The potential role of marijuana in spine surgery: a narrative review of preliminary evidence concerning pre- and post-operative consumption on patient outcomes and implications for future research

Introduction

Recent studies indicate increasing chronic pain, opioid dependency and tolerance among general and surgical populations. Analysis (1) of the National Health Interview Survey reveals that over 20% of adults in the United States experience chronic pain, leading to significant impacts on daily life, social activities and work productivity. Concurrently the opioid crisis has escalated, with opioid related rising from 9,489 to 42,245 between 2001 and 2016 (2), underscoring the critical health and social changes posed by opioid dependency and abuse.

Within the surgical context, investigations by Hill et al. (3) have revealed concerning patterns of opioid prescribing, showing that many patients are prescribed excessive amounts of opioids for common general surgical procedures such as partial mastectomy, laparoscopic cholecystectomy, and inguinal hernia repair, potentially contributing to long-term dependency and tolerance.

While surgery aims to alleviate pain and to improve patient’s quality of life, post-operative pain management remains a critical concern (4). Historically, opioids such as oxycodone, hydrocodone, and tramadol have been widely prescribed for post-surgical pain relief however, there is growing awareness of the potential risks and adverse effects associated with prolonged opioid use, such as addiction and overdose (5). As a result, recent research has focused on delineating post-operative opioid prescription and usage rates in spine surgery patients, and identifying factors that contribute to excessive opioid consumption. Rezaii et al. (6) analysed the impact of lumbar spine surgery on postoperative opioid usage in the United States veteran population. Their retrospective study found that minimal preoperative opioid exposure increased the risk of continued opioid usage postoperatively by 2.69 times compared to opioid-naive patients. These results were corroborated by Orosz et al. (7) who evaluated the percentage of unused opioids at 90 days after elective spine surgery and reported those who did not use opioids prior to surgery more frequently left opioid medication unused (58% vs. 28.4%, P<0.001).

Therefore, given the context of the opioid epidemic in the United States of America (USA), and established complications of tolerance and dependency associated with opioid use, it is imperative that efficacious alternatives are sourced and implemented, in order to reduce opioid reliance and promote a more judicious use of pain medications. Recently, there has been social and academic interest regarding the use of marijuana, cannabidiol (CBD) or delta-9-tetrahydrocannabinol (THC) for pain management. However, little is known regarding its efficacy or adverse effects in spine surgery populations and more evidence has been published since past reviews were written (8). This narrative review aims to explore the role of cannabis in pain management for spine patients and discuss the effect of chronic use on pain and surgical outcomes. We present this article in accordance with the Narrative Review reporting checklist (available at https://amj.amegroups.com/article/view/10.21037/amj-23-135/rc).

Methods

In December 2023, A narrative review was performed using PubMed, Embase, and Scopus for articles pertaining to cannabis use in spine surgery patients (following criteria outlined in Table 1), published from inception up until December 16th 2023 and published in English (or with readily available translation). A total of 1,509 studies were identified. After removing 446 duplicates, C.M. and N.W. assessed the remaining studies by title and abstract, leading to the retrieval attempt of 23 full texts. One was inaccessible, and seven lacked full texts. Six studies were further excluded for using national databases with overlapping patient data. Nine studies examining the impact of preoperative cannabis use were included. No research on cannabis as an adjunct for acute post-spine surgery pain was found. These papers underpin the subsequent narrative synthesis. Appendix 1 shows the full search strategy for each database.

Findings and discussion

Prevalence, mechanisms and applications of marijuana, CBD, and THC

In a survey (9) of 27,169 individuals from the USA and Canada, it was found that 27% reported cannabis use for medical purposes at some point. Prevalence was similar across genders but peaked among young adults. Variation also occurred with legal status: 34% in US states with legal recreational cannabis vs. 23–25% in other regions. Figure 1 shows a map depicting cannabis policy conditions at the time of the survey conducted in 2018 (8).

Figure 1 A map depicting cannabis policy conditions at the time of the survey conducted in 2018. The three categories observed are as follows: “US illegal”: this category indicates that cannabis was illegal for recreational use, and there was no legal medical market available. “US legal-recreational”: this category indicates that cannabis was legal for both recreational and medical use in the US. “US legal-medical only”: this category indicates that cannabis had a legal medical market, but recreational use remained illegal in the US. Adapted from Leung et al. (9) under the Creative Commons Attribution License (CC BY).

