Improved mental health outcomes and normalised spontaneous EEG activity in veterans reporting a history of traumatic brain injuries following participation in a psilocybin retreat
In a preliminary uncontrolled study of 21 veterans with traumatic brain injury, participation in two psilocybin retreat ceremonies was associated with large reductions in PTSD, depression and anxiety symptoms and with EEG changes (reduced frontal/temporal delta–theta power and increased alpha–beta coherence) consistent with improved emotional regulation and neural communication. These findings suggest psilocybin retreats may improve psychological wellbeing and brain connectivity in veterans with TBI and warrant larger, controlled trials.
Authors
- Blest-Hopley, G.
- Carhart-Harris, R. L.
- Emmanuel, O.
Published
Abstract
IntroductionPsilocybin, a serotonergic psychedelic, has shown therapeutic potential in treating mental health disorders by, amongst the many effects, promoting neuroplasticity and reorganising functional connectivity across cortical and subcortical networks involved in emotion and cognition. Veterans with traumatic brain injuries (TBI) often experience chronic neurological and psychological symptoms such as post-traumatic stress disorder (PTSD) and depression. This study investigates the effects of psilocybin administered in retreat settings on veterans with a history of TBI, focusing on mental health outcomes and changes in brain connectivity as measured by EEG.MethodsA total of 21 participants were recruited through the Heroic Hearts Project, which facilitated access to two six-day psilocybin retreats in Jamaica. Before the retreat, participants underwent three individual and three group coaching sessions to prepare for the experience. During the retreat, two psilocybin ceremonies were held, spaced 48 hours apart. Participants received an initial dose of 1.5g to 3.5g of dried psilocybin mushrooms, with the option to increase the second dose up to 5g. Psilocybin was administered in a tea format, under the supervision of experienced facilitators. Psychological outcomes were assessed using validated questionnaires (PCL-5, PHQ-9, STAI) at baseline (four weeks pre-retreat) and four weeks post-retreat. Electroencephalography (EEG) was used to measure brainwave activity pre- and post-treatment. Paired t-tests were used to analyze changes in psychological scores, while EEG frequency band analysis assessed changes in brain function and connectivity.ResultsImprovements were observed across several mental health measures: PTSD (PCL-5 scores decreased by 50%, p=0.010), depression (PHQ-9 scores decreased by 65%, p<0.001), and anxiety (STAI) scores decreased by 28%, p<0.001). EEG data showed decreased delta and theta power in frontal and temporal regions, indicating potential improvements in cognitive control and emotional processing. Enhanced coherence in alpha and beta bands suggested improved neural communication.DiscussionThe study suggests that psilocybin retreats might provide improvements in psychological well-being and brain connectivity in veterans with TBI. Reduced delta power and normalised theta activity suggest better emotional regulation, while improved coherence in alpha and beta bands may reflect increased cognitive engagement. Further, these preliminary outcomes provide a potential rationale for the design and implementation of larger-scale, controlled studies to validate and expand upon these initial findings.
Research Summary of 'Improved mental health outcomes and normalised spontaneous EEG activity in veterans reporting a history of traumatic brain injuries following participation in a psilocybin retreat'
Introduction
Psilocybin is a serotonergic psychedelic that acts mainly at 5-HT2A receptors and has been proposed to promote neuroplasticity and to reorganise functional connectivity in networks supporting emotion and cognition. Veterans are at elevated risk of traumatic brain injury (TBI) and commonly experience chronic neurological and psychiatric sequelae such as depression, anxiety and post-traumatic stress disorder (PTSD). Electroencephalography (EEG) studies of TBI have repeatedly documented persistent abnormalities in spectral power and coherence, most notably elevated slow-wave activity in delta and theta bands and attenuated alpha and beta rhythms, which are thought to reflect disrupted thalamocortical and cortical network function. Blest-Hopley and colleagues set out to evaluate whether participation in residential psilocybin retreats was associated with improvements in mental health and concomitant changes in resting-state EEG among veterans reporting prior TBI. The authors hypothesised that retreat attendance would reduce delta power and normalise theta activity, while increasing alpha and beta power and coherence, with effects localising primarily to frontal and temporal regions. Psychological outcomes were to be measured with validated questionnaires and neurofunctional changes assessed using pre- and post-retreat EEG recordings collected at the retreat site.
