Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Sci Rep. 2024 Sep 30;14(1):22747. doi: 10.1038/s41598-024-71344-z.

Novel endophytic fungal species Pithoascus kurdistanensis producing morphine 
compounds.

Mohammadi S(1)(2), Bahramnejad B(3), Abdollahzadeh J(4), Bashiri S(5), Vincent 
AT(1)(6), Majdi M(2), Soltani J(7), Levesque RC(8).

Author information:
(1)Institut de Biologie Intégrative et des Systèmes, Université Laval Québec, 
Québec, Canada.
(2)Department of Plant Production and Genetics, Faculty of Agriculture, 
University of Kurdistan, Sanandaj, Iran.
(3)Department of Plant Production and Genetics, Faculty of Agriculture, 
University of Kurdistan, Sanandaj, Iran. b.bahramnejad@uok.ac.ir.
(4)Department of Plant Protection, Faculty of Agriculture, University of 
Kurdistan, Sanandaj, Iran. j.abdollahzadeh@uok.ac.ir.
(5)Department of Plant Protection, Faculty of Agriculture, University of 
Kurdistan, Sanandaj, Iran.
(6)Département des Sciences Animales, Faculté dxes Sciences de l'agriculture et 
de l'alimentation, Université Laval Québec, Québec, Canada.
(7)Department of Plant Protection, Faculty of Agriculture, Bu-Ali Sina 
University, Hamadan, Iran.
(8)Institut de Biologie Intégrative et des Systèmes, Université Laval Québec, 
Québec, Canada. rclevesq@ibis.ulaval.ca.

Papaver genus, commonly known as popies, is a valuable source of alkaloids used 
in medicine, including papaverine, morphine, codeine, and thebaine. We isolated 
six endophytic fungal isolates producing morphinan alkaloids from four Papaver 
species growing in Kurdistan Province, Iran. To do this, a 1:1 mixture of 
methanol and chloroform was used to extract fungal cultures. The contents of 
morphinan alkaloids in the extracts were subsequently determined using phase 
high-performance liquid chromatography. Among the morphinan alkaloid-producing 
fungal isolates, IRAN 4653C had the highest yield giving 23.06 (mg/g) morphine 
and 2.03 (mg/g) codeine when grown in potato dextrose liquid medium. The 
identity of this isolate was examined and recognized as a new fungal species 
named as Pithoascus kurdistanesis sp. nov. based on multi-gene phylogenetic 
analyses of ITS, TEF-1α, and TUB2 sequences data and morphological features. The 
morphinan-producing endophytic fungus and the isolated Pithoascus species from 
Papaver are being reported for the first time. Accordingly, this fungus shows 
promise as a new source of valuable compounds which is illustrated and 
introduced here as a new Microascaceae member belonging to Pithoascus from 
Kurdistan Province, Iran. Moreover, the morphinan productivity of P. 
kurdistanesis was further validated by gas chromatography-mass spectrometry 
(GC-MS).

© 2024. The Author(s).

DOI: 10.1038/s41598-024-71344-z
PMCID: PMC11442975
PMID: 39349517 [Indexed for MEDLINE]

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


2. Front Pharmacol. 2024 Aug 8;15:1454601. doi: 10.3389/fphar.2024.1454601. 
eCollection 2024.

Long-term efficacy and reduced side-effects of buprenorphine in patients with 
moderate and severe chronic pain.

Papa A(1), Salzano AM(1), Di Dato MT(1), Desiderio V(2), Buonavolontà P(1), 
Mango P(1), Saracco E(1), Tammaro D(1), Luongo L(#)(3), Maione S(#)(3).

Author information:
(1)Department of Pain Management-AO "Ospedale dei Colli"-Monaldi Hospital, 
Napoli, Italy.
(2)Department of Experimental Medicine, University of Campania "Luigi 
Vanvitelli", Naples, Italy.
(3)Department of Experimental Medicine, Division of Pharmacology, University of 
Campania "Luigi Vanvitelli", Naples, Italy.
(#)Contributed equally

Erratum in
    Front Pharmacol. 2024 Sep 30;15:1491886. doi: 10.3389/fphar.2024.1491886.

