Clinical Takeaway
In this phase 3 trial of 820 adults with chronic low back pain, the full-spectrum cannabis extract VER-01 was evaluated against placebo over 12 weeks with extended follow-up periods reaching up to one year. The study design included both a randomized withdrawal phase, which helps establish whether benefits are sustained and causally linked to the treatment rather than natural disease fluctuation. Results from this rigorously controlled trial provide some of the highest-quality clinical evidence to date on cannabis-based treatment for one of the most prevalent pain conditions globally.
#1 Full-spectrum extract from Cannabis sativa DKJ127 for chronic low back pain: a phase 3 randomized placebo-controlled trial.
Citation: Karst Matthias et al.. Full-spectrum extract from Cannabis sativa DKJ127 for chronic low back pain: a phase 3 randomized placebo-controlled trial.. Nature medicine. 2025. PMID: 41023483.
Design: 5 Journal: 4 N: 2 Recency: 2 Pop: 2 Human: 1 Risk: -2
Quality Gate Alerts:
- Preclinical only
Methodological Considerations:
- Open-label design — placebo effect not excluded
Abstract: Chronic low back pain (CLBP) affects over half a billion people worldwide. Current pharmacologic treatments offer limited efficacy and carry substantial risks, warranting the development of safe and effective alternatives. This multicenter, randomized, placebo-controlled phase 3 trial evaluated the efficacy and safety of VER-01 in CLBP. It enrolled 820 adults with CLBP (VER-01, n = 394; placebo, n = 426) and included a double-blind 12-week treatment phase (phase A), a 6-month open-label extension (phase B), followed by either a 6-month continuation (phase C) or randomized withdrawal (phase D). The primary endpoint of phase A was a change in mean numeric rating scale (NRS) pain intensity, with a change in total neuropathic pain symptom inventory (NPSI) score as a key secondary endpoint in participants with a neuropathic pain component (PainDETECT > 18). The primary endpoint for phase D was time to treatment failure. The study met its primary endpoint in phase A, with a mean pain reduction of -1.9 NRS points in the VER-01 group (mean difference (MD) versus placebo = -0.6, 95% confidence interval (CI) = -0.9 to -0.3; P < 0.001). Pain further decreased to -2.9 NRS points in phase B, with effects sustained through phase C. The study also met its key secondary endpoint of phase A, with a mean NPSI decrease of -14.4 (standard error, 3.3) points from baseline in the VER-01 arm (MD versus placebo = -7.3, 95% CI = -13.2 to -1.3; P = 0.017). Although phase D did not meet its primary endpoint (hazard ratio = 0.75, 95% CI = 0.44-1.27; P = 0.288), pain increased significantly more with placebo upon withdrawal (MD = 0.5, 95% CI = 0.0-1.0; P = 0.034). In phase A, the incidence of adverse events-mostly mild to moderate and transient-was higher with VER-01 than with placebo (83.3% versus 67.3%; P < 0.001). VER-01 was well-tolerated, with no signs of dependence or withdrawal. VER-01 shows potential as a new, safe and effective treatment for CLBP. ClinicalTrials.gov registration: NCT04
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