Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Stroke. 2024 Nov 7. doi: 10.1161/STROKEAHA.124.048869. Online ahead of print.

Menstruation: An Important Indicator for Assessing Stroke Risk and Its Outcomes.

Seitz A(1), Raval AP(2)(3).

Author information:
(1)Department of Neurology, University of Washington, Seattle (A.S.).
(2)Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Department 
of Neurology, Leonard M. Miller School of Medicine, Miami, FL (A.P.R.).
(3)Bruce W. Carter Department of Veterans Affairs Medical Center, University of 
Miami, FL (A.P.R.).

In recent years, stroke incidence in older adults has declined strikingly, but 
stroke in younger women has become more common. Abnormalities of menstruation, 
the shedding of the uterine lining at the beginning of each menstrual cycle, may 
offer clues about stroke risk in young and midlife women. Endometrial and 
structural uterine abnormalities are associated with anemia and may be 
associated with hypercoagulability, possibly increasing stroke risk. Patient 
factors that influence both menstruation and stroke risk include coagulopathies, 
polycystic ovarian syndrome, endometriosis, migraine, and other systemic 
disorders, in addition to menopause. Environmental and iatrogenic factors that 
influence both menstruation and stroke risk include hormonal contraceptives, 
nicotine, xenoestrogens, phytoestrogens, oophorectomy, and hysterectomy. 
Importantly, secondary stroke prevention can affect menstruation. Our current 
review presents literature supporting the idea that abnormal menstruation may 
indicate elevated stroke risk in premenopausal women.

DOI: 10.1161/STROKEAHA.124.048869
PMID: 39508108


2. Cell Mol Neurobiol. 2024 Nov 6;44(1):74. doi: 10.1007/s10571-024-01504-2.

Synergistic Epistasis and Systems Biology Approaches to Uncover a 
Pharmacogenomic Map Linked to Pain, Anti-Inflammatory and Immunomodulating 
Agents (PAIma) in a Healthy Cohort.

Sharafshah A(1), Motovali-Bashi M(2), Keshavarz P(3), Blum K(4)(5).

Author information:
(1)Division of Genetics, Department of Cell and Molecular Biology and 
Microbiology, Faculty of Biological Science and Technology , University of 
Isfahan, Isfahan, Iran.
(2)Division of Genetics, Department of Cell and Molecular Biology and 
Microbiology, Faculty of Biological Science and Technology , University of 
Isfahan, Isfahan, Iran. mbashi@sci.ui.ac.ir.
(3)Cellular and Molecular Research Center, School of Medicine, Guilan University 
of Medical Sciences, Rasht, Iran.
(4)Division of Addiction Research and Education, Center for Sports, Exercise, 
and Mental Health, Western University Health Sciences, Pomona, CA, USA. 
drd2gene@gmail.com.
(5)Department of Psychiatry, Wright State University Boonshoft School of 
Medicine, Dayton, OH, USA. drd2gene@gmail.com.

The global public health addiction crisis has been stark, with over 
932,400 deaths in the USA and Canada from opioid overdose since 1999-2020, 
surpassing the mortality rates at the top of the HIV/AIDS epidemic. Both nations 
exhibit opioid consumption rates significantly above the norm for developed 
countries. Analgesic type of opioids present both therapeutic benefits and 
substantial health risks, necessitating balanced drug regulation, careful 
prescribing, and dedicated opioid stewardship. The role of the cytochrome P450 
2D6 (CYP2D6) system (Enzymatic functions) in metabolizing opioids highlights the 
potential of genotype-guided analgesia. By integrating Pharmacogenomics (PGx), 
this approach aims to optimize pain management, enhance safety, and reduce 
addiction risks. This understanding prompted the utilization of multifactor 
dimensionality reduction (MDR) to explore a range of phenotypes including PGx 
and gene-gene interactions (GGI) in a healthy cohort, thereby personalizing pain 
management strategies. The study sampled 100 unrelated healthy Western Iranians 
and 100 individuals from the 1000 Genome Project. Pre-testing involved searching 
for PGx annotations (variants associated with drug-gene-diseases) related to 
pain sensitivity and inflammation using the PharmGKB database, which identified 
128 relevant genes. A questionnaire helped select 100 participants who had never 
used potent opioids but also other psychoactive agents (e.g., nicotine, 
amphetamines, etc.) and disease-related drugs. Whole-exome sequencing (WES) was 
then employed to analyze these genes in an Iranian cohort. Further analyses 
included MDR for identifying synergistic gene annotations and GGI for exploring 
complex gene interactions through the Visualization of Statistical Epistasis 
Networks (ViSEN). The study identified a Pain, Anti-Inflammatory, and 
Immunomodulating agents (PAIma) panel from the 128 genes, resulting in 55,590 
annotations across 21 curated pathways. After filtering, 54 significant 
structural or regulatory variants were identified. This research also 
highlighted novel gene relationships involving the CYP3A5 gene, hsa-miR-355-5p, 
Paliperidone, and CYP2D6, which warrant further investigation. This study offers 
a novel pharmacogenetic framework that could potentially transform opioid 
prescribing practices to mitigate misuse and enhance personalized pain 
management. Further validation of these findings from multi countries and ethnic 
groups could guide clinicians in implementing DNA-based opioid prescribing, 
aligning treatment more closely with individual genetic profiles.

