Does cannabidiol reduce the adverse effects of cannabis in schizophrenia? A randomised, double-blind, cross-over trial.
Chesney et al.·NeuropsychopharmacologyImpact 4.4
HarmGRADEModerate11 citations
Samplen = 30 Pat.
Durationunclear
ControlPlacebo before vaporized cannabis
EndpointHVLT-R
Blindingdoppelblind
DesignRCT
Cannabinoidkombination
Max. dose1060.0 mg
Routeoral
”Key finding
CBD pretreatment worsened rather than improved the cognitive and psychotic effects of cannabis: verbal recall was worse (-1,3 words) and PANSS positive symptoms were higher (+2,2 points) compared to placebo.
Summary
RCT (n=30) in schizophrenia patients with cannabis use disorder; randomized, double-blind, cross-over design. CBD premedication 1000 mg vs. placebo before vaporized cannabis (THC 20-60 mg). Delayed verbal recall after CBD premedication worse than after placebo (3.5 vs. 4.8 words, MD=-1.3, 95% CI: -2.0 to -0.6, p=0.001). PANSS-P increase after CBD greater than after placebo (+5.0 vs. +2.9, MD=2.2, 95% CI: 0.6-3.7, p=0.01). CBD did not attenuate cannabis effects, but paradoxically enhanced them.
P
PopulationAdults with schizophrenia or schizoaffective disorder and comorbid cannabis use disorder, n=30
I
InterventionOral CBD 1000 mg, 3 hours before inhalation of vaporized cannabis (THC 20–60 mg)
C
ControlPlacebo (oral) before vaporized cannabis
O
OutcomeDelayed verbal recall after CBD pretreatment 3,5 words vs. 4,8 words after placebo (MD = −1,3; 95% CI: −2,0 to −0,6; p=0,001); PANSS-P increase after CBD +5,0 vs. +2,9 after placebo (MD = 2,2; 95% CI: 0,6–3,7; p=0,01)
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 sizeHarm
Citations / year★★★★★
Authors
Chesney E, Oliver D, Sarma A, Lamper AD, Slimani I, Lloyd M, Dickens AM, Welds M, Krakstrom M, Gasparini-Andre I
In patients with schizophrenia, cannabis use exacerbates symptoms and can lead to a relapse of psychosis. Some experimental studies in healthy volunteers suggest that pre-treatment with cannabidiol (CBD) may reduce these effects, but others do not. Here, we investigated whether pre-treatment with CBD ameliorates the acute adverse effects of cannabis in patients with schizophrenia. Participants (n = 30) had schizophrenia or schizoaffective disorder plus a comorbid cannabis use disorder. In a double-blind, randomised, placebo-controlled, crossover trial, participants received oral CBD 1000 mg or placebo three hours before inhaling vaporised cannabis (containing Delta(9)-tetrahydrocannabinol (THC) 20-60 mg). The primary outcome was delayed verbal recall measured with the Hopkins Verbal Learning Test-Revised. We also measured psychotic symptoms with the Positive and Negative Syndrome Scale (PANSS) - positive subscale. Delayed verbal recall after cannabis administration was 3.5 words (95% confidence interval [CI]: 2.5-4.5) following pre-treatment with CBD, compared to 4.8 words (95% CI: 3.9 to 5.8) following pre-treatment with placebo (mean difference [MD] = -1.3 [95% CI: -2.0 to -0.6]; p = 0.001). After CBD pre-treatment, inhalation of cannabis was associated with an increase in PANSS-P score of 5.0 (95% CI: 3.6 to 6.5), compared to 2.9 (95% CI: 1.5 to 4.3) following pre-treatment with placebo (MD = 2.2 [95% CI: 0.6 to 3.7]; p = 0.01). Administration of CBD did not have a significant effect on plasma concentration of THC or its active metabolite, 11-hydroxy-THC. In patients with schizophrenia and a comorbid cannabis use disorder, pre-treatment with CBD did not attenuate the acute effects of cannabis on memory impairment or psychotic symptoms, but appeared to exacerbate them. The study was registered on Clinicaltrials.gov (NCT04605393).