Disentangling the acute subjective effects of classic psychedelics from their enduring therapeutic properties.
Mazen A Atiq, Matthew R Baker, Jennifer L. Vande Voort, Maxemiliano V. Vargas, Doo-Sup Choi
Psychopharmacology May 14, 2024 DOI: 10.1007/s00213-024-06599-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Addiction Depression Psilocybin |
| Keywords | 5-ht2a Acute subjective effects Classic psychedelics Brain circuits Neurotransmitters Psychedelics hallucinogens Entheogens Neuroscience neuropsychiatry |
| Citations | 12 |
| Key findings | The review examines whether the acute subjective effects of classic psychedelics can be dissociated from their sustained therapeutic properties, considering evidence for non-psychedelic psychoplastogens. |
Abstract
Recent research with classic psychedelics suggests significant therapeutic potential, particularly for neuropsychiatric disorders. A mediating influence behind symptom resolution is thought to be the personal insight - at times, bordering on the mystical - one acquires during the acute phase of a psychedelic session. Indeed, current clinical trials have found strong correlations between the acute subjective effects (ASE) under the influence of psychedelics and their enduring therapeutic properties. However, with potential barriers to widespread clinical implementation, including the healthcare resource-intensive nature of psychedelic sessions and the exclusion of certain at-risk patient groups, there is an active search to determine whether ASE elimination can be accompanied by the retention of persisting therapeutic benefits of these class of compounds. Recognizing the aberrant underlying neural circuitry that characterizes a range of neuropsychiatric disorders, and that classic psychedelics promote neuroplastic changes that may correct abnormal circuitry, investigators are rushing to design and discover compounds with psychoplastogenic, but not hallucinogenic (i.e., ASE), therapeutic potential. These efforts have paved the discovery of 'non-psychedelic/subjective psychedelics', or compounds that lack hallucinogenic activity but with therapeutic efficacy in preclinical models. This review aims to distill the current evidence - both clinical and preclinical - surrounding the question: can the ASE of classic psychedelics be dissociated from their sustained therapeutic properties? Several plausible clinical scenarios are then proposed to offer clarity on and potentially answer this question.
Comparable studies
Other narrative reviews on psilocybin for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Psychedelics as anti-inflammatory agents Animal models and cellular studies | 2018 | Review | |
| Psychedelic Drugs in Biomedicine | 2017 | Review | |
| DARK Classics in Chemical Neuroscience: Psilocybin | 2018 | Review | |
| Psilocybin for treating substance use disorders? | 2016 | Narrative review |
Citations in the library
Cited by 12
- The intensity of the psychedelic experience is reliably associated with clinical improvements: A systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews May 1, 2025
- Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents Neuroscience & Biobehavioral Reviews September 20, 2024
- Psilocybin as Transformative Fast‐Acting Antidepressant: Pharmacological Properties and Molecular Mechanisms Fundamental and Clinical Pharmacology July 16, 2025
- Considering distinct positive emotions in psychedelic science. International Review of Psychiatry December 1, 2024
- Ethical Considerations Regarding Psychedelics for Clinical Pain Research. Journal of Pain Research 2024
and 7 more in the library
Cites 123
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- 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
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
and 118 more in the library