Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. RSC Med Chem. 2024 Oct 7. doi: 10.1039/d4md00562g. Online ahead of print.

Continuous flow synthesis of N,N-dimethyltryptamine (DMT) analogues with 
therapeutic potential.

Simoens A(1), Dejaegere A(1), Vandevelde M(1), Stevens CV(1).

Author information:
(1)Department of Green Chemistry and Technology, Synthesis, Bioresources and 
Bioorganic Chemistry Research Group, Ghent University Coupure Links 653 9000 
Ghent Belgium chris.stevens@ugent.be.

Herein, we describe the continuous flow synthesis and in-line extraction of 
N,N-dimethyltryptamine (DMT) and several of its analogues using a Fischer indole 
reaction, along with a larger gram scale synthesis (4.75 g) of the model 
compound. These products could then be quickly transformed into their respective 
fumarate salts, making them easier to handle and stable for long time storage 
using a straightforward batch procedure. Additionally, the commercially 
available drug rizatriptan benzoate could be synthesised with high purity using 
this setup. The presented method employs relatively green solvents both for the 
synthesis and purification of the target products.

This journal is © The Royal Society of Chemistry.

DOI: 10.1039/d4md00562g
PMCID: PMC11533055
PMID: 39502869

Conflict of interest statement: There are no conflicts to declare.


2. J Psychoactive Drugs. 2024 Oct 15:1-10. doi: 10.1080/02791072.2024.2413984. 
Online ahead of print.

Inhaled Dimethyltryptamine (DMT): Use Patterns and Predictors of Consumption 
Frequency.

Parnes JE(1)(2), Earleywine M(3).

Author information:
(1)Center for Alcohol and Addiction Studies, Brown University, Providence, RI, 
USA.
(2)E. P. Bradley Hospital, Riverside, RI, USA.
(3)Department of Psychology, University at Albany, State University of New York, 
Albany, NY, USA.

Despite increasing interest in psychedelics and their potential therapeutic 
effects, research on inhaled N,N-Dimethyltryptamine (DMT) remains limited. 
Inhaled DMT has a reputation for rapid, dramatic onset and a brief duration, but 
correlates of use frequency remain poorly understood. A sample recruited from 
relevant internet sites, including nearly 400 people who had inhaled DMT, 
reported substance use histories, motivations for use, DMT sources, risk 
perceptions, and other variables. Generally, participants reported initiation 
motivated by curiosity about DMT's effects, interest in psychedelics more 
broadly, and potential spiritual benefits. Those who had used other psychoactive 
substances (especially ayahuasca) and who had extracted DMT themselves reported 
inhaled DMT more frequently. Most (>60%) reported obtaining DMT from a friend 
and claimed it was "slightly difficult" to procure. Participants most commonly 
inhaled DMT from a glass pipe, in private homes, frequently alone or in small 
groups. Salient positives associated with inhaling DMT included psychologically 
cleansing or cathartic experiences. Associated challenges concerned difficult 
integration, aversive experiences, or "bad trips." Participants rated DMT as 
very or slightly safe. These data underscore the need for continued work on this 
topic to inform education and harm reduction efforts, particularly as the 
molecule's reputation for ameliorative effects receives media coverage.

DOI: 10.1080/02791072.2024.2413984
PMID: 39402982


3. 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]


4. 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.


5. 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