© 2024. The Author(s).

DOI: 10.1007/s10571-024-01504-2
PMID: 39505757 [Indexed for MEDLINE]


3. Nicotine Tob Res. 2024 Nov 7:ntae223. doi: 10.1093/ntr/ntae223. Online ahead
of  print.

The Context of the Emergency Department as a Location for a Smoking Cessation 
Intervention-Process Evaluation Findings From the Cessation of Smoking Trial in 
the Emergency Department Trial.

Notley C(1), Belderson P(1), Ward E(1), Clark LV(2), Clark A(2), Stirling S(2), 
Parrott S(3), Li J(3), Coats TJ(4), Bauld L(5), Holland R(6), Gentry S(1), 
Agrawal S(7), Bloom BM(8), Boyle A(9), Gray A(10), Morris MG(11), Pope I(1)(12).

Author information:
(1)Norwich Medical School, University of East Anglia, Norwich, UK.
(2)Norwich Clinical Trials Unit, Norwich Medical School, University of East 
Anglia, Norwich, UK.
(3)Department of Health Sciences, University of York, York, UK.
(4)Department of Cardiovascular Sciences, Leicester Medical School, University 
of Leicester, Leicester, UK.
(5)Usher Institute and SPECTRUM Consortium, College of Medicine, University of 
Edinburgh, Edinbugh, UK.
(6)Exeter Medical School, University of Exeter, Exeter, UK.
(7)University Hospitals of Leicester NHS Trust, Leicester, UK.
(8)Royal London Hospital, Barts NHS Trust, London, UK.
(9)Addenbrookes Hospital, Cambridge University Hospitals Foundation Trust, 
Cambridge, UK.
(10)Royal Infirmary Edinburgh, NHS Lothian, Edinburgh, UK.
(11)Homerton University Hospital NHS Trust, London, UK.
(12)Norfolk and Norwich University Hospital, Norwich, UK.

INTRODUCTION: Hospital emergency departments (ED) offer an opportunity to engage 
with large numbers of people who smoke to prompt cessation, although the 
acceptability of opportunistic intervention in this context has been questioned. 
This process evaluation study was embedded into the Cessation of Smoking Trial 
in the Emergency Department (COSTED) randomized controlled trial and sought to 
explore the context of intervention delivery within the ED.
AIMS AND METHODS: Qualitative interviews were conducted with participants and 
staff across six EDs participating in the COSTED randomized controlled trial. 
Interview data were thematically analyzed specifically exploring contextual 
influences. Data were triangulated with ethnographic observations.
RESULTS: In participant interviews (N = 34), it was acceptable overall to 
receive a brief opportunistic smoking cessation intervention in the ED. 
Contextual factors are impacted at a range of levels. At the micro level 
participant views and experiences combined with staff tailoring were important. 
Being given an e-cigarette starter kit by a "credible source" helped to 
legitimize vaping for smoking cessation and gave confidence in personal ability 
to switch away from tobacco. At the meso level, adaptations to intervention 
delivery were made in response to the context of the ED. Stop smoking advisors 
(N = 11) had to adapt and deliver the intervention flexibly depending on space 
and clinical need. At the macro level, hospital policies supportive of vaping 
legitimized the approach.
CONCLUSIONS: Smoking cessation outcomes reported in the main trial across sites 
were very similar because of the high credibility, acceptability, and flexible 
approach to delivering the COSTED intervention in the ED.
IMPLICATIONS: Attending a hospital ED is the right time and place to receive 
smoking cessation intervention, even for those not motivated to quit. People are 
willing to receive intervention, and clinical staff are willing to support 
intervention delivery. Despite challenges, overall the context is helpful in 
supporting people to switch away from tobacco. The intervention, with flexible 
and tailored implementation, is adaptable to different ED contexts. This 
suggests that wider implementation across NHS Trusts of the effective COSTED 
intervention is feasible and will ultimately support smoking cessation for 
people attending EDs, who may not otherwise have sought support.

© The Author(s) 2024. Published by Oxford University Press on behalf of the 
Society for Research on Nicotine and Tobacco.

DOI: 10.1093/ntr/ntae223
PMID: 39505370


4. Addiction. 2024 Nov 6. doi: 10.1111/add.16702. Online ahead of print.

Characteristics and ingredients of disposable 'Elfbar' e-cigarettes sold in the 
United States and the United Kingdom.

Leigh NJ(1), Page MK(1), Jamil H(1), Goniewicz ML(1).

Author information:
(1)Department of Health Behavior, Roswell Park Comprehensive Cancer Center, 
Buffalo, NY, USA.

