Set and Setting: A Randomized Study of Different Musical Genres in Supporting Psychedelic Therapy

Contemporary clinical research has renewed interest in classic psychedelics (agents acting at the serotonin 2A receptor such as psilocybin, LSD, and DMT) for a range of psychiatric indications including depression, anxiety related to life‑threatening illness, and substance use disorders. Psychedelic therapy historically emphasises the importance of "set" (the individual's psychological state) and "setting" (the environmental context), and music has been a near‑universal element of clinical sessions. Despite these long‑standing recommendations, there has been little experimental work isolating how specific session components such as musical selection influence subjective drug effects or therapeutic outcomes, and prior studies have had methodological limitations (for example, between‑subject designs, quasi‑randomisation, or absence of objective clinical endpoints). Strickland and colleagues set out to experimentally evaluate whether musical genre played during psilocybin sessions affects acute subjective experiences and a clinical outcome in an open‑label smoking cessation study. Using a within‑subject, counterbalanced design, participants received psilocybin sessions accompanied either by a Western classical playlist (commonly used in psychedelic therapy) or by an overtone‑based playlist emphasising instruments with strong overtone signatures (e.g. Tibetan singing bowls, gongs, didgeridoo, sitar, overtone singing). After sampling both playlists, participants chose the playlist for a third, higher‑dose session; subjective experiences (MEQ30, CEQ) and biologically verified smoking abstinence were analysed by musical condition. The study aims to inform whether standardised Western classical music is uniquely beneficial or whether alternate or individualised musical approaches might be appropriate in psychedelic therapy.

This analysis used data from an open‑label psilocybin trial for smoking cessation; additional details of the parent trial are reported elsewhere. The analytic subsample comprised 10 nicotine‑dependent adults randomised to receive different musical playlists across psilocybin sessions. Participants were required to smoke at least 10 cigarettes per day, express a desire to quit, be medically healthy on screening, have no family history of psychotic or bipolar disorders, and have no substance use disorder other than nicotine within the prior five years. The sample averaged 51 years of age (range 37–65), was predominantly male (8 men, 2 women), and largely White (9 White, 1 Asian). The study received IRB approval and participants provided informed consent. Participants completed a 15‑week treatment programme that included a manualised cognitive‑behavioural smoking cessation intervention (CBT with mindfulness and guided imagery) delivered in four weekly preparatory meetings before the first psilocybin session. Three psilocybin sessions occurred in weeks 5, 7, and 13; the first session served as the target quit date. Psilocybin was administered orally in opaque capsules: 20 mg/70 kg in the first session and 30 mg/70 kg in subsequent sessions. During sessions, staff provided nondirective interpersonal support, participants wore eye masks and listened through headphones to a music programme; music was also played through room speakers when headphones were removed. The investigator playlists were either a Western classical playlist reflecting music typically used in psychedelic therapy, or an overtone‑based playlist emphasising instruments with prominent overtone content. The order of playlists across sessions 1 and 2 was randomised and counterbalanced; about 25% of tracks overlapped between playlists and chiefly occurred in the pre‑onset and come‑down portions of sessions. Prior to session 3 participants selected which playlist would accompany that high‑dose session. Each participant also provided about 60 minutes of personally selected music that was played approximately 4 hours after dosing (near resolution of peak effects); one participant declined to include personal music. Primary acute subjective outcomes were the Mystical Experience Questionnaire (MEQ30) and the Challenging Experience Questionnaire (CEQ), completed at the end of each psilocybin session. Smoking abstinence was assessed with three measures: timeline follow‑back (self‑report), exhaled carbon monoxide (CO; Bedfont Micro III), and urinary cotinine; seven‑day point prevalence abstinence required concordant TLFB and objective verification (urine cotinine < 200 ng/mL and CO ≤ 6 ppm). Analyses used descriptive statistics and comparisons of MEQ30 and CEQ between the two randomized musical sessions via paired t‑tests with Cohen's dz effect sizes. A mixed‑effects model with a random participant intercept controlled for session dose. A between‑subjects t‑test summarised differences for the participant‑selected session. Two‑tailed tests with α = 0.05 were performed in R.

