CNS drugs
April 1, 2013
Jerome Sarris, Erica Mcintyre, David A Camfield
154 citations
A narrative review of plant-based medicines with both preclinical and clinical evidence for anxiety identified 21 herbs tested in human trials. Chronic use of Piper methysticum, Matricaria recutita, Ginkgo biloba, Scutellaria lateriflora, Silybum marianum, Passiflora incarnata, Withania somniferum, Galphimia glauca, Centella asiatica, Rhodiola rosea, Echinacea spp., Melissa officinalis, and Echium amoenum showed support for treating various anxiety disorders. Acute anxiolytic activity was found for Centella asiatica, Salvia spp., Melissa officinalis, Passiflora incarnata, and Citrus aurantium. Bacopa monnieri showed anxiolytic effects in people with cognitive decline. Current evidence does not support Hypericum perforatum or Valeriana spp. for any anxiety disorder. Conclusions are tempered by methodological issues like small sample sizes and non-replication.
CNS drugs
November 1, 2024
Roger S. McIntyre, Rakesh Jain
58 citations
Glutamate signaling has emerged as a promising target for treating major depressive disorder (MDD), a chronic condition where standard monoamine antidepressants often have delayed effects and low remission rates. This narrative review describes how glutamate dysregulation is linked to depression, based on preclinical evidence and the rapid improvement seen with ketamine in a proof-of-concept trial. While many NMDA-targeted therapies have been investigated in phase 2 or 3 trials, most were discontinued. However, two glutamate-targeted antidepressants are now FDA-approved: nasal esketamine (Spravato) for treatment-resistant depression and MDD with suicidal ideation, and oral dextromethorphan-bupropion (Auvelity) for MDD in adults. These approvals highlight glutamate's role and offer new treatment options.
CNS drugs
September 1, 2023
Antonio Inserra, Alexandre Piot, Danilo De Gregorio et al.
17 citations
Anxiety disorders are a leading cause of disability, and over half of affected individuals do not respond to standard treatments. This review of preclinical and clinical research on LSD finds that while it can worsen anxiety in the short term, it produces lasting reductions in anxiety. Only two randomized controlled trials combining LSD with psychotherapy have been conducted in patients with anxiety disorders, showing good safety and sustained decreases in anxiety. The effects may involve serotonin receptors and brain networks such as the default mode network. It remains unknown whether LSD works alone or only with psychotherapy, and whether microdosing produces the same long-term benefits as full doses.
CNS drugs
October 1, 2024
Anton Gomez-Escolar, Daniel Folch-Sanchez, Joanna Stefaniuk et al.
16 citations
Mental health disorders and substance use disorders (SUDs) contribute greatly to the global burden of disease. Psychedelics, including entactogens and dissociative substances, are being explored for SUD treatment but have less clinical evidence than for depression or PTSD. This narrative review discusses current research, therapeutic potential, and safety of psilocybin, LSD, ketamine, MDMA, and ibogaine in SUD treatment. It provides a balanced overview of potential benefits and harms in clinical settings, highlights the need for more research, and points out limitations and challenges to be addressed in future studies.
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.
CNS drugs
August 1, 2024
Liliana Patarroyo-Rodriguez, Stefanie Cavalcanti, Jennifer L Vande Voort et al.
13 citations
Anhedonia, the inability to feel pleasure, is a symptom that appears in many mental disorders beyond just depression and schizophrenia, and it is linked to worse outcomes such as higher suicide risk and poor treatment response. Although brain imaging and biomarkers have improved understanding, the neural basis of anhedonia is still not fully known. Ketamine, a fast-acting antidepressant, also seems to reduce anhedonia through a separate mechanism from its antidepressant effects. Other potential treatments are being explored, but many questions remain, highlighting the need for more research.
CNS drugs
December 1, 2023
Niloufar Pouyan, Farnaz Younesi Sisi, Alireza Kargar et al.
12 citations
A review of 28 clinical studies with 477 participants examined how lysergic acid diethylamide (LSD) affects reward processing, using the National Institute of Mental Health's Research Domain Criteria (RDoC) framework. LSD produced dose-dependent mood improvement in 20 short-term and 3 long-term studies. Its subjective and neural effects were linked to the 5-HT2A receptor. Animal studies suggested LSD could mildly reinforce conditioned place preference without aversion and reduce responsiveness to other rewards. Findings on reward learning were inconsistent but hinted at potential enhancements in associative learning. Reward valuation measures indicated possible reductions in effort expenditure for other reinforcers. The review identified areas for future research but noted limitations including diverse study designs not initially RDoC-oriented and potential bias from open-label human studies.
