The International Journal of Neuropsychopharmacology
October 21, 2022
James J Gattuso, Daniel Perkins, Simon Ruffell et al.
233 citations
Classical psychedelics like LSD, psilocybin, and ayahuasca consistently disrupt resting-state connectivity within the Default Mode Network (DMN) and increase functional connectivity between canonical resting-state networks. The DMN, a set of brain regions active during self-referencing and mind wandering, is altered in various neuropsychiatric conditions. While DMN modulation is central to some cognitive models of psychedelics, its role in their therapeutic potential remains unclear. This systematic review provides a comprehensive overview to guide future research on the neurocognitive mechanisms of these agents.
Journal of Affective Disorders Reports
February 6, 2021
Jerome Sarris, Daniel Perkins, Lachlan Cribb et al.
72 citations
Among 1,571 people who reported depression and 1,125 who reported anxiety at the time of consuming ayahuasca, 78% of those with depression said their symptoms were 'very much' improved (46%) or 'completely resolved' (32%), while 70% of those with anxiety reported 'very much' improvement (54%) or complete resolution (16%). Greater improvement was linked to mystical experiences, more ayahuasca sessions, and personal psychological insights. A small minority—2.7% with depression and 4.5% with anxiety—reported worsened symptoms. The authors note this cross-sectional survey cannot establish treatment efficacy and call for randomized controlled trials.
The Canadian Journal of Psychiatry
August 17, 2022
Joshua D. Rosenblat, Muhammad Ishrat Husain, Yena Lee et al.
58 citations
Serotonergic psychedelics are being reconsidered as potential treatments for major depressive disorder. A Canadian task force systematically reviewed clinical trials from 1990 to 2021 and found that only psilocybin and ayahuasca have been tested in contemporary studies. Two pilot studies of single-dose ayahuasca for treatment-resistant depression showed preliminary positive effects (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy for major depressive disorder showed superiority to waitlist controls and comparable efficacy and safety to escitalopram with supportive psychotherapy, with additional trials showing efficacy in cancer-related depression (Level 3 evidence).
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
November 1, 2022
Marco Solmi, Chaomei Chen, Charles Dauré et al.
55 citations
Over the past century, clinical research on psychedelics has evolved from an early focus on safety into a 'psychedelic renaissance' after the 1990s. A scientometric analysis of 31,687 documents from the Web of Science identified major research themes: hallucinogens/entheogens, entactogens, novel psychoactive substances (NPS), and dissociative substances. The field has shifted from basic science to clinical applications, including phase 2 and 3 trials and evidence synthesis. Recent trends include NPS, ketamine-associated brain changes, and ayahuasca-assisted psychotherapy. The USA and Canada lead in productivity, reflecting legislative influences. This translational evolution has already led to esketamine approval for depression and may lead to further approvals across mental and physical conditions. Toxicology screening tools for NPS are urgently needed and may follow a similar path.
Australian & New Zealand Journal of Psychiatry
March 21, 2021
Daniel Perkins, Jerome Sarris, Susan L. Rossell et al.
53 citations
Psychedelic substances such as psilocybin, ayahuasca, LSD, and MDMA are gaining renewed medical interest due to the need for new psychiatric treatments and promising study results. This viewpoint reflects on the Royal Australian and New Zealand College of Psychiatrists' Clinical Memorandum on Psychedelics and notes regulatory developments, including applications for down-scheduling and access approvals. The authors argue that rigorous research is needed to assess benefits, safety, and therapeutic mechanisms. They summarize recent findings on mechanisms of action and the psychedelic-assisted psychotherapy model, suggesting medicinal psychedelics could become a new class of psychiatric treatments when used under medical supervision with psychotherapeutic support. However, sufficiently powered trials and safety protocols are required before clinical use, and untrained practitioner access could be harmful.
BJPsych Open
July 1, 2023
Muhammad Ishrat Husain, Nicole Ledwos, Elise Fellows et al.
