Table 2 Studies of the use of CBD and CBD-containing compounds such as nabiximols in the treatment of cannabis-related disorders and levels of evidence (1–5)
From: The therapeutic role of Cannabidiol in mental health: a systematic review
Author | Diagnosis | Study design | Pharmacological agent | Strength of evidence* | Group (n) | Duration | Age range (years) | Dose range (mg) | Scales to measure the clinical outcome | Clinical outcome | Common side effects | Reference number |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Allsop et al., 2014 | Cannabis withdrawal | RCT | Nabiximols | Level 2 | Nabiximols = 27 Placebo = 24 | 6 days of nabiximols or placebo treatment, 3 days of washout, and 28-day follow-up period Total duration = 37 days | 18–65 | Starting dose = 8 sprays, total dose of 21.6 mg THC and 20 mg CBD at 4 PM and 10 PM Maximum dose = 8 sprays 4 times a day | CWS | - Nabiximols reduced CWS scores by 66% compared to 52% with placebo for duration for treatment (P = .01). - It resulted in a decrease in appetite loss, decrease in cravings (p = 0.4), irritability and aggression (p = .o1). - The time duration for cannabis withdrawal was 3.10 days with Nabiximols compared to 4.9 days with placebo (p = .04) - The retention rate was 85% with medications compared to 50% with placebo. | Decreased appetite. The number and severity of adverse events did not differ significantly between groups. | 31 |
Trigo et al., 2016 | Cannabis moderate-severe use and withdrawal | RCT | Nabiximols | Level 2 | 16 | 8 weeks | 18–50 | Nabiximols = 108 mg THC/100 mg CBD Fixed dose = 4 sprays of medications every hour Self-titrated dose: Patients were allowed to use 4 sprays as needed every hour. The maximum dose was 40 sprays/day. | MCQ, CWS, SMHSQ, DEQ, ARCI, MNWS | - Medication intake was higher on fixed regimen as compared to self-titration conditions. There was significant differences between conditions (F(3,24) = 8.561, p < 0.001). - Mean time for having feeling of “high” was clearly higher during SAU (6.6–7.3 h) compared with Sativex (2.4–3.3 h) or placebo (0.1–0.3 h), as self-reported by participants in their smoking diary (Fig. 1c) - There were lesser withdrawal during self-titrated and fixed Sativex as compared to the corresponding placebo conditions (F(7,56) = 3.860, p < 0.01). | No significant difference in side effects was observed between the experimental and placebo group. | 28 |
Trigo et al., 2018 | Cannabis moderate to severe use | RCT | Nabiximols | Level 2 | Nabiximols and weekly MET/CBT = 20 Placebo = 20 | 12 weeks | 18–65 | Nabiximols = 113.4 mg THC/105 mg CBD | BPRS, SAFTEE, HAM-A, HDRS, TLFB for cannabis, tobacco, caffeine and alcohol, FTND, ASI, BDI, DEQ, Profile of Mood States, MWC, MCQ-SF, SMHSQ | - Nabiximols was well-tolerated with a dose range of 4.1 to 12.8 sprays/day. - There was reduction in cannabis use in the nabiximols (70.5%) and placebo groups (42.6%). - Five participants in the placebo group and four participants in the nabiximols group used other recreational drugs. - High medication sub-group suggested a significant effect of time (F12,90.1 = 10.386, p < .001), no effects of treatment (F1,8.1 = 1.200, p = .305) but a significant time x treatment interaction. | No serious adverse events were observed. | 29 |
Pokorski et al., 2017 | Cannabis withdrawal | Open-label pilot study | CBD | Level 3 | 8 | 7 days | 21–62 Mean age = 40 years | CBD = 600–1200 mg/day in divided doses | CWS, daily urine sample and blood samples on day 1, 3, and 7, THC COOH and CBD quantification | - For 600 mg/day of CBD: 2 out of 5 participants completed the 7-day inpatient treatment. These 2 participants reported abstinence at follow-up (day 28) and the 3 remaining participants reported decreased cannabis use, confirmed by blood and urine analysis. - For 600 mg twice a day: of 3 participants, 2 reported abstinence and the 1 remaining one had decreased use of cannabis, confirmed by blood and urine analysis. - All participants reported a decrease in CWS score. | The participants did not report any unwanted or adverse effects of the CBD. | 32 |
Solowij et al., 2018 | Impaired cognition and elevated psychological symptoms in patients with chronic cannabis use | Open-label trial | CBD | Level 3 | 20 | 10 weeks | Median age = 25.1 years | CBD = 200 mg in divided doses | BDI, STAI-I, STAI-II, GAF, SOFAS, CAPE, RAVLT, AST | - There was an improvement in severity of depression (p = 0.017), verbal learning, memory performance, and frequency of positive psychotic-like symptoms (p = 0.025) with decreased level of distress from baseline to endpoint. - The state anxiety increased with no change in trait anxiety, functional impairment, and accuracy on cognitive tests. | No side effects were reported. | 19 |
Trigo et al., 2016 | Cannabis moderate to severe use | Case series | Nabiximols | Level 4 | 4 | 12-week follow-up phase with 4 weekly visits and 2 subsequent monthly visits | 24–43 Mean age = 35 years | Self-titrated nabiximols = 77.5–113.4 mg THC 71.5–105 mg CBD | CWC, CCQ, TLFB for cannabis, tobacco, caffeine and alcohol | - Reduction in cannabis intake from baseline to endpoint with no compensatory increase in use of other substances (F(18,54) = 4.663, p < 0.001). - The craving scores increased initially during the first 2 weeks with a subsequent reduction in craving from week 9 (F(18,54) = 7.091, p < 0.001) . - No significant difference in withdrawal scores for the duration of study (F(18,54) = 0.805, p value = non-significant) | No side effects were reported. | 30 |
Crippa et al., 2013 | Cannabis withdrawal syndrome | Case report | CBD | Level 4 | 1 | 10 days | 19 | The dose of CBD was 300 mg on day 1 and 600 mg on days 2–10. 600 mg was administered in divided doses. | MWC, WDS | - CBD resulted in faster, progressive relief from withdrawal, anxiety, and dissociative symptoms. - Marijuana withdrawal symptom checklist had drop of baseline score of 12 to zero, from 5 to zero for Withdrawal discomfort scale. - The scores for Beck Anxiety Inventory decreased from 6 to zero and 10 to zero for Beck Depression Inventory. - At 6 month follow-up, return to cannabis use but at a lower rate. | No side effects were reported. | 27 |
Shannon & Lehman, 2015 | Cannabis moderate to severe use | Case report | CBD | Level 4 | 1 | Follow-up for 129 days | 27 | Initial regimen: 24 mg CBD (6 sprays as needed during the day and 2 sprays at night). The dose was decreased to 18 mg with 6 spray at night only. | Self-reported cannabis use, PSQI, HAM-A | - Patient was able to maintain abstinence from cannabis. - Improvement in HAM-A score from 16 to 8 was reported, indicating mild anxiety. - Patient had a regular sleep schedule and scores of 7 to eight were reported. | No side effects were reported. | 33 |