Frontiers in Psychiatry
February 10, 2023
Muhammad Ishrat Husain, Nicole Ledwos, Elise Fellows et al.
47 citations
A narrative review examined the neurobiological mechanisms that may explain the rapid antidepressant effects of serotonergic psychedelics such as psilocybin, LSD, and ayahuasca. The drugs act as agonists or partial agonists at serotonin 5HT2A receptors, and their rapid effects may involve downregulation of these receptors. They also influence brain-derived neurotrophic factor and immune responses. Neuroimaging studies suggest that psychedelics may disrupt the default mode network, a brain system involved in self-referential thinking that is overactive in major depressive disorder. The review concludes that multiple competing theories are being investigated and more research is needed to identify the most robust evidence.
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.
Journal of clinical psychopharmacology
Nicole Ledwos, Joshua D Rosenblat, Daniel M Blumberger et al.
16 citations
A critical appraisal of clinical trials on serotonergic psychedelics for major depressive disorder and end-of-life distress finds that current evidence is low-level due to methodological limitations. Small randomized trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy to an active comparator, with similar preliminary positive effects for single-dose ayahuasca in treatment-resistant depression and lysergic acid diethylamide for end-of-life distress. Adverse events were mild and transient. However, small homogenous samples, expectancy bias, functional unblinding, and lack of standardized psychotherapy limit all studies. Psychedelics should remain experimental interventions used within clinical trials.
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.
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.