الفهرس 
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Abstract
Summary
New designer drugs also known as new psychoactive substances (NPS) are substances that have been developed especially to avoid existing drug control measures. Over the past few years multiple deaths reported in by international media and the medical literature have been linked to NPS products indicating the urgent need to raise awareness and educate the public and medical communities on this topic.
This work represent a comprehensive review about some of NPS as synthetic cannabinoids (SCs), synthetic cathinones, pipperazines derived designer drugs, phenethylamines, ketamine analogues, plant- based substances (kratom and salvia divinorum) and miscellaneous substances that include aminoindanes, phencyclidine-type substances and tryptamines. This review provided informations about the chemistry, pharmacology, toxicity and recent methods for detection and quantification in biological matrices for some of NPS.
NPS as Compared to traditional drugs of abuse are cheap, easy to obtain and not detectable by standard toxicology screens. Internet is playing an important role in the distribution of these substances as informations about their use and effects are freely available on the Internet.
NPS have become a global phenomenon with over 100 countries and territories from all regions of the world having reported one or more NPS. SCs and synthetic cathinones are the most common used groups. Egypt reported the emergence of plant-based substances (Salvia divinorum), SCs, ketamine and piperazines (BZP).
SCs are commonly abused new psychoactive substances. They are group of compounds with a wide range of chemical structures, have been developed by scientists with the hope of achieving selectivity toward one or the other of the cannabinoid receptors (CBRs) CB1 and CB2. SC products are distributed worldwide under countless trade names, such as ”K2”, ”Spice”, ”Aztec Gold” ”Black Mamba” and ”Voodoo”. They exert their effects by binding to CB1 and CB2 receptors. SCs are complete agonists of these receptors while THC is a partial agonist of them so; they have more potent and more toxic effects than THC.
SCs are used by oral and inhalational routes. Clinical case reports of intoxicated patients after consumption of SCs describe a variety of somatic and neuropsychiatric effects. The most prevalent side effects include tachycardia, hypertension, hyperthermia, tremors, ataxia, impairment of concentration and operational skills, agitation, paranoia, delusions, sever anxiety, nausea, vomiting, increase appetite, conjunctival injection, rhabdomyolysis and acute renal failure. Case reports of Spice tolerance, withdrawal and drug dependence have described.
Synthetic cathinones are synthetic derivatives of the natural cathinone, one of the psychoactive compounds present in Catha edulis (khat). There are at least 12 different types of synthetic cathinones, with mephedrone, methylon and MDPV being the most commonly used by the purchasers.They are emerged in the recreational drug markets as legal alternatives to amphetamine, ‘ecstasy” or cocaine and sold as ‘bath salts’ or ‘plant food. Nasal insufflation and oral ingestion are the most common routes of consumption of these substances. Their stimulatory effects are induced by elevations in synaptic catecholamine concentrations. The most common manifestations of acute toxicity include tachycardia, hypertension, hyperthermia, seizures, mydriasis, paranoid psychosis, depression, abdominal pain and vomiting. Some users developed sever complications as rhabdomyolysis, kidney damage, hyponatremia, hypoglycemia and Serotonin syndrome. Data currently available have shown that the frequent consumption of synthetic cathinones induces tolerance, dependence, craving and withdrawal syndrome after sudden suspension.
Pipera¬zine derivatives (PZDs) have emerged as a new group of recreational drugs over the last decade.1-benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) are the most commonly used PZDs. They are sought to be used for their amphetamine and MDMA like effects. PZDs are sold as ecstasy pills and consumed as capsules and tablets. The reported side effects of PZDs are tachycardia, hypertension, chest pain, agitation, anxiety, headache, tremor, mydriasis, insomnia, urine retention, nausea,vomiting and abdominal pain. More severe toxicity may include seizures, collapse, hyperthermia, extrapyramidal features and respiratory failure.
2, 5-Dimethoxy phenethylamines (2-C drugs) and PMMA are the most recently used phenethyllamines. 2-C drugs are group of newly substituted designer hallucinogens. The most recent 2C drugs to become popular are 2C-I and 2C-I-NBOMe.they are available in tablets, capsule, powder and liquid formulations. The majority of patients suffering from 2C toxicity exhibit a combination of sympathomimetic syndrome, serotonin syndrome and hallucinations.
PMMA is similar in structure to ”MDMA” but substantially more toxic. Users of PMMA report that they experienced euphoria, psychedelic effects and increased energy. Side effects of PMMA include hyperthermia, agitation, rhabdomyolysis, hallucination, arrhythmia, convulsions, sweating, headache, difficulty speaking, serotonin syndrome, coma and death.
