Evaluation of the peak experience scale as a rapid assessment tool for the strength of a psychoactive experience with 5-MeO-DMT

Psychedelic experiences are phenomenologically complex and often difficult to capture with brief instruments. Previous research has produced several multi-item questionnaires to quantify subjective features of altered states, including the 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC), the Ego-Dissolution Inventory (EDI), the Mystical Experience Questionnaire (MEQ-30) and the Challenging Experience Questionnaire (CEQ). These established tools are informative but time-consuming to administer (typically 10–20 min), and no validated instrument existed to rapidly quantify the overall intensity or profoundness of a psychedelic experience within a minute, a capability that could be useful in clinical contexts and when dosing short-acting compounds. Reckweg and colleagues developed a three-item Peak Experience Scale (PES) intended as a rapid assessment of the strength of the psychoactive experience (PsE), particularly for the short-acting psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; GH001 formulation). The PES uses three visual analogue scale (VAS) items (intensity, loss of control, and profoundness), each scored 0–100 and averaged, with an a priori pragmatic cutoff of ≥75 denoting a Peak Experience (PE). The present pooled analysis of three clinical studies aimed to compare the PES to established questionnaires (MEQ-30, CEQ, EDI, 5D-ASC), evaluate its psychometric properties (internal consistency, dimensionality), and determine whether it is sensitive to dose and suitable to guide an individualized dosing regimen (IDR) for 5-MeO-DMT.

Data were pooled from three clinical studies in which a vaporizable 5-MeO-DMT formulation (GH001) was administered either as single fixed doses (placebo [0 mg], 2 mg, 6 mg, 12 mg, 18 mg) or via an individualized dosing regimen (IDR) consisting of up to three escalating doses (6 mg, 12 mg, 18 mg) on a single day. Study 1 was a Phase I trial in healthy volunteers (n = 22) with 18 participants receiving single doses and four undergoing the IDR. Study 2 was a Phase I/II trial in patients with treatment-resistant depression (Phase I n = 8 single doses; Phase II n = 8 IDR). Study 3 was a Phase I pharmacokinetic study in healthy volunteers (n = 46) with a double-blind single-dose part followed by an open-label IDR part. In IDR conditions, doses were spaced by approximately 3 h in Studies 1 and 2 and by 1–2 h in Study 3; after each administration the PES was completed and, if a PE (average PES ≥75) had been reached, no further dosing occurred. The PES comprises three 0–100 VAS-style items assessing experience intensity, perceived loss of control, and profoundness; the mean of the three items constitutes the PES score. Comparator instruments were the 8-item EDI (mean score 0–100), the 30-item MEQ (total score from a 6-point scale), the 26-item CEQ (seven subscales, average transformed item score), and the 5D-ASC (94 items yielding five higher-order dimensions including Oceanic Boundlessness). GH001 was delivered using a standardised vapour‑generation device with participants instructed to hold their breath for 10 s after a single inhalation. Timing of PES completion was roughly 30 min post-dose in Study 3 and about 90 min in Studies 1 and 2; other questionnaires were completed immediately after the PES. Statistical procedures included evaluation of internal consistency (Cronbach's alpha) for the PES, principal component analyses (PCA) with Kaiser-Meyer-Olkin (KMO) and Bartlett’s tests to assess dimensionality, one-way ANOVAs with Dose as a factor to test dose effects (Dose levels varied slightly between questionnaires because not all were used in all studies), and Pearson’s correlations between PES scores and other scales. For IDR conditions only the rating after the final administration was included. MEQ data from two participants in Study 3 were excluded due to missing values. Analyses were performed in IBM SPSS v28 and GraphPad Prism v9.4.1. All three studies received appropriate ethics approvals and were conducted according to Good Clinical Practice and the Declaration of Helsinki.

