Biomedicine & Pharmacotherapy
August 29, 2022
Ines Erkizia-Santamaría, R. Alles-Pascual, Igor Horrillo et al.
108 citations
Psilocybin, a psychedelic drug that activates the 5-HT2A receptor, shows potential for treating neuropsychiatric diseases. In mice, psilocin (the active metabolite) binds with similar affinity to 5-HT2A, 5-HT2C, and 5-HT1A receptors. Psilocybin causes a dose-dependent head-twitch response, a sign of psychosis-like effects, which is blocked by a 5-HT2A antagonist but increased by a 5-HT2C antagonist. Body temperature rises at low doses but falls at higher doses; a 5-HT1A antagonist reverses this drop, causing hyperthermia. These findings clarify the roles of specific serotonin receptors in psilocybin's acute effects, aiding understanding of its therapeutic and side effects.
Biomedicine & Pharmacotherapy
March 24, 2022
Francisco Madrid-Gambín, Àlex Gomez‐gómez, Arnau Busquets-García et al.
14 citations
Consumption of ayahuasca increases N-acyl-ethanolamine endocannabinoids, decreases 2-acyl-glycerol endocannabinoids, and alters several large-neutral amino acids (LNAAs) in human plasma. Most LNAAs were inversely associated with nine of eleven subscales of the 5-Dimension Altered States of Consciousness Rating Scale, except tryptophan, which was positively associated. Several endocannabinoids and hexosylceramides were directly associated with ayahuasca alkaloids. Enrichment analysis confirmed dysregulation in pathways involved in serotonin and dopamine synthesis. A crosstalk between circulating LNAAs and subjective effects is suggested, independent of alkaloid concentrations, providing insights into the metabolic fingerprint and mechanism of action underlying ayahuasca experiences.
Biomedicine & Pharmacotherapy
November 13, 2025
Abdeslam Chagraoui, Luis A Haro Santillan, Renata Bocian et al.
5 citations
Ibogalogs, particularly DM506 and IBG, improve short- and long-term spatial memory in mice, while DM506 alone enhances long-term recognition memory. Tabernanthalog (TBG) showed less efficacy. These memory enhancements involve serotonin 5-HT2A and 2C receptors, as antagonists partially blocked the effects. Electrophysiological experiments linked ibogalogs to hippocampal function: TBG and DM506 increased theta rhythm power and amplitude in CA1, while volinanserin and high DM506 concentrations decreased them. DM506 enhanced NMDAR-mediated currents in CA1 neurons (EC50 = 20 ± 15 nM), blocked by Mg2+. TBG had a lower effect at high concentrations. The findings indicate ibogalogs enhance memory via 5-HT2A/2CR activation, modulating NMDAR activity and theta rhythm in hippocampal CA1.
Biomedicine & Pharmacotherapy
October 30, 2025
Rubén García‐cabrerizo, Itziar Beruete-Fresnillo, Pedro Bergas-Cladera et al.
3 citations
Oral psilocybin produces rapid and long-lasting antidepressant-like effects in adolescent rats of both sexes, alongside hallucinogenic-like head-twitch responses. Acute doses of 0.3 and 1 mg/kg induced fast behavioral changes in the forced-swim test that coincided with the timing of hallucinogenic effects. Repeated daily dosing for seven days increased hippocampal neurogenesis markers—Ki-67 (cell proliferation), NeuroD1 (neural progenitors), and BrdU (cell survival)—measured one day later. Antidepressant-like effects persisted up to 15 days after treatment and paralleled continued regulation of NeuroD1. These findings suggest oral psilocybin may offer a fast-acting, long-lasting treatment for adolescent depression, with NeuroD1 as a potential biomarker of long-term neural plasticity.
Biomedicine & Pharmacotherapy
June 17, 2026
Małgorzata Potoczna, Natalia Kasica, Małgorzata Chmielewska-Krzesińska et al.
Zebrafish larvae are increasingly used to study anxiety and stress, but it is unclear whether common behavioral tests and molecular stress markers give consistent results. This study tested several drugs with known anxiety- or depression-related effects, including diazepam, amitriptyline, and fluoxetine, along with other compounds like psilocybin. Diazepam showed the most consistent anxiety-reducing behavioral effects, but this was not accompanied by lower cortisol levels or normalized stress-related gene expression. Amitriptyline reduced cortisol but only partially affected behavior. Other drugs altered movement in ways that could reflect sedation rather than anxiety relief. The findings suggest that behavioral and molecular measures should not be treated as equivalent indicators of anxiety; instead, combining them provides a more nuanced profiling approach to identify specific drug effects and avoid misinterpretation.
Biomedicine & Pharmacotherapy
December 31, 2023
Fabregat-safont, David, Gomez-gomez, Alex, Madrid-gambin, Francisco et al.
Classical psychedelics like LSD, psilocybin, and DMT are being reconsidered for treating mental health disorders, but more human research is needed on their biological effects, mechanisms, and metabolism. Metabolic studies have robustly established the main breakdown products of these drugs in humans. However, metabolomics—which maps broader metabolic changes—remains underexplored. This review of human studies finds that while the metabolites of classical psychedelics are well characterized, the wider metabolic alterations they induce require further investigation. Integrating metabolomics with pharmacokinetics could reveal how psychedelics interact with multiple molecular targets, potentially advancing understanding of their therapeutic roles.