The European journal of neuroscience
June 1, 2017
Hector Vargas-Perez, Taryn E Grieder, Ryan Ting-A-Kee et al.
21 citations
A single dose of a 5-HT2A receptor agonist, given systemically or directly into the ventral tegmental area (VTA), blocks the aversive conditioned response to drug withdrawal in rats and mice. The treatment also prevents the neural switch from a drug-naive to a drug-dependent motivational system, which is linked to BDNF-mediated adaptations in the VTA. The findings suggest that 5-HT2A agonists may reverse a drug-dependent state and reduce withdrawal-induced aversion, offering a potential therapeutic approach for substance use disorders.
Neuroscience letters
January 18, 2024
Hector Vargas-Perez, Fernando Minauro-Sanmiguel, Ryan Ting-A-Kee et al.
2 citations
A classic theory of addiction, opponent-process theory, holds that a drug's immediate rewarding effects are followed by an aversive aftereffect that drives continued use. This study tested whether a 5-HT2A agonist (4-AcO-DMT, a psychedelic) follows that pattern in male rats. In a standard place-preference test 24 hours after dosing—when the drug had cleared—the rats showed no preference for the drug-paired location, suggesting no rewarding aftereffect. However, when the test was modified to capture only the acute drug effect, the rats did show a place preference, indicating the drug itself was rewarding. In a separate test measuring only the 24-hour aftereffect, that aftereffect also produced a strong place preference.
Neuroscience
April 6, 2026
Fernando Minauro-Sanmiguel, Hector Vargas-Perez
Mitochondrial dysfunction is a key driver of Alzheimer's disease, fueling neuroinflammation, synaptic failure, and energy collapse. Emerging preclinical evidence suggests that classic hallucinogens like psilocybin, LSD, DMT, and mescaline may restore mitochondrial integrity by activating serotonin 2A and sigma-1 receptors. In experimental models, these pathways enhance mitochondrial biogenesis, reduce oxidative stress, and preserve ER-mitochondrial coupling. DMT and 5-MeO-DMT specifically engage sigma-1 receptors at mitochondria-associated membranes, improving calcium homeostasis and cellular resilience. However, evidence for clinical efficacy in Alzheimer's remains limited and largely preclinical. This framework is presented as a hypothesis-generating model, emphasizing that neuropsychiatric safety, patient selection, and translational feasibility must be carefully addressed.