Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Molecules. 2024 Jan 25;29(3):592. doi: 10.3390/molecules29030592.

Evaluation of an Oral Fluid Collection Device and a Solid-Phase Extraction 
Method for the Determination of Coca Leaf Alkaloids by Gas Chromatography-Mass 
Spectrometry.

Cabarcos-Fernández P(1), Álvarez-Freire I(1), Rubio NC(1), Bermejo-Barrera 
AM(1), Moreda-Piñeiro A(2), Sánchez-Sellero I(1), Tabernero-Duque MJ(1).

Author information:
(1)Forensic Toxicology Service, Forensic Sciences Institute, Faculty of 
Medicine, Universidade de Santiago de Compostela, Rúa de San Francisco, s/n, 
15782 Santiago de Compostela, Spain.
(2)Trace Element, Spectroscopy and Speciation Group (GETEE), Institute of 
Materials iMATUS, Department of Analytical Chemistry, Nutrition and Bromatology, 
Faculty of Chemistry, Universidade de Santiago de Compostela, Avenida das 
Ciencias, s/n, 15782 Santiago de Compostela, Spain.

Some South American countries have ancient traditions that may pose legal 
problems, such as the consumption of coca leaves, as this can provide positive 
results for cocaine use after the analysis of biological samples. For this 
reason, it is necessary to find specific markers that help differentiate legal 
from illegal consumption, such as tropacocaine, cinnamoylcocaine, and especially 
hygrine and cuscohygrine. In this work, two techniques for collecting biological 
samples are compared: the Quantisal® Oral Fluid collection device and passive 
drooling. Once the samples were collected, they were subjected to solid-phase 
extraction for subsequent injection into GC-MS. Different validation parameters 
included in international guides have been studied to evaluate whether the 
proposed method is valid for the defined purpose, placing special emphasis on 
the study of the matrix effect and little value on GC-MS analyses. With respect 
to this parameter, an increase in the signal was found for CUS and t-CIN, but it 
was not significant for the rest of the substances studied. The recoveries have 
varied significantly depending on the way of working, being higher when working 
with standardized areas. After carrying out work with the oral fluid samples 
collected from laboratory volunteers, the method was applied to two real 
samples. The results obtained support the need for further research to overcome 
certain limitations presented by the device.

DOI: 10.3390/molecules29030592
PMCID: PMC11154435
PMID: 38338336 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no conflicts of interest.


2. Anal Methods. 2023 Nov 23;15(45):6177-6183. doi: 10.1039/d3ay01298k.

Detection of coca alkaloids in oral fluid from coca leaf (tea) consumers: using 
solid phase extraction to improve validation parameters and widen the detection 
window.

Álvarez-Freire I(1), Cabarcos-Fernández P(1), Rubio NC(1), Moreda-Piñeiro A(2), 
Tabernero-Duque MJ(1), Sánchez-Sellero I(1), Bermejo-Barrera P(2), 
Bermejo-Barrera AM(1).

Author information:
(1)Instituto de Ciencias Forenses "Luís Concheiro" (INCIFOR), Fac. de Med., 
Universidad de Santiago de Compostela, Spain. pamela.cabarcos@usc.es.
(2)Departamento de Química Analítica, Nutrición y Bromatología-Fac. de Química, 
Instituto de Materiales (iMATUS)-Universidad de Santiago de Compostela, Spain.

Hygrine and cuscohygrine, two coca leaf alkaloids, have been previously proposed 
as markers to differentiate legal and illegal cocaine consumption. This is a 
very common problem in some countries of South America, where the consumption of 
coca leaves has a long tradition. Analytical methods focusing on the assessment 
of coca leaf alkaloids, such as cuscohygrine, hygrine, tropacocaine and 
t-cinnamoylcocaine, in oral fluid are virtually non-existent in forensic 
toxicology laboratories worldwide due to their lack of application. However, the 
problem of differentiating legal and illegal cocaine use in criminal justice, 
DUID (drug-impaired driving) and WDT (workplace drug testing) programs is 
growing. Therefore, researchers are obliged to develop methods to measure coca 
leaf alkaloids (cuscohygrine, hygrine and t-cinnamoylcocaine) in biological 
matrices for further validation for routine analyses in forensic toxicology 
laboratories. This work aims to optimize a previously published separation 
method by protein precipitation in oral fluid by using solid-phase extraction 
(SPE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) 
operating in multiple reaction monitoring (MRM) mode. The use of SPE allowed the 
matrix effect and the background to be reduced in the chromatograms due to the 
obtained cleaner extracts. Consequently, improved detection and quantification 
limits were reached. Findings showed that the detection windows for coca leaf 
alkaloids were longer than three hours in real oral fluid samples from 
volunteers who drank a cup of coca tea. These detection windows are quite higher 
than those previously obtained when using the method based on separation by 
protein precipitation.

