Hallucinogenic drugs and their potential for treating fear-related disorders: Through the lens of fear extinction.
Emilija Glavonic, Milos Mitic, Miroslav Adzic
Journal of Neuroscience Research April 1, 2022 DOI: 10.1002/jnr.25017 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Ketamine MDMA Serotonin |
| Keywords | Glutamic acid Neuronal plasticity Psychotherapy |
| Citations | 20 |
| Key findings | MDMA and ketamine are highlighted as the most effective hallucinogenic therapeutics for fear-related disorders, potentially improving exposure therapy outcomes through enhanced neuroplasticity and reduced amygdala reactivity. |
Abstract
Fear-related disorders, mainly phobias and post-traumatic stress disorder, are highly prevalent, debilitating disorders that pose a significant public health problem. They are characterized by aberrant processing of aversive experiences and dysregulated fear extinction, leading to excessive expression of fear and diminished quality of life. The gold standard for treating fear-related disorders is extinction-based exposure therapy (ET), shown to be ineffective for up to 35% of subjects. Moreover, ET combined with traditional pharmacological treatments for fear-related disorders, such as selective serotonin reuptake inhibitors, offers no further advantage to patients. This prompted the search for ways to improve ET outcomes, with current research focused on pharmacological agents that can augment ET by strengthening fear extinction learning. Hallucinogenic drugs promote reprocessing of fear-imbued memories and induce positive mood and openness, relieving anxiety and enabling the necessary emotional engagement during psychotherapeutic interventions. Mechanistically, hallucinogens induce dynamic structural and functional neuroplastic changes across the fear extinction circuitry and temper amygdala's hyperreactivity to threat-related stimuli, effectively mitigating one of the hallmarks of fear-related disorders. This paper provides the first comprehensive review of hallucinogens' potential to alleviate symptoms of fear-related disorders by focusing on their effects on fear extinction and the underlying molecular mechanisms. We overview both preclinical and clinical studies and emphasize the advantages of hallucinogenic drugs over current first-line treatments. We highlight 3,4-methylenedioxymethamphetamine and ketamine as the most effective therapeutics for fear-related disorders and discuss the potential molecular mechanisms responsible for their potency with implications for improving hallucinogen-assisted psychotherapy.
Comparable studies
Other narrative reviews on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Human Pharmacology of MDMA | 2004 | Review | |
| Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research | 2001 | Review | |
| 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans | 1994 | Review | |
| (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals | 2000 | Review | |
| Amphetamine toxicities | 2010 | Review |
Citations in the library
Cited by 16
- Treatment of Posttraumatic Stress Disorder: A State-of-the-art Review. Current Neuropharmacology 2024
- Neural Mechanisms and Psychology of Psychedelic Ego Dissolution Pharmacological Reviews September 9, 2022
- The Psychedelic Future of Post-Traumatic Stress Disorder Treatment Current Neuropharmacology January 5, 2024
- Pattern breaking: a complex systems approach to psychedelic medicine Neuroscience of Consciousness 2023
- Alleviating anxiety and taming trauma: Novel pharmacotherapeutics for anxiety disorders and posttraumatic stress disorder Neuropharmacology January 6, 2023
and 11 more in the library
Cites 102
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
and 97 more in the library