Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Cannabis Cannabinoid Res. 2024 Oct 30. doi: 10.1089/can.2024.0058. Online
ahead  of print.

Minor Cannabinoid Profile of Unregulated Cannabidiol Products.

Johnson E(1), Kilgore M(2), Nuzzo P(3), Babalonis S(3)(4).

Author information:
(1)LGC Assure, Lexington, Kentucky, USA.
(2)College of Medicine, Department of Pharmacology and Nutritional Science, 
University of Kentucky, Lexington, Kentucky, USA.
(3)College of Medicine, Center on Drug and Alcohol Research, Cannabis Center, 
University of Kentucky, Lexington, Kentucky, USA.
(4)College of Medicine, Department of Behavioral Science, University of 
Kentucky, Lexington, Kentucky, USA.

Background: Although the majority of cannabinoid research has focused on 
delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), there is increasing 
interest in the therapeutic effects of other phytocannabinoid compounds (i.e., 
minor cannabinoids), as there is little known about their effects or interaction 
with CBD. The current study objective was to determine the concentrations of 15 
minor cannabinoids in unregulated, over-the-counter CBD products. Methods: A 
cross-section sample of 80 local and national brands of hemp-derived oil 
products was purchased both online and in local retail outlets in central 
Kentucky. Epidiolex® was included as a regulated control. Samples from each 
product were extracted by solvent extraction and quantified by 
liquid-chromatography tandem mass-spectrometry. The targeted cannabinoids were: 
cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabidivarinic acid, 
Δ9-tetrahydrocannabivarin, Δ9-tetrahydrocannabivarinic acid, 
Δ9-tetrahydrocannabinolic acid-A, Δ8-tetrahydrocannabinol (Δ8-THC), cannabigerol 
(CBG), cannabigerolic acid, cannabinol (CBN), cannabinolic acid, cannabicyclol 
(CBL), cannabicyclolic acid, cannabichromene (CBC) and cannabichromenic acid. 
Results: Among the unregulated products included in this analysis, the most 
frequently detected minor cannabinoids were CBDV (100% of samples tested), CBG 
(77%), CBC (72%), CBN (67%), CBL (67%), and CBDA (51%). Δ8-THC was not detected 
in any of the products tested. Concentrations of these cannabinoids varied 
widely from trace concentrations to several mg/mL (e.g., CBDA: 0.006-12.258 
mg/mL). Conclusions: These data indicate CBD products often contain minor 
cannabinoids, although the array and concentrations of these cannabinoids vary 
widely across products. The concentrations of these minor cannabinoids are 
largely absent from product labels, leaving consumers uninformed about product 
contents.

DOI: 10.1089/can.2024.0058
PMID: 39478329


2. Molecules. 2024 Sep 19;29(18):4454. doi: 10.3390/molecules29184454.

Rational Design and Modification of NphB for Cannabinoids Biosynthesis.

Xia W(1)(2), Liu S(2), Chu H(3), Chen X(1)(2), Huang L(2), Bai T(2), Jiao X(2), 
Wang W(1), Jiang H(3), Wang X(2).

Author information:
(1)New Cornerstone Science Laboratory, Shaanxi Key Laboratory of Qinling 
Ecological Intelligent Monitoring and Protection, School of Ecology and 
Environment, Northwestern Polytechnical University, Xi'an 710072, China.
(2)Jiaxing Synbiolab Technology Co., Ltd., Jiaxing 314000, China.
(3)Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of 
Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.

The rapidly growing field of cannabinoid research is gaining recognition for its 
impact in neuropsychopharmacology and mood regulation. However, 
prenyltransferase (NphB) (a key enzyme in cannabinoid precursor synthesis) still 
needs significant improvement in order to be usable in large-scale industrial 
applications due to low activity and limited product range. By rational design 
and high-throughput screening, NphB's catalytic efficiency and product diversity 
have been markedly enhanced, enabling direct production of a range of 
cannabinoids, without the need for traditional enzymatic conversions, thus 
broadening the production scope of cannabinoids, including cannabigerol (CBG), 
cannabigerolic acid (CBGA), cannabigerovarin (CBGV), and cannabigerovarinic acid 
(CBGVA). Notably, the W3 mutant achieved a 10.6-fold increase in CBG yield and 
exhibited a 10.3- and 20.8-fold enhancement in catalytic efficiency for CBGA and 
CBGV production, respectively. The W4 mutant also displayed an 9.3-fold increase 
in CBGVA activity. Molecular dynamics simulations revealed that strategic 
reconfiguration of the active site's hydrogen bonding network, disulfide bond 
formation, and enhanced hydrophobic interactions are pivotal for the improved 
synthetic efficiency of these NphB mutants. Our findings advance the 
understanding of enzyme optimization for cannabinoid synthesis and lay a 
foundation for the industrial-scale production of these valuable compounds.