DOI: 10.1039/d3ay01298k
PMID: 37937436 [Indexed for MEDLINE]


3. J Pharm Biomed Anal. 2024 Jan 20;238:115804. doi: 10.1016/j.jpba.2023.115804. 
Epub 2023 Oct 19.

Mariani wine: What's really in it? Analysis of the most popular tonic drink of 
the 19th century after 100 years of storage.

Arbouche N(1), de Lestrange A(2), Raul JS(3), Kintz P(4).

Author information:
(1)Institut de Médecine Légale, Strasbourg, France. Electronic address: 
nadia.arbouche@hotmail.it.
(2)École pratique des Hautes Études, Paris, France.
(3)Institut de Médecine Légale, Strasbourg, France.
(4)Institut de Médecine Légale, Strasbourg, France; X-Pertise Consulting, 
Mittelhausbergen, France.

During the Belle Epoque, the use of cocaine, well known to the South American 
populations, spread among the European elite in the form of a tonic drink 
created from coca leaves macerated in Bordeaux wine, the Mariani wine. Nowadays, 
bottles in circulation are extremely rare but the investigations of a Parisian 
historian led him to the discovery of a bottle of wine that belonged to Angelo 
Mariani's estate at the end of the 19th century. Our laboratory was asked to 
analyse the contents of the bottle in order to search for the main active 
compounds and to estimate the state of preservation. The analysis of the 
centenarian product collected was aimed at identifying the alcohols and solvents 
by HS-GC/FID and HS-GC/MS after dilution in water, and the main alkaloids 
contained in all the samples by LC-HRMS screening and LC-MS/MS quantification. 
The Mariani wine presented an alcohol content of 15.7°. The screening and the 
subsequent dosage revealed the following substances: cocaine (86 ng/mL), 
benzoylecgonine (383 ng/mL), cocaethylene (17 ng/mL), ecgonine methyl ester 
(130 ng/mL), caffeine, cuscohygrine, cinnamoylcocaine and synephrine. The 
alkaloids found in the Mariani wine confirm the real presence of coca leaves in 
this drink. Their low concentrations may indicate drug instability. The presence 
of cocaethylene demonstrates that it can be formed without passing through the 
liver, which was supposed to be the site of production when cocaine and ethanol 
are present in the body at the same time. These appear to be the first report in 
the literature presenting the analysis of Mariani wine with the dosage of 
cocaine derivatives.

Copyright © 2023 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.jpba.2023.115804
PMID: 37866081 [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. J Biomol Struct Dyn. 2022;40(21):10887-10898. doi: 
10.1080/07391102.2021.1951355. Epub 2021 Jul 19.

Network pharmacological evaluation of Withania somnifera bioactive 
phytochemicals for identifying novel potential inhibitors against 
neurodegenerative disorder.

Pahal S(1), Gupta A(1), Choudhary P(1), Chaudhary A(2), Singh S.

Author information:
(1)Department of Applied Sciences, Indian Institute of Information Technology 
Allahabad, Prayagraj, India.
(2)Amity Institute of Biotechnology, Amity University, Noida, India.

