|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.
The number and severity of adverse events did not differ significantly between groups.
|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.
|- 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|