The independent and combined effects of cannabis use and systemic inflammation during the early stages of psychosis: exploring the two-hit hypothesis.
Fabiana Corsi-Zuelli, Leonardo Marques, Daiane Leite Da Roza, Camila Marcelino Loureiro, Rosana Shuhama, Marta Di Forti, Paulo Rossi Menezes, Paulo Louzada-Junior, Cristina Marta Del‐Ben
Psychological Medicine December 1, 2022 DOI: 10.1017/s0033291721000726 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Cross-sectional study Peer reviewed |
|---|---|
| Sample size | 409 |
| Population | First-episode psychosis patients and community-based controls |
| Topics | Cannabis |
| Keywords | Adaptive immunity Anti-inflammatory cytokines Inflammation Innate immunity Pro-inflammatory cytokines Schizophrenia |
| Key findings | Daily cannabis use and age of onset before 17 interact with systemic inflammation to increase the odds of psychosis beyond individual effects, but cannabis consumption is not associated with increased inflammation. |
Abstract
Cannabis consumption is a modifiable risk factor associated with psychosis, but not all cannabis users develop psychosis. Animal studies suggest that an antecedent active immune system interacts with subsequent cannabis exposure and moderates the cannabis-psychosis association, supporting the two-hit hypothesis. The clinical investigations are few, and it is unclear if the immune system is a biological candidate moderating the cannabis-psychosis association or whether cannabis increases inflammation, which in turn, augments psychosis likelihood. We explored the mediating and moderating role of blood inflammation using PROCESS macro. We used data from a cross-sectional study, including 153 first-episode psychosis patients and 256 community-based controls. Participants answered the Cannabis Experience Questionnaire (cannabis frequency, age of onset, and duration), and plasma cytokines were measured [interleukin (IL)-1β, IL-6, IL-4, IL-10, tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), transforming growth factor-β (TGF-β); multiplex]. We computed an inflammatory composite score (ICS) to represent the systemic inflammatory state. Confounders included sex, age, ethnicity, educational level, body mass index, tobacco smoking, lifetime use of other drugs, and antipsychotic treatment. Mediation: Cannabis consumption was not associated with increased inflammation, thus not supporting a mediating effect of inflammation. Moderation: Daily use and age of onset <17 interacted significantly with the ICS to increase the odds of psychosis beyond their individual effects and were only associated with psychosis among those scoring medium-high in the ICS. Immune dysregulation might be part of the pathophysiology of psychosis, not explained by cannabis use or other confounders. We provide the first and initial evidence that immune dysregulation modifies the cannabis-psychosis association, in line with a two-hit hypothesis.
Comparable studies
Other cross-sectional and survey studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabis use before age 15 and subsequent executive functioning 104 chronic cannabis users (49 early-onset before age 15, 55 late-onset after age 15)... | 2011 | Observational cross-sectional study | n = 148 |
| Patterns of simultaneous polysubstance use in drug using university students Drug-using university students | 2006 | Cross-sectional survey | n = 149 |
| Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey Online survey respondents | 2020 | Cross-sectional survey | |
| User perceptions of the benefits and harms of hallucinogenic drug use: A web-based questionnaire study Users of hallucinogenic drugs who completed a web-based questionnaire | 2010 | Cross-sectional survey | n = 600 |
| Illicit Use of LSD or Psilocybin, but not MDMA or Nonpsychedelic Drugs, is Associated with Mystical Experiences in a Dose-Dependent Manner Adults recruited from the MAPS website and newsletter, most reporting use of various... | 2012 | Cross-sectional survey | n = 337 |
Citations in the library
Cites 8
- High-potency cannabis and the risk of psychosis The British Journal of Psychiatry November 30, 2009
- Long-term consequences of adolescent cannabinoid exposure in adult psychopathology Frontiers in Neuroscience November 10, 2014
- Daily use of high-potency cannabis is associated with more positive symptoms in first-episode psychosis patients: the EU-GEI case–control study Psychological Medicine March 18, 2020
- Factors Moderating the Association between Cannabis Use and Psychosis Risk: A Systematic Review Brain Science February 1, 2020
- Cannabis Use and the Risk for Psychosis and Affective Disorders Journal of dual diagnosis January 2, 2020
and 3 more in the library