Anxiety disorders (e.g., generalized anxiety disorder, panic disorder, social phobia) are the most common psychiatric disorders, with a current worldwide prevalence of 7.3% (1, 2). They were also found to be burdensome and costly to individuals and wider society (3). Despite such a widespread presence, current treatments only provide partial success rates, with pharmacological therapies (benzodiazepine and antidepressant medications) resulting in response rates (typically defined as >50% decrease in symptoms relative to baseline) of 50.8–58.3% (4, 5), and cognitive behavioral therapies (CBT) resulting in response rates of 51.7–53.6% (5, 6) in adults with anxiety disorders. Additionally, the combination of the two approaches has not been found to result in more promising outcomes, with a response rate of 54.2% (5). Further studies have concluded that the exact rate of treatment response also varies per anxiety disorder. For instance, in patients with a lifetime panic disorder, the response rates drop drastically to about 13% for each of the aforementioned therapeutic modalities (7), whereas patients with comorbid anxiety and depression tend to prematurely terminate treatment more frequently than patients with a single diagnosis (8). The above findings illustrate a rising urgency within the field of mental health for efficient fast-acting treatment options that prove efficacious for the large heterogeneous cluster that makes up anxiety disorders, and that persist after treatment.

Before criminalization of psychedelic drugs in the 1970s, studies combining administration of a psychedelic drug and psychological therapy found significant improvements in anxiety-related symptomatology (9). Recently, there has been a resurgence of interest regarding the therapeutic potential of these substances, including psilocybin, ayahuasca, and LSD, in treating an array of different mental health disorders (10–14). More modern trials have assessed the efficacy of psychedelics to reduce anxiety symptoms among patients with a life-threatening illness, and have demonstrated large significant reductions in ratings of anxiety, with a response rate of 60–80% (defined as >50% decrease in measure relative to baseline), sustained over the course of 6–12 months post treatment (15–17), and in a smaller cohort up to 4.5 years post treatment (18). Similar reductions in ratings of anxiety symptoms have been demonstrated in trials assessing the efficacy of a psychedelic to alleviate symptoms of treatment-resistant depression (12, 19, 20), and in naturalistic samples with heterogeneous mental health status (21–23). In healthy volunteers, the persisting effect of psychedelics on feelings of anxiety have been mixed, with one study reporting persisting reductions in acute (state) anxiety 1 week, and reductions in personality-related (trait) anxiety 1 month after psilocybin ingestion (24), and another study reporting no changes in trait anxiety 1 and 12 months after LSD (25). The questionable rigidity in the research design of the earlier studies, including lack of statistical analysis and validated outcome measures (9), and the promising findings of modern trials, warrant further investigation of the persisting effects of ingestion of a psychedelic drug on acute and personality-related anxiety, independent of life-threatening illness or comorbid depression. Furthermore, if psychedelic substances do reduce anxiety, it is of interest to understand what psychological processes may be at play.

The personality trait neuroticism, reflecting an individual’s tendency to experience negative emotions, sensitivity to aversive cues, and insufficient ability to cope with stress, has been found to be the personality trait that is the most strongly associated with many forms of psychopathology (26–31), and a core vulnerability factor common to anxiety and mood disorders (32). Although it has been argued that personality traits are relatively stable throughout adulthood, an array of clinical work has shown that personality is amenable to changes across the lifespan (33), with neuroticism being found to fluctuate to one standard deviation across the lifespan (34). As such, it has been suggested that reducing neuroticism should be the primary focus of therapeutic interventions when treating psychopathologies such as anxiety (33). It has been repeatedly found that ingestion of a psychedelic drug can induce rapid and persisting changes in personality traits, and particularly reductions in neuroticism, in both healthy and clinical populations (24, 35–41). Thus, given the reduction in self-rated neuroticism found after ingestion of a psychedelic, it could be suggested that one mechanism by which psychedelic substances induce persisting changes in anxiety levels could be by altering maladaptive personality structures which exacerbate anxiety. However, the relationship between psychedelic-induced changes in anxiety and psychedelic-induced changes in neuroticism has yet to be assessed.

