Molecules
May 15, 2021
Henry Lowe, Ngeh J. Toyang, Blair Steele et al.
240 citations
Psychedelic effects of plants and fungi have been known for millennia, with mushrooms being a primary natural source of psilocybin, historically used in religious ceremonies and for treating neuropsychiatric conditions. Psychedelics became stigmatized due to their association with the 1960s counterculture movement, leading to a 1970 U.S. Schedule 1 classification that halted scientific research. This prohibition delayed medical knowledge of therapeutic uses. A 2004 pilot study at UCLA on psilocybin for advanced-stage cancer patients revived interest, sparking renewed research into psilocybin's chemical properties and therapeutic potential for neuropsychiatric conditions. This review examines recent advances and current research, but is not systematic.
Molecules
January 29, 2015
Xaver Koenig, Karlheinz Hilber
123 citations
Ibogaine, a plant-derived indole alkaloid, shows promise for treating addiction by reducing drug craving and preventing relapse in both animals and humans, yet it is not a licensed therapeutic and raises safety concerns. Alarming reports of life-threatening complications and sudden deaths linked to ibogaine use have accumulated, likely due to its tendency to cause cardiac arrhythmias. This review summarizes current knowledge on ibogaine's cardiovascular effects and assesses the cardiac risks of its use in anti-addiction therapy. It also considers 18-methoxycoronaridine (18-MC), a less toxic ibogaine derivative with anti-addictive properties.
Molecules
April 13, 2022
Henry Lowe, Ngeh J. Toyang, Blair Steele et al.
53 citations
The word 'psychedelic' was coined in 1956 by psychiatrist Humphry Osmond. Psychedelic drugs like DMT, 5-MeO-DMT, LSD, MDMA, and psilocybin have been used for thousands of years in spiritual and shamanic rituals in Central and South America. After their globalization in the 1960s, strict drug laws in Western countries classified them as Schedule I drugs, creating stigma that limited research. Recently, a second wave of research focuses on psychedelics as treatments for alcohol and tobacco addiction, mood and anxiety disorders, and cancer-related depression. Evidence-based data now supports their medicinal value. They offer low physiological toxicity and abuse potential, making them promising alternatives to conventional psychiatric drugs with adverse side effects. This paper reviews their therapeutic potential in controlled clinical settings.
Molecules
March 14, 2023
Timur Zanikov, Marta Gerasymchuk, Gregory Ian Robinson et al.
48 citations
In a mouse model of systemic inflammation induced by lipopolysaccharide injection, psilocybin combined with eugenol reduced brain levels of several inflammatory cytokines. Pre-treatment with psilocybin alone or in a 1:50 combination with eugenol most effectively lowered COX-2 and TNF-α mRNA expression. Post-treatment with the 1:50 combination produced the strongest reductions across multiple markers, including IL-6 and IL-8, as measured by ELISA. Western blot confirmed decreased COX-2 and IL-1β proteins. The findings suggest that psilocybin and eugenol together have anti-inflammatory effects in the brain, potentially relevant to disorders like depression and PTSD.
Molecules
April 22, 2021
Paul Cumming, Milan Scheidegger, Dario Dornbierer et al.
45 citations
Hallucinogens such as LSD, psilocybin, and mescaline are being re-evaluated for their psychotherapeutic potential. This narrative review covers in vitro and ex vivo binding studies and molecular imaging using PET or SPECT. Early PET work with [11C]-MBL showed that most specific binding is to serotonin 5-HT2A receptors, but interactions with 5-HT1A receptors and other pathways may contribute to the unique experiences. Other important factors include blood-brain barrier permeability, metabolism, and active metabolites. Only a few PET or SPECT studies of radiolabeled hallucinogens exist, most recently using [11C]Cimbi-36. Hybrid imaging combining PET with fMRI is expected to advance future research.
Molecules
April 29, 2020
Gabriela de Oliveira Silveira, Rafael G. Dos Santos, Felipe Rebello Lourenço et al.
36 citations
Ayahuasca tea, a hallucinogenic beverage used in religious and therapeutic contexts, was tested for the stability of its main alkaloids—DMT, harmine, tetrahydroharmine, and harmaline—under three storage conditions: one year in a refrigerator (plastic or glass containers), seven days at 37°C (simulating mail transport), and three freeze-thaw cycles. DMT showed no significant degradation in any condition. However, harmala alkaloids exhibited substantial variation, including degradation and concentration increases, likely due to inter-conversion and leaching from tea precipitate. Thus, quantifying alkaloids before administration in controlled studies is essential.
