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. Author manuscript; available in PMC: 2026 Feb 24.
Published before final editing as: Am J Prev Med. 2026 Feb 13:108309. doi: 10.1016/j.amepre.2026.108309

Associations of Cannabis and Tobacco Use with Suicide Attempt, Suicide Death, and Overdose Death Among Veterans Prescribed Opioid Analgesics

Nhung Nguyen 1,*, Samuel Leonard 2, Amy L Byers 2,3,4,5, Peter C Austin 6, Erin E Krebs 7, Friedhelm Sandbrink 8,9,10, Dawn M Bravata 11,12,13, Salomeh Keyhani 2,3,4
PMCID: PMC12927608  NIHMSID: NIHMS2147846  PMID: 41692146

Abstract

Introduction:

Little is known if cannabis and tobacco use are indicators of suicide-related risks. This longitudinal study examined associations between cannabis and tobacco use with risks of suicide attempt/death and overdose death over a 2-year follow-up in a cohort of Veterans prescribed opioids.

Methods:

This study analyzed data in 2024 using a national cohort of 923,291 Veterans receiving opioid analgesics in Veterans Health Administration clinics collected during 2014–2019. Cannabis and tobacco use were assessed at cohort entry. Outcomes (suicide attempts, suicide death, overdose death) were obtained at follow-up through 2021. Cause-specific hazard models were used to examine associations between cannabis and tobacco use with each outcome, adjusting for well-established risk factors for suicide/overdose (e.g., substance use disorders, mental health, socio-demographics).

Results:

At baseline, 5.4% of the cohort used cannabis, and 39.4% used tobacco. At the end of follow-up (median follow-up time was 6.7–6.8 years), 2.2% of the sample had attempted suicide, 0.4% had died by suicide, and 0.5% had died by overdose. In adjusted models, cannabis use was associated with a higher rate of suicide attempt (hazard ratio [HR] 1.11, 95%CI: 1.06–1.15). Current use of tobacco at baseline (versus never use) was associated with a higher rate of suicide attempts (HR 1.18, 95%CI: 1.13–1.22), suicide deaths (HR 1.19, 95%CI: 1.07–1.32), and overdose deaths (HR 1.67, 95%CI: 1.51–1.83).

Conclusions:

Cannabis and tobacco use were associated with suicide attempts/deaths and overdose deaths among Veterans prescribed opioid analgesics, underscoring a need for monitoring patients who use tobacco and cannabis in this population.

Keywords: marijuana, nicotine, military, suicidality, overdose

INTRODUCTION

Veterans prescribed opioid analgesics have an elevated risk of both suicide and overdose.1 Opioids, by inducing life-threatening respiratory depression, are a leading cause of overdose mortality.2 Additionally, opioid use increases the risk of depression, further elevating the risk of suicide.3 The increased prescribing of opioids has paralleled a rise in overdose and suicide deaths in the United States (US), with 68.5% of overdose deaths and 3.6% of suicide deaths in 2017 relating to opioids.3

Cannabis and tobacco use are common among Veterans and linked to adverse health effects.4 Prevalence of cannabis use disorder in Veterans with pain has more than doubled from 1.1% in 2005 to 2.5% in 2019.5 Tetrahydrocannabinol (THC), the psychoactive component in cannabis, impairs cognition and is associated with mood disorders, which may lead to suicide.6 Although the understanding of cannabis-related harms remains limited, emerging evidence suggests that cannabis use, especially frequent and heavy use, is linked with suicidality among Veterans.7–11 Unlike opioids, cannabis does not suppress the central respiratory drive and is perceived as a safer alternative for managing pain or mitigating opioid-related side effects, dependency, and stigma.12 Although some advocate for cannabis’ potential role in reducing overdose risk, its sedative and psychoactive properties could theoretically increase overdose risk, particularly when combined with other substances. However, the relationship between cannabis use and overdose remains poorly understood, underscoring the need for investigating these associations.

