Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Chem Inf Model. 2024 Oct 14;64(19):7457-7469. doi: 10.1021/acs.jcim.4c00761.
 Epub 2024 Sep 27.

Impact of Protonation Sites on Collision-Induced Dissociation-MS/MS Using CIDMD 
Quantum Chemistry Modeling.

Lee J(1)(2), Tantillo DJ(1), Wang LP(1), Fiehn O(2).

Author information:
(1)Department of Chemistry, University of California, Davis, California 95616, 
United States.
(2)West Coast Metabolomics Center, University of California, Davis, California 
95616, United States.

Protonation is the most frequent adduct found in positive electrospray 
ionization collision-induced mass spectra (CID-MS/MS). In a parallel report Lee, 
J. J. Chem. Inf. Model. 2024, 10.1021/acs.jcim.4c00760, we developed a quantum 
chemistry framework to predict mass spectra by collision-induced dissociation 
molecular dynamics (CIDMD). As different protonation sites affect fragmentation 
pathways of a given molecule, the accuracy of predicting tandem mass spectra by 
CIDMD ultimately depends on the choice of its protomers. To investigate the 
impact of molecular protonation sites on MS/MS spectra, we compared 
CIDMD-predicted spectra to all available experimental MS/MS spectra by 
similarity matching. We probed 10 molecules with a total of 43 protomers, the 
largest study to date, including organic acids (sorbic acid, citramalic acid, 
itaconic acid, mesaconic acid, citraconic acid, and taurine) as well as aromatic 
amines including uracil, aniline, bufotenine, and psilocin. We demonstrated how 
different protomers can converge different fragmentation pathways to the same 
fragment ions but also may explain the presence of different fragment ions in 
experimental MS/MS spectra. For the first time, we used in silico MS/MS 
predictions to test the impact of solvents on proton affinities, comparing the 
gas phase and a mixture of acetonitrile/water (1:1). We also extended 
applications of in silico MS/MS predictions to investigate the impact of 
protonation sites on the energy barriers of isomerization between protomers via 
proton transfer. Despite our initial hypothesis that the thermodynamically most 
stable protomer should give the best match to the experiment, we found only weak 
inverse relationships between the calculated proton affinities and corresponding 
entropy similarities of experimental and CIDMD-predicted MS/MS spectra. 
CIDMD-predicted mechanistic details of fragmentation reaction pathways revealed 
a clear preference for specific protomer forms for several molecules. Overall, 
however, proton affinity was not a good predictor corresponding to the predicted 
CIDMD spectra. For example, for uracil, only one protomer predicted all 
experimental MS/MS fragment ions, but this protomer had neither the highest 
proton affinity nor the best MS/MS match score. Instead of proton affinity, the 
transfer of protons during the electrospray process from the initial protonation 
site (i.e., mobile proton model) better explains the differences between the 
thermodynamic rationale and experimental data. Protomers that undergo 
fragmentation with lower energy barriers have greater contributions to 
experimental MS/MS spectra than their thermodynamic Boltzmann populations would 
suggest. Hence, in silico predictions still need to calculate MS/MS spectra for 
multiple protomers, as the extent of distributions cannot be readily predicted.

DOI: 10.1021/acs.jcim.4c00761
PMCID: PMC11492807
PMID: 39329341 [Indexed for MEDLINE]


2. J Psychopharmacol. 2024 Aug;38(8):712-723. doi: 10.1177/02698811241246857.
Epub  2024 Apr 14.

Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, 
pharmacokinetics and effect on altered states of consciousness of intranasal 
BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants.

Rucker JJ(1)(2), Roberts C(3), Seynaeve M(1)(3), Young AH(1)(2), Suttle B(4), 
Yamamoto T(5), Ermakova AO(1)(3), Dunbar F(3), Wiegand F(3).

Author information:
(1)Department of Psychological Medicine, Institute of Psychiatry, Psychology & 
Neuroscience, King's College London, London, UK.
(2)The South London and Maudsley NHS Foundation Trust, Beckenham, Kent, UK.
(3)Beckley Psytech Ltd, Oxford, UK.
(4)qPharmetra, Raleigh, NC, USA.
(5)Hammersmith Medicine's Research, London, UK.

