DMT, Madness, and Healing: Psychosis Model, Therapy Model, and Their Relations to Mystical Experiences and Positive Emotionality

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.