Psychology Wiki
Register
Advertisement

Assessment | Biopsychology | Comparative | Cognitive | Developmental | Language | Individual differences | Personality | Philosophy | Social |
Methods | Statistics | Clinical | Educational | Industrial | Professional items | World psychology |

Clinical: Approaches · Group therapy · Techniques · Types of problem · Areas of specialism · Taxonomies · Therapeutic issues · Modes of delivery · Model translation project · Personal experiences ·


Benzodiazepine drug misuse
ICD-10
ICD-9
OMIM [1]
DiseasesDB [2]
MedlinePlus [3]
eMedicine article/290585
MeSH {{{MeshNumber}}}

Benzodiazepine drug misuse, sometimes called benzodiazepine drug abuse, is defined as using benzodiazepines for recreational purposes i.e. to get "high" or continuing benzodiazepines long term against medical advice.[1][2] The level of benzodiazepine misuse is as high as other common drugs of misuse. When used recreationally benzodiazepines are usually administered orally but sometimes they are taken intranasally or intravenously. Recreational use produces effects similar to alcohol intoxication[2][3] and in tests in primates benzodiazepines also produce effects similar to barbiturates,[4] with triazolam, alprazolam, clonazepam, diazepam and lorazepam having a higher abuse potential than other benzodiazepines such as oxazepam or chlordiazepoxide. A short elimination half life and potency of a benzodiazepine appears relevant to the degree of abuse potential a benzodiazepine has.[5][6]

Darke, Ross & Hall found that different benzodiazepines have different abuse potential. The more rapid the increase in the plasma level following ingestion, the greater the intoxicating effect and the more open to abuse the drug becomes. The speed of onset of action of a particular benzodiazepine correlates well with the ‘popularity’ of that drug for abuse. The two most common reasons for preference were that a benzodiazepine was ‘strong’ and that it gave a good ‘high’.[7]

Background[]

Benzodiazepines are a commonly abused class of drugs, although there is debate as to whether certain benzodiazepines have higher abuse potential than others.[8] In animal and human studies the abuse potential of benzodiazepines is classed as moderate in comparison to other drugs of abuse.[9] Benzodiazepines have serious adverse effects on the health of the individual and on society. Benzodiazepines are commonly abused by poly drug users, especially heroin addicts or alcoholics but sometimes are misused in isolation as the primary drug of misuse. They can be misused to achieve the high that benzodiazepines produce or more commonly they are used to either enhance the effects of other CNS depressant drugs, to stave off withdrawal effects of other drugs or combat the effects of stimulants. Sometimes they are used to give confidence to carry out criminal acts. As many as 30 - 50% of alcoholics are also benzodiazepine misusers.[10] Drug abusers often abuse high doses which makes serious benzodiazepine withdrawal symptoms such as psychosis or convulsions more likely to occur during withdrawal.

Benzodiazepine abuse increases risk taking behaviours such as unprotected sex and sharing of needles amongst intravenous abusers of benzodiazepines. Abuse is also associated with blackouts, memory loss, aggression, violence, and chaotic behaviour associated with paranoia, There is little support for long-term maintenance of benzodiazepine abusers and thus a withdrawal regime is indicated when benzodiazepine abuse becomes a dependence or addiction. The main source of illicit benzodiazepines are diverted benzodiazepines obtained originally on prescription; other sources include thefts from pharmacies and pharmaceutical warehouses. Benzodiazepine abuse is steadily increasing and is now a major public health problem. Benzodiazepine abuse is mostly limited to individuals who abuse other drugs, i.e. poly-drug abusers. Most prescribed users do not abuse their medication, however, some high dose prescribed users do become involved with the illicit drug scene. Abuse of benzodiazepines occurs in a wide age range of people and includes teenagers and the old. The abuse potential or drug-liking effects appears to be dose related, with low doses of benzodiazepines having limited drug liking effects but higher doses increasing the abuse potential/drug-liking properties.[11]

Health related complications[]

