These complex pharmacological activities explain the different clinical effects (i.e., anxiolytic, hypnotic, anticonvulsant, amnestic, and muscle relaxant) of BZDs. While certain NPS belonging to the BZD class possess pharmacological profiles similar to controlled pharmaceutical BZDs, clinical and pharmacological profiles of current emerging BZDs are still not well-described. In order to decrease the availability of these substances in the global illicit drug market, more effort is needed by early warning agencies to reduce the timing between formal notifications and scheduling decisions. Etizolam and phenazepam are further diverted from the regulated market and illegally imported from those countries where they are licensed therapeutic drugs 138,149. 3-Hydroxyphenazepam was identified in a seized white tablet and reported in October 2016 by Denmark. It was identified in Sweden in 10 seized white tablets labelled “XANAX” and reported to EMCDDA in October 2014 .
Combining Substances
All cases had multiple drugs; one was also positive for etizolam. In 33 cases the cause of death was reported as accidental overdose due to polydrug toxicity; subjects were known drug users or had a history of mental disorders. Acute intoxications and deaths related to DBZD, alone or in combination with other drugs of abuse, were reported in Finland, Germany, Japan, Norway, Poland, Sweden, UK and USA. In 49 reports 3-hydroxyphenazepam, adinazolam, clonazolam, etizolam, deschloroetizolam, diclazepam, flualprazolam, flubromazepam, flubromazolam, meclonazepam, phenazepam and pyrazolam were the sole or explicit contributory cause of poisoning, driving-impairment and death.
Two Deaths Due To Co-ingestion Of Phenazepam With Opiates Or Opioids
Most designer BZDs possess a liver metabolism, primarily by oxidative metabolism mediated by the CYP450 family, mainly CYP3A4 . These compounds are sold as tablets, powder, pellets, capsules or blotters, and recently liquids under their own names, at very affordable prices 37, 211, 212. However, beside these BZDs, there are also completely new and recently synthetised NPS BZDs (i.e., pyrazolam, flubromazepam, etc.), some of them were previously research trial compounds whose development did not proceed to clinical use 79, 210.
Alprazolam triazolobenzophenone is not currently controlled under the 1971 United Nations Convention on Psychotropic Substances or the 1961 Single Convention on Narcotic Drugs. It was firstly developed by the Upjohn Company in the 1980s as a water-soluble pro-drug of alprazolam for the parenteral (intravenous or intramuscular) ROA . Diclazepam is not currently controlled under the 1971 United Nations Convention on Psychotropic Substances or the 1961 Single Convention on Narcotic Drugs. Diclazepam has a long half-life of approximately 42 hours and its pharmacokinetic profile follows a biphasic elimination . In particular, a low dose is 2-4 mg, a typical dose is 4-8 mg, and a high dose is 8-12 mg or more . Flubromazepam was first identified in a sample of capsules analysed by a German university forensic institute in March 2013 69, 70, 72, 73.
However, the drug's powerful anti-anxiety and muscle relaxant properties make it twice as likely to be abused. When illegally obtained, it's often combined with other drugs, like synthetic cannabinoid products. When overdosed, phenazepam is extremely dangerous and potentially fatal.
Norfludiazepam has a significantly longer half-life compared to flurazepam (up to hours) . It is the active metabolite of flurazepam and fludiazepam and is used in the synthesis of midazolam, either as an intermediate with 2-amino-5-chloro-2'-fluorobenzophenone as the starting substance or as the starting substance itself 74, 136, 154. The substance was analytically confirmed by the Swedish National Forensic Centre using GC-MS, GC-IRD (Gas Chromatography with infrared detection), LC-HRMS and NMR 9, 135. Bromazolam was first identified in a sample of 0.74 grams of yellow powder seized by Swedish Customs in Stockholm on 3 August 2016. Bromazolam is not currently controlled under the 1971 United Nations Convention on Psychotropic Substances or the 1961 Single Convention on Narcotic Drugs. Flunitrazolam is not currently controlled under the 1971 United Nations Convention on Psychotropic Substances or the 1961 Single Convention on Narcotic Drugs.
TEK Benzo Pill/blotter Preparation (Easy Way To Dose Phenazepam)
This may reflect differences in tolerance that appear after frequent drug exposure. Similarly, blood etizolam and flualprazolam concentrations were similar in DUID cases and deaths 86,92,101,102. To date, correlations between dose and response, duration of action, metabolism, and onset of action are still poorly understood, making it harder for users to accurately dose the compound they purchased, increasing the prospect of potential intoxication. The patients may not be aware of the identity or concentration of DBZD in a drug product before suffering symptoms of intoxication . Clinicians should be asking patients about substance abuse including NPS and DBZD during routine preventive care and ED visits.
What Are The Side Effects Of Phenazepam?
It is not a scheduled drug here in the United States or in most of Western Europe. As a result, seizures of phenazepam still occasionally take place in the UK . It was originally intended for use in treating psychological problems, but the discovery of its anti-convulsant properties led to it being investigated as a possible epilepsy treatment. The early origins of phenazepam are hazy, but it is likely that the first synthesis occurred in the USSR in the mid-1970's, with the earliest mentions of it in Soviet medical literature coming from 1978. The danger in situations such as this is that people may take larger amounts of phenazepam while unaware that what they are taking is around 20 times more potent than what they believe they are taking . Later that year, 5 young people from the Scottish Borders were admitted to hospital follwing overdoses.
The onset of symptomatology occurs in minutes, effects last 5-8 hours and after-effects for 6-24 hours . There are several anecdotal reports from psychonaut fora which describe it with a “high potency which allows an effective dose of a few milligrams to be present on a paper dose (…)” 52; 54. Subsequently, powders, as well as ‘blotters’ (similar to LSD paper doses) were reported .