AIMS: To investigate the safety, tolerability, pharmacokinetics (PK) and 
pharmacodynamics (PD) of BPL-003, a novel intranasal benzoate salt formulation 
of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), in healthy participants.
METHODS: In all, 44 psychedelic-naïve participants enrolled in the double-blind, 
placebo-controlled single ascending dose study (1-12 mg BPL-003). Concentrations 
of 5-MeO-DMT and its pharmacologically active metabolite, bufotenine, were 
determined in plasma and urine. PD endpoints included subjective drug intensity 
(SDI) rating, the Mystical Experience Questionnaire (MEQ-30) and the Ego 
Dissolution Inventory (EDI).
RESULTS: BPL-003 was well tolerated at doses up to 12 mg. There were no serious 
adverse events (AEs), and most AEs were mild; the most common being nasal 
discomfort, nausea, headache and vomiting. 5-MeO-DMT was rapidly absorbed and 
eliminated; the median time to peak plasma concentration was approximately 
8-10 min and the mean terminal elimination half-life was <27 min. 5-MeO-DMT 
systemic exposure increased approximately dose-proportionally, while plasma 
bufotenine concentrations and urinary excretion of 5-MeO-DMT and bufotenine were 
negligible. The intensity of the SDI ratings was associated with plasma 
5-MeO-DMT concentrations. MEQ-30 and EDI scores generally increased with the 
BPL-003 dose; 60% of participants had a 'complete mystical experience' at 10 and 
12 mg doses. Profound and highly emotional consciousness-altering effects were 
observed with BPL-003, with a rapid onset and short-lasting duration.
CONCLUSION: The novel intranasal formulation of BPL-003 was well tolerated with 
dose-proportional increases in PK and PD effects. The short duration of action 
and induction of mystical experiences suggest clinical potential, warranting 
further trials.
CLINICAL TRIAL REGISTRATION: NCT05347849.

DOI: 10.1177/02698811241246857
PMCID: PMC11311898
PMID: 38616411 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of conflicting interestsThe 
author(s) declared the following potential conflicts of interest with respect to 
the research, authorship and/or publication of this article: C.R. is an employee 
of Beckley Psytech Ltd. M.S. is currently an employee of Beckley Psytech Ltd but 
was employed by King’s College London (until July 2022) and is currently 
completing a PhD with King’s College London. F.W. was an employee of Beckley 
Psytech Ltd when this study was undertaken. F.D. is a medical advisor to Beckley 
Psytech Ltd. A.O.E. is a consultant to Beckley Psytech Ltd. J.J.R. has received 
payments for advisory boards for Clerkenwell Health (Past), Beckley Psytech Ltd 
(Past), Delica Therapeutics (Past) and articles for Janssen. He has received 
financial assistance for attendance at conferences from Compass Pathways (past) 
and Janssen. He has been awarded grant funding (received and managed by King’s 
College London) from Compass Pathfinder, Beckley Psytech Ltd, Multidisciplinary 
Association for Psychedelic Studies, National Institute for Health Research, 
Wellcome Trust, Biomedical Research Centre at the South London and Maudsley NHS 
Foundation Trust. He has no shareholdings in pharmaceutical companies and no 
shareholdings in companies developing psychedelics. A.H.Y. is employed by King’s 
College London and he is an Honorary Consultant of South London and Maudsley NHS 
Foundation Trust (NHS UK). His independent research is funded by the National 
Institute for Health and Care Research (NIHR) Maudsley Biomedical Research 
Centre in South London and Maudsley NHS Foundation Trust and King’s College 
London. He has previously received funding from Beckley Psytech Ltd. He has 
received payments for lectures and advisory boards for Flow Neuroscience, 
Novartis, Roche, Janssen, Takeda, Noema Pharma, Compass, Astrazenaca, Boehringer 
Ingelheim, Eli Lilly, LivaNova, Lundbeck, Sunovion, Servier, Livanova, Janssen, 
Allegan, Bionomics, Sumitomo Dainippon Pharma, Sage and Neurocentrx. He has 
received grant funding from the following companies: NIMH (USA); CIHR (Canada); 
NARSAD (USA); Stanley Medical Research Institute (USA); MRC (UK); Wellcome Trust 
(UK); Royal College of Physicians (Edin); BMA (UK); UBC-VGH Foundation (Canada); 
WEDC (Canada); CCS Depression Research Fund (Canada); MSFHR (Canada); NIHR (UK). 
Janssen (UK) EU Horizon 2020. He is the Editor of the Journal of 
Psychopharmacology and Deputy Editor of BJPsych Open. He has no shareholdings in 
pharmaceutical companies. T.Y. is an employee of Hammersmith Medicine’s 
Research. The clinical trial, performed at Hammersmith Medicine’s Research, was 
sponsored by Beckley Psytech Ltd. B.S. is a consultant to Beckley Psytech Ltd.


