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Edward M Sellers - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of abuse potential of brivaracetam in healthy recreational cns depressant users p6 243
    Neurology, 2017
    Co-Authors: Kerri A. Schoedel, Armel Stockis, Edward M Sellers
    Abstract:

    Objective: To evaluate the abuse potential of brivaracetam (BRV) compared with alprazolam (ALP, positive control), placebo (PBO), and levetiracetam (LEV). Background: BRV is a new antiepileptic drug for adjunctive treatment of focal seizures in adults at a maximum dose of 50–200 mg/day taken twice daily. Design/Methods: Randomized, double-blind, triple-dummy study in healthy male and female recreational CNS depressant users aged 18–55 years, who could distinguish between ALP 2 mg and PBO. All participants received single doses of BRV (50, 200, 1000 mg), ALP (1.5, 3 mg), PBO and LEV (4000 mg) in random order separated by 7–10 days. Subjective Visual Analogue Scales (VAS) and Addiction Research Centre Inventory (ARCI) scales were completed at intervals up to 24 hours post-dose. Peak effects (E max ) were analyzed using a mixed-effect model (per-protocol population, n=44). Results: E max for both ALP doses was significantly greater versus PBO for six designated endpoints, confirming study validity. Drug-Liking VAS E max (primary endpoint) was significantly lower for BRV 50 mg than ALP 1.5 mg (p=0.001) and 3 mg (p=0.045); BRV 200 mg (supratherapeutic dose) was not different from ALP; BRV 1000 mg had a greater effect than ALP 3 mg (p=0.028). Compared with ALP, BRV had significantly fewer sedative-like effects (ARCI Pentobarbital Chlorpromazine Alcohol Group), fewer positive effects (ARCI Morphine Benzedrine Group [euphoria]; Feeling High VAS [50, 200 mg]; Good Drug Effects VAS [50 mg]), and fewer negative effects (Bad Drug Effects VAS; ARCI Lysergic Acid Diethylamide [dysphoria]). BRV was not significantly different from ALP for Overall Drug-Liking VAS (all doses) or Take Drug Again VAS (50, 200 mg). For most endpoints, BRV had significantly greater effects than PBO; BRV (50–200 mg) was not different from LEV (4000 mg). Conclusions: BRV has been placed into Schedule V (Controlled Substances Act) consistent with its having lower abuse potential than ALP which is Schedule IV. Study Supported by: UCB Pharma Disclosure: Dr. Schoedel has received personal compensation for activities with a multiple pharmaceutical and biotech companies. Dr. Stockis has received personal compensation for activities with UCB Pharma as an employee. Dr. Stockis hold stock and/or stock options with UCB Pharma. Dr. Sellers has received personal compensation for activities with DL Global Partners.

  • Assessment of the Abuse Potential of the Orexin Receptor Antagonist, Suvorexant, Compared With Zolpidem in a Randomized Crossover Study.
    Journal of Clinical Psychopharmacology, 2016
    Co-Authors: Kerri A. Schoedel, Janice Faulknor, Naama Levy-cooperman, Nicole Lewis, William P. Kennedy, Edward M Sellers, Hong Sun, Jang-ho Cha, Wen Liu
    Abstract:

    Suvorexant is a dual orexin receptor antagonist approved in the United States and Japan for the treatment of insomnia at a maximum dose of 20 mg. This randomized double-blind crossover study evaluated the abuse potential of suvorexant in 36 healthy recreational polydrug users with a history of sedative and psychedelic drug use. Single doses of suvorexant (40, 80, and 150 mg: 2-7.5 × maximum dose), zolpidem (15 and 30 mg: 1.5-3 × maximum dose), and placebo were administered, with a 10-day washout between treatments. Subjective and objective measures, including visual analog scales (VASs), Addiction Research Center Inventory, and cognitive/psychomotor tests, were evaluated for 24-hour postdose. Suvorexant had significantly greater peak effects on "drug liking" VAS (primary endpoint) than placebo. Although effects of suvorexant on abuse potential measures were generally similar to zolpidem, they remained constant across doses, whereas zolpidem often had greater effects at higher doses. Suvorexant (all doses) had significantly fewer effects than zolpidem 30 mg on secondary measures, such as "high" VAS, Bowdle VAS, and Addiction Research Center Inventory morphine-Benzedrine group. The overall incidence of abuse-related adverse events, such as euphoric mood and hallucination, was numerically lower with suvorexant than zolpidem. In agreement with its classification as a schedule IV drug, suvorexant demonstrated abuse potential, compared with placebo. The abuse potential was similar to zolpidem using certain measures, but with a reduced incidence of abuse-related adverse events. Although this suggests that the overall abuse liability of suvorexant may be lower than zolpidem, the actual abuse rates will be assessed with the postmarketing experience.