Methods
This was an observational, naturalistic study of veterans recruited via the Heroic Hearts Project who attended one of two six-day psilocybin retreats in Jamaica organised by Beckley Retreats. Inclusion required a self-reported history of suspected chronic TBI and current psychological distress; exclusion criteria applied by the programme and medical staff excluded participants with serious cardiovascular conditions, psychotic or personality disorders, or other contraindicated medical or psychiatric conditions. Participants completed three individual and three group preparatory coaching sessions prior to travel. At the time of retreat attendance none were taking contraindicated psychoactive medications; medication histories were reviewed and any necessary discontinuations were managed under physician supervision. The intervention comprised two ceremonial administrations of dried Psilocybe cubensis mushroom tea spaced 48 hours apart. Initial dried mushroom doses ranged from 1.5 g to 3.5 g with an option to increase the second dose typically to 3 g–5 g; the authors estimated these ranges corresponded approximately to 15–35 mg psilocybin for the first session but acknowledged uncertainty due to natural product variability. Small booster doses (up to 1 g) could be offered within the early onset window. All dosing decisions were made collaboratively between participants and retreat staff and sessions were facilitated by experienced personnel. Psychological measures were collected remotely at baseline (four weeks pre-retreat) and at follow-up (four weeks post-retreat) using validated questionnaires administered on a digital platform. Key instruments reported include the PTSD Checklist for DSM-5 (PCL-5), Patient Health Questionnaire (PHQ-9), State-Trait Anxiety Inventory (STAI), Rivermead Post-Concussion Questionnaire (RPQ), Quality of Life after Brain Injury (Qolibri-OS), PROMIS Sleep Disturbance scale and the Warwick-Edinburgh Mental Well-being Scale (W-EMWS), among others. Resting-state EEG was recorded at the retreat site using a 19-electrode dry-cap system (10/20 montage) with participants seated, eyes open. Recordings were obtained on day one prior to any psilocybin and again on the final day at least 36 hours after the last ceremony. EEG analyses focused on canonical frequency bands (delta, theta, alpha, beta), spectral power, spatial variance, coherence/connectivity matrices and multivariate approaches including canonical correlation analysis (CCA) and representational similarity analysis. Behavioural pre-post comparisons used paired t-tests (two-tailed), with Bonferroni correction for multiple testing; EEG within-subject comparisons used Wilcoxon signed-rank tests (a non-parametric paired test) with false discovery rate correction across electrodes. Subgroup analyses stratified participants by prior psychedelic use (psychedelic-experienced versus naive).
Results
Twenty-one male veterans provided EEG data and a subset of 13 participants completed the psychological questionnaires at both timepoints. Mean age for the EEG group was 38.52 years (SD = 6.20) and 38.15 years (SD = 6.61) for the questionnaire completers. Most participants were from the United States and educational and employment distributions were reported descriptively. Behavioural outcomes (n = 13) showed statistically significant pre-to post-retreat improvements on multiple measures. Depressive symptoms on the PHQ-9 decreased from a baseline mean of 15.538 (SD = 4.115) to 5.308 (SD = 5.186), p < 0.001, and this survived Bonferroni correction. State anxiety (STAI) decreased from 53.769 (SD = 7.259) to 38.500 (SD = 11.533), p < 0.001, also surviving correction. The Rivermead Post-Concussion Questionnaire (RPQ) decreased from 34.692 (SD = 9.013) to 18.538 (SD = 12.258), p < 0.001 (survived correction). Quality of life (Qolibri-OS) increased from 41.614 (SD = 13.764) to 67.522 (SD = 17.277), p < 0.001, surviving correction. The Military to Civilian Questionnaire (M2C) scores, indicating reintegration difficulties, decreased from 2.174 (SD = 0.677) to 0.959 (SD = 0.871), p < 0.001, and this result also survived correction. PTSD symptoms measured by PCL-5 fell from 40.769 (SD = 16.799) to 20.923 (SD = 19.410), p = 0.010, but this change did not survive Bonferroni adjustment (adjusted p = 0.235). Measures of sleep disturbance and mental well-being showed improvements that reached uncorrected significance but did not consistently survive multiple-comparisons correction. Subgroup analyses stratified by prior psychedelic exposure indicated that participants with previous psychedelic use (n = 9) showed statistically significant reductions across the primary psychological measures (PHQ-9, STAI, RPQ, M2C, PROMIS-SD) and improvements in quality of life. Psychedelic-naïve participants (n = 4) exhibited directionally similar changes that did not reach statistical significance; the authors note these subgroup comparisons are limited by small sample sizes. EEG findings (n = 21) indicated