Complications of benzodiazepine abuse include, drug related deaths due to overdose especially in combination with other depressant drugs such as opiods. Other complications include thrombophlebitis, blackouts and memory loss, deep and superficial abscesses, paranoia, deep vein thrombosis, violence and criminal behaviour, pulmonary microembolism, risk-taking sexual behaviour, rhabdomyolysis, tissue necrosis, foetal and neonatal risks if taken in pregnancy, gangrene requiring amputation, dependence, hepatitis B and C, withdrawal seizures and psychosis as well as blood borne infections such as HIV infection (caused by sharing injecting equipment).[10] Long-term use of benzodiazepines can worsen pre-existing depression and anxiety and may potentially also cause dementia with impairments in recent and remote memory functions.[12]

Use is widespread among amphetamine users, with those that use amphetamines and benzodiazepines having greater levels of mental health problems and social deterioration. Benzodiazepine injectors are almost four times more likely to inject using a shared needle than non-benzodiazepine-using injectors. It has been concluded in various studies that benzodiazepine use causes greater levels of risk and psycho-social dysfunction among drug misusers.[13] Poly-drug users who also use benzodiazepines appear to engage in more risk taking behavior. Those who use stimulant and depressant drugs are more likely to report adverse reactions from stimulant use, more likely to be injecting stimulants and more likely to have been treated for a drug problem than those using stimulant but not depressant drugs.[14]

Rates of misuse[]

Little attention has focused on the degree that benzodiazepines are abused as a primary drug of choice, but they are frequently abused alongside other drugs of abuse especially alcohol, stimulants and opiates.[15] The benzodiazepine most commonly abused can vary from country to country and depends on factors including local popularity as well as which benzodiazepines are available. Nitrazepam for example is commonly abused in Nepal and the United Kingdom,[16][17] whereas in the United States of America where nitrazepam is not available on prescription other benzodiazepines are more commonly abused.[6] In the United Kingdom and Australia there have been epidemics of temazepam abuse. Particular problems with abuse of temazepam are often related to gel capsules being melted and injected and drug related deaths.[18][19][20] Injecting most benzodiazepines is dangerous because of their relative insolubility in water (with the exception of midazolam), leading to potentially serious adverse health consequences for users.[21][22]

Benzodiazepines are a commonly misused class of drug. A study in Sweden found that benzodiazepines are the most common drug class of forged prescriptions in Sweden.[23] Very high rates of benzodiazepines detected in motor vehicle drivers often exceeding therapeutic doses have been reported in Sweden and in Northern Ireland.[24][25] One of the hallmarks of problematic benzodiazepine drug misuse is escalation of dose. Most licit prescribed users of benzodiazepines do not escalate their dose of benzodiazepines.[26]

A 2004 US government study of nationwide ED visits conducted by SAMHSA found that sedative-hypnotics in the USA are the most frequently misused pharmaceutical drug with 35% of drug related visits to the Emergency Department involving sedative hypnotics. Benzodiazepines accounted for the majority of these. Benzodiazepines are more commonly misused than opiate pharmaceuticals which accounted for 32% of visits to the emergency department. Males and females misuse benzodiazepines equally. Of drugs used in attempted suicide, benzodiazepines are the most commonly used pharmaceutical drug with 26% of attempted suicides involving benzodiazepines. Alprazolam is the most commonly misused benzodiazepine, followed by clonazepam, lorazepam and diazepam as the 4th in the USA.[27]

Motivations for drug misuse[]

Benzodiazepines have demonstrated reward seeking behaviour in animal studies.[28] Humans are motivated to misuse benzodiazepines to achieve a sedative-hypnotic high which often produces effects including feeling energetic, relaxed, drunken, talkative, pleasure and euphoria. In India up to 50-60% of heroin addicts use benzodiazepines and 20% of injecting substance misusers also inject benzodiazepines.[29] Benzodiazepines can be used counter effects of other drugs eg to "come down" from stimulants or enhance the effects of other CNS depressant drugs eg alcohol or heroin.[30][31][32][33] Compulsive benzodiazepine use is believed to be due to adaptational changes in the GABAA receptor and possibly also its effects on the opioid system. The abuse potential of sedative-hypnotics are governed mainly by their effects on the alpha1 containing GABAA receptors.[34]

