Best Legal Benzo

Benzazepam, 6-(2-chlorophenyl)-1-methyl-8-nitro-4H-[1,2,4]triazolo[4,3-a][1,4], also known as clonitrazolam, is the triazolo analogue of clonazepam [1,129]. Clonazolam is described as “incredibly strong,” resulting in severe sedation and amnesia at oral doses as low as 0.5 mg, resulting in a slight accidental overdose [78]. It was first discovered by Swedish police in yellow capsules seized in October 2014 and reported to the EMCDDA in January 2015 [51]. Two patients were admitted to the emergency room after consuming clonazolam purchased on the Internet. Clonazolam was not confirmed and the dose was estimated based on the patient`s self-report. In the other four cases, clonazolam or clonazolam and etizolam (one case) were identified. The main side effect was CNS depression. 3-Hydroxyphenazepam is an active metabolite of phenazepam (7-bromo-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepine-2-one) and ciazepam [120, 121]. It can be quantified by LC-MS/MS in a variety of post-mortem fluids (subclavium blood, femoral blood, vital blood, urine, vitreous body) and tissues (thalamus, liver and psoas muscle) [122]; and GC-MS (detection limit: 1 mg/L) [29, 123].

In one study in which healthy volunteers received an oral dose of phenazepam of 5 mg, 3-hydroxyphenazepam was detected in urine samples but not in blood samples [29]. In research on its distribution in the plasma and brains of mice, sedative and anticonvulsant properties have been reported [124-126]. It is a complete positive allosteric modulator γ GABAA receptor [73, 126, 127]. 3-hydroxyphenazepam appears to be pharmacologically active with a potency about 5 to 10 times greater than that of diazepam, probably due to the bromine atom in the molecule [128]. In addition, 3-hydroxyphenazepam is the main metabolite of levana (3-hydroxyphenazepam hemisuccinate) [125]. Researchers report that levana has a greater anticonvulsant effect than its metabolite 3-hydroxyphenazepam [125, 126, 129]. 3-hydroxyphenazepam is currently not controlled under the 1971 United Nations Convention on Psychotropic Substances or the 1961 Single Convention on Narcotic Drugs. Phenazepam, also known as “bonsai”, “zannia” or “supersleep”, is a long-acting benzodiazepine developed in the 1970s and currently used as an anxiolytic, hypnotic and to treat alcohol withdrawal syndrome in the former USSR [134]. Phenazepam was notified to the EMCDDA by Germany and the United Kingdom in July 2011.

It is metabolized by various isoforms of CYP450 to the active metabolite 3-hydroxyphenazepam [114 135]. 3-Hydroxyphenazepam was identified in a white tablet seized and reported by Denmark in October 2016. Three subjects were admitted to the emergency room after taking illegal phenazepam purchased on the Internet. Patients showed both motor and functional impairments and depressive effects. One patient had Asperger`s syndrome [110]. In May 2016, a patient was admitted to the emergency department after taking four 3-hydroxyphenazepam tablets. There are also 19 duID and one drug-related offence listed in Table 1. Of these, 11 underwent fST, 5 underwent roadside drug testing, 3 ITAs, while 1 driver refused to perform SFST, and symptoms of impairment were caused by the officer`s observations. Moderate to significant motor and functional impairments were evident in all drivers.

Heide et al. reported an additional DUID of a young driver submitted for CTI [86], who also had a phenazepam blood concentration of 120 ng/ml. The driver exceeded his ITC and was not reported to be affected. Of the sixty reported deaths, phenazepam was listed as the sole cause of death in only two cases, while the rest was due to an accidental overdose due to the toxicity of the polymedicines. New benzodiazepines in Europe – a review (June 2021) The EMCDDA is currently monitoring 30 new benzodiazepines, more than 80% of which were first detected between 2014 and 2020. Despite this relatively large number, the new benzodiazepine market in Europe is currently dominated by etizolam and flualprazolam – although this may change as both substances were placed under international control in November 2020. In 2019, EU Member States reported 1,240 seizures of new benzodiazepines (around 5% of NPS seizures). Benzodiazepines are a group of CNS sedatives that evoke feelings of calm (anxiolysis), drowsiness and sleep. They work by facilitating the binding of the inhibitory neurotransmitter GABA to various GABA receptors throughout the CNS. Because they have a lower tendency to cause life-threatening CNS depression compared to previous medications such as barbiturates, benzodiazepines are often used in medicine to treat anxiety (anxiolytics) and insomnia (sedative/hypnotic), as well as other mental illnesses such as panic attacks and panic disorder.

There is no clear separation between anxiolytics and hypnotics, as most anxiolytics induce sleep when taken at night, and most hypnotics calm down when taken during the day. Benzodiazepine poisoning may be associated with behavioral inhibition, which can lead to hostile or aggressive behavior. The effect may be more common when benzodiazepines are taken in combination with alcohol. The combined use of alcohol and benzodiazepines also increases the risk of fatal overdose, as both act as CNS sedatives. A similar lethal interaction can occur when opiates with benzodiazepines are taken as part of a polydrug use model. A significant number of problem drug users swallow, “sniff” or inject high doses of benzodiazepines to enhance the euphoric effect of opiates or minimize the unpleasant effects of psychostimulants. The EMCDDA`s annual report on the state of the drug problem in Europe highlights the fact that the simultaneous use of benzodiazepines and opiates is a major risk factor for drug-related deaths. In addition to the increased risk of fatal overdoses, the usual injection-specific conditions such as tissue damage, gangrene, and transmission of HIV and hepatitis C also occur when drugs are injected. “The new benzodiazepines have established a strong foothold in the new pharmaceutical market in Europe,” says Alexis Goosdeel, Director of the EMCDDA.

“It is likely that more substances in this group will continue to emerge as users seek new drug experiences or alternatives to unavailable prescription drugs. Drugs are everywhere today and the lines between what is legal and illegal are becoming increasingly blurred. Faced with a complex market and high demand, we need to strengthen our ability to identify, assess and respond to new benzodiazepines and the health and social damage they cause. Bramness, J., Skurtveit, S. and Morland, J. (2002), “Clinical impairment of benzodiazepines-relation between benzodiazepine concentration and impairment in appretook drivers,” Drug and Alcohol Dependence, Volume 68, No. 2, pp. 131-41.

Thirty-three benzodiazepines were listed in Annex IV to the 1971 United Nations Convention on Psychotropic Substances in 1984 (Table 1). Midazolam (1990) and Brotizolam (1995) were later added to the list. In 1995, flunitrazepam (CAS 1622-62-4) was transferred from Annex IV to Annex III because the International Narcotics Control Board (INCB) determined that it was one of the most commonly used benzodiazepines and because of its frequent diversion to the illegal market. The derivative of alprazolam triazolobenzophenone is a product of the hydrolysis of alprazolam under acidic conditions and therefore also a metabolite of alprazolam. At neutral pH, it quickly turns into alprazolam. It was first developed by upjohn in the 1980s as a water-soluble pro-drug for alprazolam for parenteral (intravenous or intramuscular) ROA [78]. There are no other data on clinical, pharmacological or toxicological properties.