Frontiers in Pharmacology
February 26, 2021
Guy A. Higgins, Nicole K. Carroll, Matthew A. Brown et al.
67 citations
Low doses of the hallucinogens ketamine and psilocybin, too small to cause perceptual effects, modestly improved motivation, attention, and impulse control in low-performing male rats. In two food-rewarded tasks, acute doses of ketamine (1–3 mg/kg) and psilocybin (0.05–0.1 mg/kg) increased break point for food and improved attentional accuracy. The benefits were small and mainly seen in rats that initially performed poorly. Both drugs produced similar patterns of effect. These findings support the idea that low, sub-perceptual doses of these drugs may have therapeutic potential for depression-related symptoms like anhedonia and cognitive dysfunction, though further research is needed.
Neuroscience
February 16, 2024
Douglas Funk, Joseph Araujo, Malik Slassi et al.
11 citations
Psilocybin increased Fos protein expression dose-dependently in the frontal cortex, nucleus accumbens, central and basolateral amygdala, and locus coeruleus of male rats, with the strongest effect in the central amygdala. Fos was expressed in both neurons and oligodendrocytes. The central amygdala, a region critical for emotional processing and learning, may be a key site where psilocybin initiates brain activation leading to neuroplastic changes underlying its therapeutic effects.
Progress in Brain Research
January 1, 2021
Guy A. Higgins, Edward M. Sellers
10 citations
Nicotine dependence, primarily from smoking and vaping, is a leading cause of preventable death, and current pharmacotherapies—nicotine replacement, bupropion, and varenicline—have limited efficacy. This chapter reviews serotonin-targeted approaches, including selective serotonin reuptake inhibitors (SSRIs), 5-HT2A receptor agonists like psilocybin, 5-HT2C receptor agonists such as lorcaserin, and 5-HT2A receptor antagonists like pimavanserin. Psilocybin shows the most promise for smoking abstinence, but findings are preliminary and face approval challenges. Preclinical tests indicate distinct profiles for these drugs, and emerging biomarkers may enable personalized smoking cessation treatment.
Journal of Psychopharmacology
August 27, 2025
Guy A. Higgins, Cam Macmillan, Inés de Lannoy et al.
1 citation
Drug discrimination procedures in rats confirm that hallucinogenic effects of psychedelics like psilocybin, LSD, DMT, and 5-MeO-DMT are mediated primarily by 5-HT2A and 5-HT1A receptors. Plasma levels of psilocin required for generalization in rats (5–52 ng/mL) overlapped with human perceptual effects, while DMT and LSD needed higher exposures in rats than in humans. The duration of drug-lever generalization followed LSD > psilocybin > 5-MeO-DMT ≥ DMT, matching clinical experience. LSD showed a disconnect between plasma exposure and generalization, similar to clinical findings. These results support the translational value of drug discrimination assays for studying psychedelics.