Patterns of Benzodiazepine Abuse and Dependence

Busto, Usoa E.; Sellers, Edward M.; Naranjo, Claudio A.; Cappell, Howard; Sanchez‐Craig, Martha; Simpkins, Jan

doi:10.1111/j.1360-0443.1986.tb00299.x

Cited by 83 publications

(31 citation statements)

References 19 publications

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“…The most popular benzodiazepines used in this study were flunitrazepam, diazepam and fluazepam. The average dose of diazepam used is higher than in other studies 1,12,17 . Zopiclone is emerging as a new drug of use with 2 people in the sample using it despite studies indicating that the drug users have "no liking" for the drug and therefore it has less potential for misuse 18 .…”

Section: Discussionmentioning

confidence: 55%

Co-abuse of opiates and benzodiazepines

et al. 1999

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The objective of the study was to assess what differences exist between individuals who are dependent on opiates and benzodiazepines and compare to those who are dependent on opiates. A questionnaire was compiled and administered to patients who had been consecutively admitted to an inpatient drug treatment unit. The prevalence of benzodiazepine dependency was 54 per cent [n=34]. Patients dependent on benzodiazepines and opiates were significantly older, had been admitted for methadone stabilisation and were more likely to have been prescribed a methadone maintenance programme prior to admission. They had used heroin longer, benzodiazepines more frequently, at larger doses for a longer duration of time and tended to use more drugs in general. They were found to be more psychologically vulnerable than those not dependent on benzodiazepines as they were significantly more likely to have described a past experience of depression and a past episode of deliberate self harm.

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Section: Discussionmentioning

confidence: 55%

Co-abuse of opiates and benzodiazepines

et al. 1999

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“…This group often uses benzodiazepines to fight off the unpleasant effects of other drugs, such as irritability and anxiety, or to amplify the 'high' from other drugs such as opioids. There are, nevertheless, reports of benzodiazepines being used for the sake of their own 'high' without being combined with other drugs, and some polydrug users define benzodiazepines as their primary drug of abuse (Griffiths and Weertz, 1997;Busto et al, 1986). Thus, there are several reasons for benzodiazepine abuse, such as physical dependence, management of the adverse effects of other drugs, or the 'high' or other positive subjective effects of the benzodiazepine itself.…”

Section: Introductionmentioning

confidence: 99%

“…For many of these users, the basic reason for abuse is physical dependence, as defined by the withdrawal symptoms following cessation. However, moderate increases in doses over time reported by these users suggest that there is an additional drug effect component that is separate from simply avoiding withdrawal symptoms (Busto et al, 1986;McCabe, 2007). As tolerance develops to this effect over time, the dose needs to be increased proportionally to achieve the same subjective effect.…”

Section: Introductionmentioning

confidence: 99%

“…One common type of user is patients who are initially prescribed benzodiazepines for legitimate use for a temporary period, but who later become abusers by extending the use period and increasing the dosage, and reaching and surpassing cumulative drug doses that are defined as 'addiction ' (O'Brien, 2005;Salzman, 1998;Griffiths and Weerts, 1997;Busto et al, 1986). For many of these users, the basic reason for abuse is physical dependence, as defined by the withdrawal symptoms following cessation.…”

Section: Introductionmentioning

confidence: 99%

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Neural Basis of Benzodiazepine Reward: Requirement for α2 Containing GABAA Receptors in the Nucleus Accumbens

