1-Acetyl-N,N-diethyllysergamide (1A-LSD, ALD-52) was first synthesized in the 1950s and found to produce psychedelic effects similar to those of LSD. Evidence suggests that ALD-52 serves as a prodrug in vivo and hydrolysis to LSD is likely responsible for its activity. Extension of the N1-alkylcarbonyl chain gives rise to novel lysergamides, which spurred further investigations into their...
The classical psychedelic drug (+)-lysergic acid diethylamide (LSD) continues to attract considerable multidisciplinary interest, and over the last eight decades, many derivatives and analogs of LSD have been synthesized. One site on the ergoline scaffold of LSD that has been frequently modified is the N1-position, with the N1-acylated LSD derivative 1-acetyl-LSD (1A-LSD, ALD-52) being one of...
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...
Recent investigations have shown that N-ethyl-N-cyclopropyl lysergamide (ECPLA) produces LSD-like behavioral effects in mice, which suggests that it may act as a hallucinogen in humans. Although the use of ECPLA as a recreational drug has been limited, key analytical data that can be used to detect ECPLA are required for future forensic and clinical investigations. ECPLA is an isomer of...
The concept of a substance acting as a prodrug for an intended drug is not new and has been known and utilized with particular benefits within medicine for efficacy and patient safety. Prodrugs of psychoactive substances are also not particularly new but this has also extended to considerations of prodrugs of new psychoactive substances (NPS). The continuing evolution of NPS has been a constant...
Abstract A number of substances based on the 1,2‐diarylethylamine template have been investigated for various potential clinical applications whereas others have been encountered as research chemicals sold for non‐medical use. Some of these substances have transpired to function as NMDA receptor antagonists that elicit dissociative effects in people who use these substances recreationally....
New psychoactive substances (NPS) are commonly referred to as 'research chemicals', 'designer drugs' or 'legal highs'. One NPS class is represented by dissociative anesthetics, which include analogues of the arylcyclohexylamine phencyclidine (PCP), ketamine and diphenidine. A recent addition to the NPS market was 4-[1-(3-methoxyphenyl)cyclohexyl]morpholine (3-MeO-PCMo), a morpholine analogue of...
Lysergic acid diethylamide (LSD) is perhaps one of the best‐known psychoactive substances and many structural modifications of this prototypical lysergamide have been investigated. Several lysergamides were recently encountered as ‘research chemicals’ or new psychoactive substances (NPS). Although lysergic acid morpholide (LSM‐775) appeared on the NPS market in 2013, there is disagreement in...
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...
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....
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,...
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...
The evolving nature of new psychoactive substances (NPS) – often referred to as ‘legal highs’, ‘designer drugs’ or ‘bath salts’ – presents an evolving challenge for toxicologists. Apart from the detection and identification of these compounds, further analytical challenges may arise from the presence of possible metabolites or degradation products which may have to be considered when devising...
OBJECTIVES: MDAI (5,6-methylenedioxy-2-aminoindane; 6,7-dihydro-5H-cyclopenta[f][1,3]benzodioxol-6-amine; 'sparkle'; 'mindy') is a psychoactive substance, sold primarily over the Internet and in 'head' shops as a 'legal high'. Synthesised and used as a research chemical in the 1990s, MDAI has structural similarities to MDMA (3,4-methylenedioxy-N-methylamphetamine) and shares its behavioural...
5-MeO-DALT (N,N-diallyl-5-methoxytryptamine) is a psychoactive substance, sold primarily over the Internet as a 'research chemical' or 'plant food'. Although details for the synthesis of this tryptamine have been available since 2004, its use as a hallucinogenic drug has been reported only occasionally in on-line user fora. It is controlled in only a few countries world-wide. There is little...