CNS drugs
April 1, 2025
Balwinder Singh
6 citations
Trauma is common, with lifetime exposure estimates from 70% for a single event to 31% for multiple events. Many recover, but some develop post-traumatic stress disorder (PTSD), a debilitating condition with a lifetime prevalence of 6.8%, higher among women and veterans. Only two FDA-approved medications exist, paroxetine and sertraline, alongside psychotherapies like trauma-focused cognitive behavioral therapy and EMDR. Early-phase trials of MDMA-assisted therapy (MDMA-AT) showed promise, leading to FDA breakthrough therapy status in 2017. Phase 3 trials found nearly 70% of participants no longer met PTSD diagnostic criteria. However, in 2024 the FDA voted against approval due to concerns about trial design, blinding failure, missing safety assessments, and potential misconduct. Ongoing research must address blinding, long-term safety, and therapy variability.
CNS drugs
December 1, 2024
Ruyun Liu, Ning Liu, Lin Ma et al.
5 citations
Major depressive disorder is a severe mental illness whose current medications often work slowly and cause side effects. The N-methyl-D-aspartate receptor (NMDAR), a type of glutamate-gated ion channel, is linked to depression based on preclinical and clinical research. The NMDAR antagonist ketamine produces rapid and lasting antidepressant effects but has psychotomimetic effects and addiction potential that limit its use. Over the past decade, evidence suggests that enhancing NMDAR function, particularly through positive allosteric modulators (PAMs), may offer antidepressant benefits with improved safety. This narrative review presents that approach as a potential novel strategy for treating depression.
CNS drugs
July 10, 2025
Eric A Miller, Christy Capone, Erica Eaton et al.
4 citations
Psychedelics have been investigated as a treatment for alcohol use disorder since the 1950s, with over a dozen clinical trials of LSD and recent trials of psilocybin and ayahuasca. Observational studies consistently show promising results, but placebo-controlled trials have produced inconsistent outcomes and methodologies. This review characterizes foundational studies, emphasizing key design factors such as the presence of a placebo (e.g., ephedrine, dextroamphetamine, diphenhydramine, or low-dose LSD) and non-pharmacological factors like treatment setting and psychotherapy. It also examines candidate mechanisms of action through a biopsychosocial lens, spanning cellular neuroplasticity, cognitive neuroscience, subjective experience, and social connection, highlighting findings on efficacy and potential mechanisms to guide future research.
CNS drugs
September 1, 2024
Emmanuelle A. D. Schindler
2 citations
Interest in using psychedelics and other psychoactive compounds to treat headache disorders is increasing. Although people have long reported therapeutic benefits from these substances, formal clinical trials have only recently begun. The effectiveness of any treatment depends on the specific headache disorder, the particular drug, and how it is used; no single protocol works for all headaches or drugs. This article discusses the careful considerations needed when evaluating classic psychedelics, ketamine, and cannabinoids as potential headache medicines.
CNS drugs
January 17, 2026
Gaëlle Rached, Anna Campana, Dimitri Fiani et al.
1 citation
Monoamine oxidase inhibitors (MAOIs) can be used safely in some patients who use psychoactive substances, but certain combinations pose potentially fatal risks. This narrative review of 219 publications found that combining MAOIs with amphetamines, the empathogen MDMA, opioids with strong serotonergic reuptake inhibition (e.g., meperidine, tramadol), or alcoholic beverages high in tyramine can lead to serotonin toxicity, hypertensive emergencies, or death. In contrast, MAOI treatment of patients who use low-tyramine alcohol, caffeine, cannabis, nicotine, sedatives, and some classic hallucinogens can likely be managed with careful monitoring. No robust human data support MAOIs as effective treatments for substance use disorders themselves.
CNS drugs
June 1, 2025
Sijia Zhang, Houtan Afshar, Peter J Colvonen et al.
1 citation
Repeated ketamine or esketamine sessions significantly reduced depression and PTSD symptoms in veterans. However, those who also had traumatic brain injury (TBI) and severe obstructive sleep apnea (OSA) did not show improvement in depression, suggesting that these comorbidities may require alternative or pre-treatment before starting ketamine or esketamine therapy.
CNS drugs
February 1, 2026
Matheus G Marques, Liliana Patarroyo-Rodriguez, Balwinder Singh
Bipolar disorder affects about 40 million people worldwide, with depression as its most disabling phase. Current treatments often work slowly, prompting interest in psilocybin, a psychedelic compound being studied in clinical trials combined with psychotherapy. Early research in bipolar II disorder (19 participants) shows encouraging results, but evidence is limited. Safety concerns include risk of mood switching and drug interactions. Regulatory hurdles, infrastructure needs, and uncertainties about the role of the psychedelic experience, especially with common bipolar medications, remain. Cautious research is needed to assess psilocybin's safety and efficacy for bipolar depression, particularly for bipolar I disorder and long-term outcomes.