Frontier mental health research: psychedelics & drug studies

Each month our editorial team sifts through hundreds of papers and curates notable findings—for practitioners and informed readers who want to stay current with the evidence. Subscribe to the monthly Research Digest for expert analysis and concise summaries of key papers.

165 papers

Antidepressant effects of ketamine in depressed patients

Robert Berman, Angela Cappiello, Amit Anand, Dan A. Oren, George R. Heninger, Dennis S. Charney, et al.
Biological Psychiatry Summary & key facts 2000 3,784 citations

In a small, carefully controlled study, seven people with major depression each received a single low-dose ketamine infusion on one day and a saline infusion on another day, without anyone knowing which was which. People who got ketamine showed clear improvement in their depressive symptoms within three days, while those…

Functional Brain Connectivity Studies Treatment of Major Depression Tryptophan and brain disorders Ketamine

A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression

Carlos A. Zarate, Jaskaran Singh, Paul J. Carlson, Nancy E. Brutsché, Rezvan Ameli, David A. Luckenbaugh, et al.
Archives of General Psychiatry Summary & key facts 2006 3,698 citations

In a small, controlled study of 18 people with treatment-resistant major depression, a single intravenous dose of the NMDA receptor antagonist ketamine (0.5 mg/kg) produced rapid drops in depression scores. Improvement began within about 2 hours and remained statistically significant compared with placebo for up to 1 week. The study…

Neurotransmitter Receptor Influence on Behavior Treatment of Major Depression Tryptophan and brain disorders

Taming THC: potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects

Ethan B. Russo
British Journal of Pharmacology Summary & key facts 2011 1,481 citations

Some research suggests that whole-plant cannabis compounds (like THC, CBD, other cannabinoids, terpenes, and flavonoids) can interact so the plant’s effects differ from CBD alone. Healthline explains three CBD types — full-spectrum, broad-spectrum, and isolate — and notes legal, safety, and labeling limits. The article says there is evidence for…

Biochemical Analysis and Sensing Techniques Cannabis and Cannabinoid Research GABA and Rice Research

Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial

James W. Murrough, Dan V. Iosifescu, Lee C. Chang, Rayan K. Al Jurdi, Charles E. Green, Andrew M. Perez, et al.
American Journal of Psychiatry Summary & key facts 2013 1,186 citations

Researchers tested a single intravenous dose of ketamine in 73 people with major depression that had not gotten better with usual treatments. In a two-site, double-blind trial, people were randomly given either ketamine or an active placebo (the anesthetic midazolam). Twenty-four hours after the infusion, people who got ketamine were…

Neuroscience and Neuropharmacology Research Treatment of Major Depression Tryptophan and brain disorders Ketamine

An Introduction to the Endogenous Cannabinoid System

Hui‐Chen Lu, Ken Mackie
Biological Psychiatry Summary & key facts 2015 1,165 citations

The endocannabinoid system (ECS) is a widespread brain signaling system made of cannabinoid receptors, naturally made lipid messengers, and the enzymes that make and break those messengers. The two best-studied messengers are 2-AG and anandamide, and they are produced and degraded by different enzyme pathways. CB1 receptors are common in…

Cannabis and Cannabinoid Research Neuroscience and Neuropharmacology Research Neurotransmitter Receptor Influence on Behavior

Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study

Vanina Popova, Ella Daly, Madhukar H. Trivedi, Kimberly Cooper, Rosanne Lane, Pilar Lim, et al.
American Journal of Psychiatry Summary & key facts 2019 839 citations

Researchers tested a nasal spray form of esketamine together with a newly started oral antidepressant in adults whose depression had not improved after trying at least two antidepressants. Over four weeks, people who got esketamine plus a new antidepressant had faster and larger drops in depression symptoms than those who…

Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes Treatment of Major Depression Tryptophan and brain disorders Ketamine

Antioxidative and Anti-Inflammatory Properties of Cannabidiol

Sinemyiz Atalay, Iwona Jarocka-Karpowicz, Elźbieta Skrzydlewska
Antioxidants Summary & key facts 2019 765 citations

This review says cannabidiol (CBD) is a non‑psychoactive cannabis compound that has antioxidant and anti‑inflammatory actions in lab and some clinical studies. CBD can act directly to neutralize reactive molecules and indirectly by changing cell signals and antioxidant enzymes. Experiments in cells and animals show CBD lowers markers of oxidative…

Cannabis and Cannabinoid Research Diet, Metabolism, and Disease GABA and Rice Research

Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression

Ella Daly, Madhukar H. Trivedi, Adam Janik, Honglan Li, Yun Zhang, Xiang Li, et al.
JAMA Psychiatry Summary & key facts 2019 726 citations

This phase 3, double-blind trial tested whether continuing esketamine nasal spray plus an oral antidepressant could delay relapse in adults with treatment-resistant depression who had already improved after an initial esketamine course. Of 297 patients who entered the randomized phase, continuing esketamine reduced relapse compared with switching to placebo nasal…

Mental Health Research Topics Treatment of Major Depression Tryptophan and brain disorders

Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation

Roger S. McIntyre, Joshua D. Rosenblat, Charles B. Nemeroff, Gerard Sanacora, James W. Murrough, Michael Berk, et al.
American Journal of Psychiatry Summary & key facts 2021 646 citations

A group of international mood-disorder experts reviewed the research on ketamine and esketamine for adults whose depression did not get better with usual antidepressants. They found that these drugs work differently from standard antidepressants and can lift symptoms more quickly for some people with treatment-resistant depression. However, the experts also…

Mental Health Research Topics Treatment of Major Depression Tryptophan and brain disorders Ketamine

Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions

Roger S. McIntyre, Mohammad Alsuwaidan, Bernhard T. Baune, Michael Berk, Koen Demyttenaere, Joseph F. Goldberg, et al.
World Psychiatry Summary & key facts 2023 586 citations

Treatment-resistant depression means depression that does not get better after usual treatments. Scientists do not all agree on one clear definition, which makes it hard to know exactly how common it is or which treatments work best. Using the definition that regulators often use, about 30% of people with depression…

Electroconvulsive Therapy Studies Transcranial Magnetic Stimulation Studies Treatment of Major Depression Ketamine

A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans

Sophie Millar, Nicole L. Stone, Andrew Yates, Saoirse E. O’Sullivan
Frontiers in Pharmacology Summary & key facts 2018 522 citations

This review collected human studies on how cannabidiol (CBD) is absorbed, distributed, and cleared. From 792 records, 24 studies reported pharmacokinetic (PK) data. Results varied by how CBD was given and by formulation. For example, smoking produced faster and higher blood levels than oral or oromucosal routes. The authors concluded…

Alcohol Consumption and Health Effects Cannabis and Cannabinoid Research Diet, Metabolism, and Disease

Chronic Pain Among Adults — United States, 2019–2021

S. Michaela Rikard, Andrea E. Strahan, Kristine M Schmit, Gery P. Guy

This CDC analysis used the 2019–2021 National Health Interview Survey to estimate how common chronic pain is among U.S. adults. In 2021, about 20.9% of adults (51.6 million people) reported pain on most days or every day for the past three months. About 6.9% (17.1 million people) had high-impact chronic…

Musculoskeletal pain and rehabilitation Opioid Use Disorder Treatment Pain Management and Opioid Use
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