Efficacy and Safety of Cannabis vs. Opioids on Lower Back Pain Reduction in Adults

AKINSHOLA JOLAOSO, BS

Philadelphia College of Osteopathic Medicine

SUMMARY POINTS

• Lower back pain can present across widespread populations as acute or chronic pain.

• Cannabis is more highly regulated than opioids as it is a Schedule 1 substance. 

• Opioids are not recommended for patients but have been prescribed.

• While there is no cure for fibromyalgia, various treatment modalities exist for symptom management and relief.

• Research on potential treatments has often conflicted or needed more quantity or quality.

• Opioids in the body play a role in the modulation of pain by acting on presynaptic μ-, κ-, and δ-opioid receptors to reduce excitatory neurotransmitter release by decreasing calcium influx in the presynaptic membrane and increasing potassium influx in the postsynaptic membrane.

ANALYSIS

Background

Opioid drugs have an extensive history of clinical use, playing a role in pain modulation and addiction, along with various physiological and pathophysiological activities, including regulating membrane homeostasis and immunity. In pain modulation, opioids act on presynaptic μ-, κ-, and δ-opioid receptors to reduce excitatory signals. Opioid mechanism of action is geared toward regulating calcium influx in the presynaptic membrane and increasing potassium influx in the postsynaptic membrane (1). Though different potencies affect this influx of electrolytes, potent opioids, including morphine, oxycodone, and fentanyl, are mainly used for moderate-to-severe pain, according to the WHO Pain Ladder Step III (2).  

The addiction potential of opioids is traced through cranial glutaminergic and dopaminergic interactive pathways. Long-term use of opioids has addictive potential and can promote neural damage, and is the most significant concern for medicinal use (3). Due to this and the associated deaths from opioid use, questions about alternate methods continue to arise.

The human body contains 2 G-protein coupled receptors, CB1 and CB2, which THC, the main bioactive ingredient in cannabis, interacts with. The binding of these G-protein-coupled receptors blocks the release of pain-inducing neurotransmitters in the central nervous system (CNS), attenuating neuropathic pain. The CB1 receptor activation has been shown to affect cognition, memory, motor control, and analgesia. The CB2 receptor activation alters cytokine release and cell migration in the CNS and PNS to suppress acute, chronic, and neuropathic pain by stimulating the release of β-endorphin from peripheral keratinocytes (4).

Cannabis is currently labeled a recreational and medicinal drug in the United States. Despite its former negative connotation, recent shifts to the social outlook combined with the evolution of medicine has driven public opinion to push for legislative action. However,  there are still obstacles to accepting medicinal marijuana as a form of treatment, including Schedule I status and a high potential for abuse (5). Yet, medical cannabis treatment (MCT) has shown a promising ability to decrease the release of neurotransmitters, decrease postsynaptic sensitivity, and reduce neural inflammation (6). 

Lower back pain (LBP) is one of the leading musculoskeletal conditions worldwide and is estimated to affect nearly 85% of the US population. LBP is a multifactorial disease with many implicated risk factors, including age, race, sex, marital status, and a significant contributor to disability in the working population, with an estimated annual loss of $28 billion in the United States (4). 

Analysis

Randomized controlled trials (RCT) present that opioids are moderately effective and safe in the short-term and intermediate-term (8). Evidence from RCTs of 4 to 15 weeks of treatment suggests that treating LBP with opioids may be more beneficial than a placebo to reduce pain. This RCT supports that opioids may provide a clinically relevant pain reduction of 30% or greater (2). Chronic opioid use for the treatment of LBP raises questions on efficacy and necessity. During 12 to 18-month treatment with opioids, results convey that they may not be superior to nonopioids for improving pain-related function or disability (2).

While opioids are very effective in treating various musculoskeletal conditions such as osteoarthritis, in addition to post-operative utilization for pain, they possess a strong potential for drug abuse and addiction (6). Although opioid-related deaths declined following its peak in 2017, trends demonstrate a rise in recent years. The benefits of opioid use come at the cost of dose-dependent risks of substance abuse disorders, addiction, overdose, and death. Alternate therapies for chronic pain are needed to mitigate these adverse outcomes and reduce societal problems related to opioid use (9).

Studies also support the idea of cannabinoids being safe and moderately effective in neuropathic pain seen with LBP (6). A systematic review by Deshpande et al. found that most patients with neuropathic pain treated with medicinal cannabis had a clinically significant decrease in pain (>2 points on a 10-point scale). A study by Hoggart et al. examined 380 patients with peripheral neuropathic pain administering oromucosal THC/CBD mixed spray over 38 weeks that resulted in clinical improvements for at least 30% of patients throughout the study (4). 