DOI: 10.3390/molecules29184454
PMCID: PMC11434003
PMID: 39339449 [Indexed for MEDLINE]

Conflict of interest statement: Jiaxing Synbiolab Technology Co., Ltd. has filed 
a Chinese patent application for the NphB-catalyzed synthesis of CBG or CBGA. W. 
Xia, X. Chen, X. Wang, and S. Liu are listed as inventors on this patent 
application. The authors declare no other competing interests.


3. Sci Rep. 2024 Jul 16;14(1):16411. doi: 10.1038/s41598-024-66420-3.

Comparison of decarboxylation rates of acidic cannabinoids between secretory 
cavity contents and air-dried inflorescence extracts in Cannabis sativa cv. 
'Cherry Wine'.

Kim ES(1), Park SH(2), Kinney CA(2)(3), Olejar KJ(3), Corredor-Perilla IC(2).

Author information:
(1)Institute of Cannabis Research, Colorado State University-Pueblo, Pueblo, CO, 
81001, USA. eunsoo.kim@csupueblo.edu.
(2)Institute of Cannabis Research, Colorado State University-Pueblo, Pueblo, CO, 
81001, USA.
(3)Department of Chemistry, Colorado State University-Pueblo, Pueblo, CO, 81001, 
USA.

Studies with secretory cavity contents and air-dried inflorescence extracts of 
the CBD-rich hemp strain, Cannabis sativa cv. 'Cherry Wine', were conducted to 
compare the decarboxylation rates of acidic cannabinoids between two groups. The 
secretory cavity contents acquired from the capitate-stalked glandular trichomes 
by glass microcapillaries, and inflorescence samples air-dried for 15 days of 
storage in darkness at room temperature were analysed by high-pressure liquid 
chromatography. The ratio of acidic cannabinoids to the total cannabinoids was 
ranging from 0.5% to 2.4% lower in the air-dried inflorescence samples compared 
to the secretory cavity samples as follows. In the secretory cavity content, the 
percentage of acidic cannabinoids to the total cannabinoids was measured as 
86.4% cannabidiolic acid (CBDA), 6.5% tetrahydrocannabinolic acid (THCA), 4.3% 
cannabichromenic acid (CBCA), 1.4% cannabigerolic acid (CBGA), and 0.6% 
cannabidivarinic acid (CBDVA), respectively. In the air-dried inflorescence, 
however, the acidic cannabinoids were detected with 84% CBDA, 4.8% THCA, 3.3% 
CBCA, 0.8% CBGA, and 0.3% Δ9-tetrahydrocannabivarinic acid (Δ9-THCVA), 
respectively. The ratio of cannabidiol (CBD) to cannabidiolic acid (CBDA) was 
close to 1:99 (w/w) in secretory cavity contents, however, it was roughly 1:20 
(w/w) in the air-dried inflorescence. In addition, Δ9-tetrahydrocannabivarin 
(Δ9-THCV) and Δ9-tetrahydrocannabivarinic acid (Δ9-THCVA) were only detected in 
the air-dried inflorescence sample, and the ratio of Δ9-THCV to Δ9-THCVA was 
about 1:20 (w/w). Besides, cannabidivarinic acid (CBDVA) was only observed in 
the secretory cavity content.

© 2024. This is a U.S. Government work and not under copyright protection in the 
US; foreign copyright protection may apply.

DOI: 10.1038/s41598-024-66420-3
PMCID: PMC11252385
PMID: 39013926 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no competing interests.


4. Anal Chim Acta. 2024 Jun 1;1306:342621. doi: 10.1016/j.aca.2024.342621. Epub 
2024 Apr 17.

In vivo profiling of phytocannabinoids in Cannabis spp. varieties via SPME-LC-MS 
analysis.

Woźniczka K(1), Trojan V(2), Urbanowicz K(3), Schreiber P(4), Zadrożna J(1), 
Bączek T(1), Smoleński RT(3), Roszkowska A(5).

Author information:
(1)Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical 
University of Gdańsk, Hallera 107, 80-416, Gdańsk, Poland.
(2)Cannabis Facility, International Clinical Research Centre, St. Anne's 
University Hospital, Pekarská 53, 60200, Brno, Czech Republic; Department of 
Natural Drugs, Faculty of Pharmacy, Masaryk University, Palackého 1946/1, 61200, 
Brno, Czech Republic.
(3)Department of Biochemistry, Faculty of Medicine, Medical University of 
Gdańsk, Dębinki 1, 80-211, Gdańsk, Poland.
(4)Cannabis Facility, International Clinical Research Centre, St. Anne's 
University Hospital, Pekarská 53, 60200, Brno, Czech Republic.
(5)Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical 
University of Gdańsk, Hallera 107, 80-416, Gdańsk, Poland. Electronic address: 
anna.roszkowska@gumed.edu.pl.

