Research published in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Brain-body integromics of the ayahuasca experience.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie June 1, 2026 Francisco Madrid-Gambin, Pablo Mallaroni, Noemí Haro et al.

Ayahuasca is a psychoactive brew containing N,N-dimethyltryptamine (DMT) and β-carboline alkaloids that induces marked alterations in perception, emotion and self-referential processing. However, the multiscale biological organization linking peripheral metabolism, brain network dynamics, neurochemistry, and subjective experience in humans remains poorly understood. Here, we applied an...

DOI: 10.1016/j.biopha.2026.119391 Full text Ayahuasca Dimethyltryptamine Connectome Integromics +2

Therapeutic potential of phytocannabinoids in depression and cognitive dysfunction: Evidence from preclinical models.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie May 1, 2026 Carla Fonseca, F. Gouveia, Soraia Silva et al.

Depression is a highly prevalent and incident mental illness. Current pharmacological therapies fail in approximately 30-40% of patients, highlighting the urgent need for novel agents with pleiotropic effects. This preclinical study aimed to identify new antidepressants and cognitive modulators among five phytocannabinoids: cannabichromene, cannabidiol, cannabidivarin, cannabigerol and...

DOI: 10.1016/j.biopha.2026.119298 Full text

LSD's rapid antidepressant effects are modulated by 5-HT2B receptors.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie July 16, 2025 Amel Bouloufa, Sarah Delcourte, Renaud Rovera et al. 12 citations

Recent clinical trials show that serotonergic psychedelics, including the prototypical hallucinogen lysergic acid diethylamide (LSD), possess a great promise for treating affective disorders. Interestingly, LSD displays strong functional activity on 5-HT2B receptors and a modulatory role of the latter receptors in anxious and depressive-like behaviors has been reported. Using behavioral and in...

DOI: 10.1016/j.biopha.2025.118348 Full text Depression LSD 5-ht2a Fast-acting antidepressants, 5-ht2b +4

Population pharmacokinetic-pharmacodynamic modeling of co-administered N,N-dimethyltryptamine and harmine in healthy subjects.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie July 9, 2025 Angela Äbelö, John W Smallridge, Robin von Rotz et al. 3 citations

N,N-dimethyltryptamine (DMT) is a psychedelic compound commonly co-administered with the monoamine oxidase inhibitor harmine in ayahuasca-inspired formulations. However, the impact of harmine on DMT pharmacokinetics (PK) and pharmacodynamics (PD) remains insufficiently characterized. In this single-blind, randomized, two-arm, factorial, dose-finding study, 16 healthy participants (9 males, 7...

DOI: 10.1016/j.biopha.2025.118329 Full text Pharmacodynamics Pharmacokinetics Psychedelics Harmine-DMT Interaction Alter +10

Can ketamine therapy overcome treatment-resistant depression in Alzheimer's disease and older adults? Preclinical and clinical evidence.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie July 1, 2025 Altamura Mario, Leccisotti Ivana, Moretti Maria Claudia et al. 5 citations

Treatment-resistant depression (TRD) presents substantial clinical challenges, particularly in patients with Alzheimer's disease (AD) and older adults experiencing late-life depression. Traditional monoaminergic therapies often fail in this population due to neurodegenerative changes that impact receptor dynamics and neurotransmitter systems. Emerging evidence suggests that N-methyl-D-aspartate...

DOI: 10.1016/j.biopha.2025.118199 Full text Esketamine Treatment-resistant depression Alzheimer’s disease Elderly population +6

Gestational THC exposure perturbates hippocampal mitochondrial respiration in the memory-impaired adolescent progeny: Is there a role for mitochondrial CB1 receptor?

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie June 2025 Gianluca Lavanco, Valentina Castelli, Cesare D'Amico et al.

Mitochondria are central to cellular energy metabolism, contributing to synaptic transmission and plasticity. The mitochondrial membranes present the cannabinoid type-1 receptor (mito-CB1R), which has been functionally linked to neuronal energy supply and cognitive processing. Prenatal exposure to Δ9-tetrahydrocannabinol (pTHC) has been associated with cognitive impairments associated with...

