Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
March 1, 2025
Klemens Egger, Javier Jareño Redondo, Jovin Müller et al.
14 citations
Ayahuasca contains DMT and harmine, but their interactions are not fully understood. In a single-blind, randomized, two-arm, factorial dose-finding study with 16 healthy participants, each received six dose combinations of DMT (0-120 mg) and harmine (0-180 mg) via a transmucosal delivery system. All combinations produced dose-dependent subjective effects lasting 4-5 hours, with peak DMT and harmine levels reaching 33 ng/mL and 49 ng/mL, respectively. The interaction was bidirectional: harmine reduced DMT metabolism, while DMT altered harmine pharmacokinetics. The formulation had a favorable safety profile, supporting further testing for affective disorders.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
June 17, 2024
Hugo R. Arias, L. Micheli, Deborah Rudin et al.
14 citations
New non-hallucinogenic iboga alkaloid derivatives, called ibogalogs (TBG, IBG, and DM506), reduce pain hypersensitivity in mouse models of neuropathic and visceral pain. IBG provided the longest pain relief at a lower dose, while DM506 acted fastest. The pain-relieving effect was blocked by the 5-HT2A receptor antagonist ketanserin, indicating that activation of the 5-HT2A receptor, not its inhibition, mediates this activity. Ibogalogs activate 5-HT2A and 5-HT6 receptors and act as inverse agonists (except TBG) at the 5-HT7 receptor. Based on prior work, 5-HT6 inhibition and 5-HT7 activation relieve pain, so these receptors are not involved. The anti-hypersensitivity activity of ibogalogs in mice is mediated by 5-HT2A receptor activation.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
May 1, 2023
Giulia Costa, Marcello Serra, Riccardo Maccioni et al.
13 citations
A standardized extract of Withania somnifera (ashwagandha), when given acutely alongside MDMA (ecstasy), protects mice from the drug's harmful effects on the brain, body temperature, and memory. MDMA alone caused degeneration of dopamine-producing neurons, inflammation (gliosis), a rise in body temperature, and impaired performance on a novel object recognition task. These effects were not prevented by pretreating mice with the extract for three days before MDMA. However, when the extract was given together with MDMA, it counteracted the loss of dopamine neurons in the substantia nigra, reduced gliosis in the striatum, normalized body temperature, and restored memory performance to levels similar to those of saline-treated controls.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
July 16, 2025
Amel Bouloufa, Sarah Delcourte, Renaud Rovera et al.
12 citations
Acute administration of LSD produces fast antidepressant- and anxiolytic-like effects in rats, along with hallucinatory-like effects and suppression of serotonin neuron activity. These effects are blocked by a selective 5-HT2B receptor antagonist, indicating they depend on activation of 5-HT2B receptors. Depletion of serotonin also prevents LSD's effects in the forced swim test and head-twitch response. In mice, LSD fails to produce antidepressant- or anxiolytic-like effects, and its hallucinogenic-like effect is not altered by 5-HT2B receptor blockade. The findings suggest LSD acts as a rapid-onset antidepressant in rats but not in mice, through mechanisms involving 5-HT2B receptor activation.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
December 31, 2023
Francisco Madrid-Gambin, David Fabregat-Safont, Alex Gomez-Gomez et al.
12 citations
Psychedelics like LSD, mescaline, DMT, ayahuasca, 5-methoxy-DMT, and psilocybin induce altered states of consciousness and are being studied for treating mental health disorders. This review examines metabolic and metabolomics studies in humans after administration of these drugs. The main metabolites for classical psychedelics have been robustly established, but the metabolic alterations they induce need further exploration. Integrating metabolomics with pharmacokinetics may help understand the therapeutic role of psychedelics by revealing molecular interactions with multiple targets.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
June 1, 2024
Xue Wu, Gehua Wen, Lei Yan et al.
11 citations
Ketamine, a drug originally used as an anesthetic and now commonly abused in China, can cause cognitive impairment by disrupting the brain's glymphatic system, which normally clears metabolic waste. In a mouse model of short-term ketamine administration, the drug increased expression of the 5-HT2c receptor in hippocampal astrocytes, leading to accumulation of the transcription factor ΔFosb. ΔFosb then bound to a specific DNA sequence in the regulatory region of the Aqp4 gene, suppressing Aqp4 expression and impairing glymphatic circulation, which resulted in cognitive deficits. This mechanism does not involve the Pten/Akt pathway and reveals a non-neuronal basis for ketamine-induced cognitive harm, informing clinical safety and withdrawal effectiveness.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
January 1, 2025
Jordi Jornet-Plaza, Sandra Ledesma-Corvi, M Julia García-Fuster
6 citations
Ketamine, approved for treatment-resistant depression in adults, shows potential as an antidepressant for adolescents but with sex-specific dose requirements and safety concerns. In rats, a single dose of 5 mg/kg produced antidepressant-like effects in females and 10 mg/kg in males, while 7-day treatment extended efficacy to lower doses. Safety assessments revealed psychomotor sensitization in adolescent females at the antidepressant dose and addiction liability in adult males re-exposed to ketamine after adolescent treatment. These findings indicate that ketamine's antidepressant effects in adolescence are dose- and sex-dependent, but the observed safety risks warrant caution before clinical translation.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
July 1, 2025
Altamura Mario, Leccisotti Ivana, Moretti Maria Claudia et al.
