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Effects of withdrawal from chronic nicotine on emotional and cognitive behaviors in adult and adolescent mice
Abstracts / Drug and Alcohol Dependence 156 (2015) e102–e182
Novel psychoactive substance use in the European Union Scott P. Novak 1 , Anders Hakansson 2 , Jens Reimer 5 , Jose Martinez-Raga 4 , Jennifer Lorvick 3 1 Behavioral Epidemiology, RTI International, Research Triangle Park, NC, United States 2 Division of Psychiatry, U of Lund, Lund, Sweden 3 RTI International, RTI, San Francisco, CA, United States 4 Teaching Unit of Psychiatry and Psychological Medicine, U of Valencia, Valencia, Spain 5 Centre for Interdisciplinary Addiction Research, Hamburg Medical, Hamburg, Germany
Aims: Novel psychoactive substances (e.g., bath salts, Krokodil, synthetic marijuana) are synthetic, semi-synthetic or natural compounds, often advertised and sold as ‘legal’ alternatives to illicit drugs. The current study is among the first population-based studies in the EU to identify their prevalence and characteristics. Methods: General population surveys, modeled after the United States’ National Survey of Drug Use and Health, were conducted by RTI International in seven European countries (29 metropolitan strata, sample n = 22,057) in 2014. Self-report (in English or native language) surveys among persons aged 12 or older were collected and weighted to achieve country-specific representative estimates. Results: The lifetime estimates for NPS ranged from 0.7% (Denmark) to 2.2% (Great Britain), with a mean of 1.8% and a population estimate of 5.5 million. An estimated 500,000 (0.5%) persons reported past-year NPS. Controlling for country, latent class models indicated six classes of past-year illicit drug use, with NPS present in a homogenous class characterized by males (AOR = 2.5, p < .001), whites at higher risk relative to black/African descent (AOR = 1.6, p < .05), and Asian (AOR = 3.3, p < .001). Youth (ages 18–24) were at higher risk for NPS relative to those ages 12–17 (AOR = 1.5, p < .001) and 35+ (AOR = 1.6, p < .001). Mood/anxiety disorders conferred higher risk of NPS compared to those with no disorder (AOR = 2.5, p < .001), or subthreshold symptom levels (AOR = 1.6, p < .001). NPS users also reported a greater use of social media. Conclusions: With the increasing erosion of geographic boundaries and increased increased communication, studies are desperately needed to identify the international landscape of drug use. Additional waves are planned to identify trends in transmission patterns between countries and population sub-groups. Financial support: Shire, NIH, RTI International, the European Drug Union. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.448 Effects of withdrawal from chronic nicotine on emotional and cognitive behaviors in adult and adolescent mice Paul A. Nucero 2 , Erica Holliday 1 , Munir G. Kutlu 1 , Thomas Gould 1 , Ellen Unterwald 3 1 Psychology, Temple University, Philadelphia, PA, United States 2 Center for Substance Abuse Research, Temple University School of Medicine, Ambler, PA, United States 3 Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, United States
Aims: Nicotine dependence correlates with increased risk for emotional, cognitive, and neurological impairments later in
e165
life. This study investigated the long-term effects of nicotine on measures of depression, drug reward, anxiety, and learning in adolescent and adult mice. Methods: Male C57BL6/J mice received saline or nicotine (12.6 mg/kg/day) for 12 days via osmotic pumps implanted on postnatal day 32 (adolescent) or 54 (adults). 24 h or 30 days after cessation of nicotine/saline, mice were tested for the conditioned rewarding effects of cocaine and morphine, depression-like behaviors using the forced swim test, anxiety-like effects with the elevated plus maze, or learning effects using contextual fear conditioning. Results: Increased depression-like responses were seen in both adolescent and adult mice when tested during acute (24 h) nicotine withdrawal (2-way ANOVA, p < 0.01). Heightened depression-like behaviors persisted when tested 30 days later in mice exposed as adolescents (p < 0.01, N = 15–16/group), but not those exposed as adults. No differences in the conditioned rewarding effects of cocaine (10 mg/kg) or morphine (5 mg/kg) between age