Likewise, tobacco use is prevalent among Veterans with pain, with about 25% of those prescribed opioid analgesics reporting smoking tobacco.13 Individuals who smoke cigarettes are more likely to be prescribed opioid analgesics for longer durations and at higher dosages compared to those who do not smoke.14 Interactions between nicotinic and opioid receptor systems can modify responses to opioid-related cues, potentially increasing susceptibility to opioid use disorders.15 Thus, it is plausible that tobacco may increase overdose risk. Tobacco is also linked to risk factors for suicide (e.g., mood disorders and depression), and the association between cigarette smoking and increased suicide risk is documented among non-Veteran populations.16–19 However, the role of tobacco in suicide and overdose risk among Veterans with prescribed opioid analgesics is understudied. Clarifying their roles as markers of suicide-related risks could inform efforts to reduce premature mortality among Veterans prescribed opioid analgesics.

Suicide and overdose are related but distinct outcomes. Overdose may be due to a suicide attempt, resulting in either non-fatal or fatal outcomes.20 About 20%–30% of overdose deaths are classified as suicides, though the true proportion may be higher due to undetermined intent.21 Apparent accidental death by overdose may be due to suicidal intent.22,23 Previous research among Veterans has focused on suicidal ideation, with fewer examining suicide attempts and deaths by suicide and overdose.24 The Veteran Health Administration (VHA) provides a unique setting to examine the relationships between cannabis and tobacco use with suicide and overdose, given that it is the largest integrated healthcare system in the US with a robust electronic health record system. Using VHA data, this study aimed to examine the associations of cannabis and tobacco use with fatal (suicide deaths, overdose deaths) and non-fatal outcomes (suicide attempts) in a national cohort of Veterans receiving opioid analgesics. Cannabis and tobacco use were hypothesized to be associated with an elevated risk of suicide and overdose outcomes in this population.

METHODS

Study sample

This retrospective cohort study used VHA data to create a cohort of 923,291 Veterans who received outpatient opioid analgesics at VA primary care clinics nationwide. All Veteran prescriptions for opioids between January 1, 2014 (as the VA Opioid Safety Initiative was launched in 201325) and December 31, 2019 (the most recent data obtained) were identified. Veterans were included in the study if they were dispensed a 28+ day supply of opioids within a single 90-day window, reflecting a meaningful course of opioid analgesics. This cutoff is more inclusive than the standard 90-day definition of long-term opioid use, while excluding patients prescribed brief courses of opioids for procedures or acute short-term conditions.26 The index date was the date of the opioid prescription that exceeded the 28-day supply within the 90-day window. Exclusion criteria included having no pain diagnosis in the 2 years before the index date (to ensure opioids were prescribed for pain and no other conditions) or end of life (e.g., receipt of palliative care or hospice), as these patients may be using cannabis/opioids for palliative purposes and cannot contribute meaningfully to the follow-up period; attending a methadone clinic, as these patients were receiving methadone for opioid use disorder and not pain; or being prescribed dronabinol/other THC medication, as these patients may have a urine drug screen positive for THC without using cannabis (Figure 1). The cohort was followed through December 31, 2021. The study was approved by the Institutional Review Board of the University of California, San Francisco, and the Research and Development Committee of the San Francisco VA Health Care System. Informed consent was waived as this was a secondary data analysis.

Figure 1:

Figure 1:

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The cohort of Veterans on prescribed opioid analgesics at baseline was followed 2 years to assess the incidence of suicide attempts, suicide death, and overdose death

Measures

Outcomes were recorded from the index date to the end of the follow-up. Suicide outcomes included suicide attempts (non-fatal attempts) and suicide deaths (fatal attempts). Overdose deaths included intentional overdose suicide, unintentional overdose death, and undetermined intent. Non-fatal suicide data were obtained from the VA’s National Consolidated Suicide Behavior tables, based on clinician reports of suicide attempts in the Suicide Behavior and Overdose Report, Comprehensive Suicide Risk Evaluation, or Suicide Prevention Applications Network (SBOR/CSRE/SPAN) reporting templates, an internal tracking system that collects patient-level information on suicide events based on reports in VA medical facilities.27–29 Deaths by suicide and overdose were captured from the Mortality Data Repository (cause-specific mortality and suicide data).30,31 Suicide death International Classification of Diseases – Tenth version (ICD-10) codes included suicide death by firearm, suicide death by hanging, suicide death by drug overdose, or suicide death by other reasons. Overdose death ICD-10 codes included accidental self-poisoning, intentional self-poisoning, and self-poisoning of undetermined intent.

