Transdiagnostic Psychological Effects of Lysergic Acid Diethylamide– and Psilocybin-Assisted Psychotherapy in Patients With and Without Substance Use Disorders
1
Addiction Psychiatry, University of Geneva, Geneva, Switzerland
Popul. Med. 2026;8(Supplement Supplement 1):
ABSTRACT
BACKGROUND:
Psychedelic-assisted psychotherapy (PAP) has been conceptualized as a transdiagnostic intervention, targeting core psychological processes shared across psychiatric disorders rather than diagnosis-specific symptom profiles. In contrast, substance use disorders (SUD) are commonly assumed to reduce treatment responsiveness, particularly in interventions for depression, where comorbidity is associated with poorer outcomes. Whether SUD meaningfully attenuates the psychological effects of PAP remains insufficiently studied.
METHODS:
We analyzed prospectively collected routine clinical data from the Geneva psychedelic-assisted psychotherapy (PAP) program. Sixty-eight adult patients with treatment-resistant depression received a single session of PAP using either psilocybin (25 mg) or lysergic acid diethylamide (LSD, 100 µg) within a standardized therapeutic framework including preparation and integration phases. Patients were stratified according to the presence (n = 17) or absence (n = 51) of comorbid substance use disorder (SUD). Depressive symptoms (Beck Depression Inventory, BDI) and trait anxiety (State-Trait Anxiety Inventory—Trait, STAI-T) were assessed at screening, prior to the psychedelic session, and one month post-session. Repeated-measures analyses were performed to examine time effects and group × time interactions.
RESULTS:
Both depressive and anxiety symptoms showed significant improvements over time (p < 0.001). No significant main effects of group and no group × time interactions were observed for either outcome (p > 0.05), indicating comparable psychological benefit in patients with and without comorbid SUD.
CONCLUSIONS:
From a public health perspective, these findings challenge the assumption that SUD inherently limit responsiveness to innovative mental health treatments. The absence of a differential effect in patients with and without comorbid SUD suggests that psychedelic-assisted psychotherapy may contribute to reducing treatment inequities, particularly for populations frequently excluded from effective care due to diagnostic boundaries. By supporting a transdiagnostic model, PAP may facilitate broader access, improve engagement across fragmented service systems, and inform more inclusive mental health policies aimed at high-burden, marginalized groups.
Psychedelic-assisted psychotherapy (PAP) has been conceptualized as a transdiagnostic intervention, targeting core psychological processes shared across psychiatric disorders rather than diagnosis-specific symptom profiles. In contrast, substance use disorders (SUD) are commonly assumed to reduce treatment responsiveness, particularly in interventions for depression, where comorbidity is associated with poorer outcomes. Whether SUD meaningfully attenuates the psychological effects of PAP remains insufficiently studied.
METHODS:
We analyzed prospectively collected routine clinical data from the Geneva psychedelic-assisted psychotherapy (PAP) program. Sixty-eight adult patients with treatment-resistant depression received a single session of PAP using either psilocybin (25 mg) or lysergic acid diethylamide (LSD, 100 µg) within a standardized therapeutic framework including preparation and integration phases. Patients were stratified according to the presence (n = 17) or absence (n = 51) of comorbid substance use disorder (SUD). Depressive symptoms (Beck Depression Inventory, BDI) and trait anxiety (State-Trait Anxiety Inventory—Trait, STAI-T) were assessed at screening, prior to the psychedelic session, and one month post-session. Repeated-measures analyses were performed to examine time effects and group × time interactions.
RESULTS:
Both depressive and anxiety symptoms showed significant improvements over time (p < 0.001). No significant main effects of group and no group × time interactions were observed for either outcome (p > 0.05), indicating comparable psychological benefit in patients with and without comorbid SUD.
CONCLUSIONS:
From a public health perspective, these findings challenge the assumption that SUD inherently limit responsiveness to innovative mental health treatments. The absence of a differential effect in patients with and without comorbid SUD suggests that psychedelic-assisted psychotherapy may contribute to reducing treatment inequities, particularly for populations frequently excluded from effective care due to diagnostic boundaries. By supporting a transdiagnostic model, PAP may facilitate broader access, improve engagement across fragmented service systems, and inform more inclusive mental health policies aimed at high-burden, marginalized groups.
| eISSN: | 2654-1459 |
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