Figure 8
Effects of AL-LAD (A) and LSZ (B) on the head twitch response. Data are presented as group means ± SEM for the entire 30-min test session. *p < 0.01, significant differences from vehicle control group (Tukey's test).
Source publication
Lysergic acid N,N-diethylamide (LSD) is perhaps one of the most intriguing psychoactive substances known and numerous analogs have been explored to varying extents in previous decades. In 2013, N6-allyl-6-norlysergic acid diethylamide (AL-LAD) and (2’S,4’S)-lysergic acid 2,4-dimethylazetidide (LSZ) appeared on the ‘research chemicals’/new psychoact...
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Introduction: In the past century, many studies suggested that LSD-assisted psychotherapy was effective for a wide range of disorders. Nowadays, there is a comeback of psychedelic research, showing again significant therapeutic potential of hallucinogenic substances. Nevertheless, there is a lack of studies with psychedelic-naïve participants. Perf...
Classic psychedelic-induced ego dissolution involves a shift in the sense of self and blurring of boundary between the self and the world. A similar phenomenon is identified in psychopathology and is associated to the balance of anticorrelated activity between the default mode network (DMN) – which directs attention inwards – and the salience netwo...
Anxiety affects 14–20% of dogs. Pharmacological treatments often fail. Psychedelics have shown to be useful for anxiety and depression in humans, but their veterinary use remains unexplored. We aimed to determine the effects of low-dose 1-cyclopropionyl-d-lysergic acid diethylamide (1cp-LSD) administered in a single dose to a dog, to observe the ef...
Recent findings have shown that psychedelics reliably enhance brain entropy (understood as neural signal diversity), and this effect has been associated with both acute and long-term psychological outcomes such as personality changes. These findings are particularly intriguing given that a decrease of brain entropy is a robust indicator of loss of...
Citations
... These compounds are mainly distributed as sheet products. LSD analogs such as N, N-7,-triethyl-4,6,6a,7,8,9-hexahydroindolo [4,3-fg] quinoline-9-carboxamide (ETH-LAD) and 7-Allyl-N,Ndiethyl-4,6,6a, 7,8,9-hexahydroindolo [4,3-fg]quinoline-9-carboxamide (AL-LAD), in which the methyl group at the N6 position of LSD is changed, and 4-Acetyl-N,Ndiethyl-7-methyl-4,6,6a, 7,8,9-hexahydroindolo [4,3-fg] quinoline-9-carboxamide (ALD-52), N,N-diethyl-7-methyl-4-propionyl-4,6,6a, 7,8,9-hexahydroindolo [4,3-fg]quinoline-9-carboxamide (1P-LSD), 4-cyclopropionyl-N,Ndiethyl-7-methyl-4,6,6a, 7,8,9-hexahydroindolo [4,3-fg] quinoline-9-carboxamide (1cP-LSD) and 4-butyryl-N,Ndiethyl-7-methyl-4,6,6a, 7,8,9-hexahydroindolo [4,3-fg]quinoline-9-carboxamide (1B-LSD), in which the N1 position is acylated, have been reported [4][5][6][7][8][9][10] (Fig. 1). It has been reported that deacylation of these N1-acylated LSD analogs occurs in vivo [11]. ...
... In the GC-MS analysis, a peak at 11.4 min showed a molecular ion ([M] + ) at m/z 335 ( Fig. S2a and S2b). After comparing the data from LC-PDA-MS and GC-MS analyses with those of the authentic compound, this compound was identified as LSZ (4) [5,16], a compound in which the diethyl moiety at position N18 of LSD has been converted to 2,4-dimethylazetidin. ...
Purpose
Many analogs of lysergic acid diethylamide (LSD) have recently appeared as designer drugs around the world. These compounds are mainly distributed as sheet products. In this study, we identified three more newly distributed LSD analogs from paper sheet products.
Methods
The structures of the compounds were determined by gas chromatography–mass spectrometry (GC–MS), liquid chromatography–photodiode array–mass spectrometry (LC–PDA–MS), liquid chromatography with hybrid quadrupole time-of-flight mass spectrometry (LC–Q-TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy.