Molecules
April 13, 2022
Beatriz Werneck Lopes Santos, Daniel C. Moreira, Tatiana Karla Dos Santos Borges et al.
25 citations
Compounds from Banisteriopsis caapi, the plant used to make ayahuasca, show anti-inflammatory potential in brain immune cells. The plant extract was separated into fractions, and known β-carbolines (harmine, harmaline, tetrahydroharmine) were tested on BV-2 microglial cells, whose overactivation contributes to central nervous system disorders. Harmine at 75.5–302 µM reduced cell viability after 2 hours and increased necrotic cells and reactive oxygen species after 24 hours. Most treatments lowered proinflammatory cytokines IL-2, IL-6, IL-17, and/or TNF, especially harmaline and fraction F5 at 2.5 µM and higher, and tetrahydroharmine at 9.3 µM and higher. These compounds may inform treatments for neurodegenerative diseases.
Molecules
February 7, 2020
Emmanouil Tsochatzis, Joao Alberto Lopes, Fabiano Reniero et al.
22 citations
A single blotter paper seized by Swedish customs was analyzed using a combination of advanced analytical techniques and chemo-informatics tools, leading to the identification of a novel lysergic acid diethylamide (LSD) derivative, 1-butyl-lysergic acid diethylamide (1B-LSD). This substance, closely related to 1-propionyl-lysergic acid diethylamide (1P-LSD), had recently appeared on the drug street market. The identification was achieved by integrating gas chromatography–mass spectrometry, liquid chromatography–high-resolution tandem mass spectrometry, Orbitrap-MS, and one- and two-dimensional nuclear magnetic resonance spectroscopy, with all data managed and evaluated through a chemo-informatics platform. The work demonstrates a workflow for identifying new psychoactive substances when sample quantity is limited or the matrix is complex.
Molecules
October 28, 2024
Ishvin Riar, Andis Klegeris, Kennedy R. Wiens et al.
21 citations
Psilocin, the active metabolite of psilocybin, can reduce certain inflammatory activities of microglia, the brain's immune cells, without affecting tumor necrosis factor secretion. In microglia-like cell lines, psilocin at non-toxic concentrations significantly inhibited phagocytosis, reactive oxygen species release, and nitric oxide production. These inhibitory effects on reactive oxygen species and nitric oxide were similar to those of selective 5-HT2R agonists 25I-NBOH and Ro60-0175, and were blocked by 5-HT2R antagonists cyproheptadine and risperidone, indicating the role of 5-HT2 receptors. Psilocin is suggested as a potential drug candidate for neuroimmune disorders like neurodegenerative diseases where reactive microglia contribute.
Molecules
November 28, 2020
Ana Y. Simão, Joana Gonçalves, Ana Gradillas et al.
19 citations
Ayahuasca, a beverage used in shamanic ceremonies and increasingly recreationally, contains beta-carboline alkaloids and N,N-dimethyltryptamine, which have hallucinogenic effects. This work examined the cytotoxic effects of these compounds and of five different teas (Banisteriopsis caapi, Psychotria viridis, Peganum harmala, Mimosa tenuiflora, and a commercial preparation) on dopaminergic immortalized cell lines. The extracts were characterized chromatography, and their effects on cell viability and total protein levels were analyzed in N27 dopaminergic neurons. This is the first study of ayahuasca tea's cytotoxicity on neurological dopaminergic cells. Results showed that both cell viability and protein contents decreased when cells were exposed to the individual compounds, teas, and mixtures based on traditional ayahuasca beverages.
Molecules
March 5, 2020
J Benko, Stanislava Vranková
18 citations
Major depressive disorder is increasingly prevalent and burdensome, posing a challenge for psychiatry. Existing antidepressants take weeks to work, have serious side effects, and fail in one-third of patients. Recent advances have identified psychoplastogens—compounds that rapidly restructure neural networks by targeting mechanisms linked to depression. Evidence suggests they produce both acute and long-term positive effects that extend beyond psychiatric diseases. Several are naturally occurring, including psilocybin, N,N-dimethyltryptamine, and 7,8-dihydroxyflavone. This article discusses their pharmacology and effects in animal and human studies.