Cannabis use (yes/no) was based on positive urine drug testing for cannabis, ICD-10 codes for cannabis use, or medical cannabis use in non-VA settings within the 2 years before the index date.32 In VA, annual urine drug screening is required for patients who are prescribed long-term opioid analgesics.25 This screening can detect THC presence. Additionally, VA clinicians have been directed to record medical cannabis use within the VA electronic health record as a non-VA medication; these data were obtained from VA pharmacy files.33

Tobacco use status was defined using a previously developed algorithm derived from ICD-10 codes, Current Procedural Terminology (CPT) codes, stop codes, smoking cessation consults, and tobacco use assessments from national clinical reminders and health factors within the 2 years before the index.34,35 The VHA collects data on tobacco use history and current use status via national clinical reminders and health factors.34,35 These assessments are administered annually in person/by telephone and include tobacco use status as “current use,” “former use,” “never use,” or “unknown.” Other data related to tobacco use were obtained from the VA electronic health record.

Covariates were obtained within the 2 years before the index date and included well-documented risk factors for suicide and overdose among Veterans (e.g., sociodemographics, substance use, or mental health disorders).36 Opioid dosing was measured as the sum of morphine milligram equivalents prescribed in the 90 days before the index date. Comorbidities were measured using the Charlson Comorbidity Index (CCI).37 Other covariates included service connection (linkage between a disability/medical condition with military service), cohort year, and cannabis legalization status for the state in which the opioid prescription was dispensed.

Statistical Analysis

Data were analyzed in 2024 using STATA 18.0 (StataCorp LLC, College Station, TX, US). Characteristics for the total sample and by cannabis/tobacco use status were summarized. The associations between cannabis and tobacco use and the hazard of suicide attempts, suicide deaths, and overdose deaths were examined using cause-specific hazard models. Each model accounted for non-suicide death/non-overdose death as competing risks. Univariate models were used to estimate unadjusted hazard ratios. Multivariable models were used to estimate adjusted hazard ratios (aHR) for cannabis and tobacco use with each outcome, controlling for all covariates. A sensitivity analysis was conducted to examine the association between the outcomes and a four-level exposure: tobacco-only use, cannabis-only use, co-use (using any cannabis within two years prior to baseline and currently using tobacco), and non-use of either substance. Another sensitivity analysis was conducted by restricting the cannabis use measure to the one year before the index date to capture more recent use. The analysis used the complete dataset, as the amount of missing data was minimal. Statistical tests were two-tailed, and statistical significance was set at p<0.05. Results were reported in accordance with the Reporting of Observational Studies in Epidemiology (STROBE) guideline.

RESULTS

The sample included 923,291 Veterans with a mean age of 60.1 years (SD=13.5), 91.5% male, 74.3%White, and 92.8% non-Hispanic (Appendix Table 1). Alcohol use disorder (11.6%) was the most common substance use disorder. Mental health problems were prevalent, with 51.7% having mental health visits, 32.6% having depression, and 29.9% receiving antidepressant medication. The characteristics were significantly different by subgroups of cannabis and tobacco use status (Table 1). Proportions of substance use and mental health disorders and psychoactive medication receipt were higher among those who used cannabis (vs. those who did not) and among those who currently smoked tobacco (vs. formerly or never smoked).

