Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Clin Chem Lab Med. 2024 May 13;62(11):2198-2204. doi: 10.1515/cclm-2024-0311. 
Print 2024 Oct 28.

OILVEQ: an Italian external quality control scheme for cannabinoids analysis in 
galenic preparations of cannabis oil.

Rotolo MC(1), Graziano S(1), Minutillo A(1), Varì MR(1), Pichini S(1), Marchei 
E(1).

Author information:
(1)National Centre on Addiction and Doping, Italian National Institute of 
Health, Rome, Italy.

OBJECTIVES: Italy legalized cannabis oil for specific medical conditions 
(neuropathic pain, refractory epilepsy and other established pathologies) in 
2015, but mandates titration of principal cannabinoids before marketing each 
batch using iphenated techniques coupled with mass spectrometry. To assess 
reliability of laboratories from the Italian National Health Service in charge 
of titrating the batches, the Italian National Institute of Health set up an 
quality control program on determination of Δ9-tetrahydrocannabinol l (THC), 
cannabidiol (CBD), Δ9-tetrahydrocannabinolic acid A (THCA-A) and cannabidiolic 
acid (CBDA) in cannabis oil preparations.
METHODS: Two rounds of exercises have been carried out since 2019, involving 
sixteen Italian laboratories. Five different cannabis oil samples (19-1A and 
19-1B for the first round and 22-1A, 22-1B and 22-1C for the second one were 
prepared and 1 mL amount of each sample was sent to the laboratories. The 
quantitative performance of each laboratory was assessed calculating the Z-score 
value, a statistical measurement for value's relationship to the mean of a group 
of values.
RESULTS: In the first round, eight out of fourteen laboratories employed an 
LC-MS while the remaining six used GC-MS. Differently, in the second round, six 
out of eleven laboratories employed a GC-MS while the remaining five used LC-MS. 
In the first round, only 28.6 % laboratories achieved an acceptable performance 
(Z-score±2), and all of them used LC-MS as analytical method. In the second 
round, none of the laboratories achieved an acceptable performance. Satisfactory 
results, based on Z-scores, were generally low (0.0-75.0 %), with only one 
exception of 100 % for THCA-A determination in sample 22-1B. In the second 
round, three false negatives (two THC and one CBD by GC-MS determination) were 
reported while no false positives were described in the blank sample. The two 
rounds yielded a mean ERR% of 42 % approximately and a mean CV% around 70 % in 
GC-MS determination. When applying LC-MS determination, the two rounds yielded a 
mean ERR% of 36 % approximately and a mean CV% around 33 %.
CONCLUSIONS: The obtained results underline the need for a clear and consistent 
protocol to be adopted by all laboratories intending to include the titration of 
oily cannabis-based products into their routinely analytical techniques. This 
emphasis on methodology standardization and participation to quality control 
schemes is essential for ensuring reliable and accurate measurements, ultimately 
enhancing the overall effectiveness and reliability of medical cannabis 
treatments.

© 2024 Walter de Gruyter GmbH, Berlin/Boston.

DOI: 10.1515/cclm-2024-0311
PMID: 38727000 [Indexed for MEDLINE]


2. J Photochem Photobiol B. 2024 May;254:112902. doi: 
10.1016/j.jphotobiol.2024.112902. Epub 2024 Mar 29.

Low UV radiation influenced DNA methylation, gene regulation, cell 
proliferation, viability, and biochemical differentiation in the cell suspension 
cultures of Cannabis indica.

Abedini M(1), Iranbakhsh A(2), Saadatmand S(1), Ebadi M(3), Oraghi Ardebili 
Z(4).

Author information:
(1)Department of Biology, Science and Research Branch, Islamic Azad University, 
Tehran, Iran.
(2)Department of Biology, Science and Research Branch, Islamic Azad University, 
Tehran, Iran. Electronic address: iranbakhsh@iau.ac.ir.
(3)Department of Biology, Damghan Branch, Islamic Azad University, Damghan, 
Iran.
(4)Department of Biology, Garmsar Branch, Islamic Azad University, Garmsar, 
Iran.

The effect of low artificial Ultraviolet (UV) on the DNA methylation remains 
controversial. This study addresses how differential photoperiods of UV 
radiation affect the biochemical and molecular behaviors of Cannabis indica cell 
suspension cultures. The cell suspensions were illuminated with the compact 
fluorescent lamps (CFL), emitting a combination of 10% UVB, 30% UVA, and the 
rest visible wavelengths for 0, 4, 8, and 16 h. The applied photoperiods 
influenced cell morphological characteristics. The 4 h photoperiod was the most 
effective treatment for improving biomass, growth index and cell viability 
percentage while these indices remained non-significant in the 16 h treatment. 
The methylation-sensitive amplified polymorphism (MASP) assay revealed that the 
UV radiation was epigenetically accompanied by DNA hypermethylation. The 
light-treated cells significantly displayed higher relative expression of the 
cannabidiolic‌ acid synthase (CBDAS) and delta9-tetrahydrocannabinolic acid 
synthase (THCAS) genes about 4-fold. The expression of the olivetolic acid 
cyclase (OAC) and olivetol synthase (OLS) genes exhibited an upward trend in 
response to the UV radiation. The light treatments also enhanced the proline 
content and protein concentration. The 4 h illumination was significantly 
capable of improving the cannabidiol (CBD) and delta-9-tetrahydrocannabinol 
(THC) concentrations, in contrast with 16 h. By increasing the illumination 
exposure time, the activity of the phenylalanine ammonia-lyase (PAL) enzyme 
linearly upregulated. The highest amounts of the phenylpropanoid derivatives 
were observed in the cells cultured under the radiation for 4 h. Taken 
collective, artificial UV radiation can induce DNA methylation modifications and 
impact biochemical and molecular differentiation in the cell suspensions in a 
photoperiod-dependent manner.

