CNS spectrums
November 20, 2024
Rafael Guimarães Dos Santos, Jaime Eduardo Cecilio Hallak
13 citations
Ayahuasca, a botanical hallucinogen traditionally used by indigenous groups in Northwestern Amazonia, is prepared from plants containing DMT and harmine. Interest in its therapeutic potential for psychiatric disorders is growing. Human studies suggest good safety and tolerability, often with improvements in depressive and anxious symptoms. However, controlled studies are few, involve small samples, single doses, and short follow-ups. Larger trials with varied doses are needed to evaluate potential benefits.
CNS spectrums
December 1, 2024
Mathieu Fradet, Carlton M Kelly, Anna J Donnelly et al.
10 citations
Psilocybin therapy shows promise as a new treatment for depression and other mental health disorders. The chapter reviews recent data on its safety and efficacy, describes how the therapy is delivered and its subjective effects, and outlines current understanding of psilocybin's pharmacology and neurobiological effects. Other psychedelic substances with therapeutic potential are also briefly discussed.
CNS spectrums
October 31, 2024
Sabrina Wong, Gia Han Le, Angela T H Kwan et al.
10 citations
A systematic review and meta-analysis of seven randomized controlled trials found that a single dose of esketamine given around childbirth significantly reduced the incidence of postpartum depression (PPD). Within one week of delivery, the odds of a PPD diagnosis were 70% lower for those who received esketamine compared to a control; between four and six weeks postpartum, the odds were 67% lower. The results suggest that esketamine may have preventive antidepressant effects during the postpartum period, with implications for both the mechanisms and clinical treatment of PPD.
CNS spectrums
January 17, 2025
Roger S McIntyre, Gregory Mattingly, Yordan Godinov et al.
9 citations
In adults with treatment-resistant depression, esketamine nasal spray combined with an oral antidepressant leads to higher remission rates than quetiapine extended-release combined with an oral antidepressant. Starting at week 8, 28.3% of esketamine-treated patients achieved remission compared to 18.6% on quetiapine, and by week 32, 55.7% versus 36.3%. Depressive symptoms improved more with esketamine from day 8 onward. Fewer patients stopped treatment due to side effects with esketamine (4.5%) than with quetiapine (10.1%). These results come from a secondary analysis of a randomized trial.
CNS spectrums
December 1, 2024
8 citations
Psilocybin shows promise for treating mood and anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, and substance use disorder, but significant evidence gaps remain. Current studies suggest psilocybin may alleviate depression, anxiety, obsessions, compulsions, and addictive behaviors, yet comparisons with standard antidepressants or anxiolytics are lacking, and optimal dosage, long-term efficacy, and safety are unclear due to trial limitations. Real-world implementation faces challenges including infrastructural requirements, personnel training, cultural stigma, and unresolved legal and ethical issues. Larger, more rigorous studies are needed to substantiate the evidence base before psilocybin can transition from research to clinical practice.
CNS spectrums
June 30, 2025
Jose Manuel Quintero, Rosa Helena Bustos, Sharon Lechtig-Wassermann et al.
6 citations
Ketamine, first made in 1962, has become important for its fast-acting and lasting antidepressant effects in people with treatment-resistant depression. Unlike older antidepressants, it works through multiple brain chemical systems, including blocking NMDA receptors and boosting AMPA receptors. It also remains a useful anesthetic and painkiller for acute and chronic pain, and shows anti-inflammatory, neuroprotective, and possible antitumor properties. However, its dissociative and hallucinogenic effects lead to recreational misuse, which can cause bladder and liver problems. Its rediscovery as an antidepressant in the early 2000s transformed psychiatric care, and research now explores its use in bipolar depression, PTSD, OCD, and substance use disorders. The review covers ketamine's many uses and the need to balance benefits with risks.
CNS spectrums
January 30, 2025
Steve O'Brien, David Nutt
5 citations
MDMA-assisted therapy (MDMA-AT) for PTSD and other behavioral disorders has a controversial history, moving from research to recreational use and back to medicine. Pivotal trials have been conducted, but recent setbacks have hindered clinical application. The chapter argues that MDMA-AT still holds potential to transform psychiatry, though its future is uncertain due to ongoing debates over ethics, methodology, and political influence.