Engin

Bakhurin

Smith

et al. 2014

Neuropsychopharmacol

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Despite long-standing concerns regarding the abuse liability of benzodiazepines, the mechanisms underlying properties of benzodiazepines that may be relevant to abuse are still poorly understood. Earlier studies showed that compounds selective for a1-containing GABA A receptors (a1GABA A Rs) are abused by humans and self-administered by animals, and that these receptors may underlie a preference for benzodiazepines as well as neuroplastic changes observed in the ventral tegmental area following benzodiazepine administration. There is some evidence, however, that even L-838, 417, a compound with antagonistic properties at a1GABA A Rs and agonistic properties at the other three benzodiazepine-sensitive GABA A receptor subtypes, is self-administered, and that the a2GABA A Rs may have a role in benzodiazepine-induced reward enhancement. Using a two-bottle choice drinking paradigm to evaluate midazolam preference and an intracranial self-stimulation (ICSS) paradigm to evaluate the impact of midazolam on reward enhancement, we demonstrated that mice carrying a histidine-to-arginine point mutation in the a2 subunit which renders it insensitive to benzodiazepines (a2(H101R) mice) did not prefer midazolam and did not show midazolam-induced reward enhancement in ICSS, in contrast to wild-type controls, suggesting that a2GABA A Rs are necessary for the reward enhancing effects and preference for oral benzodiazepines. Through a viral-mediated knockdown of a2GABA A Rs in the nucleus accumbens (NAc), we demonstrated that a2 in the NAc is necessary for the preference for midazolam. Findings imply that a2GABA A Rs in the NAc are involved in at least some rewardrelated properties of benzodiazepines, which might partially underlie repeated drug-taking behavior.

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“…In fact, high anxiety levels have been reported as a common symptom in patients withdrawn from Bzp and avoidance of these unpleasant symptoms seems to negatively reinforce continuous Bzp use, one of the main components of craving for the drug (Busto et al, 1986;Busto and Sellers, 1991). An increase in anxiety-like states is also observed in rats undergoing spontaneous diazepam withdrawal and submitted to several types of animal models of anxiety (Emmett-Oglesby et al, 1983a, 1983bFile, 1990;Greenblatt and Shader, 1974).…”

Section: Discussionmentioning

confidence: 99%

Analysis of the chronic intake of and withdrawal from diazepam on emotional reactivity and sensory information processing in rats

Ross

Castilho

Brandão

et al. 2008

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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It has been demonstrated that, on abrupt withdrawal, patients with chronic exposure can experience a number of symptoms indicative of a dependent state. In clinical patients, the earliest to arise and most persistent signal of withdrawal from chronic benzodiazepine (Bzp) treatment is anxiety. In laboratory animals, anxiety-like effects following abrupt interruption of chronic Bzp treatment can also be reproduced. In fact, signs that oscillate from irritability to extreme fear behaviours and seizures have been described already. As anxiety remains one of the most important symptoms of Bzp withdrawal, in this study we evaluated the anxiety levels of rats withdrawn from diazepam. Also studied were the effects on the motor performance and preattentive sensory gating process of rats under diazepam chronic treatment and upon 48-h withdrawal on three animal models of anxiety, the elevated plus-maze (EPM), ultrasonic vocalizations (USV) and startle + prepulse inhibition tests. Data obtained showed an anxiolytic-and anxiogenic-like profile of the chronic intake of and withdrawal from diazepam regimen in the EPM test, 22-KHz USV and startle reflex.Diazepam chronic effects or its withdrawal were ineffective in promoting any alteration in the prepulse inhibition (PPI). However, an increase of PPI was achieved in both sucrose and diazepam pretreated rats on 48-h withdrawal, suggesting a procedural rather than a specific effect of withdrawal on sensory gating processes. It is also possible that the prepulse can function as a conditioned stimulus to informing the delivery of an aversive event, as the auditory startling-eliciting stimulus. All these findings are indicative of a sensitization of the neural substrates of aversion in diazepam withdrawn animals without concomitant changes on the processing of sensory information.

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Patterns of Benzodiazepine Abuse and Dependence

Cited by 83 publications

References 19 publications

Co-abuse of opiates and benzodiazepines

Co-abuse of opiates and benzodiazepines

Neural Basis of Benzodiazepine Reward: Requirement for α2 Containing GABAA Receptors in the Nucleus Accumbens

Analysis of the chronic intake of and withdrawal from diazepam on emotional reactivity and sensory information processing in rats

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