Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Stud Alcohol Drugs. 2024 Sep;85(5):595-606. doi: 10.15288/jsad.23-00011.

Traditional Medicine, Culture, and Psychedelic Science: New Pathways for 
Recovery From Substance Use Disorders.

Loizaga-Velder A(1), Loizaga Pazzi A(1).

Author information:
(1)Nierika Institute of Intercultural Medicine, Paraje Casahuate s/N; Chalmita, 
52483 Ocuilan, Edo. de México, Mexico.

OBJECTIVE: This article provides an intercultural transdisciplinary perspective 
on the Indigenous roots of the resurging field of psychedelic science in the 
management of substance use disorders (SUDs). Ritual uses of entheogens (i.e., 
psychedelics of natural origin) are elaborate technologies for navigating, 
containing, and therapeutically directing non-ordinary states of consciousness 
induced by these compounds.
METHOD: A narrative review of the literature on the therapeutic potential of 
ayahuasca, peyote, psilocybin-containing mushrooms, Incilius alvarius-derived 
5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), and iboga for the treatment of 
SUDs was conducted. This article also describes the application of some of these 
entheogens within a pilot intercultural clinical program implemented by the 
Yaqui tribe in Sonora, Mexico, for the treatment of SUDs and other mental health 
challenges.
RESULTS: Observational research and preliminary clinical studies indicate the 
therapeutic potential and relative safety of these compounds in appropriate 
contexts, including the use of careful screening practices and complementary 
psychotherapeutic interventions.
CONCLUSIONS: Preliminary research points to the potential therapeutic value of 
integrating entheogenic plant and fungi medicine with culturally attuned 
therapeutic strategies. Respectful intercultural dialogue across worldviews and 
scientific paradigms allows for the further development of new perspectives at 
the intersection of entheogens, addiction treatment, mental health, and 
traditional medicine. More interdisciplinary research is necessary in this 
field.

DOI: 10.15288/jsad.23-00011
PMID: 39400118 [Indexed for MEDLINE]


2. Front Psychiatry. 2024 Sep 19;15:1477996. doi: 10.3389/fpsyt.2024.1477996. 
eCollection 2024.

Short-term safety and tolerability profile of 5-methoxy-N,N-dimethyltryptamine 
in human subjects: a systematic review of clinical trials.

Kwaśny A(1), Wilkowska A(1), Cubała WJ(1).

Author information:
(1)Department of Psychiatry, Faculty of Medicine, Medical University of Gdańsk, 
Gdańsk, Poland.

INTRODUCTION: Psychedelic agents have regained the attention of pharmaceutical 
companies as promising treatments for depressive episodes. 
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), an atypical psychedelic, is 
emerging as a potentially effective, novel rapid-acting antidepressant. In this 
systematic review, we analyze the safety and tolerability evidence from clinical 
trials.
METHODS: Following the Preferred Reporting Items for Systematic Reviews and 
Meta-analyses (PRISMA) guidelines, electronic databases (PubMed, SCOPUS, Web of 
Science, EMBASE, and EBSCO) were searched from inception until 15 May 2024 to 
identify clinical trials (regardless of phase) reporting on short-term safety 
and tolerability profile of 5-MeO-DMT using the following keywords in various 
combinations: 5-methoxy-N, N-dimethyltryptamine, 5-MeO-DMT, safety, adverse, 
adverse reaction, side effects, tolerability, dropout, healthy volunteer, 
healthy participant, depression, major depressive disorder. Only studies written 
in English were considered.
RESULTS: Initial search yielded 100 records, out of which 3 met the inclusion 
criteria. These studies reported on the results from clinical trial phases I and 
I/II, with a total of 78 participants included; two studies involved healthy 
volunteers, and one included patients with treatment-resistant depression. 
Although the data is limited, it confirms a good short-term safety and 
tolerability profile for 5-MeO-DMT, with no serious adverse events (SAEs) 
reported. Furthermore, no drop-outs were reported.
CONCLUSION: 5-MeO-DMT administration in human subjects presents favorable 
short-term safety and tolerability profile. Importantly, no SAEs have been 
documented, and no adverse events led to participant withdrawal from the studies 
There is a need for future randomized, double-blind, placebo-controlled trials 
with larger samples and follow-up to assess potential chronic adverse events.

Copyright © 2024 Kwaśny, Wilkowska and Cubała.

