This randomised, placebo-controlled, double-blind crossover study (n=25) found that DMT (60 mg) increased psychotic-like experiences and suggestibility in healthy volunteers, alongside strong mystical and other psychedelic effects. The links between these effects appeared to be driven more by positive emotionality than by mystical experience alone.
Paradoxically, psychedelics have long been used as models of both psychosis and therapy. After proposing mystical experiences as a link between these models for lysergic acid diethylamide (LSD), we aimed to extend and refine this framework for N,N -Dimethyltryptamine (DMT). In a randomised, placebo-controlled, double-blind, crossover study, 25 healthy participants received DMT (60mg) and an active placebo (0.6mg DMT), separated by two hours. Psychotic-like experiences were assessed via aberrant salience (Aberrant Salience Inventory [ASI]) and therapeutic-like experiences via suggestibility (Creative Imagination Scale [CIS]), including suggestion-induced mystical experiences. Psychedelic experiences were measured via the Six Dimensions and Eleven Factors of Altered States of Consciousness Questionnaire (6D-ASC and 11-ASC), Hallucinogen Rating Scale (HRS), and Mystical Experiences Questionnaire (MEQ). Compared to placebo, DMT increased all aberrant salience factors, most suggestibility modalities, including mystical experiences, and most 6D-ASC and HRS factors. Aberrant salience showed widespread correlations with psychedelic experiences, particularly mystical experiences (MEQ) and positive emotionality (e.g., Joyfulness [6D-ASC], Blissful State [11-ASC]). Suggestibility correlated with the same positive emotionality factors and inversely with negatively valenced aberrant salience (Heightened Emotionality [ASI]), emotionality (Dysphoria [HRS), and mystical experiences (Ineffability [MEQ]). In conclusion, DMT’s effects on aberrant salience and suggestibility support its role both as a psychosis and therapy model. The models’ link may be indirect with respect to mystical experiences, with emotionality playing a more crucial role. Importantly, suggestion-induced mystical experiences after DMT may suggest post-acute perceptual plasticity, informing the development of more tailored psychedelic treatments that induce, amplify, and guide therapeutic experiences.
Classic serotonergic psychedelics such as LSD and DMT can produce profound changes in perception, emotion, and cognition, and have therefore been discussed both as potential therapies and as models of psychosis. The paper notes that these two perspectives remain in tension because psychedelics may generate experiences that resemble psychotic phenomena, yet they can also produce states that patients describe as meaningful or beneficial. Earlier work by the authors using LSD suggested that mystical experiences might help bridge these psychosis and therapy models, with links to psychosis-related measures and therapeutic outcomes. However, it remained unclear whether similar patterns would be seen with DMT, particularly given its much shorter duration and the possibility that its acute effects could still support post-acute suggestibility and mystical experiences. Wießner and colleagues therefore set out to examine whether inhaled DMT increases aberrant salience, a psychosis-related construct, and suggestibility, a therapy-related construct, and how these changes relate to psychedelic experiences, mystical experiences, and positive emotionality. They also aimed to test whether suggestion administered after the acute DMT phase could induce mystical experiences, and whether this might offer a practical bridge between psychosis and therapy models. The study was framed as a follow-up to the group’s earlier LSD work, with the aim of confirming and extending those findings using a short-acting psychedelic that may be more feasible for clinical use.
