Psilocybin-assisted therapy for severe alcohol use disorder: protocol for a double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial.

BACKGROUND: A significant number of individuals with alcohol use disorder remain unresponsive to currently available treatments, which calls for the development of new alternatives. In parallel, psilocybin-assisted therapy for alcohol use disorder has recently yielded promising preliminary results. Building on extant findings, the proposed study is set to evaluate the feasibility and preliminary clinical efficacy of psilocybin-assisted therapy when incorporated as an auxiliary intervention during inpatient rehabilitation for severe alcohol use disorder. Moreover, it intends to pinpoint the modifications in the two core neurocognitive systems underscored by dual-process models of addiction. METHODS: In this double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial, 62 participants aged 21-64 years will be enrolled to undergo psilocybin-assisted therapy as part of a 4-week inpatient rehabilitation for severe alcohol use disorder. The experimental group will receive a high dose of psilocybin (30 mg), whereas the control group will receive an active placebo dose of psilocybin (5 mg), both within the context of a brief standardized psychotherapeutic intervention drawing from key elements of acceptance and commitment therapy. The primary clinical outcome is the between-group difference regarding the change in percentage of heavy drinking days from baseline to four weeks posthospital discharge, while safety and feasibility metrics will also be reported as primary outcomes. Key secondary assessments include between-group differences in terms of changes in (1) drinking behavior parameters up to six months posthospital discharge, (2) symptoms of depression, anxiety, trauma, and global functioning, (3) neuroplasticity and key neurocognitive mechanisms associated with addiction, and (4) psychological processes and alcohol-related parameters. DISCUSSION: The discussion outlines issues that might arise from our design. TRIAL REGISTRATION: EudraCT 2022-002369-14 and NCT06160232.

Early and middle latency auditory event-related potentials do not explain differences in neuropsychological performance between schizophrenia spectrum patients and matched healthy controls.

Abnormalities of early and middle latency auditory event-related potentials (ERPs) are widespread in schizophrenia and have been suggested to be associated with cognitive deficits in schizophrenia patients. In this cross-sectional study with schizophrenia patients (n=30) and psychiatrically healthy counterparts (n=31) (matched for age, sex, education), we investigated whether auditory information processing (measured via amplitudes and gating of the auditory ERPs P50, N100 and P200) correlates with neuropsychological performance across cognitive domains. The groups differed significantly in amplitudes and gating of N100 and P200 potentials as well as in neuropsychological performance, but not in P50 amplitude and gating. Neither amplitudes nor gating of auditory ERPs correlated with neuropsychological performance. Neuropsychological intergroup differences could not be explained by abnormalities in auditory information processing. Although pronounced impairments exist on the levels of both auditory information processing and cognitive performance in schizophrenia, these abnormalities are not directly associated with each other.

Visual N80 latency as a marker of neuropsychological performance in schizophrenia: Evidence for bottom-up cognitive models.

OBJECTIVE: Cognitive deficits and visual impairment in the magnocellular (M) pathway, have been independently reported in schizophrenia. The current study examined the association between neuropsychological (NPS) performance and visual evoked potentials (VEPs: N80/P1 to M- and P(parvocellular)-biased visual stimuli) in schizophrenia and healthy controls. METHODS: NPS performance and VEPs were measured in n = 44 patients and n = 34 matched controls. Standardized NPS-scores were combined into Domains and a PCA (Principal Component Analysis) generated Composite. Group differences were assessed via (M)ANOVAs, association between NPS and VEP parameters via PCA, Pearson's coefficient and bootstrapping. Logistic regression was employed to assess classification power. RESULTS: Patients showed general cognitive impairment, whereas group differences for VEP-parameters were non-significant. In patients, N80 latency across conditions loaded onto one factor with cognitive composite, showed significant negative correlations of medium effect sizes with NPS performance for M/P mixed stimuli and classified low and high performance with 70% accuracy. CONCLUSION: The study provides no evidence for early visual pathway impairment but suggests a heightened association between early visual processing and cognitive performance in schizophrenia. SIGNIFICANCE: Our results lend support to bottom-up models of cognitive function in schizophrenia and implicate visual N80 latency as a potential biomarker of cognitive deficits in schizophrenia.