Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing.

Psychedelic microdosing describes the ingestion of near-threshold perceptible doses of classic psychedelic substances. Anecdotal reports and observational studies suggest that microdosing may promote positive mood and well-being, but recent placebo-controlled studies failed to find compelling evidence for this. The present study collected web-based mental health and related data using a prospective (before, during and after) design. Individuals planning a weekly microdosing regimen completed surveys at strategic timepoints, spanning a core four-week test period. Eighty-one participants completed the primary study endpoint. Results revealed increased self-reported psychological well-being, emotional stability and reductions in state anxiety and depressive symptoms at the four-week primary endpoint, plus increases in psychological resilience, social connectedness, agreeableness, nature relatedness and aspects of psychological flexibility. However, positive expectancy scores at baseline predicted subsequent improvements in well-being, suggestive of a significant placebo response. This study highlights a role for positive expectancy in predicting positive outcomes following psychedelic microdosing and cautions against zealous inferences on its putative therapeutic value.

Positive effects of psychedelics on depression and wellbeing scores in individuals reporting an eating disorder.

PURPOSE: Psychedelic therapy is showing promise for a broad range of mental health conditions, indicative of a transdiagnostic action. While the efficacy of symptom-focused treatments for eating disorders (EDs) is limited, improved mental health and psychological wellbeing are thought to contribute to greater treatment outcomes. This study provides the first quantitative exploration of the psychological effects of psychedelics in those reporting an ED diagnosis. METHODS: Prospective, online data were collected from individuals planning to take a psychedelic drug. Twenty-eight participants reporting a lifetime ED diagnosis completed measures of depressive symptomology (Quick Inventory of Depressive Symptomology; QIDS-SR16) and psychological wellbeing (Warwick-Edinburgh Mental Wellbeing Scale; WEMWBS) 1-2 weeks before, and 2 weeks after a psychedelic experience. Twenty-seven of these participants also completed a measure of emotional breakthrough [Emotional Breakthrough Inventory (EBI)] in relation to the acute psychedelic experience. RESULTS: Bayesian t tests demonstrated overwhelming evidence for improvements in depression and wellbeing scores following the psychedelic experience. Marginal evidence was also found for a correlation between emotional breakthrough and the relevant mental health improvements. CONCLUSION: These findings provide supportive evidence for positive psychological aftereffects of a psychedelic experience that are relevant to the treatment of EDs. It is hoped that this will encourage further research and will bolster initiatives to directly examine the safety and efficacy of psychedelic assisted therapy as a treatment of EDs in future clinical trials. LEVEL OF EVIDENCE: Level III, cohort study.

Neural plasticity is modified over the human menstrual cycle: Combined insight from sensory evoked potential LTP and repetition suppression.

In healthy women, fluctuations in hormones including progesterone and oestradiol lead to functional changes in the brain over the course of each menstrual cycle. Though considerable attention has been directed towards understanding changes in human cognition over the menstrual cycle, changes in underlying processes such as neural plasticity have largely only been studied in animals. In this study we explored predictive coding and repetition suppression via the roving mismatch negativity paradigm as a model of short-term plasticity (Garrido, Kilner, Kiebel, et al., 2009), and Hebbian learning via visual sensory long-term potentiation (LTP) as a model of long-term plasticity (Teyler et al., 2005). Electroencephalography (EEG) was recorded in 20 females during their early follicular and mid-luteal phases. Event-related potential (ERP) analyses were complemented with dynamic causal modelling (DCM) to characterise changes in the underlying neural architecture. More sustained variability in the ERP response to a change in tone during the luteal phase are interpreted as a delayed habituation of the P3a component in the luteal relative to the follicular phase. The additional increased forward connection strength over tone repetitions compared to the follicular phase suggests that, in this phase, females may be less efficient when processing deviations from predicted sensory input (error). In contrast, there appears to be no reliable change in sensory LTP. This suggests that predictive coding, but not Hebbian plasticity is modified in the mid-luteal compared to the follicular phase, at least at the days of the menstrual cycle tested. This finding implicates the human menstrual cycle in complex changes in neural plasticity and provides further evidence for the importance of considering the menstrual cycle when including females in electrophysiological research.

Indexing sensory plasticity: Evidence for distinct Predictive Coding and Hebbian learning mechanisms in the cerebral cortex.

The Roving Mismatch Negativity (MMN), and Visual LTP paradigms are widely used as independent measures of sensory plasticity. However, the paradigms are built upon fundamentally different (and seemingly opposing) models of perceptual learning; namely, Predictive Coding (MMN) and Hebbian plasticity (LTP). The aim of the current study was to compare the generative mechanisms of the MMN and visual LTP, therefore assessing whether Predictive Coding and Hebbian mechanisms co-occur in the brain. Forty participants were presented with both paradigms during EEG recording. Consistent with Predictive Coding and Hebbian predictions, Dynamic Causal Modelling revealed that the generation of the MMN modulates forward and backward connections in the underlying network, while visual LTP only modulates forward connections. These results suggest that both Predictive Coding and Hebbian mechanisms are utilized by the brain under different task demands. This therefore indicates that both tasks provide unique insight into plasticity mechanisms, which has important implications for future studies of aberrant plasticity in clinical populations.

Age-related alterations in human neocortical plasticity.

Age-related changes in neuroplasticity may be central to the cognitive decline associated with healthy ageing. Modulated Long-Term Potentiation (LTP) and Long-Term Depression (LTD) have been repeatedly demonstrated in aged rodents, however the translation to human research has been limited by a scarcity of non-invasive methods for doing so. We have previously demonstrated that, following a block of high frequency presentations of a visual stimulus (referred to as a "visual tetanus"), there is a LTP-like enhancement of the N1b component of the visually evoked potential (VEP) to subsequent low frequency presentations of the same stimulus. The aims of the current study were, firstly, to use this electroencephalography (EEG) paradigm to assess age group differences in neocortical plasticity in humans, and secondly, to expand on the visual LTP paradigm by examining plasticity in another component of the VEP; the P2a. While a young participant group (N=29, age range=19-35) demonstrated the expected LTP-like enhancement of the N1b immediately following the visual tetanus, an older participant group (N=19, age range=68-91) did not. However, both age groups demonstrated a positive shift of the P2a component after repeated presentations of low frequency baseline blocks, which is hypothesized to be an LTD-like shift in the VEP. These results support the rodent literature indicating an age-related shift in threshold for LTP, but a relative preservation of the threshold for LTD. This study not only provides valuable insight into healthy age-related alterations in neocortical plasticity, but is also the first to identify an LTD-like modulation of the VEP in humans.