Neuropharmacology
January 13, 2023
Jenessa N. Johnston, Bashkim Kadriu, Josh Allen et al.
64 citations
Ketamine and serotonergic psychedelics both show promise as rapid-acting antidepressants, though through different primary mechanisms: ketamine modulates glutamate, while serotonergic psychedelics increase serotonin signaling. However, downstream effects like mTORC1 signaling and GABAA receptor activity appear similar, which may explain their shared antidepressant properties. Research on serotonergic psychedelics remains less advanced than on ketamine, and both face regulatory and methodological challenges, including difficulties with placebo controls in trials and the need for long-term observation.
Neurobiology of Stress
May 1, 2025
Alanna Kit, Kate Conway, Savannah Makarowski et al.
5 citations
Psilocybin shows therapeutic potential for stress-related neuropsychiatric disorders like depression, anxiety, PTSD, OCD, addiction, and eating disorders, but its mechanisms are complex, involving multiple body systems. This review explores how psilocybin interacts with the gut microbiota, enteric nervous system, and hypothalamic-pituitary axis, influencing bidirectional communication between peripheral and neuronal systems. Understanding these gut-brain interactions could advance psilocybin-based therapies from preparation through long-term integration, potentially extending benefits beyond psychiatric disorders to inflammatory-related conditions.
Progress in neuro-psychopharmacology & biological psychiatry
July 14, 2025
Zoe Plummer, Josh Allen, Justin Brand et al.
4 citations
Traumatic brain injury (TBI) causes neuroinflammation, oxidative stress, impaired neuroplasticity, neurotransmitter imbalances, and cell death, leading to neurological and psychiatric disorders. The serotonergic psychedelics psilocybin and 5-MeO-DMT may help treat TBI by promoting neuroplasticity, reducing inflammation, and protecting neurons. Psilocybin acts through 5-HT1A, 5-HT2A, and neurotrophic TrkB receptors, while 5-MeO-DMT targets sigma-1 receptors with neuroprotective properties. Preclinical and clinical research suggests these compounds can alleviate cognitive and affective dysfunction and neuroinflammation after TBI. The review critically examines safety, dosing, and clinical challenges, highlighting the potential of these psychedelics as adjunctive treatments in neurorehabilitation.
Molecular psychiatry
April 1, 2026
Josh Allen, Mujun Sun, Tamara L Baker et al.
1 citation
In a rat model of recurrent intimate partner violence brain injury (daily mild traumatic brain injury plus non-fatal strangulation for five days followed by 16 weeks of recovery), a single dose of psilocybin (1 mg/kg) reversed injury-induced anxiety-like behavior in the elevated plus-maze, increased sucrose preference (indicating reduced anhedonia), and improved reversal learning in the water maze and spatial memory in the Y-maze. Psilocybin also prevented the increase in microglial cells in the dorsal hippocampal molecular layer and the loss of reelin-positive cells in the subgranular zone seen in saline-treated injured rats. Pre-treatment with a 5-HT2A receptor antagonist blocked psilocybin's behavioral effects, indicating these benefits depend on 5-HT2A receptor activation.
Cell reports. Medicine
June 12, 2026
Josh Allen, Bianca Jupp, Tamara L Baker et al.
One year after a fluid-percussion traumatic brain injury, male rats showed persistent sensorimotor, learning, memory, and affective deficits; reduced serotonin 2A receptor binding; and microglial changes in the medial prefrontal cortex, including decreased process branching and enlarged soma size. A single dose of psilocybin (1 mg/kg) improved sensorimotor function, restored serotonin 2A receptor binding, and reduced microglial cell counts. These results suggest psilocybin has therapeutic potential for chronic traumatic brain injury and support further investigation of psychedelic treatments.
Research Square
February 23, 2026
Sandy R. Shultz, Josh Allen, Grace O'Regan et al.
Repeated mild traumatic brain injury in rats produced lasting deficits in mood, social behavior, and pain sensitivity. Delayed treatment with psilocybin (1 mg/kg) reversed several of these effects, including antidepressant-like effects, increased social behavior, and raised pain thresholds. Psilocybin also reduced injury-related increases in microglial density and increased the number and complexity of newborn neurons in the dentate gyrus, suggesting enhanced neuroplasticity. The findings indicate psilocybin may be a promising intervention for persistent symptoms after repeated mild traumatic brain injury.