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.

10 papers

Addiction

Based on 33 papers

Researchers are testing several new and old approaches to treat addiction. The most attention is on psychedelic-assisted psychotherapy — that is, giving a drug like psilocybin, MDMA, or ibogaine together with careful therapy — and on new drug compounds tested in animals. Some early clinical trials and many reviews call these approaches “promising,” but most evidence is still limited, mixed, or from small studies. At the same time, for some substances like methamphetamine there are no approved medicines that clearly reduce use. Animal studies and new chemical versions of old drugs show strong early results, but human safety and larger trials are still needed. Researchers also stress that the drug effect and the therapy around it (preparation, setting, and follow-up) both matter for how well treatment works.

Key findings

  • Giving psychedelic drugs together with psychotherapy has shown promising results in small clinical trials and reviews for some addictions and other mental illnesses. 15063 15051 15085 15073
  • MDMA-assisted therapy has the strongest and most consistent trial evidence for PTSD, and psychedelic therapies more broadly have growing but still limited evidence for some forms of addiction. 15063 15053 15085
  • Ibogaine has shown signs of helping with addiction in some studies, but it carries serious heart and neurological risks that stopped some earlier trials. 15085
  • Researchers made new “oxa-iboga” compounds that in lab heart-cell tests did not show the heart-rhythm risk of ibogaine, and in rats a single dose reduced long-term opioid use and relapse-like behavior. 15115
  • For methamphetamine use disorder, there are currently no approved medicines that clearly reduce cravings or lead to lasting abstinence in people. 15116
  • 5‑MeO‑DMT (a fast, short-acting psychedelic) is being explored as a possible treatment for alcohol use disorder, but the evidence is early; human reports show powerful subjective effects and brain-rhythm changes that might be relevant. 15122
  • Good preparation and therapeutic support before and after a psychedelic session — things like safety screening, building trust, and planning the setting — are widely agreed to be important for safety and likely for outcomes, but exact methods vary across studies. 15065 15051 15063
  • Some promising findings come from small studies, animal work, or historical reports. That means results may not always apply to people yet, and researchers note limits like small sample sizes and underrepresentation of people of color in trials. 15073 15095 15085
  • When ketamine is used under medical supervision for depression, large reviews find few clear cases of dependence, but patients still report worry about addictive risk and want more long-term safety data and monitoring. 8828 12365
  • In some communities, traditional healers use plant remedies for alcohol-related problems. These reports document local practices but do not prove those plants are effective in controlled clinical trials. 15118

Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms

Antonio Inserra, Danilo De Gregorio, Gabriella Gobbi
Pharmacological Reviews Summary & key facts 2020 215 citations

This review looked at many studies about classic psychedelics (like psilocybin and LSD), MDMA, ketamine, and plant medicines (like ayahuasca). The authors explain how these drugs can change the brain’s wiring, calm inflammatory processes, and shift key brain chemicals. Those actions may help explain why small clinical trials and animal…

Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies Tryptophan and brain disorders Ayahuasca Ketamine

Legal highs: staying on top of the flood of novel psychoactive substances

David Baumeister, Luis M. Tojo, Derek K. Tracy

This review explains the fast-growing problem of so-called "legal highs", which are better called novel psychoactive substances or NPS. Unknown labs keep making slightly different chemicals to avoid bans, and this led to about 80 new substances being spotted in one year. The paper groups these drugs into five main…

Forensic Toxicology and Drug Analysis Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies Cannabis Ketamine

A Multi-Level Analysis of Biological, Social, and Psychological Determinants of Substance Use Disorder and Co-Occurring Mental Health Outcomes

Cecilia Ilaria Belfiore, Valeria Galofaro, Deborah Cotroneo, Alessia Lopis, Isabella Tringali, Valeria Denaro, et al.
Psychoactives Summary & key facts 2024 40 citations

Researchers looked at sixty studies to see how biology, social life, and psychology mix together to affect substance use problems and mental health. They found that brain systems, genes, childhood experiences, parenting, personality, and existing mood or anxiety problems all interact. This makes addiction and related psychiatric symptoms complicated, especially…

Bipolar Disorder and Treatment Cannabis and Cannabinoid Research Child and Adolescent Psychosocial and Emotional Development Cannabis Other