Risk factors for misuse[]

Individuals with a substance abuse history are at an increased risk of misusing benzodiazepines.[35] Individuals with a history of abuse of alcohol or are siblings of alcoholics appear to respond differently to benzodiazepines with males experiencing increased euphoric effects and females having exaggerated responses to the adverse effects of benzodiazepines.[36][37][38][39]

Whilst all benzodiazepines have abuse potential, certain characteristics increase their potential for abuse. A short elimination half-life, high potency and a rapid onset of action are characteristics which increase the abuse potential of benzodiazepines.[40] The following table provides the elimination half-life, relevant potency to other benzodiazepines, speed of onset of action and duration of behavioural effects.[41][42]

Drug Name Common Brand Names* Onset of action Duration of action (h)** Elimination Half-Life (h) [active metabolite] Approximate Equivalent Dose***
Alprazolam Xanax, Xanor, Tafil, Alprox, Fast 3-5 6-12 hours 0.5 mg
Chlordiazepoxide Librium, Tropium, Risolid, Klopoxid Intermediate ??? 5-30 hours [36-200 hours] 25 mg
Clonazepam Klonopin, Klonapin, Rivotril, Iktorivil Intermediate 10-12 18-50 hours 0.5 mg
Clorazepate Tranxene Intermediate ??? [36-100 hours] 15 mg
Diazepam Valium, Apzepam, Stesolid, Vival, Apozepam, Hexalid, Valaxona Fast 4-6 20-100 hours [36-200] 10 mg
Estazolam ProSom Slow 6-8 10-24 h 1-2 mg
Flunitrazepam Rohypnol, Fluscand, Flunipam, Ronal Fast 6-8 18-26 hours [36-200 hours] 1 mg
Flurazepam Dalmadorm, Dalmane Fast 7-10 [40-250 hours] 15-30 mg
Lorazepam Ativan, Temesta, Lorabenz Fast 4-6 10-20 hours 1 mg
Midazolam Dormicum, Versed, Hypnovel Ultra-fast 0.5-1 3 hours (1.8-6 hours) 5 mg
Oxazepam Seresta, Serax, Serenid, Serepax, Sobril, Oxascand, Alopam, Oxabenz, Oxapax Slow ??? 4-15 hours 30 mg
Prazepam Lysanxia, Centrax Slow ??? 36-200 hours 20 mg
Quazepam Doral Slow 6 39-120 hours 20 mg
Temazepam Restoril, Normison, Euhypnos, Tenox Intermediate 5-6 8-22 hours 20 mg
Triazolam Halcion, Rilamir Fast 0.5-1 2 hours 0.25 mg

*Not all trade names are listed. Click on drug name to see a more comprehensive list.
**The duration of apparent action is usually considerably less than the half-life. With most benzodiazepines, noticeable effects usually wear off within a few hours. Nevertheless, as long as the drug is present it will exert subtle effects within the body. These effects may become apparent during continued use or may appear as withdrawal symptoms when dosage is reduced or the drug is stopped.
***Equivalent doses are based on clinical experience but may vary between individuals.[4]

Drug dependence and withdrawal effects[]

Addictiondependence1

Benzodiazepines can induce a severe benzodiazepine withdrawal syndrome as well as drug seeking behaviour.

