Etizolam is an anxiolytic drug with a pharmacologic profile similar to classic benzodiazepines like Xanax.
Whereas traditional benzodiazepines are schedule II prescription drugs in the US, etizolam is available over-the-counter in most states and some countries. I’ve used etizolam for sleep and anxiety and can vouch that it does what it’s supposed to do.
Two observations stand out about etizolam:
– It may be selective for GABA-A subunits related to stress (α1, β2, γ2).
– It has fewer side effects compared to full GABA-A agonists.
Both factors likely contribute to its rising popularity (in addition to the fact that it’s readily obtainable online sans prescription). Despite its favorable tolerability, etizolam is associated with potentially serious adverse events.
In this guide, I will discuss the common and uncommon side effects of etizolam and share some strategies to minimize etizolam’s downsides.
Side effects in general are not nearly as cut-and-dry as you might imagine. Most drugs have side effects that are serious yet rare – so a laundry list of side effects can be misleading. Consider these side effects:
– Hepatitis
– Seizures
– Hemolytic anemia
These are actually some of the more serious side effects of aspirin.
Most primary care doctors say that a big part of their job is health anxiety management. The majority of patients that come in to see a general practitioner don’t require treatment but seek to relieve their *fear* about a malady.
There are three key points you should commit to memory about etizolam’s side effects:
– **The side effects are proportional to the dose.** Side effects tend to lessen in intensity or even vanish at lower doses.
– **Don’t combine etizolam with other CNS depressants.** Alcohol, opioids, barbiturates, anesthetics, benzodiazepines – these all depress CNS activity. CNS depressants have a synergistic effect which can be dangerous and is easy to underestimate.
– **Take breaks**. If you’re using etizolam recreationally, I’d avoid chronic usage. If you’re relying on etizolam to manage anxiety or insomnia – that’s a different story. Chronic etizolam usage may impair memory consolidation so it can interfere with your intellectual function.
Etizolam 0.5 Side Effects
The side effects of etizolam 0.5 and etizolam 0.25 are equivalent. The only difference is that the magnitude of etizolam side effects is smaller at lower dosages.
Studies on Etizolam’s Side Effect Profile
One study [ref1] on the effectiveness of etizolam for anxiety found no significant changes in blood pressure, heart rate, or weight with placebo or etizolam.
The authors also reported that adverse events were not statistically different with etizolam versus placebo. However, somnolence or sleepiness was reported by 7 of 77 patients (9.1%). Four of these patients reported somnolence both with etizolam and with placebo.
Surprisingly, the study did not detect any significant differences between the etizolam 0.5 mg or placebo groups in cognitive function or anxiety measures. It may be that they used too low of a dose to properly separate the placebo and etizolam arms.
Negative Etizolam Side Effects
Etizolam is a benzodiazepine derivative. Thus, it makes sense that there’s a lot of overlap in the side effect profile of etizolam and traditional benzodiazepines.
The most common side-effects of etizolam are related to *sedation* and *musculoskeletal relaxation*.
This group of side effects includes:
– dizziness
– drowsiness
– decreased attention
– impaired coordination that may result in falls and injuries [^ref2].
– impaired driving ability and increased chances of traffic accidents [^ref3].
– decreased libido and erectile dysfunction
– melancholy and disinhibition
This suggestion is probably not best practice, but I have personally offset etizolam’s sedating effects with a cup of coffee. Most of the time I use etizolam to assist with sleep initiation, so sedation is actually not a bug but a feature. But when I take it during the day, caffeine can help in a pinch. In general, I’ve found that etizolam is much “cleaner” than other sedating drugs.
Etizolam Long-Term Side Effects
Chronic benzodiazepine use can deleteriously impact cognitive function and alter mood and behavior. However, if you use reasonable doses (e.g., 0.25-0.5mg), take frequent breaks, and avoid polypharmacy, there’s little reason to worry. If you want to educate yourself about the negative side effects of benzodiazepines, I recommend checking out benzobuddies.
Here are some long-term negative effects of etizolam that have been reported:
– loss of sex drive
– agoraphobia and social phobia
– stress, depression, anhedonia (the inability to experience pleasure)
Not everyone, however, experiences problems with long term use [^ref4]. Drugs like etizolam are also rarely associated with an altered understanding of self and environment, also known as DPDR (depersonalization-derealization disorder). If you want to learn more about DPDR, I highly recommend the TV series *Mr. Robot*.
Cognitive Side Effects
Most published literature on the topic will tell you that benzodiazepines have a negative impact on cognitive function. However, it’s not as cut-and-dry as you might think.
Here’s an excerpt from one Erowid user’s experience report on etizolam:
> Luckily I had run out of etizolam and just smoked the usual few joints but I did not realize how long this ‘comedown’ type effect would last. It took me about 3 days to let my anxiety settle and a further 7-10 days for my memory to start working properly. I found my memory was hugely impaired and not just regarding the previous two days of etizolam either, I suddenly managed to realize that I couldn’t remember ALOT of stuff that would normally require no effort to recollect. This concerned me but I kept myself calm and clean for days until I noticed it was gradually going back to normal.