DOI: 10.1016/j.biopha.2025.118144 Full text Cb1 receptor Complex-i Declarative memory Hippocampus +2

Examining the pharmacokinetic and pharmacodynamic interaction of N,N-dimethyltryptamine and harmine in healthy volunteers: Α factorial dose-escalation study.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie March 1, 2025 Klemens Egger, Javier Jareño Redondo, Jovin Müller et al. 14 citations

Ayahuasca, a traditional psychoactive Amazonian brew, usually contains N,N-dimethyltryptamine (DMT) and β-carboline (harmine, harmaline, tetrahydroharmine) monoamine oxidase inhibitors. However, the pharmacological interactions between these compounds remain incompletely understood. In this study, we developed an ayahuasca-inspired formulation containing DMT and harmine, aiming to...

DOI: 10.1016/j.biopha.2025.117908 Full text DMT Ayahuasca pharmahuasca Harmine Pharmacokinetics +5

Prolonged incubation with Δ9-tetrahydrocannabinol but not with cannabidiol induces synaptic alterations and mitochondrial impairment in immature and mature rat organotypic hippocampal slices.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie February 1, 2025 Costanza Mazzantini, Lorenzo Curti, Daniele Lana et al.

Cannabis derivatives are among the most widely used psychoactive substances in the world, which leads to growing medical concerns regarding its chronic use and abuse especially among adolescents. Exposure to THC during formative years produces long-term behavioral alterations that share similarities with symptoms of psychiatric and neurodevelopmental disorders. In this study, we have analyzed...

DOI: 10.1016/j.biopha.2024.117797 Full text 1–7 Psd95 Ucp2 Vdac1 +2

Characterizing the therapeutical use of ketamine for adolescent rats of both sexes: Antidepressant-like efficacy and safety profile.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2025 Jordi Jornet-Plaza, Sandra Ledesma-Corvi, M Julia García-Fuster 6 citations

While ketamine was approved for treatment-resistant depression in adult patients, its efficacy and safety profile for adolescence still requires further characterization. In this context, prior preclinical studies have shown that sub-anesthetic doses of ketamine during adolescence exert antidepressant-like effects in rodents in a dose- and sex-dependent manner. However, additional studies...

DOI: 10.1016/j.biopha.2024.117781 Full text Addiction Adolescence Cognition Depression treatment +4

Prenatal THC exposure drives sex-specific alterations in spatial memory and hippocampal excitatory/inhibitory balance in adolescent rats.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie December 1, 2024 Valentina Castelli, Gianluca Lavanco, Giuseppe Tringali et al.

The interaction between the main psychotropic ingredient of Cannabis, Δ⁹- tetrahydrocannabinol (THC), with the endogenous cannabinoid system (ECS) is a critical and underrated issue that deserves utmost attention. The ECS, indeed, contributes to the formation and regulation of excitatory and inhibitory (E/I) neuronal networks that in the hippocampus underly spatial memory. This study explored...

DOI: 10.1016/j.biopha.2024.117699 Full text Excitatory/inhibitory balance Hippocampus Prenatal THC Exposure Sex-related vulnerability +1

Non-hallucinogenic compounds derived from iboga alkaloids alleviate neuropathic and visceral pain in mice through a mechanism involving 5-HT2A receptor activation.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie June 17, 2024 Hugo R Arias, L. Micheli, Deborah Rudin et al. 14 citations

The aim of this study was to determine the anti-hypersensitivity activity of novel non-hallucinogenic compounds derived from iboga alkaloids (i.e., ibogalogs), including tabernanthalog (TBG), ibogainalog (IBG), and ibogaminalog (DM506), using mouse models of neuropathic (Chronic Constriction Injury; CCI) and visceral pain (dextrane sulfate sodium; DSS). Ibogalogs decreased mechanical...

DOI: 10.1016/j.biopha.2024.116867 Full text

Ketamine administration causes cognitive impairment by destroying the circulation function of the glymphatic system.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie June 1, 2024 Xue Wu, Gehua Wen, Lei Yan et al. 11 citations

Ketamine, as a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, was originally used in general anesthesia. Epidemiological data show that ketamine has become one of the most commonly abused drugs in China. Ketamine administration might cause cognitive impairment; however, its molecular mechanism remains unclear. The glymphatic system is a lymphoid system that plays a key...

DOI: 10.1016/j.biopha.2024.116739 Full text Ketamine 5-ht2c Aqp4 Cognitive impairment +6

Present and future of metabolic and metabolomics studies focused on classical psychedelics in humans.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie December 31, 2023 Francisco Madrid-Gambin, David Fabregat-Safont, Alex Gomez-Gomez et al. 12 citations

Psychedelics are classical hallucinogen drugs that induce a marked altered state of consciousness. In recent years, there has been renewed attention to the possible use of classical psychedelics for the treatment of certain mental health disorders. However, further investigation to better understand their biological effects in humans, their mechanism of action, and their metabolism in humans is...