Sedative hypnotics such as alcohol, benzodiazepines and the barbiturates are notorious for the severe physical dependence that they are capable of inducing which can result in severe withdrawal effects.[43] This severe neuroadaptation is even more profound in high dose drug users and misusers. A high degree of tolerance often occurs in chronic benzodiazepine abusers due to the typically high doses they consume which can lead to a severe benzodiazepine dependence. The benzodiazepine withdrawal syndrome seen in chronic high dose benzodiazepine abusers is similar to that seen in therapeutic low dose users but of a more severe nature. Extreme antisocial behaviours in obtaining continued supplies and severe drug-seeking behaviour when withdrawing occurs. The severity of the benzodiazepine withdrawal syndrome has been described by one benzodiazepine drug misuser who stated that[10]

I'd rather withdraw off heroin any day. If I was withdrawing from benzos you could offer me a gram of heroin or just 20mg of diazepam and I'd take the diazepam every time - I've never been so frightened in my life.

Those who use benzodiazepines intermitantly are less likely to develop a dependence and withdrawal symptoms upon dose reduction or cessation of benzodiazepines than those who use benzodiazepines on a daily basis.[10]

Misuse of benzodiazepines is widespread amongst drug misusers, however, many of these people will not require withdrawal management as their use is often restricted to binges or occasional misuse. Benzodiazepine dependence when it occurs requires withdrawal treatment. There is little evidence of benefit from long-term substitution therapy of benzodiazepines and conversely there is growing evidence of the harm of long-term use of benzodiazepines, especially higher doses. Therefore gradual reduction is recommended titrated against withdrawal symptoms.[44] For withdrawal purposes, stabalisation with a long acting agent such as diazepam is recommended before commencing withdrawal. Chlordiazepoxide (librium), a long-acting benzodiazepine is gaining attention as an alternative to diazepam however, in substance abusers dependent on benzodiazepines due to its decreased abuse potential.[15] In individuals dependent on benzodiazepines who have been using benzodiazepines long-term, taper regimes of 6-12 months have been recommended and found to be more successful. More rapid detoxifications eg of a month are not recommended as they lead to more severe withdrawal symptoms.[45]

Tolerance leads to a reduction in GABA receptors and function; when benzodiazepines are reduced or stopped this leads to an unmasking of these compensatory changes in the nervous system with the appearance of physical and mental withdrawal effects such as anxiety, insomnia, autonomic hyperactivity and possibly seizures.[40]

Some common withdrawal symptoms which can occur when stopping the use of benzodiazepines include:[10]

All sedative-hypnotics, eg alcohol, barbiturates, benzodiazepines and the nonbenzodiazepine Z-drugs have a similar mechanism of action, working on the GABAA receptor complex and are cross tolerant with each other and also have abuse potential. Use of prescription sedative-hypnotics eg the non-benzodiazepine Z-drugs often leads to a relapse back into substance misuse with one author stating this occurs in over a quarter of those who have achieved abstinence.[45]

Drug-related crime[]

Problem benzodiazepine use can be associated with various deviant behaviors, including drug-related crime. In a survey of police detainees carried out by the Australian Government, both legal and illegal users of benzodiazepines were found to be more likely to have lived on the streets, less likely to have been in full time work and more likely to have used heroin or methamphetamines in the past 30 days from the date of taking part in the survey. Benzodiazepine users were also more likely to be receiving illegal incomes and more likely to have been arrested or imprisoned in the previous year. Benzodiazepines were sometimes reported to be used alone, but most often formed part of a poly drug-using problem. Female users were more likely than men to be using heroin, whereas male users were more likely to report amphetamine use. Benzodiazepine users were more likely than non-users to claim government financial benefits and benzodiazepine users who were also poly-drug users were the most likely to be claiming government financial benefits. Those who reported using benzodiazepines alone were found to be in the mid range when compared to other drug using patterns in terms of property crimes and criminal breaches. Of the detainees reporting benzodiazepine use, one in five reported injection use, mostly of illicit temazepam, with some who reported injecting prescribed benzodiazepines. Injection was a concern in this survey due to increased health risks. The main problems highlighted in this survey were concerns of dependence, the potential for overdose of benzodiazepines in combination with opiates and the health problems associated with injection of benzodiazepines.[46]