Results
From the NMR analysis, the compounds in the four products were identified as 4-(cyclopropanecarbonyl)- N , N -diethyl-7-(prop-2-en-1-yl)-4,6,6a,7,8,9-hexahydroindolo[4,3- fg ]quinoline-9-carboxamide (1cP-AL-LAD), 4-(cyclopropanecarbonyl)- N -methyl- N -isopropyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo-[4,3- fg ]quinoline-9-carboxamide (1cP-MIPLA), N,N -diethyl-7-methyl-4-pentanoyl-4,6,6a,7,8,9-hexahydroindolo[4,3- fg ]quinoline-9-carboxamide (1V-LSD) and (2’ S ,4’ S )-lysergic acid 2,4-dimethylazetidide (LSZ). In comparison with the structure of LSD, 1cP-AL-LAD was converted at the positions at N1 and N6, and 1cP-MIPLA was converted at the positions at N1 and N18. The metabolic pathways and biological activities of 1cP-AL-LAD and 1cP-MIPLA have not been reported.
Conclusions
This is the first report showing that LSD analogs that were converted at multiple positions have been detected in sheet products in Japan. There are concerns about the future distribution of sheet drug products containing new LSD analogs. Therefore, the continuous monitoring for newly detected compounds in sheet products is important.
... Most other C8 amide substitution patterns yield greatly reduced hallucinogenic potency relative to LSD, although the conformationally restricted LSD analog (2 0 S,4 0 S)-lysergic acid 2,4-dimethylazetidide (LSZ) is an exception and retains high potency in vivo. 10,11 In addition to being the focus of medical and scientific research, LSD is also a popular recreational substance. In recent years, a large number of LSD analogs have been distributed online as "research chemicals." ...
... Many of the lysergamides that have appeared as new recreational drugs were originally synthesized during the course of scientific studies, for example, ALD-52 and AL-LAD. [11][12][13] However, entirely novel lysergamides have also been synthesized with the specific goal of developing new designer drugs. Notable examples of this phenomenon include N 1 -acylated derivatives of LSD and AL-LAD: ...
... Signals related to the N 1 -H were undetectable due to substitution, whereas in the N 1 -unsubstituted AL-LAD, this signal was shown to be around 3280 cm À1 together with a single carbonyl stretch at 1626 cm À1 . 11 The results from NMR spectroscopy experiments are summarized in Table 1 Figure 6a). Correspondingly, the same fragment was identified in the tandem mass spectrum of 1-acetyl-LSD (1A-LSD, ALD-52). ...
The development of novel lysergamides continues to occur, based on both the needs of psychedelic medicine and commercial interest in new recreational substances. The present study continues the authors’ research on novel lysergamides and describes the analytical profile of 1‐cyclopropanoyl‐AL‐LAD (IUPAC name: 1‐(cyclopropanecarbonyl)‐N,N‐diethyl‐6‐(prop‐2‐en‐1‐yl)‐9,10‐didehydroergoline‐8β‐carboxamide; 1cP‐AL‐LAD), using various chromatographic, mass spectrometric and spectroscopic methods. Analysis of a powdered sample of 1cP‐AL‐LAD, obtained from an online vendor, by high performance liquid chromatography‐electrospray ionization‐quadrupole time‐of‐flight mass spectrometry in full scan/AutoMS/MS mode revealed the detection of 17 impurities based on high‐resolution tandem mass spectral data; tentative determination of their identity was based on mass spectral grounds alone, though detection of AL‐LAD and 1P‐AL‐LAD was confirmed using available reference standards. Other tentative compound identifications included 1‐acetyl‐AL‐LAD and several other substances potentially reflecting oxidation of the N6‐allyl group as well as other positions on the ergoline ring system. These data may assist those interested in the chemistry of lysergamides. Finally, 1cP‐AL‐LAD was also detected in samples of “blotters” sold online for recreational use.
... 17,18 In recent years, both AL-LAD and ETH-LAD became available for purchase from online retailers, often distributed on small pieces of absorbent paper ("blotters"). 19,20 Reports describing their detection were first notified to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) in 2015 and 2016, respectively. 21,22 Since then, other publications have appeared describing the detection of AL-LAD and ETH-LAD by researchers located outside of Europe. ...
... Numbering according to Table 2 (ED 50 = 174.9 nmol/kg) 19 ...
