Full-Spectrum Cannabis Extract Trial in Chronic Low Back Pain

Key Takeaways

• In phase A, VER-01 was associated with greater pain reduction than placebo, and the prespecified neuropathic-pain endpoint also favored active treatment.
• Responder rates, sleep quality, physical function, quality of life, patient global impression of change, and rescue ibuprofen use all favored VER-01 in the analyses.
• Treatment-emergent adverse events and adverse event-related discontinuations were more frequent with VER-01, serious adverse events were similar between groups, and phase D did not meet its primary endpoint.

Morning pain intensity fell by 1.9 points with phase 3 randomized placebo-controlled trial of VER-01 and by 1.4 points with placebo in adults with chronic low back pain. In the multicenter phase 3 trial, the primary endpoint was change in mean weekly morning pain intensity on the 11-point numeric rating scale. The mean difference was -0.6 points (95% confidence interval, -0.9 to -0.3; P<0.001) during the blinded phase A portion of the trial.

The trial enrolled 820 adults, with 394 assigned to VER-01 and 426 to placebo, across 66 outpatient sites and university-based hospitals in Germany and Austria. Phase A included a 1-week run-in, a 3-week titration, and a 12-week double-blind placebo-controlled treatment period. Phase B then continued for 6 months in open label, phase C added another 6 months of open-label continuation, and phase D used randomized withdrawal with 4 weeks of treatment and 2 weeks of washout.

Eligible participants were at least 18 years old, had chronic low back pain for at least 3 months, had an NRS score of at least 4, and had inadequate response to or unsuitability of prior optimized nonopioid analgesics. Baseline characteristics included 56.6% female, mean age 52 years, mean BMI 29 kg/m2, 22.0% with a neuropathic pain component, 23.5% with severe pain, and 99% with prior analgesic use. Key exclusions included other painful comorbidities, severe mental illness, prior alcohol, drug, or medication abuse, and cannabis-based medicinal product use within 30 days before screening. The enrolled population had persistent symptoms despite limits with prior nonopioid treatment.

Among participants with PainDETECT scores above 18, NPSI total score fell by 14.4 points with VER-01 and by 7.2 points with placebo, for a mean difference of -7.3. The 95% confidence interval ranged from -13.2 to -1.3, and P=0.017. Responder rates also favored VER-01, with 54.1% versus 39.5% reaching at least 30% pain reduction, 32.2% versus 22.8% reaching at least 50%, and 46.9% versus 35.6% reaching at least a 2-point reduction. Sleep quality improved with a mean difference of -0.7, Roland-Morris Disability Questionnaire scores with -1.1, and SF-36 physical component summary with 2.1, all with P<0.001. Patient global impression of change response was 45.1% versus 23.4%, and rescue ibuprofen use was 10.5 versus 18.3 tablets, also with P<0.001. Benefits extended beyond pain intensity to sleep, physical function, quality of life, and rescue medication use.

VER-01 was a standardized full-spectrum Cannabis sativa extract derived from DKJ127 and standardized to 5% THC. Each 119-µl dose unit delivered 2.5 mg THC, 0.1 mg cannabigerol, and 0.02 mg cannabidiol in sesame oil. Study drug was taken orally with a dosing syringe from 30-ml amber glass bottles, and placebo matched its appearance and sensory characteristics. Dosing increased every 3 days by one dose unit in the morning and one in the evening to a maximum of 13 daily dose units. Stable nondrug therapies could continue, and randomization was 1 to 1 with stratification by neuropathic pain component. The trial used a standardized oral titration scheme rather than ad hoc cannabis exposure.

In phase A, treatment-emergent adverse events occurred in 83.3% of VER-01 recipients and 67.3% of placebo recipients, while serious adverse events were 6.2% and 6.8%, respectively. Discontinuation because of adverse events was higher with VER-01 at 17.3% versus 3.5%, and the common events were dizziness, fatigue, nausea, dry mouth, and somnolence. Most adverse events were mild to moderate and transient, with many arising during initial titration and declining over time. No deaths, no clinically important treatment-related laboratory, vital sign, or ECG changes, and no signs of dependence or withdrawal were reported. In phase D, the primary endpoint for time to treatment failure was not met, with a hazard ratio of 0.75, a 95% confidence interval of 0.44 to 1.27, and P=0.288. Pain still increased more after placebo withdrawal, with a mean difference of 0.5 and P=0.034.