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Condition

Opioid-Refractory Pain

Opioid-refractory pain is long-lasting pain that opioid medicines don't relieve well enough, or that opioids can't be used for because of side effects or risks. Palmitoylethanolamide and alpha-lipoic acid have the strongest support, with moderate evidence, and in four small cannabis studies people used less pain medication. Even so, the cannabis research was small and the evidence limited, and the other supplements looked at, such as magnesium and curcumin, have limited evidence.

Sources: PMID 18688212; PMID 22483680

Supplements studied
1
Graded outcomes
1
Trials
1
People studied
360

Evidence by supplement

  • Strong
  • Moderate
  • Limited
  • Very limited

1 supplement

Cannabis

Cannabis: outcomes studied for Opioid-Refractory Pain
GradeOutcomeEffectSizeStudiesPeopleStudies list
Analgesic Use

Small Decrease

Improves (the measure goes down)Small effect4 studies360 people

Studies that measured analgesic use

and 1 more on the Cannabis page

PainImproves (the measure goes down)6 studies360 people

Studies that measured pain

and 3 more on the Cannabis page

Sleep QualityImproves (the measure goes up)4 studies360 people

Studies that measured sleep quality

and 1 more on the Cannabis page

Depression SymptomsImproves (the measure goes down)1 study360 people

Studies that measured depression symptoms

Key findings

  • Analgesic UseCannabisImproves (the measure goes down)

The Opioid-Refractory Pain Management Support protocol

2 primary supplements · 5 supporting supplements

See the full protocol

Studies cited

15 studies from PubMed

  1. Evaluating the Suitability and Potential Efficiency of Cannabis sativa Oil for Patients with Primary Burning Mouth Syndrome: A Prospective, Open-Label, Single-Arm Pilot StudyPain Med · PMID 33123730
  2. Smoked cannabis for chronic neuropathic pain: a randomized controlled trialCMAJ · PMID 20805210
  3. Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trialPain · PMID 17997224
  4. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatmentEur J Pain · PMID 24420962
  5. Results of a Double-Blind, Randomized, Placebo-Controlled Study of Nabiximols Oromucosal Spray as an Adjunctive Therapy in Advanced Cancer Patients with Chronic Uncontrolled PainJ Pain Symptom Manage · PMID 28923526
  6. Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studiesBr J Pain · PMID 28785408
  7. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trialJ Pain · PMID 22483680
  8. Amygdala activity contributes to the dissociative effect of cannabis on pain perceptionPain · PMID 23273106
  9. Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteersAnesthesiology · PMID 18073554
  10. Lack of analgesia by oral standardized cannabis extract on acute inflammatory pain and hyperalgesia in volunteersAnesthesiology · PMID 18580179
  11. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related painJ Pain Symptom Manage · PMID 19896326
  12. Comparison of the analgesic effects of dronabinol and smoked marijuana in daily marijuana smokersNeuropsychopharmacology · PMID 23609132
  13. An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesicsJ Pain Symptom Manage · PMID 23141881
  14. Cannabinoids for adult cancer-related pain: systematic review and meta-analysisBMJ Support Palliat Care · PMID 31959586
  15. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trialNeuropsychopharmacology · PMID 18688212

Supplement stack for Opioid-Refractory Pain