Drug Testing and Analysis
October 12, 2015
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
79 citations
1-Propionyl-d-lysergic acid diethylamide hemitartrate (1P-LSD), a non-controlled derivative of LSD, was characterized and tested for LSD-like effects. Using chromatographic, mass spectrometric, infrared, and nuclear magnetic resonance methods, the compound was compared to LSD. In male C57BL/6J mice, 1P-LSD produced a dose-dependent increase in head-twitch response (HTR) counts, a behavioral marker of 5-HT2A receptor activation. 1P-LSD had about 38% of the potency of LSD (ED50 = 349.6 nmol/kg vs. 132.8 nmol/kg for LSD). Pretreatment with the selective 5-HT2A receptor antagonist M100907 abolished the HTR, confirming that the response was mediated by 5-HT2A receptor activation. These results indicate 1P-LSD produces LSD-like effects in mice, consistent with classification as a serotonergic hallucinogen, though human psychoactive effects remain unknown.
Drug Testing and Analysis
May 13, 2019
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
72 citations
1-Butanoyl-LSD (1B-LSD), a new analog of lysergic acid diethylamide (LSD), was fully characterized using multiple analytical techniques including NMR, mass spectrometry, and infrared spectroscopy, allowing clear differentiation from a similar compound, 1P-ETH-LAD. In behavioral tests with C57BL/6J mice, 1B-LSD produced a dose-dependent increase in head-twitch response, a marker of serotonergic hallucinogen activity, though with only about 14% of LSD's potency (ED50 = 976.7 nmol/kg vs. 132.8 nmol/kg for LSD). This suggests 1B-LSD has LSD-like behavioral effects and may act as a pro-drug for LSD, but further research is needed to confirm psychoactive effects in humans.
Drug Testing and Analysis
March 16, 2020
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
38 citations
1-Cylopropanoyl-LSD (1CP-LSD), a new lysergamide-based designer drug, was analyzed using multiple chemical and spectroscopic methods. Incubation with human serum converted 1CP-LSD into LSD, suggesting it may act as a prodrug for LSD in the body. In mice, 1CP-LSD induced a head-twitch response (HTR) with an ED50 of 430.0 nmol/kg, comparable to 1P-LSD (ED50 = 349.6 nmol/kg), indicating an LSD-like behavioral profile. The study includes analysis of blotters and pellets, and detected artificially induced degradation products during GC-MS analysis. Clinical studies are needed to determine its potency and effects in humans.
Neuropharmacology
November 19, 2019
Adam L. Halberstadt, Muhammad Chatha, Adam K. Klein et al.
37 citations
The ergoline d-lysergic acid diethylamide (LSD) is one of the most potent psychedelic drugs. 1-Acetyl-LSD (ALD-52) and other 1-acyl-substituted LSD derivatives, including 1-propanoyl-LSD (1P-LSD) and 1-butanoyl-LSD (1B-LSD), have appeared as designer drugs assumed to act as prodrugs for LSD. Competitive binding studies and calcium mobilization assays showed 1-acyl-substitution reduced affinity for most monoamine receptors, including 5-HT2A sites, by one to two orders of magnitude, and these derivatives had weak efficacy or acted as antagonists in Ca2+-mobilization assays. Despite this, they induced head twitches in mice with relatively high potency. High levels of LSD were detected in rat plasma after subcutaneous administration of ALD-52 and 1P-LSD, demonstrating rapid and efficient deacylation in vivo, consistent with the prediction that these compounds serve as prodrugs for LSD.
Journal of Pharmaceutical and Biomedical Analysis
May 28, 2019
Christina Grumann, Kerstin Henkel, Alexander Stratford et al.
27 citations
1-propionyl-LSD (1P-LSD), an uncontrolled derivative of LSD, requires sensitive detection methods due to its high potency. A validated LC-MS/MS method quantified 1P-LSD and LSD in urine and serum with a calibration range of 0.015-0.4 ng mL⁻¹ and limits of detection and quantification at 0.005 and 0.015 ng mL⁻¹, respectively. Stability tests showed 1P-LSD remained stable in samples stored at -20 °C, 5 °C, or room temperature for up to five days, but LSD formed at room temperature (up to 21% in serum), likely from enzymatic hydrolysis. Sodium fluoride prevented this conversion. In an intoxication case, only LSD was detected: 0.51 ng mL⁻¹ in urine and 3.4 ng mL⁻¹ in serum, suggesting rapid in-vivo hydrolysis of 1P-LSD to LSD.
Drug testing and analysis
February 1, 2019
Lea Wagmann, Simon D Brandt, Alexander Stratford et al.
26 citations
Thirteen of 17 phenethylamine-derived designer drugs (12 from the 2C-series and five FLY analogs) inhibited monoamine oxidase A (MAO-A), and 11 inhibited monoamine oxidase B (MAO-B) in an in vitro assay using heterologously expressed enzymes and hydrophilic interaction liquid chromatography-high resolution tandem mass spectrometry. For the seven drugs where MAO-A IC50 values were determined, values ranged from 10 to 125 μM; for the nine drugs with MAO-B IC50 values, the range was 1.7 to 180 μM. Because clinical information on most test drugs is lacking, a pharmacological contribution of MAO inhibition cannot be excluded, and further studies are warranted.
