Drugs and Chemicals of Concern

BENZODIAZEPINES

(Street Names: Benzos, Downers, Nerve Pills, Tranks)

December 2010
DEA/OD/ODE

Introduction:

Benzodiazepines are a class of drugs that produce central nervous system (CNS) depression and that are most commonly used to treat insomnia and anxiety. There is the potential for dependence on and abuse of benzodiazepines particularly by individuals with a history of multi-substance abuse. Alprazolam (e.g., Xanax), lorazepam (e.g., Ativan), clonazepam (e.g., Klonopin), diazepam (e.g., Valium), and temazepam (e.g., Restoril) are the five most prescribed, as well as the most frequently encountered benzodiazepines on the illicit market.

Licit Uses:

Benzodiazepines are widely prescribed drugs. According to IMS Health™, there were 45.0 million alprazolam, 26.4 million lorazepam, 24.4 million clonazepam, 14.2 million diazepam, and 8.4 million temazepam prescriptions dispensed in the U.S. in 2009. In the U.S., benzodiazepines are prescribed for their sedative-hypnotic (e.g., temazepam, triazolam, flurazepam, and estazolam), anti-anxiety (e.g., alprazolam, chlordiazepoxide, clorazepate, diazepam, lorazepam, and oxazepam), muscle relaxant (e.g., diazepam), and anti-convulsant (e.g., diazepam and clonazepam) effects. They are also used as an adjunct to anesthesia (e.g., midazolam) and for treatment of alcohol withdrawal (e.g., chlordiazepoxide) and panic disorders (e.g., alprazolam and clonazepam). Most benzodiazepines are available as tablet and capsule preparations; several are also available as injectable preparations and as syrup.

Chemistry and Pharmacology:

All benzodiazepines are composed of a benzene ring fused to a seven-member diazepine ring. Most benzodiazepines also possess a phenyl ring attached at the 5-position of the diazepine ring. Small modifications of this basic structure account for the varied pharmacologic effects of these drugs.

Benzodiazepines produce CNS depression by enhancing the effects of the major inhibitory neurotransmitter, gamma-aminobutyric acid, thereby decreasing brain activity. Benzodiazepines are classified by their duration of action that ranges from less than 6 hours to more than 24 hours. Some benzodiazepines have active metabolites that prolong their effects.

Adverse effects include increased reaction time, motor incoordination, anterograde amnesia, slurred speech, restlessness, delirium, aggression, depression, hallucinations, and paranoia. Unlike barbiturates, large doses of benzodiazepines are rarely fatal unless combined with other CNS depressant drugs, such as alcohol or opioids. Flumazenil can be administered by injection to reverse the adverse effects of benzodiazepines.

Tolerance often develops after long term use requiring larger doses to achieve the desired effect. Physical and psychological dependence may develop, whether taken under a doctor’s orders or used illicitly. Withdrawal symptoms, the severity of which is dependent on the dose, duration of use, and drug used, include anxiety, insomnia, dysphoria, tremors, and seizures. Withdrawal can be precipitated by the administration of flumazenil to individuals dependent upon benzodiazepines.

Illicit Uses:

Benzodiazepines, particularly those having a rapid onset, are abused to produce a euphoric effect. Abuse of benzodiazepines is often associated with multiple-substance abuse. Diazepam and alprazolam are used in combination with methadone to potentiate methadone’s euphoric effect. Cocaine addicts use benzodiazepines to relieve the side effects (e.g., irritability and agitation) associated with cocaine binges. Benzodiazepines are also used to augment alcohol’s effects and modulate withdrawal states. The doses of benzodiazepines taken by abusers are usually in excess of the recommended therapeutic dose. Benzodiazepines have been used to facilitate sexual assault.

The American Association of Poison Control Centers reports 78,530 case mentions, 30,896 single exposures, and 8 deaths associated with benzodiazepines in 2008. There were an estimated 271,698 emergency department visits attributed to benzodiazepines in 2008 (New DAWN ED). Of the 271,698, 104,762 were alprazolam, 48,385 were clonazepam, 26,518 were diazepam, 36,602 were lorazepam and 5,080 were temazepam. According to the 2009 National Survey for Drug Use and Health (NSDUH), 20.4 million individuals aged 12 and older have misused benzodiazepines in their lifetime.

Illicit Distribution:

Individuals abusing benzodiazepines obtain them by getting prescriptions from several doctors, forging prescriptions, or buying diverted pharmaceutical products on the illicit market. Domestic and foreign products are found in the illicit market. Alprazolam is one of the top three prescription drugs illegally encountered. In 2009, law enforcement officials submitted 35,332 alprazolam, 9,530 clonazepam, 7,123 diazepam, 2,143 lorazepam and 375 temazepam exhibits to Federal, state and local forensic laboratories for analysis. From January through June 2010, 16,816 alprazolam, 4,191 clonazepam, 2,840 diazepam, 889 lorazepam and 146 temazepam exhibits were submitted to Federal, state and local forensic laboratories.

Control Status:

Benzodiazepines are classified as schedule IV depressants under the Controlled Substances Act. Flunitrazepam is unique among the benzodiazepines in being placed in schedule IV but having schedule I penalties.

Comments and additional information are welcomed by the Drug and Chemical Evaluation Section; Fax 202-353-1263, telephone 202-307-783, or Email ODE@usdoj.gov.