The idea is that benzodiazepines interfere with the formation and consolidation of new memories and can induce anterograde amnesia [^ref6]. Yet, academic researchers have contradictory opinions regarding the effects of long-term benzodiazepine use.
There are two schools of thought. One camp maintains that short-term effects of benzodiazepine use persist into the long-term. Moreover, they are not resolved after stopping the benzodiazepine. The other camp’s view is that the underlying anxiety disorder is to blame, or that cognitive deficits in long-term benzodiazepine users happen just for a short time after the last dose.
A 2004 meta-analysis of 13 smaller studies supports the idea that short-term benzodiazepine use can have long-term effects [^ref7].
According to the 2004 meta-analysis, long-term use of benzodiazepines was associated with moderate adverse effects on all areas of cognition. Visuospatial memory was most prominently affected.
Some of the other impairments reported were decreased IQ, visuomotor coordination, information processing, verbal learning, and attention.
Yet other researchers [^ref8] question the relevance of this meta-analysis because participants were recruited from drug rehabilitation clinics. Also, concurrent drug use and psychiatric disorders were not controlled for in the study. Finally, several of the included studies ran the cognitive tests *during* benzodiazepine withdrawal, which may be responsible for the impairment.
Paradoxical Effects
Paradoxical responses are effects in the opposite direction that you might expect.
For example, benzodiazepines like etizolam sometimes increase seizures in epileptics [^ref9], even though they’re also prescribed to *treat* seizures.
Other paradoxical responses to benzodiazepines include aggression, violence, impulsivity, irritability and suicidal behavior. These are all caused by disinhibition and a breakdown of behavioral controls. Fortunately, most reports of disinhibition of this magnitude involve large doses of high-potency benzodiazepines [^ref10].
One Erowid user reports waking up after an etizolam bender missing some pills, and concludes that they took additional etizolam without remembering it:
> 6.00: we wake up from our naps feeling groggy as hell. I go to pee. I get back and notice that out of the 30 pills we had bought and received that morning, only 9 were left. The conclusion could either be, someone stole them, however, I highly doubt Sandy would ever steal from me. We had bought the pills together and even if she did steal, why not steal the entire thing? The most logical conclusion for me seem to be, and is concurrent with other reports regarding etizolam, is that somewhere during some time that neither of us can remember, someone took more pills.
This is a cautionary tale about how the disinhibiting effects of etizolam can lead you to take more of the drug than you had originally planned. While sober you might plan to take 0.5 etizolam but wind up taking much more while intoxicated.
Worsening of Psychiatric Symptoms
Sometimes etizolam has been known to exacerbate mental health conditions, though it does alleviate insomnia and anxiety.
Examples include:
– worsening of cognitive issues that are already common in anxiety disorders
– depression and suicidal ideation [^ref11]
– poor sleep quality by inhibiting slow wave sleep [^ref12]
– rebound symptoms and inter-dose withdrawal
– interfering with psychotherapy by inhibiting memory consolidation
Anxiety, insomnia, and irritability may be briefly exacerbated during withdrawal, but psychiatric symptoms after discontinuation diminish over time. Luckily, for people that have benzodiazepine-related issues, functioning significantly improves within 1 year of discontinuation.
Dependence
A big problem with the long-term use of benzodiazepines is the development of dependence and tolerance. Tolerance grows relatively quickly to the sedative-hypnotic, anticonvulsant, and muscle relaxant effects of benzodiazepines.
Further reading: A Year of RC Benzo Addiction
> I dunno how I found etizolam first, I know it was some session of late night internet surfing. I found out about it, but didn’t order it. About two weeks later, another hungover morning and I realized I had ordered a strip of etizolam tablets, ten 1 mg pills. I forgot I ordered them soon after.
> About a week later, they showed up. I was immediately skeptical of the cheap-looking Indian packaging and thought this stuff was probably garbage. I popped 4 tablets and headed to my girlfriend’s house across town.
> Once I got on the bus, I started realizing I was getting really sedated. As soon as I got off, I literally stumbled down the street and went in her house, where I fell asleep for 2 hours in the day which I never do. This was exactly like Xanax, which I loved but never used because it was always too hard to find and too expensive, it had been years since I took it.
Etizolam Withdrawal Symptoms
Discontinuation of etizolam or a sudden reduction of the dose, even after a relatively short course of treatment (three to four weeks), may result in two groups of symptoms—rebound and withdrawal.
The best way to prevent etizolam dependence is to avoid chronic usage. If you’re using etizolam on a daily basis and want to discontinue the drug, make sure to slowly taper your dosage rather than abruptly stop.
Rebound symptoms are the return of original symptoms for which the drug was prescribed in the first place. Withdrawal symptoms are new symptoms that happen when etizolam is stopped. They’re the principal indication of physical addiction [^ref13].
Here are the most frequently reported symptoms of etizolam withdrawal:
– sleeplessness
– gastrointestinal discomfort
– tremors
– agitation
– fearfulness
– muscle spasms
– anxiety
The less common effects are irritability, sweating, depersonalization, derealization, hypersensitivity to stimulation, depression, suicidal behavior, psychosis, seizures, and delirium tremens [^ref14].