... Similar to other lysergamides with a N,N-diethylamide group, iminium ions were detected at m/z 72 together with m/z 100 and m/z 128. 19,20,26-29 Compared with AL-LAD, the presence of the propanoyl group shifted some of the ions by 56 Da including the molecular ion at m/z 405 (AL-LAD: m/z 349), the retro-Diels-Alder fragment following the loss of N-allylmethanimine at m/z 336 (AL-LAD: m/z 280), or the species reflecting the loss of the N 6 -allyl group at m/z 364 (AL-LAD: m/z 308).19 A characteristic oxonium ion reflecting the presence of the N 1 -propanoyl substituent was also be observed at m/z 57, which was comparable to other N 1 -propanoyl lysergamides such F I G U R E 2 (a) Electron ionization mass spectrum of 1P-AL-LAD (isomer III). ...
Lysergic acid diethylamide (LSD) is known to induce powerful psychoactive effects in humans, which cemented its status as an important tool for clinical research. A range of analogues and derivatives has been investigated over the years, including those classified as new psychoactive substances. This study presents the characterization of the novel lysergamide N,N‐diethyl‐1‐propanoyl‐6‐(prop‐2‐en‐1‐yl)‐9,10‐didehydroergoline‐8β‐carboxamide (1P‐AL‐LAD) using various mass spectrometric, gas‐ and liquid chromatographic and spectroscopic methods. In vitro metabolism studies using pooled human liver microsomes (pHLM) confirmed that 1P‐AL‐LAD converted to AL‐LAD as the most abundant metabolite consistent with the hypothesis that 1P‐AL‐LAD may act as a prodrug. Fourteen metabolites were detected in total; metabolic reactions included hydroxylation of the core lysergamide ring structure or the N6‐allyl group, formation of dihydrodiol metabolites, N‐dealkylation, N1‐deacylation, dehydrogenation, and combinations thereof. The in vivo behavioral activity of 1P‐AL‐LAD was evaluated using the mouse head twitch response (HTR), a 5‐HT2A‐mediated head movement that serves as a behavioral proxy in rodents for human hallucinogenic effects. 1P‐AL‐LAD induced a dose‐dependent increase in HTR counts with an inverted U‐shaped dose‐response function, similar to lysergic acid diethylamide (LSD), psilocybin, and other psychedelics. Following intraperitoneal injection, the median effective dose (ED50) for 1P‐AL‐LAD was 491 nmol/kg, making it almost three times less potent than AL‐LAD (174.9 nmol/kg). Previous studies have shown that N1‐substitution disrupts the ability of lysergamides to activate the 5‐HT2A receptor; based on the in vitro metabolism data, 1P‐AL‐LAD may induce the HTR because it acts as a prodrug and is metabolized to AL‐LAD after administration to mice.
... A neutral loss of N,N-diethylformamide from the M• + might have led to the formation of the m/z 291 ion [5]. The EI+ characterization of 1B-LSD, 1P-LSD and LSD, presented by Brandt and other authors, was perfectly consistent with the results of the present study, and allows the unequivocal identification of 1B-LSD [5][6][7][8][9]. ...
The rapid dispersion of new psychoactive substances (NPS) presents challenges to customs services and analytical laboratories, which are involved in their detection and characterization. When the seized material is limited in quantity or of a complex nature, or when the target substance is present in very small amounts, the need to use advanced analytical techniques, efficient workflows and chemo-informatics tools is essential for the complete identification and elucidation of these substances. The current work describes the application of such a workflow in the analysis of a single blotter paper, seized by Swedish customs, that led to the identification of a lysergic acid diethylamide (LSD) derivative, 1-butyl-lysergic acid diethylamide (1B-LSD). Such blotter paper generally contains an amount in the range of 30–100 ug. This substance, which is closely related to 1-propionyl-lysergic acid diethylamide (1P-LSD), seems to have only recently reached the drug street market. Its identification was made possible by comprehensively combining gas chromatography with mass spectrometry detection (GC–MS), liquid chromatography coupled with high-resolution tandem MS (LC–HR-MS/MS), Orbitrap-MS and both 1D and 2D nuclear-magnetic-resonance (NMR) spectroscopy. All the obtained data have been managed, assessed, processed and evaluated using a chemo-informatics platform to produce the effective chemical and structural identification of 1B-LSD in the seized material.
... These methods have shown great utility for studying novel hallucinogens (Halberstadt and Geyer 2014;Nichols et al. 2015;Brandt et al. 2016Brandt et al. , 2017bBrandt et al. , 2019Halberstadt et al. 2016Halberstadt et al. , 2017aHalberstadt et al. , 2019aHalberstadt et al. , 2019bHalberstadt et al. , 2019c. ...
