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Slide 1 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA
Slide 2 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26%
Slide 3 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing…
Slide 4 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time
Slide 5 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000.
Slide 6 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse?
Slide 7 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2
Slide 8 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence?
Slide 9 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability
Slide 10 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex
Slide 11 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level
Slide 12 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed
Slide 13 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability
Slide 14 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80%
Slide 15 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap
Slide 16 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works
Slide 17 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use
Slide 18 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA
Slide 19 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits
Slide 20 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit
Slide 21 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services
Slide 22 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work
Slide 23 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments
Slide 24 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine
Slide 25 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000.
Slide 26 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses McLellan et al., JAMA, 2000.
Slide 27 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses McLellan et al., JAMA, 2000. Addiction is Similar to Other Chronic Illnesses Because: Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated treatments Relapses to drug abuse can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery Therefore…
Slide 28 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses McLellan et al., JAMA, 2000. Addiction is Similar to Other Chronic Illnesses Because: Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated treatments Relapses to drug abuse can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery Therefore… Full recovery is a challenge but it is possible …
Slide 29 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses McLellan et al., JAMA, 2000. Addiction is Similar to Other Chronic Illnesses Because: Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated treatments Relapses to drug abuse can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery Therefore… Full recovery is a challenge but it is possible … DAT Recovery with prolonged abstinence from methamphetamine [C-11]d-threo-methylphenidate Volkow et al., J. Neuroscience, 2001. low high Normal Control Methamphetamine Abuser (1 month detoxification) Methamphetamine Abuser (24 month abstinent)
Slide 30 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses McLellan et al., JAMA, 2000. Addiction is Similar to Other Chronic Illnesses Because: Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated treatments Relapses to drug abuse can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery Therefore… Full recovery is a challenge but it is possible … DAT Recovery with prolonged abstinence from methamphetamine [C-11]d-threo-methylphenidate Volkow et al., J. Neuroscience, 2001. low high Normal Control Methamphetamine Abuser (1 month detoxification) Methamphetamine Abuser (24 month abstinent) Treatment Reduces Drug Use and Recidivism No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare Delaware Work Release Therapeutic Community (CREST) + Aftercare 3 Years After Release (N=448) p < 0.05, compared to No Treatment group Percentage of Participants Drug-Free Arrest-Free
Slide 31 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses McLellan et al., JAMA, 2000. Addiction is Similar to Other Chronic Illnesses Because: Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated treatments Relapses to drug abuse can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery Therefore… Full recovery is a challenge but it is possible … DAT Recovery with prolonged abstinence from methamphetamine [C-11]d-threo-methylphenidate Volkow et al., J. Neuroscience, 2001. low high Normal Control Methamphetamine Abuser (1 month detoxification) Methamphetamine Abuser (24 month abstinent) Treatment Reduces Drug Use and Recidivism No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare Delaware Work Release Therapeutic Community (CREST) + Aftercare 3 Years After Release (N=448) p < 0.05, compared to No Treatment group Percentage of Participants Drug-Free Arrest-Free We Need to Keep Our Eye on the Real Target Abstinence Functionality in Family, Work and Community In Treating Addiction…