Neurodegenerative disorders are illnesses that are responsible for neuronal cell 
death and resulting in lifelong cognitive problems. Due to their unclear 
mechanism, there are no effective drugs available for the treatment. For a long 
time, herbal drugs have been used as a role model in the field of the drug 
discovery process. Withania somnifera (Ashwagandha) in the Indian medicinal 
system (Ayurveda) is used for several neuronal disorders like insomnia and 
memory loss for decades. This study aims to identify active components of W. 
somnifera (WS) as potential inhibitors for the treatment of neurodegenerative 
diseases (ND). To fulfill this objective, Network pharmacology approach, gene 
ontology, pharmacokinetics analysis, molecular docking, and molecular dynamics 
simulation (MDS) studies were performed. A total of 77 active components in WS, 
175 predicted neurodegenerative targets of WS, and 8085 ND-related targets were 
identified from different databases. The network analysis showed that the top 
ten targets APP, EGFR, MAPK1, ESR1, HSPA4, PRKCD, MAPK3, ABL1, JUN, and GSK3B 
were found as significant target related to ND. On the basis of gene ontology 
and topology analysis results, APP was found as a significant target related to 
Alzheimer's disease pathways. Molecular docking results found that Anahygrine, 
Cuscohygrine, Isopelletierine, and Nicotine showed the best binding affinities 
-5.55, -4.73, -4.04, and -4.11 Kcal/mol. Further, MDS results suggested that 
Isopelletierine and Nicotine could be used as potential inhibitors against APP 
protein and could be useful for the treatment of Alzheimer's 
disease.Communicated by Ramaswamy H. Sarma.

DOI: 10.1080/07391102.2021.1951355
PMID: 34278961 [Indexed for MEDLINE]


5. Drug Dev Ind Pharm. 2021 May;47(5):699-710. doi:
10.1080/03639045.2021.1934857.  Epub 2021 Jun 7.

Reckoning γ-Glutamyl-S-allylcysteine as a potential main protease (m(pro)) 
inhibitor of novel SARS-CoV-2 virus identified using docking and molecular 
dynamics simulation.

Parashar A(1), Shukla A(2)(3), Sharma A(4), Behl T(5), Goswami D(6), Mehta V(5).

Author information:
(1)Faculty of Pharmaceutical Sciences, Shoolini University of Biotechnology and 
Management Sciences, Solan, India.
(2)Department of Biological Sciences, Institute of Advanced Research, 
Gandhinagar, India.
(3)Department of Microbiology & Biotechnology, University School of Sciences, 
Gujarat University, Ahmedabad, India.
(4)Department of Biotechnology, Yeshiva University, New York, NY, USA.
(5)Department of Pharmacology, Chitkara University, Punjab, India.
(6)Department of Pharmacology, Govt. College of Pharmacy, Rohru, India.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 or COVID-19), 
outbreak was first reported in December 2019 in the Wuhan, China. COVID-19 
managed to spread worldwide and so far more than 9.1 million cases and more than 
4.7 lakh death has been reported globally. Children, pregnant women, elderly 
population, immunocompromised patients, and patients with conditions like 
asthma, diabetes, etc. are highly vulnerable to COVID infection. Currently, 
there is no treatment available for COVID-19 infection. Traditional medicinal 
plants have provided bioactive molecules in the past that are efficiently used 
during conditions like cancer, malaria, microbial infections, immune-compromised 
states, etc. AYUSH India has recommended the use of Curcuma longa, Allium 
sativum, Ocimum tenuiflorum, and Withania somnifera for immune-boosting during 
SARS-CoV-2 infection. In the present study, we investigated the potential of 
63-major bioactive molecules of these plants against SARS-CoV-2 main protease 
(Mpro) through docking studies and compared the results with known inhibitor 
11a. Our results proposed cuscohygrine, γ-Glutamyl-S-allylcysteine, anahygrine, 
and S-allylcystein as the potent inhibitors against Mpro identified using 
molecular docking and molecular simulation dynamics. Interestingly, these 
molecules are from A. sativum, and W. somnifera, which are known for their 
antimicrobial and immunomodulatory potential. None of the proposed molecules 
have earlier been reported as antiviral molecules. Our results predict very 
strong potential of these four-molecules against SARS-CoV-2 Mpro, especially 
γ-glutamyl-S-allylcysteine, as all four form hydrogen bonding with Glu166 that 
is a crucial residue for the formation of the biologically active dimeric form 
of Mpro. Therefore, we strongly recommend further research on these biomolecules 
against SARS-CoV-2.

DOI: 10.1080/03639045.2021.1934857
PMCID: PMC8204316
PMID: 34038246 [Indexed for MEDLINE]

Conflict of interest statement: Authors declare that they have no conflict of 
interest.