‘A large phase 3 trial in Nature Medicine has delivered a ‘stronger’ clinical signal that a proprietary cannabis extract, VER-01, can modestly reduce chronic low back pain – but the effect is small, side effects are common, and broader evidence from other pain conditions remains weak and inconsistent. Experts say the findings should temper rather than fuel enthusiasm, especially for general cannabis use or over-the-counter products.
Trial highlights: modest benefit over placebo (a very close second)
The multicentre randomized controlled trial enrolled 820 adults with chronic low back pain and compared VER-01, a standardized full‑spectrum Cannabis sativa extract containing THC, CBD and other cannabinoids, with placebo over 12–15 weeks, followed by extension phases.1
Key efficacy findings include:
- Average pain reduction of 1.9 points on an 11‑point numeric rating scale (NRS) with VER‑01 vs 1.3–1.4 points with placebo, producing a mean between‑group difference of about −0.6 NRS points (95% CI roughly −0.9 to −0.3).2
- About 42% of VER‑01 patients achieved at least 30% pain reduction vs 31% on placebo, giving a number needed to treat (NNT) of 6.8 for this threshold.3
- Secondary outcomes showed statistically significant improvements in sleep quality, physical function and patient global impression of change, with reduced use of rescue analgesics.4
Clinically, that means most participants in both arms felt somewhat better, but only a minority derived clearly meaningful extra benefit from VER‑01 beyond placebo, and the average advantage was modest.5
Safety profile: frequent adverse effects, limited durability
VER‑01’s safety signal is not benign. Adverse events (AEs) were substantially more common in the active arm:
- Any AE occurred in 83.3% of VER‑01 recipients vs 67.3% on placebo, mostly dizziness, fatigue, somnolence, nausea and related nervous‑system symptoms.6
- Treatment discontinuation due to AEs was around 17% with VER‑01 compared with 3.5% on placebo.7
- In the randomized withdrawal phase, VER‑01 did not significantly prolong time to treatment failure compared with placebo (HR 0.75; p=0.288), suggesting limited durability or strong contextual/placebo contributions. 8
Importantly, the trial reports no clear signals of abuse, dependence or withdrawal in the controlled period or the six‑month open‑label extension, but the follow‑up is still relatively short for judging long‑term neurocognitive or psychiatric risks. The absence of formal blinding checks and dedicated cognitive testing leaves some uncertainty about expectation effects and subtle harms.9
What the broader evidence shows: small gains, real harms
The VER‑01 findings sit within a larger, more sobering evidence base on cannabis‑based medicines for chronic pain. A major Cochrane review of 16 randomized trials (n=1,750) in chronic neuropathic pain – using oral THC/CBD sprays, synthetic THC (nabilone), dronabinol, and smoked herbal cannabis – found only small benefits and clear safety concerns.
Across pooled neuropathic pain studies, the review reported:
- 50% pain relief: 21% with cannabis‑based medicines vs 17% with placebo (risk difference 0.05; NNT ≈ 20; low‑quality evidence).
- 30% pain relief: 39% vs 33% (risk difference 0.09; NNT ≈ 11; moderate‑quality evidence).
- Withdrawals due to adverse events: 10% vs 5% (NNH ≈ 25; moderate‑quality evidence).
- Any nervous‑system AE (e.g. dizziness, somnolence): 61% vs 29% (risk difference 0.38; NNH ≈ 3).
- Psychiatric AEs (e.g. confusion, mood or perceptual changes): 17% vs 5% (risk difference 0.10; NNH ≈ 10).
The authors concluded that “the potential benefits of cannabis‑based medicine… in chronic neuropathic pain might be outweighed by their potential harms” and that there is no high‑quality evidence supporting any cannabis‑based product for chronic neuropathic pain. Evidence for smoked or herbal cannabis was rated very low quality and showed no clear advantage over placebo.
Although neuropathic pain differs from mechanical low back pain, both are chronic pain states in which placebo responses are high and NNTs for cannabis‑based products tend to cluster in the 6–20 range, with frequent nervous‑system and psychiatric adverse events. This broader context undercuts simple narratives that “cannabis works for chronic pain” and suggests any benefit is typically modest and tightly bound to specific formulations and trial conditions.10
Experts urge caution: specific product, specific setting
Though some investigators of this trial had a clear conflict of interest, which the literature hasn’t made clear, some specialists commenting on the VER‑01 trial have welcomed it as a methodologically stronger study than most past cannabis pain trials, (which quality and depth have all been very sub-standard) but stress several caveats:
- The results are specific to VER‑01 – a standardized, pharmaceutical‑grade extract – and cannot be generalized to smoked cannabis, edibles, or unregulated oils.11
- The effect size is small; in practice, it equates to about a 30% average pain reduction on VER‑01 vs 20% on placebo over 12 weeks.12
- Given Cochrane’s finding that cannabis‑based medicines for neuropathic pain offer only minor additional benefit over placebo with substantial nervous‑system and psychiatric AEs, routine first‑line use in back pain would be hard to justify.
Guidelines cited by the Cochrane review generally position cannabis‑based medicines, if considered at all, as third‑ or fourth‑line options after established treatments such as NSAIDs, antidepressants, anticonvulsants, and non‑pharmacologic therapies have been tried and found inadequate. Some expert groups even give a weak recommendation against routine use in neuropathic pain because of low‑quality benefits and safety concerns.
What this means for patients, clinicians and policy
Taken together, the VER‑01 trial and the Cochrane synthesis point to a cautious, tightly targeted role for cannabis‑based medicines in chronic pain:
- Not a miracle drug: VER‑01 offers statistically significant but clinically modest improvements in chronic low back pain; placebo comes a close second on most endpoints.13
- Meaningful benefit for a minority: NNTs around 6–11 for 30% pain relief – in both VER‑01 and the neuropathic pain literature – imply that many patients will not gain substantial extra benefit over optimized standard care.14
- Real risk of side effects: Dizziness, somnolence, cognitive and psychiatric symptoms are common, with NNHs as low as 3 for nervous‑system events in neuropathic pain trials, and discontinuation rates notably higher than placebo in both VER‑01 and Cochrane data.15
- Formulation matters: Evidence supports specific, trial‑tested preparations (like VER‑01 or THC/CBD oromucosal sprays), not generic plant material or over‑the‑counter products.16
- Research, not routine: Longer‑term safety, comparative effectiveness vs opioids, NSAIDs and guideline‑recommended non‑drug therapies, and performance in more heterogeneous real‑world populations all remain open questions.17
For now, chronic low back pain patients and clinicians may reasonably view VER‑01 as a potential non‑opioid option for carefully selected individuals who have not responded to established treatments and who accept a high likelihood of transient but bothersome side effects. Yet in light of the broader evidence base, these new data are better seen as an incremental advance than as proof that cannabis, in general, reliably and safely relieves chronic back pain.18
For complete research – Major Sources
- Cannabis‐based medicines for chronic neuropathic pain in adults - Mücke, M - 2018 | Cochrane Library
- Full-spectrum extract from Cannabis sativa DKJ127 for chronic low back pain: a phase 3 randomized placebo-controlled trial
- No clear evidence that cannabis-based medicines relieve chronic nerve pain | Cochrane
Dalgarno Institute
