Etizolam and Toxicity
Unapproved for medical use in the United State by the US Food and Drug Administration (FDA), etizolam is sometimes obtained as a “research chemical” from online purchase or other disreputable retail sources for illicit or non-medical use. It is used primarily as an anti-anxiety and insomnia medication in other countries, like Japan and Italy. The Drug Enforcement Administration(DEA) states has a similar chemical structure and mechanism of action as benzodiazepines. In animal studies, etizolam is 6-10 times more potent than diazepam in terms of its pharmacologic effects. Like benzodiazepines, etizolam has sedative-hypnotic, anxiolytic, anti-convulsant, muscle relaxant properties.1
Any use of etizolam in the United States is considered abuse, as the drug currently has no medically accepted uses. While it is difficult to quantify etizolam abuse within the United States, the DEA publishes that drug seizures involving etizolam have been increasing relatively recently, with 140 drug reports from 2012 through June 2014 in 21 states.1
Etizolam Side Effects and Hazards of Abuse
Common side effects of etizolam use include drowsiness, fainting, muscle weakness, headache, slurred speech, impaired cognitive abilities, and loss of motor control.4 Blepharospasm, which is when the eyelids close tightly involuntarily, may also be side effects of consistent etizolam use or abuse.3
Etizolam intoxication may be similar to intoxication with alcohol or traditional benzodiazepines. Accidents due to falling down; short-term memory loss or lapses; impaired judgment, causing a person to engage in potentially dangerous or hazardous behaviors; and decreased inhibitions, leading to possible unwanted sexual contact, are all possible side effects of etizolam abuse. The higher the dose, the more significant the potential risk factors and negative consequences may be.
Etizolam can be particularly dangerous as it is not regulated or controlled within the United States. An individual may never be entirely sure what they are buying and subsequently ingesting.
While fatal etizolam overdoses are rare, taking too much of the drug at one time or mixing it with another substance, particularly opioids or another central nervous system depressant, like alcohol or benzodiazepines, can have disastrous consequences.
Etizolam Dependence and Withdrawal
The European Journal of Pharmacology indicates that, in animal studies, etizolam administration may result in less drug tolerance and dependence than classical benzodiazepines. That being said, drug dependence is still a risk, especially with chronic use at high doses; therefore, withdrawal symptoms may occur upon discontinuation of the drug.7 Etizolam, like benzodiazepine drugs, is not meant to be taken for longer than a few months at a time and is considered a short-term solution for the temporary relief of anxiety or panic disorder symptoms. Regular and prolonged use, as well as increasing dosage frequently, increases the likelihood of physiological dependence.
A case report published by the Indian Journal of Pharmacology reported on an individual taking 2.5 mg of etizolam a day for over a month who experienced classic benzodiazepine withdrawal symptoms when the dosage was reduced or stopped.
These symptoms include:8
- Heart palpitations.
- High blood pressure.
- Drug cravings.
According to the DEA, etizolam has a half-life of 3.4 hours. 1 In dependent individuals, when etizolam wears off, withdrawal symptoms can start. Since etizolam is similar to benzodiazepine drugs, which are never recommended to be stopped “cold turkey,” medical detox may be the safest method of withdrawal management.
Detox may include the use of medications and supportive care in a specialized and medically supervised facility. Longer-acting benzodiazepine drugs may be substituted for etizolam during detox and then slowly weaned off to avoid any rebound side effects from overactivity of the central nervous system after it has been suppressed by the drug for so long. By using a tapering schedule, the dangerous and more difficult withdrawal symptoms can be managed and controlled.9
Supportive methods and encouragement provided by mental health professionals can be beneficial in medical detox as well. Beyond detox, therapeutic methods are helpful in determining the root causes of self-destructive and substance-abusing behaviors and working to modify them into more positive ones. Therapy, support groups, relapse prevention programs, counseling, education, and life skills training are all integral parts of a complete substance abuse treatment program that can aid in addiction recovery.10
Lethal Dose of Etizolam
Being similar in mechanism to other benzodiazepines, etizolam can be fatal when abused. In general, deaths involving etizolam on its own are not as common; most fatalities occur when the drug is mixed with other substances, particularly other central nervous system depressants.
