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Long-acting cocaine esterase (LACE): Assessing the treatment approach
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Abstracts / Drug and Alcohol Dependence 140 (2014) e169–e251
Long-acting cocaine esterase (LACE): Assessing the treatment approach Edward M. Sellers, M.K. Romach DL Global Partners Inc. and University of Toronto, Toronto, ON, Canada Aims: No medications have been approved for the treatment of cocaine dependence. The aim of this work was to determine the need for and commercial viability of a high turn-over cocaine esterase with high specificity and selectivity with activity for 2–4 weeks after subcutaneous injection for treatment of cocaine dependence. Methods: The Technology Transfer Office, University of Michigan requested an independent assessment of the commercial viability of this treatment approach based in part on Collins GT et al., Neuropsychopharmacology. 2012; 37:1092–1103. Thirteen internationally recognized clinical, policy and research leaders in the addiction field participated in a structured phone interview. Six were former CPDD Awardees. Results: Direct quotes – Need: “no benefit from medications; little benefit from outpatient treatment; some benefit from inpatient treatment; but nothing works”. LACE would be a “substantial advance” and “preferred treatment” if patients would take for at least 6 months. “It takes 2 years to get your life back”. Advantages: “solves the compliance problem” and “removes the reinforcing effects of cocaine” “so over time other interventions can work”. Target patients: “Any one who was motivated”; approvable indication and label “relapse prevention”. Reimbursement: “would follow as it has for buprenorphine and naltrexone”. “Higher functioning professionals with a lot to lose would pay directly”; “Accountable/Managed Care and HMOs”. “The Affordable Care Act will help”. Challenges: “patient acceptance”; “antibody formation”; “polydrug use”; “injection volume”; “need physician involvement”; “few funding sources”; “regulatory requirements”; “cost of medication”. Market size: Probably $200–350 M 3 years after approval and launch. Conclusions: LACE is potentially a superior treatment approach to cocaine dependence, commercially viable and addresses an unmet public health need. Substantial development challenges exist. Government support, an expedited efficacy development plan focused on safety combined with post-marketing studies might be considered. Financial support: Technology Transfer Office, University of Michigan. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.562 Eating high fat chow increases sensitivity of female rats to indirect-acting but not direct-acting dopamine receptor agonists Katherine M. Serafine 1 , T.A. Bentley 1 , A.E. Grenier 1 , C.P. France 1,2 1
Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States 2 Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States Aims: Diet can impact sensitivity to drugs that act indirectly (i.e. cocaine) or directly (i.e. quinpirole) on dopamine receptors. Eating high fat chow increases sensitivity of female but not male rats to cocaine-induced locomotion and sensitization. Eating high fat chow increases sensitivity of male rats to quinpirole-induced yawning and results in insulin resistance; it is not known whether this diet has similar effects in females.
Methods: Female Sprague-Dawley rats had free or restricted access (i.e., body weight matched to standard chow fed controls) to high fat chow (34.3% fat) or free access to standard chow (5.7% fat). Results: Quinpirole (0.0032–0.32 mg/kg) dose-dependently induced hypothermia and modest rates of yawning. Despite the development of insulin resistance within just 10 days of eating high fat chow, quinpirole dose–response curves for yawning and hypothermia were unchanged over 7 weeks of access to high fat chow (both groups) or standard chow. Rats eating high fat chow were more sensitive to cocaine-induced (1–17.8 mg/kg) locomotion; however, rats eating standard chow also became sensitive following repeated administration of cocaine. Conclusions: That eating high fat chow increased sensitivity of female rats to indirect-acting, but not direct-acting dopamine receptor agonists suggests that eating high fat food might increase vulnerability to abuse drugs like cocaine, particularly among females. Financial support: CPF is supported by the NIDA Senior Scientist Award (K05 DA017918). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.563 Does craving predict substance use for different substance use disorders? An ecological momentary assessment study in patients with alcohol, tobacco, cannabis and heroin dependence F. Serre 1,3 , M. Fatseas 1,3 , J. Swendsen 2 , Marc Auriacombe 1,3 1
Addiction Psychiatry, University Bordeaux/CNRS USR 3413, Bordeaux, France 2 CNRS UMR 5287 INCIA, University Bordeaux, Bordeaux, France 3 CH Ch. Perrens et CHU de Bordeaux, Bordeaux, France Aims: The objective of this study was to assess substancedependent patients in their natural environment using Ecological Momentary Assessment (EMA) to examine the prospective association between craving and substance use. Methods: A total of 132 participants beginning treatment for addiction were recruited from an outpatient treatment center and completed 2 weeks of computerized ambulatory monitoring of daily life experiences. The main substance of dependence was alcohol (n = 39), opiates (n = 32), tobacco (n = 32), or cannabis (n = 29). Patients were asked to describe in real-time their experience of craving and substance use. Data were analyzed using hierarchical linear models (HLM). Results: Craving intensity was strongly predictive of use of the substance that initiated treatment, whether substance use was measured during the same assessment ( = .429, p < 10.4), or prospectively over the subsequent 3-h period ( = .137, p = 0.002). When the prospective models were adjusted for initial substance use, craving remained a significant predictor of substance use over the subsequent 3-h period ( = .137, p = 0.002). These effects were equivalent for men and women, and did not differ by type of substance use disorder. This association was no longer significant for substance use 6 h later ( = .035, p > 0.05). Substance use was also examined as a predictor of later craving intensity, but the association was not significant when adjusting for initial craving levels. Conclusions: This study highlights the central role of craving in determining substance use during quit attempts for a wide variety of substances (legal/illegal, stimulant/sedative).