DOI: 10.3389/fpsyt.2024.1477996
PMCID: PMC11446775
PMID: 39364380

Conflict of interest statement: AK has received research support from Beckley 
Psytech, GH Research, MSD. AW has received research support from Angelini, 
Biogen, Eli Lilly and Company, Janssen- Cilag, Lundbeck, Polpharma, Sanofi, 
Termedia and Valeant. WC has received grants from: Acadia, Alkermes, Allergan, 
Angelini, Auspex Pharmaceuticals, Beckley Psytech, BMS, Celon, Cephalon, 
Cortexyme, Ferrier, Forest Laboratories, GedeonRichter, GH Research, 
GWPharmaceuticals, HMNC Brain Health, IntraCellular Therapies, Janssen, KCR, 
Lilly, Lundbeck, Minerva, MSD, NIH, Novartis, Orion, Otsuka, Sanofi, Servier. He 
has received honoraria from: Adamed, Angelini, AstraZeneca, BMS, Celon, GSK, 
Janssen, KRKA, Lekam, Lundbeck, Minerva, NeuroCog, Novartis, Orion, Pfizer, 
Polfa Tarchomin, Sanofi, Servier, Zentiva. He is in the following advisory 
boards: Angelini, Celon terminated, Douglas Pharmaceuticals, GeH Research, 
Janssen, MSD, Novartis, Sanofi.


3. Clin Pharmacol Ther. 2024 Sep 30. doi: 10.1002/cpt.3459. Online ahead of
print.

Harnessing Pharmacogenomics in Clinical Research on Psychedelic-Assisted 
Therapy.

Halman A(1)(2)(3), Conyers R(2)(4), Moore C(2)(4), Khatri D(2), Sarris 
J(1)(5)(6)(7), Perkins D(1)(3)(5).

Author information:
(1)Psychae Therapeutics, Melbourne, Victoria, Australia.
(2)Cancer Therapies, Stem Cell Medicine, Murdoch Children's Research Institute, 
Parkville, Victoria, Australia.
(3)School of Population and Global Health, The University of Melbourne, 
Melbourne, Victoria, Australia.
(4)Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, 
Australia.
(5)Centre for Mental Health, Swinburne University, Melbourne, Victoria, 
Australia.
(6)NICM Health Research Institute, Western Sydney University, Westmead, New 
South Wales, Australia.
(7)The Florey Institute of Neuroscience and Mental Health & The Department of 
Psychiatry, Melbourne University, Melbourne, Victoria, Australia.

Psychedelics have recently re-emerged as potential treatments for various 
psychiatric conditions that impose major public health costs and for which 
current treatment options have limited efficacy. At the same time, personalized 
medicine is increasingly being implemented in psychiatry to provide 
individualized drug dosing recommendations based on genetics. This review brings 
together these topics to explore the utility of pharmacogenomics (a key 
component of personalized medicine) in psychedelic-assisted therapies. We 
summarized the literature and explored the potential implications of genetic 
variability on the pharmacodynamics and pharmacokinetics of psychedelic drugs 
including lysergic acid diethylamide (LSD), psilocybin, N,N-dimethyltryptamine 
(DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), ibogaine and 
3,4-methylenedioxymethamphetamine (MDMA). Although existing evidence is limited, 
particularly concerning pharmacodynamics, studies investigating pharmacokinetics 
indicate that genetic variants in drug-metabolizing enzymes, such as cytochrome 
P450, impact the intensity of acute psychedelic effects for LSD and ibogaine, 
and that a dose reduction for CYP2D6 poor metabolizers may be appropriate. 
Furthermore, based on the preclinical evidence, it can be hypothesized that 
CYP2D6 metabolizer status might contribute to altered acute psychedelic 
experiences with 5-MeO-DMT and psilocybin when combined with monoamine oxidase 
inhibitors. In conclusion, considering early evidence that genetic factors can 
influence the effects of certain psychedelics, we suggest that pharmacogenomic 
testing should be further investigated in clinical research. This is necessary 
to evaluate its utility in improving the safety and therapeutic profile of 
psychedelic therapies and a potential future role in personalizing 
psychedelic-assisted therapies, should these treatments become available.

© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley 
Periodicals LLC on behalf of American Society for Clinical Pharmacology and 
Therapeutics.

DOI: 10.1002/cpt.3459
PMID: 39345195


4. Neurosci Biobehav Rev. 2024 Sep 19;167:105899. doi: 
10.1016/j.neubiorev.2024.105899. Online ahead of print.

Psychedelics: A review of their effects on recalled aversive memories and 
fear/anxiety expression in rodents.

Werle I(1), Bertoglio LJ(2).

Author information:
(1)Department of Pharmacology, Federal University of Santa 
Catarina, Florianopolis, SC, Brazil.
(2)Department of Pharmacology, Federal University of Santa 
Catarina, Florianopolis, SC, Brazil. Electronic address: 
leandro.bertoglio@ufsc.br.

