American Journal of Psychiatry
July 12, 2023
Guy M. Goodwin, Ekaterina Malievskaia, Gregory A. Fonzo et al.
187 citations
Psilocybin, a hallucinogen derived from mushrooms, significantly improved psychological well-being in 70% of participants in a recent drug study. Involving 100 adults undergoing therapy, those receiving psilocybin experienced enhanced emotional processing and reduced anxiety. This effect is attributed to psilocybin's influence on neurotransmitter receptors, which alters behavior and mood. Psychotherapists reported that patients showed increased openness and decreased fear of death after treatment, highlighting the potential of psychedelics like psilocybin for therapeutic use in mental health care.
Neurotherapeutics
January 25, 2024
Bryan R. Barksdale, Manoj K. Doss, Gregory A. Fonzo et al.
22 citations
Psychedelics show promise as treatments for severe psychiatric disorders, especially those resistant to standard therapies. Their effects arise from receptor binding and downstream changes in cells and genes, altering brain structure and function from individual neurons to large-scale circuits. This perspective reviews evidence on how psychedelics produce acute and lasting changes in consciousness, linking molecular, cellular, circuit, and psychological levels. A key controversy is that theoretical models from different levels of inquiry often conflict. Bridging these explanations through innovative methods and collaboration is essential to fully harness psychedelics' therapeutic potential.
American Journal of Psychiatry
January 1, 2025
Adrienne Grzenda, Gregory A. Fonzo, Aaron Wolfgang et al.
14 citations
Current evidence does not support recommending psilocybin combined with psychological support (PST) as a psychiatric treatment. More rigorous clinical trials are needed to confirm its effectiveness in larger and more diverse patient groups, determine appropriate dosing, improve blinding methods, and understand how it works and for whom it works best. Comparing it directly with other proven treatments will clarify its potential future role in treating major psychiatric disorders.
American Journal of Psychiatry
January 1, 2024
Guy M. Goodwin, Ekaterina Malievskaia, Gregory A. Fonzo et al.
12 citations
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EClinicalMedicine
September 24, 2025
Megan Hosein, Matthew J. Reid, Sarah A. Walser et al.
5 citations
Psilocybin and other psychedelics show promise as a new class of psychiatric treatments, but their rapid development risks outpacing the guidelines and infrastructure needed for safe clinical integration. A consensus statement from the US National Network of Depression Centers (NNDC) Task Group on Psychedelics and Related Compounds, comprising psychiatrists, psychologists, neuroscientists, psychedelic researchers, and healthcare consultants, recognizes psilocybin's therapeutic potential while emphasizing the need for further research. Key gaps include understanding therapeutic dosage, efficacy across diverse populations, and long-term safety. The authors call for diversified funding, collaborative research, standardized provider training, and careful ethical consideration. They advocate for a balanced approach prioritizing rigorous science and equitable access, noting the single-country focus limits international generalizability.
May 26, 2024
Hugh McGovern, Nick Wellman, Brendan Hutchinson et al.
2 citations
preprint
Psychedelics such as psilocybin show promise for treating anxiety, but how they work is unclear. This review proposes a model where anxiety disorders involve the hippocampus biasing the amygdala and salience network toward anxiety-related information, creating a self-perpetuating cycle. Psychedelics temporarily free cortical networks from this hippocampal constraint, and increased plasticity afterward allows the hippocampus to integrate new information into a less biased contextual frame, reducing anxious thoughts. The model highlights that psychedelics can acutely increase anxiety, and future research should determine optimal treatment approaches informed by cognitive neuroscience.
Neuroscience & Biobehavioral Reviews
May 30, 2026
Raquel Kosted, Manoj K. Doss, Jennifer J. Donegan et al.
1 citation
Psychedelics may enhance cognitive flexibility, but findings are mixed, with some studies showing impairment. This review proposes that acute effects of psychedelics boost learning from reward receipt, which can lead to perseveration, while post-acute effects enhance learning from reward omission, counteracting that perseveration. Different serotonin receptor subtypes (5-HT2C, 5-HT2A, 5-HT1A) may support these distinct learning processes. This hypothesis explains when psychedelics improve flexible decision-making and why insights reached under their influence can be held strongly, and it suggests strategies to reduce maladaptive belief formation.
Frontiers in Psychiatry
September 5, 2025
Nicholas J. Ahari, Gregory A. Fonzo
MDMA may help treat PTSD by affecting brain circuits involved in fear and reward. No studies have tested MDMA on specific phobias. This article proposes a model of MDMA-assisted therapy that combines biological, psychological, and social factors, informed by emotional processing theory, inhibitory learning, and cognitive behavioral interpersonal theory. It applies this model to spider phobia, a common animal phobia, suggesting a novel one-session treatment. The authors hypothesize that MDMA's neurobiological and prosocial effects can enhance emotional processing and learning during exposure, reducing avoidance and phobia symptoms. This framework could guide integration of exposure therapies with MDMA and other psychedelics for fear-based conditions.