Marijuana, a product of cannabis sativa, has been used for medical purposes for thousands of years (10). Its psychoactive effects are mainly attributed to THC, which acts on cannabinoid (CB1) receptors in the brain which are mapped to chromosome 6 (11,12). CB1 receptors primarily affect the central nervous system, while CB2 receptor, which THC also acts on as a weak partial agonist, influences immune cells and cytokine release (13). CBD is another key cannabis component, known for its analgesic, anxiolytic and anti-inflammatory effects. It acts as a weak CB1 allosteric modulator and influences several pathways (14).

Cannabis can be consumed orally, topically or through inhalation including either smoking or vaporization (14). Smoking offers rapid onset of effects, while oral intake peaks at about 6 hours with a half-life of 20–30 hours. When inhaled, THC’s bioavailability is around 30%, whereas its bioavailability drops to between 4% and 12% when taken orally. This compound is highly lipid soluble and is distributed in fatty tissues with about 1% of an given dose reaching the brain (15).

CBD has been approved by the Food and Drug Administration (FDA) for seizure-related disorders (16) and has shown efficacy in treating these conditions particularly in children with Dravet and Lennox-Gastaut syndromes (17). CBD is also used for chemotherapy-induced nausea and vomiting, spasticity in multiple sclerosis, Tourette syndrome and short-term sleep disturbances.

Further research (18) assessed cannabis’ effectiveness in non-surgical treatment of back pain. Promising results showed that THC and its synthetic derivatives dronabinol and nabilone can lead to significant reductions in back pain without serious adverse effects. This raises the question of whether cannabis or its derivatives may form part of an opioid-sparing regime following spine surgery.

Traditional pain management in spine surgery

Pain following spine surgery is typically most severe within the first 12 hours (19). This is due to the release of pain-related peptides stimulated by cytokines and chemokines, as well as combined neuropathic, nociceptive, and inflammatory pain elements (20). The process begins with activation of nociceptors which are sensitive to various chemical mediators like prostaglandins and bradykinin that are released during tissue injury. Once activated, the nociceptors send electrical signals to the spinal cord through A-delta fibers and C fibers and ultimately to the brain (21). This transmission involves multiple neurotransmitters and pathways which may modulate the transmission, resulting in a complex pain experience (22).

Opioids alleviate this pain by binding to specific mu-opioid receptors in the brain and spinal cord, primarily found in regions associated with pain modulation. In the brain, opioids inhibit pain signal transmission and alter perception, while in the spinal cord, opioids prevent the release of neurotransmitters such as substance P and glutamate, reducing pain signal transmission. Additionally, opioids may exert peripheral analgesic effects although this process remains elusive (23). Figure 2 illustrates the anatomical pathways of pain and CB1R expression in the brain and spinal cord.

Figure 2 Pain anatomical pathways and CB1R expression. Ascending pain pathways (in red) are carried from the body periphery through sensory neurons of dorsal root ganglia that synapse mainly with laminae I to III in the dorsal spinal cord. Projection neurons make connections with brain areas such as the thalamus and cortex. The descending pathways (in blue), responsible for pain modulation, involve areas such as the periaqueductal grey matter and amygdala, ending in the dorsal spinal cord. The CB1R distribution is heterogeneous in pain pathway areas, being more concentrated in regions such as cortex and CeA. Adapted from Campos et al. (21) under the Creative Commons Attribution License (CC BY). LA, lateral amygdala; CeA, central amygdala; BlA, basolateral amygdala.

In contrast to opioids that primarily have central effects, CBD and marijuana have a more varied impact due to their interactions with both CB1 and CB2 receptors throughout the body, offering both analgesic and anti-inflammatory effects.

Marijuana and pain

Marijuana for acute postoperative pain relief

Preclinical studies suggest cannabinoids may reduce reliance on opioids for acute pain relief (24), but clinical evidence remains unconvincing and no rigorous data yet exists to support its use following spine surgery. However, several randomized controlled trials (RCTs) in related specialties can provide insight for spine surgeons regarding cannabinoid use vs. opioid use for acute pain relief.

