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Table 1 Studies of CBD use in the treatment of schizophrenia and psychosis in Parkinson’s disease and levels of evidence (1 to 5)*

From: The therapeutic role of Cannabidiol in mental health: a systematic review

AuthorDiagnosisPharmacological agentStudy designStrength of evidence*Group (n)DurationAge range (years)Dose range (mg)Scales to measure the clinical outcomeClinical outcomeCommon side effectsReference number
al., 2010
SchizophreniaCBDRCTLevel 2CBD 300 mg = 9
CBD 600 mg = 8
Placebo = 10
1 month> 18CBD = 300 or 600 mgSCWT- The SCWT and skin conductance were recorded at baseline and 1 month after the initial test. Patients received CBD or placebo before the test.
- In the first session, there was significant SCWT effect on electrodermal response factor only (F1,16 = 5.98; p < 0.05) related to time taken to complete board I.
- The mean time required for the responsive group was 77.8 (SEM = 11.7) and for the non-responsive it was was 119.7 (SEM = 12.3).
- In the second assessment, a significant effect for number of errors on board II (F2,16 = 6.027; p = 0.014). The group that received CBD 600 mg had a higher score compared to the other two.
- SCWT score improved in the placebo and 300 mg group, but the improvement was smaller in the 600 mg CBD group.
The improvement in participants given CBD 600 mg was smaller due to sedation.
No side effects were reported.18
Leweke et al., 2012SchizophreniaCBDRCTLevel 2CBD = 20
Amisulpride = 19
4 weeks18–50- Participants were started on 200 mg/day of CBD or amisulpride
- The dose was increased by 200 mg/day in the 1st week.
- The total dose was 200 mg four times daily (800 mg/day)
BPRS, PANSS, EPS, serum prolactin, body weight- Patients in both groups reported a comparable improvement in PANSS and BPRS (1.0, 95% confidence interval 12.6 to 14.6, P = 0.884.
- CBD inhibited FAAH activity and increased intrinsic anandamide signaling, resulting in antipsychotic properties. There was a a statistically significant association between higher anandamide levels and decrease in psychotic symptoms in patients treated with cannabidiol (P = .0012)
Treatment with CBD was associated with lower risk of EPS, less weight gain, and a lower increase in prolactin level - a predictor of galactorrhea and sexual dysfunction.9
Boggs et al., 2018SchizophreniaCBDRCTLevel 2CBD = 18
Placebo = 18
6 weeks18–65CBD = 600 mg/dayMCCB, PANSS- For MCCB Composite score, there was no effect of drug or time, but a significant drug × time effect was observed (F (1, 32) = 5.94; p = 0.02).
- There was only improvement in placebo-treated subjects time (F (1, 32) = 4.84; p = 0.03).
- Lack of improvement in psychotic symptoms on PANSS (F (3, 101) = 1.66; p = 0. 18).
Mild sedation was reported in 20% of participants compared to 5% in placebo.22
McGuire et al., 2018SchizophreniaCBDRCTLevel 2CBD = 43
Placebo = 45
6 weeks18–651000 mg/dayPANSS, SANS, CGI, GAF, BACS- The percentage of responders (patients with an improvement 20% in PANSS total score) was high in CBD group compared to placebo group, however, it could not reach statistical significance.
- About 78.6% of participants improved in CBD group on CGI-I scores (CGI-I: treatment difference = 20.5, 95% CI = − 0.8, − 0.1 p = 0.018) compared to 54.6% in placebo arm.
- CBD group had an improvement in their global functioning (treatment difference = 3.0, 95% CI = -0.4, 6.4; p = 0.08) and cognitive performance (treatment difference = 1.31, 95% CI = − 0.10, 2.72; p = 0.068), however, it could not reach statistical significance.
Mild transient GI discomfort, hyperlipidemia.23
Zuardi et al., 2006SchizophreniaCBDCase seriesLevel 4345 days22–231–5 days = Placebo
6–35 days = Participants were started on 40 mg twice a day, titrated to 1280 mg/day depending on efficacy and tolerability.
36–40 days = Placebo Last 15 days = Olanzapine
BPRS, PANSS, CGI- Case 1: During CBD phase, symptoms improved at 1280 mg/day, followed by worsening of symptoms after CBD discontinuation.
- Case 2: No improvement with CBD and partial improvement with olanzapine, requiring clozapine.
- Case 3: Slight improvement with CBD. However, this patient failed to respond to olanzapine, clozapine, or haloperidol decanoate.
No side effects were reported.24
Zuardi et al., 1995SchizophreniaCBDCase reportLevel 414 weeks191–4 days: Placebo
4–30 days: CBD oil was increased to 1500 mg/day in divided doses.
31–34 days: Placebo
After 35 days: Haloperidol was started.
BPRS- Open BPRS scores improved from 42 to 13 and blind BPRS scores improved from 50 to 30, for an improvement of 69 and 69%, respectively.
- Improvements in following factors of BPRS: thought disturbance (62.5 to 25%), hostility-suspiciousness (83.3 to 33.3%), anxiety-depression (62.5 to 18.8%), activation (58.3 to 16.7%), and anergia (31.3 to 0.0%).
No side effects were reported.25
Zuardi et al., 2009Psychosis in Parkinson’s diseaseCBDOpen-label pilot studyLevel 364 weeksMean age 58.8 ± 14.9 yearsThe initial dose of 150 mg was increased to 400 mg at the end of week 4, with an increase of 150 mg/week.BPRS, PPQ- There was an improvement on total scores of BPRS (P < 0.001) and four BPRS factors scores (Thinking disorder p = 0.002, Withdrawal-retardation P = 0.007, Anxious-depression p = 0.003, Activation p = 0.005) including positive and negative symptoms.
- A reduction in scores of PPQ (P = 0.001) was observed at the endpoint of study.
No adverse effect on cognitive functioning was reported.26
  1. BACS: Brief Assessment of Cognition in Schizophrenia, BPRS: Brief Psychiatric Rating Scale, CBD: cannabidiol, CGI: Clinical Global Impressions, EPS: extrapyramidal symptoms, GAF: Global Assessment of Functioning, GI: Gastrointestinal, MCCB: MATRICS Consensus Cognitive Battery, PANSS: Positive and Negative Syndrome Scale, PPQ: Parkinson Psychosis Questionnaire, RCT: randomized controlled trial, SANS: Scale for the Assessment of Negative Symptoms, SCWT: Stroop Color Word Test, Δ9-THC: Δ9-tetrahydrocannabinol
  2. *The Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence was used to grade the quality of evidence (OCEBM, 2019). Level 1 evidence is for systematic review of RCTs or individual RCT of narrow confidence interval, Level 2 for cohort studies or systematic review of cohort studies, Level 3 for case-control studies or systematic review of case-control studies, and Level 4 for case-series for studies focused on therapy, prevention, etiology and harm (OCEBM, 2019)