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

DOI: 10.1016/j.jphotobiol.2024.112902
PMID: 38569457 [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.


3. Cannabis Cannabinoid Res. 2024 Mar 21. doi: 10.1089/can.2023.0172. Online
ahead  of print.

Does the Quantification of Δ9-Tetrahydrocannabinolic Acid A in Serum/Plasma 
Provide Any Additional Information About Consumption Pattern from Drivers Under 
the Influence of Cannabis?

Höfert L(1), Baumann S(1), Dreßler J(1), Becker S(1).

Author information:
(1)Department Forensic Toxicology, Faculty of Medicine, Institute of Forensic 
Medicine, Leipzig University, Leipzig, Germany.

Introduction: Δ9-tetrahydrocannabinolic acid A (THCA-A) is one of the main 
ingredients of cannabis plants and is converted to the psychoactive substance 
Δ9-tetrahydrocannabinol (THC) by decarboxylation during heating above ∼90°C. 
During the consumption of cannabis, a varying proportion of THCA-A is absorbed 
into the body. Therefore, the quantification of THCA-A in serum/plasma might 
provide additional information on consumption behavior in driving under the 
influence of cannabis cases. Materials and Methods: In this study, an already 
established gas-chromatography mass-spectrometry (GC-MS) method for the 
quantification of THC, 11-OH-THC, and THC-COOH in serum and plasma samples was 
extended to include THCA-A. This validated method was then applied to 1228 
routinely achieved serum/plasma samples from drivers suspected of cannabis 
consumption in Western Saxony. Two different grouping systems for 
chronic/occasional consumption, one system for acute/subacute consumption, 
Huestis formulas, and the cannabis influence factor (CIF) were used for 
evaluation. Results: Method validation showed appropriate results for forensic 
toxicological routine analysis. Limit of detection and lower limit of 
quantification (LLOQ) for THCA-A were 0.3 and 1.0 ng/mL, respectively. 
Reproducibility was <11% and accuracy ranged between 104% and 107%. THCA-A was 
stable in native samples at least for 2 weeks at room temperature or 4°C as well 
as 1 month at -20°C. Freeze-thaw stability for three cycles and processed sample 
stability over 3 days was proven. A total of 865 cases with a THC concentration 
above the German analytical cutoff of 1 ng/mL as well as the analytical LLOQs of 
0.9 and 2.5 ng/mL for 11-OH-THC and THC-COOH, respectively, were included in 
further statistical analysis. In 407 (47.1%) of these samples, THCA-A was 
quantifiable. Different statistical analyses indicated a correlation between 
THCA-A and THC concentrations in cases of chronic and acute consumption. In 
addition, an increase of chronic and acute cases with increasing THCA-A 
concentrations was observed. However, no correlation between THCA-A and CIF was 
found. Discussion: These data show that THCA-A might be an additional indicative 
marker to provide information about consumption frequency and acuteness. 
Additional studies with known consumption frequencies and times are required to 
verify these findings.

DOI: 10.1089/can.2023.0172
PMID: 38512708


4. Heliyon. 2023 Apr 17;9(4):e15545. doi: 10.1016/j.heliyon.2023.e15545. 
eCollection 2023 Apr.

Repositioning Cannabinoids and Terpenes as Novel EGFR-TKIs Candidates for 
Targeted Therapy Against Cancer: A virtual screening model using CADD and 
biophysical simulations.

Daoui O(1), Mali SN(2), Elkhattabi K(3), Elkhattabi S(1), Chtita S(4).

Author information:
(1)Laboratory of Engineering, Systems and Applications, National School of 
Applied Sciences, Sidi Mohamed Ben Abdellah-Fez University, P.O. Box 72, Fez, 
Morocco.
(2)Department of Pharmaceutical Sciences and Technology, Birla Institute of 
Technology, Mesra, India, 835215.
(3)Department of Fundamental Sciences, Faculty of Dental Medicine, Mohammed V 
University in Rabat, Morocco.
(4)Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben 
M'Sik, Hassan II University of Casablanca, P.O. Box 7955, Casablanca, Morocco.