Slide 32 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses McLellan et al., JAMA, 2000. Addiction is Similar to Other Chronic Illnesses Because: Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated treatments Relapses to drug abuse can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery Therefore… Full recovery is a challenge but it is possible … DAT Recovery with prolonged abstinence from methamphetamine [C-11]d-threo-methylphenidate Volkow et al., J. Neuroscience, 2001. low high Normal Control Methamphetamine Abuser (1 month detoxification) Methamphetamine Abuser (24 month abstinent) Treatment Reduces Drug Use and Recidivism No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare Delaware Work Release Therapeutic Community (CREST) + Aftercare 3 Years After Release (N=448) p < 0.05, compared to No Treatment group Percentage of Participants Drug-Free Arrest-Free We Need to Keep Our Eye on the Real Target Abstinence Functionality in Family, Work and Community In Treating Addiction… Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA HIV/AIDS Research
Slide 33 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses McLellan et al., JAMA, 2000. Addiction is Similar to Other Chronic Illnesses Because: Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated treatments Relapses to drug abuse can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery Therefore… Full recovery is a challenge but it is possible … DAT Recovery with prolonged abstinence from methamphetamine [C-11]d-threo-methylphenidate Volkow et al., J. Neuroscience, 2001. low high Normal Control Methamphetamine Abuser (1 month detoxification) Methamphetamine Abuser (24 month abstinent) Treatment Reduces Drug Use and Recidivism No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare Delaware Work Release Therapeutic Community (CREST) + Aftercare 3 Years After Release (N=448) p < 0.05, compared to No Treatment group Percentage of Participants Drug-Free Arrest-Free We Need to Keep Our Eye on the Real Target Abstinence Functionality in Family, Work and Community In Treating Addiction… Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA HIV/AIDS Research Drug Use Has Played a Prominent Role in the HIV/AIDS Epidemic In Several Ways Disease Transmission IV Drug Use Drug User Disinhibition Leading to High Risk Sexual Behaviors Progression of Disease
Slide 34 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses McLellan et al., JAMA, 2000. Addiction is Similar to Other Chronic Illnesses Because: Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated treatments Relapses to drug abuse can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery Therefore… Full recovery is a challenge but it is possible … DAT Recovery with prolonged abstinence from methamphetamine [C-11]d-threo-methylphenidate Volkow et al., J. Neuroscience, 2001. low high Normal Control Methamphetamine Abuser (1 month detoxification) Methamphetamine Abuser (24 month abstinent) Treatment Reduces Drug Use and Recidivism No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare Delaware Work Release Therapeutic Community (CREST) + Aftercare 3 Years After Release (N=448) p < 0.05, compared to No Treatment group Percentage of Participants Drug-Free Arrest-Free We Need to Keep Our Eye on the Real Target Abstinence Functionality in Family, Work and Community In Treating Addiction… Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA HIV/AIDS Research Drug Use Has Played a Prominent Role in the HIV/AIDS Epidemic In Several Ways Disease Transmission IV Drug Use Drug User Disinhibition Leading to High Risk Sexual Behaviors Progression of Disease Acceleration of HIV Degeneration of Dopamine Cells With Cocaine
Slide 35 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses McLellan et al., JAMA, 2000. Addiction is Similar to Other Chronic Illnesses Because: Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated treatments Relapses to drug abuse can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery Therefore… Full recovery is a challenge but it is possible … DAT Recovery with prolonged abstinence from methamphetamine [C-11]d-threo-methylphenidate Volkow et al., J. Neuroscience, 2001. low high Normal Control Methamphetamine Abuser (1 month detoxification) Methamphetamine Abuser (24 month abstinent) Treatment Reduces Drug Use and Recidivism No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare Delaware Work Release Therapeutic Community (CREST) + Aftercare 3 Years After Release (N=448) p < 0.05, compared to No Treatment group Percentage of Participants Drug-Free Arrest-Free We Need to Keep