Efficacy and safety of VER-01, a standardized full-spectrum cannabis extract, in chronic

OG Article By Matthias Karst, Winfried Meissner, Sabine Sator, Jens Keßler, Volker Schoder & Winfried Häuser Watch Today's LIVE Episode on X and Rumble

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October 17, 2025

low back pain: results from a randomized, double-blind, placebo-controlled phase 3 trial

Body: With over half a billion prevalent cases in 2020, low back pain is globally the leading cause for work loss, disability and reduced quality of life across all ages and in both sexes 1 , 2. Low back pain is a mixed pain condition with nociceptive, nociplastic and neuropathic pain characteristics 3. When pain persists for more than 3 months, it is defined as chronic low back pain (CLBP). CLBP is often associated with severe impairments in sleep quality and physical function, which further contribute to the overall disease burden 4 , 5. The treatment of CLBP involves a multimodal treatment approach combining pharmacological and nonpharmacological interventions, the latter including physical activity, exercise and physiotherapy 6 , 7 , 8 , 9 , 10.

Pharmacological treatment options include the short-term use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, NSAIDs are not suitable for long-term treatment due to severe side effects, including gastrointestinal ulcers, bleeding and an increased risk for cardiovascular events 11 , 12. For patients requiring long-term analgesic treatment, opioids are frequently used, despite severe side effects and safety concerns. Approximately 20% of patients on long-term therapy experience opioid abuse, dependence, tolerance development and withdrawal symptoms 13. The widespread use of opioids for CLBP combined with their high risk for dependence, misuse and fatal overdoses has substantially contributed to the global opioid epidemic, resulting in hundreds of thousands of deaths worldwide 14 , 15.

Accordingly, several clinical practice guidelines now advise against the use of opioids 6 , 7, and there is widespread consensus among healthcare professionals, patient organizations and regulators on the urgent need to develop new nonaddictive analgesics for the short- and long-term treatment of CLBP with a superior safety profile. The limitations of existing treatments and the stagnation in the development of new analgesics have fueled growing public and scientific interest in the use of cannabis-based medicines for the management of chronic pain. However, the quality of evidence supporting the clinical use of cannabis-based products remains low, primarily due to small sample sizes, short treatment durations, inconsistent dosing regimens, heterogeneous outcome measures and variability across cannabis-based preparations 16 , 17 , 18 , 19.

As naturally occurring botanical substances, cannabis plants exhibit substantial heterogeneity. Variability in the botanical raw material and manufacturing processes contributes to a substantial variety of product compositions, including levels of bioactive constituents 20 , 21. Consequently, findings obtained with one cannabis extract cannot be extrapolated to others without appropriate comparative data. To ensure reproducible results, it is therefore essential to adequately characterize the investigational product and establish consistency across batches.

The investigational product VER-01 was comprehensively characterized using chromatographic and spectrometric methods to quantify cannabinoids, terpenes, flavonoids, carotenes, phytosterols, vitamins and fats, and chromatographic fingerprinting confirmed batch-to-batch consistency across multiple lots of VER-01. By providing a large-scale, placebo-controlled phase 3 trial of adequate duration using a chemically well-defined, full-spectrum cannabis extract in CLBP, this study addresses a critical gap in the clinical research of cannabis-based pharmacotherapy in chronic pain.

Results

Patient disposition and baseline characteristics

Between 7 July 2021 and 30 June 2023, 1,157 patients were assessed for eligibility and 820 participants were randomly assigned to VER-01 ( n = 394) or placebo ( n = 426; Fig. 1). A total of 525 participants continued to phase B, 155 continued to phase C and 116 participants were randomly assigned to VER-01 ( n = 52) or placebo ( n = 64) in phase D (Figs. 1 and 2). A total of 815 participants were included in the efficacy analysis of phase A, whereas 116 participants were included in that of phase D. The last visit of the study was on 26 March 2024.

Fig. 1: CONSORT chart of the trial.

The efficacy, safety and tolerability analyses included all randomized participants who received at least one dose of the study medication during the respective study phase.

Fig. 2: Trial design.

a , The trial design of phase A. b , The trial design of phases B–D. WO, washout.

Overall, the two groups in phase A were balanced with respect to baseline characteristics (Table 1). A total of 180 participants (22.0%) had a neuropathic pain component, and 193 (23.5%) were suffering from severe pain (numeric rating scale (NRS) ≥ 7) at baseline. A total of 461 participants (56.6%) were female, with a mean age of 52 years and a mean body mass index (BMI) of 29 kg m −2, showing no notable differences between the two groups.