BACKGROUND: Chronic pain significantly impacts quality of life and poses 
substantial public health challenges. Buprenorphine, a synthetic analog of 
thebaine, is recognized for its potential in managing moderate to severe chronic 
pain with fewer side effects and a lower incidence of tolerance compared to 
traditional opioids.
OBJECTIVE: This retrospective study aimed to assess the long-term efficacy and 
safety of buprenorphine transdermal patches in patients with moderate and severe 
chronic pain, with a focus on pain relief sustainability and tolerance 
development.
METHODS: This retrospective observational study involved 246 patients prescribed 
buprenorphine transdermal patches. We evaluated changes in pain intensity using 
the Numeric Rating Scale (NRS), assessed opioid tolerance based on FDA 
guidelines for morphine-equivalent doses, and measured patient-reported outcomes 
through the Patients' Global Impression of Change (PGIC). Any adverse events 
were also recorded.
RESULTS: Over the 36-month period, there was a significant reduction in NRS 
scores for both moderate and severe pain patients, demonstrating buprenorphine's 
sustained analgesic effect. Tolerance measurement indicated that no patients 
required increases in morphine-equivalent doses that would meet or exceed the 
FDA's threshold for opioid tolerance (60 mg/day of morphine or equivalent). 
Additionally, patient satisfaction was high, with the PGIC reflecting 
significant improvements in pain management and overall wellbeing. The side 
effects were minimal, with skin reactions and nausea being the most commonly 
reported but manageable adverse events.
CONCLUSION: The study findings validate the long-term use of buprenorphine 
transdermal patches as an effective and safe option for chronic pain management, 
maintaining efficacy without significant tolerance development. These results 
support the continued and expanded use of buprenorphine in clinical settings, 
emphasizing its role in reducing the burdens of chronic pain and opioid-related 
side effects. Further research is encouraged to refine pain management protocols 
and explore buprenorphine's full potential in diverse patient populations.

Copyright © 2024 Papa, Salzano, Di Dato, Desiderio, Buonavolontà, Mango, 
Saracco, Tammaro, Luongo and Maione.

DOI: 10.3389/fphar.2024.1454601
PMCID: PMC11338866
PMID: 39175543

Conflict of interest statement: The 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. The author(s) declared that 
they were an editorial board member of Frontiers, at the time of submission. 
This had no impact on the peer review process and the final decision.


3. BMC Plant Biol. 2024 Jul 24;24(1):700. doi: 10.1186/s12870-024-05412-x.

Developing benzylisoquinoline alkaloid-enriched opium poppy via CRISPR-directed 
genome editing: A review.

Aghaali Z(1), Naghavi MR(2).

Author information:
(1)Department of Genetics and Plant Breeding, Faculty of Agriculture, Tarbiat 
Modares University, Tehran, Iran.
(2)Division of Plant Biotechnology, Department of Agronomy and Plant Breeding, 
College of Agricultural and Natural Resources, University of Tehran, Karaj, 
Iran. mnaghavi@ut.ac.ir.

Among plant-derived secondary metabolites are benzylisoquinoline alkaloids 
(BIAs) that play a vital role in medicine. The most conspicuous BIAs frequently 
found in opium poppy are morphine, codeine, thebaine, papaverine, sanguinarine, 
and noscapine. BIAs have provided abundant clinically useful drugs used in the 
treatment of various diseases and ailments With an increasing demand for these 
herbal remedies, genetic improvement of poppy plants appears to be essential to 
live up to the expectations of the pharmaceutical industry. With the advent of 
clustered regularly interspaced short palindromic repeats 
(CRISPR)/CRISPR-associated9 (Cas9), the field of metabolic engineering has 
undergone a paradigm shift in its approach due to its appealing attributes, such 
as the transgene-free editing capability, precision, selectivity, robustness, 
and versatility. The potentiality of the CRISPR system for manipulating 
metabolic pathways in opium poppy was demonstrated, but further investigations 
regarding the use of CRISPR in BIA pathway engineering should be undertaken to 
develop opium poppy into a bioreactor synthesizing BIAs at the industrial-scale 
levels. In this regard, the recruitment of RNA-guided genome editing for 
knocking out miRNAs, flower responsible genes, genes involved in competitive 
pathways, and base editing are described. The approaches presented here have 
never been suggested or applied in opium poppy so far.

© 2024. The Author(s).

DOI: 10.1186/s12870-024-05412-x
PMCID: PMC11267691
PMID: 39048937 [Indexed for MEDLINE]

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


4. J Exp Bot. 2024 Jul 24:erae317. doi: 10.1093/jxb/erae317. Online ahead of
print.

Genomic and Cell-Specific Regulation of Benzylisoquinoline Alkaloid Biosynthesis 
in Opium Poppy.

Hong UVT(1)(2), Tamiru-Oli M(1)(2), Hurgobin B(1)(2), Lewsey MG(1)(2)(3).

Author information:
(1)Australian Research Council Research Hub for Medicinal Agriculture, La Trobe 
University, AgriBio Building, Bundoora, VIC 3086, Australia.
(2)La Trobe Institute for Sustainable Agriculture and Food, Department of Plant, 
Animal and Soil Sciences, La Trobe University, AgriBio Building, Bundoora, VIC 
3086, Australia.
(3)Australian Research Council Centre of Excellence in Plants for Space, AgriBio 
Building, La Trobe University, Bundoora, VIC 3086, Australia.