BACKGROUND AND AIMS: As of 2023, Elfbar remains the most popular brand of 
disposable e-cigarette available in the United States (US) and United Kingdom 
(UK), with similar flavor options in both countries. At the time of this study, 
5% nicotine Elfbar BC5000 was the only version available in the US, whereas 2% 
Elfbar 600 was the most popular in the UK. This study measured differences in 
nicotine content and form, aerosol emissions and flavoring chemicals in the US 
and UK Elfbar products.
METHOD: A convenience sample of eight Elfbar devices sold in the US and UK, 
consisting of two Elfbar models with four identical flavor options (Peach Ice, 
Strawberry Banana, Strawberry Ice and Strawberry Kiwi) purchased between 
December 2022 and February 2023, were laboratory tested. We measured nicotine 
concentration, form and total content. We also determined aerosol emissions and 
estimated the nicotine dose delivery per puff. We identified solvents and 
flavoring chemicals in these products.
RESULTS: Elfbar products within the same country had similar nicotine content, 
concentration, form and solvents, but they differed in flavoring chemicals. US 
Elfbar contained, on average, higher volume (mean ± standard 
deviation = 6.5 ± 0.5 versus 1.8 ± 0.3 ml) of nicotine solution with a higher 
concentration (41.8 ± 2.3 versus 19.7 ± 1.2 mg/ml) than the UK Elfbar. An 
estimated dose of nicotine delivered per puff was four times higher from US 
Elfbar than UK Elfbar. There were differences in the type and amount of 
flavoring chemicals used in US and UK Elfbars, including a higher concentration 
of a synthetic coolant WS-23 in US Elfbar than in UK Elfbar (17.8 ± 1.5 versus 
12.9 ± 5.4 mg/ml).
CONCLUSIONS: Because the amount of nicotine found in the US Elfbar e-cigarettes 
is equivalent to that found in eight UK Elfbar e-cigarettes, people who use 
Elfbar sold in the US have access to much more nicotine from a single device 
than those who use Elfbar sold in the United Kingdom.

© 2024 Society for the Study of Addiction.

DOI: 10.1111/add.16702
PMID: 39505323


5. Toxicology. 2024 Nov 4:153986. doi: 10.1016/j.tox.2024.153986. Online ahead of
 print.

Activation of α7 Nicotinic Acetylcholine Receptor Augments Nerve Growth Factor 
Action on PCtrk Cells.

Mutoh T(1), Niimi Y(2), Ueda A(1).

Author information:
(1)Department of Neurology and Neuroscience, Fujita Health University Hospital, 
Toyoake, Aichi 470-1192, Japan.
(2)Department of Neurology and Neuroscience, Fujita Health University Hospital, 
Toyoake, Aichi 470-1192, Japan. Electronic address: tmutoh@fujita-hu.ac.jp.

Although cigarette smoking is known to be a critical risk factor for various 
organ systems and cancers, accumulating evidence indicates that nicotine - a 
main constituent of cigarette smoking - can exert neuroprotective effects on 
neuronal cells through nicotinic acetylcholine receptors (nAChRs). However, the 
precise molecular mechanisms for nicotinic neuroprotective actions remain to be 
fully elucidated. In this study, we examine the effects of agonists, such as 
nicotine and PNU282987, on tropomyosin-related kinase (Trk)-dependent 
neuroprotective pathways in PC12 cells overexpressing a Trk neurotrophin 
receptor (PCtrk cells). We found that even considerably higher concentrations 
(mM range for nicotine and µM range for PN282987) of nAChR agonists exert 
favorable effects, such as the augmentation of nerve growth factor (NGF)-induced 
Trk neurotrophin receptor autophosphorylation of tyrosine residues and 
NGF-induced neurite extension. Moreover, nicotine upregulated reactive oxygen 
species (ROS) levels in the cells. ROS production was completely cancelled by 
pretreatment with Mito-Tempo, a mitochondria-targeted antioxidant, indicating 
that the main source of ROS production by nicotine was mitochondria. 
Furthermore, treatment with nAChR agonists appeared to induce autophagic flux, 
as evidenced by the upregulation of LC3-II expression in cells. Furthermore, 
sucrose density ultracentrifugation of nicotine-treated cells clearly disclosed 
the augmented recruitment of α7nAChR protein into the lipid rafts fraction of 
the membrane. Intriguingly, a pull-down assay of anti-Trk antibody 
immunoprecipitates clearly included α7nAChR protein, indicating that Trk and 
α7nAChR proteins form a complex. These results reveal a new molecular 
interaction between activated α7nAChR and Trk protein that may serve as a new 
molecular basis of nicotine-induced neuroprotective action.

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

DOI: 10.1016/j.tox.2024.153986
PMID: 39505136

Conflict of interest statement: Declaration of Competing Interest The authors 
declare the following financial interests/personal relationships which may be 
considered as potential competing interests: Tatsuro Mutoh reports financial 
support was provided by the Ministry of Education, Culture, Sports, Science, and 
Technology (MEXT) of Japan. Tatsuro Mutoh reports a relationship with the 
Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan 
that includes: funding grants. If there are other authors, they declare that 
they have no known competing financial interests or personal relationships that 
could have appeared to influence the work reported in this paper. Conflict of 
interest All authors declare COI regarding the present study.