Ketamine is a well-known anesthetic, its potent hallucinogenic and dissociate effects have afforded ketamine as a recreational drug used. Recently, the most common synthetic analogue of ketamine is methoxetamine. Severe side effects as paranoia, anxiety, respiratory depression, tachycardia, nystagmus, laryngospasm and pulmonary edema have been reported in users.
Salvia divinorum is a naturally occurring herb that has been used in Mexico for centuries. It is administered via chewing or smoking routes. Its desired effects include a state of “trance” that is similar to that produced by ketamine and canna¬bis. Effects of salvia intoxi¬cation include anxiety, dysphoria, confusion, language im¬pairments and fear associated with “bad trips”.
Kratom is a tree found in tropical and subtropical regions of South East Asia. The fresh leaves are chewed while the powder form is brewed into tea. It has been used for its opium-like effect. Heavy use can lead to adverse effects as seizures, profound sedation, nausea, vomiting and tremors.
Miscellaneous group of NPS is not commonly used. Aminoindanes have been sold as NPS for their ability to produce effects similar to MDMA. They are commonly found in powder form and crystals. There is very limited information on the PCP analogues. Acute PCP intoxication results in a wide range of behavioral and psychological effects, from mild neurologic and physiologic abnormalities, stupor to deep coma. Manifestations of behavioral toxicity resemble psychiatric syndromes.
The use of tryptamines remains limited but appears to have increased over the past five years. Synthetic tryptamines produce hallucinogenic effects in humans due to the structural similarities between these tryptamines and some naturally occurring hallucinogenic tryptamines as psilocybin and psilocin. Tryptamines users exhibit vital signs abnormalities as, tachypnea, hypertension and hyperthermia. Reports of trismus,
anxiety, diarrhea, nausea, vomiting, abdominal pain, diaphoresis, palpitations, mydriasis rhabdomyolysis and renal failure are also described.
New designer drugs will remain an ongoing challenge for physicians, toxicologists, public health authorities and law enforcement agenesis in the next years. No specific antidotes are available for designer drug toxicity and activated charcoal is not useful unless there has been significant oral ingestion. Most non psychiatric symptoms are self-limited and resolve within one to several days with supportive treatment. Unpleasant psychological effects of acute intoxication, as anxiety, agitation and paranoia can be managed with supportive treatment.
Analysis of new designer drugs is a major problem as it takes some time to add brand new substances in mass spectra libraries in order to make them detectable in routine screenings. Specific immunoassays for new designer drugs do not exist and cross-reactivities with common routine assays have not been investigated systematically, they are known for only very few compounds. The most commonly used methods for analysis of these substances in biological samples as plasma, blood and urine are GC-MS/MS and LC-MS/MS after sample preparation with liquid-liquid extraction or solid-phase extraction
Conclusion
Drug abuse is a persistent public health problem worldwide and a disturbing new trend is the increased recreational use of so-called designer drugs or NPS. Widespread abuse of NPS is a complex problem with no simple solutions as novel drugs continue to emerge more rapid than drug control measures.
The continuous emergence of NPS poses constant challenges for both clinical and forensic toxicologists. NPS pose obvious health risks because there is no quality control in their production, their pharmacological effects are poorly understood and clinical data are limited to cases from emergency room admissions. The effects of NPS are often much more potent than the illicit drugs which they are intended to mimic. Most NPS are not detected by routine toxicology screens.
Young persons who present to emergency room admissions with agitation and cardiovascular and/or psychiatric manifestations of unclear origin and whose drug screening tests are negative may be suffering from intoxication with a NPS.
Recommendations
• More basic research in animal models is needed to understand the accurate pharmacology of NPS and to evaluate the consequences of their acute and chronic exposure.
• There is a need for evidence-based-treatment recommendations for acute intoxications. New strategies to analyze these compounds in clinical and forensic cases are needed as most NPS are not detected by routine toxicology screens.
• Education of physicians in emergency room and general hospitals about classes of NPS and their most common side effects
• Newly developed analytical methods for detecting NPS must be made widely available to assist in identifying novel substances as they emerge in the recreational drug market rapidly.
• Coordination among emergency medical personnel, forensic toxicologists, scientific researchers, law enforcement, and policymakers is essential to foster more effective responses in dealing with this evolving drug-abuse phenomenon.
• Controlling the influx of NPS from overseas laboratories is a complex political and economic issue which will need international cooperation.
• Measures against the role of internet in distribution of NPS must be taken.
• Projects like the European ”The Psychonaut Web Mapping Project” which is a web scanning system to identify and categorise novel recreational drugs/psychoactive compounds, and new trends in drug use based on information available on the Internet are needed.