41 citations
A proof-of-concept randomized controlled trial will test whether combining the psychedelic psilocybin with risperidone, a drug that blocks the serotonin 2A receptor, can block psilocybin's psychedelic effects while preserving its antidepressant action in adults with treatment-resistant depression. Sixty participants will be randomly assigned to receive psilocybin plus risperidone, psilocybin alone, or placebo plus risperidone, all with 12 hours of manualized psychotherapy. Feasibility and tolerability will be assessed through recruitment, retention, and adverse events. If successful, this approach could make psilocybin therapy more acceptable and accessible by eliminating the need for a psychedelic experience and continuous monitoring.
Journal of Psychopharmacology
December 14, 2022
Nicole Ledwos, Justyne D. Rodas, Muhammad Ishrat Husain et al.
20 citations
A systematic review of five studies (two exploratory studies, two case reports, and one prospective study) found limited evidence on the therapeutic potential of psychedelics for body dysmorphic disorder and eating disorders. Effects on symptoms were identified mostly through thematic analyses and self-reports. The review concludes that more research is needed to determine the safety and efficacy of psychedelics in these conditions and suggests avenues for future exploration.
Australian & New Zealand Journal of Psychiatry
November 22, 2019
Sally Meikle, Paul Liknaitzky, Susan L. Rossell et al.
19 citations
Psilocybin, a psychedelic drug, is gaining attention as a potential treatment for depression due to its mechanism of action, benefits in early trials, and relatively low side effect burden. This viewpoint outlines key unresolved issues for its clinical use: identifying which patients are most likely to benefit or experience adverse effects, understanding longer-term outcomes, and clarifying the role of psychotherapeutic support alongside the drug. There are also opportunities to better understand the neurobiology underlying its effects.
CNS drugs
October 1, 2022
Niloufar Pouyan, Zahra Halvaei Khankahdani, Farnaz Younesi Sisi et al.
16 citations
A systematic review of psilocybin research organized by the Research Domain Criteria (RDoC) framework found that psilocybin has beneficial effects across multiple domains, particularly on positive valence systems, negative valence systems, and social processes. Short-term (23 assessments) and long-term (15 assessments) benefits were reported for positive valence systems. For the negative valence system, 12 outcome measures indicated increased fear, 19 showed no significant effect, and 7 parameters indicated lowered sustained threat over the long term. Thirty-four outcome measures revealed short-term alterations in social systems, including enhanced perception and understanding of others and affiliation. Cognitive systems findings mostly reported dyscognitive effects. Seven studies suggested transdiagnostic effects.
Australian & New Zealand Journal of Psychiatry
May 3, 2023
Susan L. Rossell, Sally Meikle, M.l. Williams et al.
14 citations
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March 1, 2023
David Nutt, David Castle
4 citations
Psychedelic agents such as psilocybin, MDMA, ayahuasca, and LSD are being reinvestigated for their therapeutic potential in psychiatry. Psilocybin, found in 'magic mushrooms,' has been used to reduce distress in people with depression and anxiety related to life-ending cancers. MDMA has shown lasting efficacy for severe posttraumatic stress disorder. These compounds integrate psychotherapy with biological treatments, challenging established psychiatric practice and offering new insights into brain function and healing. The book covers the history, clinical aspects, risks, side effects, and precautions of these drugs.
Acta Neuropsychiatrica
February 8, 2024
Negar Sayrafizadeh, Nicole Ledwos, Muhammad Ishrat Husain et al.
3 citations
Aggression may be influenced by monoamine neurotransmitters, particularly when altered by illicit substances, but not all such substances are linked to increased aggression. This narrative review examined the associations between serotonergic psychedelics and MDMA with aggressive behavior by screening 555 articles, ultimately including 17 studies (14 on MDMA, 3 on serotonergic psychedelics). Findings were mixed: some studies indicated increased aggression following psychedelics, while others suggested protective effects. Limitations included varied definitions of psychedelics, lack of standardized outcome measures, and failure to control for confounds. Further research is needed as psychedelic studies expand.