ANOVAs indicated a significant, dose-related effect of 5-MeO-DMT on multiple subjective measures. The PES showed the largest effect size for Dose (F(5,78) = 27.271, p < 0.001, partial η2 = 0.636). Significant Dose effects were also observed for the EDI (F(4,33) = 9.836, p < 0.001, partial η2 = 0.544), the MEQ (F(5,76) = 10.024, p < 0.001, partial η2 = 0.397), the overall 5D-ASC (F(4,33) = 2.984, p = 0.033, partial η2 = 0.266), and 5D-ASC subscales Oceanic Boundlessness (F(4,33) = 3.048, p = 0.03, partial η2 = 0.27) and Reduction of Vigilance (F(4,33) = 3.096, p = 0.029, partial η2 = 0.273). There were no significant Dose effects on the CEQ total score (F(5,78) = 1.548, p = 0.185, partial η2 = 0.09) or on several 5D-ASC subscales (Anxious Ego Dissolution, Visual Restructuralization, Auditory Alterations). Psychometric analyses supported the PES as a unidimensional and reliable measure. Cronbach's alpha for the three PES items was 0.896, indicating high internal consistency. A PCA of the three PES items showed a single dominant component (eigenvalue = 2.506) explaining 83.5% of the variance; the item loadings on that component were 0.944 (Intensity), 0.894 (Loss of Control), and 0.902 (Profoundness). A separate PCA that included PES, MEQ, EDI, 5D-ASC and CEQ identified two principal components: the first explained 68.4% of variance and was strongly associated with PES, MEQ, EDI and 5D-ASC, while a second component explained 19.4% and was driven primarily by CEQ ratings, together accounting for 87.8% of variance. Correlation analyses showed moderate to strong positive relationships between PES scores and the EDI, MEQ, and several 5D-ASC subscales (Oceanic Boundlessness, Anxious Ego Dissolution, Visual Restructuralization). The PES correlated only weakly with the CEQ (r = 0.29, p = 0.007). Two 5D-ASC subscales—Auditory Alterations (r(38) = 0.174, p = 0.297) and Reduction of Vigilance (r(38) = 0.132, p = 0.43)—did not correlate significantly with the PES. The authors note that correlations were not corrected for multiple comparisons, but state that significant correlations would have survived a Bonferroni correction. The IDR condition yielded the highest occurrence of PEs, with almost 86% of participants reaching a PE under the IDR regimen (final administration ratings used in analyses).

Reckweg and colleagues interpret the pooled findings as supporting the PES as a rapid, reliable, and unidimensional measure of the strength of a 5-MeO-DMT experience. The PES demonstrated the largest dose-related effect among the tested instruments and showed strong internal consistency; PCA results indicated that the three PES items capture a single construct that aligns with measures of ego dissolution and mystical-type or transformative experiences as assessed by the MEQ, EDI and 5D-ASC. The CEQ, by contrast, loaded on a distinct component and correlated only weakly with the PES, consistent with the CEQ measuring challenging or aversive aspects of the acute experience. The authors highlight practical implications for pharmacology and clinical dosing: in conjunction with safety monitoring, the PES could facilitate rapid assessment of whether a given inhaled 5-MeO-DMT dose has reached sufficient experiential magnitude and thus inform same-day re-dosing decisions during an individualized dosing regimen (IDR). The pooled results indicate the IDR was particularly effective at eliciting PEs, with the highest proportion of participants reaching the predefined PES cutoff under IDR. Limitations acknowledged by the investigators include that the PES has so far only been applied in studies of 5-MeO-DMT, so generalisability to other psychedelics or alternative methods of inducing altered states remains unestablished. The measure's brevity limits its capacity to capture the nuanced or challenging facets of psychedelic experience, for which longer instruments like the CEQ, MEQ and 5D-ASC still provide value. The authors also note that the PES’s predictive validity for clinical outcomes is not yet demonstrated; although a small sample in Study 2 suggested PEs predicted therapeutic responses in treatment-resistant depression, larger samples are required to evaluate test–retest reliability, discriminant validity and whether PES-determined PEs reliably forecast symptom improvement. Finally, the authors point out that other experiential predictors of therapeutic benefit (for example, psychological insight or emotional breakthrough) are receiving attention, and it remains to be determined how the PES relates to those constructs.