Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Medicine (Baltimore). 2024 Oct 11;103(41):e39309. doi: 
10.1097/MD.0000000000039309.

Integrated network pharmacology and transcriptomics to reveal the mechanism of 
Passiflora against depressive disorder: An observational study.

Wang W(1), Zhai GQ(1), Xin M(2), Li J(1), Liao JJ(1), Liang J(3), Li CB(2).

Author information:
(1)Department of Urology, Guangxi Hospital Division of The First Affiliated 
Hospital, Sun Yat-sen University, Nanning, Guangxi Zhuang Autonomous Region, PR 
China.
(2)Agro-food Science and Technology Research Institute, Guangxi Academy of 
Agricultural Sciences, Nanning, Guangxi Zhuang Autonomous Region, PR China.
(3)Psychopsychology Department, People's Hospital of Guangxi Zhuang Autonomous 
Region, Nanning, Guangxi Zhuang Autonomous Region, PR China.

Relevant studies have pointed out that Passiflora could relieve depressive 
disorder (DD) related symptoms, such as anxiety and insomnia, but its mechanism 
in DD has not been reported. In this study, DD-related transcriptome data was 
extracted from the Gene Expression Omnibus (GEO) database. Subsequently, 50 
differentially expressed genes (DEGs) were screened by "limma," and the 
enrichment analysis of these DEGs revealed that they were associated with 
neuro-inflammatory-related signaling pathways, including IL-17, TNF, NF-kappa B, 
etc signaling pathways. Then, CCDC58, CXCL5, EGR1, LOC101929855, SCML1, and 
THBS1 were screened as biomarkers of DD by the least absolute shrinkage and 
selection operator (LASSO) analysis. Moreover, Harmaline, Harmine, Quercetin, 
and Kaempferol were the key chemically active ingredients of Passiflora. 
Noticeable, THBS1 and Quercetin were connected closely. In addition, the 
quantitative real-time polymerase chain reaction (qRT-PCR) confirmed that the 
key biomarkers (EGR1 and THBS1) were significantly lowly expressed in DD 
samples. In summary, we identified 2 key biomarkers of DD and 4 key chemically 
active ingredients of Passiflora. The potential mechanism of antidepressant 
effect of DD associated with neuro-inflammatory responses and neurotransmitter 
function. These might related to the synergistic activity of its key active 
ingredients with TNF-α, IL-1β, IL-6, etc, which work with EGR1 and THBS1 to 
regulate IL-17, NF-kappa B, TNF, etc signaling pathways. These findings might 
help to deepen the understanding of the mechanism of Passiflora in clinical 
treatment of DD.

Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.

DOI: 10.1097/MD.0000000000039309
PMCID: PMC11479432
PMID: 39465851 [Indexed for MEDLINE]

Conflict of interest statement: The authors report there are no competing 
interests to declare.


2. J Cell Mol Med. 2024 Oct;28(19):e70124. doi: 10.1111/jcmm.70124.

The enhancing effects of selenomethionine on harmine in attenuating pathological 
cardiac hypertrophy via glycolysis metabolism.

Chen Q(1), Wang WY(1), Xu QY(1)(2), Dai YF(1), Zhu XY(1), Chen ZY(3), Sun 
N(1)(2), Leung CH(4), Gao F(5), Wu KJ(1).

Author information:
(1)Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, P. R. China.
(2)Department of Physiology and Pathophysiology, State Key Laboratory of Medical 
Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, P. 
R. China.
(3)Department of Cardiology, Heart Center of Fujian Province, Fujian Medical 
University Union Hospital, Fuzhou, Fujian, P. R. China.
(4)State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
Chinese Medical Sciences, University of Macau, Macao, P. R. China.
(5)Department of cardiology, Beijing An Zhen Hospital, Capital Medical 
University, Chaoyang, Beijing, P. R. China.

