Experience, plasticity, and context: Beyond single-level models of antidepressant action.
David Eckert
Journal of Psychopharmacology August 17, 2026 DOI: 10.1177/02698811261473402 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Neuroplasticity |
| Keywords | Psychedelics Psychoplastogens Subjective experience Treatment-resistant depression trd |
| Key points | Argues that psychedelic efficacy should not be framed as a binary between experience and mechanism, but as a complementary model where receptor signaling, network reorganization, subjective experience, and psychotherapeutic context interact. Subjective experience may be clinically meaningful without being biologically indispensable, and neuroplasticity is an enabling condition but not sufficient alone. |
Abstract
The re-emergence of serotonergic psychedelics has introduced rapid-acting antidepressant effects and has been widely described as a paradigmatic shift in depression treatment. Recently, there has been intense debate about whether the acute subjective effects of psychedelics are necessary for their therapeutic efficacy or merely byproducts of underlying neuroplastic processes. Recent conceptualizations of "psychoplastogens" emphasize rapid induction of neuroplasticity as a potential common pathway across mechanistically diverse rapid-acting antidepressants. Here, some argue that the psychedelic experience itself may not be required for enduring therapeutic change while others highlight the clinical and existential significance of the subjective experience and its integration within structured psychotherapeutic settings. This Perspective argues that the debate is often framed too narrowly as a binary opposition between experience and mechanism and opts for a complementary model in which receptor-level signalling, network reorganization, subjective experience, and psychotherapeutic context represent interacting dimensions of a single intervention architecture. Within this framework, subjective experience may be clinically meaningful without being biologically indispensable, while neuroplasticity may constitute an enabling condition without being sufficient in isolation. Rather than asking whether experience or mechanism is primary, the clinically relevant question becomes under which conditions, for which patients, and within which care structures different plasticity-inducing interventions, hallucinogenic or non-hallucinogenic, are most appropriate. This question is further complicated by methodological challenges in isolating those contributions empirically. Psychedelic research thus challenges not only neurobiological models of depression but also existing assumptions about how pharmacological and psychotherapeutic processes converge in antidepressant treatment.
Comparable studies
Other theoretical and historical papers on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics | 2020 | Theoretical or philosophical paper | |
| Does Psychedelic Therapy Have a Transdiagnostic Action and Prophylactic Potential? | 2021 | Theoretical or philosophical paper | |
| A complex systems perspective on psychedelic brain action. | 2023 | Theoretical or philosophical paper | |
| Critical Period Plasticity as a Framework for Psychedelic-Assisted Psychotherapy | 2021 | Theoretical or philosophical paper | |
| Therapeutic mechanisms of psychedelics and entactogens. | 2023 | Theoretical or philosophical paper |
Citations in the library
Cites 48
- 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
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Frontiers in Pharmacology January 17, 2018
- Global Street Food: la cocina de la calle Diseño interior 2009
and 43 more in the library