systematic changes after the retreat. Spectral analyses revealed reductions in delta power and theta power localized especially to frontal and temporal regions, and modulation of alpha and beta activity with increased beta power observed in frontal and central regions. Spatial variance of band power increased post-retreat for theta (p = 4.17 × 10^-6), alpha (p = 1.00 × 10^-6) and beta (p = 1.00 × 10^-6) bands, while delta variance showed a more modest increase (p ≈ 0.039). Pairwise and electrode-wise comparisons identified enhanced inter-band distinction—particularly increased segregation between delta and higher-frequency bands—at electrodes including P3, C3, C4, P4, Cz, T5 and A2. Connectivity analyses showed changes in coherence patterns: pre-retreat recordings displayed widespread moderate connectivity without clear clustering, whereas post-retreat matrices exhibited strengthened connectivity especially in frontal and central regions. The authors report the delta band showed the most pronounced post-treatment enhancement in connectivity strength, while beta-band connectivity remained widespread with some frontal strengthening. Multivariate analyses (CCA, representational similarity) suggested a post-retreat reconfiguration toward more homogeneous within-subject patterns and increased inter-individual convergence. The authors note they did not collect adverse event data and therefore provide no safety statistics.
Discussion
Blest-Hopley and colleagues interpret their observational findings as evidence that participation in a structured psilocybin retreat was associated with multidimensional improvements in mental health and measurable changes in resting-state EEG among veterans reporting prior TBI. After Bonferroni correction, statistically robust improvements were observed in depressive symptoms, state anxiety, post-concussive symptoms, quality of life and civilian reintegration. PTSD symptom reductions and other wellbeing measures improved but did not survive correction and are therefore presented cautiously. In terms of neurophysiology, the authors propose that reductions in delta and theta power and increased spatial variance and inter-band segregation reflect enhanced oscillatory specificity and improved neural integration, particularly across frontal, temporal and central regions implicated in TBI. Increased beta activity and frontal-parietal connectivity are discussed as consistent with prior work linking beta oscillations to recovery trajectories. Multivariate findings suggesting more homogeneous post-retreat brain representations are interpreted as potential indicators of network reorganisation and greater functional synchronisation. The authors acknowledge several limitations that constrain causal inference and generalisability. The study is observational, unblinded and lacks a control group, so non-specific factors such as expectancy, group support, natural recovery or other retreat elements may account for some or all observed changes. Sample sizes were small (EEG n = 21, psychological n = 13), subgroup analyses were underpowered (psychedelic-naïve n = 4), and adverse events were not collected. EEG acquisition used a dry-cap system with potential signal-quality limitations, and post-retreat EEGs were obtained at least 36 hours after dosing so residual drug effects cannot be fully excluded. The authors also note pharmacokinetic uncertainty arising from natural mushroom preparations and emphasise that mechanistic biological claims (for example regarding synaptogenesis, BDNF, mTOR, or anti-inflammatory effects) remain speculative because corresponding biomarkers were not measured in this protocol. Given these caveats, the authors recommend larger, rigorously controlled studies—ideally randomised, placebo-controlled trials with standardised dosing, comprehensive safety monitoring, longer follow-up and more granular connectivity metrics—to determine whether the observed clinical and EEG changes can be causally attributed to psilocybin and to clarify underlying mechanisms. They also suggest future work should be powered to test whether specific EEG changes predict or mediate clinical improvements.
Conclusion
The study reports that veterans with self-reported TBI who attended structured psilocybin retreats experienced significant reductions in depressive and anxiety symptoms, improvements in quality of life and reintegration, and changes in resting-state EEG indicative of reduced slow-wave dominance and increased higher-frequency differentiation and connectivity. While these findings support the potential therapeutic value of psilocybin retreats for this population, the authors emphasise that the observational design, small sample sizes, lack of control conditions and other methodological constraints preclude definitive attribution of effects to psilocybin alone. They call for larger, controlled trials with standardised dosing, biomarker assessment and comprehensive safety monitoring to validate and extend these preliminary observations.
