Effects of short-term cannabidiol treatment on response to social stress in subjects at clinical high risk of developing psychosis

E Appiah-Kusi,S Bhattacharyya,M Colizzi,L Valmaggia,P Mcguire,M G Bossong,N Petros,V Mondelli,R Wilson

doi:10.1007/s00213-019-05442-6

E Appiah-Kusi, S Bhattacharyya + Show 7 more

Open Access

https://doi.org/10.1007/s00213-019-05442-6

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Abstract

RationaleStress is a risk factor for psychosis and treatments which mitigate its harmful effects are needed. Cannabidiol (CBD) has antipsychotic and anxiolytic effects.ObjectivesWe investigated whether CBD would normalise the neuroendocrine and anxiety responses to stress in clinical high risk for psychosis (CHR) patients.MethodsThirty-two CHR patients and 26 healthy controls (HC) took part in the Trier Social Stress Test (TSST) and their serum cortisol, anxiety and stress associated with public speaking were estimated. Half of the CHR participants were on 600 mg/day of CBD (CHR-CBD) and half were on placebo (CHR-P) for 1 week.ResultsOne-way analysis of variance (ANOVA) revealed a significant effect of group (HC, CHR-P, CHR-CBD (p = .005) on cortisol reactivity as well as a significant (p = .003) linear decrease. The change in cortisol associated with experimental stress exposure was greatest in HC controls and least in CHR-P patients, with CHR-CBD patients exhibiting an intermediate response. Planned contrasts revealed that the cortisol reactivity was significantly different in HC compared with CHR-P (p = .003), and in HC compared with CHR-CBD (p = .014), but was not different between CHR-P and CHR-CBD (p = .70). Across the participant groups (CHR-P, CHR-CBD and HC), changes in anxiety and experience of public speaking stress (all p’s < .02) were greatest in the CHR-P and least in the HC, with CHR-CBD participants demonstrating an intermediate level of change.ConclusionsOur findings show that it is worthwhile to design further well powered studies which investigate whether CBD may be used to affect cortisol response in clinical high risk for psychosis patients and any effect this may have on symptoms.

Highlights

Stress plays a major role in the onset and maintenance of psychosis (Pruessner et al 2017)
This outlines that clinical high risk (CHR) participants had more cannabis use than healthy controls at baseline but that cannabis use rates were the same between the Placebo and CBD groups
We found that CHR patients under placebo treatment (CHR-P) had a blunted cortisol response to the Trier Social Stress Test (TSST) compared with healthy controls (HC)

Summary

Introduction

Stress plays a major role in the onset and maintenance of psychosis (Pruessner et al 2017). Exposure to stress in early (Beards et al 2013) and adult (van Winkel et al 2008) life has been linked to an increased risk for psychosis. The hypothalamic-pituitary-adrenal (HPA) axis is a key neuroendocrine regulatory system mediating the biological response to stress. Accumulating evidence suggests that a dysfunction in the HPA-axis might underlie the psychosis continuum (Pruessner et al 2017). A recent review of the evidence (Appiah-Kusi et al 2016) suggests that in response to a stressor, patients with established psychosis and those at clinical high risk (CHR) for psychosis (Day et al 2014; Pruessner et al 2013) tend to exhibit a blunted cortisol response to both social stress and awakening.

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