Effects of psychedelic microdosing versus conventional ADHD medication use on emotion regulation, empathy, and ADHD symptoms in adults with severe ADHD symptoms: A naturalistic prospective comparison study.

Adults with attention-deficit hyperactivity disorder (ADHD) often struggle with emotion regulation (ER), impacting their empathic skills and relationships. ADHD medication might not be as effective for ER issues as for ADHD symptoms. Microdosing (MD) psychedelics has shown promise for ADHD treatment and previous studies reported social-emotional benefits. Two online prospective studies investigated MD effects on ER and empathy in adults with severe ADHD symptoms across three assessments: baseline, two-, and four-week post-initiation. Study 1 examined adults initiating MD on their own (n = 233, n = 64, and n = 44) and found positive effects on ER (cognitive reappraisal and expressive suppression) and aspects of empathy (perspective-taking and personal distress). Study 2, including a control group and an ADHD symptom scale, compared individuals only MD (n = 180, n = 50, and n = 38) to individuals using conventional ADHD medication (n = 37, n = 27, and n = 28). After 4 weeks, ADHD symptoms were lower in the MD group. Only improvements in expressive suppression persisted after adding the control group. This study indicates the positive effects of MD psychedelics on ADHD symptoms and ER in adults with severe ADHD symptoms while lacking evidence for effects on empathy.

Trait mindfulness and personality characteristics in a microdosing ADHD sample: a naturalistic prospective survey study.

Background: Microdosing (MD), repeatedly taking psychedelics in small, non-hallucinogenic amounts, has been practiced by individuals to relieve attention deficit hyperactivity disorder (ADHD) symptoms. Generally, adults diagnosed with ADHD have lower levels of mindfulness and differ in personality structure from non-ADHD adults. How MD affects mindfulness and personality in adults with ADHD remains unexplored. Aim: This study aimed to investigate the effects of 4 weeks of MD on mindfulness and personality traits in adults diagnosed with ADHD and those experiencing severe ADHD symptoms. It was expected that mindfulness and the personality traits conscientiousness, extraversion, agreeableness, and openness would increase and neuroticism would decrease after 4 weeks of MD compared to baseline. It was explored if using conventional ADHD medication alongside MD and/or having comorbidities influenced MD-induced effects. Methods: An online prospective naturalistic design was used to measure participants before MD initiation and 2 and 4 weeks later. Validated self-report measures were used assessing mindfulness (15-item Five Facet Mindfulness Questionnaire) and personality traits (10-item version of the Big Five Inventory) at three time points. Results: The sample included n = 233, n = 66, and n = 44 participants at the three time points, respectively. Trait mindfulness, specifically description and non-judging of inner experience, was increased, and neuroticism was decreased after 4 weeks of MD compared to baseline. The remaining personality traits remained unchanged. Using conventional medication and/or having comorbid diagnoses did not change the MD-induced effects on mindfulness and personality traits after 4 weeks. Conclusion: MD induced changes in otherwise stable traits. Future placebo-controlled studies are warranted to confirm whether these changes occur in a controlled setting.

Antidepressant effects of a psychedelic experience in a large prospective naturalistic sample.

