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Unique Effects of Sedatives, Dissociatives, Psychedelics, Stimulants, and Cannabinoids on Episodic Memory: A Review and Reanalysis of Acute Drug Effects on Recollection, Familiarity, and Metamemory

View ORCID ProfileManoj K. Doss, View ORCID ProfileJason Samaha, View ORCID ProfileFrederick S. Barrett, Roland R. Griffiths, View ORCID ProfileHarriet de Wit, View ORCID ProfileDavid A. Gallo, View ORCID ProfileJoshua D. Koen
doi: https://doi.org/10.1101/2022.05.20.492842
Manoj K. Doss
1Department of Psychiatry and Behavioral Sciences, Center for Psychedelic & Consciousness Research
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  • For correspondence: mdoss3@jhmi.edu
Jason Samaha
2Psychology Department, University of California, Santa Cruz
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Frederick S. Barrett
1Department of Psychiatry and Behavioral Sciences, Center for Psychedelic & Consciousness Research
3Department of Psychological and Brain Sciences, Johns Hopkins University
4Department of Neuroscience, Johns Hopkins University School of Medicine
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Roland R. Griffiths
1Department of Psychiatry and Behavioral Sciences, Center for Psychedelic & Consciousness Research
4Department of Neuroscience, Johns Hopkins University School of Medicine
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Harriet de Wit
5Department of Psychiatry and Behavioral Neuroscience, University of Chicago
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David A. Gallo
6Department of Psychology, University of Chicago
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Joshua D. Koen
7Department of Psychology, University of Notre Dame
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Abstract

Despite distinct classes of psychoactive drugs producing putatively unique states of consciousness, there is surprising overlap in terms of their effects on episodic memory and cognition more generally. Episodic memory is supported by multiple subprocesses that have been mostly overlooked in psychopharmacology and could differentiate drug classes. Here, we reanalyzed episodic memory confidence data from 10 previously published datasets (28 drug conditions total) using signal detection models to estimate 2 conscious states involved in episodic memory and 1 consciously-controlled metacognitive process of memory: the retrieval of specific details from one’s past (recollection), noetic recognition in the absence of retrieved details (familiarity), and accurate introspection of memory decisions (metamemory). We observed that sedatives, dissociatives, psychedelics, stimulants, and cannabinoids had unique patterns of effects on these mnemonic processes dependent on which phase of memory (encoding, consolidation, or retrieval) was targeted. All drugs at encoding except stimulants impaired recollection, and sedatives, dissociatives, and cannabinoids at encoding impaired familiarity. The effects of sedatives on metamemory were mixed, whereas dissociatives and cannabinoids at encoding tended to enhance metamemory. Surprisingly, psychedelics at encoding tended to enhance familiarity and did not impact metamemory. Stimulants at encoding and retrieval enhanced metamemory, but at consolidation, they impaired metamemory. Together, these findings may have relevance to mechanisms underlying unique subjective phenomena under different drug classes, such as blackouts from sedatives or déjà vu from psychedelics. This study provides a framework for interrogating drug effects within a domain of cognition beyond the global impairments on task performance typically reported in psychopharmacology.

Public significance statement This systematic review and reanalysis of several datasets indicate that sedatives (alcohol, zolpidem, triazolam), dissociatives (ketamine, dextromethorphan), psychedelics (psilocybin, MDMA), stimulants (dextroamphetamine, dextromethamphetamine), and cannabinoids (THC) can each have idiosyncratic effects on episodic memory, differentially impairing certain mnemonic processes while sparing or even facilitating others. Such findings inform how different drugs can produce unique subjective phenomena and provide a framework for future work to differentiate the effects of psychoactive drugs within a domain of cognition.

Competing Interest Statement

M.K.D. is an advisor to Ocean Bio Ltd., VCENNA, Inc., and Arcadia Medicine. F.S.B. is an advisor to Wavepaths. R.R.G. is a board member of the Heffter Research Institute. H.d.W. is an advisor to Schedule I Therapeutics, Gilgamesh Pharmaceutics, and PharmAla Biotech. None of these companies had any involvement with the research presented here. J.S., D.A.G., and J.D.K. have no competing interests to declare.

Footnotes

  • https://osf.io/ehsg4/

  • *This work was supported by the National Institute on Drug Abuse grants T32DA007209 (M.K.D.), R01DA03889 (R.R.G.), R01DA02812 (H.d.W). J.D.K. was supported by a National Institute on Aging grant (R56AG068149) during preparation of this manuscript. This work was also supported by the Heffter Research Institute, the Steven and Alexandra Cohen Foundation, Tim Ferriss, Blake Mycoskie, Matt Mullenweg, and Craig Nerenberg.

  • • M.K.D. is an advisor to Ocean Bio Ltd., VCENNA, Inc., and Arcadia Medicine. F.S.B. is an advisor to Wavepaths. R.R.G. is a board member of the Heffter Research Institute. H.d.W. is an advisor to Schedule I Therapeutics, Gilgamesh Pharmaceutics, and PharmAla Biotech. None of these companies had any involvement with the research presented here. J.S., D.A.G., and J.D.K. have no competing interests to declare.

  • • A subset of the analyses here were presented as posters at the College on Problems of Drug Dependence 81st annual meeting and the Psychonomic Society 60th annual meeting.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Unique Effects of Sedatives, Dissociatives, Psychedelics, Stimulants, and Cannabinoids on Episodic Memory: A Review and Reanalysis of Acute Drug Effects on Recollection, Familiarity, and Metamemory
Manoj K. Doss, Jason Samaha, Frederick S. Barrett, Roland R. Griffiths, Harriet de Wit, David A. Gallo, Joshua D. Koen
bioRxiv 2022.05.20.492842; doi: https://doi.org/10.1101/2022.05.20.492842
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Unique Effects of Sedatives, Dissociatives, Psychedelics, Stimulants, and Cannabinoids on Episodic Memory: A Review and Reanalysis of Acute Drug Effects on Recollection, Familiarity, and Metamemory
Manoj K. Doss, Jason Samaha, Frederick S. Barrett, Roland R. Griffiths, Harriet de Wit, David A. Gallo, Joshua D. Koen
bioRxiv 2022.05.20.492842; doi: https://doi.org/10.1101/2022.05.20.492842

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