Table 1:

Sample characteristics by cannabis use and tobacco use status

Characteristics Cannabis Tobacco
No use Cannabis use Current use Former use Never use Unknown
(N=873,286) (N=50,005) (N=363,424) (N=171,379) (N=193,747) (N=194,741)
Sociodemographic
Age, years M(SD) 60.4 (13.5) 54.7 (11.7) 57.1 (12.2) 63.8 (12.9) 59.4 (14.5) 63.0 (13.8)
Sex
 Male 798,270 (91.4%) 46,555 (93.1%) 335,254 (92.2%) 161,306 (94.1%) 168,873 (87.2%) 179,392 (92.1%)
 Female 75,016 (8.6%) 3,450 (6.9%) 28,170 (7.8%) 10,073 (5.9%) 24,874 (12.8%) 15,349 (7.9%)
Race
 White 652,734 (74.7%) 33,494 (67.0%) 271,947 (74.8%) 135,280 (78.9%) 133,172 (68.7%) 145,829 (74.9%)
 Black 148,247 (17.0%) 12,777 (25.6%) 64,867 (17.8%) 21,987 (12.8%) 44,354 (22.9%) 29,816 (15.3%)
 American Indian/Alaska Native 8,281 (0.9%) 557 (1.1%) 3,658 (1.0%) 1,672 (1.0%) 1,708 (0.9%) 1,800 (0.9%)
 Native Hawaiian/Pacific Islander 7,112 (0.8%) 377 (0.8%) 2,593 (0.7%) 1,347 (0.8%) 1,694 (0.9%) 1,855 (1.0%)
 Asian 4,506 (0.5%) 137 (0.3%) 1,221 (0.3%) 753 (0.4%) 1,067 (0.6%) 1,602 (0.8%)
 More than one race 7,805 (0.9%) 557 (1.1%) 3,237 (0.9%) 1,422 (0.8%) 1,886 (1.0%) 1,817 (0.9%)
 Unknown 44,601 (5.1%) 2,106 (4.2%) 15,901 (4.4%) 8,918 (5.2%) 9,866 (5.1%) 12,022 (6.2%)
Ethnicity
 Hispanic or Latino 43,264 (5.0%) 2,543 (5.1%) 13,265 (3.7%) 9,503 (5.5%) 13,116 (6.8%) 9,923 (5.1%)
 Not Hispanic or Latino 810,526 (92.8%) 46,615 (93.2%) 343,100 (94.4%) 158,005 (92.2%) 176,354 (91.0%) 179,682 (92.3%)
 Unknown 19,496 (2.2%) 847 (1.7%) 7,059 (1.9%) 3,871 (2.3%) 4,277 (2.2%) 5,136 (2.6%)
Married 467,515 (53.5%) 16,830 (33.7%) 159,492 (43.9%) 101,210 (59.1%) 110,128 (56.8%) 113,515 (58.3%)
Housing insecurity 53,543 (6.1%) 10,150 (20.3%) 39,404 (10.8%) 7,146 (4.2%) 9,732 (5.0%) 7,411 (3.8%)
Lack of social support 8,136 (0.9%) 1,135 (2.3%) 4,817 (1.3%) 1,376 (0.8%) 1,617 (0.8%) 1,461 (0.8%)
Substance use disorder
Alcohol use disorder 91,715 (10.5%) 15,376 (30.7%) 70,505 (19.4%) 12,350 (7.2%) 12,980 (6.7%) 11,256 (5.8%)
Stimulant use disorder 21,948 (2.5%) 7,606 (15.2%) 22,348 (6.1%) 2,354 (1.4%) 2,852 (1.5%) 2,000 (1.0%)
Opioid use disorder 20,381 (2.3%) 4,846 (9.7%) 16,423 (4.5%) 2,936 (1.7%) 3,224 (1.7%) 2,644 (1.4%)
Benzodiazepine use disorder 4,091 (0.5%) 1,256 (2.5%) 3,712 (1.0%) 554 (0.3%) 686 (0.4%) 395 (0.2%)
Other drug use disorders 28,362 (3.2%) 9,637 (19.3%) 27,699 (7.6%) 3,428 (2.0%) 3,846 (2.0%) 3,026 (1.6%)
Substance use disorder visits 45,405 (5.2%) 10,876 (21.7%) 38,086 (10.5%) 5,948 (3.5%) 7,143 (3.7%) 5,104 (2.6%)
Mental health disorder
Depression 276,821 (31.7%) 23,948 (47.9%) 135,657 (37.3%) 50,365 (29.4%) 63,277 (32.7%) 51,470 (26.4%)
Psychosis 20,450 (2.3%) 3,193 (6.4%) 13,398 (3.7%) 3,305 (1.9%) 3,956 (2.0%) 2,984 (1.5%)