Psychopharmacology
February 14, 2019
Adam L. Halberstadt, Landon M. Klein, Muhammad Chatha et al.
25 citations
The lysergamide ECPLA, a close structural analog of LSD, binds with high affinity to serotonin, adrenergic, and dopamine receptors, and acts as a potent agonist at the 5-HT₂A receptor, which mediates psychedelic effects. In mice, ECPLA induced head twitches with an ED₅₀ of 317.2 nmol/kg, about 40% as potent as LSD. Two other analogs, LAMPA (ED₅₀ = 358.3 nmol/kg) and MIPLA (ED₅₀ = 421.7 nmol/kg), showed similar or slightly lower potency. These findings indicate that ECPLA, MIPLA, and LAMPA share pharmacological properties with LSD and other lysergamide hallucinogens.
Neuropharmacology
January 1, 2019
Adam L Halberstadt, Muhammad Chatha, Alexander Stratford et al.
25 citations
Rigid analogs of phenylalkylamine hallucinogens, such as 2C-B-FLY and Bromo-DragonFLY (DOB-DFLY), have emerged as recreational drugs. In mice, the head twitch response—a behavior mediated by the 5-HT2A receptor—was used to compare potencies. DOB (ED50 = 0.75 μmol/kg) and 2C-B (ED50 = 2.43 μmol/kg) induced the response. Benzodifurans DOB-DFLY (ED50 = 0.20 μmol/kg) and 2C-B-DFLY (ED50 = 1.07 μmol/kg) showed significantly higher potency than their non-rigid counterparts. Tetrahydrobenzodifurans DOB-FLY (ED50 = 0.67 μmol/kg) and 2C-B-FLY (ED50 = 1.79 μmol/kg) were approximately equipotent. Three novel tetrahydrobenzodifurans were active but had relatively low potency.
Drug Testing and Analysis
May 16, 2020
Christina Grumann, Kerstin Henkel, Simon D. Brandt et al.
23 citations
1P-LSD, a non-controlled alternative to LSD, acts as a prodrug that converts almost entirely into LSD in the human body. In two volunteers, oral and intravenous doses of 100 μg 1P-LSD were administered. After oral intake, only LSD was detected in serum and urine, with a terminal elimination half-life of about 6.4 hours. Intravenous 1P-LSD was detectable for only a few hours, while LSD persisted much longer. The bioavailability of LSD from oral 1P-LSD was nearly 100%. Subjective drug effects and altered states of consciousness scores were comparable to those from LSD, supporting the prodrug hypothesis. Oral administration produced higher 5D-ASC scores than intravenous.
Drug testing and analysis
October 1, 2019
Lea Wagmann, Nora Hempel, Lilian H J Richter et al.
20 citations
Three new psychoactive substances of the 2C-FLY series—2C-E-FLY, 2C-EF-FLY, and 2C-T-7-FLY—were studied to determine how the body metabolizes them and how they can be detected in toxicological tests. Using rat urine and human liver S9 fractions analyzed by LC-HRMS/MS, 32 metabolites were identified. Main metabolic steps were hydroxylation and N-acetylation, catalyzed by CYP2D6, CYP3A4, FMO3, NAT1, and NAT2. Deamination by MAO-A and B was also observed. Polymorphisms or drug interactions may cause interindividual differences. Standard urine screening approaches using GC-MS, LC-MSn, and LC-HRMS/MS were suitable for detecting intake, but common metabolites of 2C-E-FLY and 2C-EF-FLY must be considered when interpreting results.
Drug Testing and Analysis
November 27, 2021
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
19 citations
A new LSD derivative called 1-valeroyl-LSD (1V-LSD, or "Valerie") has appeared on the online market. It is a higher homolog of earlier derivatives like ALD-52, 1P-LSD, and 1B-LSD. The study analytically characterized 1V-LSD using mass spectrometry, chromatography, NMR, and Raman spectroscopy. In mice, 1V-LSD induced a head-twitch response, a behavioral proxy for human hallucinogenic effects, in a dose-dependent manner. Its median effective dose was 373 nmol/kg, about a third the potency of LSD (ED50 = 132.8 nmol/kg). 1V-LSD likely acts as a prodrug that is hydrolyzed to LSD, but further studies on its biotransformation and receptor pharmacology are needed.
Drug Testing and Analysis
May 7, 2022
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
14 citations
The lysergamide 1P-AL-LAD is characterized and tested in vitro and in mice. In pooled human liver microsomes, 1P-AL-LAD converts to AL-LAD as the most abundant metabolite, supporting the idea that it acts as a prodrug. Fourteen metabolites are detected, including hydroxylation and deacylation products. In mice, 1P-AL-LAD produces a dose-dependent increase in head twitch response, a behavioral proxy for human hallucinogenic effects, with an inverted U-shaped dose-response curve. Its median effective dose is 491 nmol/kg, almost three times less potent than AL-LAD (174.9 nmol/kg). The prodrug mechanism likely explains its activity despite N1-substitution disrupting 5-HT2A receptor activation.