Our Eye on the Real Target Abstinence Functionality in Family, Work and Community In Treating Addiction… Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA HIV/AIDS Research Drug Use Has Played a Prominent Role in the HIV/AIDS Epidemic In Several Ways Disease Transmission IV Drug Use Drug User Disinhibition Leading to High Risk Sexual Behaviors Progression of Disease Acceleration of HIV Degeneration of Dopamine Cells With Cocaine Proportions of AIDS Cases in Adults & Adolescents by Exposure in the USA Source: Centers for Disease Control and Prevention (CDC) Men who have sex with men (MSM) Injection drug use Heterosexual contact MSM who inject drugs Year of Diagnosis % of Cases 70 60 50 40 30 20 10 0 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 Drugs of Abuse Have Had A Major Impact on the HIV/AIDS Epidemic
Slide 36 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses McLellan et al., JAMA, 2000. Addiction is Similar to Other Chronic Illnesses Because: Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated treatments Relapses to drug abuse can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery Therefore… Full recovery is a challenge but it is possible … DAT Recovery with prolonged abstinence from methamphetamine [C-11]d-threo-methylphenidate Volkow et al., J. Neuroscience, 2001. low high Normal Control Methamphetamine Abuser (1 month detoxification) Methamphetamine Abuser (24 month abstinent) Treatment Reduces Drug Use and Recidivism No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare Delaware Work Release Therapeutic Community (CREST) + Aftercare 3 Years After Release (N=448) p < 0.05, compared to No Treatment group Percentage of Participants Drug-Free Arrest-Free We Need to Keep Our Eye on the Real Target Abstinence Functionality in Family, Work and Community In Treating Addiction… Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA HIV/AIDS Research Drug Use Has Played a Prominent Role in the HIV/AIDS Epidemic In Several Ways Disease Transmission IV Drug Use Drug User Disinhibition Leading to High Risk Sexual Behaviors Progression of Disease Acceleration of HIV Degeneration of Dopamine Cells With Cocaine Proportions of AIDS Cases in Adults & Adolescents by Exposure in the USA Source: Centers for Disease Control and Prevention (CDC) Men who have sex with men (MSM) Injection drug use Heterosexual contact MSM who inject drugs Year of Diagnosis % of Cases 70 60 50 40 30 20 10 0 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 Drugs of Abuse Have Had A Major Impact on the HIV/AIDS Epidemic International Research Collaboration NIDA International Program Components Post-Doctoral Research Fellowship Technical Consultation Scientific Exchange Information Dissemination
Slide 37 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses McLellan et al., JAMA, 2000. Addiction is Similar to Other Chronic Illnesses Because: Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated treatments Relapses to drug abuse can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery Therefore… Full recovery is a challenge but it is possible … DAT Recovery with prolonged abstinence from methamphetamine [C-11]d-threo-methylphenidate Volkow et al., J. Neuroscience, 2001. low high Normal Control Methamphetamine Abuser (1 month detoxification) Methamphetamine Abuser (24 month abstinent) Treatment Reduces Drug Use and Recidivism No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare Delaware Work Release Therapeutic Community (CREST) + Aftercare 3 Years After Release (N=448) p < 0.05, compared to No Treatment group Percentage of Participants Drug-Free Arrest-Free We Need to Keep Our Eye on the Real Target Abstinence Functionality in Family, Work and Community In Treating Addiction… Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA HIV/AIDS Research Drug Use Has Played a Prominent Role in the HIV/AIDS Epidemic In Several Ways Disease Transmission IV Drug Use Drug User Disinhibition Leading to High Risk Sexual Behaviors Progression of Disease Acceleration of HIV Degeneration of Dopamine Cells With Cocaine Proportions of AIDS Cases in Adults & Adolescents by Exposure in the USA Source: Centers for Disease Control and Prevention (CDC) Men who have sex with men (MSM) Injection drug use Heterosexual contact MSM who inject drugs Year of Diagnosis % of Cases 70 60 50 40 30 20 10 0 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 Drugs of Abuse Have Had A Major Impact on the HIV/AIDS Epidemic International Research Collaboration NIDA International Program Components Post-Doctoral Research Fellowship Technical Consultation Scientific Exchange Information Dissemination Why focus on drug abuse internationally? Drug abuse is a global phenomenon 5 percent of people aged 15-64 II. Intertwined dual-epidemics of drug addiction & HIV/AIDS HIV Infections Attributed to Injection Drug Use and Risky Sexual Behaviors Related to Drug Abuse UNODC 2005 World Drug Report III. Take advantage of unique opportunities to advance scientific knowledge through research