The paper reports data from a previously published project on the safety and tolerability of inhaled DMT, including harms and unintended events. The researchers used a randomised, double-blind, placebo-controlled, crossover design with two treatment sessions: DMT and an active placebo, separated by a 2-hour washout period. Participants were randomly assigned to treatment order. The study was approved by the relevant ethics committee, registered on ClinicalTrials.gov, and conducted in line with the Declaration of Helsinki, Good Clinical Practice, and psychedelic research guidelines. The sample comprised 26 healthy, right-handed volunteers aged 18 to 60 years, recruited through online advertisements and word of mouth between April and July 2023. All had at least one prior DMT experience. Candidates underwent medical and psychiatric screening, and participants were asked to abstain from psychedelics for two weeks and from alcohol and other drugs for three days before participation. One participant was excluded because a different inhalation volume had been used, leaving a final sample of 25. The extracted text describes the sample as predominantly White, single, highly educated, employed, non-religious but spiritual, and experienced with ayahuasca. DMT was inhaled as 60 mg vapourised material delivered into a 2-L balloon at 200°C for 10 seconds. The active placebo was 0.6 mg DMT, intended to mimic smell and colour minimally. Participants inhaled from the balloon and held the vapour for 3 seconds. The procedures were practised beforehand using air-filled balloons. The extracted text notes that inhalation quality was satisfactory except for one session. Psychedelic experiences were assessed with several standard questionnaires, including the 5D-ASC, 6D-ASC, 11-ASC, the Hallucinogen Rating Scale (HRS), and the Mystical Experiences Questionnaire (MEQ). Aberrant salience was measured with the Aberrant Salience Inventory (ASI), including a Brazilian Portuguese translation and state adaptation with five factors. Suggestibility was measured using the Creative Imagination Scale (CIS), with two parallel versions balanced and counterbalanced across participants and treatments. The CIS included an additional mystical item based on a hypnotic protocol. Sessions were conducted in a university hospital psychedelic research unit furnished like a modern living room, with at least one experienced researcher present throughout. Baseline measurements were taken at 7:30 a.m., DMT or placebo was given at 9:00 a.m., and the suggestibility task was administered during the post-acute phase at 9:30 a.m., when acute effects had largely subsided. Questionnaires on psychedelic experience and aberrant salience followed. The second session repeated the same structure, and the alternate drug was administered at 11:10 a.m. Final medical evaluation took place later the same day. Outcomes were analysed using repeated-measures general linear models with within-subject factor drug and between-subjects factor drug order. The researchers tested main effects of drug, order, and drug-by-order session effects, estimated effect sizes using partial eta squared, and used Spearman correlations to examine associations between DMT-induced changes in aberrant salience, suggestibility, and psychedelic experience. The significance threshold was two-tailed α = 0.05, with Bonferroni correction applied post hoc for multiple testing. Additional exploratory and sensitivity analyses were also performed, including analyses using alternative factor structures.
Compared with placebo, DMT increased multiple psychedelic experience measures. On the 6D-ASC, significant increases were reported for Oceanic Boundlessness, Dread of Ego Dissolution, Visionary Restructuralization, Joyfulness, and Auditory Alterations, but not Vigilance Reduction. On the HRS, DMT increased Vision, Meaningfulness, Euphoria, Somesthesia, Auditory and Minor Senses, Dysphoria, and Liking; the increase in Volition did not survive correction for multiple testing. The extracted text states that there were no significant order or session effects for these measures. DMT also increased suggestibility in the post-acute phase. The total CIS score was higher under DMT than placebo, and several modalities increased as well: Internal Ambience, Sensation, Mystical, External Ambience, and Weight. Taste did not differ significantly. Because some participants fell asleep during later items, those items were excluded when sleep was reported by the participant or judged by the investigators, which reduced the analysable sample for some CIS items and for the total score. The authors initially report uncorrected p-values for the suggestibility analyses because the mystical component was exploratory and they wanted comparability with their earlier LSD work. No order or session effects were observed. For aberrant salience, the paper reports that DMT increased the total ASI score and all five factors. The exact values are not fully reproduced in the extracted text, but the authors describe the effects as robust. They also note that the results were broadly comparable to their earlier LSD study. In the final sample of 25 participants, the first enrollee was excluded because of a different inhalation volume. Correlational analyses showed numerous moderate to strong positive associations between DMT-induced changes in aberrant salience and psychedelic experience scales. Correlations ranged from rs = 0.52 to 0.89 and were seen across 6D-ASC, 11-ASC, HRS, and MEQ measures, especially for mystical-type experiences and positive emotionality. Suggestibility showed a similar but more selective pattern. The total CIS score correlated positively with Joyfulness, Blissful State, and Insightfulness. In contrast, some CIS subscales correlated negatively with negatively valenced measures: External Ambience with Heightened Emotionality, Internal Ambience with Dysphoria, and Sensation with Ineffability. Additional analyses using older factor structures again showed generally positive correlations between aberrant salience and psychedelic experience, while one mystical suggestibility item correlated negatively with HRS Agitation. The text suggests that the overall pattern was consistent across the main and alternative analyses, although not all secondary correlations are fully reproduced in the extracted passage.