Bipolar disorder 32,261 (3.7%) 5,034 (10.1%) 21,062 (5.8%) 5,073 (3.0%) 6,210 (3.2%) 4,950 (2.5%)
Post-traumatic stress disorder (PTSD) 33,117 (3.8%) 3,996 (8.0%) 15,200 (4.2%) 6,832 (4.0%) 10,116 (5.2%) 4,965 (2.5%)
Anxiety 132,806 (15.2%) 12,887 (25.8%) 67,919 (18.7%) 23,854 (13.9%) 30,378 (15.7%) 23,542 (12.1%)
Mental health visits 440,620 (50.5%) 36,592 (73.2%) 213,910 (58.9%) 79,826 (46.6%) 100,057 (51.6%) 83,419 (42.8%)
Medication treatment
Antidepressants 257,836 (29.5%) 18,188 (36.4%) 116,857 (32.2%) 48,943 (28.6%) 58,852 (30.4%) 51,372 (26.4%)
Benzodiazepines 141,043 (16.2%) 9,684 (19.4%) 66,126 (18.2%) 26,347 (15.4%) 28,543 (14.7%) 29,711 (15.3%)
Gamma-aminobutyric acid (GABA) 206,883 (23.7%) 14,148 (28.3%) 92,642 (25.5%) 40,951 (23.9%) 46,331 (23.9%) 41,107 (21.1%)
Prescribed Opioid dose, Mean (SD) 100.5 (324.5) 125.4 (390.2) 126.9 (385.3) 90.0 (296.5) 76.8 (238.1) 90.5 (314.2)
Charlson Comorbidity score, M(SD) 2.9 (2.2) 2.2 (1.9) 2.5 (2.0) 3.4 (2.2) 2.8 (2.2) 3.1 (2.2)
Other characteristics
Military sexual trauma 16,187 (1.9%) 1,658 (3.3%) 7,751 (2.1%) 2,497 (1.5%) 5,066 (2.6%) 2,531 (1.3%)
Service connection 569,086 (65.2%) 31,327 (62.6%) 225,972 (62.2%) 109,092 (63.7%) 137,270 (70.9%) 128,079 (65.8%)
Cohort year
 2014 573,522 (65.7%) 29,284 (58.6%) 247,668 (68.1%) 108,206 (63.1%) 115,389 (59.6%) 131,543 (67.5%)
 2015 123,358 (14.1%) 7,721 (15.4%) 48,410 (13.3%) 24,010 (14.0%) 29,481 (15.2%) 29,178 (15.0%)
 2016 78,237 (9.0%) 5,288 (10.6%) 30,205 (8.3%) 15,656 (9.1%) 20,063 (10.4%) 17,601 (9.0%)
 2017 46,764 (5.4%) 3,425 (6.8%) 17,993 (5.0%) 9,305 (5.4%) 12,789 (6.6%) 10,102 (5.2%)
 2018 30,154 (3.5%) 2,441 (4.9%) 11,588 (3.2%) 6,656 (3.9%) 9,136 (4.7%) 5,215 (2.7%)
 2019 21,251 (2.4%) 1,846 (3.7%) 7,560 (2.1%) 7,546 (4.4%) 6,889 (3.6%) 1,102 (0.6%)
Cannabis legalization status
 Illegal 204,206 (23.4%) 9,945 (19.9%) 93,188 (25.6%) 36,668 (21.4%) 47,877 (24.7%) 36,418 (18.7%)
 Medical 599,746 (68.7%) 34,815 (69.6%) 245,099 (67.4%) 119,911 (70.0%) 131,864 (68.1%) 137,687 (70.7%)
 Recreational 68,435 (7.8%) 5,211 (10.4%) 24,915 (6.9%) 14,697 (8.6%) 13,712 (7.1%) 20,322 (10.4%)
 Unknown 899 (0.1%) 34 (0.1%) 222 (0.1%) 103 (0.1%) 294 (0.2%) 314 (0.2%)
Outcomes
Suicide attempt 17,763 (2.0%) 2,662 (5.3%) 11,335 (3.1%) 2,499 (1.5%) 3,695 (1.9%) 2,896 (1.5%)
Suicide death 2,989 (0.3%) 241 (0.5%) 1,604 (0.4%) 515 (0.3%) 514 (0.3%) 597 (0.3%)
Overdose death 3,960 (0.5%) 639 (1.3%) 3,102 (0.9%) 427 (0.3%) 520 (0.3%) 550 (0.3%)
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Note: Proportions are column percentages; p-values <0.001 for all comparison across subgroups of cannabis use and tobacco use.

