Etizolam is available as a prescription medication in Japan and parts of Europe, but it is not used medicinally in the United States. The drug is not currently scheduled as a controlled substance by the United States Drug Enforcement Administration (DEA), but several states classify it as an illicit drug.1 It is a Schedule I drug in some states and unscheduled in other states.
The DEA reports that etizolam is sometimes obtained online or purchased from retail locations that have labeled the substance as a “research chemical”.1
Xanax (alprazolam) is a drug of the benzodiazepine class. Xanax has a relatively fast onset of action and a short half-life compared to other benzodiazepines—in other words, its effects are felt quickly but also wear off rather quickly.2 Xanax is a DEA Schedule IV controlled substance, indicating that it may be prescribed for medical use, but has some potential for abuse and dependence.2
Medicinal Uses of Etizolam and Xanax
The treatment indications for etizolam in countries where it is prescribed are similar to those of benzodiazepines like Xanax.
Taking these drugs results in:3
- A significant decline in subjective feelings of anxiety.
- Relaxation and sedation.
Common medicinal uses for benzodiazepines and thienodiazepines include:3
- Anxiolytic properties—to management of anxiety and panic disorder.
- Hypnotic properties—for short-term management of insomnia.
- Anticonvulsant properties—to control seizures and muscle spasm.
Other medicinal uses for both drugs include anesthetic induction, being used as skeletal muscle relaxants, and in the treatment of other issues with anxiety that occur in neurological and other psychiatric disorders aside from anxiety disorders (e.g., depression).3
Mechanism of Action
The mechanism of action for benzodiazepines and for etizolam is also similar. Both drugs interact with GABA (gamma-aminobutyric acid) receptors to increase the effect of that neurotransmitter when it binds to and activates the receptor. GABA is the major inhibitory neurotransmitter in the central nervous system, and it functions to modulate various physiological processes by slowing down the firing rates of neurons. Both etizolam and Xanax are central nervous system depressant drugs.3
Abuse of Etizolam and Xanax
There do not appear to be reliable statistics or data on the abuse of etizolam in the US: however, according to the World Health Organization (WHO), it is a drug of abuse in countries outside the United States where it is prescribed for medical uses.4 In addition, the drug has been listed as a drug of concern in the US due to rising numbers of reports from poison control centers and emergency departments of individuals being admitted for issues associated with the use and abuse of the drug.5 The DEA has indicated that there were more than 2,400 etizolam-related drug reports received from 44 states from 2012 through 2018. 1
Xanax is the most prescribed benzodiazepine according to data provided by the Substance Abuse and Mental Health Services Administration (SAMHSA). According to the data in 2016, about 4.3 million individuals reported misusing alprazolam products (the benzodiazepine in Xanax) at least once.6 However, Xanax may not always be a primary drug of abuse. When the drug is abused, it is commonly used in combination with other intoxicating substances, most often other benzodiazepines, alcohol, or prescription narcotic pain medications.6
An individual who has developed a substance use disorder to either Xanax or etizolam would be diagnosed with a sedative, hypnotic, or anxiolytic use disorder according to the diagnostic criteria or by the American Psychiatric Association (APA).7
Though not a complete list, such diagnostic criteria would include: 7
- Having significant problems with controlling use of the drug in numerous contexts.
- Significant impairment, distress, or dysfunction in more than one area of life associated with the drug.
- Significant cravings to use the drug.
- Continued use of the drug despite problems with functioning, physical health, or emotional health.
- Developing signs of physical dependence on the drug.
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Tolerance develops rapidly to etizolam and Xanax with consistent use. For this reason, when used medicinally, drugs like Xanax and etizolam are generally used for short-term pharmaceutical management while other longer-term interventions (most often behavioral interventions) can be implemented. As many individuals who abuse these drugs for nonmedical purposes take them in higher-than-prescribed doses and/or more frequently than indicated, tolerance can develop even more rapidly. The development of tolerance commonly results in even more accelerated patterns of use that, in turn, hastens the development of significant physiological dependence to these drugs—which all but guarantees the arrival of an unpleasant and at times dangerous withdrawal syndrome when attempts are made to curtail or quit continued drug use.