BACKGROUND: Over the last two decades, a number of studies have highlighted the potential of psychedelic therapy. However, questions remain to what extend these results translate to naturalistic samples, and how contextual factors and the acute psychedelic experience relate to improvements in affective symptoms following psychedelic experiences outside labs/clinics. The present study sought to address this knowledge gap. AIM: Here, we aimed to investigate changes in anxiety and depression scores before versus after psychedelic experiences in naturalistic contexts, and how various pharmacological, extrapharmacological and experience factors related to outcomes. METHOD: Individuals who planned to undergo a psychedelic experience were enrolled in this online survey study. Depressive symptoms were assessed at baseline and 2 and 4 weeks post-psychedelic experience, with self-rated Quick Inventory of Depressive Symptomatology (QIDS-SR-16) as the primary outcome. To facilitate clinical translation, only participants with depressive symptoms at baseline were included. Sample sizes for the four time points were N = 302, N = 182, N = 155 and N = 109, respectively. RESULTS: Relative to baseline, reductions in depressive symptoms were observed at 2 and 4 weeks. A medicinal motive, previous psychedelic use, drug dose and the type of acute psychedelic experience (i.e. specifically, having an emotional breakthrough) were all significantly associated with changes in self-rated QIDS-SR-16. CONCLUSION: These results lend support to therapeutic potential of psychedelics and highlight the influence of pharmacological and non-pharmacological factors in determining response. Mindful of a potential sample and attrition bias, further controlled and observational longitudinal studies are needed to test the replicability of these findings.

Psychedelic experience dose-dependently modulated by cannabis: results of a prospective online survey.

RATIONALE: Classic psychedelics are currently being studied as novel treatments for a range of psychiatric disorders. However, research on how psychedelics interact with other psychoactive substances remains scarce. OBJECTIVES: The current study aimed to explore the subjective effects of psychedelics when used alongside cannabis. METHODS: Participants (n = 321) completed a set of online surveys at 2 time points: 7 days before, and 1 day after a planned experience with a serotonergic psychedelic. The collected data included demographics, environmental factors (so-called setting) and five validated questionnaires: Mystical Experience Questionnaire (MEQ), visual subscales of Altered States of Consciousness Questionnaire (ASC-Vis), Challenging Experience Questionnaire (CEQ), Ego Dissolution Inventory (EDI) and Emotional Breakthrough Inventory (EBI). Participants were grouped according to whether they had reported using no cannabis (n = 195) or low (n = 53), medium (n = 45) or high (n = 28) dose, directly concomitant with the psychedelic. Multivariate analysis of covariance (MANCOVA) and contrasts was used to analyse differences in subjective effects between groups while controlling for potential confounding contextual 'setting' variables. RESULTS: The simultaneous use of cannabis together with classic serotonergic psychedelics was associated with more intense psychedelic experience across a range of measures: a linear relationship was found between dose and MEQ, ASC-Vis and EDI scores, while a quadratic relationship was found for CEQ scores. No relationship was found between the dose of cannabis and the EBI. CONCLUSIONS: Results imply a possible interaction between the cannabis and psychedelic on acute subjective experiences; however, design limitations hamper our ability to draw firm inferences on directions of causality and the clinical implications of any such interactions.

Turn on, Tune in, and Drop out: Predictors of Attrition in a Prospective Observational Cohort Study on Psychedelic Use.

BACKGROUND: The resurgence of research and public interest in the positive psychological effects of psychedelics, together with advancements in digital data collection techniques, have brought forth a new type of research design, which involves prospectively gathering large-scale naturalistic data from psychedelic users; that is, before and after the use of a psychedelic compound. A methodological limitation of such studies is their high attrition rate, particularly owing to participants who stop responding after initial study enrollment. Importantly, study dropout can introduce systematic biases that may affect the interpretability of results. OBJECTIVE: Based on a previously collected sample (baseline n=654), here we investigated potential determinants of study attrition in web-based prospective studies on psychedelic use. METHODS: Logistic regression models were used to examine demographic, psychological trait and state, and psychedelic-specific predictors of dropout. Predictors were assessed 1 week before, 1 day after, and 2 weeks after psychedelic use, with attrition being defined as noncompletion of the key endpoint 4 weeks post experience. RESULTS: Predictors of attrition were found among demographic variables including age (ß=0.024; P=.007) and educational levels, as well as personality traits, specifically conscientiousness (ß=-0.079; P=.02) and extraversion (ß=0.082; P=.01). Contrary to prior hypotheses, neither baseline attitudes toward psychedelics nor the intensity of acute challenging experiences were predictive of dropout. CONCLUSIONS: The baseline predictors of attrition identified here are consistent with those reported in longitudinal studies in other scientific disciplines, suggesting their transdisciplinary relevance. Moreover, the lack of an association between attrition and psychedelic advocacy or negative drug experiences in our sample contextualizes concerns about problematic biases in these and related data.