3. Biochim Biophys Acta Biomembr. 2024 Apr;1866(4):184304. doi: 
10.1016/j.bbamem.2024.184304. Epub 2024 Feb 24.

Spectroscopic behavior of bufotenine and bufotenine N-oxide: Solvent and pH 
effects and interaction with biomembrane models.

Almeida E Silva G(1), Galvão Wakui V(2), Kato L(2), Marquezin CA(3).

Author information:
(1)Instituto de Física, Universidade Federal de Goiás, CEP 74690-900, Goiânia, 
GO, Brazil.
(2)Instituto de Química, Universidade Federal de Goiás, CEP 74690-900, Goiânia, 
GO, Brazil.
(3)Instituto de Física, Universidade Federal de Goiás, CEP 74690-900, Goiânia, 
GO, Brazil. Electronic address: cassia_m@ufg.br.

Bufotenine is a fluorescent analog of Dimethyltryptamine (DMT) that has been 
widely studied due to its psychedelic properties and biological activity. 
However, little is known about its spectroscopic properties in different media. 
Thus, we present in this work, for the first time, the spectroscopic behavior of 
bufotenine and bufotenine N-oxide by means of their fluorescence properties. 
Both molecules exhibit changes in optical absorption and emission spectra with 
variations in pH of the medium and in different solvents. Assays in the presence 
of biomembranes models, like micelles and liposomes, were also performed. In 
surfactants titration experiments, the spectral shift observed in fluorescence 
shows the interaction of both molecules with pre-micellar structures and with 
micelles. Steady state anisotropy measurements show that both bufotenine and 
bufotenine N-oxide, in the studied concentration range, interact with liposomes 
without causing changes in the fluidity of the lipid bilayer. These results can 
be useful in studies that aim at searching for new compounds, inspired by 
bufotenine and bufotenine N-oxide, with relevant pharmacological activities and 
also in studies that use these molecules as markers of psychiatric disorders.

Copyright © 2024 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.bbamem.2024.184304
PMID: 38408695 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest The authors 
declare that they have no known competing financial interests or personal 
relationships that could have appeared to influence the work reported in this 
paper.


4. Int J Biol Macromol. 2024 Mar;260(Pt 2):129539. doi: 
10.1016/j.ijbiomac.2024.129539. Epub 2024 Jan 18.

Cloning, characterization and specificity of a new aromatic-L-amino-acid 
decarboxylases from Bufo bufo gargarizans.

Xie Y(1), Feng X(1), Tao J(1), Gao Q(1), Li Y(1), Liu X(1), Xia M(2), Wang D(3).

Author information:
(1)School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical 
University, Benxi 117004, China.
(2)School of Life Science and Biological Pharmacy, Shenyang Pharmaceutical 
University, Shenyang 110016, China.
(3)School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical 
University, Benxi 117004, China. Electronic address: dongwang@syphu.edu.cn.