The acute withdrawal syndrome for Xanax and etizolam may involve a similar set of symptoms. In some instances—in a phenomenon known as protracted withdrawal—symptoms of withdrawal persist well beyond the more commonly experienced acute time period.
Acute withdrawal: An acute phase of withdrawal typically begins within a few days after the person has discontinued the drug. For sedative drugs with shorter half-lives like Xanax (~11-12 hours), withdrawal symptoms may appear rather rapidly; similarly for etizolam (half-life ~4-5 hours), the symptoms of withdrawal may develop quite quickly.8 Symptoms in the acute phase are typically intense, uncomfortable, and due to seizure risks, may even be life-threatening in some instances. Depending on the individual’s level of physical dependence, the acute phase may last for several days up to several weeks.8
Symptoms may include some of the following:8
- Feelings of anxiety (rebound anxiety).
- Insomnia, irritability, or restlessness.
- Significant depression, emotional lability.
- Strong cravings to use the drug.
- Fever, perspiration, chills.
- Nausea, vomiting, appetite loss, and/or stomach cramps.
- Irregular heartbeat and/or hypertension.
- Tremors or seizures.
Protracted withdrawal: Should it develop, the symptoms of a more protracted withdrawal persist beyond the point that many symptoms in the acute phase start to subside. The peak of the acute symptoms will occur within 1-2 weeks after their onset, but for individuals with severe abuse, issues may last longer. The protracted phase consists of symptoms that occur in the acute phase and the onset of psychological symptoms, such as depression and cravings, if these were not experienced the acute phase. The protracted phase can run for several weeks in some individuals. Seizure potential is decreased during this phase but remains a possibility.8
The standard treatment for acute withdrawal from either drug is to place the individual under the supervision of a psychiatrist or addiction medicine physician and initiate them on a longer-acting benzodiazepine (e.g., Valium) taper.8
Over time, the physician slightly decreases the dose at specific intervals to wean the person off the drug. A medical detox program for sedative-hypnotic drugs may take some time, as withdrawal from these substances is often quite problematic, but it is a far safer method of discontinuation, reduces relapse potential, and results in far less distress than using a cold-turkey approach.8
From start to finish, a treatment protocol for an individual recovering from abuse of either drug will likely include similar therapeutic elements. Such effective components of comprehensive treatment for substance abuse may include: 9
- A thorough assessment of the individual to identify all areas of concern and treatments to address them.
- Placement in a medical detox program for safe withdrawal management.
- Initiation of therapy and peer support group participation.
- Participation in aftercare program(s) after completion of initial detox and rehabilitation.
- Continued abstinence and, when needed, additional treatment measures for long-term recovery maintenance.
Because both Xanax and etizolam are central nervous system depressant drugs, there is a potential for overdose on either drug. Overdose on either drug can be potentially fatal, and any individual who is suspected of overdosing on these drugs should receive emergency medical treatment.10
Signs of overdose include:
- Significant lethargy, unconsciousness, or a comatose state.
- Significant confusion, incoherence when speaking, and problems with motor coordination.
- Significantly decreased breathing rate.
- DEA. Etizolam.; 2018. https://www.deadiversion.usdoj.gov/drug_chem_info/etizolam.pdf. Accessed June 20, 2019.
- FDA. Xanax. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018276s044,021434s006lbl.pdf. Accessed June 20, 2019.
- Etizolam | Drugbank. https://www.drugbank.ca/drugs/DB09166. 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.
- 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.
- Substance Abuse and Mental Health Services Administration. Results from the 2016 National Survey on Drug Use and Health: Detailed Tables.; 2017.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5®) – American Psychiatric Association
- 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.
- Kang M, Ghassemzadeh S. Benzodiazepine Toxicity. StatPearls Publishing; 2019. http://www.ncbi.nlm.nih.gov/pubmed/29489152. Accessed June 20, 2019.
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