Abstract
Introduction: GERD is one of the most diagnosed digestive disorders globally, with an estimated 20% prevalence in the US. Marijuana use in the US, and globally, has shown a consistent uptrend. This study aims to detect any relationship between marijuana use and GERD complications. Methods: We used the National Inpatient Sample dataset for 2016-2020 for this retrospective study. Our outcomes were reflux esophagitis and Barrett’s esophagus, with Marijuana use being the predictor variable. We performed a chi-square test, descriptive analysis, as well as simple and multiple logistic regressions to assess associations.
Results: 4,633,135 adults were diagnosed with GERD. Approximately 0.16% of patients had reflux esophagitis, while 1.18% had Barrett’s esophagus. Alcohol (2.04%), marijuana (1.96%), and more than one-tenth used cigarettes (12.21%). Majority of the study population are female (57.56%), white (77.51%) and ≥65 years (58.03%). Marijuana users (aOR = 1.801 [1.389-2.335], P < .0001) were more likely to have reflux esophagitis or Barrett’s esophagus (1.226 [1.054-1.426], 0.0081) compared to non-users. Conclusion: Marijuana use is associated with GERD complications. Therefore, we recommend educating patients with GERD on making healthy lifestyle choices, such as abstaining from or moderating the use of substances like marijuana. Additional studies are required to define safe amounts of recreational marijuana.
Keywords: lifestyle, marijuana, cannabis, GERD, reflux esophagitis, Barrett’s esophagus
“Our study observed a high risk of Barrett’s esophagus, a premalignant lesion in the esophagus, in patients with GERD who also use marijuana.”
Introduction
The backward flow of stomach contents into the esophagus is the hallmark of gastroesophageal reflux disease (GERD), a common and chronic gastrointestinal disorder characterized with symptoms like acid regurgitation and heartburn. 1 In Western countries, GERD affects approximately 20% of adults, with U.S. prevalence estimates ranging from 18.1% to 27.8%. While men have a slightly higher occurrence, a meta-analysis suggests that women report GERD symptoms more frequently. 2 Several factors such as aging, obesity, and certain lifestyle choices have been linked to the rising prevalence of GERD. Obesity is significantly associated with GERD by elevating intra-abdominal pressure, which subsequently promotes the reflux of gastric contents into the esophagus. 3 Moreover, GERD results from physiological factors such as lower esophageal sphincter dysfunction and hiatal hernia. 2 Lifestyle decisions have a significant impact on the pathophysiology of GERD; for example, cigarette smoking is a well-known risk factor for GERD.2,4 Additionally, levels of physical activity matter; while recreational physical activity appears beneficial, occupational physical activity may raise the risk of GERD. 4
Marijuana use is one such lifestyle risk that is receiving more attention and may have consequences for those with GERD. 5 In the United States, 16% of adults report frequently smoking marijuana, with younger adults reporting especially high consumption rates. 6 This could be a result of the growing trend of marijuana use legalization in several states in the U.S. Although well-known for its medicinal benefits, which are not limited to analgesia and hunger stimulation, there is growing concern about how it may affect gastrointestinal health. 5 The potential link between marijuana use and gastroesophageal reflux disease (GERD) has been the focus of several studies, yielding mixed findings. 5 Research indicates that Δ9-tetrahydrocannabinol (Δ9-THC), the primary psychoactive component of marijuana, influences lower esophageal sphincter (LES) function through multiple mechanisms. Studies in healthy volunteers have shown that Δ9-THC reduces basal LES pressure, with effects peaking around 100 minutes after ingestion before gradually returning to baseline, which may weaken the barrier against reflux. 7 In parallel, animal studies confirm that Δ9-THC dose-dependently inhibits transient LES relaxations, the main triggers for reflux, an effect reversed by CB1 receptor antagonists, thus reinforcing the role of these receptors in modulating LES function. 7 Other mechanisms of marijuana include delayed gastric emptying, prolonging acid exposure in the esophagus and potentially worsening GERD symptoms. 8 The absence of CB1 receptors in preganglionic vagal motor neurons projecting to the gastric fundus or LES suggests that these receptors do not directly modulate vagal motor output. Instead, their effects are mediated via central activation pathways. 9 While these findings highlight the complex interplay between the endocannabinoid system and LES modulation, the overall impact of marijuana on reflux disease remains unclear, warranting further research into its long-term effects and potential therapeutic targets within the CB1 receptor pathway.
