Progress report of the NIDA Addiction Research Center.

Dr, Jasinski; Ca, Haertzen; Je, Henningfield; Re, Johnson; Hm, Makhzoumi; Miyasato, K

doi:10.1037/e468552004-001

Cited by 29 publications

(23 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The finding that benzodiazepines are less efficacious reinforcers than pentobarbital is consistent with two human drug self-administration studies in drug abusers which showed that pentobarbital was chosen more frequently than diazepam in choice tests (Griffiths et al 1980b) and that pentobarbital maintained higher and more consistent rates of drug self-administration than diazepam (Griffiths et al 1979). It is also consistent with several human studies that measured subjective effects in drug abusers and showed that, compared to a benzodiazepine (chlordiazepoxide, diazepam, triazolam), pentobarbital either produced greater ratings of liking or euphoria (Griffiths et al 1980b;Jasinski et al , 1983Roache and Griffiths 1985) or fewer dysphoric changes in mood ). Likewise, the animal data indicating that benzodiazepines have a greater reinforcing efficacy than several classic low abuse liability sedatives are consistent with three human drug self-administration studies.…”

Section: Falk and Tangsupporting

confidence: 81%

Benzodiazepine self-administration in humans and laboratory animals - implications for problems of long-term use and abuse

1997

View full text Add to dashboard Cite

Drug reinforcement may represent the primary behavioral-pharmacological mechanism underlying two types of problematic use of benzodiazepines--recreational abuse by polydrug abusers and inappropriate chronic use by patients. High dose polydrug abuse for the purpose of getting high is readily recognized as a significant social problem. Inappropriate chronic benzodiazepine use is more subtle but relatively common: for anxiolytics, 36% of past-year users (3% of the adult population in the US) report using these drugs for 4 consecutive months or longer. The risks of such long-term use are much better documented than the benefits. This paper provides a current review of various problems that have been identified with the long-term use and the recreational abuse of benzodiazepines, including memory impairment, risk of accidents, falls and hip fractures in the elderly, a withdrawal syndrome, brain damage, overuse in the elderly, overuse by chronic pain patients, overuse by alcoholics and recreational abuse among alcoholics and polydrug abusers. A comprehensive review of the literature on benzodiazepine reinforcing effects in humans and laboratory animals is also provided. Drug self-administration studies in humans and laboratory animals provide models of both types of problematic benzodiazepine use. Recreational abuse of benzodiazepines has been modeled in human research with polydrug abusers and in laboratory animal studies, which show that the reinforcing effect of benzodiazepines is intermediate relative to other sedative compounds and is increased in subjects with histories of previous sedative drug self-administration. The problem of inappropriate long-term use of benzodiazepines by people without histories of drug abuse has been partially modeled in human studies showing that benzodiazepines function as reinforcers in subjects with anxiety, insomnia, and histories of moderate alcohol consumption, and in preclinical studies showing stable, low-rate benzodiazepine self-injection with concurrent physical dependence under conditions of continuous availability. Both human and animal research suggests that the drug history and current behavioral context may be important in the establishment of benzodiazepines as reinforcers. Limited human and animal research provides little support for the common belief that physical dependence enhances benzodiazepine reinforcement.

show abstract

Section: Falk and Tangsupporting

confidence: 81%

Benzodiazepine self-administration in humans and laboratory animals - implications for problems of long-term use and abuse

1997

View full text Add to dashboard Cite

show abstract

“…Consistent with these animal data is also the observation in humans that in drug abusers maintained on moderate doses of methadone (25-45 mg/day), buprenorphine did not produce any clear signs of opiate-antagonistic effects and withdrawal (while naloxone produced characteristic antagonistic and hydromorphone produced characteristic agonists effects in these subjects) (Jasinski et al 1983;Strain et al 1992). Also, if buprenorphine is used as a maintenance drug, the induction onto buprenorphine in heroin addicts was tolerated without any untoward withdrawal effects when using an appropriate schedule (Bickel et al 1988a;Johnson et al 1989;Levin et al 1997).…”

Section: Induction Of Withdrawal By Buprenorphine In Subjects Dependesupporting

confidence: 62%

Behavioral pharmacology of buprenorphine, with a focus on preclinical models of reward and addiction

Tzschentke¹

2002

Psychopharmacology

View full text Add to dashboard Cite

Since buprenorphine is a potent opioid drug, the issue of addiction and dependence in this context is an important one. Although there are still some gaps in the behavioral pharmacological characterization of buprenorphine, the general conclusion that can be drawn from the reviewed literature is that despite the high affinity of buprenorphine for the mu receptor it appears to be a remarkably safe drug, with a benign overall side effect profile and low addictive and dependence-inducing potential. This favorable side effect profile appears to be due, to a large extent, to the partial agonistic properties of the drug, in combination with its particular receptor kinetics (i.e. very slow dissociation from the mu receptor after binding).

show abstract

“…However, the clinical use of morphine is limited by the drug's high degree of abuse liability, which is also true of other analgesics that produce morphine-like subjective effects (Jasinski and Nutt 1973). The results of recent studies raise the possibility that metabolites of morphine contribute to the abuse liability of the parent compound.…”

Section: Introductionmentioning

confidence: 98%

Comparison of the discriminative and antinociceptive effects of morphine and its glucuronide metabolites after central or systemic administration in the rat

Easterling

Holtzman

1998

Psychopharmacology

View full text Add to dashboard Cite

The potential of centrally (ICV) or systemically (SC) administered M6G to substitute for morphine in a drug discrimination task was characterized in the present study. Rats with a cannula in the lateral cerebral ventricle were trained to discriminate between injections of morphine (3 mg/kg, SC) and saline using a discrete-trial avoidance/escape procedure. Substitution tests were conducted with SC or ICV morphine, morphine-3-beta-D-glucuronide (M3G), or morphine-6-beta-D-glucuronide (M6G) and response latency in a tail-flick test was measured before each session began. The stimulus effects of morphine (ED50=1.02 mg/kg SC or 2.1 microg/kg ICV) were fully shared by M6G, with potency dependent on route of administration (ED50=3.12 mg/kg SC or 0.34 microg/kg ICV). The stimulus effects of M6G were highly correlated with its antinociceptive activity (r=0.84 SC or 0.46 ICV) and, at equipotent systemic doses, they lasted longer (t1/2=391 min) than those of morphine (t1/2=185 min). M3G was inactive in both procedures by both routes of administration. Naltrexone SC, given 30 min prior to testing, completely attenuated the stimulus effects of ICV M6G (AD50=0.011 mg/kg), indicating that they are mediated by opioid receptors. The results of this study suggest that M6G might contribute to the interoceptive effects of morphine that underlie its potential for abuse.

show abstract

Progress report of the NIDA Addiction Research Center.

Cited by 29 publications

References 0 publications

Benzodiazepine self-administration in humans and laboratory animals - implications for problems of long-term use and abuse

Benzodiazepine self-administration in humans and laboratory animals - implications for problems of long-term use and abuse

Behavioral pharmacology of buprenorphine, with a focus on preclinical models of reward and addiction

Comparison of the discriminative and antinociceptive effects of morphine and its glucuronide metabolites after central or systemic administration in the rat

Contact Info

Product

Resources

About