Psychedelic medicines for mood disorders: current evidence and clinical considerations
Jerome Sarris, Diego Pinzon Rubiano, Kimberley Day, Nicole Leite Galvão‐coelho, Daniel Perkins
Current Opinion in Psychiatry November 15, 2021 DOI: 10.1097/yco.0000000000000759 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Randomized Placebo-controlled Peer reviewed |
|---|---|
| Interventions | Psilocybin N N-dimethyltryptamine/ayahuasca Lysergic acid diethylamide MDMA microdosing of psychedelics |
| Topics | Anxiety MDMA Psilocybin Serotonin |
| Keywords | Mood disorders Hallucinogen Clinical psychology |
| Citations | 12 |
| Key findings | Psychedelic-assisted therapy shows encouraging results for mood disorders, but definitive Phase III evidence is lacking except for MDMA for PTSD. |
Abstract
Purpose of review Despite advances in treatment modalities for mood disorders over recent decades, further therapeutic options are still required. Increased research is occurring, with the pursuit of psychedelic-based pharmacotherapies for a range of mood disorders and other conditions. Recent findings Serotonergic psychedelics have been found to modulate brain networks underlying various psychiatric disorders, as well promoting neurogenesis and neuroplasticity. Randomized placebo-controlled trials have found psilocybin with psychological support effective at treating depression, including treatment-resistant depression; with emergent research also signalling N , N -dimethyltryptamine/ayahuasca also as a potential option for the treatment of depression. Lysergic acid diethylamide has been found to have anxiolytic effects, whereas 3,4-methylenedioxymethamphetamine (MDMA) has been used effectively to treat post-traumatic stress disorder (PTSD), with Phase III clinical trial evidence. Microdosing of psychedelics is a growing phenomenon that has shown benefits in some preclinical data; however, a recent self-directed controlled trial reported no evidence of improved mood. Summary Current research with medicinal psychedelics, usually as an adjunct to psychotherapy, has shown encouraging results in treating mood disorders. However, there are challenges regarding blinding and sample sizes remain small, and there have been no definitive Phase III studies (aside from MDMA for PTSD). Further work exploring novel formulations, interface with pharmacogenomics and the microbiome, and inflammatory pathways can be advised.
Comparable studies
Other narrative reviews on MDMA for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Clinical applications of hallucinogens: A review. | 2016 | Review | |
| MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults. Individuals who have received MDMA for research purposes | 2016 | Review | n = 1,133 |
| Long-Term Neuropsychiatric Consequences of "Ecstasy" (MDMA): A Review Chronic recreational users of ecstasy (MDMA), including adolescents | 2002 | Review | |
| A review of emerging therapeutic potential of psychedelic drugs in the treatment of psychiatric illnesses | 2020 | Review | |
| Top Ten Tips Palliative Care Clinicians Should Know About Psychedelic-Assisted Therapy in the Context of Serious Illness. Palliative care clinicians and patients | 2022 | Review |
Citations in the library
Cited by 16
- Where do we go next in antidepressant drug discovery? A new generation of antidepressants: a pivotal role of AMPA receptor potentiation and mGlu2/3 receptor antagonism Expert Opinion on Drug Discovery August 8, 2022
- Chronic Treatment With Psilocybin Decreases Changes in Body Weight in a Rodent Model of Obesity Frontiers in Psychiatry May 18, 2022
- Role of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors and psychedelics in the treatment of major depressive disorder: A perspective on mechanistic insight and current status. European Journal of Pharmacology August 15, 2025
- Moderators of ayahuasca’s biological antidepressant action Frontiers in Psychiatry December 5, 2022
- Psilocybin for clinical indications: A scoping review Journal of Psychopharmacology August 13, 2024
and 11 more in the library
Cites 58
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
and 53 more in the library