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METHODS
This study employed a comprehensive, multidimensional approach to assess the therapeutic effects of psilocybin administered in retreat settings among combat veterans with a history of TBI and currently presenting with psychological distress.
RESULTS
Data collection was structured to capture a wide range of psychological, behavioural, cognitive, and neurophysiological measures. The study used a combination of digital platforms for demographic and psychological questionnaires (Alchemer) and EEG conducted at the retreat centre.
CONCLUSION
Our findings from this observational study of veterans experiencing psychological distress and with a history of TBI provide further evidence for the multidimensional therapeutic benefits of psilocybin retreats. After applying Bonferroni correction, the results indicate statistically significant improvements in depressive symptoms (PHQ-9), anxiety (STAI), quality of life (Qolibri-OS), and reintegration difficulties (M2C) scores four weeks post-retreat. These findings highlight the potential positive outcomes from attendance at the retreat. However, while improvements were observed for PTSD symptoms (PCL-5), sleep disturbances (PROMIS-SD), and mental well-being (W-EMWS), these results did not survive the Bonferroni correction and should be interpreted with caution. Noteworthy, the significant improvement in Rivermead Post-Concussion Questionnaire scores can support the potential of psilocybin retreat programs in alleviating subjective symptoms of TBI. Overall, the results suggest promising therapeutic benefits, though further studies with larger sample sizes and more rigorous controls are necessary to confirm these findings. Subgroup analyses controlling for prior psychedelic experience further clarified these results (Supplementary Material S1). Significant improvements across multiple behavioural and wellbeing outcomes were predominantly observed in psychedelicexperienced participants, while psychedelic-naïve individuals demonstrated trends toward improvement without reaching statistical significance. Given the small number of psychedelicnaïve participants (n = 4), these differences should be interpreted cautiously. Nonetheless, the consistency of directional effects across groups might suggest that prior psychedelic exposure may enhance -but is not necessary for-the therapeutic response to psilocybin in structured retreat settings. These improvements in mental health and wellbeing have been shown previously by use of psilocybin in both retreat settings, naturalistic environments, and clinical settings for major depressive disorder (MDD)and anxiety. Furthermore, evidence of psychedelic retreat programs in general have shown Connectivity circles illustrating the coherence between electrodes for pre-retreat and post-retreat recordings across delta, theta, alpha, and beta bands. similar findings for improved mental health and wellbeing in military veteransand the wider populations. In line with our hypothesis and prior literature on EEG abnormalities in TBI, neurofunctional evaluation postretreat revealed systematic modulation of frequency band power and connectivity, suggesting enhanced neural integration and cognitive-emotional regulation. Consistent with this, statistical testing showed that variance in band power increased significantly post-retreat for theta, alpha, and beta bands, with spatially resolved differences detected across key centroparietal and temporal electrodes. These findings indicate enhanced functional differentiation of oscillatory activity, particularly in frequency bands associated with attention and emotional regulation. Pre-to post-retreat comparisons of frequency band correlations indicated a reduction in delta dominance and a reconfiguration of cross-frequency interactions. In particular, the weakening of deltabeta correlations-often elevated in TBI and associated with disrupted cortical control-suggests improved filtering of irrelevant stimuli and enhanced vigilance. Simultaneously, the emergence of theta-alpha connectivity patterns may reflect more effective cognitive and emotional processing, consistent with prior work linking these bands to memory integration and affective regulation. Frequency bands head plots revealed pre-to post-retreat, reductions in delta power, particularly in frontal and temporal regions-areas classically affected in TBI (38)-signal, potentially pointing towards improvements in emotional regulation and processing control. The normalisation of abnormal theta activity-which increase is among the most consistently reported EEG abnormalities in TBI patients-in temporal lobes post-retreat, may suggest enhanced emotional processing. Modulation of alpha power specifically decreased activity in frontal and central regions, which can indicate heightened attention and improved cognitive processing directed towards emotional information. Beta band power increases, especially in frontal and parietal regions, point to greater cognitive engagement and sensory integration, aligning with prior intracranial EEG findings linking beta oscillations to recovery