Lysergic N,N-diethylamide (LSD) is perhaps one of the most intriguing psychoactive substances known and numerous analogs have been explored to a varying extent in previous decades. In 2013, N6-allyl-6-norlysergic acid diethylamide (AL-LAD) and (2’S,4’S)-lysergic acid 2,4-dimethylazetidide (LSZ) have appeared on the ‘research chemicals’ / new psychoactive substances (NPS) market in both powdered...
In recent years, use of psychoactive synthetic stimulants has grown rapidly. 5-(2-Aminopropyl)indole (5-IT) is a synthetic drug associated with a number of fatalities, that appears to be one of the newest 3,4-methylenedioxymethamphetamine (MDMA) replacements. Here, the monoamine-releasing properties of 5-IT, its structural isomer 6-(2-aminopropyl)indole (6-IT), and MDMA were compared using in...
New psychoactive substances (NPS) are not tested for their cytochrome P450 (CYP) inhibition potential before consumption. Therefore, this potential was explored for tryptamine-derived NPS (TDNPS) including alpha-methyl tryptamines (AMTs), dimethyl tryptamines (DMTs), diallyl tryptamines (DALTs), and diisopropyl tryptamines (DiPTs) using test substrates preferred by the Food and Drug...
1‐Propionyl‐ d ‐lysergic acid diethylamide hemitartrate (1P‐LSD) has become available as a ‘research chemical’ in the form of blotters and powdered material. This non‐controlled derivative of d ‐lysergic acid diethylamide (LSD) has previously not been described in the published literature despite being closely related to 1‐acetyl‐LSD (ALD‐52), which was developed in the 1950s. This study...
The rise in new psychoactive substances that are available as 'research chemicals' (RCs) remains a significant forensic and legislative challenge. A number of arylcyclohexylamines have attracted attention as RCs and continue to be encountered, including 3-MeO-PCP, 3-MeO-PCE and 3-MeO-PCPr. These compounds are commonly perceived as ketamine-like dissociative substances and are believed to act...
A series of N-benzylated-5-methoxytryptamine analogues was prepared and investigated, with special emphasis on substituents in the meta position of the benzyl group. A parallel series of several N-benzylated analogues of 2,5-dimethoxy-4-iodophenethylamine (2C-I) also was included for comparison of the two major templates (i.e., tryptamine and phenethylamine). A broad affinity screen at...
2-Amino-1-(4-bromo-2,5-dimethoxyphenyl)ethan-1-one (bk-2C-B) has been recently offered for purchase by a variety of Internet retailers. This substance may be considered a cathinone analogue of the phenethylamine 2-(4-bromo-2,5-dimethoxyphenyl)ethan-1-amine (2C-B) which suggests that it may have psychoactive effects in humans. A test purchase of bk-2C-B was carried out and its identity was...
The structurally diverse nature of the 1,2-diphenylethylamine template provides access to a range of substances for drug discovery work but some have attracted attention as 'research chemicals'. The most recent examples include diphenidine, i.e. 1-(1,2-diphenylethyl)piperidine and 2-methoxydiphenidine, i.e. 1-[1-(2-methoxyphenyl)-2-phenylethyl]piperidine (MXP, methoxyphenidine, 2-MXP) that have...
2-Methoxydiphenidine, i.e. 1-[1-(2-methoxyphenyl)-2-phenylethyl]piperidine, also known as 'MXP' or '2-MeO-diphenidine' (or 2-MXP), has been available as a 'research chemical' since 2013 as a purported alternative to the 'dissociative anesthetics' methoxetamine and ketamine. Three deaths which involved the detection of 2-MXP in post-mortem blood and urine were encountered in forensic casework....
The recent occurrence of deaths associated with the psychostimulant cis-4,4'-dimethylaminorex (4,4'-DMAR) in Europe indicated the presence of a newly emerged psychoactive substance on the market. Subsequently, the existence of 3,4-methylenedioxy-4-methylaminorex (MDMAR) has come to the authors' attention and this study describes the synthesis of cis- and trans-MDMAR followed by extensive...
Substances with the diphenylethylamine nucleus represent a recent addition to the product catalog of dissociative agents sold as 'research chemicals' on the Internet. Diphenidine, i.e. 1-(1,2-diphenylethyl)piperidine (1,2-DEP), is such an example but detailed analytical data are less abundant. The present study describes the synthesis of diphenidine and its most obvious isomer,...