... To date, we have tested a variety of hallucinogens in the HTR paradigm (Halberstadt andGeyer 2013, 2014;Brandt et al. 2017b;Klein et al. 2018;Halberstadt et al. 2019aHalberstadt et al. , 2019b. ...
Serotonergic hallucinogens such as lysergic acid diethylamide (LSD) induce head twitches in rodents via 5-HT2A receptor activation. The goal of the present investigation was to determine whether a correlation exists between the potency of hallucinogens in the mouse head-twitch response (HTR) paradigm and their reported potencies in other species, specifically rats and humans. Dose-response experiments were conducted with phenylalkylamine and tryptamine hallucinogens in C57BL/6J mice, enlarging the available pool of HTR potency data to 40 total compounds. For agents where human data are available (n = 36), a strong positive correlation (r = 0.9448) was found between HTR potencies in mice and reported hallucinogenic potencies in humans. HTR potencies were also found to be correlated with published drug discrimination ED50 values for substitution in rats trained with either LSD (r = 0.9484, n = 16) or 2,5-dimethoxy-4-methylamphetamine (r = 0.9564, n = 21). All three of these behavioral effects (HTR in mice, hallucinogen discriminative stimulus effects in rats, and psychedelic effects in humans) have been linked to 5-HT2A receptor activation. We present evidence that hallucinogens induce these three effects with remarkably consistent potencies. In addition to having high construct validity, the HTR assay also appears to show significant predictive validity, confirming its translational relevance for predicting subjective potency of hallucinogens in humans. These findings support the use of the HTR paradigm as a preclinical model of hallucinogen psychopharmacology and in structure-activity relationship studies of hallucinogens. Future investigations with a larger number of test agents will evaluate whether the HTR assay can be used to predict the hallucinogenic potency of 5-HT2A agonists in humans.
... Hence, although head twitches may have limited value as a model of hallucinogenesis (Canal and Morgan, 2012), the HTR assay may be useful for investigations of the in vivo potency relationships of hallucinogens. A preliminary regression analysis, including seven compounds from the present investigation (mescaline, escaline, proscaline, TMA, 3C-E, TMA-2, and MEM) and five agents tested previously (LSD, AL-LAD, DOB, 2C-B, and 2C-I; Brandt et al., 2017a;Geyer, 2013, 2014;Halberstadt et al., 2019), demonstrated that HTR-derived ED 50 values are significantly correlated (r = 0.9761, p < 0.0001) with human hallucinogenic potency data collected by A.T. Shulgin Shulgin, 1991, 1997). Studies are currently underway in our laboratory to examine the relationship between HTR potency and human hallucinogenic potency for a much larger series of compounds. ...
Background:
In recent years, there has been increasing scientific interest in the effects and pharmacology of serotonergic hallucinogens. While a large amount of experimental work has been conducted to characterize the behavioral response to hallucinogens in rodents, there has been little systematic investigation of mescaline and its analogs. The hallucinogenic potency of mescaline is increased by α-methylation and by homologation of the 4-methoxy group but it not clear whether these structural modifications have similar effects on the activity of mescaline in rodent models.
Methods:
In the present study, the head twitch response (HTR), a 5-HT2A receptor-mediated behavior induced by serotonergic hallucinogens, was used to assess the effects of mescaline and several analogs in C57BL/6J mice. HTR experiments were conducted with mescaline, escaline (4-ethoxy-3,5-dimethoxyphenylethylamine) and proscaline (3,5-dimethoxy-4-propoxyphenylethylamine), their α-methyl homologs TMA (3,4,5-trimethoxyamphetamine), 3C-E (4-ethoxy-3,5-dimethoxyamphetamine) and 3C-P (3,5-dimethoxy-4-propoxyamphetamine), and the 2,4,5-substituted regioisomers TMA-2 (2,4,5-trimethoxyamphetamine), MEM (4-ethoxy-2,5-dimethoxyamphetamine) and MPM (2,5-dimethoxy-4-propoxyamphetamine).
Results:
TMA induced the HTR and was twice as potent as mescaline. For both mescaline and TMA, replacing the 4-methoxy substituent with an ethoxy or propoxy group increased potency in the HTR assay. By contrast, although TMA-2 also induced the HTR with twice the potency of mescaline, potency was not altered by homologation of the 4-alkoxy group in TMA-2.