Opium poppy is a crop of great commercial value as a source of several opium 
alkaloids for the pharmaceutical industries including morphine, codeine, 
thebaine, noscapine and papaverine. Most enzymes involved in benzylisoquinoline 
alkaloids (BIAs) biosynthesis in opium poppy have been functionally 
characterized, and opium poppy currently serves as a model system to study BIA 
metabolism in plants. BIA biosynthesis in opium poppy involves two biosynthetic 
gene clusters associated respectively with the morphine and noscapine branches. 
Recent reports have shown that genes in the same cluster are co-expressed, 
suggesting they might also be co-regulated. However, the transcriptional 
regulation of opium poppy BIA biosynthesis is not well studied. Opium poppy BIA 
biosynthesis involves three cell types associated with the phloem system: 
companion cells, sieve elements and laticifers. The transcripts and enzymes 
associated with BIA biosynthesis are distributed across cell types, requiring 
the translocation of key enzymes and pathway intermediates between cell types. 
Together, these suggest that the regulation of BIA biosynthesis in opium poppy 
is multilayered and complex, involving biochemical, genomic, and physiological 
mechanisms. In this review, we highlight recent advances in genome sequencing 
and single cell and spatial transcriptomics with a focus on how these efforts 
can improve our understanding of the genomic and cell-specific regulation of BIA 
biosynthesis. Such knowledge is vital for opium poppy genetic improvement and 
metabolic engineering efforts targeting the modulation of alkaloid yield and 
composition.

© The Author(s) 2024. Published by Oxford University Press on behalf of the 
Society for Experimental Biology.

DOI: 10.1093/jxb/erae317
PMID: 39046316


5. Sci Rep. 2024 Jul 15;14(1):16309. doi: 10.1038/s41598-024-67190-8.

Phylogeography and genetic structure of Papaver bracteatum populations in Iran 
based on genotyping-by-sequencing (GBS).

Rahmati R(1), Nemati Z(2)(3), Naghavi MR(4), Pfanzelt S(1)(5), Rahimi A(6), 
Kanzagh AG(7), Blattner FR(8).

Author information:
(1)Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), 
Gatersleben, Germany.
(2)Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), 
Gatersleben, Germany. za.nemati@gmail.com.
(3)Institute for Medical Microbiology and Hospital Hygiene, Goethe University 
Frankfurt,, Frankfurt/M., Germany. za.nemati@gmail.com.
(4)Division of Biotechnology, Department of Agronomy and Plant Breeding, 
Agricultural and Natural Resources College, University of Tehran, Karaj, Iran.
(5)Bavarian Natural History Collections, Botanical Garden München-Nymphenburg, 
Munich, Germany.
(6)Department of Plant Production and Genetics, Faculty of Agriculture and 
Natural Resources, Urmia University, Urmia, Iran.
(7)Department of Biology, Science and Research Branch, Islamic Azad University, 
Tehran, Iran.
(8)Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), 
Gatersleben, Germany. blattner@ipk-gatersleben.de.

Papaver bracteatum, known for its high thebaine content and absence of morphine, 
has emerged as a promising alternative to opium poppy for codeine production. In 
this study, our objective was to create a diverse panel representing the natural 
variation of this species in Iran. To achieve this, we employed 
genotyping-by-sequencing to obtain genome-wide distributed single-nucleotide 
polymorphisms (SNPs) for phylogeographic analysis, population structure 
assessment, and evaluation of genetic diversity within P. bracteatum 
populations. A total of 244 P. bracteatum individuals from 13 distinct 
populations formed seven genetic groups, along with one highly admixed 
population. We observed a clear split between the populations inhabiting the 
Alborz Mts. in the east and Zagros Mts. in the west. In between these mountain 
ranges, the population of Kachal Mangan exhibited a high degree of genetic 
admixture between both genetic groups. At or after the end of the last glacial 
maximum, when climate conditions rapidly changed, all P. bracteatum populations 
experienced a strong demographic bottleneck reducing the already small effective 
population sizes further before they increased to their recent strengths. Our 
results suggest that the ongoing climate change together with human pressure on 
the species' habitats and limited seed-dispersal ability are potential factors 
contributing today to rising genetic isolation of P. bracteatum populations. Our 
results provide genetic data that can be used for conservation measures to 
safeguard the species' genetic diversity as a resource for future breeding 
approaches in this medicinally important species.

© 2024. The Author(s).

DOI: 10.1038/s41598-024-67190-8
PMCID: PMC11251027
PMID: 39009644 [Indexed for MEDLINE]

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