DOI: 10.1016/j.biopha.2023.115775 Full text Ayahuasca Dimethyltryptamine Lysergic acid diethylamide Psilocybin +8

Abused drug-induced intracranial self-stimulation is correlated with the alteration of dopamine transporter availability in the medial prefrontal cortex and nucleus accumbens of mice.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie November 8, 2023 Yong-Qing Zhang, Hyun Kyu Min, Eunchong Hong et al.

Intracranial self-stimulation (ICSS) of the medial forebrain bundle in mice is an experimental model use to assess the relative potential of reward-seeking behaviors. Here, we used the ICSS model to evaluate the abuse potential of 18 abused drugs: 3-Fluoroethamphetamine (3-FEA); methylphenidate; cocaine; dextroamphetamine; alpha-Pyrrolidinobutyrophenone (α-PBT); 4'-Fluoro-4-methylaminorex...

DOI: 10.1016/j.biopha.2023.115860 Full text

The synergistic mechanism of action of Dajianzhong decoction in conjunction with ketamine in the treatment of depression.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie September 2023 Chan Li, Jiping Zhang, Hanhe Liu et al.

Depression is a multifactorial syndrome with a variety of underlying pathological mechanisms. While ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, exhibits a rapid antidepressant action in the central never system (CNS), the potential addiction and psychotomimetic adverse effects of ketamine limit its chronic use in clinical practice. Therefore, it is necessary to discover an...

DOI: 10.1016/j.biopha.2023.115137 Full text Depression Ketamine Djzt Gut-brain axis +2

Therapeutic effects of methimazole on 3,4-methylenedioxymethamphetamine-induced hyperthermia and serotonergic neurotoxicity.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie August 1, 2023 I-Hsun Li, Tsung-Ta Liu, Ying-Chen Chen et al.

3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug, however over 200 studies demonstrate that acute (e.g. hyperthermia, rhabdomyolysis) and chronic (e.g. neurotoxicity) toxicity effects of MDMA were observed in different animals. Methimazole (MMI), an inhibitor of thyroid hormone synthesis, was found to significantly reduce the HSP72 expression of heat stress induced in...

DOI: 10.1016/j.biopha.2023.114880 Full text MDMA Forced swimming test Hyperthermia Methimazole +2

Withania somnifera influences MDMA-induced hyperthermic, cognitive, neurotoxic and neuroinflammatory effects in mice.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie May 1, 2023 Giulia Costa, Marcello Serra, Riccardo Maccioni et al. 13 citations

Withania somnifera (WS) is utilized in Ayurvedic medicine owing to its central and peripheral beneficial properties. Several studies have accrued indicating that the recreational amphetamine-related drug (+/-)- 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) targets the nigrostriatal dopaminergic system in mice, inducing neurodegeneration and gliosis, causing acute hyperthermia and cognitive...

DOI: 10.1016/j.biopha.2023.114475 Full text Ecstasy Ashwagandha Body temperature Gliosis +2

Prenatal ketamine exposure impairs prepulse inhibition via arginine vasopressin receptor 1A-mediated GABAergic neuronal dysfunction in the striatum.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie April 1, 2023 Aeseul Kim, Sun Mi Gu, Haemiru Lee et al. 5 citations

Ketamine is a widely used anesthetic with N-methyl-D-aspartate (NMDA) receptor antagonism. Exposure to ketamine and NMDA receptor antagonists may induce psychosis. However, the mechanism underlying the effects of ketamine on the immature brain remains unclear. In this study, NMDA receptor antagonists, ketamine and methoxetamine, were administered to pregnant F344 rats (E17). These regimens...

DOI: 10.1016/j.biopha.2023.114318 Full text Methoxetamine N-methyl-d-aspartate receptor Prepulse inhibition Δ-aminobutyric acid

Ketamine-induced antidepressant like effects in mice: A possible involvement of cannabinoid system.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie April 1, 2019 Fatemeh Khakpai, Mohaddeseh Ebrahimi-Ghiri, Sakineh Alijanpour et al.

The purpose of this study was to explore the possible interaction between ketamine and cannabinoid system in the modulation of depression-related responses using the forced swimming test (FST), tail suspension test (TST) and open-field test (OFT) in mice. Our results revealed that intra-peritoneal (i.p.) injection of ketamine (5 and 10 mg/kg), a non-competitive NMDA antagonist, dose-dependently...

DOI: 10.1016/j.biopha.2019.108717 Full text

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