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Table 1 Medicinal cannabis trials in mental disorders

From: Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review

Mental Disorder#Cannabinoid(s) StudiedMethodologyResultsClinical Comment
Social Anxiety
 Bergamaschi [38]CBD (600 mg)24 treatment-naïve patients with Social Anxiety were blindly allocated to receive CBD or placebo 1.5 h before a simulated public speaking test. 12 unmedicated healthy controls also completed the test. Self-reports on the Visual Analogue Mood Scale, and Negative Self-Statement scale, and physiological measures were taken at six time points during the testPre-test CBD administration in Social Anxiety patients versus placebo, resulted in significantly reduced anxiety, cognitive impairment and discomfort in speech performance, and significantly decreased hyper-alertness in anticipatory speech. CBD and control groups however did not differ, reflecting similar response profiles during the public speaking testThe initial positive studies suggest that CBD may be a beneficial safe option (a larger confirmatory study needed)
 Crippa [39]CBD (400 mg)Compared regional cerebral blood flow activity in 10 treatment-naïve patients with SAD who were given CBD or placebo, in a double-blinded crossover mannerCBD compared to placebo, resulted in significantly lower subjective anxiety, and modulated blood flow in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus, and right posterior cingulate gyrus
 Greer [54]Cannabis (not defined)Analysed retrospectively collected CAPS data from 80 patients with PTSDPatients reported > 75% decrease in CAPS scores when they were using cannabis compared to periods when they were notNo firm evidence yet, however initial case analyses suggest this application may be of benefit to manage PTSD symptoms, reduce anxiety, and improve sleep
 Elms [53]CBD (capsule or spray; mean dosage at week-8 of 49 mg)Open label retrospective case study data from 11 adult patients with PTSD. Data assessed over 8 weeksMean PTSD symptoms on the PCL-5 reduced by 28%. Actual statistical data analysis not conducted
 Portenoy [60]Nabiximols: THC (2.7 mg) and CBD (2.5 mg)263 patients with advanced cancer and opioid-refractory pain were randomly allocated to receive placebo or nabiximols daily at low (1–4 sprays), medium (6–10 sprays) or high (11–16 sprays) doses, for 5 weeks. Pre/post-measures included average pain, worst pain, sleep disruption, quality of life and moodReports of pain relief were significantly greater for nabiximols than placebo overall, especially in the low- and medium-dose groups. There were no other significant group differences. Adverse events were dose-related with only the high-dose group reporting a decrease in moodNo evidence for use in depression, however higher doses of THC-predominant medicines may in fact lower mood
 Shannon [69]CBD capsules (25 mg) + liquid (6–25 mg)Patient (10 y.o. girl with prior early childhood trauma) was prescribed fish oil (750 mg daily) + 1 CBD oil capsule daily for 5 months. CBD liquid (12–24 mg) was added to the regime for 1 month and reduced to 6–12 mg p.r.n (or ‘when needed’). Sleep assessed monthly via SDSCSDSC scores decreased over the 5-month period, indicating an increase in sleep quality and quantityOnly case study and secondary outcome evidence at present. Encouraging as a potential use pending controlled studies, however next-day effects need to be assessed in terms of somnolence and cognitive functioning
 Johnson [71]Nabiximols: THC (2.7 mg) and CBD (2.5 mg) OR THC only (2.7 mg)43 patients, with advanced cancer and opioid-refractory pain, self-administered daily nabiximols or THC-only sprays for 5 weeks. Safety, tolerability, pain and quality of life were assessedAcross groups, pain decreased at every visit, and showed pre−/post improvement with insomnia and fatigue
 Shannon [70]CBD capsules (mainly 25 mg/day)A retrospective case series of 72 adults given CBD for anxiety and sleep complaints at a psychiatric clinic, as an adjunct to usual treatment. Assessed monthly over 12 weeksAnxiety scores on the HAMA decreased within the first month in 79% of the sample and remained decreased during the study duration. PSQI sleep score improved within the first month in 67%, but fluctuated over time. Data appeared to not be statistically significant for the group presenting with a primary complaint of anxiety (those with sleep disturbance fared better)
 Leweke [99]CBD (600–800 mg)42 individuals with schizophrenia were randomly assigned to receive 600–800 mg of CBD or amisulpride over 4 weeks. The PANSS and BPRS were administered every 14 days. Blood was also collectedBoth treatments were effective in reducing PANSS and BPRS scores at each time point. CBD was tolerated better, with fewer side effects reported. Anandamide levels were higher in the CBD group post-treatmentAvoid any use of high THC in youth. 600 mg–1200 mg of CBD per day may be effective as an adjunct for +ve and -ve symptoms
 McGuire [101]CBD (1000 mg)88 antipsychotic-treated patients with schizophrenia were randomly given placebo or CBD alongside existing medication for 6 weeks. Pre/post-trial measures included the PANSS, Brief Assessment of Cognition in Schizophrenia, Global Assessment of Functioning, Clinical Global Impressions of Improvement and Severity scales.The CBD group reported lower positive symptom scores, and were more likely to be rated as improved and less severely ill than the placebo group. The CBD group also showed improvements in the cognitive domain of motor speed compared to placebo. CBD was tolerated well with similar adverse event rates reported between the groups
 Boggs [102]CBD (600 mg)36 individuals with schizophrenia were randomised to receive CBD or placebo adjunctively to current antipsychotic medication for 6 weeks. PANSS and MCCB were assessed pre/post-trialBoth groups showed improvement on PANSS scores and only the placebo group improved on the MCCB. Similar side effects were noted between the groups, with more sedation evident in the CBD group
Bipolar Disorder
 Zuardi [105]CBD (600–1200 mg)Two patients with bipolar I disorder were administered CBD for 30 days with 5 days of placebo pre/post-trial. Patients were assessed on the YMRS and BPRS every 7 daysOne patient showed improvements in YMRS and BPRS scores while on CBD plus olanzapine but no additional improvement during CBD monotherapy. The second patient had no symptom improvement with any dose of CBD. Both tolerated CBD well with no side effects reported.Not presently recommended. CBD appears not to be effective in attenuating mania
 Cooper [108]Nabiximols: THC (2.7 mg) and CBD (2.5 mg)30 adults with ADHD were randomly prescribed nabiximols or placebo for 6 weeks. A participant’s optimal dose was decided at day 14. The QBT assessed cognitive performance and activity level (head movements), Conners Adult ADHD Rating Scale rated ADHD symptoms, and self-reports to examine emotional labilityThe nabiximols group showed an improvement in QBT scores that approached significance. Nominally significant improvements in ADHD symptoms were also found for the nabiximols group compared to placeboPotentially may be effective in managing some ADHD symptoms however more research is needed. Lower THC formulas alleviate concerns about cognitive impairment
  1. # First Author; THC Tetrahydrocannabinol, CBD Cannabidiol, QBT Quantitative Behavioural Test, PANSS Positive and Negative Syndrome Scale, MCCB MATRICS Consensus Cognitive Battery, HAMA Hamilton Anxiety rating Scale, PSQI Pittsburgh Sleep Quality Index, YMRS Young Mania Rating Scale, BPRS Brief Psychiatric Rating Scale, SDSC Sleep Disturbance Scale for Children, CAPS Clinician Administered Posttraumatic Scale; PLC-5 = PTSD checklist for DSM-5