Dr. Chris Shade

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Natural Alternatives to NSAID

In recent years, the opioid epidemic has been covered extensively in the news media and framed as an urgent public health issue. However, opioids aren’t the only pain-relieving drugs we should be concerned about. Research indicates that nonsteroidal anti-inflammatory drugs (NSAIDs) are also widely misused in the United States and have a slew of alarming side effects, including an increased risk of gut inflammation, leaky gut, and heart attack.1,2

As public knowledge of the harmful effects of NSAIDs grows, more and more people are seeking out natural alternatives for quenching pain and inflammation. The exploding curcumin and CBD markets, the growth of which have been triggered largely by consumers seeking alternative solutions for pain and inflammation relief, are evidence of this trend.3,4 Read on to learn about the health risks of NSAIDs and why you should try natural alternatives instead for safe, effective pain and inflammation relief.

How do NSAIDs work?

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of drugs that relieve pain, fevers, and inflammation. Common NSAIDs include:

  • Advil/Motrin (ibuprofen)
  • Aleve (naproxen sodium)
  • Aspirin
  • Celebrex
  • Cambia/Cataflam/Voltaren (diclofenac)
  • Indocin (indomethacin)

NSAIDs exert their effects on the body by inhibiting the synthesis of prostaglandins, a group of lipid-based compounds that have hormone-like effects in the body and play an essential role in the inflammatory cascade. Prostaglandins are synthesized by an enzyme called COX, which is directly inhibited by NSAIDs.5 There are two main types of COX enzymes: COX-1 and COX-2. Different types of NSAIDs selectively target one or both of these enzymes, leading to various side effects.

The Health Risks of NSAIDs

A growing body of evidence indicates that NSAIDs adversely impact the gastrointestinal, cardiovascular, and renal systems.6 COX-1-selective NSAIDs primarily affect the gastrointestinal tract, triggering peptic ulcers and dangerous GI bleeds.7 NSAIDs also disrupt the integrity of the cells that comprise the wall of the intestine, promoting leaky gut and systemic inflammation.8

COX-2-selective NSAIDs, on the other hand. primarily impact the cardiovascular system. Use of these drugs is associated with an increased risk of heart attack.9 Emerging research suggests that NSAIDs may also increase the risk of certain types of cancer, including endometrial carcinoma.10

Unfortunately, doctors are not informing patients adequately about the potential harms of NSAIDs.  A recent survey indicated that only a quarter of patients advised to take NSAIDs by their physician are counseled about possible adverse effects.11 Furthermore, the purported benefits of NSAIDs, such as the often-publicized “heart-protective” effects of aspirin, may be overblown, as the drug appears to have zero beneficial impact on healthy life span in older adults.12

Natural Alternatives to NSAIDs

The dangerous side effects of NSAIDs have led to increased interest, both in the scientific community and the general public, in natural alternatives for relieving pain and inflammation. CBD, curcumin, turmeric essential oils and Boswellia stand out as potent, yet safer, options for alleviating pain and restoring a healthy inflammatory balance.

 CBD

Cannabidiol (CBD) is a phytocannabinoid found in the Cannabis plant. It has demonstrated promising effects on pain management and inflammation relief.

Cannabinoids demonstrate the therapeutic potential for difficult-to-treat pain.13 CBD may assist with migraine and headache relief, chronic neuropathic pain, and pain triggered by arthritis, cancer, and multiple sclerosis.14,13  Unlike NSAIDs, CBD does not interact with COX at pharmacologically relevant dosages. However, endocannabinoids do appear to prevent the excessive expression of COX-2. 13,15

CBD alleviates pain by interacting with TRPV and GPR receptors, which are involved in pain reception, and by increasing circulating levels of anandamide, which has pain-relieving properties.16,17,18  Research suggests that CBD does not induce tolerance and that it does not cause withdrawal symptoms upon discontinuation, a problem posed by NSAIDs. 19

Hemp-based compounds besides cannabidiol also offer anti-inflammatory and analgesic benefits. Cannabichromene and cannabigerol, non-psychoactive phytocannabinoids, reduce inflammation and pain and may relax tight muscles.20,13  Several phytocannabinoids and other hemp-based compounds are selective COX-2 inhibitors, suggesting similar mechanisms of action as NSAIDs, but without side effects.21,22