This study examines the potential of Cannabis sativa L. plants to be repurposed 
as therapeutic agents for cancer treatment through designing of hybrid Epidermal 
growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). A set of 50 
phytochemicals was taken from Cannabinoids and Terpenes and subjected for 
screening using Semi-flexible and Flexible Molecular Docking methods, MM-GBSA 
free binding energy computations, and pharmacokinetic/pharmacodynamic (ADME-Tox) 
predictions. Nine promising phytochemicals, Cannabidiolic acid (CBDA), 
Cannabidiol (CBD), Tetrahydrocannabivarin (THCV), Dronabinol (Δ-9-THC), 
Delta-8-Tetrahydrocannabinol (Δ-8-THC), Cannabicyclol (CBL), 
Delta9-tetrahydrocannabinolic acid (THCA), Beta-Caryophyllene (BCP), and 
Gamma-Elemene (γ-Ele) were identified as potential EGFR-TKIs natural product 
candidates for cancer therapy. To further validate these findings, a set of 
Molecular Dynamics simulations were conducted over a 200 ns trajectory. This 
hybrid early drug discovery screening strategy has the potential to yield a new 
generation of EGFR-TKIs based on natural cannabis products, suitable for cancer 
therapy. In addition, the application of this computational strategy in the 
virtual screening of both natural and synthetic chemical libraries could support 
the discovery of a wide range of lead drug agents to address numerous diseases.

© 2023 The Authors. Published by Elsevier Ltd.

DOI: 10.1016/j.heliyon.2023.e15545
PMCID: PMC10148140
PMID: 37128337

Conflict of interest statement: The authors reported in the manuscript has no 
any conflict of interest.


5. Am J Vet Res. 2023 Feb 21;84(4):ajvr.22.11.0197. doi: 10.2460/ajvr.22.11.0197.
 Print 2023 Apr 1.

Twice-daily oral administration of a cannabidiol and cannabidiolic acid-rich 
hemp extract was well tolerated in orange-winged Amazon parrots (Amazona 
amazonica) and has a favorable pharmacokinetic profile.

Sosa-Higareda M(1), Guzman DS(2), Knych H(3), Lyubimov A(4), Zakharov A(4), 
Gomez B(4), Beaufrère H(2).

Author information:
(1)William T. Pritchard Veterinary Medical Teaching Hospital, School of 
Veterinary Medicine, University of California-Davis, Davis, CA.
(2)Department of Medicine and Epidemiology, School of Veterinary Medicine, 
University of California-Davis, Davis, CA.
(3)K. L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary 
Medicine, University of California-Davis, Davis, CA.
(4)Department of Pharmacology, Toxicology Research Laboratory, College of 
Medicine, University of Illinois, Chicago, IL.

OBJECTIVE: To determine the pharmacokinetics of 8 cannabinoids and 5 metabolites 
after oral administration of single and multiple doses of a cannabidiol 
(CBD)-cannabidiolic acid (CBDA)-rich hemp extract to orange-winged Amazon 
parrots (Amazona amazonica) as well as to evaluate the extract's adverse 
effects.
ANIMALS: 12 birds.
PROCEDURES: Based on pilot studies, a single-dose study based on 30/32.5 mg/kg 
of cannabidiol/cannabidiolic acid of a hemp extract was administered orally to 8 
fasted parrots, and 10 blood samples were collected over 24 hours after 
administration. After a 4-week washout period, the hemp extract was administered 
orally to 7 birds at the previous dose every 12 hours for 7 days, and blood 
samples were collected at the previous time points. Cannabidiol, 
Δ9-tetrahydrocannabinol, cannabinol, cannabichromene, cannabigerol, 
cannabidiolic acid, cannabigerolic acid, Δ9-tetrahydrocannabinolic acid, and 5 
specific metabolites were measured by liquid 
chromatography-tandem/mass-spectrometry, and pharmacokinetic parameters were 
calculated. Adverse effects and changes in the plasma biochemistry and lipid 
panels were evaluated.
RESULTS: Pharmacokinetic parameters for cannabidiol, cannabidiolic acid, 
Δ9-tetrahydrocannabinol, Δ9-tetrahydrocannabinolic acid, and the metabolite 
11-hydroxy-9-tetrahydrocannabinol were established. For the multiple-dose study, 
cannabidiol/cannabidiolic acid mean Cmax was 337.4/602.1 ng/mL with a tmax of 30 
minutes and a terminal half-life of 8.6/6.29 hours, respectively. No adverse 
effects were detected during the multidose study. The predominant metabolite was 
11-hydroxy-9-tetrahydrocannabinol.
CLINICAL RELEVANCE: Twice daily oral administration of the hemp extract based on 
30 mg/kg/32.5 mg/kg of cannabidiol/cannabidiolic acid was well tolerated and 
maintained plasma concentrations considered to be therapeutic in dogs with 
osteoarthritis. Findings suggest different cannabinoid metabolism from mammals.

DOI: 10.2460/ajvr.22.11.0197
PMID: 36795552 [Indexed for MEDLINE]