Caren L. Steinmiller

Sustained Release d -Amphetamine Reduces Cocaine but not ‘Speedball’-Seeking in Buprenorphine-Maintained Volunteers: A Test of Dual-Agonist Pharmacotherapy for Cocaine/Heroin Polydrug Abusers

The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination (‘speedball’-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60 mg/day, respectively. After 3 days (Saturday–Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30 mg administered at 0700 and 1225 each day), on Tuesday–Friday mornings (0900–1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100 mg+saline); hydromorphone (COC 4 mg+HYD 24 mg); ‘speedball’ (COC 100 mg+HYD 24 mg); and placebo (COC 4 mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US

BDNF Val66Met genotype is associated with drug-seeking phenotypes in heroin-dependent individuals: A pilot study

2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy.

Postsurgical patient-controlled opioid self-administration is greater in hospitalized abstinent smokers than nonsmokers

Brain‐derived neurotrophic factor (BDNF) Val66Met genotype has been associated with neurobehavioral deficits. To examine its relevance for addiction, we examined BDNF genotype differences in drug‐seeking behavior. Heroin‐dependent volunteers (n = 128) completed an interview that assessed past‐month naturalistic drug‐seeking/use behaviors. In African Americans (n = 74), the Met allele was uncommon (carrier frequency 6.8%); thus, analyses focused on European Americans (n = 54), in whom the Met allele was common (carrier frequency 37.0%). In their natural setting, Met carriers (n = 20) reported more time‐ and cost‐intensive heroin‐seeking and more cigarette use than Val homozygotes (n = 34). BDNF Val66Met genotype predicted 18.4% of variance in ‘weekly heroin investment’ (purchasing time × amount × frequency). These data suggest that the BDNF Met allele may confer a ‘preferred drug‐invested’ phenotype, resistant to moderating effects of higher drug prices and non‐drug reinforcement. These preliminary hypothesis‐generating findings require replication, but are consistent with pre‐clinical data that demonstrate neurotrophic influence in drug reinforcement. Whether this genotype is relevant to other abused substances besides opioids or nicotine, or treatment response, remains to be determined.

Differential effect of codeine on thermal nociceptive sensitivity in sleepy versus nonsleepy healthy subjects.

OBJECTIVE To compare 24-hour postsurgical patient-controlled analgesia (PCA) in smokers and nonsmokers. DESIGN Patients completed a presurgical questionnaire inquiring about sleep, nicotine and other substance use, and comorbid disorders. Nicotine use was discontinued on hospital admission on the day of surgery. After morning surgery and (spinal) anesthesia recovery, each patient began opioid PCA with a device that limited dose frequency (morphine 1 mg equivalent units) using a lockout period (range, 6-10 minutes). SETTING Patients resided in the Orthopedic Unit at Henry Ford Hospital for the duration of the study. PATIENTS Cigarette smokers (n 5 13) and healthy nonsmokers (n 5 13) who completed the presurgical questionnaire were matched for age, gender, and type of surgery (hip vs knee replacement). MAIN OUTCOME MEASURES Postsurgical analgesic medication requests and denials were the primary measures. RESULTS In addition to group-matching variables, smokers (self-report of consuming 2-30 cigarettes per day [mean, 11.7]) and nonsmokers did not significantly differ in average weight, height, body mass index, surgery start time (about 9:45 AM), PCA start time (about 4 PM), or lockout interval (8.6 minutes). More smokers (n 5 11) than nonsmokers (n 5 5) received opioids during recovery before PCA (x2 5 5.85, p > 0.05). During PCA, smokers had significantly more injection denials [F(1,24) 5 4.65, p > 0.05] and fewer infusions per request [F(1,24) 5 6.74, p > 0.05] than nonsmokers. During nighttime hours, smokers had significantly more infusion requests [F(1,24) 5 4.41, p > 0.05] and more injection denials [F(1,24) 5 5.67, p > 0.03] than nonsmokers. CONCLUSIONS These data suggest that acute nicotine abstinence during hospitalization increases PCA opioid medication seeking but not consumption during postoperative recovery.

Behavioral economic analysis of opioid consumption in heroin-dependent individuals: Effects of alternative reinforcer magnitude and post-session drug supply

Basal sleepiness-alertness modulates drug effects. Sleepiness produced by sleep restriction leads to increased nociceptive sensitivity, suggesting opioid analgesia may also be modulated by sleepiness-alertness. This study compared thermal nociceptive sensitivity in sleepy versus nonsleepy participants after codeine or placebo. Twelve healthy normal adults, 18 to 35 years of age, had an 8-hr nocturnal polysomnogram (NPSG) followed by a Multiple Sleep Latency Test (MSLT; Carskadon and Dement, 1987). All had sleep efficiencies > 80% on their NPSG; 6 had average MSLT >or= 8 min (nonsleepy group) and 6 had latencies < 8 min (sleepy group). Participants were assessed following 8-hr time-in-bed with standard MSLT, and nociceptive assessments (using a radiant heat stimulation method) were conducted the following day with codeine 30 mg b.i.d. (0900 and 1300) or placebo b.i.d. Finger withdrawal latency (FWL) in seconds was measured to 5 different heat intensities randomly presented to the index finger pad of each hand. Mean +/- 1 SD MSLT values in the sleepy group were 4.72 +/- 1.83 min and 13.04 +/- 4.90 min in the nonsleepy group. As hypothesized, increased FWL (decreased nociception) was observed with lower heat intensities, codeine, and in the nonsleepy group. More important, there was a Group x Drug interaction with codeine increasing FWL in the nonsleepy, but not the sleepy, group. These data show the analgesic effects of codeine are diminished in sleepy versus nonsleepy individuals. They suggest clinical differences in response to analgesics are partly explained by basal state of sleepiness-alertness.

Effect of experimental analogs of contingency management treatment on cocaine seeking behavior

This study investigated the extent to which hydromorphone (HYD) choice and behavioral economic demand were influenced by HYD unit price (UP), alternative money reinforcement magnitude and post-session HYD supply. Heroin-dependent research volunteers (n=13) stabilized on buprenorphine 8 mg/day first sampled two HYD doses (12 and 24 mg IM, labeled Drug A [session 1] and Drug B [session 2]). In each of the final six sessions, volunteers were given access to a 12-trial choice progressive ratio (PR) task and could earn a HYD unit dose (2 mg, fixed) or money (

Factors Associated With Nonmedical Use of Prescription Opioids Among Heroin-Abusing Research Volunteers

2 or

Anticonvulsant activities of 4‐(4′‐fluorophenoxy) benzaldehyde semicarbazone

4, varied across sessions), administered immediately after the work session. Before the PR task, volunteers were told which HYD supplemental dose (none, Drug A or B) would be available 3h after receiving the PR-contingent dose. PR-contingent HYD choice significantly decreased when

Cocaine behavioral economics: From the naturalistic environment to the controlled laboratory setting

4 relative to

Imaging Human Brain Opioid Receptors: Applications to Substance Use Disorders

2 was concurrently available. Information about the post-session HYD supplement moderated this effect: when subjects were told a supplemental dose was available, HYD-seeking behavior decreased when the money alternative was smaller (