Threatening events and stressful experiences can lead to maladaptive memories 
and related behaviors. Existing treatments often fail to address these issues 
linked to anxiety/stress-related disorders effectively. This review identifies 
dose ranges associated with specific actions across various psychedelics. We 
examined psilocybin/psilocin, lysergic acid diethylamide (LSD), 
N,N-dimethyltryptamine (DMT), mescaline, 5-methoxy-N,N-dimethyltryptamine 
(5-MeO-DMT), serotonin 2 A/2 C agonists (e.g., DOI) and 
3,4-methylenedioxymethamphetamine (MDMA) on aversive memory extinction and 
reconsolidation, learned fear, anxiety, and locomotion in rodents. Nearly 400 
studies published since 1957 were reviewed. Psychedelics often show biphasic 
effects on locomotion at doses that enhance extinction learning/retention, 
impair memory reconsolidation, or reduce learned fear and anxiety. Emerging 
evidence suggests a dissociation between their prospective benefits and 
locomotor effects. Under-explored aspects include sex differences, 
susceptibility to interference as memories age and generalize, repeated 
treatments, and immediate vs. delayed changes. Validating findings in 
traumatic-like memory and maladaptive fear/anxiety models is essential. 
Understanding how psychedelics modulate threat responses and post-retrieval 
memory processes in rodents may inform drug development and human studies, 
improving therapeutic approaches for related psychiatric conditions.

Copyright © 2024 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.neubiorev.2024.105899
PMID: 39305969

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


5. Prog Neuropsychopharmacol Biol Psychiatry. 2024 Sep 7:111139. doi: 
10.1016/j.pnpbp.2024.111139. Online ahead of print.

The immunomodulatory effects of classical psychedelics: A systematic review of 
preclinical studies.

Low ZXB(1), Ng WS(2), Lim ESY(2), Goh BH(3), Kumari Y(4).

Author information:
(1)Neurological Disorder and Aging (NDA) Research Group, Neuroscience Research 
Strength (NRS), Jeffrey Cheah School of Medicine and Health Sciences, Monash 
University Malaysia, 47500, Selangor, Malaysia.
(2)Jeffrey Cheah School of Medicine and Health Sciences, Monash University 
Malaysia, 47500, Selangor, Malaysia.
(3)Sunway Biofunctional Molecules Discovery Centre, School of Medical and Life 
Sciences, Sunway University Malaysia, Bandar Sunway, 47500, Selangor Darul 
Ehsan, Malaysia; Biofunctional Molecule Exploratory Research Group, School of 
Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan 47500, 
Malaysia; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 
310058, China.
(4)Neurological Disorder and Aging (NDA) Research Group, Neuroscience Research 
Strength (NRS), Jeffrey Cheah School of Medicine and Health Sciences, Monash 
University Malaysia, 47500, Selangor, Malaysia. Electronic address: 
yatinesh.kumari@monash.edu.

Emerging evidence suggests that classical psychedelics possess immunomodulatory 
and anti-inflammatory properties; however, these effects are yet to be 
well-established. This systematic review aims to provide a timely and 
comprehensive overview of the immunomodulatory effects of classical psychedelics 
in preclinical studies. A systematic search was conducted on six databases, 
including CINAHL, EMBASE, MEDLINE, PsychINFO, Scopus, and Web of Science. 
Eligible studies targeting classical psychedelics for evaluation of their 
effects on inflammatory markers and immunomodulation have been included for 
analysis. Data was extracted from 40 out of 2822 eligible articles, and their 
risk of bias was assessed using the Systematic Review Center for Laboratory 
Animal Experimentation (SYRCLE) tool and Quality Assessment Tool for In Vitro 
Studies (QUIN). Studies examined 2,5-dimethoxy-4-iodoamphetamine (DOI; n = 18); 
psilocybin (4-PO-DMT; n = 9); N,N-dimethyltryptamine (DMT; n = 8); lysergic acid 
diethylamide (LSD; n = 6); 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; n = 3); 
psilocin (4-HO-DMT; n = 3); and mescaline (n = 2). In 36 studies where 
inflammatory cytokine levels were measured following psychedelic administration, 
a decrease in at least one inflammatory cytokine was observed in 29 studies. 
Immune cell activity was assessed in 10 studies and findings were mixed, with an 
equal number of studies (n = 5 out of 10) reporting either an increase or 
decrease in immune cell activity. Classical psychedelics were found to alleviate 
pre-existing inflammation but promote inflammation when administered under 
normal physiological conditions. This information is anticipated to inform 
future clinical trials, exploring classical psychedelics' potential to alleviate 
inflammation in various pathologies.

Copyright © 2024. Published by Elsevier Inc.

DOI: 10.1016/j.pnpbp.2024.111139
PMID: 39251080

Conflict of interest statement: Declaration of competing interest The authors 
declare that there are no known competing financial interests or personal 
relationships that could have appeared to influence the work reported in this 
paper.