The authors interpret this study as the first to examine the link between DMT’s psychosis and therapy models while also testing whether post-acute mystical experiences can be induced by suggestion. They argue that DMT robustly increased both aberrant salience and multimodal suggestibility, supporting the idea that a single psychedelic state can engage both psychosis-related and therapeutic-related processes. At the same time, they emphasise that these processes are phenomenologically distinct and only partly overlapping. Wießner and colleagues say the correlation pattern strengthens the connection between aberrant salience and psychedelic phenomenology, especially mystical experiences and positive emotionality. They highlight that suggestibility was positively associated with pleasant affect, which they see as a new connection between the therapy model and positive emotionality, while negative correlations with emotional aberrant salience, dysphoria, and ineffability point to links with negatively valenced and mystical-related aspects. In their view, the findings from both the present DMT study and their previous LSD work suggest that short- and long-acting psychedelics share psychotic-like and therapeutic-like dimensions. The discussion also notes that post-acute suggestions were able to induce mystical experiences, which the authors present as potentially relevant for optimising psychedelic treatments by deliberately inducing, amplifying, and guiding therapeutic experiences. They further suggest that positive emotionality may provide an affective bridge between psychosis and therapy models. The authors compare their results with earlier research showing that psychedelic states share some features with psychosis but also differ in important ways, particularly in emotional valence, sensory profile, and reality monitoring. They argue that DMT may be especially useful as a psychosis model for positive symptoms and for meaning-making, and that aberrant salience may be part of the mechanism through which psychedelic experiences develop. They also note that classic psychedelics, particularly DMT, may model positive emotionality more directly than some other substances. Several limitations are acknowledged. Blinding was difficult because of DMT’s distinctive smell, taste, and subjective effects, which may have influenced suggestibility outcomes. The active placebo may have had some effect of its own. The 2-hour washout does not fully exclude carryover, although none was detected statistically. The sample was small and homogeneous, limiting generalisability, especially to clinical populations. The authors also point to psychometric limitations, including the unvalidated Intensity scale, lack of formal Portuguese validation for the HRS, potential inequivalence in suggestibility items, and the possibility that splitting the mystical item reduced depth of experience. Sleep during later CIS items may have introduced bias and reduced power. Finally, they caution that the initial lack of multiple-testing correction was used for comparability with their LSD study and should be interpreted carefully.
The authors conclude that the DMT findings extend their earlier LSD work by showing similar effects on aberrant salience and suggestibility, supporting the generalisation of concurrent psychotic-like and therapeutic-like processes across short- and long-acting psychedelics. They state that the correlations reinforce a close link between aberrant salience and mystical experiences across substances, and that positive emotionality may provide a novel bridge between the psychosis and therapy models. They also conclude that suggestion can induce post-acute mystical experiences after DMT, which they present as having clinical relevance for shaping psychedelic experiences.
This work reports data from a previously published project on the safety and tolerability of inhaled DMT, including harms or unintended events.
We used a randomised, double-blind, placebo-controlled, crossover design with two treatment sessions (DMT, active placebo), separated by a 2-hour washout period, which has previously yielded no residual physiological effects. Participants were randomly assigned to the drug order (DMT-placebo, placebo-DMT), using simple randomisation (randomizer.org). The study received approval by the ethics committee (University Hospital Onofre Lopes [HUOL], Federal University of Rio Grande do Norte [UFRN]; #67.303.623.6.0000.5292), registered at clinicaltrials.gov (, registered 02/06/2023), and conducted according to the Declaration of Helsinki, Good Clinical Practice (GCP), and psychedelic research guidelines. No patients or members of the public were involved in the design, conduct, reporting, or dissemination of this study. No important changes to outcomes or analyses were made after trial commencement.
