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.
The American journal of psychiatry
January 1, 2025
Aaron Wolfgang, Gregory A. Fonzo, Joshua C. Gray et al.
47 citations
MDMA-assisted therapy (MDMA-AT) using pharmaceutical-grade MDMA in controlled clinical settings is a safe and efficacious treatment for PTSD. After three MDMA administrations supported by psychotherapy, 67%–71% of individuals with PTSD no longer meet diagnostic criteria, compared with 32%–48% for placebo-assisted therapy, and effects persist at long-term follow-up. Unlike recreational use, which is confounded by adulterants and lack of precautions, MDMA-AT uniquely induces prosocial effects of trust and self-compassion while maintaining cognitive clarity. The review distinguishes evidence from recreational and therapeutic settings, describes neurobiological mechanisms, clinical evidence, public health and policy considerations, and future research directions.
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.
Drugs
November 1, 2024
Manoj K. Doss, Annamarie Demarco, Joseph E Dunsmoor et al.
14 citations
PTSD involves abnormalities in memory, and psychedelics may help treat it by affecting multiple memory systems. Most research has focused on fear conditioning and extinction, which are limited models. A review of 25 studies found that the acute effects of psychedelics can enhance extinction learning, which is impaired in PTSD, though they may also enhance fear conditioning. Post-acute effects may also boost extinction learning. PTSD and psychedelics both impair hippocampal-dependent episodic memory formation, but psychedelics may enhance cortical-dependent semantic learning, potentially helping integrate trauma memories and disrupt maladaptive beliefs. More research is needed on episodic memory consolidation, retrieval, and reconsolidation, and on post-acute effects across all memory phases.
American Journal of Psychiatry
January 1, 2024
Guy M. Goodwin, Ekaterina Malievskaia, Gregory A. Fonzo et al.
12 citations
No Summary
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.
Journal of psychopharmacology (Oxford, England)
February 5, 2026
Benjamin R. Lewis, Matthew J Reid, Andrew M Novick et al.
Clinical trials of classical psychedelics like psilocybin for mental health conditions face unique challenges that may persist if these treatments enter clinical practice. Four categories of challenges with trial participants are identified: treatment nonresponse, expectancy effects and functional unblinding, post-session psychological difficulties, and contagion effects. Management strategies for study teams to mitigate these risks are described. The National Network of Depression Centers and similar organizations can guide best practices to responsibly advance this promising field.
Journal of Affective Disorders
February 4, 2026
Raquel Kosted, Alli Waddell, Ken Adolph et al.
Depression symptoms improved over time in patients receiving five ketamine infusions, with faster initial improvement that slowed later. Higher scores on the Adverse Childhood Experiences (ACE) survey were linked to greater symptom reduction, regardless of whether patients received ketamine-assisted therapy or infusions alone. Younger adults showed a stronger response to infusions alone compared to ketamine-assisted therapy, while older adults showed the opposite pattern. The association between higher ACE scores and greater symptom reduction was particularly pronounced in younger adults and reversed in older adults. These findings suggest ketamine may offer a targeted benefit for people with early life stress, especially younger adults.
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.
The Psychiatric clinics of North America
June 1, 2024
Lewis Leone, Bryan McSpadden, Annamarie Demarco et al.
Psychedelic-assisted therapy varies widely in how it is implemented, and there is no agreement on the best way to combine the drug experience with psychotherapy. This systematic review evaluates existing approaches to integrating psychotherapy with psychedelics and offers recommendations for developing and optimizing evidence-based treatments that combine both elements to maximize therapeutic benefit and enable clear scientific conclusions.