BJPsych Open
December 15, 2025
Nicole Ledwos, Jenna Baer, Muhammad Ishrat Husain et al.
2 citations
Up to 60% of people with obsessive–compulsive disorder (OCD) do not respond to standard treatments such as selective serotonin reuptake inhibitors, antipsychotic augmentation, or cognitive–behavioural therapy. This open-label pilot trial will test whether a single 25 mg dose of psilocybin combined with psychological support is feasible, tolerable, and safe for ten adults with treatment-resistant OCD. Clinical improvement will be measured with the Yale–Brown Obsessive–Compulsive Scale. Exploratory brain imaging, electroencephalogram, and transcranial magnetic stimulation-electroencephalogram measures will examine changes in dynamic connectivity and brain dynamics before, during, and up to one week after dosing. Results will inform the design of larger randomized trials and help clarify neurobiological mechanisms of psilocybin-assisted therapy.
Therapeutic Advances in Psychopharmacology
September 1, 2025
Sally Meikle, Olivia Carter, Paul Liknaitzky et al.
2 citations
In an open-label pilot trial, two 25 mg doses of psilocybin combined with psychotherapy produced a clinically meaningful reduction in depressive symptoms at 3 weeks in people with treatment-resistant depression. The average improvement was sustained at 20 weeks, but individual responses varied: two participants showed lasting benefit, three relapsed, and two did not improve. Mindset before dosing, spiritual experiences, and perceptual changes during the session predicted treatment trajectory, whereas treatment expectations did not. No serious adverse events occurred. The findings support further research into tailoring psilocybin therapy to individual variability.
The International Journal of Neuropsychopharmacology
August 1, 2025
N Acevdo, David Castle, Susan L. Rossell
Obsessive compulsive disorder, body dysmorphic disorder, and anorexia nervosa share overlapping cognitive-behavioral and neurobiological features, yet conventional treatments often yield suboptimal outcomes. Psilocybin-assisted psychotherapy shows transdiagnostic potential by improving insight, emotional regulation, and well-being. This paper presents a protocol for an open-label basket trial testing psilocybin-assisted psychotherapy across these three conditions. The protocol was developed from scoping reviews, an international Delphi study on best practices, and qualitative interviews with patients. It uses a transdiagnostic, non-directive approach, includes a psychoeducation booklet and video, a treatment manual for clinicians, clinician- and patient-reported outcomes, opt-in additional support, and long-term follow-up.
The International Journal of Neuropsychopharmacology
August 1, 2025
Susan Meikle, Olivia Carter, Paul Liknaitzky et al.
A small pilot trial of psilocybin with psychotherapy for treatment-resistant depression found a clinically meaningful reduction in depressive symptoms three weeks after the second dose, with an average improvement of 7.14 points on the depression scale and a large effect size. However, individual responses varied widely: two participants showed lasting improvement, three relapsed, and two saw no substantial benefit. Mindset before dosing and spiritual or perceptual experiences during the session predicted treatment trajectory, but prior expectations did not. The study supports further research into tailoring psychedelic therapy to individual differences.
Psychedelics as Psychiatric Medications
March 1, 2023
David Castle, Nicole Ledwos, David Nutt
The renewed scientific interest in psychedelics and related drugs is promising for treating mental health disorders and addictions, but many questions remain unanswered. Key uncertainties include how these drugs work in the brain, how their biological effects interact with psychological support to produce therapeutic change, the duration of benefits, and long-term safety. The necessity of the psychedelic experience for therapeutic benefit, safe delivery of psychological support, integration into mainstream healthcare, funding, therapist training, and gold-standard trial designs addressing blinding, placebo response, and expectancy bias are all outstanding issues that need resolution as research expands across more disorders.