A further psychological process which may be of particular salience when discussing therapeutic efficacy for anxiety, and which psychedelics have been repeatedly found to enhance, are mindfulness capacities (10, 22, 23, 42–46). Mindfulness has been described as “paying attention in a particular way: on purpose, in the present moment, and non-judgmentally” (47). It is generally considered multifaceted, including capacities such as being able to: notice or attend to internal feelings, thoughts, and external simulation (“observing”), label feelings, thoughts and experience with words (“describing”), attending to what is happening in the present moment (“acting with awareness”), take a non-evaluative stance toward internal thoughts and feelings (“non-judgment of inner experience”), and being able to allow emotions and thoughts to come and go, without being interfered by them (“non-reactivity to inner experience”). Given that one of the core components of anxiety disorders is the practice of excessive rumination on non-present fears, leading to a vicious circle of higher levels of physical arousal and more worrying (48), individuals suffering from anxiety disorders typically lack or have lower levels of mindfulness capacities (49). Accordingly, it has been shown that interventions which enhance mindfulness capacities, such as mindfulness-based stress reduction training (MBSR), can be an effective form of treatment for people with anxiety disorders (50), resulting in higher efficiency and improvement rates than cognitive-behavioral group therapy (51). That said, the relationship between psychedelic-induced changes in mindfulness capacities, and psychedelic-induced changes in anxiety, has yet to be assessed.

Finally, another important factor when thinking about therapeutic applications is the longevity of effects. Usually when taking conventional anxiolytics the treatment duration will vary but might extend over months (5, 6). For psychedelics, persisting effects on personality or wellbeing can be found up to 12 months after a single dose administration (25), whereas increased mindfulness capacities have been found to persist up to 3 months (43). It has been suggested by some studies that the intensity or quality of the psychedelic experience determines the treatment outcome (52–54). Specifically, it has been repeatedly found that psychedelic-induced mystical-type experiences and ego dissolution, the latter a phenomenon characterized by the reduction in self-referential awareness, disruption self-world boundaries, and increased feelings of unity with one’s surroundings (55), correlates with long-term (positive) outcomes (23, 52–54, 56–58). Thus, in the present study we also assessed whether we could predict sub-acutechanges in anxiety based on acute ratings of ego dissolution.

In sum, anxiety symptoms and disorders evoke a notable impact on people’s lives, yet the existing treatment options are of limited success. Based on this and previous findings of psychedelic-induced alleviation of anxiety in clinical populations, the present study was designed to assess the sub-acute effects of psilocybin in self-reported healthy retreat attendees on state and trait anxiety, when taken in a supportive group setting. The population is informative to investigate as sub-clinical, “healthy” samples often report meaningful anxiety symptoms that impact one’s well-being and quality of life (59–63), however, due to the lack of clinically established severity of symptoms, it is unlikely that this population is recruited into randomized clinical trials. Thus, this sample of retreat attendees presents an opportunity to explore psychedelic-induced effects in a clinically under-represented, but highlighly salient sample. Additionally, the retreat setting presents an opportunity to assess the feasibility and efficacy of group sessions with psychedelic substances, a likely increasingly popular context upon regulatory rescheduling of psychedelic compounds, as well as a potentially more cost- and time-efficient clinical therapeutic approach. In this context, we also aimed to replicate the previously reported findings on the substance’s ability to increase mindfulness capacities and decrease neuroticism (10, 22, 23, 37–39, 43, 44, 46). As previously rationalized, that such changes may be related to reductions in anxiety, we further aimed to assess whether changes in mindfulness capacities and neuroticism correlated with changes in anxiety. Lastly, we wanted to assess the relationship between psychedelic-induced changes in state and trait anxiety and ego dissolution.

We hypothesized that, compared to baseline, reductions in state and trait anxiety and neuroticism would be observed 24 h and 7 days after ingestion of psilocybin, whereas mindfulness capacities would be enhanced. Furthermore, we hypothesized that reductions in ratings on both aspects of anxiety would be negatively correlated with enhancements in mindfulness capacities and positively correlated with reductions in the personality trait, neuroticism. Finally, we hypothesized that positive changes in ratings of anxiety would be correlated with higher subjective ratings of ego dissolution, the latter measured with the Ego Dissolution Inventory (55).

The impact of anxiety symptoms and disorders on people’s lives and the treatment challenges are well-known within the field of mental health (2, 5, 7, 83, 84). The current study investigated the effects of a single administration of psilocybin on ratings of state and trait anxiety across retreat attendees, when taken in a supportive retreat setting. We further explored hypothesized psychological processes which may predict reductions in anxiety. Compared to baseline measures, we observed medium to large reductions in state anxiety ratings, and medium decreases in trait anxiety ratings, which persisted over a 1 week period post the ingestion of psilocybin. Additionally, we found enhancements in self-rated mindfulness capacities and alterations in personality traits at 1 week post ceremony. Regarding the post-retreat changes in anxiety, analyses showed that ratings of neuroticism and ego dissolution were the most strongly correlated with reductions in trait and state anxiety, respectively.