Using online advertisements and word of mouth, we recruited 26 healthy, right-handed volunteers (18 to 60 years) with at least one experience with DMT (04-07/2023). Sample size was estimated based on previous studies. Candidates underwent a medical and psychiatric screening and selection criteria check. Participants gave written informed consent and had to abstain from psychedelics for two weeks and from alcohol and other drugs for three days before study participation.
DMT (purity 98.9% ±0.18) was isolated from organically and regionally grown Mimosa tenuiflora tree roots. For inhalation, 60 mg DMT were vapourised (Volcano® Medic 2, Storz & Brickel GmbH & Co, Tuttlingen, Germany) at 200°C for 10 sec into a 2-L balloon. As an active placebo, a very small DMT dose (0.6 mg) was vapourised to minimally mimic smell and colour. Participants emptied the lungs, inhaled, and retained the vapour for 3 sec. Before the first treatment, the procedures were trained with air-filled balloons. Inhalation quality was satisfactory except for one session (DMT in subject #6).
Psychedelic experiences was measured regarding Intensity, the Five Dimensions, Six Dimensions, and Eleven Factors of Altered States of Consciousness Questionnaire (5D-, 6D-and 11-ASC), Hallucinogen Rating Scale (HRS), and Mystical Experiences Questionnaire (MEQ)(Supplemental Methods). Most main drug effects for these scales are reported elsewhere; for this work, we correlated the deltas (Δ = DMT - placebo) of significantly altered measurement with aberrant salience and suggestibility.
The Aberrant Salience Inventory (ASI) measures trait aberrant salience using 29 yes-no items, yielding a total score and five factors (Increased Significance, Senses Sharpening, Impending Understanding, Heightened Emotionality, Heightened Cognition ). The Brazilian Portuguese translation and state measurement adaptation confirmed the five-factor structure beyond supporting a four-factor solution(Supplemental Methods; table).
Suggestibility was measured by the Creative Imagination Scale (CIS), comprising 10 guided imagery items of different sensory modalities (e.g., auditory, tactile), rated on a 5-point Likert scale (0 = not at all the same; 4 = almost exactly the same). We divided the items into two parallel versions (A and B), applied in balanced order across participants and counterbalanced across treatments. The items yield a total score and the sensory modalities Weight, Sensation, Taste, External Ambience, Internal Ambience and an additional item Mystical, based on a previous hypnotic protocol(for details on task adaptation, application, and mystical item, see Supplemental Methods).
The study was conducted at the university hospital's Psychedelic Research Unit. The room was furnished in a modern living room style and at least one experienced researcher always remained with the participant. Sessions started at 7:30 a.m. with baseline measurements. At 9:00 a.m., DMT or placebo was administered, followed by physiological and biochemical measurements, with acute DMT effects lasting around 20 min. At 9:30 a.m., during the postacute DMT phase, the suggestibility task was conducted, lasting 20 min. Afterwards, psychedelic experience and aberrant salience questionnaires were applied. Hereafter, the second session repeated the same procedures. At 11:10 a.m., participants received the other corresponding drug. At 12:54 p.m., participants underwent final medical evaluations, received lunch, and were released into the care of a family member or friend.
Each scale factor/item was analysed using a Repeated Measures General Linear Model (GLM) with the within-subject factor drug (DMT, placebo) and the between-subjects factor drug order (DMT-placebo, placebo-DMT). Main effects of drug, order, and session (drug×order) were evaluated. Effect sizes were estimated using partial eta squared (η p ²). Spearman correlations were calculated of DMT-induced aberrant salience and suggestibility with psychedelic experiences (Δ = DMT - placebo). Significance level was α = 0.05, two-tailed. The p-values were Bonferroni-corrected post hoc for multiple testing by factor number plus total score, unless stated otherwise. No interim analyses or stopping guidelines were prespecified. Analyses were conducted using IBM SPSS Statistics (v.22). Additional exploratory and sensitivity analyses (e.g., correlations and alternative factor structures) were conducted and were not pre-specified.
