169: High-dose cannabidiol in spinal cord injury chronic neuropathic pain: An RCT and brain imaging study

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic neuropathic pain, Pharmacological treatments

Background and Aims: This is the first randomised, placebo controlled trial to evaluate high dose cannabidiol (CBD) with concurrent brain imaging in people with spinal cord injury (SCI) neuropathic pain. Chronic neuropathic pain is common after SCI, yet current treatments have limited efficacy and significant side effects1,2. Cannabidiol (CBD), a non-intoxicating component of cannabis, has demonstrated efficacy in preclinical models of neuropathic pain3–5. In individuals with SCI chronic neuropathic pain, we investigated the effect of high-dose (800 mg/day) CBD on pain intensity and associated changes in brain activity using magnetic resonance imaging (MRI).

Methods: This randomised, double-blinded, crossover clinical trial recruited adults with SCI and chronic neuropathic pain. Participants were randomised to one of two treatment orders and received oral CBD and placebo over two six-week treatment periods, separated by a four-week washout. Treatment was titrated to 800 mg/day over two weeks. The primary outcome was change in self-reported pain intensity on a 0 (no pain) to 10 (worst pain imaginable) Visual Analogue Scale. The secondary outcome was the association between changes in pain and regional on-going brain activity, assessed using arterial spin labelling (ASL) MRI acquired immediately prior-to and following each arm.

Results: Forty participants were randomised, with 38 included in the primary outcome analysis (n=6 female) and 22 in the MRI analysis. A significant treatment-x-phase effect was observed for pain intensity (p<0.001), with pairwise comparison revealing lower pain on CBD treatment (mean±SEM: 3.82±0.23) compared to placebo (mean difference=−0.54, SEM=0.15, p<0.001). Pain intensity did not differ between pre-treatments (mean-difference<0.01, SEM=0.17). ASL image analysis revealed positive correlations between changes in pain intensity and cerebral blood flow in brain regions implicated in affective processing and pain modulation. These regions showed little to no changes during placebo treatment.

Conclusions: CBD significantly reduced self-reported neuropathic pain intensity and was generally well tolerated. Pain reductions were associated with changes in regional on-going brain activity, primarily within affective and modulatory pain-processing brain regions. provide strong clinical and mechanistic evidence supporting high dose CBD as a promising therapeutic approach for SCI neuropathic pain and suggest that its effects are mediated, in part, by central modulation of affective pain processing.

References: 1 Hunt C, Moman R, Peterson A, et al. Prevalence of chronic pain after spinal cord injury: a systematic review and meta-analysis. Reg Anesth Pain Med 2021; 46: 328–36.
2 Baastrup C, Finnerup NB. Pharmacological Management of Neuropathic Pain Following Spinal Cord Injury. CNS Drugs 2008; 22: 455–75.
3 Millar S a., Stone N l., Bellman Z d., Yates A s., England T j., O’Sullivan S e. A systematic review of cannabidiol dosing in clinical populations. British Journal of Clinical Pharmacology 2019; 85: 1888–900.
4 Finn DP, Haroutounian S, Hohmann AG, Krane E, Soliman N, Rice ASC. Cannabinoids, the endocannabinoid system, and pain: a review of preclinical studies. Pain 2021; 162: S5–25.
5 Silva-Cardoso GK, Lazarini-Lopes W, Hallak JE, et al. Cannabidiol effectively reverses mechanical and thermal allodynia, hyperalgesia, and anxious behaviors in a neuropathic pain model: Possible role of CB1 and TRPV1 receptors. Neuropharmacology 2021; 197: 108712.

Presenting Author: Rebecca V Robertson
Submitting Author: Rebecca Robertson

Senior Author: Iain S McGregor & Luke A Henderson

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Rebecca V Robertson: Ph.D. - University of Sydney
• Anastasia Suraev: Ph.D. - University of Sydney
• Danielle McCartney: Ph.D. - University of Sydney
• Allan Peng: B.Sc. - University of Sydney
• Rebecca Gordon: B.Sc. - University of Sydney
• Callum Morse: MD - Prince of Wales Hospital
• Claire L Boswell-Ruys: Ph.D. - Prince of Wales Hospital
• Kevin A Keay: Ph.D. - University of Sydney
• Elizabeth A Cairns: Ph.D. - University of Sydney
• Sachin Shetty: MD - Prince of Wales Hospital
• Iain S McGregor: Ph.D. - University of Sydney
• Luke A Henderson: Ph.D. - University of Sydney