  • positive and negative subjective effects of extended release oxymorphone versus controlled release oxycodone in recreational opioid users
    Journal of opioid management, 2011
    Co-Authors: Kerri A. Schoedel, Stephen O Mcmorn, Mstat Bijan Chakraborty, Susan L Potts, R Kathleen N Zerbe, Edward M Sellers
    Abstract:

    Objective: To compare the subjective effects of oxymorphone extended release (OM-ER ) versus oxycodone controlled release (OC-CR ). Design: Randomized, double-blind, crossover study. Setting: Inpatient unit. Subjects: Healthy, nondependent recreational opioid users. Interventions: Single intact oral tablets that were placebo or contained OM-ER (15 and 30 mg) or OC-CR (30 and 60 mg). Doses were representative of mid-range doses for chronic pain and were calculated using an established opioid conversion table. Main outcome measures: Visual Analog Scales, Subjective Drug Value (SDV), and Addiction Research Center Inventory (ARCI) measured positive, negative, and balance effects and pupillometry. Equianalgesic comparisons were between OM-ER 15 mg versus OC-CR 30 mg (low doses) and OM-ER 30 mg versus OC-CR 60 mg (high doses). Results: Thirty-five subjects received all five treatments. Positive subjective effects were lower for OM-ER 15 mg versus OC-CR 30 mg and for OM-ER 30 mg versus OC-CR 60 mg in ARCI Morphine Benzedrine Group (p ≤ 0.01 for both), Good Effects (p < 0.001 for both), Rush (p < 0.001 for both), and High VAS (p < 0.001 for both). Nausea was higher with OC-CR (p ≤ 0.02), and Bad Effects were higher for OC-CR 60 mg versus OM-ER 30 mg (p < 0.001). Balance effects were lower for OM-ER versus OC-CR (Drug Liking, p < 0.001; Overall Drug Liking, p ≤ 0.006; SDV, p ≤ 0.008), except for Take Drug Again (p < 0.001 for OC-CR 30 mg versus OM-ER 15 mg; p = 0.18 for high-dose group). Euphoric mood, nausea, somnolence, vomiting, and dizziness were more common with OC-CR than OM-ER. Limitations: Single-dose design; use of healthy, recreational opioid users. Conclusions: At equianalgesic doses, single oral intact OM-ER produced lower positive, negative, and balance subjective effects than OC-CR , indicating that analgesic potency may not necessarily be reflected in subjective/objective effects.

  • reduced cognitive and psychomotor impairment with extended release oxymorphone versus controlled release oxycodone
    Pain Physician, 2010
    Co-Authors: Kerri A. Schoedel, Stephen O Mcmorn, Bijan Chakraborty, Kathleen Zerbe, Edward M Sellers
    Abstract:

    BACKGROUND Opioids provide effective pain control, yet have risks including adverse events (AEs) (e.g., constipation, nausea/vomiting, sedation) and cognitive/psychomotor effects. OBJECTIVE To compare cognitive and psychomotor effects of oxymorphone extended release (OM-ER) versus oxycodone controlled release (OC-CR). STUDY DESIGN Randomized, double-blind, 5-way crossover SETTING Single inpatient research unit METHODS Nondependent recreational opioid users were administered single intact oral tablets of placebo, OM-ER (15 and 30 mg), and OC-CR (30 and 60 mg), separated by a 7- to 21-day washout. The divided attention (DA) test measured psychomotor impairment (e.g., manual tracking [e.g., percentage over road], target accuracy [e.g., target hits], reaction time [hit latency]). Visual analog scales measured alertness/drowsiness, agitation/relaxation, and dizziness. Sedative, stimulant, and dysphoric effects were measured using the Addiction Research Center Inventory Pentobarbital-Chlorpromazine-Alcohol (PCAG), Benzedrine Group (BG), and Lysergic Acid Diethylamide (LSD) scales, respectively. Comparisons were made between equianalgesic doses (OM-ER 15 mg vs OC-CR 30 mg; OM-ER 30 mg vs OC-CR 60 mg), within active drug doses, and between active drugs and placebo using least squares (LS) mean difference of the peak maximum (Emax) or minimum (Emin) effect using linear mixed model analysis of covariance. RESULTS Thirty-five participants received all 5 treatments. Peak cognitive and psychomotor impairment (LS mean [SE]) was less with OM-ER than equianalgesic doses of OC-CR for reaction time (Emax hit latency, longer if impaired; 571.2 [13.4] vs 588.1 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], P<0.001 for OM-ER 30 mg vs OC-CR 60 mg, respectively); tracking accuracy (Emin percentage over road, lower if impaired; 71.4 [2.4] vs 65.3 [2.4], P=0.007; 69.9 [2.4] vs 59.4 [2.4], P<0.001), and target accuracy (Emin target hits percentage, lower if impaired; 81.0 [3.1] vs 74.5 [3.1], P=0.02; 79.4 [3.1] vs 66.1 [3.1], P<0.001). Several other DA measures showed that OC-CR, especially 60 mg, produced more psychomotor impairment than equianalgesic OM-ER. Compared to OM-ER, OC-CR produced more dizziness (Emax, P<0.001 for OM-ER 15 mg vs OC-CR 30 mg and for OM-ER 30 mg vs OC-CR 60 mg), drowsiness (Emax, P<0.001 for both equianalgesic dose groups), relaxation (Emin, P=0.003 for OM-ER 15 mg vs OC-CR 30 mg; P=0.001 for OM-ER 30 mg vs OC-CR 60 mg), dysphoria (Emax LSD, P<0.001 for both equianalgesic dose groups), and sedation (Emax, PCAG; P<0.001 for both equianalgesic dose groups) and less stimulation (BG, Emin; P=0.01 for OM-ER 15 mg vs OC-CR mg; P<0.001 for OM-ER 30 mg vs OC-CR 60 mg). Several AEs occurred more commonly with OC-CR than OM-ER (e.g., euphoria, nausea, somnolence, vomiting, dizziness). LIMITATIONS Participants were young, healthy volunteer nondependent recreational drug users, and only single doses were evaluated. The effects of tampering or higher doses were not assessed. CONCLUSION Single oral intact low and high doses of OM-ER produced less cognitive and psychomotor impairment plus less sedation than equianalgesic OC-CR in this exploratory study. ClinicalTrials.gov registration NCT00955110.