CNS spectrums
November 21, 2024
Elena Koning, Elvina M Chu, Elisa Brietzke
5 citations
Psychedelics alter consciousness and have been used for centuries by indigenous communities, but only recently studied as therapeutic tools in psychotherapy. Since the early twentieth century, psychedelic-assisted psychotherapy has been explored for neuropsychiatric conditions with rigid thought patterns and treatment resistance. This emerging field has faced opposition from mid-twentieth century counterculture associations, media sensationalism, legislative restrictions, and scientific criticisms like 'breaking the blind' and 'excessive enthusiasm.' This perspective article examines that historical opposition and its implications for the field's credibility. Drawing lessons from history can aid clinical research in psychiatry amid drug policy reform.
CNS spectrums
June 1, 2024
Jennifer Kern Sliwa, Ronaldo R Naranjo, Ibrahim Turkoz et al.
5 citations
In adults with treatment-resistant depression, adding esketamine nasal spray to a newly initiated oral antidepressant led to greater improvement in depressive symptoms than oral antidepressant plus placebo spray. Across two short-term trials, the group receiving esketamine plus oral antidepressant showed a mean reduction of 12.8 points on the Patient Health Questionnaire-9 (PHQ-9) at 28 days, compared with 10.3 points in the placebo group, a statistically significant difference. 77.1% of patients in the esketamine group achieved a clinically meaningful improvement (at least a 6-point drop) versus 64% in the placebo group. In a separate relapse-prevention study, 57.3% of patients on esketamine plus oral antidepressant maintained remission (PHQ-9 score ≤4) versus 44.2% on oral antidepressant plus placebo. The self-reported PHQ-9 results aligned with clinician-rated Montgomery-Åsberg Depression Rating Scale scores.
CNS spectrums
November 20, 2024
Angela T H Kwan, Moiz Lakhani, Gurkaran Singh et al.
4 citations
Ketamine shows potential for treating PTSD, OCD, and alcohol use disorders beyond its established use for depression. A systematic review and meta-analysis of 44 studies found that ketamine significantly reduced PTSD symptoms measured by the PCL-5 (average decrease of 28 points) and CAPS-5 (average decrease of 14 points), and OCD symptoms measured by the Y-BOCS (average decrease of 8 points). For alcohol use disorders, ketamine treatment was associated with reduced urge to drink, higher abstinence rates, and longer time to relapse. However, the small number of randomized controlled trials highlights the need for more research on ketamine's short- and long-term benefits and risks for these conditions.
CNS spectrums
August 12, 2025
Gia Han Le, Sabrina Wong, Stavroula Bargiota et al.
3 citations
G protein-coupled receptors (GPCRs) are involved in many bodily processes. Traditional drug classification divides ligands into agonists or antagonists. Biased agonism is a newer concept where a drug selectively activates one intracellular signaling pathway over another, such as G protein versus β-arrestin pathways. This narrative review of literature up to April 2025 describes distinct mechanisms of antagonism and agonism beyond conventional models. Biased agonism has shown potential for greater efficacy, as with the incretin receptor agonist tirzepatide, and improved safety, as with certain serotonergic psychedelics and opioids. Preclinical evidence suggests biased agonism could improve psychiatric and neurological treatments by differentially activating pathways, pending clinical validation.
CNS spectrums
December 12, 2024
Alberto Carrara
2 citations
A neuroethical framework integrates neuroscience and philosophy to examine how different levels of consciousness—from interoception to self-awareness—shape free will and autonomy, especially in psychiatric and neurological disorders. The analysis proposes a multidimensional, bottom-up approach linking neurobiological processes to distinct types of freedom, such as 'intero-freedom' tied to internal bodily states and 'self-freedom' linked to higher self-awareness. This stratification shows how neurological conditions can impair patients' freedom of choice, raising ethical concerns. The framework aims to guide more tailored treatments that restore autonomy and respect dignity, advocating for healthcare policies that enhance personal freedom for those with mental health challenges.