Condition

Chronic pain

Chronic pain is pain that lasts beyond three to six months, as changes in the nervous system leave the pain system oversensitive. Omega-3 fatty acids and vitamin D have the most support among supplements, rated moderate, and a trial of the spinal drug ziconotide found a modest edge over placebo for pain intensity. Even so, that gain was small, and N-acetylcysteine showed no clear difference for pain in the one study reviewed.

Sources: PMID 16716870

Supplements studied: 5
Medicines and peptides: 1
Graded outcomes: 10
Trials: 4
People studied: 3,232

Evidence by supplement

Strong
Moderate
Limited
Very limited

5 supplements

Cannabis

Cannabis: outcomes studied for Chronic pain
Grade	Outcome	Effect	Size	Studies	People
	Analgesic Use Small Decrease	Improves (the measure goes down)	Small effect	4 studies	399 people
Studies that measured analgesic use Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trialNeuropsychopharmacology · PMID 18688212 Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trialJ Pain · PMID 22483680 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 and 1 more on the Cannabis page
	Pain	Improves (the measure goes down)		6 studies	399 people
Studies that measured pain 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 Comparison of the analgesic effects of dronabinol and smoked marijuana in daily marijuana smokersNeuropsychopharmacology · PMID 23609132 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 and 3 more on the Cannabis page
	Sleep Quality	Improves (the measure goes up)		4 studies	399 people
Studies that measured sleep quality Cannabinoids for adult cancer-related pain: systematic review and meta-analysisBMJ Support Palliat Care · PMID 31959586 A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatmentEur J Pain · PMID 24420962 Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trialPain · PMID 17997224 and 1 more on the Cannabis page

Electric Nerve Stimulation

Electric Nerve Stimulation: outcomes studied for Chronic pain
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Pain Intensity Moderate Decrease - SMD -0.96 vs placebo during/after treatment (moderate-certainty evidence)	Improves (the measure goes down)	Moderate effect		4,841 people
	Pain vs Standard Care Moderate Decrease - SMD -0.72 vs standard care treatments	Improves (the measure goes down)	Moderate effect		3,155 people

N-Acetylcysteine

Pain
Quality of Life: improves

N-Acetylcysteine: outcomes studied for Chronic pain
Grade	Outcome	Effect	Size	Studies	People
	Pain No effect		NoneNo effect	1 study	286 people
Studies that measured pain Efficacy and Safety of N-Acetylcysteine for the Management of Chronic Pain in Adults: A Systematic Review and Meta-Analysis.Pain Med · PMID 33560443
	Quality of Life	Improves (the measure goes up)			198 people

Spirulina

Bilirubin
Blood glucose: improves
Blood Clotting: improves

Spirulina: outcomes studied for Chronic pain
Grade	Outcome	Effect	Size	Studies	People
	Bilirubin No effect		NoneNo effect	1 study	24 people
Studies that measured bilirubin Clinical Safety of a High Dose of Phycocyanin-Enriched Aqueous Extract from Arthrospira (Spirulina) platensis: Results from a Randomized, Double-Blind, Placebo-Controlled Study with a Focus on Anticoagulant Activity and Platelet ActivationJ Med Food · PMID 27362442
	Blood glucose	Improves (the measure goes down)		1 study	24 people
Studies that measured blood glucose Hypocholesterolemic effect of spirulina in patients with hyperlipidemic nephrotic syndromeJ Med Food · PMID 12487756
	Blood Clotting	Improves (the measure goes up)			24 people
	Creatinine	Improves (the measure goes up)			24 people
	P-Selectin	Improves (the measure goes up)			24 people
	Pain	Improves (the measure goes down)			24 people
	Serum Platelets	Improves (the measure goes up)			24 people
	Urea	Improves (the measure goes up)			24 people

Curcumin

Pain: improves

Curcumin: outcomes studied for Chronic pain
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Pain	Improves (the measure goes down)		14 studies	15 people
Studies that measured pain Efficacy of Curcuma longa in relieving pain symptoms of knee osteoarthritis patients: a systematic review and meta-analysis of clinical trials.J Rheum Dis · PMID 39712249 Curcuma longa extract reduces inflammatory and oxidative stress biomarkers in osteoarthritis of knee: a four-month, double-blind, randomized, placebo-controlled trialInflammopharmacology · PMID 27761693 Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled studyBMC Complement Altern Med · PMID 29316908 and 11 more on the Curcumin page

Prescription medicines and peptides studied, for context

These are not supplements. Most need a prescription, and some are research compounds with no approved use. They are listed so the supplement evidence above can be read against them.

1 medicine or peptide

Ziconotide (Prialt)

Long-term Pain Control: improves
Pain Intensity Reduction: improves
Opioid-Refractory Pain: improves

Ziconotide (Prialt): outcomes studied for Chronic pain
Outcome	Effect	Size	Studies
Long-term Pain Control Stable pain scores over 3 years in 644-patient study. No evidence of tolerance development. 119 patients treated >360 days.	Improves (the measure goes down)	Moderate effect	23 studies
Pain Intensity Reduction RCT: 14.7% VASPI improvement vs 7.2% placebo (P=0.036). Significant improvement with slow titration protocol.	Improves (the measure goes down)	Moderate effect	22 studies
Opioid-Refractory Pain Effective in patients refractory to intrathecal morphine and other opioids. Provides option when tolerance develops to opioids.	Improves (the measure goes down)	Moderate effect	22 studies
Quality of Life Improved quality of life reported in patients with treatment-resistant chronic pain in long-term studies.	Improves (the measure goes up)	Moderate effect	16 studies
Function and Mobility Improvements in physical function observed alongside pain reduction in clinical trials.	Improves (the measure goes up)	Small effect	16 studies

Key findings

Analgesic UseCannabisImproves (the measure goes down)
Pain IntensityElectric Nerve StimulationImproves (the measure goes down)
Pain vs Standard CareElectric Nerve StimulationImproves (the measure goes down)

The Chronic Pain Supportive Care protocol

2 primary supplements · 7 supporting supplements

Omega-3 Fatty Acids2–4 g EPA+DHA daily
Vitamin D2,000–4,000 IU daily (higher if deficient)

See the full protocol

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Studies cited

3 studies from PubMed

Effect of Anti-Inflammatory Diets on Pain in Rheumatoid Arthritis: A Systematic Review and Meta-AnalysisNutrients · PMID 34959772
Reduced pain and analgesic use after acoustic binaural beats therapy in chronic pain - A double-blind randomized control cross-over trialEur J Pain · PMID 32564499
Cognitive behavioral therapy for insomnia in people with chronic musculoskeletal pain. A systematic review and dose-response meta-analysis.Sleep Med · PMID 39111059