The impact of cannabidiol treatment on resting state functional connectivity, prefrontal metabolite levels and reward processing in recent-onset patients with a psychotic disorder.
van Boxel et al.·Journal of Psychiatric ResearchImpact 3.0
CBD induced significant changes in functional connectivity in the default mode network, but showed no effects on prefrontal metabolites or brain activity during reward processing.
Summary
n=31 patients with first-episode psychosis (≤5 years after diagnosis); adjunctive CBD 600 mg/day vs. placebo over 28 days. CBD treatment significantly altered functional connectivity in the default mode network (DMN; time×treatment interaction p=0.037): increase in the CBD arm (0.59±0.39 → 0.80±0.32) vs. decrease under placebo (0.77±0.37 → 0.62±0.33). Decrease in positive symptomatology correlated with decreasing glutamate (p=0.029) and NAA levels (p=0.019) only in the CBD group. No effect on prefrontal metabolite concentrations or reward processing.
P
PopulationPatients with recently occurring psychosis (<5 years after diagnosis), stable phase, n=31
I
InterventionAdjunctive CBD 600 mg/day orally, 28 days, in addition to standard therapy
C
ControlPlacebo (adjunctive), 28 days
O
OutcomeSignificant change in functional connectivity in the default mode network (DMN) under CBD vs. placebo (time × treatment interaction p=0,037); no significant effects on prefrontal metabolite concentrations or brain activity during reward processing
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
Downgraded for
Imprecision
Quality profile
Sample size★★★★★
BlindingDouble-blind
Effect sizeMixed
Citations / year★★★★★
Authors
van Boxel R, Gangadin SS, Janssen H, van der Steur S, van der Vinne LJC, Dortants L, Pelgrim TAD, Draisma LWR, Tuura R, van der Meer P, Batalla A, Bossong MG
The first clinical trials with cannabidiol (CBD) as treatment for psychotic disorders have shown its potential as an effective and well-tolerated antipsychotic agent. However, the neurobiological mechanisms underlying the antipsychotic profile of CBD are currently unclear. Here we investigated the impact of 28-day adjunctive CBD or placebo treatment (600 mg daily) on brain function and metabolism in 31 stable recent-onset psychosis patients (<5 years after diagnosis). Before and after treatment, patients underwent a Magnetic Resonance Imaging (MRI) session including resting state functional MRI, proton Magnetic Resonance Spectroscopy (H-MRS) and functional MRI during reward processing. Symptomatology and cognitive functioning were also assessed. CBD treatment significantly changed functional connectivity in the default mode network (DMN; time x treatment interaction p=0.037), with increased connectivity in the CBD (from 0.59±0.39 to 0.80±0.32) and reduced connectivity in the placebo group (from 0.77±0.37 to 0.62±0.33). Although there were no significant treatment effects on prefrontal metabolite concentrations, we showed that decreased positive symptom severity over time was associated with both diminishing glutamate (p=0.029) and N-acetyl-aspartate (NAA; neuronal integrity marker) levels (p=0.019) in the CBD, but not the placebo group. CBD treatment did not have an impact on brain activity patterns during reward anticipation and receipt or functional connectivity in executive and salience networks. Our results show that adjunctive CBD treatment of recent-onset psychosis patients induced changes in DMN functional connectivity, but not prefrontal metabolite concentrations or brain activity during reward processing. These findings suggest that DMN connectivity alteration may be involved in the therapeutic effects of CBD.