  • comparative abuse liability and pharmacological effects of meprobamate triazolam and butabarbital
    Journal of Clinical Psychopharmacology, 2003
    Co-Authors: Laurie Zawertailo, Usoa E Busto, Howard L Kaplan, David J Greenblatt, Edward M Sellers
    Abstract:

    Implementation of regulations to control the prescribing of benzodiazepines in New York State in 1989 resulted in a 55% decrease in benzodiazepine prescribing, with a concomitant increase in the rates of prescribing older sedative-hypnotic compounds such as butabarbital (30% increase) and meprobamate (125% increase). In a double-blind, crossover, placebo-controlled study, we compared the behavioral and pharmacological effects of triazolam, meprobamate, and butabarbital in 14 recreational drug users. Placebo and three doses each of triazolam, meprobamate, and butabarbital were administered to each subject in a random order. Objective tests (motor performance, concentration) and subjective response questionnaires measured drug effects. Triazolam, meprobamate, and butabarbital showed comparable negative dose-response slopes on the objective measures. On the basis of these objective data, equivalent doses for the three compounds were determined to be as follows: 0.5 mg triazolam = 2,400 mg meprobamate = 400 mg butabarbital. Subjective effects data on equivalent doses show that butabarbital produced the highest peak score on Cole/ARCI Abuse Potential, ARCI Pentobarbital Chlorpromazine Alcohol Group (PCAG), and "drug strength" scales. Triazolam and butabarbital produced equivalent results on ARCI Morphine Benzedrine Group (MBG), Cole/ARCI Euphoria, and "drug liking" scales. Meprobamate was indistinguishable from placebo on euphoria and abuse potential scales. Behavioral economics analysis indicated a price crossover point two times higher for butabarbital (400 mg) than for any other drug condition. These data indicate a comparative abuse liability of butabarbital > triazolam > or = meprobamate, suggesting that the prescribing restrictions on benzodiazepines had little net benefit on abuse risk in the population and may have increased the risk of overdose morbidity and mortality.

Kerri A. Schoedel - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of abuse potential of brivaracetam in healthy recreational cns depressant users p6 243
    Neurology, 2017
    Co-Authors: Kerri A. Schoedel, Armel Stockis, Edward M Sellers
    Abstract:

    Objective: To evaluate the abuse potential of brivaracetam (BRV) compared with alprazolam (ALP, positive control), placebo (PBO), and levetiracetam (LEV). Background: BRV is a new antiepileptic drug for adjunctive treatment of focal seizures in adults at a maximum dose of 50–200 mg/day taken twice daily. Design/Methods: Randomized, double-blind, triple-dummy study in healthy male and female recreational CNS depressant users aged 18–55 years, who could distinguish between ALP 2 mg and PBO. All participants received single doses of BRV (50, 200, 1000 mg), ALP (1.5, 3 mg), PBO and LEV (4000 mg) in random order separated by 7–10 days. Subjective Visual Analogue Scales (VAS) and Addiction Research Centre Inventory (ARCI) scales were completed at intervals up to 24 hours post-dose. Peak effects (E max ) were analyzed using a mixed-effect model (per-protocol population, n=44). Results: E max for both ALP doses was significantly greater versus PBO for six designated endpoints, confirming study validity. Drug-Liking VAS E max (primary endpoint) was significantly lower for BRV 50 mg than ALP 1.5 mg (p=0.001) and 3 mg (p=0.045); BRV 200 mg (supratherapeutic dose) was not different from ALP; BRV 1000 mg had a greater effect than ALP 3 mg (p=0.028). Compared with ALP, BRV had significantly fewer sedative-like effects (ARCI Pentobarbital Chlorpromazine Alcohol Group), fewer positive effects (ARCI Morphine Benzedrine Group [euphoria]; Feeling High VAS [50, 200 mg]; Good Drug Effects VAS [50 mg]), and fewer negative effects (Bad Drug Effects VAS; ARCI Lysergic Acid Diethylamide [dysphoria]). BRV was not significantly different from ALP for Overall Drug-Liking VAS (all doses) or Take Drug Again VAS (50, 200 mg). For most endpoints, BRV had significantly greater effects than PBO; BRV (50–200 mg) was not different from LEV (4000 mg). Conclusions: BRV has been placed into Schedule V (Controlled Substances Act) consistent with its having lower abuse potential than ALP which is Schedule IV. Study Supported by: UCB Pharma Disclosure: Dr. Schoedel has received personal compensation for activities with a multiple pharmaceutical and biotech companies. Dr. Stockis has received personal compensation for activities with UCB Pharma as an employee. Dr. Stockis hold stock and/or stock options with UCB Pharma. Dr. Sellers has received personal compensation for activities with DL Global Partners.

  • abuse liability assessment of eslicarbazepine acetate in healthy male and female recreational sedative users a phase i randomized controlled trial
    Epilepsy & Behavior, 2016
    Co-Authors: Naama Levycooperman, Kerri A. Schoedel, Bijan Chakraborty, David Blum, Hailong Cheng
    Abstract:

    Abstract Rationale Eslicarbazepine acetate (ESL) is a once-daily oral antiepileptic drug for the treatment of partial-onset seizures. Adverse events such as dizziness and somnolence reported in clinical studies suggest that ESL has detectable central nervous system (CNS) effects in addition to its antiepileptic effects. This Phase I study evaluated the abuse liability of ESL compared with that of alprazolam (ALP) and placebo (PBO) in recreational CNS depressant users. Methods In this single-dose, randomized, double-blind, PBO- and active-controlled crossover study, healthy recreational CNS depressant users who could discern between ALP 2 mg and PBO received single oral doses of each of the following treatments with a washout interval of ≥ 7 days between each treatment: ESL (800 mg, 1600 mg, 2000 mg, and 2400 mg); ALP (1.5 mg and 3.0 mg); and PBO. Subjective measures, including visual analog scales (VASs) e.g., Drug-Liking (primary endpoint), and Addiction Research Center Inventory (ARCI) Morphine–Benzedrine Group (MBG), Pentobarbital Chlorpromazine Alcohol Group (PCAG), and Lysergic Acid Diethylamide Group scales were evaluated at multiple time points up to 24 h postdose. Cognitive effects were evaluated using the Choice Reaction Time (CRT), Divided Attention (DAT) and Hopkins Verbal Learning Task—Revised tests. Principal results Peak scores for Drug-Liking VAS (maximum effect [E max ]) were significantly higher for both ALP doses than for PBO (p  max was significantly lower for all ESL doses than both ALP doses (p  max for ESL 800 mg was similar to that for PBO (least squares [LS] mean difference: 3.6; p = 0.19). At the three higher ESL doses (1600 mg and the supratherapeutic doses of 2000 mg and 2400 mg), Drug-Liking VAS E max was significantly higher than for PBO, although the differences were minimal (LS mean difference: 9.3–13.3 out of 100). For most secondary subjective endpoints (i.e., Good Effects VAS and High VAS, ARCI-MBG, Take Drug Again VAS, Overall Drug-Liking VAS, and ARCI-PCAG; p  Conclusion This study demonstrated that single doses of ESL may have less abuse liability than ALP in recreational sedative users. Although ESL had detectable subjective effects and showed some drug-‘liking’ at higher doses, the magnitude of these effects was small.