Slide 38 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses McLellan et al., JAMA, 2000. Addiction is Similar to Other Chronic Illnesses Because: Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated treatments Relapses to drug abuse can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery Therefore… Full recovery is a challenge but it is possible … DAT Recovery with prolonged abstinence from methamphetamine [C-11]d-threo-methylphenidate Volkow et al., J. Neuroscience, 2001. low high Normal Control Methamphetamine Abuser (1 month detoxification) Methamphetamine Abuser (24 month abstinent) Treatment Reduces Drug Use and Recidivism No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare Delaware Work Release Therapeutic Community (CREST) + Aftercare 3 Years After Release (N=448) p < 0.05, compared to No Treatment group Percentage of Participants Drug-Free Arrest-Free We Need to Keep Our Eye on the Real Target Abstinence Functionality in Family, Work and Community In Treating Addiction… Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA HIV/AIDS Research Drug Use Has Played a Prominent Role in the HIV/AIDS Epidemic In Several Ways Disease Transmission IV Drug Use Drug User Disinhibition Leading to High Risk Sexual Behaviors Progression of Disease Acceleration of HIV Degeneration of Dopamine Cells With Cocaine Proportions of AIDS Cases in Adults & Adolescents by Exposure in the USA Source: Centers for Disease Control and Prevention (CDC) Men who have sex with men (MSM) Injection drug use Heterosexual contact MSM who inject drugs Year of Diagnosis % of Cases 70 60 50 40 30 20 10 0 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 Drugs of Abuse Have Had A Major Impact on the HIV/AIDS Epidemic International Research Collaboration NIDA International Program Components Post-Doctoral Research Fellowship Technical Consultation Scientific Exchange Information Dissemination Why focus on drug abuse internationally? Drug abuse is a global phenomenon 5 percent of people aged 15-64 II. Intertwined dual-epidemics of drug addiction & HIV/AIDS HIV Infections Attributed to Injection Drug Use and Risky Sexual Behaviors Related to Drug Abuse UNODC 2005 World Drug Report III. Take advantage of unique opportunities to advance scientific knowledge through research NIDA Supports International Drug Abuse Research In Numerous Ways Fund international research Provide training and exchange opportunities Set international research priorities Organize & sponsor conferences and meetings Binational agreements Dissemination of information
Slide 39 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses McLellan et al., JAMA, 2000. Addiction is Similar to Other Chronic Illnesses Because: Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated treatments Relapses to drug abuse can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery Therefore… Full recovery is a challenge but it is possible … DAT Recovery with prolonged abstinence from methamphetamine [C-11]d-threo-methylphenidate Volkow et al., J. Neuroscience, 2001. low high Normal Control Methamphetamine Abuser (1 month detoxification) Methamphetamine Abuser (24 month abstinent) Treatment Reduces Drug Use and Recidivism No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare Delaware Work Release Therapeutic Community (CREST) + Aftercare 3 Years After Release (N=448) p < 0.05, compared to No Treatment group Percentage of Participants Drug-Free Arrest-Free We Need to Keep Our Eye on the Real Target Abstinence Functionality in Family, Work and Community In Treating Addiction… Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA HIV/AIDS Research Drug Use Has Played a Prominent Role in the HIV/AIDS Epidemic In Several Ways Disease Transmission IV Drug Use Drug User Disinhibition Leading to High Risk Sexual Behaviors Progression of Disease Acceleration of HIV Degeneration of Dopamine Cells With Cocaine Proportions of AIDS Cases in Adults & Adolescents by Exposure in the USA Source: Centers for Disease Control and Prevention (CDC) Men who have sex with men (MSM) Injection drug use Heterosexual contact MSM who inject drugs Year of Diagnosis % of Cases 70 60 50 40 30 20 10 0 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 Drugs of Abuse Have Had A Major Impact on the HIV/AIDS Epidemic International Research Collaboration NIDA International Program Components Post-Doctoral Research Fellowship Technical Consultation Scientific Exchange Information Dissemination Why focus on drug abuse internationally? Drug abuse is a global phenomenon 5 percent of people aged 15-64 II. Intertwined dual-epidemics of drug addiction & HIV/AIDS HIV Infections Attributed to Injection Drug Use and Risky Sexual Behaviors Related to Drug Abuse UNODC 2005 World Drug Report III. Take advantage of unique opportunities to advance scientific knowledge through research NIDA Supports International Drug Abuse Research In Numerous Ways Fund international research Provide training and exchange opportunities Set international research priorities Organize & sponsor conferences and meetings Binational agreements Dissemination of information Where Do We Need to Go From Here? We Need to… Advance the SCIENCE Erase the STIGMA and to… Erase the STIGMA and to…