trajectories in TBI. This was further supported by increased beta-band spatial variance across electrodes and greater inter-band segregation from delta activity, particularly over P3, Cz, and T5, suggesting functional reorganisation of beta activity within frontal-parietal networks. Frequency bands power distribution retreat reveals significant changes pre-and post-retreat towards improved symmetry. This shift towards symmetry in the temporal lobes' theta power, might indicate improved emotional processing and information encoding. Partial shift towards symmetry in post-retreat alpha power suggests localised improvements in emotional processing, as frontal alpha asymmetries might indicate avoidance motivation and emotional dysfunction. In parietal lobes, increased beta power indicates improved attention, visual processing, and multisensory integration. The connectivity matrices analysed pre-and post-retreat reveal notable changes in patterns of brain connectivity, with increased connectivity strength observed particularly in the delta band, which exhibited the most pronounced post-treatment enhancement. Stronger connections emerged in frontal and central regionsareas frequently implicated in higher-order cognitive and emotional processing and overall brain stability. While these patterns are suggestive of enhanced neural integration, we caution that the functional significance of these changes remains speculative. Limitations such as the absence of direct connectivity metrics (e.g., phase-locking value, graph-theoretic measures) and the lack of behavioural correlations constrain our ability to definitively attribute these findings to functional improvements. As such, these connectivity changes should be considered preliminary. Future studies incorporating more granular connectivity analyses and direct links to clinical outcomes will be essential to clarify their mechanistic relevance. These patterns align with a more distributed network architecture, as indicated by the absence of distinct modular organisation or lateralisation. Representational similarity analysis (RSM) further supported this observation, revealing a convergence toward more homogeneous brain activity patterns across individuals following the retreat. However, limitations such as the lack of specific connectivity measures and clinical context information make it challenging to definitively link observed changes to treatment effects or functional improvements. Overall, the findings suggest enhanced communication within and between crucial brain regions, pot en tially associated wit h cognitive im provem en ts following treatment. CCA of frequency band power revealed strong positive correlations in frontal and parietal lobes, which are critical for higher-order cognitive processes. The increased connectivity strength in these regions post-retreat indicated improved regulation of cognitive and emotional processes, with delta and beta bands showing the most significant enhancements in functional connectivity. The post-retreat analysis of overall network connectivity indicated substantial changes, suggesting potential improvements in integration and synchronisation within the brain network following the retreat. This enhanced integration may be associated with the observed psychological improvements, as more coordinated neural activity is crucial for effective cognitive processing and emotional regulation. Subtle asymmetries observed in the pre-retreat data become less apparent postretreat, possibly indicating a greater balance in specialised functions across hemispheres. Mechanistically, the observed changes across the paradigms investigated in this study may result from psilocybin effects on modulation of synaptogenesis, neurogenesis, neuronal plasticity, and neuroinflammation modulation. The underlying mechanisms include the upregulation of immediate early genes, like c-fos, and brain-derived neurotrophic factor (BDNF), as well as the activation of the tyrosine kinase B receptor and mammalian target of rapamycin (mTOR) signalling pathways. C-fos regulates cellular processes such as proliferation, differentiation, and survival (73-75), while BDNF is essential for neuronal transmission, survival, and synaptic plasticity Neuroinflammation plays a critical role in TBI, driving secondary damage via cytokine release and microglial activation. As noted by Thome et al., acute phases of TBI are characterised by profound neuroinflammation, a process that stimulates the generation and release of proinflammatory cytokines including IL-1a and IL-1b. Psilocybin has shown potential in mitigating this response by inhibiting lipopolysaccharide (LPS)induced TNF-a and IL-1b production in human macrophagesand reducing microglial TNF-a levels in hippocampal cultures. While psilocybin's potential anti-inflammatory effects have been reported in preclinical studies, we did not measure inflammatory markers in this study; thus, such mechanisms remain speculative in our context, and should be explored in future research.
Study Details
- Study Typeindividual
- Populationhumans
- Characteristicsopen labelbrain measuresfollow up
- Journal
- Compound
- Topics