  • Assessment of the Abuse Potential of the Orexin Receptor Antagonist, Suvorexant, Compared With Zolpidem in a Randomized Crossover Study.
    Journal of Clinical Psychopharmacology, 2016
    Co-Authors: Kerri A. Schoedel, Janice Faulknor, Naama Levy-cooperman, Nicole Lewis, William P. Kennedy, Edward M Sellers, Hong Sun, Jang-ho Cha, Wen Liu
    Abstract:

    Suvorexant is a dual orexin receptor antagonist approved in the United States and Japan for the treatment of insomnia at a maximum dose of 20 mg. This randomized double-blind crossover study evaluated the abuse potential of suvorexant in 36 healthy recreational polydrug users with a history of sedative and psychedelic drug use. Single doses of suvorexant (40, 80, and 150 mg: 2-7.5 × maximum dose), zolpidem (15 and 30 mg: 1.5-3 × maximum dose), and placebo were administered, with a 10-day washout between treatments. Subjective and objective measures, including visual analog scales (VASs), Addiction Research Center Inventory, and cognitive/psychomotor tests, were evaluated for 24-hour postdose. Suvorexant had significantly greater peak effects on "drug liking" VAS (primary endpoint) than placebo. Although effects of suvorexant on abuse potential measures were generally similar to zolpidem, they remained constant across doses, whereas zolpidem often had greater effects at higher doses. Suvorexant (all doses) had significantly fewer effects than zolpidem 30 mg on secondary measures, such as "high" VAS, Bowdle VAS, and Addiction Research Center Inventory morphine-Benzedrine group. The overall incidence of abuse-related adverse events, such as euphoric mood and hallucination, was numerically lower with suvorexant than zolpidem. In agreement with its classification as a schedule IV drug, suvorexant demonstrated abuse potential, compared with placebo. The abuse potential was similar to zolpidem using certain measures, but with a reduced incidence of abuse-related adverse events. Although this suggests that the overall abuse liability of suvorexant may be lower than zolpidem, the actual abuse rates will be assessed with the postmarketing experience.

  • positive and negative subjective effects of extended release oxymorphone versus controlled release oxycodone in recreational opioid users
    Journal of opioid management, 2011
    Co-Authors: Kerri A. Schoedel, Stephen O Mcmorn, Mstat Bijan Chakraborty, Susan L Potts, R Kathleen N Zerbe, Edward M Sellers
    Abstract:

    Objective: To compare the subjective effects of oxymorphone extended release (OM-ER ) versus oxycodone controlled release (OC-CR ). Design: Randomized, double-blind, crossover study. Setting: Inpatient unit. Subjects: Healthy, nondependent recreational opioid users. Interventions: Single intact oral tablets that were placebo or contained OM-ER (15 and 30 mg) or OC-CR (30 and 60 mg). Doses were representative of mid-range doses for chronic pain and were calculated using an established opioid conversion table. Main outcome measures: Visual Analog Scales, Subjective Drug Value (SDV), and Addiction Research Center Inventory (ARCI) measured positive, negative, and balance effects and pupillometry. Equianalgesic comparisons were between OM-ER 15 mg versus OC-CR 30 mg (low doses) and OM-ER 30 mg versus OC-CR 60 mg (high doses). Results: Thirty-five subjects received all five treatments. Positive subjective effects were lower for OM-ER 15 mg versus OC-CR 30 mg and for OM-ER 30 mg versus OC-CR 60 mg in ARCI Morphine Benzedrine Group (p ≤ 0.01 for both), Good Effects (p < 0.001 for both), Rush (p < 0.001 for both), and High VAS (p < 0.001 for both). Nausea was higher with OC-CR (p ≤ 0.02), and Bad Effects were higher for OC-CR 60 mg versus OM-ER 30 mg (p < 0.001). Balance effects were lower for OM-ER versus OC-CR (Drug Liking, p < 0.001; Overall Drug Liking, p ≤ 0.006; SDV, p ≤ 0.008), except for Take Drug Again (p < 0.001 for OC-CR 30 mg versus OM-ER 15 mg; p = 0.18 for high-dose group). Euphoric mood, nausea, somnolence, vomiting, and dizziness were more common with OC-CR than OM-ER. Limitations: Single-dose design; use of healthy, recreational opioid users. Conclusions: At equianalgesic doses, single oral intact OM-ER produced lower positive, negative, and balance subjective effects than OC-CR , indicating that analgesic potency may not necessarily be reflected in subjective/objective effects.

  • reduced cognitive and psychomotor impairment with extended release oxymorphone versus controlled release oxycodone
    Pain Physician, 2010
    Co-Authors: Kerri A. Schoedel, Stephen O Mcmorn, Bijan Chakraborty, Kathleen Zerbe, Edward M Sellers
    Abstract:

    BACKGROUND Opioids provide effective pain control, yet have risks including adverse events (AEs) (e.g., constipation, nausea/vomiting, sedation) and cognitive/psychomotor effects. OBJECTIVE To compare cognitive and psychomotor effects of oxymorphone extended release (OM-ER) versus oxycodone controlled release (OC-CR). STUDY DESIGN Randomized, double-blind, 5-way crossover SETTING Single inpatient research unit METHODS Nondependent recreational opioid users were administered single intact oral tablets of placebo, OM-ER (15 and 30 mg), and OC-CR (30 and 60 mg), separated by a 7- to 21-day washout. The divided attention (DA) test measured psychomotor impairment (e.g., manual tracking [e.g., percentage over road], target accuracy [e.g., target hits], reaction time [hit latency]). Visual analog scales measured alertness/drowsiness, agitation/relaxation, and dizziness. Sedative, stimulant, and dysphoric effects were measured using the Addiction Research Center Inventory Pentobarbital-Chlorpromazine-Alcohol (PCAG), Benzedrine Group (BG), and Lysergic Acid Diethylamide (LSD) scales, respectively. Comparisons were made between equianalgesic doses (OM-ER 15 mg vs OC-CR 30 mg; OM-ER 30 mg vs OC-CR 60 mg), within active drug doses, and between active drugs and placebo using least squares (LS) mean difference of the peak maximum (Emax) or minimum (Emin) effect using linear mixed model analysis of covariance. RESULTS Thirty-five participants received all 5 treatments. Peak cognitive and psychomotor impairment (LS mean [SE]) was less with OM-ER than equianalgesic doses of OC-CR for reaction time (Emax hit latency, longer if impaired; 571.2 [13.4] vs 588.1 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], P<0.001 for OM-ER 30 mg vs OC-CR 60 mg, respectively); tracking accuracy (Emin percentage over road, lower if impaired; 71.4 [2.4] vs 65.3 [2.4], P=0.007; 69.9 [2.4] vs 59.4 [2.4], P<0.001), and target accuracy (Emin target hits percentage, lower if impaired; 81.0 [3.1] vs 74.5 [3.1], P=0.02; 79.4 [3.1] vs 66.1 [3.1], P<0.001). Several other DA measures showed that OC-CR, especially 60 mg, produced more psychomotor impairment than equianalgesic OM-ER. Compared to OM-ER, OC-CR produced more dizziness (Emax, P<0.001 for OM-ER 15 mg vs OC-CR 30 mg and for OM-ER 30 mg vs OC-CR 60 mg), drowsiness (Emax, P<0.001 for both equianalgesic dose groups), relaxation (Emin, P=0.003 for OM-ER 15 mg vs OC-CR 30 mg; P=0.001 for OM-ER 30 mg vs OC-CR 60 mg), dysphoria (Emax LSD, P<0.001 for both equianalgesic dose groups), and sedation (Emax, PCAG; P<0.001 for both equianalgesic dose groups) and less stimulation (BG, Emin; P=0.01 for OM-ER 15 mg vs OC-CR mg; P<0.001 for OM-ER 30 mg vs OC-CR 60 mg). Several AEs occurred more commonly with OC-CR than OM-ER (e.g., euphoria, nausea, somnolence, vomiting, dizziness). LIMITATIONS Participants were young, healthy volunteer nondependent recreational drug users, and only single doses were evaluated. The effects of tampering or higher doses were not assessed. CONCLUSION Single oral intact low and high doses of OM-ER produced less cognitive and psychomotor impairment plus less sedation than equianalgesic OC-CR in this exploratory study. ClinicalTrials.gov registration NCT00955110.

Katharina M. Rentsch - One of the best experts on this subject based on the ideXlab platform.

  • Generation of metabolites by an automated online metabolism method using human liver microsomes with subsequent identification by LC-MS(n), and metabolism of 11 cathinones
    Analytical and Bioanalytical Chemistry, 2012
    Co-Authors: Daniel M. Mueller, Katharina M. Rentsch
    Abstract:

    Human liver microsomes (HLMs) are used to simulate human xenobiotic metabolism in vitro. In forensic and clinical toxicology, HLMs are popularly used to study the metabolism of new designer drugs for example. In this work, we present an automated online extraction system we developed for HLM experiments, which was compared to a classical offline approach. Furthermore, we present studies on the metabolism of 11 cathinones; for eight of these, the metabolism has not previously been reported. Metabolites were identified based on MS^2 and MS^3 scans. Fifty-three substances encompassing various classes of drugs were employed to compare the established offline and the new online methods. The metabolism of each of the following 11 cathinones was studied using the new method: 3,4-methylenedioxy- N -benzylcathinone, benzedrone, butylone, dimethylcathinone, ethylone, flephedrone, methedrone, methylone, methylethylcathinone, naphyrone, and pentylone. The agreement between the offline and the online methods was good; a total of 158 metabolites were identified. Using only the offline method, 156 (98.7%) metabolites were identified, while 151 (95.6%) were identified using only the online method. The metabolic pathways identified for the 11 cathinones included the reduction of the keto group, desalkylation, hydroxylation, and desmethylenation in cathinones containing a methylenedioxy moiety. Our method provides a straightforward approach to identifying metabolites which can then be added to the library utilized by our clinical toxicological screening method. The performance of our method compares well with that of an established offline HLM procedure, but is as automated as possible.

