ACS Omega
July 1, 2020
Jessica Sable, Tura Patterson, Gary Tarpley et al.
41 citations
A new chemical process produces over one kilogram of high-purity psilocybin, the active compound in psychedelic mushrooms, using a second-generation synthesis designed for large-scale manufacturing. The method improves on earlier procedures by optimizing the Speeter-Anthony tryptamine synthesis to create the intermediate psilocin with better control and impurity removal. It then directly phosphorylates psilocin with phosphorous oxychloride, avoiding a complex benzyl-protecting group strategy used in previous methods. This approach addresses challenges in yield, purity, atom economy, and suitability for pilot plant-scale reactors, providing a more efficient and consistent route for producing psilocybin under current Good Manufacturing Practices.
ACS Omega
December 2, 2020
Alexander M. Sherwood, Romain Claveau, Rafael Lancelotta et al.
38 citations
A multigram-scale process was developed to produce 5-MeO-DMT, a psychedelic natural product from the toad Incilius alvarius, for clinical use. An optimized Fischer indole reaction yielded 5-MeO-DMT freebase, which was converted to the 1:1 succinate salt, producing 136 g of crystalline active pharmaceutical ingredient with 99.86% purity by HPLC and a net yield of 49%. The report details in-process monitoring, validated analytical methods, impurity formation and removal, and solid-state characterization essential for clinical development.
ACS Omega
July 2, 2020
A.r. Chadeayne, Duyen N. K. Pham, Brian G. Reid et al.
31 citations
Aeruginascin, a naturally occurring tryptamine found in magic mushrooms, is thought to produce its effects through an active metabolite. This metabolite was synthesized and its structure confirmed. Competitive radioligand binding assays showed it binds with high affinity to human serotonin receptors 5-HT1A, 5-HT2A, and 5-HT2B, but does not bind to the 5-HT3 receptor, contrary to earlier predictions.
ACS Omega
April 1, 2022
Luisina Castelli Rodríguez, Andrés Mariño López, Guillermo Moyna et al.
28 citations
Ayahuasca, a psychedelic beverage from the Amazon, is made by boiling Banisteriopsis caapi vine with DMT-containing plants. Using NMR and LC-MS/MS, this study analyzed both soluble and insoluble components of ayahuasca samples. For the first time, fructose was detected as a major component, and the alkaloid harmine was found in suspended solids. The major alkaloids identified were DMT, harmine, tetrahydroharmine, harmaline, and harmol. A new quantitative NMR method was developed and validated to simultaneously quantify these alkaloids.
ACS Omega
July 6, 2021
Bruno González, Catherine Fagúndez, Alejandro Peixoto de Abreu Lima et al.
18 citations
An optimized process extracts voacangine from Voacanga africana root bark using a direct acetone-based procedure, yielding approximately 0.8% of the dried root bark weight. The major alkaloids isolated are iboga-vobasinyl dimers, such as voacamine and voacamidine, which constitute about 3.7% of the bark. Because these dimers contain the voacangine moiety, a further optimized cleavage step produces additional voacangine at about 50% isolated molar yield. Applying both extraction and dimer cleavage nearly doubles the total voacangine obtained from the plant material compared to direct extraction alone.
ACS Omega
September 24, 2019
Meghan Grace Appley, Samira Beyramysoltan, Rabi Ann Musah
18 citations
Several plant-based 'legal highs' designated by the United Nations as plants of concern can be reliably identified by their headspace chemical profiles. Using direct analysis in real-time high-resolution mass spectrometry (DART-HRMS), the headspace volatiles of 15 species—including Cannabis sativa, Mitragyna speciosa, and Salvia divinorum—were analyzed. Intraspecies similarities and interspecies differences were observed. Supervised random forest classification achieved 99% accuracy in distinguishing species. A conformal predictor based on this classifier was valid at an 8% significance level with an error rate of 0. The technique demonstrates proof-of-concept for a database to detect and identify plant-based legal highs through headspace analysis.
ACS Omega
October 27, 2020
Megan I. Chambers, Meghan G. Appley, Cameron M. Longo et al.