Pathological cardiac hypertrophy, a common feature in various cardiovascular 
diseases, can be more effectively managed through combination therapies using 
natural compounds. Harmine, a β-carboline alkaloid found in plants, possesses 
numerous pharmacological functions, including alleviating cardiac hypertrophy. 
Similarly, Selenomethionine (SE), a primary organic selenium source, has been 
shown to mitigate cardiac autophagy and alleviate injury. To explores the 
therapeutic potential of combining Harmine with SE to treat cardiac hypertrophy. 
The synergistic effects of SE and harmine against cardiac hypertrophy were 
assessed in vitro with angiotensin II (AngII)-induced hypertrophy and in vivo 
using a Myh6R404Q mouse model. Co-administration of SE and harmine significantly 
reduced hypertrophy-related markers, outperforming monotherapies. Transcriptomic 
and metabolic profiling revealed substantial alterations in key metabolic and 
signalling pathways, particularly those involved in energy metabolism. Notably, 
the combination therapy led to a marked reduction in the activity of key 
glycolytic enzymes. Importantly, the addition of the glycolysis inhibitor 
2-deoxy-D-glucose (2-DG) did not further potentiate these effects, suggesting 
that the antihypertrophic action is predominantly mediated through glycolytic 
inhibition. These findings highlight the potential of SE and harmine as a 
promising combination therapy for the treatment of cardiac hypertrophy.

© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by 
Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

DOI: 10.1111/jcmm.70124
PMCID: PMC11443162
PMID: 39351650 [Indexed for MEDLINE]

Conflict of interest statement: The authors confirm that this article content 
has no conflict of interest.


3. J Psychopharmacol. 2024 Oct;38(10):897-910. doi: 10.1177/02698811241282637.
Epub  2024 Sep 27.

Meditating on psychedelics. A randomized placebo-controlled study of DMT and 
harmine in a mindfulness retreat.

Meling D(1)(2), Egger K(1)(3)(4), Aicher HD(1)(3)(5), Jareño Redondo J(1), 
Mueller J(1), Dornbierer J(1)(3), Temperli E(1), Vasella EA(1), Caflisch 
L(1)(5), Pfeiffer DJ(1), Schlomberg JT(1)(5)(6), Smallridge JW(1), Dornbierer 
DA(1), Scheidegger M(1)(3).

Author information:
(1)Psychedelic Research and Therapy Development, Department of Adult Psychiatry 
and Psychotherapy, Psychiatric University Clinic Zurich, University of Zurich, 
Zurich, Switzerland.
(2)Department of Psychosomatic Medicine and Psychotherapy, Medical 
Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 
Freiburg, Germany.
(3)Neuroscience Center Zurich, Swiss Federal Institute of Technology Zurich, 
University of Zurich, Zurich, Switzerland.
(4)Department of Nuclear Medicine, Bern University Hospital, Bern, Switzerland.
(5)Department of Psychology, University of Zurich, Zurich, Switzerland.
(6)Digital Society Initiative, University of Zurich, Zurich, Switzerland.

BACKGROUND: In recent years, both meditation and psychedelics have attracted 
rapidly increasing scientific interest. While the current state of evidence 
suggests the promising potential of psychedelics, such as psilocybin, to enhance 
meditative training, it remains equivocal whether these effects are specifically 
bound to psilocybin or if other classical psychedelics might show synergistic 
effects with meditation practice. One particularly promising candidate is 
N,N-dimethyltryptamine (DMT), an active ingredient of ayahuasca.
AIM: This study aims to investigate the effect of the psychedelic substance DMT, 
combined with the monoamine oxidase inhibitor harmine (DMT-harmine), on 
meditative states, compared to meditation with a placebo.
METHOD: Forty experienced meditators (18 females and 22 males) participated in a 
double-blind, placebo-controlled study over a 3-day meditation retreat, 
receiving either placebo or DMT-harmine. Participants' levels of mindfulness, 
compassion, insight, and transcendence were assessed before, during, and after 
the meditation group retreat, using psychometric questionnaires.
RESULTS: Compared to meditation with a placebo, meditators who received DMT and 
harmine self-attributed greater levels of mystical-type experiences, non-dual 
awareness, and emotional breakthrough during the acute substance effects and, 
when corrected for baseline differences, greater psychological insight 1 day 
later. Mindfulness and compassion were not significantly different in the 
DMT-harmine group compared to placebo. At 1-month follow-up, the meditators who 
received DMT and harmine rated their experience as significantly more personally 
meaningful, spiritually significant, and well-being-enhancing than the 
meditators who received placebo.
CONCLUSION: Investigating the impact of DMT-harmine on meditators in a 
naturalistic mindfulness group retreat, this placebo-controlled study highlights 
the specific effects of psychedelics during meditation.
TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05780216.