Methods
The National Inpatient Sample dataset from 2016 to 2020 was used to select patients with a GERD diagnosis for this study. This dataset was accessed at: https://www.hcup-us.ahrq.gov. 10 The study examined reflux esophagitis and Barrett’s esophagus as outcomes, with marijuana use as the main predictor. However, the dataset did not include information on the amount, frequency, or route of marijuana use. Sociodemographic factors, comorbidities, and substance use such as alcohol and cigarettes were confounders because they could influence the outcome (GERD complications) and interact with marijuana use. A chi-square test of categorical variables was performed, and descriptive analysis, simple logistic regression, and multiple logistic regressions were conducted to assess potential interactions between marijuana and GERD complications while controlling for confounders. The level of significance was set at P-value < .05. All analyses were conducted with statistical software SAS version 9.4 (SAS Institute Inc., Cary, NC, USA).
Results
4,633,135 patients (weighted frequency) were diagnosed with GERD during this 5-year study period. Approximately 0.16% of patients had reflux esophagitis, 1.18% had Barrett’s esophagus, 2% used alcohol (2.04%), 1.96% used marijuana, and more than one-tenth used cigarettes (12.21%). One-fifth is obese (19.87%), and the majority are female (57.56%), white (77.51%), and ≥65 years (58.03%). (Table 1) Both marijuana users (aOR = 1.801 [1.389-2.335], P < .0001) and alcohol users (1.925 [1.499-2.472], P < .0001) were more likely to have reflux esophagitis. (Table 2) Additionally, marijuana users (1.226 [1.054-1.426], P = .0081) and alcohol users (1.298 [1.143-1.473], P < .0001) were more likely to have Barrett’s esophagus. (Table 3) Furthermore, males of any age were more likely (1.649 [1.582-1.720], P < .0001) to have Barrett’s esophagus. Lastly, non-White were less likely to have Barrett’s esophagus. (Table 3)
Table 1.
Characteristics of Study Population With Diagnosis of GERD.
| Variables | Weighted Frequencies (%) | p-values |
|---|---|---|
| Age | <.0001 | |
| 18-24 years | 55,705 (1.202%) | |
| 25-34 years | 187,900 (4.056%) | |
| 35-44 years | 283,835 (6.126 %) | |
| 45-54 years | 496,990 (10.727%) | |
| 55-64 years | 919,865 (19.854%) | |
| ≥65 years | 2,688,840 (58.035%) | |
| Reflux esophagitis | <.0001 | |
| Absent | 4,625,645 (99.838%) | |
| Present | 7,490 (0.162%) | |
| Barrett’s Esophagus | .0001 | |
| Absent | 4,578,485 (98.820%) | |
| Present | 54,650 (1.180%) | |
| Race/ethnicity | <.0001 | |
| White | 3,593,045 (77.551%) | |
| Black | 615,120 (13.277%) | |
| Hispanic | 342,390 (7.390%) | |
| Asian/ Pacific Islander | 3,386 (1.782%) | |
| Length of Hospital | <.0001 | |
| ≤3 days | 1,596,480 (34.458%) | |
| >3 days | 3,036,655 (65.542%) | |
| Sex | <.0001 | |
| Male | 1,966,280 (42.440%) | |
| Female | 2,666,855 (57.560%) | |
| BMI | <.0001 | |
| Non-obese | 3,712,475 (80.129%) | |
| Obese | 920,660 (19.871%) | |
| Alcohol use | <.0001 | |
| Absent | 4,538,520 (97.958%) | |
| Present | 94,615 (2.042%) | |
| Marijuana use | <.0001 | |
| Absent | 4,542,355 (98.041%) | |
| Present | 90,780 (1.959%) | |
| Cigarette smoking | <.0001 | |
| Absent | 4,067,090 (87.783%) | |
| Present | 566,045 (12.217%) | |
| Hospital location | <.0001 | |
| Rural | 459,992 (9.928%) | |
| Urban non-teaching | 825,700 (17.822%) | |
| Urban teaching | 3,347,443 (72.250%) | |
| Insurance | ||
| Medicaid | 522,095 (11.269%) | <.0001 |
| Medicare | 2,906,105 (62.724%) | |
| Self-pay | 93,535 (2.019%) | |
| Private | 980,565 (21.164%) | |
| Other | 130,835 (2.824%) | |
| Total | 4,633,135 (100%) | |
*BMI-body mass index.
Table 2.
Bivariate and Multivariate Logistic Regression of Marijuana use as a Lifestyle Factor and Reflux Esophagitis.