At baseline, 5.4% of the sample had used cannabis in the prior two years, and 39.4% were currently using tobacco. The median follow-up time in the cohort was 6.7–6.8 years. At the end of the follow-up, 2.2% of the sample had attempted suicide, 0.4% had died by suicide, and 0.5% died by overdose (Figure 1). Of the overdose deaths, 86.8% were unintentional, 8.1% were intentional, and 5.1% were due to unknown reasons.

Proportions of suicide attempts, suicide deaths, and overdose deaths were higher among those who used cannabis (5.3%, 0.5%, and 1.3%, respectively) than those who did not (Table 1). Those who currently smoked tobacco (vs. formerly or never smoked) had greater proportions of suicide attempts (3.1%), suicide deaths (0.4%), and overdose deaths (0.9%).

Proportions of cannabis and tobacco use were disproportionately high among those with suicide attempt/death and overdose death: 13.0% used cannabis and 55.5% currently used tobacco among those with suicide attempt; 7.5% and 49.7%, respectively, among those with suicide deaths; and 13.9% and 67.5%, respectively, among those with overdose deaths (Appendix Table 2).

In the unadjusted models, cannabis use at baseline (versus nonuse) was significantly associated with a higher rate of suicide attempt, suicide death, and overdose death at follow-up (Appendix Table 3). Current tobacco use was significantly associated with a higher rate of all outcomes.

After adjusting for covariates (Table 2), cannabis use at baseline was significantly associated with a higher rate of suicide attempts (aHR=1.11, 95%CI=1.06–1.15) but not significantly associated with suicide deaths (aHR=1.03, 95%CI=0.89–1.18) and overdose deaths (aHR=0.95, 95%CI = 0.87–1.04). Current use of tobacco (versus never use) was associated with a higher rate of suicide attempts (aHR=1.18, 95%CI=1.13–1.22), suicide deaths (aHR=1.19, 95%CI=1.07–1.32), and overdose deaths (aHR=1.67, 95%CI=1.51–1.83). Many covariates were significantly associated with the outcomes. For example, those with substance use and mental health disorders had a higher rate of suicide attempts/deaths and overdose deaths.

Table 2:

Factors associated with suicide and overdose outcomes among Veterans with prescribed opioid analgesics