Benzodiazepines are also sometimes used for drug facilitated sexual assaults and robbery, however, alcohol remains the most common drug involved in drug facilitated assaults. The muscle relaxant, disinhibiting and amnesia producing effects of benzodiazepines are the pharmacological properties which make these drugs effective in drug-facilitated crimes.[47][48]

Drug regulation and enforcement[]

Europe[]

Temazepam abuse and seizures have been falling in the UK probably due to its reclassification as Schedule III controlled drug with tighter prescribing restrictions and the resultant reduction in availability.[49] A total of 2.75 million temazepam capsules were seized in the Netherlands by authorities between 1996 and 1999.[50] In Northern Ireland statistics of individuals attending drug addiction treatment centers found that benzodiazepines were the 2nd most commonly reported main problem drugs (31 percent of attendees). Cannabis was the top with 35 percent of individuals reporting it as their main problem drug. The statistics showed that treatment for benzodiazepines as the main problematic drug had more than doubled from the previous year and was a growing problem in Northern Ireland.[51]

Oceania[]

Benzodiazepines are common drugs of abuse in Australia and New Zealand, particularly among those who may also be using other illicit drugs. The intravenous use of temazepam poses the greatest threat to those who misuse benzodiazepines. Simultaneous consumption of temazepam with heroin is a potential risk factor of overdose. An Australian study of non-fatal heroin overdoses, noted that 26% of heroin users had consumed temazepam at the time of their overdose. This is consistent with a NSW investigation of coronial files from 1992. Temazepam was found in 26% of heroin-related deaths. Temazepam, including tablet formulations, are used intravenously. In an Australian study of 210 heroin users who used temazepam, 48% had injected it. Although abuse of benzodiazepines has decreased over the past few years, temazepam continues to be a major drug of abuse in Australia. In certain states like Victoria and Queensland, temazepam accounts for most benzodiazepine sought by forgery of prescriptions and through pharmacy burglary. Darke, Ross & Hall found that different benzodiazepines have different abuse potential. The more rapid the increase in the plasma level following ingestion, the greater the intoxicating effect and the more open to abuse the drug becomes. The speed of onset of action of a particular benzodiazepine correlates well with the ‘popularity’ of that drug for abuse. Darke, Ross & Hall found that temazepam rated significantly higher than the next most liked drug, nimetazepam. The two most common reasons for this preference were that it was the ‘strongest’ and that it gave a good ‘high’.[52]

North America[]

Abuse of benzodiazepine drugs is a serious problem in North America. The pills normally can be sold for $0.50 to $5.00 per pill. The most frequently abused of the benzodiazepines in both the United States and Canada are alprazolam, clonazepam, lorazepam and diazepam.[53]

East and Southeast Asia[]

Abuse of benzodiazepines is a serious problem throughout East and Southeast Asia. The Central Narcotics Bureau of Singapore seized 94,200 nimetazepam tablets in 2003. This is the largest nimetazepam seizure recorded since nimetazepam became a controlled drug under the Misuse of Drugs Act in 1992.[54] Together with temazepam abusers, they accounted for 47% of the abusers arrested in 2005.[55] In Singapore, both temazepam and nimetazepam are Class A Schedule I controlled drugs. Similar strict laws apply to both of these benzodiazepines all across Asia. In Hong Kong, all benzodiazepines are regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance.[56][57]

Legal status[]

In the United States, benzodiazepines are Schedule IV drugs under the Federal Controlled Substances Act, even when not on the market (for example, nitrazepam and bromazepam). Flunitrazepam is subject to more stringent regulations in certain states and temazepam prescriptions require specially coded pads in certain states. In Canada, all benzodiazepines are in Schedule 4 of the Controlled Drugs and Substances Act.[58]

In the United Kingdom, the benzodiazepines are Schedule IV controlled drugs, except for flunitrazepam, temazepam and midazolam, which are Schedule III controlled drugs and carry stronger penalties for possession and trafficking.[59][60]

In the Netherlands, since October 1993, benzodiazepines are all placed on List 2 of the Opium Law. A prescription is needed for possession of all benzodiazepines.[61]