A 2006 RCT (25) comparing nabilone, a synthetic THC derivative, with placebo or ketoprofen in major orthopaedic and gynaecological procedures, showed no pain relief or reduction in nabilone use at low dose (1 mg). Surprisingly, a 2-mg dose of nabilone led to increased pain and opioid use, contradicting the biological gradient one may assume given preclinical predictions.

In 2011 (26), GW842166, a CB2-agonist akin to CBD, was randomized against ibuprofen or placebo for post-surgical pain in 123 patients following surgical wisdom tooth extraction. While ibuprofen significantly lowered pain scores compared to placebo, GW842166, at any dose, had no effect.

CBD’s efficacy was again queried in the CANBACK trial (27) for acute non-traumatic back pain in patients presenting to the emergency department. Participants received either 400 mg CBD or placebo alongside standard regular and breakthrough pain treatments. CBD showed no advantage over placebo in pain reduction, opioid use or hospital stay. Alaia et al. (28) studied buccal CBD in cannabis-naive patients after arthroscopic rotator cuff repair surgeries revealing a statistically significant pain reduction immediately post-surgery with both 25 or 50 mg doses, however these benefits were not sustained and no benefit was seen at day 7 or beyond. Haffar et al.’s study (29) using topical CBD after knee arthroplasty also found no improvement compared to placebo.

Pramhas et al. (30) tackled perceived issues of underdosing and infrequent administration in previous research by prescribing 600 mg of CBD daily, divided into three doses, to patients with knee osteoarthritis over a 2-month period. Their results found CBD inferior to paracetamol alone.

Although the potential of higher THC/CBD ratio formulations for improved pain relief remains uncertain, current evidence demands that spine surgeons remain circumspect regarding the efficacy of cannabinoids such as THC and CBD in managing both acute and postoperative pain. Randomized trials across disciplines have consistently found traditional analgesics to provide more effective pain control in such settings.

Marijuana for chronic back pain

Chronic back pain presents a significant challenge, as most conventional pain medications are unsuitable for long-term use. Cannabis is a controversial treatment option for chronic pain due to inconsistent study results and the varying methodological quality of published investigations. This has led authors to dub the field “The Bermuda triangle of low-quality studies, countless meta-analyses and conflicting recommendations” (31).

Numerous RCTs investigating various types of chronic pain find no evidence of benefit when assessing the effect of medicinal cannabis (32-34). Trials focusing specifically on chronic back pain are limited in number.

In 2006, Pinsger et al. (35) conducted a pilot study including 30 participants to assess nabilone’s effectiveness in treating refractory chronic back pain from degenerative diseases. This double-blinded, placebo-controlled study included a 14-week crossover phase with two 4-week treatment periods and 2-week washout intervals. Subsequently, patients, still blinded, chose either placebo or nabilone for a 16-week period. Dosage was self-determined (1–4 capsules/day), and outcomes included pain scores and quality of life assessments. Among 30 patients, nabilone showed notable improvements in pain and quality of life with a majority choosing it over placebo.

Rintala et al. (34) conducted a randomized, double-blinded crossover study comparing the efficacy of dronabinol vs. the active control diphenhydramine in managing central neuropathic pain after spinal cord injury. Participants were selected via convenience sampling and all pain medications were stopped before the experiment. They were offered acetaminophen and oxycodone for breakthrough pain during all phases of the study including at baseline and washout periods. Seven eligible participants completed the experiment and authors found reported pain intensity was not significantly different between the two medications.

A 2019 study by Yassin et al. (36) examined medical cannabis’ analgesic effect on 31 patients with chronic low back pain secondary to fibromyalgia. After an initial 3-month phase with standard pain therapies, patients received medical cannabis (1:4 THC:CBD) via smoking or vaporization alongside standard treatments. Assessments at baseline, 3 and 6 months showed significant pain and functional improvements with cannabis addition, without major adverse effects.

These studies, with small patient groups and disparate results, raise concerns about publication bias and type 1 error, particularly given the broader context of cannabis research in chronic pain. Also, their maximum follow-up of 6 months may not capture long-term effects, like tolerance. The differing results reported by investigators may be partly explained by variation in THC:CBD activity of the chosen drug. A recent meta-analysis (37) supports this assertion finding oral, synthetic formulations with high THC activity may be associated with short term improvements in chronic pain although patients were also found to be at an increased risk of dizziness and sedation. The International Association for the Study of Pain (IASP), in their statement (38) published in March 2021, notably refrained from endorsing cannabis due to a lack of robust research.