17 citations
A rapid method using direct analysis in real time-high-resolution mass spectrometry (DART-HRMS) quantifies N,N-dimethyltryptamine (DMT) in ayahuasca brews without lengthy sample preparation. The technique also identifies the beverage by detecting secondary metabolites from its plant ingredients. Analysis of six ayahuasca brews made with different combinations of DMT- and harmala alkaloid-containing plants found DMT levels ranging from 45.7 to 230.5 mg/L, consistent with values from conventional methods.
ACS Omega
May 7, 2018
Lee E. Dunlap, David E. Olson
15 citations
The quaternary ammonium salt byproduct forms at an exceedingly slow rate when DMT is exposed to dichloromethane (DCM), only accumulating significantly after prolonged contact. The byproduct is readily extracted into water. DMT can be exposed to DCM for less than 30 minutes with minimal risk of degradation, and the byproduct is not observed after aqueous extraction. Alternative solvents should be used for longer contact times. These findings have implications for preparing pharmaceuticals with the DMT structural core in high yields and purities.
ACS Omega
July 5, 2022
Grant C. Glatfelter, Duyen N. K. Pham, Donna Walther et al.
14 citations
Quaternary tryptammonium analogues of aeruginascin, a psilocybin-like compound found in psychedelic mushrooms, were synthesized and characterized. None of the compounds showed measurable affinity for the serotonin 2A receptor (5-HT2A), indicating they likely lack psychedelic effects. Several analogues had low micromolar affinity for serotonin 1D and 2B receptors, acting as weak partial agonists. Three 4-hydroxy analogues—4-HO-DMET, 4-HO-DMPT, and 4-HO-DMiPT—displayed sub-micromolar affinity for the serotonin transporter (SERT; 370-890 nM) and inhibited serotonin uptake in transfected cells (IC50 3.3-12.3 μM) and rat brain tissue (IC50 0.31-3.5 μM). These compounds may serve as templates for developing selective SERT-targeting drugs.
ACS Omega
December 20, 2021
Jay B. Nair, Linda B Hakes, Berra Yazar-Klosinski et al.
12 citations
A fully validated cGMP synthesis of up to 5 kg (≈30,000 patient doses) of MDMA has been achieved for the first time, using a four-step process starting from a noncontrolled material. The overall yield was 41–53% over four steps, and chemical purity exceeded 99.9% by HPLC in all validation trials. This cGMP-compliant MDMA will support ongoing clinical trials and potential future therapeutic use if FDA approval is obtained.
ACS Omega
July 10, 2025
Taynah Pereira Galdino, Lucas C Oliveira, Mateus A Luz et al.
5 citations
A validated HPLC-DAD method quantifies psilocybin and psilocin in psychedelic mushroom extracts for medicinal use. Following Brazilian ANVISA guidelines, the method achieved detection limits of 1.58 mg/L for psilocybin and 1.70 mg/L for psilocin, with quantification limits of 4.78 and 5.17 mg/L, respectively. Recovery intervals ranged from 80–120% for psilocybin and 98–116% for psilocin. The mushroom samples contained 2.57% psilocybin and 0.16% psilocin. Accurate measurement of these compounds supports their reliable use in therapeutic contexts, emphasizing the need for precise quantification in developing safe medical treatments.
ACS Omega
April 29, 2025
Cláudia Mancilha Rocha, Larissa Magalhães de Almeida Melo, Augusto César Carvalho Santos et al.
5 citations
A new screening method combining a color change and an electrochemical signal can identify LSD and related drugs (NBOHs, NBOMes, 2Cs) on blotter papers. The method uses Emerson's reagent to produce a color change and a voltammetric measurement on a graphite electrode to detect the drugs. It provides three distinct responses for NBOHs, allowing unambiguous identification, and can distinguish between different drug types. The technique is stable (less than 2.3% variability), sensitive (detection limit of 0.3 μg per mL), and works across a wide concentration range (10 to 1000 μg per mL). When tested on 33 real seized samples, the results matched those from standard confirmatory methods, offering a simple and fast tool for forensic screening.