In East Asia and Southeast Asia, temazepam and nimetazepam are often heavily controlled and restricted. In certain countries, triazolam, flunitrazepam, flutoprazepam and midazolam are also restricted or controlled to certain degrees. In Hong Kong all benzodiazepines were reclassified as dangerous drugs and are regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. Previously only brotizolam, flunitrazepam and triazolam were classed as dangerous drugs.[62]

Internationally, benzodiazepines are categorized as Schedule IV controlled drugs, apart from flunitrazepam is a Schedule III drug under the Convention on Psychotropic Substances.[63]

See also[]

References[]

  1. (24 January 2008) "Treatment of sedative-hypnotic dependence" Cambridge Textbook of Effective Treatments in Psychiatry, 1st, 402, Cambridge University Press.
  2. 2.0 2.1 Griffiths RR, Johnson MW (2005). Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds. J Clin Psychiatry 66 Suppl 9: 31–41.
  3. Sheehan MF, Sheehan DV, Torres A, Coppola A, Francis E (1991). Snorting benzodiazepines. Am J Drug Alcohol Abuse 17 (4): 457–68.
  4. Woolverton WL, Nader MA (December 1995). Effects of several benzodiazepines, alone and in combination with flumazenil, in rhesus monkeys trained to discriminate pentobarbital from saline. Psychopharmacology (Berl.) 122 (3): 230–6.
  5. Griffiths RR, Lamb RJ, Sannerud CA, Ator NA, Brady JV (1991). Self-injection of barbiturates, benzodiazepines and other sedative-anxiolytics in baboons. Psychopharmacology (Berl.) 103 (2): 154–61.
  6. 6.0 6.1 Griffiths RR, Wolf B (August 1990). Relative abuse liability of different benzodiazepines in drug abusers. J Clin Psychopharmacol 10 (4): 237–43.
  7. Australian Government, Medical Board (2004). ACT MEDICAL BOARD - STANDARDS STATEMENT - PRESCRIBING OF BENZODIAZEPINES. (PDF) medicalboard.act.gov.au. URL accessed on 13 February 2009.
  8. (1st December 2003) Medical Toxicology, 3rd, USA: Lippincott Williams & Wilkins.
  9. Griffiths RR, Weerts EM (November 1997). Benzodiazepine self-administration in humans and laboratory animals--implications for problems of long-term use and abuse. Psychopharmacology (Berl.) 134 (1): 1–37.
  10. 10.0 10.1 10.2 10.3 10.4 Professor C Heather Ashton (2002). BENZODIAZEPINE ABUSE. Drugs and Dependence. Harwood Academic Publishers. URL accessed on September 25, 2007.
  11. (11 April 2002) "Benzodiazepine abuse" Drink, Drugs and Dependence: From Science to Clinical Practice, 1st, 197–211, Routledge.
  12. (1 July 2008) The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 4th, United States of America: American Psychiatric Publishing Inc.
  13. Darke S, Ross J, Cohen J (1994). The use of benzodiazepines among regular amphetamine users. Addiction 89 (12): 1683–90.
  14. Williamson S, Gossop M, Powis B, Griffiths P, Fountain J, Strang J (1997). Adverse effects of stimulant drugs in a community sample of drug users. Drug Alcohol Depend 44 (2–3): 87–94.
  15. 15.0 15.1 (20 December 2006) Drug Abuse Handbook, 2nd, USA: CRC Press.
  16. Chatterjee A, Uprety L, Chapagain M, Kafle K (1996). Drug abuse in Nepal: a rapid assessment study. Bull Narc 48 (1-2): 11–33.
  17. Garretty DJ, Wolff K, Hay AW, Raistrick D (January 1997). Benzodiazepine misuse by drug addicts. Annals of clinical biochemistry 34 (Pt 1): 68–73.
  18. Wilce H (June 2004). Temazepam capsules: What was the problem?. Australian Prescriber 27: 58–9.
