Development of Medications for Heroin and Cocaine Addiction and Regulatory Aspects of Abuse Liability Testing

PREFACE: What Do You Mean by “Translational Research”? An Enquiry Through Animal and Translational Models for CNS Drug Discovery: Reward Deficit Disorders

“…Furthermore, Rocha and colleagues present a very valuable discussion on the assessment of and regulatory aspects of abuse liability potential of candidate drugs. 16 The study of addictions has evolved considerably since the early theories of mesolimbic dopamine reward and motivated behavior ( cf ., [87][88][89] ). Central to this evolving conceptual framework is the cyclical nature of addiction and associated neural adaptations in which impulsivity and loss of control play a central role.…”

“…Cocaine and alcohol withdrawal, on the other hand, are associated more with psychological symptoms such as depression, fatigue, anxiety and irritability, although sleep disturbances such as insomnia are prominent. 16,93,104 These are powerful inducers to relapse, 90 and the prevention of relapse is a major therapeutic goal. 15,93,94 As discussed in the fi rst volume of this book series, allostatic changes in response to chronic stress is thought to underlie many psychiatric disorders and consequently there is a great degree of comorbidity between psychiatric and reward defi cit disorders.…”

“…94 Buprenorphine (Subutex®), buprenorphine/naloxone (Suboxone®) and methadone are substitution or replacement therapies for opiate (heroin) abuse, and there are currently no effective medications to treat cocaine addiction, although GABA B receptor agonists such as baclofen (Kemstro®/Lioresal®), the ␣ 1 adrenergic agonist ( inter alia ) modafi nil (Provigil®), dopamine D 2 partial agonists (aripiprazole, Abilify®), or D 1 antagonists (ecopipam) have been evaluated. 16,19 In general though, the treatment of reward defi cit and impulse control disorders combine pharmacological interventions with various forms of psychosocial counseling and behavioral therapy such as cognitive behavioral therapy. 16,24,106,107 In addition to the NIH initiatives supporting academic, industrial and government collaborations described above, NIDA has interacted directly with academia and industry for 20 years in the search for effective pharmacological treatments of drug abuse.…”

“…16,19 In general though, the treatment of reward defi cit and impulse control disorders combine pharmacological interventions with various forms of psychosocial counseling and behavioral therapy such as cognitive behavioral therapy. 16,24,106,107 In addition to the NIH initiatives supporting academic, industrial and government collaborations described above, NIDA has interacted directly with academia and industry for 20 years in the search for effective pharmacological treatments of drug abuse. Initially this collaboration consisted of soliciting compounds from various pharmaceutical companies with the commitment of screening them for anti-drug abuse potential; promising compounds would then be passed on to academic and commercial groups contracted by NIDA for secondary evaluation, and toxicological and pharmacokinetic testing.…”

“…124 Substances being abused are self-administered directly by both animals and humans. 15,16,93,94,106,116 However, modeling of the neurobiological and psychological substrates and the neurological consequences of reward defi cit disorders relies greatly on procedures developed for psychiatry and neurology. In Volume 1 of this book series Miczek 86 proposes eight conceptual principles for translational research.…”