Mystical experiences during magnesium-Ibogaine are associated with improvements in PTSD symptoms in veterans

Sample and descriptive findings: All 30 participants completed baseline and immediate-post clinical assessments; 23 met diagnostic criteria for PTSD at baseline on the MINI. The BAT‑L TBI counts included extreme outliers (three participants reported TBI counts ‘‘in the thousands’’), and the researchers imputed those three values as five times the standard deviation for statistical purposes. MEQ30 completion was mostly within 3–7 days post-dosing except for three delayed completions (34–35 days), which were examined in sensitivity analyses. Primary clinical outcome: The LMM showed a significant MEQ30 × time interaction for baseline→immediate-post on CAPS‑5 scores: unstandardised B_adj = −5.89, F(1,56) = 13.65, p < .001, 95% CI [−9.08, −2.70]. In practical terms, every 1‑point increase on the MEQ30 average (0–5 scale; equivalent to a 30‑point increase on the raw MEQ30) was associated with an expected 5.89‑point greater reduction in CAPS‑5 from baseline to immediate-post. A Spearman correlation corroborated this (rho = −0.53, p = .003). The association persisted at 1 month: MEQ30 × time interaction B = −4.45, F(1,56) = 7.79, p = .007, 95% CI [−7.64, −1.26], with Spearman rho = −0.49, p = .007. MEQ30 subscales: LMMs for the MEQ30 subscales (mystical, positive mood, transcendence of space/time, ineffability) largely showed similar associations with CAPS‑5 reductions; all subscale × time interactions were significant except for the ineffability subscale at the baseline→1‑month contrast. The authors interpreted this as no single subscale driving the effect and consistent with MEQ30 functioning as a largely unidimensional measure. Secondary clinical outcomes: MEQ30 total score was significantly associated with reductions in depression (MADRS) and anxiety (SIGH‑A) at both immediate-post and 1‑month timepoints. No significant association was found between MEQ30 total score and change in functional disability (WHODAS‑2.0). EEG/neurophysiological outcomes: For global PAF, the MEQ30 × time interaction was non‑significant for baseline→immediate-post (B = −0.098, F(1,45) = 0.561, p = .46, 95% CI [−0.36, 0.17]) but significant for baseline→1‑month (B = −0.38, F(1,45) = 8.15, p = .006, 95% CI [−0.65, −0.11]). Spearman correlation between MEQ30 total and change in PAF baseline→1‑month was rho = −0.49, p = .019. No significant MEQ30 × time interactions were observed for the other EEG measures of interest (band power, theta/beta ratio, LZc). Sensitivity and supplementary analyses: Excluding the three participants who completed the MEQ30 substantially later did not materially alter the findings, and correlations between MEQ30 scores and delay to completion did not indicate an effect of completion timing. Analyses including ibogaine dose (mg/kg) as a covariate did not show dose effects on primary outcomes. Age, CES total, and number of TBIs were not significant predictors in the LMMs.

E. and colleagues interpret these results as evidence that, within this open‑label cohort of combat veterans with TBI, greater intensity of mystical experiences during magnesium‑ibogaine treatment was associated with larger reductions in PTSD symptoms both immediately and one month later. The observed effect size for the primary correlation was moderate (rho ≈ 0.53) with a confidence interval spanning from weak to strong effects; the association attenuated slightly but remained significant at one month. The authors note that causal inference is not possible from these correlational data and acknowledge that mystical experiences might be an epiphenomenon rather than a mechanistic mediator. The authors offer possible psychological mechanisms by which mystical experiences may facilitate PTSD improvement: profound feelings of connection or sacredness may create a safer context for trauma reprocessing, experiences of ‘‘ego dissolution’’ could loosen rigid self‑schemas (e.g. beliefs of being irreparably damaged), and enhanced connectedness may reduce dissociation. On the neurophysiological side, the association between higher MEQ30 scores and sustained reductions in global PAF at one month suggests a potential neural correlate. The authors link slowed PAF to reductions in hyperarousal and to decreased top‑down inhibitory control, invoking the REBUS model (which proposes that psychedelics relax top‑down predictive priors) as a conceptual framework; sustained PAF slowing may reflect longer‑term relaxation of top‑down constraints with relevance to arousal and attention systems. The authors discuss strengths of the work, notably that this is the first study to examine mystical experience in relation to clinical and EEG outcomes after magnesium‑ibogaine in a TBI/PTSD veteran population, using clinician‑administered PTSD assessment and objective neurophysiology. They also acknowledge multiple limitations: the open‑label design and absence of a control condition preclude disentangling pharmacological effects from expectancy; the MEQ30 may not capture relevant constructs such as connectedness, may emphasise positive rather than adverse aspects of the experience, and its overlap with other acute subjective effects complicates specificity claims. Timing of MEQ30 completion (most participants completed it after integration sessions) could bias recall. The ineffability subscale's lack of significance at one month may reflect limited reliability due to only three items. The authors also note that animal data showing antidepressant-like effects from some non‑hallucinogenic analogues raise the possibility that subjective mystical content may not be strictly necessary for therapeutic outcomes, emphasising uncertainty about mechanism. For future research, E. and colleagues recommend longer follow‑up to assess durability, randomized controlled trials (including dose or active control conditions) to address expectancy and causal inference, larger and more diverse samples for generalisability, EEG recording during the dosing session to better characterise neural correlates of the acute subjective experience, psychometric work on the MEQ30 in the context of ibogaine (and use of alternative or additional measures that capture connectedness, emotional breakthrough, and negative acute effects), and broader investigation of subjective phenomenology that may mediate clinical benefit.