ACS Omega
January 10, 2023
Megan I. Chambers, Justine E Giffen-Lemieux, Rabi A. Musah
5 citations
A direct analysis in real time-high-resolution mass spectrometry (DART-HRMS) method rapidly screens and quantifies salvinorin A in Salvia divinorum plant material without lengthy sample pretreatment. Raw Salvia leaves contained an average of 1.54 mg/g of salvinorin A, while enhanced leaf extracts had between 13.0 and 53.2 mg/g. Cholesterol served as a suitable internal standard for quantification. The approach bypasses traditional chromatographic sample preparation, enabling faster assessment of psychoactive plant materials.
ACS Omega
February 7, 2022
Robert B. Kargbo, Alexander M. Sherwood, Poncho Meisenheimer et al.
5 citations
A thermodynamically controlled crystallization process for psilocybin, a serotonergic agonist granted breakthrough therapy status for depression, produces crystals with stronger interactions, a controlled particle size distribution, and an improved impurity profile compared to a faster, kinetically controlled process that yields smaller particles. Real-time monitoring with high-resolution inline microscopy measured particle size and metastable zone width and nucleation induction. Water recrystallization forms polymorph B (trihydrate) independently of the method, while polymorph A (anhydrate) and polymorph H (anhydrate) depend on drying: room-temperature vacuum drying yields mainly polymorph A, and heating even at low temperatures produces a mixture of polymorphs A and H.
ACS Omega
August 27, 2024
Marcelo N. Costa, Livia Goto-Silva, Juliana Nascimento et al.
3 citations
Exposure to LSD alters the abundance of hundreds of proteins in lab-grown human brain tissue, affecting pathways related to protein quality control, energy metabolism, and the brain's ability to rewire itself. Mass spectrometry revealed changes in protein synthesis, folding, and degradation, as well as in glycolysis and oxidative phosphorylation. Follow-up experiments showed that LSD also promotes the growth of neuronal extensions, supporting its influence on neuroplasticity. These molecular changes may help explain how psychedelics could produce therapeutic effects in neuropsychiatric disorders.
ACS Omega
May 13, 2026
Darío Martínez-afani, Breno A. Soares, Jaime Mella-Raipán et al.
1 citation
A set of 22 tryptamine and 22 5-methoxytryptamine derivatives with various N-benzyl substituents were synthesized and tested for affinity and potency at serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors. The data enabled QSAR analysis, which showed that meta-substitution on the benzyl ring improves activity, while para-substitution reduces it. These effects are attributed to favorable van der Waals interactions at the meta position and steric hindrance at the para position. The findings suggest that N-benzyltryptamines, previously overlooked as psychedelic ligands, could be leads for treating cognitive disorders, substance abuse, or depression.
ACS Omega
November 10, 2025
Luisina Castelli Rodríguez, Guillermo Morera, Sandra Lupo et al.
1 citation
An optimized extraction protocol and a quantitative nuclear magnetic resonance (qNMR) spectroscopy method enable accurate, nondestructive quantification of the psychoactive tryptamines psilocybin and psilocin in dried Psilocybe cubensis mushrooms. Using both 1H and 31P NMR, the method detects and measures both alkaloids simultaneously with high reproducibility. Analysis of user-provided and laboratory-grown samples reveals substantial variability in total tryptamine content and in the psilocybin-to-psilocin ratio, suggesting that storage conditions affect alkaloid stability. Compared to conventional chromatography, qNMR provides a rapid, calibration-free alternative for routine analysis, potentially supporting quality control in clinical and regulatory settings for psychedelic mushrooms.
ACS Omega
September 16, 2025
Lucas Cordeiro de Oliveira, Taynah Pereira Galdino, Marcelo Da Silva Pedro et al.
1 citation
N,N-Dimethyltryptamine (DMT), a plant-derived alkaloid, shows therapeutic potential for mental health disorders. An efficient method was established to extract, isolate, and characterize DMT from Mimosa tenuiflora, comparing root bark and stem bark. The stem bark method (sample 2C) yielded 3.45% pure DMT (0.172 g from 5.0003 g powder) and a robust phytochemical profile with alkaloids, tannins, and flavonoids. Characterization confirmed DMT identity via FTIR, HPLC-DAD (retention time 11.81 min), and GC-MS (retention time 16.4 min, 88% spectral similarity). Thermogravimetric analysis showed thermal stability up to 135 °C. Cellular viability exceeded 85% at therapeutic concentrations, with reduction only at 100 μg/mL (53 ± 21%), possibly due to overexposure. Sample 2C is a promising candidate for standardized DMT pharmaceutical formulations.
