Table 2

Data extraction

Study (author/year)Research question/aimStudy designPatient population/settingInterventionComparatorPrimary outcomeSecondary outcome(s)Withdrawal from study due to adverse eventsRisk of bias
Lichtman et al 201819To assess adjunctive nabiximols (Sativex) in patients with advanced cancer with chronic pain unalleviated by optimised opioid therapyPhase III, double-blind, randomised placebo-controlled trial
2-week titration period followed by 3-week treatment period
Patients with advanced cancer
Average cancer-related pain
Numeric Rating Scale (NRS) scores >4 and ≤8 despite optimised opioid therapy (morphine equivalents dose/day ≥90 mg)
114 centres
Nabiximols oral mucosal spray (n=199) started as one spray/day, titrated by one additional spray/day (maximum daily dosage of 10 sprays)Placebo (n=198)Median per cent improvements in average pain NRS score from baseline to end of treatment in the nabiximols and placebo groups were 10.7% vs 4.5% (p=0.0854)—ITT populationMean change from baseline to end of treatment: average pain NRS score, worse pain NRS score
Estimated treatment difference for daily maintenance opioid dose 1.46 (p=0.6410), daily breakthrough opioid dose −1.84 (p=0.4217) and daily total opioid dose −0.34 (p=0.9328)
40 (20.1%) nabiximols patients and 35 (17.7%) placebo patientsLow in all domains
Fallon et al 201718
Study 1
To assess the analgesic efficacy of adjunctive Sativex in patients with advanced cancer with chronic pain unalleviated by optimised opioid therapyPhase III, double-blind, randomised, placebo-controlled trial
2-week titration period followed by 3-week treatment period
Advanced cancer and average pain NRS scores ≥4 and ≤8 at baseline, despite optimised opioid therapy (morphine equivalents dose/day ≥90 mg)
101 centres
Sativex (n=200)
Started as one spray/day, titrated by one additional spray/day (maximum daily dosage of 10 sprays)
Placebo (n=199)Per cent improvement in average daily pain NRS scores from baseline, Sativex 7.2% vs placebo 9.5% (median difference 1.84%, 95% CI −6.19% to 1.50%; p=0.274)Estimated treatment effect: for average pain NRS score 0.12, 95% CI −0.18 to 0.42 (p=0.434), for worse pain NRS score 0.11, 95% CI −0.21 to 0.44 (p=0.496)
Estimated treatment effect: for daily maintenance opioid dose −3.63, 95% CI −10.80 to 3.55 (p=0.321), for daily breakthrough opioid dose −4.17, 95% CI −8.76 to 0.42 (p=0.075), for daily total opioid dose −9.35, 95% CI −18.81 to 0.12 (p=0.053)
38 (19%) in nabiximols group vs 29 (14.6%) placebo groupLow in all domains
Fallon et al 201718
Study 2
To assess the analgesic efficacy of adjunctive Sativex in patients with advanced cancer with chronic pain unalleviated by optimised opioid therapyPhase III, double-blind, randomised, placebo-controlled trial, enrichment enrolment with randomised withdrawal design
2-week titration period followed by 5-week treatment period
Advanced cancer and average pain NRS scores ≥4 and ≤8 at baseline, despite optimised opioid therapy
(morphine equivalents dose/day ≥90 mg)
65 centres
All patients (n=406) titration of Sativex for 10 days, followed by 4 days of Sativex at the titrated dose.
