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.

97 papers

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

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

Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression

Guy M. Goodwin, Scott T. Aaronson, Oscar Alvarez, Peter C. Arden, Annie Baker, James Bennett, et al.
New England Journal of Medicine Summary & key facts 2022 980 citations

Compass Pathways reported early results from its first Phase 3 trial of synthetic psilocybin (COMP360) for treatment‑resistant depression. In 258 patients, the 25 mg dose showed a statistically significant improvement versus placebo on the MADRS depression scale at week 6 (a 3.6‑point difference, p < 0.001). The Data and Safety…

Chemical synthesis and alkaloids Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies

Review of the Endocannabinoid System

Hui‐Chen Lu, Ken Mackie

This review describes the endocannabinoid system (ECS) as a widespread network of natural cannabinoids, cannabinoid receptors (mainly CB1 and CB2), and the enzymes that make and break those chemicals. The ECS helps shape brain development and adjusts how neurons communicate. The authors note that THC is the main psychoactive part…

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

Psychedelics reopen the social reward learning critical period

Romain Nardou, Edward J. Sawyer, Young Jun Song, M. F. Wilkinson, Yasmin Padovan‐Hernandez, Júnia L. de Deus, et al.
Nature Summary & key facts 2023 303 citations

Researchers gave different psychedelic drugs to mice and found the drugs could reopen a window of brain plasticity used for learning social rewards. This reopened window went along with changes in a social hormone system in a key reward area of the brain and with changes in genes that control…

Chemical synthesis and alkaloids Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies Psilocybin

Towards an understanding of psychedelic-induced neuroplasticity

Abigail E. Calder, Gregor Hasler
Neuropsychopharmacology Summary & key facts 2022 272 citations

This review looks at studies about classic psychedelics (like LSD, psilocybin, and DMT/ayahuasca) and their effects on neuroplasticity — the brain’s ability to change. Animal studies show these drugs can raise genes tied to plasticity and cause dendrite and synapse growth. Human results are mixed, especially when studies use blood…

Biochemical Analysis and Sensing Techniques Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies

Individual differences in extraversion and dopamine genetics predict neural reward responses

Michael X Cohen, Jennifer Young, Jong Min Baek, Christopher Kessler, Charan Ranganath
Cognitive Brain Research Summary & key facts 2005 271 citations

Researchers ran two fMRI studies using a gambling task to see how personality and a dopamine gene relate to brain reward signals. Rewards were given either right after a response (Study 1) or after a 7.5-second wait (Study 2). The studies found that people’s extraversion scores and whether they carried…

Functional Brain Connectivity Studies Neural and Behavioral Psychology Studies Neurotransmitter Receptor Influence on Behavior

The social brain and reward: social information processing in the human striatum

Jamil P. Bhanji, Mauricio R. Delgado

This 2014 review explains that the brain’s reward system — especially a region called the striatum — responds not only to things like food or money but also to social outcomes such as praise. The authors summarize many studies showing that the striatum carries signals when people evaluate social rewards,…

Neural and Behavioral Psychology Studies Neuroendocrine regulation and behavior Neurotransmitter Receptor Influence on Behavior

Inclusion of people of color in psychedelic-assisted psychotherapy: a review of the literature

Timothy I. Michaels, Jennifer Purdon, Alexis Collins, Monnica T. Williams
BMC Psychiatry Summary & key facts 2018 247 citations

The authors reviewed psychedelic-assisted psychotherapy studies published from 1993 to 2017 to see how many people of color took part. They found 18 studies with about 280 people. About 82% of participants were non-Hispanic White, while only small percentages were African American, Latino, Asian, indigenous, or mixed race. Because so…

Natural Compound Pharmacology Studies Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies Ayahuasca LSD

Attention-deficit-hyperactivity disorder and reward deficiency syndrome

Kenneth Blum, Amanda Lih Chuan Chen, Eric R. Braverman, David E. Comings, Thomas J.H. Chen, Vanessa Arcuri, et al.

This paper reviews genetic studies that link several genes to higher risk for ADHD. It says problems in the brain's reward system—especially low dopamine activity—may make people seek things that raise dopamine. The authors propose that these gene variants form a “reward deficiency syndrome” (RDS) that may include ADHD, and…

Attention Deficit Hyperactivity Disorder Bipolar Disorder and Treatment Neurotransmitter Receptor Influence on Behavior

A systematic study of microdosing psychedelics

Vince Polito, Richard J. Stevenson
PLoS ONE Summary & key facts 2019 234 citations

This observational study followed 98 people who microdosed psychedelics over six weeks and found that people reported better psychological functioning on days they took a microdose, but there was little evidence that those effects lasted into the next days. Among 63 people who completed formal tests before and after the…

Chemical synthesis and alkaloids Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies

Psychedelic-Assisted Psychotherapy: A Paradigm Shift in Psychiatric Research and Development

Eduardo Ekman Schenberg
Frontiers in Pharmacology Summary & key facts 2018 229 citations

This paper describes psychedelic-assisted psychotherapy, which means giving drugs like ketamine, MDMA, psilocybin, LSD or ibogaine together with guided therapy. The authors say this approach has shown promising safety and benefits so far, even for people who did not get better with usual treatments. They also argue that these therapies…

Chemical synthesis and alkaloids Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies Ibogaine Ketamine
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