Acute symptoms generally occur as an outcome of sudden or over-accelerated withdrawal. Sudden withdrawal can be dangerous. Thus, gradual decrease regimen is recommended [ref15].
Benzodiazepines have a reputation with patients and doctors for causing a serious withdrawal syndrome. Yet, this is in large part because of the withdrawal process is poorly managed. Rapid withdrawal from etizolam exacerbates the withdrawal syndrome and increases the failure rate.
A gradual and slow withdrawal customized to the individual along with emotional support is the most effective way to manage withdrawal.
Non-benzodiazepine sedatives are best avoided during etizolam withdrawal as they’re cross-tolerant with etizolam and can reinforce a habit. During withdrawal, fluoroquinolone antibiotics are best avoided because they aggravate withdrawal symptoms. Antipsychotics usually are not advocated for benzodiazepine withdrawal (or other CNS depressant withdrawal states).
Withdrawal from long-term etizolam use is in the end valuable for many dependent individuals. Cessation of chronic benzodiazepines use often leads to improved physical and mental health especially in the elderly. Some long-term users report continued benefit from taking benzodiazepines, but this perceived benefit may be simply from suppression of withdrawal effects.
[ref1]: De candia MP, Di sciascio G, Durbano F, et al. Effects of treatment with etizolam 0.5 mg BID on cognitive performance: a 3-week, multicenter, randomized, double-blind, placebo-controlled, two-treatment, three-period, noninferiority crossover study in patients with anxiety disorder. Clin Ther. 2009;31(12):2851-9.
[ref2]: Ballenger JC (2000). “Benzodiazepine receptors agonists and antagonists”. In Sadock VA, Sadock BJ, Kaplan HI. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry (7th ed.). Lippincott Williams & Wilkins. pp. 2317–23.
[ref3]: Rapoport MJ, Lanctôt KL, Streiner DL, et al. Benzodiazepine use and driving: a meta-analysis. J Clin Psychiatry. 2009;70(5):663-73.
[ref4]: Hammersley D, Beeley L (1996). “The effects of medication on counseling”. In Palmer S, Dainow S, Milner P. Counselling: The BACP Counselling Reader. 1. Sage. pp. 211–4. ISBN 978-0-8039-7477-7.
[ref5]: Stewart SA (2005). “The effects of benzodiazepines on cognition” (PDF). The Journal of Clinical Psychiatry. 66 Suppl 2 (Suppl 2): 9–13. PMID 15762814.
[ref6]: Ballenger JC (2000). “Benzodiazepine receptors agonists and antagonists”. In Sadock VA, Sadock BJ, Kaplan HI. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry (7th ed.). Lippincott Williams & Wilkins. pp. 2317–23. ISBN 0-683-30128-4].
[ref7]: Stewart SA (2005). “The effects of benzodiazepines on cognition” (PDF). The Journal of Clinical Psychiatry. 66 Suppl 2 (Suppl 2): 9–13. PMID 15762814.
[ref8]: Barker MJ, Greenwood KM, Jackson M, Crowe SF (2004). “Cognitive effects of long-term benzodiazepine use: a meta-analysis”. CNS Drugs. 18 (1): 37–48. doi:10.2165/00023210-200418010-00004. PMID 14731058
[ref9]: Riss J, Cloyd J, Gates J, Collins S (August 2008). “Benzodiazepines in epilepsy: pharmacology and pharmacokinetics”. Acta Neurologica Scandinavica. 118 (2): 69–86. doi:10.1111/j.1600-0404.2008.01004.x. PMID 18384456.
[ref10]: Paton C (2002). “Benzodiazepines and disinhibition: a review” (PDF). Psychiatr Bull R Coll Psychiatr. 26 (12): 460–2. doi:10.1192/pb.26.12.460.
[ref11]: Michelini S, Cassano GB, Frare F, et al. (1996). “Long-term use of benzodiazepines: tolerance, dependence and clinical problems in anxiety and mood disorders.”. Pharmacopsychiatry. 29: 127–134.
[ref12]: Tasman A, Kay J, Lieberman JA, eds. (2008). Psychiatry (3rd ed.). Chichester, England: John Wiley & Sons. pp. 1186–1200, 2603–2615. ISBN 978-0470065716.
[ref13]: Chouinard G (2004). “Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound” (PDF). The Journal of Clinical Psychiatry. 65 Suppl 5 (Suppl 5): 7–12. PMID 15078112.
[ref14]: Harrison PC, Gelder MG, Cowen P (2006). “The misuse of alcohol and drugs”. Shorter Oxford Textbook of Psychiatry (5th ed.). Oxford University Press. pp. 461–2. ISBN 0-19-856667-0.]
[ref15]: Lader M, Tylee A, Donoghue J (2009). “Withdrawing benzodiazepines in primary care”. CNS Drugs. 23 (1): 19–34. doi:10.2165/0023210-200923010-00002. PMID 19062773.