Bijan Chakraborty - One of the best experts on this subject based on the ideXlab platform.

  • abuse liability assessment of eslicarbazepine acetate in healthy male and female recreational sedative users a phase i randomized controlled trial
    Epilepsy & Behavior, 2016
    Co-Authors: Naama Levycooperman, Kerri A. Schoedel, Bijan Chakraborty, David Blum, Hailong Cheng
    Abstract:

    Abstract Rationale Eslicarbazepine acetate (ESL) is a once-daily oral antiepileptic drug for the treatment of partial-onset seizures. Adverse events such as dizziness and somnolence reported in clinical studies suggest that ESL has detectable central nervous system (CNS) effects in addition to its antiepileptic effects. This Phase I study evaluated the abuse liability of ESL compared with that of alprazolam (ALP) and placebo (PBO) in recreational CNS depressant users. Methods In this single-dose, randomized, double-blind, PBO- and active-controlled crossover study, healthy recreational CNS depressant users who could discern between ALP 2 mg and PBO received single oral doses of each of the following treatments with a washout interval of ≥ 7 days between each treatment: ESL (800 mg, 1600 mg, 2000 mg, and 2400 mg); ALP (1.5 mg and 3.0 mg); and PBO. Subjective measures, including visual analog scales (VASs) e.g., Drug-Liking (primary endpoint), and Addiction Research Center Inventory (ARCI) Morphine–Benzedrine Group (MBG), Pentobarbital Chlorpromazine Alcohol Group (PCAG), and Lysergic Acid Diethylamide Group scales were evaluated at multiple time points up to 24 h postdose. Cognitive effects were evaluated using the Choice Reaction Time (CRT), Divided Attention (DAT) and Hopkins Verbal Learning Task—Revised tests. Principal results Peak scores for Drug-Liking VAS (maximum effect [E max ]) were significantly higher for both ALP doses than for PBO (p  max was significantly lower for all ESL doses than both ALP doses (p  max for ESL 800 mg was similar to that for PBO (least squares [LS] mean difference: 3.6; p = 0.19). At the three higher ESL doses (1600 mg and the supratherapeutic doses of 2000 mg and 2400 mg), Drug-Liking VAS E max was significantly higher than for PBO, although the differences were minimal (LS mean difference: 9.3–13.3 out of 100). For most secondary subjective endpoints (i.e., Good Effects VAS and High VAS, ARCI-MBG, Take Drug Again VAS, Overall Drug-Liking VAS, and ARCI-PCAG; p  Conclusion This study demonstrated that single doses of ESL may have less abuse liability than ALP in recreational sedative users. Although ESL had detectable subjective effects and showed some drug-‘liking’ at higher doses, the magnitude of these effects was small.

  • reduced cognitive and psychomotor impairment with extended release oxymorphone versus controlled release oxycodone
    Pain Physician, 2010
    Co-Authors: Kerri A. Schoedel, Stephen O Mcmorn, Bijan Chakraborty, Kathleen Zerbe, Edward M Sellers
    Abstract:

    BACKGROUND Opioids provide effective pain control, yet have risks including adverse events (AEs) (e.g., constipation, nausea/vomiting, sedation) and cognitive/psychomotor effects. OBJECTIVE To compare cognitive and psychomotor effects of oxymorphone extended release (OM-ER) versus oxycodone controlled release (OC-CR). STUDY DESIGN Randomized, double-blind, 5-way crossover SETTING Single inpatient research unit METHODS Nondependent recreational opioid users were administered single intact oral tablets of placebo, OM-ER (15 and 30 mg), and OC-CR (30 and 60 mg), separated by a 7- to 21-day washout. The divided attention (DA) test measured psychomotor impairment (e.g., manual tracking [e.g., percentage over road], target accuracy [e.g., target hits], reaction time [hit latency]). Visual analog scales measured alertness/drowsiness, agitation/relaxation, and dizziness. Sedative, stimulant, and dysphoric effects were measured using the Addiction Research Center Inventory Pentobarbital-Chlorpromazine-Alcohol (PCAG), Benzedrine Group (BG), and Lysergic Acid Diethylamide (LSD) scales, respectively. Comparisons were made between equianalgesic doses (OM-ER 15 mg vs OC-CR 30 mg; OM-ER 30 mg vs OC-CR 60 mg), within active drug doses, and between active drugs and placebo using least squares (LS) mean difference of the peak maximum (Emax) or minimum (Emin) effect using linear mixed model analysis of covariance. RESULTS Thirty-five participants received all 5 treatments. Peak cognitive and psychomotor impairment (LS mean [SE]) was less with OM-ER than equianalgesic doses of OC-CR for reaction time (Emax hit latency, longer if impaired; 571.2 [13.4] vs 588.1 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], P<0.001 for OM-ER 30 mg vs OC-CR 60 mg, respectively); tracking accuracy (Emin percentage over road, lower if impaired; 71.4 [2.4] vs 65.3 [2.4], P=0.007; 69.9 [2.4] vs 59.4 [2.4], P<0.001), and target accuracy (Emin target hits percentage, lower if impaired; 81.0 [3.1] vs 74.5 [3.1], P=0.02; 79.4 [3.1] vs 66.1 [3.1], P<0.001). Several other DA measures showed that OC-CR, especially 60 mg, produced more psychomotor impairment than equianalgesic OM-ER. Compared to OM-ER, OC-CR produced more dizziness (Emax, P<0.001 for OM-ER 15 mg vs OC-CR 30 mg and for OM-ER 30 mg vs OC-CR 60 mg), drowsiness (Emax, P<0.001 for both equianalgesic dose groups), relaxation (Emin, P=0.003 for OM-ER 15 mg vs OC-CR 30 mg; P=0.001 for OM-ER 30 mg vs OC-CR 60 mg), dysphoria (Emax LSD, P<0.001 for both equianalgesic dose groups), and sedation (Emax, PCAG; P<0.001 for both equianalgesic dose groups) and less stimulation (BG, Emin; P=0.01 for OM-ER 15 mg vs OC-CR mg; P<0.001 for OM-ER 30 mg vs OC-CR 60 mg). Several AEs occurred more commonly with OC-CR than OM-ER (e.g., euphoria, nausea, somnolence, vomiting, dizziness). LIMITATIONS Participants were young, healthy volunteer nondependent recreational drug users, and only single doses were evaluated. The effects of tampering or higher doses were not assessed. CONCLUSION Single oral intact low and high doses of OM-ER produced less cognitive and psychomotor impairment plus less sedation than equianalgesic OC-CR in this exploratory study. ClinicalTrials.gov registration NCT00955110.

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  • abuse liability assessment of eslicarbazepine acetate in healthy male and female recreational sedative users a phase i randomized controlled trial
    Epilepsy & Behavior, 2016
    Co-Authors: Naama Levycooperman, Kerri A. Schoedel, Bijan Chakraborty, David Blum, Hailong Cheng
    Abstract:

    Abstract Rationale Eslicarbazepine acetate (ESL) is a once-daily oral antiepileptic drug for the treatment of partial-onset seizures. Adverse events such as dizziness and somnolence reported in clinical studies suggest that ESL has detectable central nervous system (CNS) effects in addition to its antiepileptic effects. This Phase I study evaluated the abuse liability of ESL compared with that of alprazolam (ALP) and placebo (PBO) in recreational CNS depressant users. Methods In this single-dose, randomized, double-blind, PBO- and active-controlled crossover study, healthy recreational CNS depressant users who could discern between ALP 2 mg and PBO received single oral doses of each of the following treatments with a washout interval of ≥ 7 days between each treatment: ESL (800 mg, 1600 mg, 2000 mg, and 2400 mg); ALP (1.5 mg and 3.0 mg); and PBO. Subjective measures, including visual analog scales (VASs) e.g., Drug-Liking (primary endpoint), and Addiction Research Center Inventory (ARCI) Morphine–Benzedrine Group (MBG), Pentobarbital Chlorpromazine Alcohol Group (PCAG), and Lysergic Acid Diethylamide Group scales were evaluated at multiple time points up to 24 h postdose. Cognitive effects were evaluated using the Choice Reaction Time (CRT), Divided Attention (DAT) and Hopkins Verbal Learning Task—Revised tests. Principal results Peak scores for Drug-Liking VAS (maximum effect [E max ]) were significantly higher for both ALP doses than for PBO (p  max was significantly lower for all ESL doses than both ALP doses (p  max for ESL 800 mg was similar to that for PBO (least squares [LS] mean difference: 3.6; p = 0.19). At the three higher ESL doses (1600 mg and the supratherapeutic doses of 2000 mg and 2400 mg), Drug-Liking VAS E max was significantly higher than for PBO, although the differences were minimal (LS mean difference: 9.3–13.3 out of 100). For most secondary subjective endpoints (i.e., Good Effects VAS and High VAS, ARCI-MBG, Take Drug Again VAS, Overall Drug-Liking VAS, and ARCI-PCAG; p  Conclusion This study demonstrated that single doses of ESL may have less abuse liability than ALP in recreational sedative users. Although ESL had detectable subjective effects and showed some drug-‘liking’ at higher doses, the magnitude of these effects was small.