Oral cannabidiol (CBD), tetrahydrocannabinol (THC), or their combination did not decrease pain among patients with peripheral neuropathic pain who had a history of treatment failure. These findings, from a randomized, double-blind trial, were published in the European Journal of Pain.
Patients (N=115) with peripheral neuropathic pain were recruited between 2018 and 2021 at 3 sites in Denmark and randomly assigned in a 1:1:1:1 ratio to receive THC 25 mg (n=28), CBD 50 mg (n=27), THC 25 mg plus CBD 50 mg (n=30), or placebo (n=30) taken twice daily. During the first 4 weeks, doses were titrated up, and participants were instructed to discontinue increasing the dose when there was a sufficient effect or if they experienced intolerance. The dose reached at week 4 was maintained through week 8. The primary outcome was change in the numeric rating scale (NRS) score for pain.
The median age of the study population was 65 (range, 22-95) years, the median duration of pain was 60 (range, 10-2017) months, mean NRS score was 6.5 (standard deviation [SD], 1.3) points, and the most common prior therapy was gabapentin or pregabalin (n=115). Neuropathic etiologies included polyneuropathy (n=95), diabetic polyneuropathy (n=26), nerve damage (n=11), and postherpetic neuralgia (n=9).
A greater than 30% reduction in pain score was reported by 18 patients receiving CBD/THC, 12 receiving THC, and 9 receiving CBD compared with 17 receiving placebo. Improvement in the Patient Global Impression of Change (PGIC) score was reported by 16 patients receiving CBD/THC, 16 patients receiving THC, and 7 patients receiving CBD compared with 14 receiving placebo.
In the intention-to-treat analysis, CBD had a significant effect on pain (impact, 0.76; 95% CI, 0.02-1.49; P =.042), but neither THC (P =.406) nor CBD/THC (P =.603) were effective.
Neither CBD, THC, nor CBD/THC were superior to placebo for symptoms of burning pain, pressing and squeezing, pain paroxysms, or evoked pain as evaluated using the Neuropathic Pain Symptom Inventory (NPSI). The study authors report that CBD was actually less effective than placebo in reducing evoked pain.
No effects on paracetamol consumption, quality of life, or psychomotor function were reported with active treatment.
In subgroup analyses, active treatment was not superior to placebo for pain, quality of life, mood, or pain-related sleep disturbance.
Nausea and diarrhea were reported more frequently among recipients of CBD/THC compared with prior to treatment (11% vs 1% and 11% vs 3%, respectively).
Recruitment to this study was terminated early for logistic reasons, and the target sample size was not reached.
This study did not identify clear pain-relieving effects from CBD and/or THC in the setting of peripheral neuropathic pain with prior treatment failure. The study authors commented, “This is the first study to examine the effect of CBD alone in neuropathic pain and it found no better effect of CBD than of placebo. Actually, in the [per protocol population], CBD reduced pain less than placebo, and less effect of CBD than of placebo was also seen with some secondary pain outcomes.” These data therefore do not support cannabis-based analgesic strategies for neuropathic pain.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Zubcevic K, Petersen M, Bach FW, et al. Oral capsules of tetra-hydro-cannabinol (THC), cannabidiol (CBD) and their combination in peripheral neuropathic pain treatment. Eur J Pain. Published online December 26, 2022. doi:10.1002/ejp.2072