  19. Ashton H (2002). "Benzodiazepine Abuse" Drugs and Dependence, London & New York: Harwood Academic Publishers. URL accessed 2007-11-25.
  20. Hammersley R, Cassidy MT, Oliver J (1995). Drugs associated with drug-related deaths in Edinburgh and Glasgow, November 1990 to October 1992. Addiction 90 (7): 959–65.
  21. Eric C, Wang, Felix S, Chew. (2006). MR Findings of Alprazolam Injection into the Femoral Artery with Microembolization and Rhabdomyolysis. Radiology Case Reports 1 (3).
  22. DB00404 (Alprazolam). DrugBank.
  23. Bergman U, Dahl-Puustinen ML (1989). Use of prescription forgeries in a drug abuse surveillance network. Eur J Clin Pharmacol 36 (6): 621–3.
  24. Jones AW, Holmgren A, Kugelberg FC (April 2007). Concentrations of scheduled prescription drugs in blood of impaired drivers: considerations for interpreting the results. Ther Drug Monit 29 (2): 248–60.
  25. Cosbey SH (December 1986). Drugs and the impaired driver in Northern Ireland: an analytical survey. Forensic Sci Int 32 (4): 245–58.
  26. Lader MH (1999). Limitations on the use of benzodiazepines in anxiety and insomnia: are they justified?. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 9 Suppl 6: S399–405.
  27. United States Government, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES (2004). Drug Abuse Warning Network, 2004: National Estimates of Drug-Related Emergency Department Visits. Substance Abuse and Mental Health Services Administration. URL accessed on 9 May 2008.
  28. Thiébot MH, Le Bihan C, Soubrié P, Simon P. (1985). Benzodiazepines reduce the tolerance to reward delay in rats.. Psychopharmacology (Berl). 86 (1-2): 147–52.
  29. PRAVIN SHANKER PRASAD, RAJAT RAY, RAKA JAIN, B.S.CHAVAN (2001). ABUSE LIABILITY OF NITRAZEPAM: A STUDY AMONG EXPERIENCED DRUG USERS. Indian Journal of Pharmacology 33: 357–362.
  30. (Apr 2003). The effects of alprazolam on conditioned place preferences produced by intravenous heroin.. Pharmacology, biochemistry, and behavior 75 (1): 75–80.
  31. MARCIA LANE. Xanax, alcohol mix kills 2. St. Augustine Record. URL accessed on 10 December 2008.
  32. Wright State University and the University of Akron. OSAM - O- GRAM Highlights of Statewide Drug Use Trends. (PDF) Ohio Government. URL accessed on 10 December 2008.
  33. Detective Eladio M. Paez. STATEMENT ON RAVES AND CLUB DRUGS TO THE SUBCOMMITTEE ON CRIME, CONGRESS OF THE UNITED STATES, HOUSE OF REPRESENTATIVES. GOV House Judiciary. URL accessed on 10 December 2008.
  34. (1 July 2008) The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 4th, United States of America: American Psychiatric Publishing Inc.
  35. Hoffmann–La Roche. Mogadon. RxMed. URL accessed on 26 May 2009.
  36. (Sep 1988). Abuse liability and clinical pharmacokinetics of alprazolam in alcoholic men.. The Journal of clinical psychiatry 49 (9): 333–7.
  37. (Jul 1996). Liability to alprazolam abuse in daughters of alcoholics.. The American journal of psychiatry 153 (7): 956–8.
  38. (Jun 2000). Increased sensitivity to alprazolam in females with a paternal history of alcoholism.. Psychopharmacology 150 (2): 150–62.
  39. (May 1998). Functional magnetic resonance imaging of alprazolam-induced changes in humans with familial alcoholism.. Psychiatry research 82 (2): 69–82.
  40. 40.0 40.1 Longo LP, Johnson B (April 2000). Addiction: Part I. Benzodiazepines--side effects, abuse risk and alternatives. Am Fam Physician 61 (7): 2121–8.
