High Nociplastic Pain Levels Linked to Lower Therapeutic Effects of Cannabis

Higher levels of nociplastic pain (NPP) are associated with higher analgesic intake, higher odds of substituting cannabis for medications, a higher side effect burden, and a lower therapeutic effect from cannabis, according to results of a cross-sectional study published in The Clinical Journal of Pain.

In a previous study, patients with increased levels of NPP experienced less improvement in their quality of life and reported fewer decreases in opioid consumption compared with patients with lower NPP levels. Building on these findings, additional research was conducted to evaluate self-reported outcomes of medical cannabis use for management of chronic pain and to explore the relationship between NPP contributions and current medication use, use of cannabis for treating other symptoms and conditions, cannabis use preferences, and cannabis-related side effects.

Between January and August 2018, investigators collected data on NPP via a confidential, anonymous online survey of 1213 patients (59% women; mean [SD] age, 49.4 [± 13.6] years) recruited through medical cannabis dispensaries, certification clinics, and social media.

Because fibromyalgia is considered the prototypical condition, the severity and extent of patients’ pain was measured using the 2011 Fibromyalgia Survey Criteria; higher scores were associated with more severe fibromyalgia symptoms and were used as a surrogate for the degree of NPP. Based on their Fibromyalgia Survey scores, patients were assigned to 1 of 4 NPP quartiles: minimal, mild, moderate, and high.

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Among the survey respondents, 61% used pain-related medication; the most common medication classes used were NSAIDs (used by 30%), opioid analgesics (used by 16%), and benzodiazepines (used by 13%). Participants in the “moderate” and “high” NPP quartiles were more likely to substitute medications than those in the “mild” and “minimal” quartiles. Compared with patients in the “minimal” NPP quartile, those in the “mild,” “moderate,” and “high” quartiles had 1.7 (95% CI, 1.25-2.38; P =.001), 2.9 (95% CI, 2.2-4.1; P <.0001), and 3.8 (95% CI, 2.7-5.3; P <.0001) times higher odds, respectively, of substituting cannabis for an opioid analgesic. Patients in the “moderate” and “high” quartiles were also more likely to report substituting cannabis for benzodiazepines than those in the “minimal” NPP quartile.

Patients reported experiencing a mean (SD) of 4.8 (± 3.2) cannabis-related side effects, and the number of side effects increased with the degree of NPP. Notably, patients in higher NPP quartiles reported lower improvements in pain and health with cannabis use.

Study limitations included recall bias regarding the self-report questions; the inability to adequately assess temporality, which may have impacted both perceptions of treatment efficacy and assessment of relationships between cannabinoid preferences and administration routes as determinants of pain management success; and the possibility of selection bias caused by oversampling of patients (from dispensaries and medical cannabis certification clinics) who had experienced positive effects of cannabis.

The researchers concluded, “Most participants successfully reported substituting cannabinoids for analgesic medication and reported improvement in pain and general health since cannabinoid initiation.” They added, “However, those with greater NPP were discovered to have a mixture of greater analgesic use, greater analgesic substitution for cannabinoids, higher symptom burden (eg, anxiety, sleep disturbance), and less improvement in pain and health. Rigorous, prospective longitudinal studies and clinical trials are necessary to better elucidate the role of cannabinoids in nociplastic pain management.”

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.


Scott JR, Williams DA, Harte SE, et al. Relationship between nociplastic pain involvement and medication use, symptom relief, and adverse effects among people using medical cannabis for chronic pain. Clin J Pain. Published October 12, 2023. doi:10.1097/AJP.0000000000001164

This article originally appeared on Clinical Pain Advisor

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