Molecules
December 5, 2023
Marjolein Doesburg-Van Kleffens, Amy Marisa Zimmermann-Klemd, Carsten Gründemann
13 citations
Peyote (Lophophora williamsii) contains alkaloids including pellotine, anhalonidine, hordenine, and mescaline. Mescaline produces psychoactive effects by activating the serotonin 5-HT2A receptor, which triggers calcium release from the endoplasmic reticulum. Research is evaluating mescaline's therapeutic potential, with outcomes strongly influenced by mindset and context (set and setting), including ceremonies and culture. This overview summarizes current knowledge on peyote and mescaline metabolism, mechanism of action, and clinical applications. It presents their potential benefits in a new light, exemplifying how nature-based, ritually enriched treatment can combine with innovative Western medicine.
Molecules
September 13, 2021
Joana Gonçalves, Miguel Castilho, Tiago Rosado et al.
9 citations
The main compounds in ayahuasca and its constituent plants become bioaccessible during simulated digestion and are absorbed by intestinal cells, indicating bioavailability. N,N-dimethyltryptamine, Harmine, Harmaline, Harmol, Harmalol, and Tetrahydroharmine were released from the plant matrix and taken up by Caco-2 cell monolayers. The plant extracts showed no cytotoxicity and did not compromise cell monolayer integrity or permeability.
Molecules
March 4, 2021
Matilde Calderoni, Maddalena Altare, Luca Mastracci et al.
8 citations
The illegal online trade of Peganum harmala seeds, which contain monoamine oxidase (MAO) inhibiting alkaloids used in hallucinogenic preparations like ayahuasca, poses forensic and safety challenges. This work demonstrates two complementary identification methods: optical and electron microscopy for visual seed identification, and a real-time qPCR test that detects P. harmala DNA with species specificity down to less than 1 picogram. The qPCR assay accurately quantifies the presence of P. harmala seeds or seed fragments in complex herbal mixtures, providing a reliable indication of a product's potential danger.
Molecules
February 4, 2026
Monica Patrícia Esperança, N. N. S. Gomes, Maria Graça Campos
1 citation
Substance Use Disorder (SUD) causes about 600,000 deaths yearly, mainly from opioid use. Current treatments are limited because they target only isolated brain processes and fail to address key mechanisms like glutamatergic hyperactivity, low dopamine in reward pathways, and dysfunction in control networks, leading to high relapse rates. Ibogaine, an alkaloid from the Tabernanthe iboga plant, has re-emerged as a candidate due to its ability to modulate multiple pathways linked to addiction. However, its clinical use is hindered by fragmented evidence, lack of regulatory frameworks, inconsistent product quality, and cardiac safety concerns. This scoping review synthesizes preclinical and clinical data on ibogaine for SUD, focusing on withdrawal, craving, dose-response, and cardiac risks, and outlines conditions for further investigation.
Molecules
June 18, 2026
Mengxuan Dong, Yi Zhang, Manzhu Cao et al.
Psilocybin, a psychedelic drug with reported anxiolytic and antidepressant potential, is rapidly metabolized to its active metabolite psilocin. Behavioral tests in zebrafish exposed to three doses (20, 40, and 80 μM) for 4 hours showed pronounced hyperactivity and disrupted swimming patterns, with significant increases in zone transitions and shuttle frequency. Mass spectrometry imaging revealed that psilocin distributed widely across tissues including eye, brain, heart, liver, and kidney, with marked accumulation in the brain and periportal liver regions. Relative psilocin signal intensity increased dose-dependently, and the dose-dependent increase in both behavioral hyperactivity and brain psilocin levels suggests a consistent relationship with a central site of action. These findings demonstrate the utility of mass spectrometry imaging for studying drug distribution and offer insights into the biological effects and potential risks of psilocybin.
Molecules
April 18, 2026
Flor Eréndira Sánchez-cortés, Nelly Maritza Vega-Rivera, Raúl Iván Escamilla-Orozco et al.
Microdosing an aqueous extract of Psilocybe cubensis mushrooms produces anxiolytic and antidepressant-like effects in mice comparable to a single macrodose and the antidepressant fluoxetine. Over ten days of repeated microdosing, the extract also altered brain electrical activity (electrocorticography), promoted dendritic maturation in hippocampal neurons, and changed corticosterone levels. These findings suggest that P. cubensis may offer a therapeutic alternative for anxiety and depression, with microdosing providing benefits similar to larger doses.
Molecules
February 26, 2021
Ana Y. Simão, Joana Gonçalves, Ana Gradillas et al.
correction
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