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Etizolam Abuse and Side Effects

Marketed for medicinal use as a sedative-hypnotic drug with muscle-relaxing, insomnia-reducing, and anti-anxiety properties, etizolam is a thienodiazepine (pharmacologically indistinct from the benzodiazepine class of drugs) available in a number of other countries, such as Japan. It is not currently approved for use in the United States.1

  • Etizolam is chemically similar to benzodiazepines such as diazepam (Valium) and has comparable central nervous system depressant effects. Like Valium and other benzodiazepines, it has anxiety-reducing, sedating, anticonvulsant, and muscle-relaxing effects.
  • However, both animal and clinical studies indicate that etizolam is 6-10 times more potent than Valium at eliciting its various pharmacological effects.2
  • In illicit forms, etizolam may be found in tablet or powder forA woman sitting depressedm. It is sometimes administered on blotter paper that can be placed on the tongue for oral absorption.2

Etizolam Abuse

  • Illicit use of etizolam is growing. Near the end of 2014, the Blue Ridge Poison Centre in Virginia noted an upward trend in Poison Control Center calls around the country, as well as internet searches, and lists the medication as a drug of concern.3
  • The DEA notes that illicit purchases of the drug may occur online, where it has been marketed as a “research chemical”.2
  • Etizolam (called “etiz” or “etizzy” on the street) may be abused for its reinforcing, sedative effects.4 The Drug Enforcement Administration (DEA) noted a significant rise in etizolam drug reports in the span of just 5 years from 3 in 2012 to 898 in 2017.2

Warning Signs

Because etizolam is a Schedule I substance in the United States, simply having the substance is in violation of federal law and could itself be a warning sign of abuse.

Continued use despite negative side effects may also be taken as a warning sign of problematic use. Adverse effects of etizolam use may include:2,5

  • Excessive sedation/sleepiness.
  • Depression.
  • Confusion.
  • Impaired cognitive functioning.
  • Impaired coordination.
  • Changes to vision.
  • Slurred speech.
  • Libido changes.
  • Tremors.

Etizolam is not marketed in the U.S. but is widely available online, so suspicious packages arriving at the person’s home (for example, from other countries) may serve as another red flag.

Other warning signs of a growing problem with etizolam that may eventually develop in an addiction (sedative-hypnotic use disorder) include:6

  • Decreased work productivity/poor performance.
  • Increase in school absences and/or a drop in grades.
  • Increased isolation.
  • Avoidance of personal responsibilities.
  • Abandoning previously enjoyed hobbies.
  • Needing more of the drug to experience the desired effects.
  • Going through withdrawal when etizolam use is cut back or ended.

Etizolam Overdose

  • According to the World Health Organization (WHO), there have been increasing reports of misuse and several deaths associated with etizolam abuse.7 Serious adverse outcomes are more likely when sedative-hypnotics are combined other drugs that depress the central nervous system, such as alcohol.8
  • The combination compounds the depressant effects, such as sedation and respiratory depression, and may result in life-threatening overdose.9 According to a 2017 WHO expert peer review of etizolam, all known cases of etizolam-related deaths at the time involved other substances such as alcohol and opioids.10

Little information is published about overdose of etizolam specifically, but signs of a benzodiazepine overdose include:6,11,12

  • Rapidly shifting mood.
  • Extreme drowsiness.
  • Muscle weakness.
  • Slowed pulse.
  • Severely slowed or stopped breathing.
  • Coma.

An overdose should be considered a medical emergency. If you suspect an overdose in your or someone else, call 911 immediately.

Dependence and Withdrawal

Etizolam, like benzodiazepines, is associated with some potential for physiological dependence. As dependence develops, the body becomes increasingly reliant on the drug to function normally. Significant reductions in the dose or a complete cessation of use may result in the onset of acute withdrawal, the symptoms of which may be severe.

The acute etizolam withdrawal syndrome may include symptoms characteristic of benzodiazepine withdrawal, including:1,6

  • Anxiety.
  • Agitation.
  • Insomnia.
  • Cravings.
  • Rapid pulse rate.
  • Sweating.
  • Tremors.

Stopping a drug like etizolam suddenly, without medical supervision and guidance, is never a good idea. Etizolam is chemically similar to benzodiazepines, which are associated with serious, sometimes life-threatening symptoms including hallucinations and grand mal seizures.6 Medical detox is the safest and smoothest way to begin recovery from etizolam, benzodiazepine, or other sedative addiction.