Drug Testing and Analysis
May 22, 2021
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
12 citations
Lysergic acid diethylamide (LSD) is a potent psychoactive substance of clinical interest, and its analogs, including N-methyl-N-isopropyl isomer (MIPLA), have appeared on the street market. This report describes analytical methods to differentiate MIPLA from LSD and the N-methyl-N-propyl isomer (LAMPA) under routine conditions. Gas chromatography-solid phase infrared spectroscopy was particularly helpful. GC-electron ionization-tandem mass spectrometry of the m/z 72 iminium ion distinguished the three isomers on mass spectral grounds alone. Derivatization with BSTFA improved GC separation. LC-Q-MS and in-source collision-induced dissociation differentiated MIPLA and LAMPA based on distinct m/z 239 ion ratios. An alternative LC-MS/MS method improved separation but LSD co-eluted with iso-LSD; comparing ion ratios at m/z 324.2 > 223.2 and 324.2 > 208.2 facilitated differentiation. Two blotters contained 180 and 186 μg MIPLA per blotter.
Drug testing and analysis
January 1, 2025
Pierce V Kavanagh, Folker Westphal, Benedikt Pulver et al.
8 citations
A novel LSD derivative, 1-dodecanoyl-LSD (1DD-LSD), was synthesized and tested in mice to see if it produces LSD-like effects. The compound induced a head-twitch response in C57BL/6J mice with a median effective dose of 2.17 mg/kg (3.60 μmol/kg). LSD was 27-fold more potent than 1DD-LSD under similar conditions. Other homologues, such as ALD-52 and 1-propanoyl-LSD, also showed considerably higher potency, suggesting that hydrolysis of the 1-dodecanoyl moiety may be less efficient in vivo. The increased lipophilicity of 1DD-LSD might cause it to be sequestered in fat, reducing enzymatic hydrolysis. Further studies are needed to assess its activity in humans and its potential as a long-acting prodrug for LSD.
Drug testing and analysis
March 1, 2023
Pierce V Kavanagh, Folker Westphal, Benedikt Pulver et al.
7 citations
A new lysergamide, 1cP-AL-LAD, was analyzed using chromatographic, mass spectrometric, and spectroscopic methods. A powdered sample from an online vendor contained 17 impurities, including AL-LAD and 1P-AL-LAD (confirmed by reference standards) and tentatively identified compounds such as 1-acetyl-AL-LAD and oxidation products of the N6-allyl group and ergoline ring. The substance was also found in blotter paper samples sold online for recreational use. These findings provide analytical data for researchers interested in lysergamide chemistry.
Drug testing and analysis
December 3, 2024
Simon D Brandt, Pierce V Kavanagh, Sarah Gare et al.
5 citations
1-(2-furoyl)-lysergic acid diethylamide (1F-LSD, SYN-L-005) is a novel analog of the recently detected recreational drug 1-(thiophene-2-carbonyl)-LSD (1T-LSD). Both substances are N1-acylated LSD derivatives that bind to the 5-HT2A receptor, the primary site of action for psychedelic drugs. In C57BL/6J mice, 1F-LSD and 1T-LSD induced the head-twitch response, a 5-HT2A-mediated behavior, and were hydrolyzed to LSD after administration. These findings indicate that both compounds exhibit LSD-like properties and likely act as prodrugs for LSD, releasing the active drug in the body.
Drug testing and analysis
February 1, 2024
Simon D Brandt, Pierce V Kavanagh, Folker Westphal et al.
5 citations
N-ethyl-N-isopropyllysergamide (EIPLA), an isomer of the psychedelic lysergamide ETH-LAD, shows LSD-like properties in preclinical tests. Mass spectrometry, chromatography, and NMR spectroscopy distinguished EIPLA from ETH-LAD by their structural features. Blotter extracts contained 96.9 ± 0.5 μg and 85.8 ± 2.8 μg of EIPLA base. In mice, EIPLA induced head-twitch responses (ED50 = 234.6 nmol/kg), about half the potency of LSD (ED50 = 132.8 nmol/kg), consistent with serotonergic psychedelic effects. Analytical data are provided to aid forensic and clinical identification.
Drug testing and analysis
April 1, 2025
Simon D Brandt, Pierce V Kavanagh, Sarah Gare et al.
4 citations
A newly developed LSD derivative, 1-hexanoyl-LSD (1H-LSD), was characterized analytically and tested in mice using the head-twitch response assay, a behavioral proxy for psychedelic activity. 1H-LSD induced head-twitch responses with a median effective dose of 192.4 μg/kg, making it roughly as potent as the known analog 1A-LSD (ALD-52) under similar conditions. Like other N1-acylated LSD derivatives, 1H-LSD is expected to be hydrolyzed to LSD in the body, acting as a prodrug. It is not yet known whether this compound has appeared on the recreational drug market or in research chemical supplies.