Conclusions:
The potency relationships for these compounds in mice closely parallel the human hallucinogenic data. These findings are consistent with evidence that 2,4,5- and 3,4,5-substituted phenylalkylamine hallucinogens exhibit distinct structure-activity relationships. These results provide additional evidence that the HTR assay can be used to investigate the structure-activity relationships of serotonergic hallucinogens.
... Even N-methyl-N-propyl lysergamide (LAMPA,, an isomer of LSD with similar hydrophobicity, is markedly less potent (Abramson and Rolo 1967). One exception is the conformationally restricted LSD analog (2′S,4′S)-lysergic acid 2,4-dimethylazetidide (LSZ), which retains high 5-HT 2A affinity and potency in rodent behavioral models (Nichols et al. 2002;Brandt et al. 2017a). ...
... LSD has been a popular recreational drug since the mid-1960s. Although the use of LSD has occurred at relatively stable levels, in recent years, several other lysergamides have been distributed as new psychoactive substances (NPS) or "research chemicals" (Brandt et al. 2016(Brandt et al. ,2017a(Brandt et al. ,b,2018. Most of the new lysergamides, including N 6 -allyl-6norlysergic acid diethylamide (AL-LAD), N 6 -ethyl-6norlysergic acid diethylamide (ETH-LAD), LSZ, and lysergic acid morpholide (LSM-775), were originally synthesized during the course of scientific research (Gogerty and Dille 1957;Hoffman and Nichols 1985;Nichols et al. 2002). ...
... The HTR is commonly used as a behavioral proxy in rodents for human hallucinogenic effects because it can reliably d i s t i n g u i s h b e t w e e n h a l l u c i n o g e n i c a n d n o nhallucinogenic 5-HT 2A receptor agonists (Gonzalez-Maeso et al. 2007). LSD and analogs such as AL-LAD and LSZ induce HTRs in mice with high potency (Corne and Pickering 1967;Halberstadt and Geyer 2013;Brandt et al. 2017a). HTR studies were conducted in C57BL/6 J mice to assess whether ECPLA activates 5-HT 2A receptors and produces LSD-like behavioral effects in vivo. ...
Rationale
The lysergamide lysergic acid diethylamide (LSD) is a prototypical classical hallucinogen with remarkably high potency. LSD remains a popular recreational drug but is also becoming an important research tool for medical and neuroscience studies. Recently, several lysergamides that are close structural analogs of LSD have been sold as recreational drugs, which suggests that further studies are needed to explore the pharmacological properties of these compounds.
Objective
In this present investigation, another LSD congener, N-ethyl-N-cyclopropyl lysergamide (ECPLA), which to date has not been marketed as a recreational substance, was evaluated for its pharmacological features relative to those previously reported for LSD. The experiments focused on interactions with the 5-HT2A receptor, which is responsible for mediating the psychedelic effects of LSD and other hallucinogens.
Methods
Competitive binding assays were performed to measure the affinity of ECPLA for 27 monoamine receptors. The ability of ECPLA to activate human 5-HT2 receptor subtypes was assessed using calcium mobilization assays. Head twitch response (HTR) studies were conducted in C57BL/6J mice to determine whether ECPLA activates 5-HT2A receptors in vivo. Two other N-alkyl substituted lysergamides, N-methyl-N-isopropyl lysergamide (MIPLA) and N-methyl-N-propyl lysergamide (LAMPA), were also tested in the HTR paradigm for comparative purposes.
Results
ECPLA has high affinity for most serotonin receptors, α2-adrenoceptors, and D2-like dopamine receptors. Additionally, ECPLA was found to be a potent, highly efficacious 5-HT2A agonist for Gq-mediated calcium flux. Treatment with ECPLA induced head twitches in mice with a median effective dose (ED50) of 317.2 nmol/kg (IP), which is ~ 40% of the potency observed previously for LSD. LAMPA (ED50 = 358.3 nmol/kg) was virtually equipotent with ECPLA in the HTR paradigm whereas MIPLA (ED50 = 421.7 nmol/kg) was slightly less potent than ECPLA.
Conclusions
These findings demonstrate that the pharmacological properties of ECPLA, MIPLA, and LAMPA are reminiscent of LSD and other lysergamide hallucinogens.