DOI: 10.1177/02698811241282637
PMCID: PMC11487865
PMID: 39340164 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of conflicting interestsThe 
author(s) declared the following potential conflicts of interest with respect to 
the research, authorship, and/or publication of this article: DM, KE, HDA, JJR, 
JM, JD, ET, EAV, LC, DJP, JTTS, and JWS report having no conflicts of interest 
with respect to research, authorship, and/or publication of this article. MS and 
DAD declare that they co-founded Reconnect Labs, an academic spin-off at the 
University of Zurich, focused on the development of psychedelic medicines for 
mental health.


4. Biomedicines. 2024 Sep 3;12(9):2009. doi: 10.3390/biomedicines12092009.

Increased Myocardial MAO-A, Atrogin-1, and IL-1β Expression in Transgenic Mice 
with Pancreatic Carcinoma-Benefit of MAO-A Inhibition for Cardiac Cachexia.

Stelter K(1), Alabssi A(1), Bonaterra GA(1), Schwarzbach H(1), Fendrich V(2), 
Slater EP(2), Kinscherf R(1), Hildebrandt W(1).

Author information:
(1)Institute for Anatomy and Cell Biology, Department of Medical Cell Biology, 
Philipps-University of Marburg, Robert-Koch-Str. 8, 35032 Marburg, Germany.
(2)Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University 
of Marburg, 35032 Marburg, Germany.

Cancer cachexia (CC) continues to challenge clinicians by massively impairing 
patients' prognosis, mobility, and quality of life through skeletal muscle 
wasting. CC also includes cardiac cachexia as characterized by atrophy, 
compromised metabolism, innervation and function of the myocardium through 
factors awaiting clarification for therapeutic targeting. Because monoamine 
oxidase-A (MAO-A) is a myocardial source of H2O2 and implicated in myofibrillar 
protein catabolism and heart failure, we presently studied myocardial MAO-A 
expression, inflammatory cells, and capillarization together with transcripts of 
pro-inflammatory, -angiogenic, -apoptotic, and -proteolytic signals (by qRT-PCR) 
in a 3x-transgenic (LSL-KrasG12D/+; LSL-TrP53R172H/+; Pdx1-Cre) mouse model of 
orthotopic pancreatic ductal adenoarcinoma (PDAC) compared to wild-type (WT) 
mice. Moreover, we evaluated the effect of MAO-A inhibition by application of 
harmine hydrochloride (HH, 8 weeks, i.p., no sham control) on PDAC-related 
myocardial alterations. Myocardial MAO-A protein content was significantly 
increased (1.69-fold) in PDAC compared to WT mice. PDAC was associated with an 
increased percentage of atrogin-1+ (p < 0.001), IL-1β+ (p < 0.01), COX2+ (p < 
0.001), and CD68+ (p > 0.05) cells and enhanced transcripts of pro-inflammatory 
IL-1β (2.47-fold), COX2 (1.53-fold), TNF (1.87-fold), and SOCS3 (1.64-fold). 
Moreover, PDAC was associated with a reduction in capillary density (-17%, p < 
0.05) and transcripts of KDR (0.46-fold) but not of VEGFA, Notch1, or Notch3. 
Importantly, HH treatment largely reversed the PDAC-related increases in 
atrogin-1+, IL-1β+, and TNF+ cell fraction as well as in COX2, IL-1β, TNF, and 
SOCS3 transcripts, whereas capillary density and KDR transcripts failed to 
improve. In mice with PDAC, increased myocardial pro-atrophic/-inflammatory 
signals are attributable to increased expression of MAO-A, because they are 
significantly improved with MAO-A inhibition as a potential novel therapeutic 
option. The PDAC-related loss in myocardial capillary density may be due to 
other mechanisms awaiting evaluation with consideration of cardiomyocyte size, 
cardiac function and physical activity.

