Psychedelics and mindfulness: A systematic review and meta-analysis

Radakovic and colleagues frame their review against a renewed research interest in classic serotonergic psychedelics (for example psilocybin, LSD, DMT/ayahuasca and mescaline) and a well-established literature on mindfulness-based practices. Psychedelics produce a range of subjective effects and their therapeutic potential has been reported across conditions such as depression, addiction and cancer-related distress. Mindfulness — broadly defined as present-moment, non-judgemental awareness encompassing attention, acceptance and attitude — is measured by a variety of psychometric instruments (for example the Five Facet Mindfulness Questionnaire, FFMQ; the Mindful Attention Awareness Scale, MAAS; and the Philadelphia Mindfulness Scale, PHLMS). Prior narrative and some quantitative reviews suggested psychedelics might enhance wellbeing, openness and mindfulness-like capacities, but no systematic review had specifically synthesised evidence on how psychedelic use affects facets or characteristics of mindfulness. This paper therefore set out to investigate whether psychedelic use is associated with increases in mindfulness overall and in specific mindfulness facets. In addition to a systematic review across clinical and non-clinical samples, the investigators conducted an exploratory random-effects meta-analysis of pre–post mindfulness data where enough numerical information was available, with the aim of identifying any consistent effects across studies and mindfulness subdomains.

The review protocol was registered on PROSPERO (CRD42019160973) and the review was conducted according to PRISMA guidance. Searches covered multiple electronic databases (MEDLINE, Embase via OVID; PsycINFO and AMED via EBSCO), forward and backward citation tracking (including Scopus), specialist bibliographies (MAPS), websites of relevant organisations and retreats, and grey literature; the initial search covered literature to 10 December 2019 and was updated on 18 January 2021. Search terms combined psychedelic-related terms (for example 'psilocybin', 'ayahuasca', 'DMT', 'LSD') with mindfulness-related terms ('mindfulness', 'meditation', 'attention', 'consciousness'). Eligibility criteria included primary and secondary empirical studies in English that measured mindfulness in relation to psychedelic use in adults (≥18 years); all study designs except systematic reviews were eligible and there were no restrictions on clinical versus non-clinical populations. Two reviewers independently screened titles/abstracts and full texts, with disagreements resolved by discussion and, if needed, a third reviewer. Extracted data included study design, participant characteristics, intervention details, mindfulness measures and quantitative pre/post data (means, standard deviations, sample size, p-values). Study quality was appraised independently by two reviewers using National Heart, Lung, and Blood Institute Study Quality Assessment Tools. For synthesis the investigators performed descriptive comparison of study characteristics and an exploratory meta-analysis using R (meta package). Studies eligible for meta-analysis were pre–post designs with complete subdomain scores on the FFMQ (or extractable numerical data). Where numerical data were not provided, authors were contacted twice; if unavailable, the team estimated means and standard deviations by extracting values from published graphs. Standardised mean differences (with 95% confidence intervals and study weights) were calculated. Heterogeneity was assessed using Q (chi-square) and I2 statistics and prediction intervals were used to aid clinical interpretation. Where studies had multiple intervention groups, means and SDs were pooled for analysis.

