Benzodiazepines: Uses, Abuse, And Novel Designer Drugs.pdf

Benzodiazepines are a class of drugs that produce central nervous system (CNS) depression and are most commonly used to treat insomnia and anxiety. The five benzodiazepines that are most commonly prescribed and encountered on the illicit market are Alprazolam (e.g., Xanax), lorazepam (e.g., Ativan), clonazepam (e.g., Klonopin), diazepam (e.g., Valium), and temazepam (e.g., Restoril). In recent years, the trafficking and abuse of "novel designer benzodiazepines" has dramatically increased.

Benzodiazepines are widely prescribed drugs, with total prescriptions dispensed in the United States in 2024 being approximately 30.5 million for alprazolam, 21.4 million for clonazepam, 19.8 million for lorazepam, 8.2 million for diazepam, and 3.8 million for temazepam. They are prescribed for their sedative-hypnotic, anti-anxiety, muscle relaxant, and anti-convulsant effects.

All benzodiazepines are composed of a benzene ring fused to a seven-member diazepine ring, with most possessing 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. They are classified by their duration of action, which 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.

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 include anxiety, insomnia, dysphoria, tremors, and seizures.

Benzodiazepines are abused to produce a euphoric effect, often associated with multiple-substance abuse. Diazepam and alprazolam are used in combination with methadone to potentiate methadone's euphoric effect. Those who misuse cocaine or other stimulants may also use benzodiazepines to relieve side effects associated with cocaine or stimulant binges.

Benzodiazepines are also used to augment alcohol's effects and modulate withdrawal states. Those who misuse sedative hypnotics often use prescription benzodiazepines in excess of the recommended therapeutic dose. Additionally, benzodiazepines have long been associated with drug-facilitated sexual assault through the use of prescription medication.

According to the United Nations Office on Drugs and Crime, benzodiazepine-type novel psychoactive substances (NPS) continue to constitute the greatest number of NPS reported to the Tox-Portal, accounting for 47% of all NPS cases associated with postmortem investigations and 67% of all DUID cases.

Individuals who abuse benzodiazepines obtain these substances by collecting prescriptions from several doctors, forging prescriptions, or buying diverted pharmaceutical products on the illicit market. One of the top three prescription drugs diverted from the licit market is alprazolam.

Benzodiazepines are controlled in schedule IV of the Controlled Substances Act, with the exception of flualprazolam, etizolam, clonazolam, flubromazolam, and diclazepam, which are placed in schedule I. Flunitrazepam is unique among the benzodiazepines, being a schedule IV substance with schedule I penalties.