Baseline characteristics of participants with a neuropathic pain component were consistent across both treatment groups and matched those of all participants. Additionally, the demographics and baseline characteristics of participants in phases B, C and D were similar to those in phase A (Extended Data Tables 1– 3). The most frequent concurrent diseases were hypertension (35.3%) and obesity (32.0%). In total, 99% of patients reported prior use of analgesics, with nonsteroidal anti-inflammatory and antirheumatic drugs being the most frequently reported medication (96.7%). The proportion of participants with at least two prior optimized analgesic therapies was balanced between arms, with 95.4% in the VER-01 arm and 94.8% in the placebo arm.

Table 1 Demographics and other trial baseline characteristics for participants starting phase A

Efficacy

Pain intensity at baseline was moderate to severe in both groups, with a mean NRS pain intensity of 6.1 (s.d. = 1.2) for VER-01 and 6.0 (s.d. = 1.2) for placebo.

The study met its primary endpoint in phase A. Mean pain intensity significantly decreased from baseline by −1.9 (s.e. = 0.2) NRS points in the VER-01 arm compared to −1.4 (s.e. = 0.2) in the placebo arm. VER-01 demonstrated a greater pain reduction compared to placebo with a mean difference (MD) of −0.6 (95% confidence interval (CI) = −0.9 to −0.3; P < 0.001). The difference between VER-01 and placebo was significantly in favor of VER-01 in every single study week of the 12-week treatment phase, showing consistent improvement over time (Fig. 3a). Sensitivity analyses using both last observation carried forward (LOCF) and baseline observation carried forward (BOCF) imputation yielded similar results to the primary analysis and remained statistically significant (Supplementary Tables 10 and 11). Post hoc analysis revealed no statistical interaction between treatment and sex (Supplementary Table 4).

Fig. 3: Effect of VER-01 on NRS pain and NPSI scores as compared with Placebo.

a , Mean NRS pain intensity in phases A and B, as measured on an 11-point NRS for each study week of the placebo-controlled study phase A (VER-01, n = 390; placebo, n = 425) and the open-label phase B (VER-01, n = 524). b , Mean NPSI total scores for the subgroup of participants with a neuropathic pain component during phase A (VER-01, n = 88; placebo, n = 91). c , Change in mean NRS pain intensity after randomized withdrawal in phase D (VER-01, n = 51; placebo, n = 63). All bars display the range from mean ± s.e. of the mean. BL, baseline; W, week; Titr., titration.

The difference between VER-01 and placebo was even more pronounced in participants with a neuropathic pain component (MD = −1.5, 95% CI = −2.2 to −0.9; P < 0.001). Moreover, post hoc analyses revealed particularly pronounced effects of VER-01 in participants with severe pain (MD = −1.0, 95% CI = −1.8 to −0.1; P = 0.011).

The study also met its key secondary endpoint in phase A, with significant improvements in neuropathic symptoms (as measured by the Neuropathic Pain Symptom Inventory (NPSI)) among participants with a PainDETECT score >18 at baseline. The mean NPSI total scores at baseline were comparable between groups, with 47.1 (s.d. = 17.2) for VER-01 and 48.7 (s.d. = 16.4) for placebo. The mean NPSI total score decreased by −14.4 (s.e. = 3.3) points from baseline in the VER-01 arm compared to −7.2 (s.e. = 2.8) in the placebo arm, with an MD of −7.3 (95% CI = −13.2 to −1.3; P = 0.017).

The difference between VER-01 and placebo was significantly in favor of VER-01 for every single visit of the treatment phase, showing consistent improvement over time (Fig. 3b). Compared to placebo, VER-01 reduced superficial spontaneous pain (MD = −1.3, 95% CI = −2.4 to −0.3; P = 0.015), deep spontaneous pain (MD = −1.2, 95% CI = −2.2 to −0.3; P = 0.001), evoked pain (MD = −1.14, 95% CI = −1.9 to −0.4; P = 0.003) and abnormal sensations (MD = −1.29, 95% CI = −2.2 to −0.4; P = 0.006).

The results of the primary and key secondary endpoints were further supported by all secondary efficacy endpoints (Table 2). The rate of participants with a ≥30% pain reduction was significantly higher for VER-01 compared to placebo (54.1% versus 39.5%), resulting in a number needed to treat to benefit (NNTB) of 6.8 (95% CI = 4.42–15.05; P < 0.001). Similarly, the rate of participants with a ≥50% pain reduction (32.2% versus 22.8%; P = 0.010) and a ≥2-point pain reduction (46.9% versus 35.6%; P = 0.001) was significantly higher in the VER-01 arm. Moreover, participants in the VER-01 arm took only about half the amount of rescue medication compared to participants in the placebo arm (mean (s.d.) = 10.5 (14.2) versus 18.3 (53.8) ibuprofen tablets; P < 0.001).

Table 2 Secondary endpoints of phase A

Additionally, participants in the VER-01 group reported significant improvements in both sleep quality and physical function. Sleep quality improved by −2.2 NRS points in the VER-01 arm compared to −1.5 in the placebo arm, with an MD of −0.7 NRS points (95% CI, −1.0