Sustained, Multifaceted Improvements in Mental Well-Being Following Psychedelic Experiences in a Prospective Opportunity Sample.

In the last 15 years, psychedelic substances, such as LSD and psilocybin, have regained legitimacy in clinical research. In the general population as well as across various psychiatric populations, mental well-being has been found to significantly improve after a psychedelic experience. Mental well-being has large socioeconomic relevance, but it is a complex, multifaceted construct. In this naturalistic observational study, a comprehensive approach was taken to assessing well-being before and after a taking a psychedelic compound to induce a "psychedelic experience." Fourteen measures of well-being related constructs were included in order to examine the breadth and specificity of change in well-being. This change was then analysed to examine clusters of measures changing together. Survey data was collected from volunteers that intended to take a psychedelic. Four key time points were analysed: 1 week before and 2 weeks, 4 weeks, and 2 years after the experience (N = 654, N = 315, N = 212, and N = 64, respectively). Change on the included measures was found to cluster into three factors which we labelled: 1) "Being well", 2) "Staying well," and 3) "Spirituality." Repeated Measures Multivariate Analysis of Variance revealed all but the spirituality factor to be improved in the weeks following the psychedelic experience. Additional Mixed model analyses revealed selective increases in Being Well and Staying Well (but not Spirituality) that remained statistically significant up to 2 years post-experience, albeit with high attrition rates. Post-hoc examination suggested that attrition was not due to differential acute experiences or mental-health changes in those who dropped out vs. those who did not. These findings suggest that psychedelics can have a broad, robust and sustained positive impact on mental well-being in those that have a prior intention to use a psychedelic compound. Public policy implications are discussed.

Emotional breakthrough and psychedelics: Validation of the Emotional Breakthrough Inventory.

BACKGROUND: Psychedelic therapy is gaining recognition and the nature of the psychedelic experience itself has been found to mediate subsequent long-term psychological changes. Much emphasis has been placed on the occurrence of mystical-type experiences in determining long-term responses to psychedelics yet here we demonstrate the importance of another component, namely: emotional breakthrough. METHODS: Three hundred and seventy-nine participants completed online surveys before and after a planned psychedelic experience. Items pertaining to emotional breakthrough were completed one day after the psychedelic experience, as were items comprising the already validated Mystical Experience Questionnaire and the Challenging Experience Questionnaire. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores were used to predict changes in well-being (Warwick-Edinburgh Mental Wellbeing Scale) in a subsample of 75 participants with low well-being baseline scores (⩽45). RESULTS: Factor analyses revealed six emotional breakthrough items with high internal consistency (Cronbach's alpha=0.932) and supported our prior hypothesis that emotional breakthrough is a distinct component of the psychedelic experience. Emotional breakthrough scores behaved dose-dependently, and were higher if the psychedelic was taken with therapeutic planning and intent. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores combined, significantly predicted subsequent changes in well-being (r=0.45, p=0.0005, n=75), with each scale contributing significant predictive value. Emotional breakthrough and Mystical Experience Questionnaire scores predicted increases in well-being and Challenging Experience Questionnaire scores predicted less increases. CONCLUSIONS: Here we validate a six-item 'Emotional Breakthrough Inventory'. Emotional breakthrough is an important and distinct component of the acute psychedelic experience that appears to be a key mediator of subsequent longer-term psychological changes. Implications for psychedelic therapy are discussed.

From Egoism to Ecoism: Psychedelics Increase Nature Relatedness in a State-Mediated and Context-Dependent Manner.