... 1P-LSD (1-propionyl-LSD), AL-LAD (6-allyl-6-nor-LSD) and LSZ 2,4-dimethylazetidide) [65,66]. ...
... Die in den Folgejahrzehnten in der wissenschaftlichen Literatur beschriebenen Derivate des LSD wie z. B. AL-LAD werden seit dem Jahr 2013 zunehmend in Drogenszenen vermarktet (Brandt et al. 2017;Brandt et al. 2015). DMT wurde erstmals 1931 vom Chemiker Richard Manske synthetisiert und klinisch durch die Psychiater Böszörményi und Szára (Böszörményi und Szára 1958) in Ungarn untersucht, die es als Substitut für das aufgrund politischer Spannungen nicht mehr verfügbare LSD verwendeten (Gallimore und Luke 2015). ...
Psychedelika (klassische bzw. serotonerge Halluzinogene) sind psychoaktive Substanzen, welche Wahrnehmung, Affekte sowie eine Reihe kognitiver Prozesse intensiv verändern können. Die Mehrheit ihrer Vertreter gilt als physiologisch sicher und nicht addiktiv. Ihre Geschichte reicht bis in prähistorische Zeit zurück. Mit der Entdeckung der Wirkstoffe Meskalin, Lysergsäurediethylamid (LSD), Dimethyltryptamin (DMT) und Psilocybin begann sowohl ihre wissenschaftliche Erforschung als auch die Verbreitung ihres nicht medizinischen Gebrauchs. Psychedelika stellen eine pharmakologisch, psychometrisch und tierexperimentell abgrenzbare Substanzklasse dar, die zunehmend im Interesse der medizinischen Grundlagen- und Therapieforschung steht. Dieses Kapitel strebt hinsichtlich der relevanten Wissensgebiete einen ausgewogenen Kurzüberblick über die Substanzklasse und ihre wichtigsten Vertreter an, wobei dem historisch komplexen Wirkgefüge zwischen Medizin- und Sozialgeschichte der Substanzklasse ein Schwerpunkt gewidmet ist.
... Since the first use of lysergic acid diethylamide (LSD) in 1943 by Albert Hofmann (Hofmann, 1980), many similarly structured compounds have emerged such as ALD-52, AL-LAD (or Aladdin), ETH-LAD, PRO-LAD, LSZ and 1P-LSD, to name just a few (Brandt et al., 2017;Brandt et al., 2016;Peyton & Shulgin, 1994;Watts, Mailman, Lawler, Neve, & Nichols, 1995). The increased speed of emergence of these new psychoactive substances (NPS) is partially driven by legislative processes chasing a synthesise-proscribe-synthesise model (Reuter & Pardo, 2017). ...
... LSD analogues and LSD share the same lysergic backbone. However, they present slight variations in their chemical structure, such as AL-LAD's modification at the N6-position (Brandt, et al., 2017). These lysergide derivatives act as an agonist of the 5-HT2A receptor (Brandt, et al., 2016), generally considered the mediator of hallucinogenic effects behaviourally and subjectively (Geyer & Vollenweider, 2008). ...
... nmol/kg) and LSZ equipotent (ED50 = 114.2 nmol/kg, Brandt, et al., 2017). These varying potencies shown in mice do not reflect reported dosages in humans. ...
Objective:
This study aimed to describe self-reported patterns of use and effects of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and the characteristics of those who use them.
Methods:
An anonymous self-selected online survey of people who use drugs (Global Drug Survey 2016; N = 96,894), which measured perceived drug effects of LSD and its analogues.
Results:
Most LSD analogue users (91%) had also tried LSD. The proportion of U.K. and U.S. respondents reporting LSD analogue use in the last 12 months was higher than for LSD only. LSD analogue users described the effects as psychedelic (93%), over half (55%) obtained it online, and almost all (99%) reported an oral route of administration. The modal duration (8 hr) and time to peak (2 hr) of LSD analogues were not significantly different from LSD. Ratings for pleasurable high, strength of effect, comedown, urge to use more drugs, value for money, and risk of harm following use were significantly lower for LSD analogues compared with LSD.
Conclusions:
LSD analogues were reported as similar in time to peak and duration as LSD but weaker in strength, pleasurable high, and comedown. Future studies should seek to replicate these findings with chemical confirmation and dose measurement.