Medical Detox

  • Stopping a medication like etizolam suddenly is not safe. Etizolam is a relatively short-acting benzodiazepine-type medication,1 and it may be replaced during medical detox with longer-acting benzodiazepines that are slowly tapered after introduction to mitigate withdrawal and curb drug cravings.13,14
  • Medical detox is commonly provided in a specialty facility that provides around-the-clock medical monitoring and care to stabilize the withdrawing individual and manage their symptoms, often with the use of medications.
  • Outpatient detox may be an option but is usually reserved for people strongly committed to recovery, with less pronounced physical dependence, who have not been abusing other substances, and who have a strong support system at home.14

Addiction Treatment

  • The initial goal of detox is to stabilize an individual physically and mentally, and it is an important step in a substance abuse treatment plan. Beyond detox, behavioral therapies, such as cognitive behavioral therapy (CBT) and motivational interviewing (MI), may be part of a comprehensive treatment and recovery model. CBT helps individuals to explore the way their thoughts and emotions translate into actions, and teaches new and healthier ways to cope with stress, anxiety, and cravings.15
  • By learning new techniques through group and individual therapy sessions, newly recovering individuals can determine what their personal triggers may be and how to avoid and manage them in the future without reaching for mind-altering substances.16
  • The severity of the dependence and the length of time it takes for a person to become dependent on, or even addicted to, etizolam differ from person to person. Someone taking high doses more frequently for a long period of time is likely to be more heavily dependent on the drug than a more casual user, for example.
  • Polydrug abuse, or the abuse of other drugs or alcohol in conjunction with etizolam, is likely to increase the side effects of, and potential dependence on, both substances as well. Underlying medical or mental health conditions, as well as family history and genetic factors, may also be involved in the development of a dependence on or addiction to drugs.
  • If the brain is dependent on etizolam, or another benzo, when the drug is suddenly removed, a kind of rebound effect may occur. Anxiety, depression, agitation, and insomnia, which were all dampened by the drug, may return in full force.

In addition to these powerful psychological side effects, muscle tremors and life-threatening seizures may also occur during withdrawal from a benzodiazepine. For this reason, etizolam should not be stopped “cold turkey” after dependence has been established. Other potential side effects of benzo withdrawal include:

  • Muscle weakness or tension.
  • Vivid dreams.
  • Mental fogginess.
  • Irritability.
  • Short-term memory loss.
  • Headaches.
  • Drug cravings.
  • Trouble feeling pleasure.

Instead of just stopping a drug like etizolam suddenly, it may be recommended to slowly lower the dosage over a set amount of time through a tapering, or weaning off, schedule set up and monitored by medical professionals, the International Medical Case Reports Journal reports.

This is often accomplished through medical detox, which is provided in a specialty facility that provides around-the-clock medical monitoring and care to stabilize an individual and manage withdrawal symptoms, often with the use of medications.

Etizolam is considered a short-acting benzodiazepine-type medication, and it may be replaced with longer-acting benzos during detox to mitigate withdrawal and curb drug cravings. Other medications may be used to help with specific symptoms of withdrawal as well.

 

References:

  1. Gupta, S., & Garg, B. (2014). A case of etizolam dependence. Indian journal of pharmacology46(6), 655–656.
  2. U.S. Drug Enforcement Administration. (2018). Etizolam.
  3. World Health Organization. (2015). Etizolam (INN) Pre-Review Report.
  4. Home Office. (2017). Control of Etizolam, related drugs and U-47,700.
  5. U.S. National Library of Medicine, PubChem. (n.d.). Etizolam.
  6. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: Author.
  7. World Health Organization. (2017). ETIZOLAM: Critical Review Report.
  8. The United States Attorney’s Office. (2017). Four Indicted for Roles in Selling Illegal Depressant Etizolam over the Internet.
  9.  O’Connell, Charles W.Saitman, Alec M. et al. (2015). Overdose of Etizolam: The Abuse and Rise of a Benzodiazepine Analog. Annals of Emergency Medicine, 65(4), 465 – 466.
  10. World Health Organization. (2017). Expert Peer Review for Etizolam.
  11. Center for Substance Abuse Research. (2013). Benzodiazepines.
  12. DrugBank. (2019). Diazepam.
  13. Nishii, S., Hori, H., Kishimoto, T., & Nakamura, J. (2014). A successful case of dose reduction in etizolam dependence using fine granules: a case report. International medical case reports journal7, 121–122. doi:10.2147/IMCRJ.S67103
  14. Center for Substance Abuse Treatment. Detoxification and Substance Abuse Treatment. Treatment Improvement Protocol (TIP) Series, No. 45. HHS Publication No. (SMA) 15-4131. Rockville, MD: Center for Substance Abuse Treatment, 2006.
  15. National Institute on Drug Abuse. (2018). Behavioral Therapies.
  16. National Institute on Drug Abuse. (2018). Principles of Effective Treatment.
About The Contributor
Scot Thomas, M.D.
Senior Medical Editor, American Addiction Centers
Dr. Thomas received his medical degree from the University of California, San Diego School of Medicine. During his medical studies, Dr. Thomas saw firsthand the multitude of lives impacted by struggles with substance abuse and addiction, motivating... Read More