Presently, there is an interest in using CBD rather than THC for medicinal purposes. THC interacts directly with CB1/CB2 receptors; however, CBD does not. Instead, CBD encourages the body to make use of native cannabinoids. Focusing on a combination of medicinal cannabis, THC's neurotransmitter and cytokine inhibitory actions, paired with the serotonergic and neuroexcitatory inhibiting properties of CBD on THC, provide a new, plausible means for pain management, especially LBP (4).

Cannabis is not approved by the Food and Drug Administration (FDA) and is considered an illicit drug by the US Drug Enforcement Agency (DEA). However, several US states allow permit registration under specific medical guidelines (6). Cannabis has been tightly regulated with a Schedule I status due to stigma and hopes to prevent abuse for its pleasure-seeking effects. Moreover, these barriers have delayed innovative research and its medical use (10). 

Opiate treatment alone presented minimal improvement in most evaluated functional outcomes. The addition of MCT to opioids resulted in a significant reduction in LBP (11). Currently, limited data supports MCT as a complete replacement for opioids. However, population studies show that the legalization of MCT has been associated with reduced mortality due to opioid overdose, reduced opioid-related hospitalizations, and decreased opioid prescription” (7).

Discussion

Low back pain afflicts a vast population of the United States, as such, it is imperative to find effective and safe treatment options. Opioids have been historically significant in decreasing the pain patients experience; however, other alternatives may provide less addictive effects. Cannabis, though an illicit drug, has displayed significant pain reduction. Moreover, as a combination therapy, it allows for lower doses of opioids. There is still a need for research on the long-term effects of cannabinoids, as it has been limited due to systematic and social barriers. When considering increasing cannabis use, it is essential to consider the absence of long-term research and potential side effects.

REFERENCES

1. Feng Y, He X, Yang Y, Chao D, Lazarus LH, Xia Y. Current research on opioid receptor  function. Curr Drug Targets. 2012 Feb;13(2):230-46. Accessed June 26, 2023.

2. Nury, Edrisa,*; Schmucker, Christinea; Nagavci, Blina; Motschall, Edithb; Nitschke, Kaia; Schulte, Erikac; Wegwarth, Odettec,d; Meerpohl, Joerg J.a,e. Efficacy and safety of strong opioids for chronic noncancer pain and chronic low back pain: a systematic review and meta-analyses. PAIN 163(4):p 610-636, April 2022. | DOI: 10.1097/j.pain.0000000000002423. Accessed June 27, 2023.

3. Khalid N, Singh A. Cannabis Versus Opioids for Pain. [Updated 2023 Jan 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK573080/. Accessed June 26, 2023.

4. Bridgeman MB, Abazia DT. Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting. P T. 2017 Mar;42(3):180-188. PMID: 28250701; PMCID: PMC5312634. Accessed June 26, 2023.

5. Khalid N, Singh A. Cannabis Versus Opioids for Pain. [Updated 2023 Jan 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK573080/. Accessed June 26, 2023.

6. Helen Senderovich, Hayley Wagman, Dennis Zhang, Danusha Vinoraj, Sarah Waicus; The Effectiveness of Cannabis and Cannabis Derivatives in Treating Lower Back Pain in the Aged Population: A Systematic Review. Gerontology 1 June 2022; 68 (6): 612–624. https://doi.org/10.1159/000518269. Accessed June 27, 2023.

7. Knox, Jeffrey MD*; Orchowski, Joseph MD*; Scher, Danielle L. MD†; Owens, Brett D MD‡; Burks, Robert PhD§; Belmont, Philip J. MD†. The Incidence of Low Back Pain in Active Duty United States Military Service Members. Spine 36(18):p 1492-1500, August 15, 2011. | DOI: 10.1097/BRS.0b013e3181f40ddd. Accessed June 26, 2023.

8. Petzke, F, Klose, P, Welsch, P, Sommer, C, Häuser, W. Opioids for chronic low back pain: An updated systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks of double-blind duration. Eur J Pain. 2020; 24: 497– 517. https://doi.org/10.1002/ejp.1519. Accessed June 27, 2023.

9. Greis A, Renslo B, Wilson-Poe A R, et al. (January 20, 2022) Medical Cannabis Use Reduces Opioid Prescriptions in Patients With Chronic Back Pain. Cureus 14(1): e21452. DOI 10.7759/cureus.21452. Accessed June 26, 2023.

10. ElSohly MA, Radwan MM, Gul W, Chandra S, Galal A. Phytochemistry of Cannabis sativa L. Prog Chem Org Nat Prod. 2017;103:1-36. Accessed June 26, 2023.

11. Yassin M, Oron A, Robinson D. Effect of adding medical cannabis to analgesic treatment in patients with low back pain related to fibromyalgia: an observational cross-over single centre study. Clin Exp Rheumatol. 2019 Jan-Feb;37 Suppl 116(1):13-20. Epub 2018 Oct 30. PMID: 30418116. Accessed June 26, 2023.