ACS Omega
September 15, 2025
Taynah Pereira Galdino, Antônio Braz de Medeiros Bisneto, Marcelo Da Silva Pedro et al.
1 citation
An active pharmaceutical ingredient (API) extracted from Psilocybe mushrooms yielded approximately 20% of target compounds, with psilocybin and psilocin contents of 3.26% and 0.34%, respectively. The API showed high purity, stability, solubility in polar solvents, low toxicity, and compliance with limits for heavy metals and microbes. It is compatible with polymeric matrices for controlled release. The work demonstrates the feasibility of a standardized psilocybin-based API for treating mental disorders.
ACS Omega
June 23, 2026
Elena Bray, Grant C. Glatfelter, Alexander D. Maitland et al.
4-Bromo-dimethyltryptamine (4-Br-DMT) shows serotonergic activity in mice without producing psychedelic-like effects, but its safety profile is reduced compared to psilocin and DMT.
ACS Omega
January 7, 2026
Ana Barovic, Monica Pittiglio, Justin Barrett et al.
A tablet sold under the brand name Party Duck and an unlabeled powder were analyzed with nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and liquid chromatography/mass spectrometry. Both products contained 4-hydroxy-N-methyl-N-ethyltryptamine (4-HO-MET), a synthetic psychedelic similar to psilocin. The tablets held an average of 2.82 or 1.45 mg of 4-HO-MET per tablet, and the powder qualitatively contained the same compound. These results show that 4-HO-MET is present in commercially available products and underscore the need for rigorous analytical methods to monitor tryptamine derivatives in unregulated markets.
ACS Omega
August 26, 2025
Roman Boča, Juraj Štofko, Cyril Rajnák
Nine psychotropic small molecules with phenyl and aliphatic amine groups—phenethylamine, amphetamine, ephedrine, pseudoephedrine, methamphetamine, MDMA, MDEA, MDA, and MDAI—were analyzed computationally in water using two quantum chemical methods: Density Functional Theory (B3LYP) and a post-Hartree-Fock method (DLPNO-CCSD-(T)). Each molecule was studied as a neutral, cationic, and anionic species, plus protonated forms from hydrochloride salts. Properties calculated included ionization energy, electron affinity, electronegativity, chemical hardness, electrical and magnetic properties, and thermodynamic quantities. Several correlations emerged, such as between molar mass and dipole polarizability, and between ionization energy and oxidation potential. Electron removal during ionization was tracked via changes in atomic spin densities and NMR shielding constants.
ACS Omega
September 24, 2024
Ana Y Martínez, Alexis Caballero, Rodrigo Ramírez et al.
Psychedelics alter thoughts, feelings, and perceptions of reality, with lysergic acid diethylamide being the most potent. This investigation analyzed 27 serotonergic psychedelic molecules, which act as serotonin agonists. The electron acceptance capacity of these compounds correlates with their potency: the best electron acceptor is the most potent drug. Additionally, molecules with greater global softness, indicating higher polarizability, also show greater potency. These findings advance understanding of the mechanism of action of psychotropic drugs.
ACS Omega
August 29, 2019
H. Elbardisy, Christopher W. Foster, J. Marron et al.
A new high-performance liquid chromatography method simultaneously detects and quantifies four halide derivatives of the psychoactive NBOMe compounds, often sold as LSD on blotter papers. Two detection systems were compared: photodiode array and amperometric detection using graphite screen-printed electrodes. Linear calibration ranges were 10–300 and 20–300 μg mL⁻¹ for the two systems, with detection limits of 4.6–6.7 and 9.7–18 μg mL⁻¹, respectively. The method successfully analyzed the four NBOMe derivatives in bulk form, in the presence of LSD and common adulterants, and on simulated blotter papers, yielding satisfactory recoveries. The approach is proposed for routine forensic analysis.