The cannabis terpenoids β-caryophyllene, myrcene, and α-pinene also have anti-inflammatory and analgesic benefits. β-caryophyllene reduces inflammation and protects the gastrointestinal mucosa.23 Myrcene blocks the production of the pro-inflammatory prostaglandin E2, while α-pinene inhibits prostaglandin E1 and protects the lining of the stomach.24

Curcumin and Turmeric Essential Oils

Curcumin is a bright yellow compound found in turmeric root, a plant revered for millennia in Indian Ayurvedic medicine for its analgesic and anti-inflammatory effects. Modern-day research supports the traditional uses of turmeric, demonstrating the inhibitory effects of curcumin on many inflammatory and pain-signaling pathways, including NF-κB, phospholipase A2, COX-2 and LOX pathways, and interleukin production.25

Interestingly, curcumin offers a similar degree of pain relief as ibuprofen and diclofenac sodium but without the adverse effects of these drugs.25 Preclinical research suggests that it has analgesic effects in experimental migraine, and combined with omega-3 fatty acids, can prevent migraine onset by downregulating COX-2 and nitric oxide synthase.26,27

Curcumin is just one of several beneficial compounds found in turmeric root. Turmeric root also contains potent essential oils that enhance the anti-inflammatory effects of curcumin.28,29

Boswellia

Boswellia is a resin derived from the Boswellia serrata, (commonly known as Frankincense) tree. It inhibits enzymatic pathways involved in the inflammatory response and, combined with curcumin, alleviates arthritic pain.30,31,32 Two Boswellia phytochemicals, an oleo-gum resin and acetyl-11-keto-β-boswellic acid (AKBA), have been found to decrease inflammation inside colon cells, reduce reactive oxygen species, and inhibit breakdown of the intestinal barrier, suggesting a role for this botanical in the maintenance of a healthy intestinal inflammatory balance.33 These effects are a far cry from those of NSAIDs, which increase intestinal inflammation and leaky gut!

The next time you wake up with an achy back or feel a headache coming on, reach for cannabidiol extract, curcumin, and boswellia instead of an NSAID. These natural compounds can inhibit multiple pathways that contribute to pain and inflammation while also sparing your gut and heart from the harmful effects of NSAIDs. Your entire body will thank you!