Slide 40 - HIV/AIDS Research Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25 >25 Addiction is a Developmental Disease: It Starts Early 26% Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000. Do Adolescents React Differently than Adults to Substances of Abuse? Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2 Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Why do some people become addicted while others do not? Vulnerability We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S .003 .01 .03 .1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80% Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap Prevention Works Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use HIV/AIDS Research Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA Source: Adapted from Volkow et al., Neuropharmacology, 2004. Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits This is why treatment is essential This is why addicts can’t just quit Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services Treatment Can Work We Are Using Science to Develop Even Better Treatments Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses McLellan et al., JAMA, 2000. Addiction is Similar to Other Chronic Illnesses Because: Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated treatments Relapses to drug abuse can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery Therefore… Full recovery is a challenge but it is possible … DAT Recovery with prolonged abstinence from methamphetamine [C-11]d-threo-methylphenidate Volkow et al., J. Neuroscience, 2001. low high Normal Control Methamphetamine Abuser (1 month detoxification) Methamphetamine Abuser (24 month abstinent) Treatment Reduces Drug Use and Recidivism No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare No treatment CREST Dropouts CREST Completers CREST Completers + Aftercare Delaware Work Release Therapeutic Community (CREST) + Aftercare 3 Years After Release (N=448) p < 0.05, compared to No Treatment group Percentage of Participants Drug-Free Arrest-Free We Need to Keep Our Eye on the Real Target Abstinence Functionality in Family, Work and Community In Treating Addiction… Treatment Interventions (New Targets & New Strategies) Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA HIV/AIDS Research Drug Use Has Played a Prominent Role in the HIV/AIDS Epidemic In Several Ways Disease Transmission IV Drug Use Drug User Disinhibition Leading to High Risk Sexual Behaviors Progression of Disease Acceleration of HIV Degeneration of Dopamine Cells With Cocaine Proportions of AIDS Cases in Adults & Adolescents by Exposure in the USA Source: Centers for Disease Control and Prevention (CDC) Men who have sex with men (MSM) Injection drug use Heterosexual contact MSM who inject drugs Year of Diagnosis % of Cases 70 60 50 40 30 20 10 0 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 Drugs of Abuse Have Had A Major Impact on the HIV/AIDS Epidemic International Research Collaboration NIDA International Program Components Post-Doctoral Research Fellowship Technical Consultation Scientific Exchange Information Dissemination Why focus on drug abuse internationally? Drug abuse is a global phenomenon 5 percent of people aged 15-64 II. Intertwined dual-epidemics of drug addiction & HIV/AIDS HIV Infections Attributed to Injection Drug Use and Risky Sexual Behaviors Related to Drug Abuse UNODC 2005 World Drug Report III. Take advantage of unique opportunities to advance scientific knowledge through research NIDA Supports International Drug Abuse Research In Numerous Ways Fund international research Provide training and exchange opportunities Set international research priorities Organize & sponsor conferences and meetings Binational agreements Dissemination of information Where Do We Need to Go From Here? We Need to… Advance the SCIENCE Erase the STIGMA and to… Erase the STIGMA and to… For More Information NIDA Public Information: www.nida.nih.gov www.drugabuse.gov NIDA International Program: www.international.drugabuse.gov www.drugabuse.gov
 

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