(1) Background: There appears to be a growing disconnection between humans and their natural environments which has been linked to poor mental health and ecological destruction. Previous research suggests that individual levels of nature relatedness can be increased through the use of classical psychedelic compounds, although a causal link between psychedelic use and nature relatedness has not yet been established. (2) Methods: Using correlations and generalized linear mixed regression modelling, we investigated the association between psychedelic use and nature relatedness in a prospective online study. Individuals planning to use a psychedelic received questionnaires 1 week before (N = 654), plus one day, 2 weeks, 4 weeks, and 2 years after a psychedelic experience. (3) Results: The frequency of lifetime psychedelic use was positively correlated with nature relatedness at baseline. Nature relatedness was significantly increased 2 weeks, 4 weeks and 2 years after the psychedelic experience. This increase was positively correlated with concomitant increases in psychological well-being and was dependent on the extent of ego-dissolution and the perceived influence of natural surroundings during the acute psychedelic state. (4) Conclusions: The here presented evidence for a context- and state-dependent causal effect of psychedelic use on nature relatedness bears relevance for psychedelic treatment models in mental health and, in the face of the current ecological crisis, planetary health.

Predicting Responses to Psychedelics: A Prospective Study.

Responses to psychedelics are notoriously difficult to predict, yet significant work is currently underway to assess their therapeutic potential and the level of interest in psychedelics among the general public appears to be increasing. We aimed to collect prospective data in order to improve our ability to predict acute- and longer-term responses to psychedelics. Individuals who planned to take a psychedelic through their own initiative participated in an online survey (www.psychedelicsurvey.com). Traits and variables relating to set, setting and the acute psychedelic experience were measured at five different time points before and after the experience. Principle component and regression methods were used to analyse the data. Sample sizes for the five time points were N = 654, N = 535, N = 379, N = 315, and N = 212 respectively. Psychological well-being was increased 2 weeks after a psychedelic experience and remained at this level after 4 weeks. Higher ratings of a "mystical-type experience" had a positive effect on the change in well-being after a psychedelic experience, whereas the other acute psychedelic experience measures, i.e., "challenging experience" and "visual effects", did not influence the change in well-being after the psychedelic experience. Having "clear intentions" for the experience was conducive to mystical-type experiences. Having a positive "set" as well as having the experience with intentions related to "recreation" were both found to decrease the likelihood of having a challenging experience. The baseline trait "absorption" and higher drug doses promoted all aspects of the acute experience, i.e., mystical-type and challenging experiences, as well as visual effects. When comparing the relative contribution of different types of variables in explaining the variance in the change in well-being, it seemed that baseline trait variables had the strongest effect on the change in well-being after a psychedelic experience. These results confirm the importance of extra-pharmacological factors in determining responses to a psychedelic. We view this study as an early step towards the development of empirical guidelines that can evolve and improve iteratively with the ultimate purpose of guiding crucial clinical decisions about whether, when, where and how to dose with a psychedelic, thus helping to mitigate risks while maximizing potential benefits in an evidence-based manner.

Psychedelics and the essential importance of context.

Psychedelic drugs are making waves as modern trials support their therapeutic potential and various media continue to pique public interest. In this opinion piece, we draw attention to a long-recognised component of the psychedelic treatment model, namely 'set' and 'setting' ­ subsumed here under the umbrella term 'context'. We highlight: (a) the pharmacological mechanisms of classic psychedelics (5-HT2A receptor agonism and associated plasticity) that we believe render their effects exceptionally sensitive to context, (b) a study design for testing assumptions regarding positive interactions between psychedelics and context, and (c) new findings from our group regarding contextual determinants of the quality of a psychedelic experience and how acute experience predicts subsequent long-term mental health outcomes. We hope that this article can: (a) inform on good practice in psychedelic research, (b) provide a roadmap for optimising treatment models, and (c) help tackle unhelpful stigma still surrounding these compounds, while developing an evidence base for long-held assumptions about the critical importance of context in relation to psychedelic use that can help minimise harms and maximise potential benefits.