The first subject (order DMT-placebo) received a different inhalation volume and was therefore excluded from all analyses (for the CONSORT flow diagram, see figure). So, the final sample consisted of 25 subjects (age = 33 ± 6 years; female = 13; male = 12). These were predominantly White, single, highly educated, employed, non-religious but spiritual, and experienced with ayahuasca (14 ± 19 times).
Regarding 6D-ASC, DMT, compared to placebo, increased Oceanic Boundlessness, Dread of Ego Dissolution, Visionary Restructuralization, Joyfulness, and Auditory Alterations (all p ≤ 0.001), but not Vigilance Reduction (Fig.). Regarding HRS, DMT increased Vision, Meaningfulness, Euphoria, Somesthesia, Auditory and Minor Senses (all p ≤ 0.001), Dysphoria, and Liking (both p ≤ 0.030), while the increases in Volition did not survive multiple testing correction (Fig.). No order or session effects reached significance. For detailed GLM values, estimated marginal means, and standard deviations, see Table.
Several subjects fell asleep, especially during later task items after approximately 15 min of eyes-closed suggestion exposure. Therefore, participants were asked whether they had fallen asleep (yes/no) and investigators independently evaluated sleep status (yes/unsure/no) and affected items. Items were excluded from analyses whenever participant or investigator indicated sleep, resulting in reduced sample sizes (item #4 External Ambience: n = 21; item #5 Internal Ambience and item #6 Mystical: n = 17; total scale: n = 15; for details, see Supplementary Results). To enhance comparability with our previous LSD findingsand given the exploratory nature of the suggestion-induced mystical experiences, we initially explored uncorrected p-values. Compared to placebo, DMT increased total suggestibility (p < 0.001) and the modalities Internal Ambience (p = 0.002), Sensation (p = 0.009), Mystical (p = 0.022), External Ambience (p = 0.035), and Weight (p = 0.036), but not Taste (Fig.; Table). No order or session effects were observed. Corrected p-values were additionally analysed for comparison with aberrant salience and psychedelic scales (see
Regarding aberrant salience, numerous moderate to high positive correlations emerged for the total score and factors (ΔASI) with psychedelic experiences (Δ6D-ASC, Δ11-ASC, ΔHRS, ΔMEQ), with r s -values ranging from 0.52 to 0.89 (Table; for scatterplots of total scores, see Fig.). This included relationships with mystical-type experiences (e.g., Oceanic Boundlessness, Experience of Unity, Sacredness) and positive emotionality (e.g., Joyfulness, Blissful State, Euphoria, Positive Mood; Fig.). For suggestibility, some moderate to high correlations emerged. The total score (ΔCIS) correlated positively with Joyfulness (Δ6D-ASC; r s =0.79, p = 0.003), Blissful State (Δ11-ASC; r s =0.67, p = 0.038), and Insightfulness (Δ11-ASC; r s =0.70, p = 0.021; Fig.), indicating associations with positive emotionality similar to those observed for aberrant salience. Contrastingly, negative correlations emerged between External Ambience (ΔCIS) and Heightened Emotionality (ΔASI, r s =-0.68, p = 0.004), between Internal Ambience (ΔCIS) and Dysphoria (ΔHRS, r s =-0.65, p = 0.029), and between Sensation (ΔCIS) and Ineffability (ΔMEQ; r s =-0.60, p = 0.010; Fig.; Table), pointing to inverse relationships of suggestibility with negatively valenced aberrant salience, negative emotionality, and specific aspects of mystical experiences. Given the associations of both aberrant salience and suggestibility with mystical experiences and positive emotionality, we developed a conceptual model linking the psychosis model, therapy model, and psychedelic experiences (Fig.). Additionally, for comparison with previous studies, we correlated aberrant salience and suggestibility with earlier factor structures of 5D-ASCand HRS. Moderate to high positive correlations emerged again between ΔASI and psychedelic scales (r s =0.56 to 0.70), whereas a negative correlation appeared for ΔCIS Mystical with Agitation (ΔHRS; r s =-0.73, p = 0.005; table). Moreover, to align with our previous LSD findings using the original ASI factor composition, we repeated the analyses with this structure. No correlations were found of ΔASI with ΔCIS, but with psychedelic scales similar to those observed for the Brazilian ASI (r s =0.
