Condition

Pain Relief

Pain is an experience shaped by both tissue damage and how the nervous system processes signals, and chronic pain can wear down daily life. Topical capsaicin has the strongest evidence, with curcumin at a moderate level, and one trial of about 1,500 people found headaches improved with caffeine alongside acetaminophen after spinal anesthesia. Cannabis and serrapeptase have only limited evidence from small studies, so their results remain uncertain.

Sources: PMID 24672232; PMID 39371383

Supplements studied: 6
Graded outcomes: 4
Trials: 11
People studied: 5,222

Evidence by supplement

Strong
Moderate
Limited
Very limited

6 supplements

Caffeine

Caffeine: outcomes studied for Pain Relief
Grade	Outcome	Effect	Size	Studies	People
	Headaches Small Improvement	Improves (the measure goes down)	Small effect	1 study	1,503 people
Studies that measured headaches The Prophylactic Effect of Acetaminophen and Caffeine on Post Dural Puncture Headache after Spinal Anesthesia for Cesarean Section: A Randomized Double-Blind Clinical Trial.Iran J Med Sci · PMID 39371383
	Rating of Perceived Exertion	Improves (the measure goes up)		3 studies	15 people
Studies that measured rating of perceived exertion The effects of low-dose caffeine on perceived pain during a grip to exhaustion taskJ Strength Cond Res · PMID 21522070 Caffeine ingestion, affect and perceived exertion during prolonged cyclingAppetite · PMID 21605608 Effect of caffeine intake on pain perception during high-intensity exerciseInt J Sport Nutr Exerc Metab · PMID 21411832
	Pain	Changes; see studies		1 study	4,262 people
Studies that measured pain Caffeine as an analgesic adjuvant for acute pain in adultsCochrane Database Syst Rev · PMID 25502052

Cannabis

Cannabis: outcomes studied for Pain Relief
Grade	Outcome	Effect	Size	Studies	People
	Analgesic Use Small Decrease	Improves (the measure goes down)	Small effect	4 studies	177 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	252 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
	Body Temperature	Improves (the measure goes up)			18 people

Serrapeptase

Inflammation: improves
Pain: improves

Serrapeptase: outcomes studied for Pain Relief
Grade	Outcome	Effect	Size	Studies	People
	Inflammation Small Decrease	Improves (the measure goes down)	Small effect	4 studies	150 people
Studies that measured inflammation A randomized, double-blind, placebo-controlled study comparing the efficacy and safety of paracetamol, serratiopeptidase, ibuprofen and betamethasone using the dental impaction pain modelInt J Oral Maxillofac Surg · PMID 19168326 A multi-centre, double-blind study of serrapeptase versus placebo in post-antrotomy buccal swellingPharmatherapeutica · PMID 6366808 [Reduction of postoperative swelling. Objective measurement of swelling of the upper ankle joint in treatment with serrapeptase-- a prospective study]Fortschr Med · PMID 2647603 and 1 more on the Serrapeptase page
	Pain	Improves (the measure goes down)		1 study	150 people
Studies that measured pain The treatment of breast engorgement with Serrapeptase (Danzen): a randomised double-blind controlled trialSingapore Med J · PMID 2688125

Selenium

Migraine Frequency: improves
Migraine Severity: improves
Nitric Oxide: improves

Selenium: outcomes studied for Pain Relief
Outcome	Effect	Size	People
Migraine Frequency Small Decrease	Improves (the measure goes down)	Small effect	72 people
Migraine Severity	Improves (the measure goes down)		72 people
Nitric Oxide	Improves (the measure goes up)		72 people

Curcumin

Pain: improves

Curcumin: outcomes studied for Pain Relief
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

Magnesium

Pain: improves

Magnesium: outcomes studied for Pain Relief
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Pain	Improves (the measure goes down)		1 study	64 people
Studies that measured pain The effect of preoperative oral magnesium oxide on the severity of postoperative pain among women undergoing hysterectomy.Ir J Med Sci · PMID 35022952

Key findings

HeadachesCaffeineImproves (the measure goes down)
Analgesic UseCannabisImproves (the measure goes down)
InflammationSerrapeptaseImproves (the measure goes down)

The General Pain Relief Support protocol

2 primary supplements · 8 supporting supplements

Curcumin500–2,000 mg bioavailable curcumin daily
Omega-3 Fatty Acids2–4 g EPA+DHA daily

See the full protocol

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Studies cited

2 studies from PubMed

Binaural Beats Reduce Postoperative Morphine Consumption in Older adults After Total Knee Replacement SurgeryAltern Ther Health Med · PMID 32412916
The Use of Honey for Cicatrization and Pain Control of Obstetric Wounds: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Nutrients · PMID 38257078