or nicotine exposure were found. Adolescent mice, but not adults, exposed to nicotine showed a non-significant increase in anxiety (lower open arm time) when tested after 30 days of abstinence. Nicotine exposure during adolescence caused deficits in contextual fear learning indicated by lower levels of freezing to the context as compared to saline controls. Conclusions: These results demonstrate that nicotine exposure and withdrawal can have long-term effects on emotional and cognitive functioning, particularly when nicotine exposure occurs during the critical period of adolescence. Potential mechanisms underlying this age-specific response are under investigation. Financial support: Supported in part by PA Department of Health. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.449 Physiologic effects of dronabinol during opioid withdrawal in humans Paul A. Nuzzo 1 , Michelle R. Lofwall 1 , Samy-Claude Elayi 2 , Katie Gill 1 , Shanna Babalonis 1 , Sharon L. Walsh 1 1
Behavioral Science, Center on Drug and Alcohol Research, Univ of Kentucky, Lexington, KY, United States 2 Internal Medicine, Univ of Kentucky, Lexington, KY, United States Aims: Dronabinol, a CB1 agonist, is currently being evaluated for its efficacy in relieving opioid withdrawal (see abstract by Gill et al.). This abstract reports on safety outcomes from that proof-ofconcept study. Methods: Ten healthy non-treatment seeking adult volunteers with opioid dependence completed this within-subject, randomized, double-blind study. Participants were inpatients maintained on oral oxycodone (OC) 30 mg at 8 am, and 12, 6 & 10 pm daily. Placebo (P) was substituted for three OC doses preceding each experimental session (sessions >72 h apart) to ensure that opioid withdrawal was present. Initial test doses (one/session) included P, OC (30 and 60 mg), and dronabinol (DB: 5, 10, 20, and 40 mg). DB 40 mg was replaced with 30 mg due to safety concerns. Physiologic parameters [e.g., systolic and diastolic blood pressure (SBP, DBP), heart rate (HR)] were measured before and for 6 h after drug administration. Analyses excluded DB 40 mg data; n = 10 for all doses except n = 7 for DB 30 mg. Results: Only two volunteers received DB 40 mg; both experienced sustained sinus tachycardia (i.e., HR > 100 bpm) for ∼2.5 h
Novel psychoactive substance use in the European Union Scott P. Novak 1 , Anders Hakansson 2 , Jens Reimer 5 , Jose Martinez-Raga 4 , Jennifer Lorvick 3 1 Behavioral Epidemiology, RTI International, Research Triangle Park, NC, United States 2 Division of Psychiatry, U of Lund, Lund, Sweden 3 RTI International, RTI, San Francisco, CA, United States 4 Teaching Unit of Psychiatry and Psychological Medicine, U of Valencia, Valencia, Spain 5 Centre for Interdisciplinary Addiction Research, Hamburg Medical, Hamburg, Germany
Aims: Novel psychoactive substances (e.g., bath salts, Krokodil, synthetic marijuana) are synthetic, semi-synthetic or natural compounds, often advertised and sold as ‘legal’ alternatives to illicit drugs. The current study is among the first population-based studies in the EU to identify their prevalence and characteristics. Methods: General population surveys, modeled after the United States’ National Survey of Drug Use and Health, were conducted by RTI International in seven European countries (29 metropolitan strata, sample n = 22,057) in 2014. Self-report (in English or native language) surveys among persons aged 12 or older were collected and weighted to achieve country-specific representative estimates. Results: The lifetime estimates for NPS ranged from 0.7% (Denmark) to 2.2% (Great Britain), with a mean of 1.8% and a population estimate of 5.5 million. An estimated 500,000 (0.5%) persons reported past-year NPS. Controlling for country, latent class models indicated six classes of past-year illicit drug use, with NPS present in a homogenous class characterized by males (AOR = 2.5, p < .001), whites at higher risk relative to black/African descent (AOR = 1.6, p < .05), and Asian (AOR = 3.3, p < .001). Youth (ages 18–24) were at higher risk for NPS relative to those ages 12–17 (AOR = 1.5, p < .001) and 35+ (AOR = 1.6, p < .001). Mood/anxiety disorders conferred higher risk of NPS compared to those with no disorder (AOR = 2.5, p < .001), or subthreshold symptom levels (AOR = 1.6, p < .001). NPS users also reported a greater use of social media. Conclusions: With the increasing erosion of geographic boundaries and increased increased communication, studies are desperately needed to identify the international landscape of drug use. Additional waves are planned to identify trends in transmission patterns between countries and population sub-groups. Financial support: Shire, NIH, RTI International, the European Drug Union. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.448 Effects of withdrawal from chronic nicotine on emotional and cognitive behaviors in adult and adolescent mice Paul A. Nucero 2 , Erica Holliday 1 , Munir G. Kutlu 1 , Thomas Gould 1 , Ellen Unterwald 3 1 Psychology, Temple University, Philadelphia, PA, United States 2 Center for Substance Abuse Research, Temple University School of Medicine, Ambler, PA, United States 3 Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, United States
Aims: Nicotine dependence correlates with increased risk for emotional, cognitive, and neurological impairments later in
e165
life. This study investigated the long-term effects of nicotine on measures of depression, drug reward, anxiety, and learning in adolescent and adult mice. Methods: Male C57BL6/J mice received saline or nicotine (12.6 mg/kg/day) for 12 days via osmotic pumps implanted on postnatal day 32 (adolescent) or 54 (adults). 24 h or 30 days after cessation of nicotine/saline, mice were tested for the conditioned rewarding effects of cocaine and morphine, depression-like behaviors using the forced swim test, anxiety-like effects with the elevated plus maze, or learning effects using contextual fear conditioning. Results: Increased depression-like responses were seen in both adolescent and adult mice when tested during acute (24 h) nicotine withdrawal (2-way ANOVA, p < 0.01). Heightened depression-like behaviors persisted when tested 30 days later in mice exposed as adolescents (p < 0.01, N = 15–16/group), but not those exposed as adults. No differences in the conditioned rewarding effects of cocaine (10 mg/kg) or morphine (5 mg/kg) between age or nicotine exposure were found. Adolescent mice, but not adults, exposed to nicotine showed a non-significant increase in anxiety (lower open arm time) when tested after 30 days of abstinence. Nicotine exposure during adolescence caused deficits in contextual fear learning indicated by lower levels of freezing to the context as compared to saline controls. Conclusions: These results demonstrate that nicotine exposure and withdrawal can have long-term effects on emotional and cognitive functioning, particularly when nicotine exposure occurs during the critical period of adolescence. Potential mechanisms underlying this age-specific response are under investigation. Financial support: Supported in part by PA Department of Health. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.449 Physiologic effects of dronabinol during opioid withdrawal in humans Paul A. Nuzzo 1 , Michelle R. Lofwall 1 , Samy-Claude Elayi 2 , Katie Gill 1 , Shanna Babalonis 1 , Sharon L. Walsh 1 1
Behavioral Science, Center on Drug and Alcohol Research, Univ of Kentucky, Lexington, KY, United States 2 Internal Medicine, Univ of Kentucky, Lexington, KY, United States Aims: Dronabinol, a CB1 agonist, is currently being evaluated for its efficacy in relieving opioid withdrawal (see abstract by Gill et al.). This abstract reports on safety outcomes from that proof-ofconcept study. Methods: Ten healthy non-treatment seeking adult volunteers with opioid dependence completed this within-subject, randomized, double-blind study. Participants were inpatients maintained on oral oxycodone (OC) 30 mg at 8 am, and 12, 6 & 10 pm daily. Placebo (P) was substituted for three OC doses preceding each experimental session (sessions >72 h apart) to ensure that opioid withdrawal was present. Initial test doses (one/session) included P, OC (30 and 60 mg), and dronabinol (DB: 5, 10, 20, and 40 mg). DB 40 mg was replaced with 30 mg due to safety concerns. Physiologic parameters [e.g., systolic and diastolic blood pressure (SBP, DBP), heart rate (HR)] were measured before and for 6 h after drug administration. Analyses excluded DB 40 mg data; n = 10 for all doses except n = 7 for DB 30 mg. Results: Only two volunteers received DB 40 mg; both experienced sustained sinus tachycardia (i.e., HR > 100 bpm) for ∼2.5 h