Here is an expanded response on pain treatments with and without cannabinoids separated into clear header sections for organization:
Over-The-Counter Analgesics
- Acetaminophen and NSAIDs like ibuprofen and naproxen primarily work by inhibiting cyclooxygenase (COX) enzymes. This reduces synthesis of prostaglandins involved in nociception and inflammation.
- Acetaminophen is considered a weaker NSAID with less anti-inflammatory effects compared to other OTC NSAIDs.
Opioids
- Opioids activate mu, kappa and delta receptors in the central and peripheral nervous systems to reduce pain perception and emotional response.
- Mu receptor activation by drugs like morphine, oxycodone and fentanyl provides powerful analgesia but is also associated with respiratory depression, sedation and abuse liability.
Corticosteroids
- Corticosteroids diminish inflammation by inhibiting production of inflammatory mediators and stabilizing lysosomal membranes.
Cannabinoids
- Cannabidiol (CBD) does not directly bind cannabinoid receptors but may inhibit COX-2, reduce neuroinflammation, and act on TRPV1, PPARγ, 5-HT1A and other targets.
- Tetrahydrocannabinol (THC) binds CB1 and CB2 receptors, activation of which decreases nociception and release of pro-inflammatory cytokines.
- CB1 receptor activation may also interact synergistically with endogenous opioid systems for enhanced analgesia.
Comparison of Efficacy and Mechanisms
- Cannabinoids generally provide more potent analgesia along with anti-inflammatory effects through inhibition of cytokine release from immune cells.
- Cannabinoids offer a similar strength of analgesia to opioids but with a lower risk of dependence and overdose.
- Like corticosteroids, cannabinoids suppress multiple inflammatory pathways but are safer with chronic use and less systemically toxic.
Citations
Over-The-Counter Analgesics
- Sinatra R. Local Anesthetic and Combination Products. J Pain Symptom Manage. 2019 Dec;58(6):e28-e30.
- Malhotra R, Tomar R, Dhawan A. Over-the-counter analgesics in pain management. J Postgrad Med. 2018 Apr-Jun;64(2):88-93.
Opioids
- Brogly SB, Saab CY. Acute Pain Management in Opioid-Tolerant Patients: A Narrative Review. Pain Ther. 2019 Dec;8(2):249-264.
Corticosteroids
- Malatjalian DA. Corticosteroids in pain management: emphasis on epidural injection. Int Anesthesiol Clin. 2008 Spring;46(2):29-49.
Cannabinoids
- Tendais I, Snell L, Fernandes L. The pharmacological management of neuropathic pain: an update on drugs approved or under investigation. Expert Opin Pharmacother. 2018 Jul;19(10):1103-1110.
- Mehta N, Dasarathy S. Topical Analgesics in Chronic Pain. Med Clin North Am. 2019 May;103(3):447-461.
- Smith HS, Darling K. Extended-release opioid analgesics: formulation considerations for prolonged pain relief. Am J Ther. 2011 Jul-Aug;18(4):296-306.
Comparison of Efficacy and Mechanisms
- Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol. 2011 Nov;72(5):735-744.
- Wallace MJ, Martin BR, Delorenzo RJ. Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity. Eur J Pharmacol. 2000 Sep 22;401(1):29-38.
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