Table 1. Overview of Included Studies and Principal Findings for Controlled Clinical Trials.
| Author, year of publication | Population (no. of participants) | Study design | CBD dose and scheme | Formulation/route | Primary outcome | Measures | Effect |
|---|---|---|---|---|---|---|---|
| Anxiety | |||||||
| Bergamaschi et al (2011) [17] | Social anxiety disorder patients (24) | IR parallel group trial | 600 mg; single dose | Oral capsules | Anxiety | Visual analogue mood scale (sub-scales; anxiety, cognitive impairment, discomfort and alert) | CBD significantly reduced anxiety, cognitive impairment, discomfort and alert during simulation public speaking test |
| Crippa et al (2011) [22] | Social anxiety disorder patients (10) | IR cross-over trial | 400 mg; single dose | Oral capsules | Anxiety | Visual analogue mood scale | Acute administration reduced subjective anxiety |
| Arndt et al (2017) [25] | Healthy volunteers (38) | IR cross-over trial | 300, 600 and 900 mg; single dose | Oral solution | Reactivity to negative stimuli | Behavioral tasks | Single doses of CBD had little effect on reactions to negative emotional stimuli |
| Crippa et al (2004) [21] | Healthy volunteers (10) | IR cross-over trial | 400 mg; single dose | Oral capsules | Anxiety | Visual analogue mood scale (sub-scales; anxiety, physical sedation, mental sedation and other feelings and attitudes) | CBD significantly decreased subjective anxiety and increased mental sedation |
| Zuardi et al (2017) [19] | Healthy volunteers (60) | IR parallel group trial | 100, 300 and 900 mg; single dose | Oral capsules | Anxiety | Visual analogue mood scale (anxiety and sedation factors) | CBD 300 mg reduced subjective anxiety measures and presented lower sedation level when compared with clonazepam. This was not observed with CBD 100 and 900 mg. |
| Martin-Santos et al (2012) [23] | Healthy volunteers (16) | NR controlled trial | 600 mg; single dose | Oral | Anxiety | Spielberger State Anxiety Inventory, visual analogue mood scale | There was no difference between CBD and placebo on anxiety levels. |
| Bhattacharyya et al (2010) [24] | Healthy volunteers (15) | NR controlled trial | 600 mg; single dose | Oral capsules | Anxiety | Visual analogue mood scale- tranquilization and calming sub-scale. | CBD single dose reduced anxiety levels. |
| Linares et al (2019) [18] | Healthy volunteers (57) | IR parallel group trial | 150, 300 and 600 mg; single dose | Oral capsules | Anxiety | Visual analogue mood scale | 300 mg of CBD significantly reduced anxiety during simulation public speaking test |
| Das et al (2013) [27] | Healthy volunteers (48) | IR parallel group trial | 32 mg; single dose | Inhalation/vaporized | Extinction and consolidation | Skin conductance and shock expectancy measures | CBD enhanced consolidation of extinction learning |
| Hindocha et al (2015) [26] | High and low cannabis use and high and low schizotipy (48) | CR cross-over trial | 16 mg; single dose | Inhalation/vaporized | Emotional processing | Computer-based emotional processing task | CBD improved recognition of emotional facial affect. |
| Hundal et al (2018) [20] | Non-clinical high paranoid group (32) | IR parallel group trial | 600 mg; single dose | Oral capsules | Anxiety | Beck’s anxiety inventory | CBD apparently seemed to increase anxiety levels. |
| Psychotic disorders | |||||||
| Hallak et al (2010) [31] | Schizophrenia patients (28) | IR parallel group trial | 300 or 600 mg; single dose | Oral capsules | Cognitive functioning | Stroop color word test | 300 and 600 mg of CBD do not lead to cognitive improvement |
| Boggs et al (2018) [28] | Chronic schizophrenia patients (42) | IR parallel group trial | 600 mg/day; 6 weeks | Oral capsules | Psychotic symptoms, cognitive functioning | Positive and negative syndrome scale T score of MATRICS consensus cognitive battery | Psychotic symptoms improved in both groups without significant difference, cognitive functioning improved only in placebo group. |
| Leweke et al (2012) [29] | Acutely psychotic patients (32) | IR parallel group triala | 200 mg/day up to 800 mg/day; 4 weeks | Oral capsules | Psychotic symptoms | Positive and negative syndrome scale; brief psychiatric rating scale | CBD is as effective as amisulpride in improving psychotic symptoms |
| McGuire et al (2018) [30] | Schizophrenia patients (88) | IR parallel group trial | 1,000 mg/day; 6 weeksb | Oral solution | Psychotic symptoms | Positive and negative syndrome scale, clinical global impressions scale | Treatment with CBD improved positive psychotic symptoms and clinicians’ impressions of illness improvement. |
| Cognitive functioning, level of functioning | Brief assessment of cognition in schizophrenia; global assessment of functioning scale | Improvement in cognitive performance and in the level of overall functioning with CBD although does not reach statistical significance. | |||||
| Hundal et al (2018) [20] | Non-clinical high paranoid group (32) | IR parallel group trial | 600 mg; single dose | Oral capsules | Persecutory ideation | State social paranoia scale, community assessment of psychic experiences scale | CBD had no effect on precursory thinking and psychotic-like experiences |
| Cannabis use disorder | |||||||
| Haney et al (2016) [32] | Healthy cannabis smokers (32) | IR cross-over trial | 200, 400 and 800 mg; single dose | Oral capsules | Cannabis subjective effects | Subjective mood and drug effects measured with visual analogue scale | CBD did not alter the subjective effects of smoked cannabis |
| Nicotine addiction | |||||||
| Morgan et al (2013) [33] | Tobacco smokers (24) | IR parallel group trial | 400 µg; 1 week | Inhalation/vaporized | Reduction in the number of cigarettes smoked | Number of cigarettes smoked | CBD reduced the number of cigarettes smoked during treatment and at follow-up |
| Hindocha et al (2018) [34] | Tobacco smokers (30) | IR parallel group trial | 800 mg; single dose | Oral capsules | Nicotine withdrawal | Visual probe task and pleasantness rating task | CBD reduced the salience and pleasantness of cigarette cues, compared with placebo but did not influence tobacco craving or withdrawal |
| Dyslipidemia | |||||||
| Jadoon et al (2016) [35] | Patients with type 2 diabetes and dyslipidemia (62) | IR parallel group trial | 200 mg/day; 13 weeks | Oral capsules | HDL cholesterol concentrations | Enzymatic calorimetric assays | CBD did not produce any effect on HDL levels compared to placebo |
| Crohn’s disease | |||||||
| Naftali et al (2017) [36] | Patients with diagnosis of Crohn’s disease (19) | IR parallel group trial | 20 mg/day; 8 weeksb | Sublingual oil | Disease activity | Crohn’s disease activity index | A reduction in disease activity at the end of the study but no significant difference with placebo. |
| Ulcerative colitis | |||||||
| Irving et al (2018) [37] | Patients with mild to moderate ulcerative colitis (60) | IR parallel group trial | 50 mg up to 250 mg/day; 10 weeksa, b, c | Oral capsules | Remission at the end of treatment | Mayo score of ≤ 2 | The primary endpoint was negative but CBD may be beneficial for symptomatic treatment of ulcerative colitis |
aActive-controlled trial, amisulpride. bConcomitant treatment. cCBD-rich botanical extracts capsules contained other compound (up to 4.7% THC). IR: individually randomized; NR: non-randomized; CR: cluster randomized; CBD: cannabidiol; HDL: high-density lipoprotein.