Neuropsychological Functioning in Users of Serotonergic Psychedelics – A Systematic Review and Meta-Analysis

Abstract

Background: Serotonergic psychedelics (SPs) like LSD, psilocybin, DMT, and mescaline are a heterogeneous group of substances that share agonism at 5-HT2a receptors. Besides the ability of these substances to facilitate profoundly altered states of consciousness, persisting psychological effects have been reported after single administrations, which outlast the acute psychedelic effects. In this review and meta-analysis, we investigated if repeated SP use associates with a characteristic neuropsychological profile indicating persisting effects on neuropsychological function.Methods: We conducted a systematic review of studies investigating the neuropsychological performance in SP users, searching studies in Medline, Web of Science, embase, ClinicalTrials.gov, and EudraCT. Studies were included if they reported at least one neuropsychological measurement in users of SPs. Studies comparing SP users and non-users that reported mean scores and standard deviations were included in an exploratory meta-analysis.Results: 13 studies (N = 539) published between 1969 and 2020 were included in this systematic review. Overall, we found that only three SPs were specifically investigated: ayahuasca (6 studies, n = 343), LSD (5 studies, n = 135), and peyote (1 study, n = 61). However, heterogeneity of the methodological quality was high across studies, with matching problems representing the most important limitation. Across all SPs, no uniform pattern of neuropsychological impairment was identified. Rather, the individual SPs seemed to be associated with distinct neuropsychological profiles. For instance, one study (n = 42) found LSD users to perform worse in trials A and B of the Trail-Making task, whereas meta-analytic assessment (5 studies, n = 352) of eleven individual neuropsychological measures indicated a better performance of ayahuasca users in the Stroop incongruent task (p = 0.03) and no differences in the others (all p > 0.05).Conclusion: The majority of the included studies were not completely successful in controlling for confounders such as differences in non-psychedelic substance use between SP-users and non-users. Our analysis suggests that LSD, ayahuasca and peyote may have different neuropsychological consequences associated with their use. While LSD users showed reduced executive functioning and peyote users showed no differences across domains, there is some evidence that ayahuasca use is associated with increased executive functioning.

The potential of 5‐methoxy‐N,N‐dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action

“… 182 The literature on potential neuropsychological improvements following classic psychedelics is scant. Preliminary evidence shows an association between the DMT‐containing brew ayahuasca and subacute improvements in executive functioning, 185 which is an important domain for treatment outcome. 186 There are, however, no reports of 5‐MeO‐DMT and its potential effects on neuropsychological improvement.…”

Cognitive functioning associated with acute and subacute effects of classic psychedelics and MDMA - a systematic review and meta-analysis

“…Notably, even regular high-frequent use of psychedelics has not been associated with persisting, long-term impairment of cognitive functioning 8 , 9 . In contrast, research on how psychedelics affect cognition during the acute and subacute period of drug effects has not yet revealed a clear pattern 10 .…”

“…Psychedelics, in particular, have been shown to induce sustained sub-acute effects 7 not currently detected in MDMA use. Furthermore, psychedelic use appears to be mostly non-toxic in terms of neuropsychological functioning 8 , 9 , while research in MDMA users often suggest persistent cognitive deficits, particularly in memory functioning 27 – 31 . However, these MDMA-related findings remain disputed, with some authors arguing that reported differences are more likely to stem from pre-morbid differences rather than substance-induced cognitive dysfunction 32 , 33 , and may be less pronounced than initially reported 33 , 34 .…”

Psychedelic Cognition—The Unreached Frontier of Psychedelic Science

“…One of the most neglected aspects in the research of psychedelics is their effect on cognition and its distinctive domains. A recent systematic review and meta-analysis looking at the neuropsychological functioning in users of serotonergic psychedelics only included 13 studies ( Basedow et al, 2021 ). So far most of the efforts have been centered around mental health outcomes ( De Gregorio et al, 2021 ), effects on brain activity ( Carhart-Harris et al, 2016b ), and guidelines for therapy ( Holoyda, 2020 )---but not substantially and specifically on acute and long-term impact on cognitive function.…”