Mystical experiences (MEQ30) tended to be higher during overtone‑based sessions compared with Western classical sessions. Mean MEQ30 scores were 0.68 (SD = 0.20) for overtone‑based sessions and 0.52 (SD = 0.21) for Western classical sessions; this corresponded to a medium effect size (Cohen's dz = 0.57) but did not reach statistical significance (paired comparison p = 0.107). In a mixed‑effects model controlling for psilocybin dose, the musical‑genre difference remained of similar magnitude (b = 0.14, p = 0.108); higher MEQ30 scores were also observed in 30 mg/70 kg sessions compared with 20 mg/70 kg sessions (b = 0.14, p = 0.102), though these dose‑related effects likewise did not reach significance. Challenging experiences measured by the CEQ showed no meaningful differences by musical genre. Mean CEQ scores were 0.33 (SD = 0.20) for overtone‑based sessions and 0.34 (SD = 0.22) for Western classical sessions; the genre comparison was nonsignificant (p = 0.74) with a very small effect (Cohen's dz = -0.11). When participants selected the playlist for the third (high‑dose) session, 6 of 10 (60%) chose the overtone‑based playlist. In that participant‑selected session, mean MEQ30 scores were 0.70 (SD = 0.26) for those who selected Western classical and 0.58 (SD = 0.16) for those who selected overtone‑based music; this between‑group difference was not significant (p = 0.41). CEQ scores in session 3 were similar across selections (Western classical mean 0.29, SD = 0.17; overtone mean 0.26, SD = 0.15; p = 0.79). Biologically confirmed smoking abstinence at end of treatment and follow‑up was reported by musical selection for the final session. Among participants who selected Western classical for session 3, 2 of 4 (50%) were abstinent at end of treatment and remained abstinent through subsequent assessments (6 months, 12 months, and long‑term follow‑up). Among those who selected overtone‑based music, 5 of 6 (83.3%) were abstinent at end of treatment, and 4 of 6 (66.6%) remained abstinent through long‑term follow‑up. The parent study reported a substantive clinical benefit of the intervention overall; the current analysis indicates a modest advantage in abstinence rates for those who selected the overtone‑based playlist, though the small sample size limits inference.

Strickland and colleagues interpret these data as a first experimental within‑subject test of how musical genre may influence psychedelic session experiences and a clinical behavioural outcome. They report a trend toward greater mystical‑type experiences during sessions with overtone‑based music compared with Western classical music, but emphasise that this difference did not achieve statistical significance in the small sample. Challenging experiences did not differ by musical genre, and the clinical smoking‑cessation outcome was broadly similar across participant‑selected musical genres, with a modest numerical advantage for those choosing the overtone‑based playlist. The investigators position these findings against the historical standard that Western classical music is inherently superior for supporting psychedelic therapy. They suggest the data challenge that assumption and raise the possibility that sounds outside traditionally defined musical genres may effectively support psychedelic sessions. The authors also note an implication for individualisation: when participants selected their preferred playlist for the final session the pattern of acute effects differed in a way that suggests personalised music selection may warrant further experimental study. Several limitations are acknowledged. The subsample was small (N = 10), constraining statistical power and generalisability. The study did not collect detailed measures of participants' subjective musical experience such as liking or resonance, which limits interpretation of how individual music preference influenced outcomes. Some overlap between playlists (≈25% of tracks) occurred, primarily during pre‑onset and come‑down periods, potentially reducing contrast between conditions. The open‑label design cannot disentangle genre effects from expectancy or placebo influences, although the authors argue the format more closely mirrors likely clinical practice and permitted the randomised within‑subject comparison. Finally, between‑subject findings from the participant‑selected session are limited relative to the within‑subject comparisons. Overall, the researchers conclude that no clear superiority of Western classical music was identified and advocate for parametric, experimental study of session components. They propose that processes for generating patient‑specific musical selections, or otherwise individualising musical support, should be explored in future work to optimise therapeutic outcomes across diverse populations. The authors call for follow‑up studies that include larger samples, measurement of subjective musical responses, and experimental tests of personalised versus standardised musical approaches.