The present study’s findings are in line with results from historical (clinical) studies, which suggest reductions of anxiety symptoms after a combination of psychedelic drug administration and psychological therapy (85). Similarly, recent clinical studies have found reductions of anxiety in patients with life-threatening illness and/or comorbid treatment-resistant depression after administration of psilocybin (16, 17, 19, 20), LSD (15), and ayahuasca (12). Our findings complement clinical work by demonstrating sub-acute reductions in both anxiety estimates in a self-reported healthy population, whom demonstrate STAI ratings under the clinical threshold (69). This population is informative because sub-clinical, psychologically “healthy” samples often report meaningful anxiety symptoms that impact daily life, including feelings of distress and impairments in cognitive functioning, work performance, and sleep quality (59–63). Importantly, as these symptoms do not meet diagnostic criteria for a clinical disorder, such symptoms often go untreated, and such populations are often under-represented in clinical trials. Thus, the current findings provide preliminary evidence that psilocybin-assisted psychotherapy may also be a treatment option for individuals with sub-clinical anxiety symptoms, if they choose to seek an intervention for their symptoms.

That said, two previous experimental studies assessing the effect of a psychedelic on anxiety symptoms in healthy volunteers have demonstrated mixed results. Whereas one study showed reductions in state anxiety 1 week post administration, and reductions in trait anxiety 1 month post-administration, of a high dose of psilocybin (25 mg/70 kg), another study found no changes in trait anxiety one and 12 months after a high dose of LSD (200 μg) (24, 25). Additionally, previous naturalistic work with individuals reporting heterogenous mental health status also found reductions in anxiety after participation in a 5-MeO-DMT ceremony (22), however a more recent placebo-controlled observational study found that state anxiety ratings decreased 24 h after volunteers ingested either a placebo, or the psychedelic substance ayahuasca, during the context of a group retreat (86). Taking these findings together, one could hypothesize that the significant reduction in anxiety-related symptoms in our self-reported healthy sample is due to both pharmacological and extra-pharmacological factors. A noteworthy extra-pharmacological factor in our study, and some of the previously mentioned studies (22, 86), is the consumption of a psychedelic drug in a group context. Psychedelic drugs have been found to modulate social cognition and interpersonal experiences (87), and individuals whom have undergone psychedelic therapy with psychological support have indicated that increased feelings of social connectedness were an important aspect of the therapeutic process (88). Thus taking together the aforementioned reports, as well as reports from historical research with psychedelic-assisted group therapy [see (89), for a review], it could be hypothesized that the incorporation of groups into psychedelic-assisted psychotherapy may enhance therapeutic outcomes (89). Whereas contemporary psychedelic-assisted group therapy trials are currently limited to one (90), outside of the clinical setting psychedelic drugs have been used for centuries in traditional communal settings. Thus, the retreat setting captured in this study adds further evidence to the feasibility and efficacy of group sessions with psychedelic substances. The latter should also be highlighted, as it will likely be an increasingly popular context upon regulatory rescheduling of psychedelic compounds, as well as a potentially more cost- and time-efficient clinical therapeutic approach.

In line with previous studies (37–39), we detected 1-week decreases in trait neuroticism, which has been shown to be strongly associated with the acuity and comorbidity levels of a range of mental disorders (77, 78). Interestingly, levels of neuroticism have been found to correlate positively with frontolimbic serotonin 5-HT_2A receptor binding, the latter being the main target of psychedelic drugs (28, 91), suggesting direct 5-HT_2A agonism may be the biological basis by which these substances alter neuroticism. Findings from the current and previous studies suggest that a psychedelic-assisted intervention can reduce levels of neuroticism, which are related to reductions in anxiety ratings in our study, and could be related to reductions of symptoms of comorbid conditions such as depression or post-traumatic stress disorder as seen in other studies. We also found post-retreat increases in trait agreeableness, which is in line with a previous naturalistic work done by Weiss et al. (41). Other studies have shown either no changes in agreeableness post-psilocybin experience in depressed patients (37) or higher agreeableness scores among psychedelics users when compared to the general population (38). In contrast with other studies (20, 43), we did not observe meaningful changes in openness. The changes observed in the present study were marginally significant and of moderate effect size (p = 0.06: d = 0.5), which may have been due to dropout rate and decreased power during the 1-week assessment. In sum, the effects of psychedelic substances on neuroticism seem to be more robust and more frequently reported, compared to changes in other personality traits such as agreeableness or openness.