The Journal of Cardiology Cases reports that etizolam can cause a toxic and fatal arrhythmia, especially when it is used in combination with other medications. Taking more than the recommended medical dose or taking etizolam with other drugs can amplify the toxicity of the drug and raise the odds for a lethal dose.12
There are many factors that can contribute to overdose risks, including metabolic rates, body size, age, and general state of health. It is important to remember that etizolam has no accepted medical use within the United States and therefore no amount is considered to be safe.
It is important to remember that etizolam has no accepted medical use within the United States and therefore no amount is considered to be safe.
While etizolam has yet to be classified as a controlled substance federally, WHO reports it has been declared as such in Arizona, Alabama, Florida, Arkansas, Indiana, Georgia, Mississippi, and Virginia.
Since etizolam is illegal to buy and sell in America, it is likely obtained on the black market. As a result, it can be difficult to know exactly what is in the product. Other chemicals or toxins may be used to “cut” the drug, or there may be a variety of additives in the unregulated substance. Any mixture of etizolam with other drugs exacerbates the possible negative side effects, and a lethal dose may involve a smaller amount of the drug.
- DEA. Etizolam.; 2018. https://www.deadiversion.usdoj.gov/drug_chem_info/etizolam.pdf. Accessed June 20, 2019.
- 2 Investigators: Feds Target Sedative, Etizolam, Teens Are Using – CBS Chicago. https://chicago.cbslocal.com/2014/09/18/2-investigators-legal-narcotic-has-caught-feds-attention. Accessed June 21, 2019.
- World Health Organization. Etizolam (INN) Pre-Review Report Agenda Item 5.7 Expert Committee on Drug Dependence Thirty-Seventh Meeting. https://www.who.int/medicines/access/controlled-substances/5.7_Etizolam_PreRev.pdf. Accessed June 21, 2019.
- Etizolam | Drugbank. https://www.drugbank.ca/drugs/DB09166. Accessed June 21, 2019.
- CDC. Increases in Drug and Opioid Overdose Deaths — United States, 2000–2014. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6450a3.htm. Accessed June 21, 2019.
- OConnell CW, Sadler CA, Tolia VM, Ly BT. Overdose of Etizolam: The Abuse and Rise of a Benzodiazepine Analog. Ann Emerg Med. 2015;65:465-466.
- Sanna E, Busonero F, Talani G, et al. Low tolerance and dependence liabilities of etizolam: Molecular, functional, and pharmacological correlates. Eur J Pharmacol. 2005;519(1-2):31-42.
- Gupta S, Garg B. A case of etizolam dependence. Indian J Pharmacol. 2014;46(6):655-656.
- Vorma H, Naukkarinen H, Sarna S, Kuoppasalmi K. Long-term outcome after benzodiazepine withdrawal treatment in subjects with complicated dependence. Drug Alcohol Depend. 2003;70(3):309-314.
- Principles of Effective Treatment | National Institute on Drug Abuse (NIDA). https://www.drugabuse.gov/publications/principles-drug-addiction-treatment-research-based-guide-third-edition/principles-effective-treatment. Accessed June 21, 2019.
- Roche. VALIUM ® Brand of Diazepam TABLETS. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013263s083lbl.pdf. Accessed June 21, 2019.
- Amino M, Yoshioka K, Ikari Y, Inokuchi S. Long-term myocardial toxicity in a patient with tizanidine and etizolam overdose. J Cardiol Cases. 2016;13(3):78-81.
- WHO. Expert Committee on Drug Dependence Thirty-Ninth Meeting Expert Peer Review for Etizolam. https://www.who.int/medicines/access/controlled-substances/Etizolam-PeerReview2.pdf. Accessed June 21, 2019