Abstracts / Drug and Alcohol Dependence 140 (2014) e169–e251
Long-acting cocaine esterase (LACE): Assessing the treatment approach Edward M. Sellers, M.K. Romach DL Global Partners Inc. and University of Toronto, Toronto, ON, Canada Aims: No medications have been approved for the treatment of cocaine dependence. The aim of this work was to determine the need for and commercial viability of a high turn-over cocaine esterase with high specificity and selectivity with activity for 2–4 weeks after subcutaneous injection for treatment of cocaine dependence. Methods: The Technology Transfer Office, University of Michigan requested an independent assessment of the commercial viability of this treatment approach based in part on Collins GT et al., Neuropsychopharmacology. 2012; 37:1092–1103. Thirteen internationally recognized clinical, policy and research leaders in the addiction field participated in a structured phone interview. Six were former CPDD Awardees. Results: Direct quotes – Need: “no benefit from medications; little benefit from outpatient treatment; some benefit from inpatient treatment; but nothing works”. LACE would be a “substantial advance” and “preferred treatment” if patients would take for at least 6 months. “It takes 2 years to get your life back”. Advantages: “solves the compliance problem” and “removes the reinforcing effects of cocaine” “so over time other interventions can work”. Target patients: “Any one who was motivated”; approvable indication and label “relapse prevention”. Reimbursement: “would follow as it has for buprenorphine and naltrexone”. “Higher functioning professionals with a lot to lose would pay directly”; “Accountable/Managed Care and HMOs”. “The Affordable Care Act will help”. Challenges: “patient acceptance”; “antibody formation”; “polydrug use”; “injection volume”; “need physician involvement”; “few funding sources”; “regulatory requirements”; “cost of medication”. Market size: Probably $200–350 M 3 years after approval and launch. Conclusions: LACE is potentially a superior treatment approach to cocaine dependence, commercially viable and addresses an unmet public health need. Substantial development challenges exist. Government support, an expedited efficacy development plan focused on safety combined with post-marketing studies might be considered. Financial support: Technology Transfer Office, University of Michigan. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.562 Eating high fat chow increases sensitivity of female rats to indirect-acting but not direct-acting dopamine receptor agonists Katherine M. Serafine 1 , T.A. Bentley 1 , A.E. Grenier 1 , C.P. France 1,2 1
Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States 2 Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States Aims: Diet can impact sensitivity to drugs that act indirectly (i.e. cocaine) or directly (i.e. quinpirole) on dopamine receptors. Eating high fat chow increases sensitivity of female but not male rats to cocaine-induced locomotion and sensitization. Eating high fat chow increases sensitivity of male rats to quinpirole-induced yawning and results in insulin resistance; it is not known whether this diet has similar effects in females.
Methods: Female Sprague-Dawley rats had free or restricted access (i.e., body weight matched to standard chow fed controls) to high fat chow (34.3% fat) or free access to standard chow (5.7% fat). Results: Quinpirole (0.0032–0.32 mg/kg) dose-dependently induced hypothermia and modest rates of yawning. Despite the development of insulin resistance within just 10 days of eating high fat chow, quinpirole dose–response curves for yawning and hypothermia were unchanged over 7 weeks of access to high fat chow (both groups) or standard chow. Rats eating high fat chow were more sensitive to cocaine-induced (1–17.8 mg/kg) locomotion; however, rats eating standard chow also became sensitive following repeated administration of cocaine. Conclusions: That eating high fat chow increased sensitivity of female rats to indirect-acting, but not direct-acting dopamine receptor agonists suggests that eating high fat food might increase vulnerability to abuse drugs like cocaine, particularly among females. Financial support: CPF is supported by the NIDA Senior Scientist Award (K05 DA017918). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.563 Does craving predict substance use for different substance use disorders? An ecological momentary assessment study in patients with alcohol, tobacco, cannabis and heroin dependence F. Serre 1,3 , M. Fatseas 1,3 , J. Swendsen 2 , Marc Auriacombe 1,3 1
Addiction Psychiatry, University Bordeaux/CNRS USR 3413, Bordeaux, France 2 CNRS UMR 5287 INCIA, University Bordeaux, Bordeaux, France 3 CH Ch. Perrens et CHU de Bordeaux, Bordeaux, France Aims: The objective of this study was to assess substancedependent patients in their natural environment using Ecological Momentary Assessment (EMA) to examine the prospective association between craving and substance use. Methods: A total of 132 participants beginning treatment for addiction were recruited from an outpatient treatment center and completed 2 weeks of computerized ambulatory monitoring of daily life experiences. The main substance of dependence was alcohol (n = 39), opiates (n = 32), tobacco (n = 32), or cannabis (n = 29). Patients were asked to describe in real-time their experience of craving and substance use. Data were analyzed using hierarchical linear models (HLM). Results: Craving intensity was strongly predictive of use of the substance that initiated treatment, whether substance use was measured during the same assessment ( = .429, p < 10.4), or prospectively over the subsequent 3-h period ( = .137, p = 0.002). When the prospective models were adjusted for initial substance use, craving remained a significant predictor of substance use over the subsequent 3-h period ( = .137, p = 0.002). These effects were equivalent for men and women, and did not differ by type of substance use disorder. This association was no longer significant for substance use 6 h later ( = .035, p > 0.05). Substance use was also examined as a predictor of later craving intensity, but the association was not significant when adjusting for initial craving levels. Conclusions: This study highlights the central role of craving in determining substance use during quit attempts for a wide variety of substances (legal/illegal, stimulant/sedative).