Lastly, the present study aimed to further explore hypothesis-driven correlational relationships between changes in mindfulness and neuroticism and changes in anxiety. Although there was an increase in mindfulness capacities following intake of psilocybin, there were no strong associations between changes in mindfulness capacities and anxiety ratings. In regards to neuroticism, in line with theoretical conceptualizations of neuroticism and trait anxiety as stable, personality-dependent dispositions, we found that sub-acute and 1-week reductions in trait anxiety were most strongly correlated with reductions in neuroticism. Namely, change scores in neuroticism and trait anxiety shared about 89% of the variance variability, pointing out a strong interdependency between the two variables. Although trait anxiety and neuroticism inherently share overlapping constructs, it is important to state that they are not identical (92, 93). Neuroticism via the BFI consists of facets much broader than the construct of trait anxiety via the STAI, including anxiety, angry hostility, depression, self-consciousness, impulsivity, and vulnerability. Future studies should assess what facets of neuroticism correlate with trait anxiety, and what facets overlap with trait anxiety.

Additionally, we also found that the strongest correlator of sub-acute and 1-week changes in state anxiety were ratings of ego dissolution, sharing about 32% of the variance. Specifically, the higher the rating of ego dissolution during the acute experience, the larger the decrease in state anxiety scores both 24 h and 1 week after the experience. A recent review of twenty studies assessing the clinical response to psychedelics in patients with a range of psychological disorders concluded that the main predictive factor of a response to a psychedelic is the intensity of the acute psychedelic experience (94). That said, it has yet to be systematically assessed whether such a “peak” experience is necessary for long-term outcomes (95), or whether the subjective experiences elicited by psychedelic substances are merely epiphenomena of the underlying neurobiological mechanisms, the latter which are conveying any beneficial effects. Additionally, it is possible that other psychological components play important roles in mediating long-term outcomes of psychedelic experience, for instance insight/breakthrough or catharsis, suggestibility, and reliving of trauma have been suggested as important factors determining the psychedelic experience (15, 88, 96–100). Therefore, we should remain cautious when developing and interpreting specific theoretical frameworks of psychedelics’ (psychological) mechanisms of action and focus future efforts on testing these frameworks in the context of experimental studies.

The objectives were tested using a naturalistic, observational design, with attendees of psilocybin ceremonies. Although, this sort of setting has high rates of ecological validity, as it closely resembles a typical environment associated with psychedelic usage (101–104), it also comes with a range of confounding variables, including lack of control over participant inclusion or substance administration The present study was conducted with a self-selected sample of self-determined healthy individuals. To have an indication of the amount of truffles individuals took, we asked for a sample that was analyzed afterward and we asked how much truffles participants consumed. This allows comparisons between findings of our study and that of controlled studies. Another point is that longitudinal studies traditionally come with high dropout rates (105, 106); our study was not different in that sense. The concern of such dropouts is that they could create problematic biases in the data, with for example only those individuals experiencing benefits from the experience being motivated to continue responding to the questions. A recent study investigating potential determinants of study attrition in web-based prospective studies on psychedelic use identified that baseline predictors of attrition (i.e., age, educational levels, and personality traits) were consistent with those reported in longitudinal studies in other scientific disciplines, suggesting their transdisciplinary relevance (80). Moreover, they did not find an association between attrition and psychedelic advocacy or negative drug experiences, advocating against the concerns about problematic biases in these and related data. Finally, the absence of a control group or placebo hampers the ability to draw hard conclusions as to pharmacological vs. extra-pharmacological effects, as it has been found that the retreat setting alone also produces changes in psychological outcomes (86). Future studies should be designed to further assess the contribution of pharmacological versus extra-pharmacological factors [see e.g., (107) for a thorough discussion and recommendations].

Taken together, the present study suggests persisting reductions in anxiety symptoms and trait neuroticism, and increases in mindfulness capacities, after ingestion of psilocybin in a supportive group setting. Given the important role of set and setting on the outcome of psychedelic experience (102, 104), future studies should systematically evaluate the contribution of these extra-pharmacological factors to the treatment outcome, in order to optimize therapeutic strategies. Additionally, naturalistic retreat studies such as this, as well as modern clinical trials (90), are beginning to demonstrate feasibility, safety, and efficacy of group sessions with psychedelics, across different disorders. As it is likely that psychedelic-assisted psychotherapy will be costly and time-consuming for both the patient and the practitioners, future studies exploring the feasibility of group therapy could potentially substantially lower treatment costs, resulting in a more financially accessible treatment option.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Ethics Review Committee of Psychology and Neuroscience, Maastricht University, Faculty of Psychology and Neuroscience, Maastricht, Netherlands. The patients/participants provided their written informed consent to participate in this study.

NM, KK, and JR conceived of the presented idea. NM and MU collected the data. MK and NM conducted the statistical analysis. MK, NM, and KK prepared the first draft of the manuscript. All authors discussed the results and contributed to the final manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.