In humans pinazepam acts as a pure anxiolytic agent in that it does not possess to any significant degree the other pharmacological characteristics of benzodiazepines. For toxicity in children 2 years old or younger, read "10 surprising substances that can kill a toddler." So, let’s keep informed of their side effects and drug interactions and let’s remain vigilant for ourselves and our loved ones. Its delayed effect, which can take 2-3 hours, compounds its dangers by inviting the inexperienced user to re-dose.
Classification
Conceptualization, M.A.H. and F.P.B.; investigation, P.B.; data curation, P.B. Further studies, professional training and analytical development are required to reduce the undercounting and underreporting of the cases in order to obtain robust and consistent epidemiological data. Clinical and forensic toxicologists are on the front line, in cooperation with public health safety institutions, to identify emerging DBZD in cases of intoxication, drug offenses and unexplained deaths. The present data should inform interpretation of DBZD-related deaths and apprise law enforcement, clinicians and ED personnel on the dangers of DBZD. For attributing the cause of death, each case must be assessed individually, taking into account the circumstances surrounding the death, drug tolerance and postmortem redistribution. Furthermore, the newest DBDZ may have high cross-reactivity with common BZD immunoassays, which often do not distinguish between designer and prescribed BZD.
Dosage (Posology) And Method Of Administration
Phenazepam was reported to EMCDDA in July 2011 by Germany and UK. A young man was admitted to the ED in December 2014 after ingesting approximately 100 tablets (600 mg) of meclonazepam. Meclonazepam is structurally related to clonazepam and was reported for the first time to EMCDDA in August 2014 after identification in 145 seized capsules in Sweden . Abdul et al. reported two additional deaths in which flubromazolam was found in femoral blood at concentrations of 8 and 16 ng/mL . Eleven flubromazolam DUID cases were reported; in two, driving impairment was assessed by CTI, while in the remaining nine, a SFST was performed by officers.
- Clonazolam was classified as a Class C drug by the May 2017 amendment to the Misuse of Drugs Act 1971 in the UK .
- It was added to the list of controlled substances under the Misuse of Drugs Act 1971 in 2012.
- There are no clinically significant anecdotal reports from psychonaut fora describing the clinical effects of methylclonazepam so far.
- Some are also sold on the illicit drugmarket as counterfeit forms of traditional BZDs or as either adulterants or diluents in heroin or other synthetic opioids/cannabinoids.
- Fonazepam is normally consumed in a tablet (or in powder) form and administered in doses ranging from 0.5 to 3 mg 51, 52, 54.
Phenazepam is a long-acting benzodiazepine and anxiolytic used for anxiety in Russia—it’s an illicit drug in the United States. The drug's effect was so specific and so toxic it led to new scientific understanding of the disease. Sometimes the effects are things no one expected.
Although benzodiazepines are widely used prescription drugs, phenazepam doesn't have an accepted medical use in the U.S. Emily continued taking Insulin and Metformin (anti-diabetic drugs) at their usual dose even though she wasn’t able to eat very much for three days. In three additional case reports from the United States during the study period, liquid chromatography/mass spectroscopy was used to confirm the presence of etizolam, flubromazolam, and clonazolam in biological samples from patients suspected of ingesting a designer benzodiazepine 10,24,25. Specific assays for several designer benzodiazepines and their metabolites have only recently been described 20–22, contributing to a lack of exposure and mortality data. This rise of NPS has been particularly prevalent in Europe where the EMCDDA via the European Early Warning System (EU-EWS) is now monitoring over 620 substances, with 20 of these being benzodiazepines (European Monitoring Centre for Drugs and Drug Addiction, 2017).
Pharmacokinetic data suggest an elimination half-life of about 100 hours and anticonvulsant properties . The onset of symptomatology is reported after minutes, and effects may last more than 18 hours and after-effects more than 36 hours . Phenazepam has been reported to be used to enhance the euphoric effects of opioids (particularly, to “boost” methadone doses), to alleviate withdrawal or abstinence syndrome (i.e., between heroin ‘fixes’), to potentiate the effects of alcohol and to temper/balance cocaine ‘highs’ 28, 50, 54.
3-Hydroxyphenazepam is an active metabolite of both phenazepam (7-bromo-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one) and cinazepam 120, 121. Cloniprazepam is usually sold online in 2.5 mg capsules and available is in packs of 20, 60, 120 and 240 and it appears to exert similar effects to clonazepam . The substance was analytically confirmed by GC-MS, GC-IR (gas chromatography infrared spectrometry), LC-HRMS (Liquid Chromatography-High Resolution Mass Spectrometry) and NMR 70, 110, 118, 119. Cloniprazepam was first identified in a seizure of 25 white capsules by Swedish Police in Sundsvall on 2 December 2015. Cloniprazepam is not currently controlled under the 1971 United Nations Convention on Psychotropic Substances or the 1961 Single Convention on Narcotic Drugs.
In some cases, people have taken what they thought was a typical dose of Valium but was actually a high dose of phenazepam. Using the drug in this way can lead to overdose or death, especially in high doses. Phenazepam is sometimes used as a recreational drug for its euphoric effects. In the U.S., it is not classified as a controlled substance.
There are no clinically significant anecdotal reports from psychonaut fora describing the clinical effects of methylclonazepam so far. Furthermore, it has also been reported to exert both facilitative and depressive effects on paradoxical sleep in cats, depending on the dose . There are no clinically significant anecdotal reports from psychonaut fora describing the clinical effects of thionordazepam so far. Therefore, it has been supposed to possess similar pharmacological and toxicological properties to flunitrazepam (i.e., hypnotic and pre-anesthetic effects) . It has been reported that metizolam causes effects similar to etizolam, even though it is half as potent and with around a 60% longer t ½ .