5-Hydroxytryptamine (5-HT) and its derivative bufotenine, which possess 
important physiological functions, are the primary active components in the 
secretions of toad parotid and skin gland. However, the biosynthetic pathway of 
these substances remains unclear in toads. To characterize toad's 
Aromatic-L-amino-acid decarboxylase (AADC), the key enzyme in the predicted 5-HT 
derivatives biosynthetic pathway, the full-length cDNA of AADC from Bufo bufo 
gargarizans (BbgAADC) was cloned from the parotoid gland of B. bufo gargarizans. 
The recombinant BbgAADC exhibited optimal expression in E. coli BL21 (DE3) 
containing pCold-BbgAADC after induction for 16 h at 15 °C with 0.3 mM IPTG, 
resulting in substantial yields of soluble proteins. The enzymological 
properties of BbgAADC were assessed, and it was determined that the optimal 
reaction temperature was 37 °C, the optimal pH was 8.6, and the optimum molar 
ratio of pyridoxal-5'-phosphate (PLP) to BbgAADC was found to be 3.6:1. 
Additionally, high substrate specificity was observed, as BbgAADC could catalyze 
the production of 5-HT from 5-hydroxytryptophan (5-HTP) but not dopamine or 
tryptamine from levodopa or tryptophan, respectively. The Km of the recombinant 
protein BbgAADC was 0.2918 mM and the maximum reaction rate (Vmax) was 
1.182 μM·min-1 when 5-HTP was used as substrate. The Kcat was 0.0545 min-1, and 
Kcat/Km was 0.1868 mM-1·min-1. To elucidate the mechanism of BbgAADC, molecular 
docking was performed with PLP and 5-HTP, or the external aldimine formed by 
5-HTP and PLP. The results indicated that the active sites for BbgAADC to bind 
with PLP were K303, H192, N300, A148, F309, T246, A273, and T147. W71, Y79, F80, 
P81, T82, H192, T246, N300, H302, F309, and R477 served as catalytically active 
sites for the binding of BbgAADC to 5-HTP. Furthermore, R447, W71, S149, N300, 
A148, and T147 of BbgAADC were involved in the decarboxylation reaction of the 
aldimine formed by PLP and 5-HTP.

Copyright © 2024 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.ijbiomac.2024.129539
PMID: 38244737 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest The authors 
declare no conflict of interest. The founding sponsors had no role in the design 
of the study, in the collection, analyses, or interpretation of data, in the 
writing of the manuscript, or in the decision to publish the results.


5. Se Pu. 2023 Nov;41(11):976-985. doi: 10.3724/SP.J.1123.2023.07013.

[Determination of amanita peptide and tryptamine toxins in wild mushrooms by 
high performance liquid chromatography-tandem mass spectrometry].

[Article in Chinese]

Liu LQ(1)(2), Chen JZ(1)(2), Fu WS(1)(2)(3)(4), Tang CY(2)(3).

Author information:
(1)School of Public Health, Fujian Medical University, Fuzhou 350122, China.
(2)Fujian Provincial Key Laboratory for Zoonosis Research, Fujian Center for 
Disease Control and Prevention, Fuzhou 350012, China.
(3)School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 
350122, China.
(4)Food Science College of Fujian Agriculture and Forestry University, Fuzhou 
350002, China.

The discovery and identification of mushroom toxins has long been an important 
area in the fields of toxicology and food safety. Mushrooms are widely favored 
for their culinary and medicinal value; however, the presence of potentially 
lethal toxins in some species poses a substantial challenge in ensuring their 
safe consumption. Therefore, the development of a robust and sensitive 
analytical method is necessary for accurately identifying the risks associated 
with mushroom consumption. The study of mushroom toxins, which are characterized 
by their diversity and substantial variations in chemical structures, present a 
considerable challenge for achieving precise and high-throughput analysis. To 
address this issue, the present study employed a robust approach combining a 
solid-phase extraction (SPE) purification technique with high performance liquid 
chromatography-tandem mass spectrometry (HPLC-MS/MS) to establish an analytical 
method for the detection and quantification of five amatoxins and two 
tryptamines (psilocybin and bufotenine) present in some mushrooms. Several 
optimization procedures were undertaken, including optimizing the 
chromatographic conditions, mass spectrometric parameters, and sample extraction 
and purification. The procedure involved the extraction of dry mushroom powder 
with methanol containing 0.3% formic acid, followed by purification using a 
strong cation exchange cartridge (SCX). The analytes were separated on a T3 
chromatographic column (100 mm×2.1 mm, 1.8 μm) using mobile phases of 
acetonitrile and 5 mmol/L ammonium acetate solution containing 0.1% formic acid. 
The multiple reaction monitoring (MRM) mode was employed for data acquisition. 
Amatoxins were quantified using matrix-matched standard calibration curves, 
whereas isotopic internal standards were used to quantify tryptamine. The 
results showed that all seven toxins exhibited good linearities (r2>0.99) within 
the optimized concentration range. The limits of detection (LODs) for 
bufotenine, psilocybin, and amatoxins were determined as 2.0, 5.0, and 10 μg/kg, 
respectively, while the limits of quantification (LOQs) were determined as 5.0, 
10, and 20 μg/kg, respectively. The LOD and LOQ values further underscore the 
ability of the method to detect minute quantities of toxins, making it 
particularly well suited for screening food samples for potential contamination. 
Using dried shiitake mushroom powder as the matrix, the recoveries of the two 
tryptamines ranged from 80.6% to 117%, with relative standard deviations (RSDs) 
ranging from 1.73% to 5.98%, while the recoveries of amatoxins ranged from 71.8% 
to 115%, with RSDs varying from 2.14% to 9.92% at the three concentration 
levels. The consistent and satisfactory recoveries of amatoxins and tryptamines 
demonstrated the ability of this method to accurately quantify the target 
analytes even in a complex matrix. Comparison with the results of supplementary 
test method recognized by State Administration for Market Regulation for food 
(BJS 202008) demonstrated comparable results, indicating no significant 
differences (p>0.05) in amatoxin contents. The newly developed method is rapid, 
accurate, precise, meets the required standards, and is suitable for the 
detection of seven toxins in wild mushrooms. As part of the application of this 
method, a comprehensive investigation of the distribution of toxins in wild 
mushrooms from Fujian Province was undertaken. In this study, 59 wild mushroom 
samples from nine cities were collected in the Fujian province. Species 
identification was conducted using rDNA-internal transcribed space (rDNA-ITS) 
molecular barcode technology, which revealed the presence of toxins in the two 
samples. Notably, one specimen named Amanita fuligineoides contained α-amanitin, 
β-amanitin, and phalloidin in quantities of 607, 377, and 69.0 mg/kg, 
respectively. Additionally, another sample, identified as Tricholomataceae, had 
a psilocybin concentration of 12.6 mg/kg.

