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Bidirectional relationships between cannabis use, anxiety and depressive symptoms in the mediation of the association with psychotic experience: further support for an affective pathway to psychosis

Rajiv Radhakrishnan, L. Pries, G. Erzin, M. Ten Have, RON DE Graaf, S. van Dorsselaer, N. Gunther, M. Bak, Bart P. F. Rutten, Jim van Os, S. Guloksuz

Psychological Medicine September 12, 2022 DOI: 10.1017/s0033291722002756 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Longitudinal cohort study (mediation analysis) Peer reviewed
Population Participants in the second Netherlands Mental Health Survey and Incidence Study
Topics Anxiety Cannabis
Key findings The authors report a bidirectional relationship between cannabis use, anxiety/depressive symptoms, and psychotic experiences. Cannabis use mediated the path from earlier anxiety or depression to later psychotic experiences only slightly (1.00% and 1.4% of the total effect, respectively), whereas anxiety and depressive symptoms mediated the path from earlier cannabis use to later psychotic experiences more strongly (17% and 37%, respectively).

Abstract

Abstract Background Empirical evidence suggests that people use cannabis to ameliorate anxiety and depressive symptoms, yet cannabis also acutely worsens psychosis and affective symptoms. However, the temporal relationship between cannabis use, anxiety and depressive symptoms and psychotic experiences (PE) in longitudinal studies is unclear. This may be informed by examination of mutually mediating roles of cannabis, anxiety and depressive symptoms in the emergence of PE.

Methods: Data were derived from the second longitudinal Netherlands Mental Health Survey and Incidence Study. Mediation analysis was performed to examine the relationship between cannabis use, anxiety/depressive symptoms and PE, using KHB logit in STATA while adjusting for age, sex and education status.

Results: Cannabis use was found to mediate the relationship between preceding anxiety, depressive symptoms and later PE incidence, but the indirect contribution of cannabis use was small (for anxiety: % of total effect attributable to cannabis use = 1.00%; for depression: % of total effect attributable to cannabis use = 1.4%). Interestingly, anxiety and depressive symptoms were found to mediate the relationship between preceding cannabis use and later PE incidence to a greater degree (% of total effect attributable to anxiety = 17%; % of total effect attributable to depression = 37%).

Conclusion: This first longitudinal cohort study examining the mediational relationship between cannabis use, anxiety/depressive symptoms and PE, shows that there is a bidirectional relationship between cannabis use, anxiety/depressive symptoms and PE. However, the contribution of anxiety/depressive symptoms as a mediator was greater than that of cannabis.

Comparable studies

Other observational and cohort studies on cannabis for anxiety, most cited first.

Study Year Design Participants
Former chronic methylenedioxymethamphetamine (MDMA or ecstasy) users report mild depressive symptoms Former chronic ecstasy users 2001 Observational cohort n = 29
Rates and correlates of cannabis-associated psychotic symptoms in over 230,000 people who use cannabis International sample of people who use cannabis (PWUC) 2022 Observational cohort n = 233,475
Who Turns to Amazonian Medicine for Treatment of Substance Use Disorder? Patient Characteristics at the Takiwasi Addiction Treatment Center Patients with substance use disorders seeking treatment 2020 Observational study
Long-Term Mental Health and Wellbeing Outcomes Associated with Naturalistic Ayahuasca Consumption. Adults with no prior exposure to ayahuasca participating in neo-shamanic ayahuasca... 2025 Prospective cohort study n = 66
Naturalistic use of psychedelics is associated with longitudinal improvements in anxiety and depression during global crisis times. Citizen science cohort recruited agnostically to an interest in drug use 2025 Observational cohort n = 242,260

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