References

  1. Singh G. Gastrointestinal complications of prescription and over-the-counter nonsteroidal anti-inflammatory drugs: a view from the ARAMIS database. Arthritis, rheumatism, and aging medical information system. Am J Ther. 2000; 7(2): 115-121. View Abstract
  2. Varga Z, et al. Cardiovascular risk of nonsteroidal anti-inflammatory drugs: An under-recognized public health issue. Cureus. 2017; 9(4): e1144. View Full Paper
  3. “Curcumin market size worth $1.30 billion by 2025 | CAGR 12.3%: Grand View Research, Inc. PR Newswire. 3 Sep 2018. View Article
  4. Weisul K. The next gold rush is the $22 billion CBD business–and this Florida company is ready to win. Inc. 16 Sep 2019. View Article
  5. Ricciotti E, Fitzgerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011; 31(5): 986-1000. View Full Paper
  6. Harirforoosh S, et al. Adverse effects of nonsteroidal anti-inflammatory drugs: an update of gastrointestinal, cardiovascular, and renal complications. J Pharm Pharm Sci. 2013; 16(5): 821-847. View Abstract
  7. Rogers MAM, et al. The influence of nonsteroidal anti-inflammatory drugs on the gut microbiome. Clin Microbiol Infect. 2016; 22(2): 178. E1-178.e9. View Abstract
  8. Sigthorsson G, et al. Intestinal permeability and inflammation in patients on NSAIDs. Gut. 1998; 43: 506-511. View Full Paper
  9. Bally M, et al. Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data. BMJ. 2017; 357. View Abstract
  10. Brasky TM, et al. Nonsteroidal anti-inflammatory drugs and endometrial carcinoma mortality and recurrence. J Natl Cancer Inst. 2017; 109(3): 1-10. View Abstract
  11. Babelghaith SD, et al. Knowledge of patients on safe medication use in relation to nonsteroidal anti-inflammatory drugs. Saudi J Anaesth. 2019; 13(2): 106-111. View Full Paper
  12. “Daily low-dose aspirin found to have no effect on healthy life span in older people.” National Institutes of Health. 16 Sep 2018. View Full Paper
  13. Russo EB. Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag. 2008; 4(1): 245-259. View Full Paper
  14. Baron EP. Medicinal properties of cannabinoids, terpenes, and flavonoids in Cannabis, and benefits in migraine, headache, and pain: An update on current evidence and Cannabis science. Headache. 2018; 58(7): 1139-1186. View Abstract
  15. Costa B, et al. Therapeutic effect of the endogenous fatty acid amide, palmitoylethanolamide, in acute rat inflammation: inhibition of nitric oxide and cyclo-oxygenase systems. Br J Pharmacol. 2002; 137(4): 413-420. View Full Paper
  16. Guerrero-Alba R, et al. Some prospective alternatives for treating pain: The endocannabinoid system and its putative receptors GPR18 and GPR55. Front Pharmacol. 2019; [online]. View Full Paper
  17. Muller C, et al. Cannabinoid ligands targeting TRP channels. Front Mol Neurosci. 2018; 11: 487. View Abstract
  18. Malek N, et al. Alterations in the anandamide metabolism in the development of neuropathic pain. Biomed Res Int. 2014; 2014: 686908. View Full Paper
  19. Wade DT, et al. Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis. Mult Scler. 2006; 12(5): 639-645. View Abstract
  20. Izzo AA, et al. Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice. Br J Pharmacol. 2012; 166(4): 1444-1460. View Full Paper
  21. Takeda S, et al. Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis. Drug Metab Dispos. 2008; 36(9): 1917-1921. View Abstract
  22. Ruhaak LR, et al. Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biol Pharm Bull. 2011; 34(5): 774-778. View Abstract
  23. Fidyt K, et al. β‐caryophyllene and β‐caryophyllene oxide—natural compounds of anticancer and analgesic properties. Cancer Med. 2016; 5(10): 3007-3017. View Full Text
  24. De Almeida Pinheiro M, et al. Gastroprotective effect of alpha-pinene and its correlation with antiulcerogenic activity of essential oils obtained from Hyptis species. Pharmacogn Mag. 2015; 11(41): 123-130. View Full Text
  25. Daily JW, et al. Efficacy of turmeric extracts and curcumin for alleviating the symptoms of joint arthritis: A systematic review and meta-analysis of randomized clinical trials. J Med Food. 2016; 19(8): 717-729. View Full Text
  26. Bulboaca AE, et al. Preemptive analgesic and antioxidative effect of curcumin for experimental migraine. Biomed Res Int. 2017; 2017: 4754701.
  27. Abdolahi M, et al. The neuromodulatory effects of ω-3 fatty acids and nano-curcumin on the COX-2/ iNOS network in migraines: A clinical trial study from gene expression to clinical symptoms. Endocr Metab Immune Disord Drug Targets. 2019; 19(6): 874-884. View Abstract
  28. Toden S, et al. Essential turmeric oils enhance anti-inflammatory efficacy of curcumin in dextran sulfate sodium-induced colitis. Sci Rep. 2017; 7: 814.
  29. Dosoky NS, et al. Chemical composition and biological activities of essential oils of Curcuma species. Nutrients. 2018; 10(9): 1196. View Full Paper
  30. Haroyan A, et al. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. BMC Complement Altern Med. 2018; 18: 7. View Full Paper
  31. Prabhavathi K, et al. A randomized, double-blind, placebo-controlled, cross over study to evaluate the analgesic activity of Boswellia serrata in healthy volunteers using mechanical pain model. Indian J Pharmacol. 2014; 46(5): 475-479. View Full Paper
  32. Majeed M, et al. A pilot, randomized, double‐blind, placebo‐controlled trial to assess the safety and efficacy of a novel Boswellia serrata extract in the management of osteoarthritis of the knee. Phytother Res. 2019; 33(5): 1457-1468. View Full Paper
  33. Catanzaro D, et al. Boswellia serrata preserves intestinal epithelial barrier from oxidative and inflammatory damage. PLoS One. 2015; 10(5): e0125375. View Full Paper

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