DOI: 10.3390/biomedicines12092009
PMCID: PMC11428447
PMID: 39335522

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


5. J Psychopharmacol. 2024 Oct;38(10):911-923. doi: 10.1177/02698811241273772.
Epub  2024 Sep 20.

A Phase 1 single ascending dose study of pure oral harmine in healthy 
volunteers.

Ables JL(1)(2)(3), Israel L(1), Wood O(3), Govindarajulu U(4), Fremont RT(1), 
Banerjee R(1), Liu H(3), Cohen J(1), Wang P(3), Kumar K(5), Lu G(6), DeVita 
RJ(5), Garcia-Ocaña A(6), Murrough JW(1)(2)(7), Stewart AF(3).

Author information:
(1)Department of Psychiatry, Depression and Anxiety Center for Discovery and 
Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
(2)Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New 
York, NY, USA.
(3)Department of Medicine, Diabetes, Obesity and Metabolism Institute, Icahn 
School of Medicine at Mount Sinai, New York, NY, USA.
(4)Department of Population Health Science and Policy, Center for Biostatistics, 
Icahn School of Medicine at Mount Sinai, New York, NY, USA.
(5)Department of Pharmacological Sciences, Drug Discovery Institute, Icahn 
School of Medicine at Mount Sinai, New York, NY, USA.
(6)Department of Molecular and Cellular Endocrinology, Arthur Riggs Diabetes and 
Metabolism Research Institute, City of Hope Medical Center, Duarte, CA, USA.
(7)VISN 2 Mental Illness Research, Education, and Clinical Center (MIRECC), 
James J. Peters VA Medical Center, Bronx, NY, USA.

BACKGROUND: Harmine is a component of the hallucinogenic brew, Ayahuasca, which 
also contains the psychoactive compound, N, N-dimethyltryptamine. Whether 
pharmaceutical-grade harmine hydrochloride (HCl) has psychoactive effects, the 
doses at which these might occur, and the dose-response relationship to side 
effects and safety in humans are unknown.
METHODS: We conducted a Phase 1, open-label single ascending dose trial in 
healthy adults with normal body mass index and no prior psychiatric illness. The 
primary goal was to determine the maximum tolerated dose (MTD) of oral 
pharmaceutical-grade harmine HCl and to characterize safety and tolerability. A 
secondary goal was to ascertain whether any oral dose has psychoactive effects.
RESULTS: Thirty-four adult participants, aged 18-55 years, were screened for 
study eligibility. Twenty-five participants met eligibility criteria and were 
randomized to a single dose of 100, 200, 300, or 500 mg of harmine HCl, 
respectively, using a continuous reassessment method. The most common adverse 
events (AEs) observed were gastrointestinal and/or neurological, dose-related, 
and of mild to moderate severity. The MTD was determined to be between 100 and 
200 mg and is weight-based, with 90% of those participants receiving >2.7 mg/kg 
experiencing a dose-limiting toxicity. No serious AEs of harmine HCl were 
identified.
CONCLUSIONS: Harmine HCl can be orally administered to healthy participants in 
doses <2.7 mg/kg with minimal or no AEs. Doses >2.7 mg/kg are associated with 
vomiting, drowsiness, and limited psychoactivity. This study is the first to 
systematically characterize the psychoactive effects of pharmaceutical quality 
harmine in healthy participants.

DOI: 10.1177/02698811241273772
PMID: 39301926 [Indexed for MEDLINE]