  41. (1 July 2008) The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 4th, United States of America: American Psychiatric Publishing Inc.
  42. Shader RI, Greenblatt DJ (1981). The use of benzodiazepines in clinical practice. Br J Clin Pharmacol 11 Suppl 1: 5S–9S.
  43. Dr Ray Baker. Dr Ray Baker's Article on Addiction: Benzodiazepines in Particular. URL accessed on 14 Febrruary 2009.
  44. National Treatment Agency for Substance Misuse (2007). Drug misuse and dependence - UK guidelines on clinical management. (PDF) Department of Health.
  45. 45.0 45.1 (1st October 2006) Substance Use Disorders: A Practical Guide, 2nd, 103–121, USA: Lippincott Williams and Wilkins.
  46. Loxley W (2007). Benzodiazepine use and harms among police detainees in Australia. Trends Issues Crime Crim Justice (336).
  47. (Jun 2000). Drug-facilitated sexual assault ('date rape').. South Med J 93 (6): 558–61.
  48. (Apr 2004). Drug-facilitated robbery or sexual assault: problems associated with amnesia.. Ther Drug Monit 26 (2): 206–10.
  49. The Scottish Government. Statistical Bulletin - DRUG SEIZURES BY SCOTTISH POLICE FORCES, 2005/2006 AND 2006/2007. (PDF) Crime and justice series. scotland.gov.uk. URL accessed on 13 February 2009.
  50. INCB (1999). Operation of the international drug control system. (PDF) incb.org. URL accessed on 13 February 2009.
  51. Northern Ireland Government (2008). Statistics from the Northern Ireland Drug Misuse Database: 1 April 2007 – 31 March 2008. (PDF) Department of Health and Social Services and Public Safety.
  52. Australian Government, Medical Board (2004). ACT MEDICAL BOARD - STANDARDS STATEMENT - PRESCRIBING OF BENZODIAZEPINES. (PDF) medicalboard.act.gov.au. URL accessed on 13 February 2009.
  53. United States Government, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES (2006). Drug Abuse Warning Network, 2006: National Estimates of Drug-Related Emergency Department Visits. Substance Abuse and Mental Health Services Administration. URL accessed on 9 February 2009.
  54. Central Narcotics Bureau, Singapore Government (2003). Drug Situation Report 2003. cnb.gov.sg. URL accessed on 13 February 2009.
  55. Hong Kong Government. Suppression of Illicit Trafficking and Manufacturing. (PDF) nd.gov.hk. URL accessed on 13 February 2009.
  56. Hong Kong Government, Hong Kong Ordinances. DANGEROUS DRUGS ORDINANCE - SCHEDULE 1. hklii.org.
  57. (1995). Use and abuse of benzodiazepines in Hong Kong 1990-1993--the impact of regulatory changes.. Journal of toxicology. Clinical toxicology 33 (6): 597–602.
  58. Benzodiazepines. DEA Briefs & Background, Drugs and Drug Abuse, Drug Descriptions. U.S. Drug Enforcement Administration. URL accessed on 2009-05-27.
  59. Blackpool NHS Primary Care Trust. Medicines Management Update. United Kingdom National Health Service. URL accessed on 2009-05-27.
  60. UK, Gov. List of Drugs Currently Controlled Under The Misuse of Drugs Legislation. Misuse of Drugs Act UK. URL accessed on 2009-05-27.
  61. Opium Law. Dutch Government. URL accessed on 2009-05-27.
  62. Lee KK, Chan TY, Chan AW, Lau GS, Critchley JA (1995). Use and abuse of benzodiazepines in Hong Kong 1990–93—the impact of regulatory changes. J. Toxicol. Clin. Toxicol. 33 (6): 597–602.
  63. International Narcotics Control Board (2003). List of psychotropic substances under international control. (PDF) incb.org. URL accessed on 2008-12-17.


This page uses Creative Commons Licensed content from Wikipedia (view authors).
Advertisement