BACKGROUND: In vivo solid-phase microextraction (SPME) is a minimally invasive, 
non-exhaustive sample-preparation technique that facilitates the direct 
isolation of low molecular weight compounds from biological matrices in living 
systems. This technique is especially useful for the analysis of 
phytocannabinoids (PCs) in plant material, both for forensic purposes and for 
monitoring the PC content in growing Cannabis spp. plants. In contrast to 
traditional extraction techniques, in vivo SPME enables continuous tracking of 
the changes in the level of PCs during plant growth without the need for plant 
material collection. In this study, in vivo SPME utilizing biocompatible C18 
probes and liquid-chromatography coupled to quadrupole time-of flight mass 
spectrometry (LC-Q-TOF-MS) is proposed as a novel strategy for the extraction 
and analysis of the acidic forms of five PCs in growing medicinal cannabis 
plants.
RESULTS: The SPME method was optimized by testing various parameters, including 
the extraction phase (coating), extraction and desorption times, and the 
extraction temperature. The proposed method was validated with satisfactory 
analytical performance regarding linearity (10-3000 ng/mL), limits of 
quantification, and precision (relative standard deviations below 5.5 %). The 
proposed method was then successfully applied for the isolation of five acidic 
forms of PCs, which are main components of growing medicinal cannabis plants. As 
a proof-of-concept, SPME probes were statically inserted into the inflorescences 
of two varieties of Cannabis spp. plants (i.e., CBD-dominant and 
Δ9-THC-dominant) cultivated under controlled conditions for 30 min extraction of 
tetrahydrocannabinolic acid (Δ9-THCA), cannabidiolic acid (CBDA), cannabigerolic 
acid (CBGA), cannabiviarinic acid (CBVA), and tetrahydrocannabivarinic acid 
(THCVA).
SIGNIFICANCE AND NOVELTY: The results confirmed that the developed 
SPME-LC-Q-TOF-MS method is a precise and efficient tool that enables direct and 
rapid isolation and analysis of PCs under in vivo conditions. The proposed 
methodology is highly appealing option for monitoring the metabolic pathways and 
compositions of multiple PCs in medicinal cannabis at different stages of plant 
growth.

Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.

DOI: 10.1016/j.aca.2024.342621
PMID: 38692790 [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.


5. Front Vet Sci. 2024 Apr 12;11:1356463. doi: 10.3389/fvets.2024.1356463. 
eCollection 2024.

Pharmacokinetics and tolerability of single-dose enteral cannabidiol and 
cannabidiolic acid rich hemp in horses (Equus caballus).

Thomson ACS(1), McCarrel TM(2), Zakharov A(3), Gomez B(3), Lyubimov A(3), 
Schwark WS(4), Mallicote MF(2), Portela DA(1), Bisiau AL(2), Wakshlag JJ(5).

Author information:
(1)Department of Comparative, Population, and Diagnostic Medicine, College of 
Veterinary Medicine, University of Florida, Gainesville, FL, United States.
(2)Department of Large Animal Clinical Sciences, College of Veterinary Medicine, 
University of Florida, Gainesville, FL, United States.
(3)Department of Pharmacology, College of Medicine, University of Illinois, 
Chicago, IL, United States.
(4)Department of Molecular Medicine, College of Veterinary Medicine, Cornell 
University, Ithaca, NY, United States.
(5)Department of Clinical Sciences, College of Veterinary Medicine, Cornell 
University, Ithaca, NY, United States.

The pharmacokinetics and tolerability of cannabinoids and their metabolites were 
determined in eight horses after enteral administration of a commercial 
CBD/CBDA-rich hemp oil product. Each horse was administered 2 mg/kg or 8 mg/kg 
CBD/CBDA or no treatment in a randomized cross-over design. Serial serum samples 
collected over 48 h were analyzed by high performance liquid chromatography with 
tandem mass spectrometry. Plasma chemistry analysis was performed at 0 h and 
24 h. Vital parameters, pedometry, and blinded mentation and gait evaluations 
were recorded at intervals up to 24 h. Manure production and gastrointestinal 
transit time were tracked for 48 h after oil administration. The median maximal 
concentration of CBD and CBDA were 5.2 and 36.95 ng/mL in the 2 mg/kg group, 
respectively; and 40.35 and 353.56 ng/mL in the 8 mg/kg group. The median 
half-life of elimination was not calculated for the 2 mg/kg CBD treatment due to 
lack of time points above the lower quantifiable limit beyond the Cmax while it 
was 7.75 h in the 8 mg/kg group. CBDA absorption was biphasic. Pharmacokinetic 
parameters for tetrahydrocannabinol, tetrahydrocannabinolic acid, cannabigerolic 
acid, and 7-carboxy cannabidiol are also reported. No significant differences in 
any of the measured tolerability parameters were demonstrated between treatment 
groups. Single-dose enteral administration of CBD/CBDA-rich hemp extract up to 
8 mg/kg does not appear to produce neurologic, behavioral, or gastrointestinal 
effects in horses.

Copyright © 2024 Thomson, McCarrel, Zakharov, Gomez, Lyubimov, Schwark, 
Mallicote, Portela, Bisiau and Wakshlag.

DOI: 10.3389/fvets.2024.1356463
PMCID: PMC11047043
PMID: 38681854

Conflict of interest statement: JW and WS are paid consultants of Ellevet 
Sciences. The remaining authors declare that the research was conducted in the 
absence of any commercial or financial relationships that could be construed as 
a potential conflict of interest.