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Does acute stress play a role in the lasting therapeutic effects of psychedelic drugs?


Psychedelic drugs, when used in the context of psychotherapy, can produce significant and long-lasting memories with enduring beneficial effects. Yet, the behavioral and neurobiological mechanisms that underlie these beneficial effects remain a mystery. Here, we suggest that both the quality and durability of memories of the drug-facilitated therapeutic experience may be mediated, in part, by the acute stress responses induced by the drugs. It is known that high doses of psychedelic drugs activate autonomic and hormonal stress responses. For evolutionarily adaptive reasons, acute stress is known to i) instill meaning to the immediate context in which it is experienced, and ii) lead to the formation of salient and lasting memories of the events surrounding the stress. Thus, the stress-inducing effect of psychedelic drugs may contribute to the reported sense of meaning, as well as the durability of the memory of the drug experience. When used in a therapeutic context these actions may i) enhance the salience of insights gained during the experience and ii) strengthen the memories formed by these experiences. Future empirical studies will help to determine whether acute stress contributes to the emotional significance and lasting effects of psychedelic-assisted psychotherapy.

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HdW wrote the manuscript, and MH and AKB provided valuable input and suggestions.

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Correspondence to H. de Wit.

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Competing interests

HdW is supported by PHS DA02812. HdW is a scientific advisor for Gilgamesh Pharmaceuticals and Awakn Life Sciences, and serves on the Board of Directors of PharmAla Biotech. MH is supported by the Swedish Research Council 2013–07434 and the Knut and Alice Wallenberg Foundation. He has in the past 5 years received consulting fees, research support, or other compensation from Indivior, Camurus, Molteni, BrainsWay, Aelis Farma, Lundbeck and Janssen Pharmaceuticals, and he is an Associate Editor of Neuropsychopharmacology. AKB has nothing to disclose.

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de Wit, H., Heilig, M. & Bershad, A.K. Does acute stress play a role in the lasting therapeutic effects of psychedelic drugs?. Neuropsychopharmacol. 48, 1422–1424 (2023).

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