To our knowledge, this is the first study to examine the link between the DMT psychosis and therapy models, beyond exploring the feasibility of inducing post-acute mystical experiences via suggestion. DMT robustly increased both aberrant salience and multimodal suggestibility, supporting the engagement of concurrent psychotic-and therapeutic-related processes. However, these processes appear phenomenologically distinct and partially dissociable with the altered state. Importantly, post-acute suggestions induced mystical experiences, highlighting potential strategies to optimise psychedelic treatments by amplifying and guiding therapeutic experiences. Correlations between aberrant salience and psychedelic experiences further support a close link of psychotic-like features with mystical phenomenology and positive emotionality. Positive correlations of suggestibility with pleasant affect reveal novel connections between therapy model and positive emotionality, whereas negative correlations with emotional aberrant salience, dysphoria, and ineffability indicate associations with negatively valenced, psychosis-and mystical-related aspects. Together with our LSD results, the findings suggest generalised psychotic-and therapeutic-like dimensions across short-and long-acting psychedelics and reveal novel connections between psychosis and therapy models through mystical experiences and positive emotionality.
DMT increased all 6D-ASC factors except Vigilance Reduction, replicating our previous 5D-ASC findings. Again, Visionary Restructuralization and Oceanic Boundlessness were most pronounced, with weaker increases in Auditory Alterations and Dread of Ego Dissolution. The 6D-ASC more strongly captured visual and auditory dimensions, likely due to slightly modified item composition. The additional Joyfulness dimension on ecstasy, meaning, and well-being was comparable to Oceanic Boundlessness levels. Similarly, survey data showed for DMT particularly strong visual, mystical, and joyful effects and less hypovigilance, anxious, and auditory experiences. DMT increased all HRS factors except Volition, with pronounced visual and less somaesthetic effects, similar to previously factors. Unlike earlier factors of overall Agitation/Affect, the updated structure distinguished Euphoria and Dysphoria, with stronger increases in positive than negative affect. Liking was increased despite high placebo ratings. Auditory and Minor Senses covered a broader sensory range than previous factors, including smell, touch, and synaesthesia. Volition increases in onebut not anothernor the current structure, likely reflect item inversions -earlier items emphasised physiological control loss and current items acceptance, awareness, and control. Contrasting the earlier Quality of the Experience, Meaningfulness more directly captures meaning-making, a common feature of psychedelic experiences. Overall, our findings align with multi-study data on diverse psychedelics, closely matching high-dose DMT on meaning and visual experiences, despite higher volition, liking, auditory, and somesthesia.
