Piperazine derivatives, a class of amphetamine-like compounds that include BZP (benzylpiperazine) and TFMPP (trifluoromethylphenylpiperazine), are making a comeback as “legal ecstasy.” Often perceived as safe by the public, side effects can range from minimal to life-threatening. Taking BZP and TFMPP at the same time causes an increased effect of dopamine and serotonin, similar to MDMA. Severe symptoms include seizures, hyperthermia, hyponatremia, dystonic reactions, rhabdomyolysis, renal failure, metabolic acidosis, DIC, and respiratory failure. 20 In recent years, piperazine derivatives have been sold in the form of ecstasy pills or under the names `Frenzy`, `Bliss`, `Charge`, `Herbal ecstasy`, `A2`, `Legal X` and `Legal E`. Although piperazine-based designer drugs have a reputation for being safe, they can lead to distorted perception after ingestion. There are several reports of toxic symptoms experienced by users after taking drugs. Piperazine compounds are derived from piperazine, a cyclic molecule containing two opposing nitrogen atoms and four carbon atoms distributed in between, originally used as an antihelminthic agent in the 1950s. Synthetic drugs of this class can be divided into benzylpiperazines such as benzylpiperazine (BZP) and its analogue methylenedioxy methylenedioxy methylenedioxy (MDBP) and phenylpiperazines such as chlorophenylpiperazine (CPP), trifluoromethylphenylpiperazine (TFMPP) and methoxyphenylpiperazine (MeOPP). A third group includes thienylmethylpiperazines.
Chlorophenylpiperazine is an active metabolite of drugs such as trazodone and nefazodone, which are used as antidepressants. A survey conducted in the United Kingdom found that piperazines are among the most common active ingredients in tablets purchased from internet service providers. Piperazine-derived compounds are therefore new synthetic drugs whose abuse has increased remarkably worldwide.21 Most of the available data on the subjective and physiological side effects of dissociatives have focused on ketamine and PCP, with virtually no scientific information available to the best of the authors` knowledge of any of the dissociative NPS currently on the market. The latest EMCDDA report [EMCDDA, 2014] on methoxetamine shows that there are currently no data assessing the behavioural or psychological effects of the drug and makes no reference to other arylcyclohexylamines. Nevertheless, most anecdotal reports from users report effects comparable to those of ketamine, although of varying intensity and length (EMCDDA, 2014; Hofer et al., 2012]. In 2003, Dillon and colleagues published a groundbreaking study of subjective and physiological patterns in 100 recreational ketamine users [Dillon et al. 2003]. The most frequently reported physiological effects (>25%) were increased heart rate, nausea, vomiting, pyrexia, blurred vision, speech disturbances and analgesia, while subjective effects (>25%) dizziness, dissociation from the environment, dissociation from the body, auditory and visual hallucinations, confusion, excitement, relaxation of associations, unusual thoughts, memory impairment, euphoria, visual distortions, new bodily sensations, weightlessness and other altered bodies. Perceptions and sense of lack of time. Of these, most psychological experiences (13 of 16) were considered positive by the majority of participants; Although the most common physiological symptoms were not as pleasant, only three of the seven symptoms were declared positive.
Muetzelfeldt and colleagues [Muetzelfeldt et al. 2008] reduced 90 ketamine users into three distinct groups, frequent users, rare “recreational users” and ex-users (>3 months abstention), and found that a total of 88% had a positive introduction experience with the drug. Among the most positive effects on initiation were feelings of dissociation, contentment, intense cheerfulness and pleasure in feeling intense; These feelings extended to current use, in addition to enjoying the experience of being stoned and relaxed. On the other hand, subjective experiences unpleasant for frequent users included impaired sociability, jaded affect, bad mood, dissociation, and paranoia. For users during initiation, negative side effects also included nausea and vomiting, as well as a feeling of loss of control. At higher doses, users sometimes experience the infamous “K hole,” described by one user as “tunnel vision that then rises above the body like a near-death experience” (Critchlow, 2006, p. 1212). The risk of dying from an acute dose of ketamine is considered quite rare: between 1993 and 2006, four deaths were identified, in the United Kingdom, where ketamine was the only drug detected [Schifano et al.
2008]. In medical settings, unintentional administration of very high single doses of ketamine has been inadvertently reported in children without side effects, which were up to 100 times higher than recommended [Green et al. 1999]. However, dissociative drug poisoning could potentially lead to risky and careless behaviours, and the highest risk of mortality was accidental death while intoxicated (Jansen, 2000; Stewart, 2001], i.e. motor vehicle accidents [Cheng et al., 2005]. It`s no secret that most people like to seek thrills. More than 34% of adults in the UK have used illegal drugs at some point in their lives. The Psychoactive Substances Act does not replace this Act. As a result, this means that everything that was previously illegal is still illegal, and drugs that are considered “legal highs” are now also illegal. Ketamine was first used in medical practice as an alternative anesthetic for PCP. Although both have a safe cardiovascular and respiratory profile, ketamine has been shown to have a shorter half-life with fewer psychotomimetic effects, making it a preferred option [Domino et al.
1965]. Regardless, its strong dissociative effect on postoperative patients was a cause for concern and it was soon removed from traditional human anesthesia, although it retains niche roles as a pediatric anesthetic and in veterinary practice (where it earned the pejorative nickname “horse sedative”). Ketamine and PCP are arylcyclohexylamines with an aryl group attached to a cyclohexane ring and basic amine function. The first amine of this class, 1-(1-phenylcyclohexyl)amine (PCA), was reported in 1907 [Kursanov, 1907], although specimens of the PCP and ketamine classes were first marketed by Parke Davis 50 and 60 years later, respectively. PCP became a Class A drug in the United Kingdom and a Schedule II drug in the United States in the late 1970s; Ketamine, which was thought to have a lower potential for abuse, was widely used until the late 1990s, when it was classified as a Schedule III drug in the United States. In the UK, ketamine was first classified as Class C in 2005, although it was recently replaced by a Class B controlled drug in June 2014. Other historical analogues of first-generation arylcyclohexylamine include 1-[1-(thiophen-2-yl)cyclohexyl]piperidine (TCP, tenocyclidine), 1-(1-phenylcyclohexyl)pyrrolidine (PCPy, rolicyclidine), N-ethyl-1-phenylcyclohexylamine (PCE, eticyclidine). These were first synthesized by Parke Davis [Levy et al. 1960; Kalir et al., 1969] and were subsequently controlled by the Misuse of Drugs Act in the United Kingdom in 1984, shortly after PCP, as Class A drugs and were never widely available.
The main effects of almost all psychoactive drugs, including the so-called legal highs, can be described using the following four main categories.