While spine surgeons might consider medical cannabis as part of a bespoke plan for chronic back pain, especially when conventional options are found inadequate, current evidence does not support a major shift in prescribing practices.

Outcomes after spine surgery among chronic marijuana users

Chronic cannabis use may negatively impact surgical outcomes (39). Cannabinoids are highly lipid soluble and accumulate in fatty tissue, leading to slow elimination (40). Low doses may increase sympathetic tone, causing tachycardia and hypertension, while high doses enhance parasympathetic tone leading to dose-dependent bradycardia and hypotension (40). Smoking cannabis has been linked to increased respiratory complications, a greater risk of myocardial infarction and stroke, and vasoconstrictive effects impairing wound healing (39). Long-term use may cause tolerance due to CB1 and CB2 receptor downregulation, increasing post-operative pain medication requirements (41).

In a study of 1,335 patients undergoing various surgeries (42), those who reported current cannabis use, regardless of purpose, experienced poorer outcomes before and after surgery. On the day of surgery, these patients reported more pain, functional impairment, fatigue, anxiety and depression compared to non-users (all P<0.01). Cannabis users had higher pre- and post-operative opioid use however by 6 months, there was no difference in surgical site pain or treatment effectiveness between groups. Similar results were seen via analyses of patients included in the 2012–2015 (39) and 2016–2019 (43) National Inpatient Sample Database where a diagnosis of cannabis use disorder (CUD) was associated with an increased risk of perioperative complications and mortality.

Large investigations of patients undergoing orthopaedic procedures such as total hip and knee arthroplasty suggest that preoperative cannabis users report higher postoperative pain scores, poorer sleep quality, and decreased surgical satisfaction relative to non-users (44,45).

Recent studies investigating the impact of marijuana use before spine surgery yielded mixed results, with a common finding being increased postoperative opioid dependence among cannabis users. Lambrechts et al. (46) studied 240 patients undergoing anterior cervical decompression and fusion (ACDF), finding that preoperative marijuana use did not significantly affect patient reported outcome measures (PROMs) but was associated with higher reoperation rates and prolonged opioid use post-surgery. Similarly, Khalid et al. (47) observed that patients using cannabis prior to spine surgery were more likely to develop opioid dependence postoperatively.

Razzouk et al. (48) conducted a retrospective study on 198 patients undergoing elective ACDF, noting that active cannabis users required significantly more opioids postoperatively than former users or nonusers. Moon et al. (49) reviewed 220 patients after posterior lumbar fusion (PLF) finding that regular cannabis users needed larger opioid doses post-surgery, despite being younger and having lower Charlson Comorbidity Index (CCI) scores compared to nonusers.

A multicentre database study (50) comparing outcomes in lumbar fusion patients with CUD against matched controls revealed that CUD patients had longer hospital stays and were more prone to deep vein thrombosis, respiratory failure and myocardial infarction. Evidence obtained via equivalent methodology by separate investigators suggests cannabis users are up to 80% more likely to experience pseudarthrosis following transforaminal lumbar interbody fusion (TLIF) (51).

Conversely, a retrospective study (52) of 102 patients scheduled for TLIF, finds marijuana does not significantly affect Oswestry Disability Index at 12 months. This was calculated via multivariate regression controlling for age, sex, body mass index (BMI), and extent of fusion. Of note, the marijuana-using group was significantly younger (mean age 52.6 years) than the control group (mean age 61.8 years). While the regression aimed to account for all group differences, more frequent comorbidities in the older control group could have obscured the effect of preoperative marijuana use in the younger group. The authors then extended their investigation enrolling new patients for a further 2 years (53) and subsequent analysis of one-to-one matched patients found no difference in rate of postoperative complications between marijuana users and controls. Dettori et al. (54) similarly find no difference between cannabis users and nonusers following TLIF with cannabis patients being almost 10 years younger on average.

Another investigation (55) of 259 patients propensity matched 3:1 according to age, CCI, smoking status, and levels operated on, who received lumbar fusion found preoperative marijuana use was a statistically significant predictor of spine reoperation within 3 years (odds ratio =2.34, P=0.04). However, cannabis use was not found to significantly influence PROMs. Trenchfield et al. (56) report corroborating evidence with marijuana use significantly increasing the risk of reoperation within 3 years of lumbar decompression with a non-significant increase in opioid use 1 year following surgery.