Recommendations for Reducing the Risk of Cannabis Use-Related Adverse Psychosis Outcomes: A Public Mental Health-Oriented Evidence Review

Benedikt Fischer, Wayne Hall, Thiago Marques Fidalgo, Eva Hoch, Bernard Le Foll, María Elena Medina‐Mora, et al.
Journal of Dual Diagnosis Summary & key facts 2023 24 citations

This paper reviewed studies since 2016 to identify cannabis-related factors linked with higher risk of psychosis. It found that personal and genetic vulnerability, earlier age of first use, more frequent use, higher-THC products, how cannabis is taken, and using other drugs all raise the odds of cannabis-related psychosis. Evidence that…

Bipolar Disorder and Treatment Cannabis and Cannabinoid Research Homelessness and Social Issues Cannabis

Ketamine treatment for depression: qualitative study exploring patient views

Sagar Jilka, Clarissa Mary Odoi, Emma Wilson, Sazan Meran, Sara Simblett, Til Wykes
PubMed Central (PMC) Summary & key facts 2021 23 citations

Researchers ran three focus groups with 14 people who have depression but had not tried ketamine. Participants saw ketamine as promising but were worried about its reputation as a party drug, possible long-term harms, and how it would be monitored. They wanted clear public information, better evidence about long-term safety,…

Alcoholism and Thiamine Deficiency Treatment of Major Depression Tryptophan and brain disorders Ketamine

Pharmacological Treatments for Methamphetamine Use Disorder: Current Status and Future Targets

Justin R. Yates

This paper reviews what medicines have been tested to treat methamphetamine use disorder in animals and people. The authors say there are still no approved drugs that reliably cut cravings or help people stop using meth. Some medicines helped in animal tests but did not lower meth use in people,…

Cholinesterase and Neurodegenerative Diseases Neuroscience and Neuropharmacology Research Neurotransmitter Receptor Influence on Behavior Other

Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models

Václav Havel, Andrew C. Kruegel, Benjamin Bechand, Scot McIntosh, Leia S. Stallings, Alana Hodges, et al.
Nature Communications Summary & key facts 2024 14 citations

Researchers made new versions of the psychedelic drug ibogaine, called oxa-iboga compounds, by changing part of the chemical structure. In lab tests on human heart cells these new compounds did not show the heart-rhythm risk that ibogaine can cause. In tests with male rats, a single dose or a short…

Alkaloids: synthesis and pharmacology Chemical synthesis and alkaloids Neurotransmitter Receptor Influence on Behavior Ibogaine

Is there a risk of addiction to ketamine during the treatment of depression? A systematic review of available literature

Gianmarco Ingrosso, Anthony J. Cleare, Mário F. Juruena
PubMed Summary & key facts 2025 13 citations

This systematic review looked at 16 studies of ketamine used to treat adults with depression, covering 2,174 patients. The authors found few clear cases of tolerance or dependence (four patients) and conclude that, overall, ketamine appears relatively safe for depression when given under medical supervision, with careful monitoring and dosing.…

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

The potential of 5‐methoxy‐N,N‐dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action

Stephan Tap
Addiction Biology Summary & key facts 2024 11 citations

This paper is a first look at whether the fast-acting psychedelic 5‑MeO‑DMT might help people with alcohol use disorder. The authors reviewed existing studies in humans and animals and found early signs that 5‑MeO‑DMT can cause intense mystical feelings and a loss of self-boundaries, and that it changes brain rhythms…

Cannabis and Cannabinoid Research Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies LSD Other

Ayahuasca and Its Main Component N,N-Dimethyltryptamine (DMT) for the Treatment of Mental Disorders: Mechanisms of Action, Clinical Studies, and Tools to Explore the Human Mind

Alice Melani, Giorgia Papini, Marco Bonaso, Letizia Biso, Shivakumar Kolachalam, Nicola Luigi Bragazzi, et al.
Biomedicines Summary & key facts 2026 0 citations

This paper reviews research on ayahuasca and its main ingredient, DMT, and how they might help with mental health. Ayahuasca is a plant brew that makes DMT work when you drink it because it also contains chemicals that stop the body from breaking DMT down. Lab studies and a small…

Alkaloids: synthesis and pharmacology Forensic Toxicology and Drug Analysis Psychedelics and Drug Studies Ayahuasca MDMA
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