupe OAT at 6 months. Methods: Opiate-dependent patients not currently in addiction treatment who were admitted to a general medical hospital were identified by daily chart review of all hospital admissions and clinical interview by addiction specialist nurse or physician. Eligible, consenting patients (not alcohol dependent, no benzodiazepine mis-use) were randomized to 5-day Bupe detoxification protocol (DETOX) or Bupe induction, intra-hospital dose stabilization, and post-discharge transition to maintenance Bupe OAT (LINKAGE). Intention to treat outcomes at 6months included entry into outpatient OAT, days receiving OAT, and OAT retention at 6-months. Results: Among 119 participants, mean age was 40.1 (±11.8), 85 (71.4%) were male, 50 (42.0%) were non-Hispanic Caucasian, 35 (29.4%) were African-American, and 25 (21.0%) were Latino. LINKAGE and DETOX arms did not differ significantly (all p values >.4) on demographic characteristics. Compared to those in the DETOX (n=58), participants randomized to LINK-AGE (n=61) were significantly ( 2 =43.3, p< .001) more likely toenterBupe (73.8%vs13.8%)by6-months.Amongpersons who entered outpatient OAT, mean buprenorphine treatment days were 93.2 (±57.0) and 57.0 (±56.7) in the LINKAGE (n=45) and DETOX (n=8) arms, respectively. 14 (31.1%) of the persons in LINKAGE who initiated suboxone treatment were still engaged in treatment at the end of 6-months. Conclusions: LINKAGE was able to enroll 75% of these out-oftreatment opiate dependent persons in OAT. Compared to standard inpatient detox, initiation of and linkage to Bupe treatment is an effective means for engaging medically hospitalized patients who are not specifically seeking care for their addictions in long-term opiate Bupe treatment. Financial support: NIH/NIDA Award number R01DA02622301. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.351 Separate and combined effects of gabapentin and 9-THC doses in cannabis users discriminating 9-THC Joshua A. Lile, T. Kelly, L. Hays University of Kentucky, Lexington, KY, United States Aims: The aimof the present study is to determine the influence of gabapentin on the interoceptive effects of 9-THC in cannabis users. Gabapentin is being tested because recent clinical trial data indicate that it is effective at reducing cannabis use in dependent individuals seeking treatment. Methods: The interoceptive effects of 9-THC are measured using a pharmacologically specific and sensitive drugdiscrimination procedure. During a sampling phase, subjects receive 30mg 9-THC, which is identified by a unique letter code (e.g., Drug X). During a control phase, subjects are required to correctly identify when they received Drug X or Not Drug X (i.e., placebo). Finally, a test phase is conducted in which 9-THC (0, 5, 15 and 30mg) is administered alone and in combination with gabapentin (0, 600 and 1200mg). We hypothesize that gabapentin will substitute for the 9-THC discriminative stimulus, and shift the discriminative-stimulus effects of 9-THC leftward/upward. Data are analyzed using ANOVA. In addition to the drug-discrimination task, several other measures are collected to determine a profile of 9-THC and gabapentin effects, including heart rate, blood pressure, temperature, self-report questionnaires, time estimation, and performance on psychomotor tasks. Five subjects who reported regular cannabis use have completed the protocol; three are enrolled. Recruitment will continue until the target number of subjects have completed. Results: Drug doses and combinations have beenwell tolerated in all subjects. To date, 9-THC is functioning as a discriminative stimulus and producing effects typical of cannabinoids in humans. Initial results arealso consistentwith thehypothesis that theeffects of gabapentin overlap with 9-THC, and that 9-THC effects are enhanced when given in combination with gabapentin. Conclusions: These results suggest that one mechanism by whichgabapentinmight facilitate cannabis abstinence is producing effects that overlapwith cannabinoids, thereby addressing some of the signs and symptoms that reportedly make abstinence difficult. Financial support: Supported by NIH grants DA025605, DA031766 and UL1TR000117. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.352