蘑菇毒素种类繁多,化学结构差异大,为了实现蘑菇中毒素的准确、高通量分析,本文采用固相萃取净化技术,以高效液相色谱-串联质谱法(HPLC-MS/MS)为分析手段,建立了蘑菇中5种鹅膏肽类、2种色胺类蘑菇毒素的分析方法。优化了色谱条件、质谱参数和样品提取净化方法,蘑菇干粉以含0.3%甲酸的甲醇提取,强阳离子交换柱(SCX)净化后,待测样液用T3色谱柱分离,以含0.1%甲酸的5 
mmol/L乙酸铵水溶液、乙腈为流动相进行梯度洗脱,采用多反应监测模式(MRM)扫描,以基质匹配标准曲线法对鹅膏肽毒素定量,以同位素内标法对色胺类毒素定量。结果显示,7种毒素在一定的浓度范围内与峰面积(或峰面积比)均呈良好的线性关系(r2>0.99)。蟾蜍色胺、脱磷裸盖菇素、鹅膏肽类毒素的检出限(LOD)分别为2.0、5.0、10 
μg/kg,定量限(LOQ)分别为5.0、10、20 
μg/kg;以香菇干粉为基质,在3个水平下加标,5种鹅膏肽类毒素的回收率为71.8%~115%,相对标准偏差(RSD)为2.14%~9.92%; 
2种色胺类毒素的回收率为80.6%~117%, RSD为1.73%~5.98%;与国家市场监管总局食品补充检验方法BJS 
202008进行比对,结果表明鹅膏毒素含量具有可比性,无显著性差异(p>0.05)。该方法简便、快速,准确度和精密度较高,符合要求,适用于野生蘑菇中7种蘑菇毒素的检测。采用该法开展了福建省野生蘑菇中蘑菇毒素分布情况的调查,在全省9个设区市采集了59份野生蘑菇样品,采用核糖体DNA内转录间隔区(rDNA-ITS)分子条形码技术进行了种属鉴定,在2份样品中检测出了蘑菇毒素,在1份拟灰花纹鹅膏(Amanita 
fuligineoides)干粉提取物中检出α-鹅膏毒肽、β-鹅膏毒肽和二羟鬼笔毒肽,含量分别为607、377、69.0 
mg/kg;在1份口蘑科(Tricholomataceae)蘑菇中检出脱磷裸盖菇素,含量为12.6 mg/kg。

DOI: 10.3724/SP.J.1123.2023.07013
PMCID: PMC10654875
PMID: 37968816 [Indexed for MEDLINE]