| Variables | Unadjusted OR (95% CI) | p-values | Adjusted OR (95% CI) | p-values |
|---|---|---|---|---|
| 25-34 years | 1.575 (0.866-2.863) | .1367 | 1.601 (0.880-2.914) | .1235 |
| 35-44 years | 2.147 (1.243-3.708) | .0062 | 2.199 (1.268-3.814) | .0050 |
| 45-54 years | 1.518 (0.875-2.635) | .1375 | 1.577 (0.904-2.752) | .1088 |
| 55-64 years | 1.566 (0.910-2.696) | .1055 | 1.650 (0.948-2.869) | .0763 |
| ≥65 years | 1.215 (0.708-2.085) | .4806 | 1.278 (0.728-2.244) | .3936 |
| Black | 1.105 (0.949-1.287) | .1969 | 1.016 (0.870-1.186) | .8422 |
| Hispanic | 1.052 (0.868-1.276) | .6042 | 0.965 (0.794-1.175) | .7251 |
| Asian/Pacific Islander | 0.721 (0.462-1.126) | .1502 | 0.702 (0.448-1.099) | .1218 |
| Male | 1.140 (1.029-1.262) | .0119 | 1.098 (0.989-1.218) | .0790 |
| Alcohol use | 2.286 (1.805-2.894) | <.0001 | 1.925 (1.499-2.472) | <.0001 |
| Marijuana use | 2.238 (1.737-2.883) | <.0001 | 1.801(1.389-2.335) | <.0001 |
| Cigarette smoking | 1.165 (1.001-1.356) | .0048 | 0.943 (0.801-1.110) | .4807 |
| Medicaid | 1.144 (0.836-1.567) | .4001 | 1.042 (0.756-1.437) | .8011 |
| Medicare | 0.861 (0.643-1.154) | .3162 | 1.020 (0.758-1.373) | .8959 |
| Self-pay | 1.339 (0.887-2.020) | .1646 | 1.163 (0.768-1.761) | .4749 |
| Private | 0.922 (0.693-1.263) | .6143 | 0.910 (0.661-1.252) | .5628 |
| Obese | 0.931 (0.817-1.061) | .2834 | 0.899 (0.789-1.026) | .1134 |
| Rural hospital | 0.670 (0.528-0.851) | .0010 | 0.678 (0.534-0.863) | .0016 |
| Urban non-teaching | 1.170 (0.993-1.378) | .0608 | 1.189 (1.009-1.400) | .0386 |
*Reference groups: age; 18-24 years, race/ethnicity- white, sex-female, alcohol use, marijuana use, cigarette smoking- non-users, insurance- other payer, obesity- nonobese, hospital location- urban teaching hospital.
Table 3.
Bivariate and Multivariate Logistic Regression of Marijuana use as a Lifestyle Factor and Barrett’s Esophagus.
| Variables | Odds Ratio (95% CI) | p-values | Adjusted Odds Ratio (95% CI) | p-values |
|---|---|---|---|---|
| 25-34 years | 2.227 (1.277-3.883) | .0048 | 2.183 (1.252-3.809) | .0060 |
| 35-44 years | 4.704 (2.754-8.033) | <.0001 | 4.269 (2.499-7.294) | <.0001 |
| 45-54 years | 7.514 (4.435-12.732) | <.0001 | 6.471 (3.813-10.980) | <.0001 |
| 55-64 years | 10.035 (5.935-16.967) | <.0001 | 8.196 (4.838-13.883) | <.0001 |
| ≥65 years | 10.864 (6.432-18.349) | <.0001 | 8.657 (5.102-14.690) | <.0001 |
| Black | 0.183 (0.162-0.207) | <.0001 | 0.199 (0.175-0.225) | <.0001 |
| Hispanic | 0.410 (0.368-0.456) | <.0001 | 0.448 (0.403-0.499) | <.0001 |
| Asian/Pacific Islander | 0.423 (0.343-0.521) | <.0001 | 0.428 (0.347-0.527) | <.0001 |
| Male | 1.750 (1.679-1.825) | <.0001 | 1.649 (1.582-1.720) | <.0001 |
| Alcohol use | 1.304 (1.151-1.476) | <.0001 | 1.298 (1.143-1.473) | <.0001 |
| Marijuana use | 0.865 (0.746-1.003) | .0544 | 1.226 (1.054-1.426) | .0081 |
| Cigarette smoking | 0.958 (0.900-1.019) | .1716 | 1.038 (0.973-1.108) | .2548 |
| Medicaid | 0.660 (0.570-0.763) | <.0001 | 1.059 (0.916-1.225) | .4375 |
| Medicare | 1.173 (1.032-1.334) | .0146 | 1.155 (1.016-1.313) | .0275 |
| Self-pay | 0.702 (0.565-0.872) | .0014 | 1.230 (1.075-1.407) | .8437 |
| Private | 1.041 (0.909-1.191) | .5649 | 0.979 (0.788-1.214) | .0025 |
| Obese | 0.931 (0.817-1.061) | <.0001 | 0.997 (0.945-1.051) | .8980 |
| Rural hospital | 0.774 (0.687-0.873) | <.0001 | 0.690 (0.614-0.776) | <.0001 |
| Urban non-teaching | 0.934 (0.863-1.012) | .0952 | 0.881 (0.816-0.952) | .0014 |
*Reference groups: Age; 18-24 years, race/ethnicity- white, sex- female, alcohol use, marijuana use, cigarette smoking- non-users, insurance- other payer, obesity- nonobese, hospital location- urban teaching hospital.