A retrospective study of 432 patients conducted by Shah et al. (57), investigated the effects of preoperative cannabis on outcomes after cervical spinal fusion. Half of included patients were reported as regular cannabis users. Both cohorts experienced comparable rates of 90-day medical, surgical, and overall complications (5.6% vs. 3.7%, P≤0.430) and 2-year revisions (4.3% vs. 2.8%, P=0.430). However, cannabis users had higher 90-day readmission rates (11.6% vs. 6.0%, P=0.042). The investigators conclude that baseline cannabis dependence/abuse was associated with increased 90-day readmission odds following cervical fusion.

Viewed in aggregate the available evidence aligns with intuition and suggests that long-term cannabis use has a negative impact on pain control post-operatively possibly due to tolerance and may lead to longer lengths of stay and more frequent revisions after spine surgery. It is plausible that cannabis, when smoked frequently, will impart postoperative cardiopulmonary sequelae akin to those associated with tobacco. Some studies that suggest no significant difference between cannabis users and controls are likely influenced by confounding factors, as cannabis-using cohorts are often substantially younger and less comorbid than their control counterparts. While little evidence is available to guide surgeons, it is prudent when trailing to cannabinoids for pain relief that smoked or vaporized formulations are avoided due to the possibility of greater surgical morbidity.

A summary of findings is outlined in Table 2.

Future directions for research

As the incidence of complex spine surgery rises, effectively managing postoperative pain becomes ever more important due to the typically high pain scores reported after such procedures. While opioids are a vital component of multi-modality pain management, concerns surrounding tolerance and dependency necessitate the exploration of alternative approaches. Preclinical studies show cannabis’ analgesic potential, however clinical research on its effectiveness in acute and chronic pain states is inconclusive. Current literature provides scant support for prescribing cannabis or its derivatives for acute or postoperative pain encountered by spine services. Some studies suggest a benefit to exogenous cannabinoids for chronic back pain, however similar investigations of analogous chronic pain syndromes contradict these findings and meta-analyses in this area have often found conflicting results which are difficult to reconcile. The optimal dosage, frequency and treatment duration of cannabis remain uncertain, with no long-term studies available to guide clinicians.

The bulk of cannabis research as it pertains to spine surgery details the impact of chronic use on postoperative outcomes, finding generally negative results such as increased postoperative opioid dependency and more frequent postoperative complications. However, this evidence is derived from retrospective studies which likely have not fully controlled for confounders. Higher quality research in this area would be beneficial to determine if cannabis is causal or merely a bystander in this relationship. Overall, this narrative review qualitatively evaluates the current literature surrounding exogenous cannabinoid use for acute pain and chronic pain in patients undergoing spine surgery. Extending beyond studies that investigate the effects of cannabis on patients undergoing isolated procedures such as cervical spinal fusion (57) and 1-to-2 level lumbar fusion (48), we aggregated data from eight distinct retrospective studies evaluating chronic cannabis use and outcomes after spine surgery, in order to offer novel and more comprehensive insights on the impact of chronic cannabis use on pain management and surgical outcomes both pre-operatively and post-operatively.

Conclusions

Based on this review, spine surgeons should approach the use of marijuana in their patients with caution. While cannabis may serve as part of a multimodal approach for chronic pain management, its role in postoperative pain relief and its possible influence on surgical outcomes necessitates a careful individualised assessment. Surgeons should consider the patient’s complete medical history including marijuana use when planning surgery and postoperative care. Future researchers should endeavour to perform larger, randomised trials with longer follow-up periods to better understand long-term pain effects and surgical outcomes. THC and CBD activity of the investigated compound should be strictly defined to facilitate meaningful comparison between studies.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Mark Lambrechts and Brian Karamian) for the series “Degenerative Spine Disease” published in AME Medical Journal. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://amj.amegroups.com/article/view/10.21037/amj-23-135/rc

Peer Review File: Available at https://amj.amegroups.com/article/view/10.21037/amj-23-135/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://amj.amegroups.com/article/view/10.21037/amj-23-135/coif). The series “Degenerative Spine Disease” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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