Abuse liability

Anxiety disorders are common in the population of opioid-addicted individuals however, treatment studies are lacking. It is uncertain whether the frequency of anxiety disorders contributes to high rates of illicit use of benzodiazepines, which is common in methadone maintenance programs (Ross and Darke 2000). Increased toxicity has been observed when benzodiazepines are co-administered with some opioids (Borron et al. 2002 Caplehorn and Drummer 2002). Although there is an interesting report of clonazepam maintenance treatment for methadone maintenance patients who abuse benzodiazepines, further studies are needed (Bleich et al. 2002). Unfortunately, buspirone, which has low abuse liability, was not effective in an anxiety treatment study in opioid-dependent subjects (McRae et al. 2004). Current clinical practice is to prescribe SSRIs or other antidepressants that have antianxiety actions for these patients. Carefully controlled benzodiazepine prescribing is advocated by some practitioners. 

Benzodiazepines have a low risk for abuse in anxiety disorder patients without a history of alcohol or other substance abuse. Among the benzodiazepines there may be a spectrum of abuse liability, with drugs that serve as prodrugs for desmethyldiazepam (e.g., clorazepate), slow-onset agents (e.g., oxazepam), and partial agonists (e.g., abecarnil) having the least potential for abuse. However, there is no currently marketed benzodiazepine or related drug that is free of potential for abuse. 

Ciraulo DA, Nace EP Benzodiazepine treatment of anxiety or insomnia in substance abuse patients. Am J Addict 9 276—284, 2000 Ciraulo DA, Barnhill JG, Greenblatt DJ, et al Abuse liability and clinical pharmacokinetics of alprazolam in alcoholic men. J Clin Psychiatry 49 333—337, 1988a... 

Ciraulo DA, Sands BE, Shader RI Critical review of liability for benzodiazepine abuse among alcoholics. Am J Psychiatry 145 1501-1506, 1988b Ciraulo DA, Barnhill JG, Ciraulo AM, et al Parental alcoholism as a risk factor in benzodiazepine abuse a pilot smdy. Am J Psychiatry 146 1333-1335, 1989 Ciraulo DA, Antal EJ, Smith RB, et al The relationship of alprazolam dose to steady-state plasma concentrations. J Clin Psychopharmacol 10 27—32, 1990 Ciraulo DA, Sarid-Segal O, Knapp C, et al Liability to alprazolam abuse in daughters of alcoholics. Am J Psychiatry 153 956-958, 1996 Ciraulo DA, Barnhill JG, Ciraulo AM, et al Alterations in pharmacodynamics of anxiolytics in abstinent alcoholic men subjective responses, abuse liability, and electroencephalographic effects of alprazolam, diazepam, and buspirone. J Clin Pharmacol 37 64-73, 1997... 

Griffiths RR, Wolf B Relative abuse liability of different benzodiazepines in drug abusers. J Clin Psychopharmacol 10 237-243, 1990 Griffiths RR, Weerts EM Benzodiazepine self-administration in humans and laboratory animals—implications for problems of long-term use and abuse. Psycho-pharmacology (Berl) 134 1-37, 1997... 

Mumford GK, Evans SM, Fleishaker JC, et al Alprazolam absorption kinetics affects abuse liability. Clin Pharmacol Ther 57 356—365, 1995a... 

Williams H, Oyefeso A, Ghodse AH Benzodiazepine misuse and dependence among opiate addicts in treatment. It J Psychol Med 13 62-64, 1996 Wiseman SM, Spencer-Peet J Prescribing for alcoholics a survey of drugs taken prior to admission to an alcoholism unit. Practitioner 229 88—89, 1985 Wolf B, Grohmann R, Biber D, et al Benzodiazepine abuse and dependence in psychiatric inpatients. Pharmacopsychiatry 22 54—60, 1989 Wood MR, Kim JJ, Han W, et al Benzodiazepines as potent and selective bradykinin B1 antagonists. J Med Chem 46 1803—1806, 2003 Zawertailo LA, Busto UE, Kaplan HL, et al Comparative abuse liability and pharmacological effects of meprobamate, triazolam, and butabarbital. J Clin Psycho-pharmacol 23 269-280, 2003... 

Ator NA, Griffiths RR Principles of drug abuse liability assessment in laboratory animals. Drug Alcohol Depend 70(suppl) 55—72, 2003... 

Toluene, volatile nitrites, and anesthetics, like other substances of abuse such as cocaine, nicotine, and heroin, are characterized by rapid absorption, rapid entry into the brain, high bioavailability, a short half-life, and a rapid rate of metabolism and clearance (Gerasimov et al. 2002 Pontieri et al. 1996, 1998). Because these pharmacokinetic parameters are associated with the ability of addictive substances to induce positive reinforcing effects, it appears that the pharmacokinetic features of inhalants contribute to their high abuse liability among susceptible individuals. 

Griffiths, RR. Brady, J.V. and Bradford, L.D. Predicting the abuse liability of drugs with animal drug self-administration procedures Psyehomotor stimulants and hallueinogens. Adv Behav Pharmacol 2 163-208, 1979. 

Griffiths, RR. Brady, J.V. and Snell, J.D. Relationship between anorectic and reinforcing properties of appetite suppressant drugs Implieations for assessment of abuse liability. Biol Psychiatry 13 283-290, 1978. 

TESTING DRUGS FOR PHYSICAL DEPENDENCE POTENTIAL AND ABUSE LIABILITY. Joseph V. Brady, Ph.D., and Scott E. Lukas, Ph.D., eds. 

Foltin, R. W., The importance of drug self-administration studies in the analysis of abuse liability An analysis of caffeine, nicotine, anabolic steroids, and designer drugs. Annual Meeting of the American Academy of Psychiatrists in Alcoholism and Addictions (1990, Santa Monica, California). American Journal on Addictions Spr Vol 1(2), 139-149, 1992. 

The dopaminergic system plays a role in the abuse liability for some, if not most, drugs. The stimulants — opiates, marijuana, nicotine, and ethanol — all interact directly or indirectly with... 

Hematological toxicity 10 Neuropsychiatric effects/ abuse liability/dependency 12... 

Drug discrimination is also an imporfanf sfandard technique used in assessments of the abuse liability of novel psychoactive compounds, with relevance to attempts to develop novel nicotinic agonists for use as cognitive enhancers. 

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