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

Classic serotonergic psychedelics are receiving renewed attention as adjuncts to psychotherapy for a range of psychiatric conditions, and acute subjective effects—such as perceptual alterations, intensified emotion, mystical-type experiences and ego-dissolution—are thought to mediate therapeutic benefit. Beyond psychedelic dose, non-pharmacological factors commonly labelled 'set' (mindset, expectations) and 'setting' (environmental context) influence the character and intensity of these experiences. Despite increasing clinical interest, little quantitative research has examined how psychedelics interact acutely with other psychoactive drugs in naturalistic use. Kuc and colleagues aimed to address this gap by examining whether concomitant cannabis use modulates the subjective quality of a serotonergic psychedelic experience. The study sought to quantify associations between self-reported cannabis dose taken alongside a psychedelic and scores on validated measures of mystical experience, visual alterations, challenging experiences, ego dissolution and emotional breakthrough, while attempting to account for contextual confounders such as aspects of setting and guiding framework.

This was a prospective, naturalistic online survey recruiting adults who intended to take a serotonergic psychedelic. Ethical approval was obtained from the Imperial College London committees. Participants completed two key surveys: a baseline assessment seven days before the planned psychedelic experience and a post-experience survey one day after. Inclusion criteria were age ≥18, adequate English, and intention to use a serotonergic psychedelic (examples listed included psilocybin, LSD/1P-LSD, ayahuasca, DMT/5-MeO-DMT, mescaline and related compounds). The final analysed sample comprised 321 participants who completed both time points. Post-experience data collected included the specific psychedelic used and a subjective report of its dose (recoded to a 1–5 Likert scale using LSD-equivalent ranges), whether cannabis or other drugs were used during the session and, for each concomitant drug, a subjective categorisation of 'none', 'low', 'medium' or 'high' (recoded 0–3 for cannabis). Participants also reported setting and guiding-framework variables (for example, retreat versus party context, shamanic framework, live singing/chanting and disruptions). The primary subjective outcomes were five standardised instruments: the Mystical Experience Questionnaire (MEQ), the visual subscales of the Altered States of Consciousness Questionnaire (ASC-Vis), the Challenging Experience Questionnaire (CEQ), the Ego Dissolution Inventory (EDI) and the Emotional Breakthrough Inventory (EBI). Scores were computed following standard procedures described in the survey. For analysis, participants were grouped by reported cannabis dose during the psychedelic experience: none, low, medium or high. Potential confounders were identified by one-way ANOVAs testing variables that differed across cannabis groups; retreat setting, party setting, shamanic framework, live singing and disruptions were initially flagged, and multicollinearity assessments (Pearson correlations, variance inflation factor with cutoff VIF < 5) led to exclusion of 'retreat setting' to avoid redundancy. Multivariate analysis of covariance (MANCOVA) was then performed with the five questionnaire scores as dependent variables and cannabis dose group as a fixed factor; Pillai's trace was used as the multivariate statistic for robustness to assumption violations. Covariates were standardised and post hoc Bonferroni correction applied for pairwise comparisons. Complementary regression modelling treated cannabis dose as a continuous ordinal predictor (0–3) and compared linear, quadratic and cubic fits using Bayesian Information Criterion (BIC) for model selection, with setting covariates included.

