Psychedelic-Assisted Therapy for Substance Use Disorders and Potential Mechanisms of Action
Open accessAbstract
Substance use disorders (SUD) represent a significant public health issue with a high need for novel and efficacious treatment options. In light of this high unmet need, recent results reporting beneficial outcomes of psychedelic-assisted therapy in SUD are particularly relevant. However, several questions remain with regard to this treatment approach. The clinical mechanisms of action of psychedelic substances in the treatment of SUD are not well understood. Closing this knowledge gap is critical to inform and optimize the psychotherapeutic embedding of the acute substance administration. In this chapter, we discuss potential mechanisms that have implications on psychotherapeutic approaches including induced neuroplasticity, alterations in brain network connectivity, reward and emotion processing, social connectedness, insight, and mystical experiences. Furthermore, we outline considerations and approaches that leverage these mechanisms in order to optimize the therapeutic embedding by maximizing synergy between substance effects and psychotherapy. Understanding the mechanisms of action, developing psychotherapeutic approaches accordingly, and evaluating their synergistic efficacy in scientific studies will be critical to advance the framework of psychedelic-assisted therapy for addiction, create evidence-based approaches, and achieve the best treatment outcome for patients with SUD.
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This long-term dysregulation has been hypothesized to underpin the learning difficulties observed in patients with severe alcohol use disorder, constituting a major challenge to fostering beneficial change through psychotherapy.
“This long-term dysregulation has been hypothesized to underpin the learning difficulties observed in patients with sAUD, thereby constituting a major challenge to fostering beneficial change through psychotherapy [29].”
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‘Hitting Highs at Rock Bottom’: LSD Treatment for Alcoholism, 1950–1970
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Psychedelic Therapy Utilizing LSD in the Treatment of the Alcoholic Patient: A Preliminary Report
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Self-citationA motivational intervention trial to reduce cocaine use.
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Synaptic plasticity mechanisms common to learning and alcohol use disorderPreprint
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Flagged first, then by citations
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Rieser, N. M., Bitar, R., Halm, S., Rossgoderer, C., Gubser, L. P., Thévenaz, M., Kreis, Y., von Rotz, R., Nordt, C., Visentini, M., et al. (2025) · EClinicalMedicine · doi:10.1016/j.eclinm.2025.103149 · Cited by 61 · see citing works
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“Another hypothesized mechanism is psilocybininduced neuroplasticity (49).”
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Dynamic regulation of the extracellular matrix in reward memory processes: a question of time
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“This long-term dysregulation has been hypothesized to underpin the learning difficulties observed in patients with sAUD, thereby constituting a major challenge to fostering beneficial change through psychotherapy [29].”
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What Is Psychedelic Experience?
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Psychedelics‐Inspired Drug Discovery
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- Authors
- Rieser, N. M., Herdener, M., & Preller, K. H.
- Affiliations
- University of Zurich (CH)
- Corresponding author
- Rieser, Nathalie M.
- Venue
- Current Topics in Behavioral Neurosciences
- Publisher
- Springer International Publishing
- Published
- 2021
- Volume
- 56
- Pages
- 187-211
- ISSN
- 1866-3370 (ISSN-L)
- 1866-3389
- OpenAlex
- W4200162407
- Cited by
- 37
- References
- 110
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 7 · 2023: 19 · 2022: 1
- FWCI
- 54.97
- Type
- book chapter
- Language
- en
- Open access
- green
- www.zora.uzh.ch
- Licence
- Locations
- Current topics in behavioral neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Keywords
- psychedelic therapy, substance use disorders, addiction treatment, mechanism of action, neuroplasticity, brain network connectivity, reward processing, emotional processing, social connectedness, insight, mystical experience, psychotherapy
- MeSH terms
- Emotions, Hallucinogens, Humans, Psychotherapy, Psychotropic Drugs, Substance-Related Disorders
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