Discussion
This study aimed to evaluate the association between marijuana use and GERD complications, mainly reflux esophagitis and Barrett’s esophagus. We found that patients with GERD who also consumed marijuana were more likely to have reflux esophagitis (1.801 [1.389-2.335], P < .001) or Barrett’s esophagus (1.226 [1.054-1.426], P = .008) as complications of GERD compared to non-marijuana users. A similar study by Kaur A et al. which evaluated the association between marijuana use and GERD complications, 11 showed a higher prevalence of esophagitis in marijuana users compared to non-users. This result aligns with our study, showing a greater risk of reflux esophagitis and Barrett's esophagus in marijuana users compared to non-users.
The positive relationship between marijuana use and reflux esophagitis could be related to the significant reduction in basal lower esophageal sphincter (LES) pressure after marijuana use, and/or the increased transient lower esophageal sphincter relaxation (TLESR),7,12 culminating in the repeated backflow of stomach acid into the esophagus and worsening of symptoms.
Our study observed a high risk of Barrett’s esophagus, a premalignant lesion in the esophagus, in patients with GERD who also use marijuana. Only a few case reports on Barrett’s esophagus in patients using marijuana have been documented in medical literature. Levy J et al. reported a long-segment Barrett’s esophagus in a patient with chronic marijuana use. 13 Furthermore, a similar pattern of GERD-related complications was observed among alcohol users. This finding is supported by studies conducted by Akiyama T et al. and Chen SH et al. which assessed the impact of alcohol consumption on GERD-related outcomes.14,15
In addition to lifestyle factors, several sociodemographic factors including age, sex, race/ethnicity, insurance type, and hospital location were significantly associated with Barrett’s esophagus among adults with GERD. The risk of developing Barrett’s esophagus increased with age, with the highest risk observed in individuals aged ≥65 years and those covered by Medicare (Table 3). These findings are consistent with those of Johnson DA et al. who reported an age-related increase in GERD complications. 16
Additionally, our study found that GERD complications were less likely to be diagnosed in rural or non-urban teaching hospitals compared to urban teaching hospitals (Table 3). This may reflect limited access to gastrointestinal specialists and endoscopic services in these settings, resulting in patients with suspected complications being referred to urban centers for advanced care. We also observed that Barrett’s esophagus was more likely in male compared to female, but significantly less likely in minority groups including Black, Hispanic, and Asian individual compared to White adults, aligning with findings from Corley DA et al. 17
The introduction of medical marijuana, which is commonly used for cancer-related pain, chemotherapy-related emesis, muscle spasms in multiple sclerosis, HIV-related muscle wasting, and the legalization of recreational marijuana, has further increased the number of marijuana users and the likelihood of cannabis use disorder (CUD) in our societies. 18 Recognizing that cessation of marijuana use may be challenging, we recommend the adoption of evidence-based approaches like the Lower-Risk Marijuana Use guidelines to limit the initiation of marijuana in non-users and also cut down the frequency and quantity of marijuana in chronic users. 19
Furthermore, Gates et al. analyzed several psychosocial interventions to address CUD, such as cognitive behavioral therapy (CBT) and motivational enhancement therapy (MET), which would also contribute to controlling and limiting the use of marijuana.20,21 Currently, no pharmacological intervention has been approved for CUD, but there is ongoing research. 21 Potential barriers to limit the use of cannabis in the community include a lack of awareness of the need for treatment and different treatment options, as well as the social stigma associated with seeking treatment for cannabis. 9
A major strength of this study is that it utilized the largest and most diverse national inpatient dataset. We also identified marijuana use as a contributing risk factor to reflux esophagitis and Barrett’s esophagus and created awareness of the increased risk among marijuana users while advocating for advocating for regulation of marijuana use, especially among GERD patients. The study findings were limited by: Firstly, as a cross-sectional study, we could only identify an association between marijuana use and reflux esophagitis and Barrett’s esophagus, not causation. Secondly, the study dataset did not identify the frequency, form, or quantity of marijuana use associated with these complications.
Conclusion
Our study results found that marijuana use is associated with reflux esophagitis and Barrett’s esophagus in patients with GERD. These insights need to be incorporated into the management plans of these patients through educating them about the risk of GERD complications among marijuana users, while also advocating for screening and moderation of marijuana use. Further research to quantify the amount, frequency and the form of marijujana use that is linked to GERD complications is recommended.
Footnotes
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
Ethical Statement
Ethical approval
This study used publicly available, de-identified data and did not require IRB approval.
ORCID iDs
Adedeji Adenusi https://orcid.org/0009-0003-5838-887X
Abdelaziz Mohamed https://orcid.org/0009-0004-1927-659X
MarkAnthony Ntow https://orcid.org/0009-0002-6155-3162
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