This special issue provides a multidisciplinary snapshot of recent developments of the broader, arguably phenomenal, changes to the drug market that have occurred in the past decade related to the rise of the new drug phenomenon. This change is largely a result of the growing commodification by entrepreneurs, and increasingly, by criminal groups, of a huge range of psychoactive substances not...
During the second half of 2013, a total of 26 deaths involving para-methyl-4-methylaminorex (4,4'-DMAR) were reported to the European Monitoring Centre for Drugs and Drug Addiction. While aminorex and 4-methylaminorex (4-MAR) are known psychostimulants, nothing is known about the comparatively new para-methyl analog. Analytical characterization of two independent samples obtained from online...
5-(2-Aminopropyl)indole (5-IT) is a psychoactive compound that has recently been associated with several fatal and non-fatal intoxications in a number of European countries. There are indications that acute effects may include symptoms of monoaminergic (e.g. serotonin) toxicity and one mechanism involved in the increase of serotonin levels includes the inhibition of monoamine oxidase. This...
The concept of a 'derivative' is used widely in chemistry, where its precise meaning depends on the circumstances. However, numerous examples of derivative also occur in domestic drugs legislation, some of which stem from the 1961 United Nations Single Convention on Narcotic Drugs. There is a commonly held view that only 'first-order' derivatives should be considered: substances that can be...
Classic examples of psychoactive arylcycloalkylamines include ketamine and 1-(1-phenylcyclohexyl)piperidine (PCP) and many others serve as important structural templates for neuropharmacological research. The recent emergence of PCP analogues that can be obtained from internet retailers requires the implementation of appropriate monitoring strategies for harm reduction purposes. Access to...
The powerful psychoactive features of N,N-dimethyltryptamine (DMT) have sparked the imagination of many research disciplines for several decades. One of the key chemical features associated with compound identity is the determination of melting points. The descriptions of both melting points and morphology associated with DMT free base have long been a source of interest and discussion,...
A novel analytical approach combining solid-phase microextraction (SPME)/gas chromatography ion trap mass spectrometry (GC-IT-MS) was developed for the detection and quantification N,N-dimethyltryptamine (DMT), a powerful psychoactive indole alkaloid present in a variety of South American indigenous beverages, such as ayahuasca and vinho da jurema. These particular plant products, often used...
Cathinones are a class of drugs used to treat various medical conditions including depression, obesity, substance abuse, and muscle spasms. Some "designer" cathinones, such as methcathinone, mephedrone, and methylone, are used nonclinically for their stimulant or entactogenic properties. Given the recent rise in nonmedical use of designer cathinones, we aimed to improve understanding of...
It is known from clinical studies that some patients attempt to cope with the symptoms of post-traumatic stress disorder (PTSD) by using recreational drugs. This review presents a case report of a 19-year-old male patient with a spectrum of severe PTSD symptoms, such as intense flashbacks, panic attacks, and self-mutilation, who discovered that some of his major symptoms were dramatically...
The absence of reference material is a commonly experienced difficulty among medical and forensic professionals tasked with identifying new psychoactive substances that are encountered for the first time. The identification of newly emerging substances lies at the heart of forensic and clinical analysis, and a proactive public health policy calls for a thorough analysis of the properties of new...
The nonmedical use of 'designer' cathinone analogs, such as 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxymethcathinone (methylone), is increasing worldwide, yet little information is available regarding the mechanism of action for these drugs. Here, we employed in vitro and in vivo methods to compare neurobiological effects of mephedrone and methylone with those produced by the...
Salvia divinorum is a hallucinogenic plant with ethnopharmacological and recreational uses. It differs from classic serotonergic hallucinogens such as LSD and psilocin in both phenomenology and potent agonist activity of the active component salvinorin A at κ-opioid receptors. Awareness of S. divinorum has grown recently, with both an increase in its public representation and concern over its...
The agony and the ecstasy associated with the area of illicit drugs is a matter of constant interest today. Prevalence of use, availability of reference standards, and novel detection methods provide many challenging and exciting opportunities, particularly when dealing with increasing levels of novelty and complexity within a globalized world. This special issue aims to present a snapshot of a...
The increased interest in N,N-dialkyl tryptamines is a reflection of their diverse range of biologically active properties. Deuterated derivatives are of interest for use as internal standards in bioanalytical or pharmacological assays. The present study reports on the synthesis of twelve novel 5-ethoxy-N,N-dialkyl-[α,α,β,β-H(4) ]-tryptamines and their [α,α,β,β-D(4) ]-counterparts following the...