Patients with
a ≥15% improvement from baseline in pain score were randomised 1:1 to Sativex (n=103) or placebo (n=103)
Placebo (n=103)During the treatment period, Sativex group mean change in average daily pain NRS scores increased from 3.2 to 3.7 while the analogous values in the placebo group were 3.1 and 3.6, respectively. The estimated treatment effect −0.02, 95% CI −0.42 to 0.38 (p=0.917)
78/406 failure to demonstrate a 15% improvement in average pain NRS score during titration
Estimated treatment effect: for per cent improvement in average pain NRS score −1.23, 95% CI −9.05 to 6.59 (p=0.757), for worse pain NRS score −0.32, 95% CI −0.73 to 0.09 (p=0.124)
Estimated treatment effect: for daily maintenance opioid dose −8.93, 95% CI −19.69 to 1.84 (p=0.104), for daily breakthrough opioid dose 1.81, 95% CI −10.34 to 13.96 (p=0.769), for daily total opioid dose −7.11, 95% CI −23.92 to 9.69 (p=0.405)
 71 (17.5%) in the titration period nabiximols vs placebo: 21 (20.4%) vs 13 (12.6%) in the 5-week double-blind treatment periodLow in all domains
Lynch et al 201420To investigate nabiximols in the treatment of chemotherapy-induced neuropathic painDouble-blind randomised, placebo-controlled cross-over pilot study
Had an extension phase where 10 participants were given nabiximols to use up to 6 months
Titration phase followed by 4-week treatment period and a 2-week washout period
Patients with established chemotherapy-induced neuropathic pain average 7-day intensity pain of NRS ≥4Nabiximols (n=9) (oral mucosal cannabis-based spray)Placebo (n=9)A 0–10 point numeric rating scale for pain intensity (NRS-PI)
No statistically significant difference between the treatment and the placebo groups
Quantitative sensory testing (dynamic tactile allodynia and pinprick hyperalgesia)
No statistically significant effect as compared with a placebo
No withdrawals due to adverse effectsLow in all domains
Portenoy et al 201217To evaluate the efficacy and safety of nabixomols in three dose ranges in patients with cancer pain not controlled with opioidsRandomised, double-blind, placebo-controlled, graded-dose study.
5-day to 14-day baseline period, a 5-week titration and treatment period, and
a post-study visit after 2 weeks. The maximum duration was 9 weeks
Patients with advanced cancer and opioid-refractory pain average pain—NRS scores ≥4 and ≤8 at baseline
84 centres
(360 randomised,
263 completed)
Nabiximols at a low dose (n=71) (1–4 sprays/day), medium dose (n=67) (6–10 sprays/day) or high dose (n=59) (11–16 sprays/day)Placebo (n=66)30% reduction in baseline pain in the mean 11-point NRS not statistically different between active drug and placebo (p=0.59)Continuous responder analysis of average daily pain from baseline to end of study demonstrated that the proportion of patients reporting analgesic benefit was greater for nabiximols than placebo (p=0.035)
In the low-dose group, the adjusted mean change in pain score was −1.5 points on the 11-point NRS (95% CI −1.28 to 0.22; p=0.006) and for medium dose was −1.1 points (95% CI −0.89 to 0.18; p=0.19) groups compared with placebo
No significant difference between groups in the use of regular opioids, or number of opioids used for breakthrough pain
Using the opioid composite score, more patients in the nabiximols groups had a better responder profile compared with those in the placebo group (54% vs 43%, OR 1.54, 95% CI 0.95 to 2.5; p=0.077)
Total nabiximols 53 (19.8%)
13 (14.3%) Nabiximols at a low dose
15 (17.2%) Nabiximols at a medium dose
25 (27.8%) Nabiximols at a high dose
16 (17.6%) placebo
Adverse events were dose related; only the high-dose group had more adverse events compared with placebo
Low in all domains
Johnson et al 201016Efficacy of THC:CBD and THC vs placebo, in relieving pain in patients with advanced cancer with pain uncontrolled by opioidsDouble-blind, randomised,
placebo-controlled, parallel-group study
2-day baseline followed by 2-week treatment period
177 patients with cancer pain (NRS scores ≥4), who experienced inadequate analgesia despite chronic opioid dosing, entered a 2-week study (2-day baseline and 2-week treatment).
Patients were randomised to THC:CBD extract (n=60), THC extract (n=58) or placebo (n=59)
28 centres
THC:CBD extract (n=60)
THC extract (n=58)
Placebo (n=59)Change from baseline in mean pain
NRS score was statistically significant for THC:CBD compared with placebo
(improvement of −1.37 vs −0.69).
THC extract was a significant change (−1.01 vs −0.69).
No significant difference between groups on the no of days breakthrough medication was used
Twice as many patients taking THC:CBD showed a reduction of more than 30% from baseline pain NRS score when compared with placebo (23 (43%) vs 12 (21%)). The OR of responders between THC:CBD and placebo was 2.81 (95% CI 1.22 to 6.5; p=0.006).
THC group responders were similar to placebo (12 (23%) vs 12 (21%))
No of days of use of breakthrough medication was similar among all groups (p=0.70). There was a reduction observed in the mean no of daily doses of all breakthrough medications (THC:CBD −0.19; THC −0.14; placebo −0.15), but the difference in change from baseline between treatment groups was not significantly different
THC:CBD 10 (16.7%), THC extract 7 (12%), placebo 3 (5%)Low in all domains
  • ITT, intention to treat.