Of 654 sign-ups, 321 participants completed the analysed surveys. The sample mean age was 30.6 ± 11 years and 68.8% were male. LSD was the most commonly reported psychedelic (50.2%), followed by psilocybin (29.3%); other serotonergic compounds were less frequent. Overall, 39.3% of participants reported using cannabis during the psychedelic session: 16.5% at low dose, 14.0% at medium dose and 8.7% at high dose. Rates of concomitant alcohol, stimulant and tobacco use varied across cannabis groups and were reported in the results, with higher tobacco use among cannabis users. Univariate ANOVAs indicated that several setting-related variables differed across cannabis groups; after accounting for multicollinearity the covariates included in main models were party setting, shamanic framework, live singing and disruptions. The psychedelic dose (the participants' self-reported psychedelic dose category) was distributed equally across cannabis groups and thus was not used as a covariate. MANCOVA indicated a multivariate effect of cannabis dose on the set of subjective measures (Pillai's trace = 0.097, p = 0.009). Regression model selection using BIC identified the best-fitting polynomial for each outcome. A positive linear dose–response relationship was observed for MEQ (p = 0.015), ASC-Vis (p = 0.007) and EDI (p = 0.010), indicating higher scores on mystical-type experience, visual alterations and ego-dissolution with increasing reported cannabis dose. The CEQ followed a quadratic relationship (p = 0.004), where low cannabis doses were associated with lower overall challenging-experience scores but higher doses associated with increased challenging experiences. No significant relationship was found between cannabis dose and EBI scores; however, the authors note that higher cannabis doses compressed the top range of EBI scores and similarly reduced the bottom range of MEQ scores. Subscale analyses of the CEQ showed significant effects for Fear, Grief and Insanity subscales: for Fear and Insanity the pattern was lowest scores in the low-cannabis group, then medium, then no-cannabis, with highest scores in the high-cannabis group; for Grief the lowest scores were in the low-cannabis group and the highest in the no-cannabis group. The authors report that effect sizes were generally small and present raw means and standard deviations in supplementary tables. Pairwise comparisons and full parameter estimates are presented in the supplementary material.

Kuc and colleagues interpret their findings as evidence that concomitant cannabis use is associated with measurable modulation of acute psychedelic subjective effects, reporting dose-dependent increases in mystical-type experiences, visual alterations and ego dissolution, and a non-linear (quadratic) relationship with challenging experiences. They consider several possible explanations. One is a direct pharmacological interaction: cannabinoids and psychedelics may share or influence serotonergic systems, with preclinical data suggesting interactions between cannabinoid signalling and 5-HT receptors and human data indicating that components of cannabis can modulate serotonin-related neurotransmission. The researchers also note that cannabis itself produces phenomenological effects that overlap with some psychedelic effects and that cultural/contextual factors shape the subjective action of cannabis and psychedelics alike. The authors highlight the biphasic nature of cannabis effects as a plausible account of the CEQ findings: low doses can be anxiolytic while higher doses may be anxiogenic, and the THC:CBD ratio may critically influence whether cannabis tends toward anxiolysis or anxiogenesis. They point out specific safety-relevant observations, particularly that high cannabis dose was associated with higher scores on CEQ subscales related to fear and 'insanity', and suggest caution when considering cannabis use alongside psychedelics, especially in vulnerable populations given concerns about psychotomimetic effects. Several limitations are acknowledged that constrain causal inference and interpretation. Dosing for both psychedelics and cannabis was self-reported and categorical rather than measured, with no precise timing or route of cannabis administration recorded. The ordinal nature of cannabis dose and potential bias in subjective dose assessment limit precision about dose–response relationships. Lifetime and recent histories of cannabis and psychedelic use were not collected, so prior tolerance or sensitisation could not be accounted for. The design was observational and naturalistic, so residual confounding and reverse causation (for example, participants using cannabis to modulate an already unfolding experience) cannot be excluded. Effect sizes were generally small, and the authors note that some statistical significance (for MEQ) did not survive conservative correction in supplementary analyses. Finally, they frame the study as hypothesis-generating and argue that controlled laboratory research is required to determine causality and underlying biological mechanisms. In terms of implications, the researchers suggest the results have relevance for harm reduction messaging for recreational users and may eventually inform therapeutic practice, though they caution against assuming benefit or safety without further evidence. They advocate for further controlled studies that measure dose precisely, record timing and route of administration, and include drug-use history as covariates.

The study offers a first quantitative, naturalistic indication that concomitant cannabis consumption is associated with dose-dependent modulation of the acute subjective psychedelic experience. Higher reported cannabis doses were linked to greater mystical-type experiences, visual alterations and ego-dissolution, while challenging experiences showed a non-linear pattern with lower scores at low cannabis doses and higher scores at high cannabis doses, notably on the 'insanity' subscale. Given the prevalence of combined use, the authors suggest these findings are pertinent to harm reduction and may eventually inform therapeutic considerations, but emphasise that controlled research is needed before clinical recommendations can be made.