DMT increased total aberrant salience and all factors, supporting its role as a psychosis model capturing salience disturbances and exaggerated meaning attribution. Effects are comparable to LSD, suggesting generalised aberrant salience alterations across psychedelics. However, DMT mean scores were slightly, possibly due to shorter durations or less well-remembered effects. Both DMT and LSD most strongly increased Senses Sharpening, indicating enhanced sensory perception across short-and long-acting psychedelics, which is widely reportedand thought to contribute to noetic and insight experiences. Total and Increased Significance were similarly strong expressed, reflecting core phenomena of aberrant salience and consistent with literature highlighting meaning-making as central psychedelic phenomenon. Heightened Emotionality showed similar effects, aligning with euphoric and overwhelming feelings widely reported under psychedelics. Contrastingly, Impending Understanding was slightly weaker and Heightened Cognition stronger than in our LSD study. Contrastingly, the original factors showed comparable effects, suggesting psychometric rather than ontological differences, with the Brazilian ASI Impending Understanding consisting of only one item with most other items reassigned to Heightened Cognition (table S1, S2; figure). Clinically, these experiences resemble psychiatrist Klaus Conrad's concept of apophany in the prodromal phase of schizophrenia, characterised by pervasive senses of estrangement, neutral events acquiring personal significance, and disturbed boundaries between internal meaning attribution and external perception, but also by great apprehension. The results implicate aberrant salience as a possible mechanism in psychedelic experiences. Aberrant salience is linked to psychosis-related symptoms across clinical, subclinical, and non-clinical populationsand modulated by external factors including cannabis useand meditation. Such modulability may underlie psychedelic-induced sensory intensification and enhanced meaning-making. Similarly, the entropic processing framework proposes for psychedelic and psychotic phenomena that reduced sensory gating and loosened cognitive schemas increase information density and attentional scope, fostering altered salience, hyperassociative thinking and expanded meaning attribution. Historically, psychedelic and psychosis research have emphasised different aspects, limiting their comparability. Psychedelic research focuses on mysticism, compassion, support, and context, whereas psychosis research emphasises symptomatologies, functioning, restraint, and safety concerns. Nevertheless, comparative work highlights both convergences and distinctions. DMT best modelled positive symptoms (formal thought disorder, inappropriate affect), characteristic of early psychosis, while the non-classic psychedelic ketamine was more associated with negative symptoms (disturbed attention, distorted body perception, catatonia-like phenomena), resembling later or chronic psychosis. Psychedelic experiences involve more reality monitoring, visual alterations, positive affect, and transient durations, while clinical psychosis is marked by poorer reality monitoring, more auditory disturbances, negative affect, recurrent involuntary episodes, and functional impairment. The closest overlap may be strong existential or metaphysical meaning attribution. Together with these findings, our results suggest that classic psychedelics -particularly DMT -best model positive emotionality -associated with both aberrant salience and suggestibility -may provide a more direct link between the two models.
Blinding was challenging due to DMT's characteristic vapour, odour, taste, and unmistakable subjective effects, potentially influencing suggestibility outcomes. Future studies should test improved placebos that better mimic vapour properties, such as combining inert smoke (e.g., glycerine) with very low DMT doses. The placebo (0.6 mg DMT) may have produced subjective and pharmacological effects. The 2-hour washout period limits exclusion of carryover effects, although none were statistically detected. The small, homogeneous sample -predominantly young, White, single, well-educated, non-religious, and DMT-experiencedlimits generalisability, highlighting the need for larger, diverse samples particularly in clinical populations. Psychometric limitations also apply. The Intensity scale is unvalidated and the HRS lacks formal Portuguese validation. Non-parallel suggestibility items, together with LSD-and DMT-induced increases in Weight, caution against overinterpretation due to potential measurement inequivalence. Splitting the long mystical itemmay have reduced experience depth. Conceptually, aberrant salience may capture only specific psychosis-related processes (e.g., hallucinations, delusions) rather than broader, emotional, cognitive, and behavioural dimensions. Similarly, suggestibility likely reflects only part of psychedelic therapeutic processes. Participant exclusions due to sleep during later CIS items may introduce bias and reduced statistical power. The initial lack of multiple-testing correction to enhance comparability with our LSD results warrants cautious interpretation.
Overall, the DMT findings extend our LSD results, showing similar effects on aberrant salience and suggestibility and supporting the generalisation of concurrent psychotic-and therapeutic-like processes across short-and long-acting psychedelics. Correlations further confirm a close link between aberrant salience and mystical experiences across substances. Furthermore, aberrant salience and suggestibility were associated with positive emotionality, suggesting a novel affective bridge between the psychosis and therapy models. Importantly, suggestions were able to induce post-acute mystical experiences, highlighting clinical potential for inducing, amplifying, and guiding therapeutically relevant psychedelic experiences.
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