Searches returned 1805 records and 13 studies met inclusion criteria. The included literature comprised eight ayahuasca studies, two psilocybin studies, two 5-MeO-DMT studies and one study of mixed serotonergic psychedelics. Study designs were predominantly pre–post without a control group (11 studies); one was a cross-sectional survey and one was a randomised controlled trial. Across all studies total N = 530 participants, with individual study samples ranging from 10 to 152. Mean age calculated from 10 studies was 44.9 years (SD 1.6) and the mean proportion male across 12 studies was 53.4% (SD 14%). Three studies recruited participants with clinical conditions (depression, borderline personality disorder-like presentations, and addiction) and the remainder recruited non-clinical samples. Timing of mindfulness measurement varied: of 12 studies that reported timing, 75% (N = 9) collected outcomes immediately or ~24 hours post-ingestion and 25% (N = 3) collected outcomes between two weeks and three months; longer-term follow-up (1 week to 6 months) occurred in 41.7% (N = 5) of studies. Quality appraisal judged the overall methodological quality as fair. Common limitations were small samples, lack of sample size calculations, absence of control groups, and variability in intervention delivery (notably dose, ceremony/setting and facilitator practices) — the latter being especially pertinent for ayahuasca studies where ritual context and batch alkaloid variability can affect standardisation. Measures of mindfulness varied: nine studies used the FFMQ (three used the short form), two used MAAS, one used PHLMS, and one used the Freiburg Mindfulness Inventory plus the Toronto Mindfulness Scale. Intervention delivery ranged from researcher-administered dosing to ceremonial administration by experienced facilitators; in many studies dose quantities were determined by facilitators rather than strictly pre-specified, and one study used self-administered sub-threshold dosing. Regarding outcomes, all but one study reported a statistically significant improvement in at least one mindfulness domain either acutely, sub-acutely or at follow-up. Seven studies reported significant increases on the FFMQ non-judgemental inner experience domain (acceptance-related), and five studies reported increases on the non-reactivity domain; both are interpreted as facets of the acceptance dimension of mindfulness. Several studies (three) reported significant increases on the observation and acting-with-awareness domains (attention-related facets), particularly those administered in preplanned ayahuasca ceremonies; the description facet increased in only one study. Some studies reported sustained increases at follow-up time points (for example seven days, one month, two months). A few studies noted that participants with prior meditation experience had higher baseline or augmented responses, and one study that included a mindfulness-training comparison reported ayahuasca-associated increases in non-judgemental scores independent of training. The exploratory subgroup meta-analysis included six pre–post studies that used ayahuasca and provided complete FFMQ subdomain scores. Results indicated small but statistically significant overall effects favouring ayahuasca for acting with awareness and non-reactivity, with no significant heterogeneity reported for these facets. The non-judgemental inner experience facet also showed a small but significant overall effect, though prediction intervals suggested varying effects across settings. The observation facet exhibited a medium level of heterogeneity and did not show a significant pooled effect. The investigators noted the small number of studies and small sample sizes limited precision of effect estimates and heterogeneity assessment.

Radakovic and colleagues interpret the evidence as indicating that psychedelic use, particularly ayahuasca ingestion, is associated with increases on mindfulness measures, with the strongest and most consistent effects observed on acceptance-related facets (non-judgemental inner experience and non-reactivity) and some evidence for gains in acting with awareness. The authors suggest these changes may help with psychological challenges linked to self-criticism, impulsive reactivity, and distractibility, and that increases in acceptance may underlie therapeutic benefits observed in clinical research. Comparisons reported in some studies indicate that psychedelic-associated increases in certain mindfulness facets can be comparable to, or greater than, scores reported for meditators; one included psilocybin study found increased trait mindfulness versus placebo. The investigators note potential mechanistic overlap between psychedelics and psychological therapies that emphasise acceptance and present-moment awareness (for example Acceptance and Commitment Therapy, Dialectical Behaviour Therapy, and Mindfulness-Based Stress Reduction), and propose that psychedelic-assisted mindfulness approaches warrant further study. However, they caution that the evidence base has limitations: overall study quality was fair, most studies lacked comparator control groups, dosing and delivery were heterogeneous (ceremonial versus laboratory settings, facilitator-dependent dosing), and timing of outcome measurement was inconsistent. The authors also acknowledge the possibility of publication bias and that small sample sizes in the meta-analysis reduce confidence in pooled estimates and heterogeneity metrics. Practical challenges specific to ayahuasca research — such as standardising dose and controlling ceremonial elements without altering intervention fidelity — are emphasised. For future research the paper recommends more randomised controlled trials and prospective cohort studies, harmonisation of mindfulness outcome measures and follow-up timeframes, pre-specification and control of dose (for example using a single batch), and detailed reporting of set and setting (including preparatory and integration procedures). They also suggest directly comparing psychedelic users with non-using controls and further exploration of how participant characteristics (for example prior meditation experience) and non-specific factors (time, attention, expectations, facilitator experience) influence outcomes.

This systematic review and exploratory meta-analysis found that psychedelic ingestion — most evidence coming from ayahuasca studies — is associated with increases in mindfulness measures, particularly facets related to acceptance (non-judgemental inner experience and non-reactivity) and, to a lesser extent, acting with awareness. The authors conclude that further high-quality, controlled research with standardised measures, dosing and reporting of set and setting is needed to clarify the relationship between psychedelics and specific mindfulness facets.