5 citations
Ketamine and its derivatives, esketamine and arketamine, may provide rapid and robust antidepressant effects for older adults with treatment-resistant depression, including those with Alzheimer's disease. A systematic review of 19 human clinical studies and 8 preclinical studies found that these NMDA receptor antagonists can alleviate depressive symptoms in this population, potentially offering advantages over standard treatments like memantine due to a broader mechanism of action. However, neurodegenerative changes in older adults can affect receptor dynamics, and the evidence suggests these drugs are promising but require further investigation.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
April 1, 2023
Aeseul Kim, Sun Mi Gu, Haemiru Lee et al.
5 citations
Prenatal exposure to NMDA receptor antagonists like ketamine and methoxetamine in pregnant rats leads to psychosis-like behaviors in their offspring, including hyperactivity and reduced prepulse inhibition (PPI), a measure of sensorimotor gating. These effects are linked to increased expression of the arginine vasopressin receptor 1A (Avpr1a) in the striatum, and artificially overexpressing Avpr1a in the striatum also impairs PPI. Additionally, the treatments raise levels of glutamate decarboxylase 67 (GAD67) and GABA in the striatum, indicating that prenatal NMDA receptor blockade disrupts GABAergic neuron function and sensorimotor gating through Avpr1a regulation.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
July 9, 2025
Angela Äbelö, John W Smallridge, Robin von Rotz et al.
3 citations
The psychedelic compound DMT is often taken with harmine, a monoamine oxidase inhibitor, as in ayahuasca, but how harmine alters DMT's effects was not well understood. In a study of 16 healthy adults, six combinations of buccal DMT (0-120 mg) and harmine (0-180 mg) were given. Harmine increased DMT's bioavailability and prolonged its absorption, leading to higher and more sustained blood levels. The intensity of subjective psychedelic effects rose with dose, and harmine potentiated these effects at higher DMT doses. A mathematical model captured these relationships and individual variability, offering a foundation for more personalized dosing in psychedelic therapy.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
June 1, 2026
Francisco Madrid-Gambin, Pablo Mallaroni, Noemí Haro et al.
The psychedelic state induced by ayahuasca arises from coordinated, system-level interactions between peripheral metabolism and brain network dynamics, rather than isolated neurochemical events. In 20 experienced ceremonial users, the subjective dimensions of oceanic boundlessness, visionary restructuralization, and auditory alterations covaried with circulating DMT and β-carbolines, shifts in lipid, amino acid, and energy metabolism, and reconfiguration of dorsal attention and default mode network connectivity. Shared features across these experiences were most strongly linked to endocannabinoid-related N-acylethanolamines, acylglycerols, and ceramides, extending beyond canonical serotonergic models to downstream lipid-signaling and metabolic processes. The findings offer translational insight into metabolic pathways that may modulate brain function and subjective response.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
February 1, 2025
Costanza Mazzantini, Lorenzo Curti, Daniele Lana et al.
A seven-day exposure to THC reduced pre- and post-synaptic proteins (synaptophysin, vGlut1, PSD95) in both immature and mature hippocampal slices, while CBD increased PSD95 only in immature slices. THC also lowered membrane passive properties and intrinsic excitability and increased sEPSCs in immature CA1 pyramidal cells. Both cannabinoids impaired mitochondrial function by reducing mRNA expression of mitobiogenesis genes (VDAC1, UCP2, TFAM). THC, but not CBD, caused tissue disorganization and morphological changes in CA1 pyramidal neurons, astrocytes, and microglia in both slice types. These findings help explain the adolescent brain's vulnerability to psychotropic cannabinoids.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
August 1, 2023
I-Hsun Li, Tsung-Ta Liu, Ying-Chen Chen et al.
Methimazole (MMI), a drug that inhibits thyroid hormone synthesis, alleviates several harmful effects of MDMA (ecstasy) in male rats. MMI reduced MDMA-induced hyperthermia (overheating) and increased heat loss through peripheral vasodilation. PET scans showed that MDMA raised glucose uptake in skeletal muscles, which MMI pretreatment prevented. Immunohistochemistry revealed that MMI lessened the loss of serotonin transporter fibers, a sign of neurotoxicity caused by MDMA. In the forced swimming test, rats given MMI swam longer and were immobile less, indicating more active behavior. The findings suggest MMI lowers body temperature, reduces neurotoxicity, and promotes excited behavior, though further research is needed for clinical use.