Suicide attempt
Adjusted HR (95%CI)
N=922,319		 Suicide death
Adjusted HR (95%CI)
N=922,332		 Overdose death
Adjusted HR (95%CI)
N=922,332
Cannabis use (yes vs. no) 1.11 (1.06 – 1.15)*** 1.03 (0.89 – 1.18) 0.95 (0.87 – 1.04)
Tobacco use (ref = Never use)
Current use 1.18 (1.13 – 1.22)*** 1.19 (1.07 – 1.32)*** 1.67 (1.51 – 1.83)***
Former use 0.98 (0.93 – 1.03) 1.01 (0.90 – 1.15) 1.03 (0.90 – 1.17)
Unknown 1.04 (0.99 – 1.09) 1.04 (0.93 – 1.18) 1.18 (1.05 – 1.33)**
Sociodemographic
Age, years 0.96 (0.96 – 0.96)*** 0.99 (0.99 – 1.00)*** 0.96 (0.96 – 0.97)***
Sex (Female vs. Male) 1.05 (1.01 – 1.10)* 0.40 (0.33 – 0.47)*** 0.67 (0.60 – 0.75)***
Race (ref = White)
 Black or African American 0.80 (0.77 – 0.83)*** 0.27 (0.23 – 0.31)*** 0.83 (0.76 – 0.90)***
 American Indian or Alaska Native 1.27 (1.13 – 1.42)*** 0.83 (0.57 – 1.19) 0.58 (0.40 – 0.84)**
 Native Hawaiian or Other Pacific Islander 1.08 (0.93 – 1.25) 1.05 (0.72 – 1.54) 0.91 (0.63 – 1.31)
 Asian 1.02 (0.86 – 1.21) 0.75 (0.42 – 1.36) 0.69 (0.41 – 1.17)
 More than one race 1.07 (0.94 – 1.21) 1.04 (0.74 – 1.47) 1.00 (0.75 – 1.34)
 Unknown 0.86 (0.79 – 0.93)*** 1.25 (1.07 – 1.47)** 1.09 (0.93 – 1.28)
Ethnicity (ref = Hispanic/Latino)
 Not Hispanic/Latino 0.93 (0.88 – 0.98)** 1.78 (1.46 – 2.18)*** 1.34 (1.15 – 1.55)***
 Unknown 0.80 (0.70 – 0.92)** 1.84 (1.37 – 2.49)*** 1.28 (0.97 – 1.68)
Married 0.90 (0.88 – 0.93)*** 0.79 (0.73 – 0.85)*** 0.55 (0.52 – 0.59)***
Housing insecurity 1.40 (1.34 – 1.46)*** 0.73 (0.63 – 0.84)*** 1.47 (1.36 – 1.59)***
Lack of social support 1.36 (1.25 – 1.47)*** 1.07 (0.80 – 1.43) 0.95 (0.80 – 1.12)
Substance use disorders
Stimulant use disorder 1.47 (1.40 – 1.55)*** 0.85 (0.69 – 1.04) 1.66 (1.50 – 1.83)***
Alcohol use disorder 1.44 (1.39 – 1.50)*** 1.45 (1.31 – 1.61)*** 1.20 (1.11 – 1.30)***
Opioid use disorder 1.29 (1.22 – 1.36)*** 1.22 (1.03 – 1.44)* 2.58 (2.36 – 2.82)***
Benzodiazepine use disorder 1.15 (1.06 – 1.25)*** 1.18 (0.88 – 1.58) 1.31 (1.14 – 1.50)***
Other drug use disorders 1.28 (1.22 – 1.35)*** 1.13 (0.96 – 1.33) 1.61 (1.46 – 1.77)***
Substance use disorder visits (yes. vs. no) 1.23 (1.18 – 1.29)*** 1.12 (0.98 – 1.29) 1.11 (1.02 – 1.22)*
Mental health
Depression 1.42 (1.38 – 1.47)*** 1.25 (1.14 – 1.36)*** 0.97 (0.91 – 1.05)
Psychosis 1.60 (1.52 – 1.68)*** 1.16 (0.97 – 1.40) 0.96 (0.85 – 1.08)
Bipolar disorder 1.84 (1.77 – 1.92)*** 1.46 (1.28 – 1.66)*** 1.18 (1.07 – 1.29)***
PTSD 1.18 (1.11 – 1.25)*** 1.07 (0.85 – 1.35) 1.04 (0.87 – 1.23)
Anxiety 1.07 (1.04 – 1.10)*** 1.03 (0.94 – 1.12) 1.18 (1.10 – 1.26)***
Mental health visits (yes. vs. no) 1.69 (1.61 – 1.76)*** 1.11 (1.01 – 1.22)* 1.55 (1.42 – 1.69)***
Medication treatment
Benzodiazepines 1.27 (1.22 – 1.31)*** 1.63 (1.50 – 1.77)*** 1.65 (1.54 – 1.77)***
Antidepressants 1.36 (1.32 – 1.40)*** 1.22 (1.13 – 1.33)*** 1.05 (0.98 – 1.12)
GABA 1.11 (1.07 – 1.14)*** 1.02 (0.94 – 1.11) 1.29 (1.21 – 1.37)***
Prescribed Opioid dose 1.00 (1.00 – 1.00)*** 1.00 (1.00 – 1.00)*** 1.00 (1.00 – 1.00)***
Charlson score 1.02 (1.01 – 1.04)*** 1.01 (0.98 – 1.03) 0.98 (0.96 – 1.00)*
Other characteristics
Military sexual trauma 1.38 (1.30 – 1.47)*** 1.20 (0.93 – 1.54) 0.96 (0.81 – 1.14)
Service connection 1.00 (0.96 – 1.03) 0.45 (0.41 – 0.48)*** 0.33 (0.31 – 0.35)***
Cohort year 1.06 (1.05 – 1.08)*** 0.99 (0.95 – 1.03) 1.00 (0.96 – 1.04)
Cannabis legalization status (ref = Illegal)
 Medical 1.06 (1.02 – 1.10)*** 1.08 (0.99 – 1.18) 1.14 (1.06 – 1.23)***
 Recreational 1.19 (1.12 – 1.26)*** 1.20 (1.03 – 1.39)* 1.19 (1.05 – 1.35)**
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Note:

***

p<0.001,

**

p<0.01,

*

p<0.05;

HR: Hazard ratio.

In the sensitivity analysis, both tobacco-only use and cannabis-only use (vs. non-use of either) were associated with a higher rate of all outcomes (Appendix Table 4). Co-use was associated with a higher rate of suicide attempts and overdose deaths compared with non-use of either, but not significantly associated with suicide deaths. Results from the sensitivity analysis restricting cannabis use to the year before the index date are similar to the main findings (Appendix Table 5).

DISCUSSION

In this very large longitudinal cohort of Veterans prescribed opioid analgesics between 2014–2021, cannabis and tobacco use were differentially associated with suicide and overdose outcomes. After accounting for well-known risk factors for suicide and overdose, cannabis use at baseline (versus no use) was associated with a higher rate of suicide attempts at follow-up but was not associated with an increased rate of suicide or overdose death. Current use of tobacco (versus never use) was associated with an increased rate of all the outcomes (suicide attempts, suicide deaths, and overdose deaths). The effect sizes were smaller in the adjusted associations compared to the unadjusted ones, indicating that the associations between cannabis and tobacco use with suicide and overdose were attenuated after controlling for other risk factors.

Findings on cannabis use and suicide attempts are consistent with previous research among Veterans.4,10,38 Cannabis use may contribute to acute intoxication and chronic impairment of cognitive and emotional functioning, increasing vulnerability to suicidal thoughts and behaviors.11 The adjusted associations between cannabis use and suicide death and overdose death were not statistically significant. The potential role of cannabis in overdose harm reduction remains controversial. While some ecological studies suggest a link between cannabis legalization and decreased overdose mortality, more recent research has found no such association.39,40 However, these studies are prone to ecological fallacy and lack individual-level risk assessments. This study found no association between cannabis use and overdose death at the individual level after adjusting for well-known risk factors, although unadjusted models indicated an increased risk of overdose death associated with cannabis use.

Findings align with previous research on Veterans and non-veterans, which has also identified associations between tobacco use and suicide and overdose mortality. While psychiatric disorders may partially mediate the link between tobacco use and suicide, this study and others have demonstrated that tobacco is independently associated with suicide attempts and deaths, after accounting for mental health comorbidities.41,42 Studies indicate that current smoking is linked to an increased risk of developing opioid use disorder,15,17,43 which may explain the observed association between tobacco use and the heightened risk of overdose death.

Tobacco use often co-occurs with cannabis, and 46.2% of Veterans who use cannabis report smoking cigarettes, compared to 22.0% of those who do not use cannabis.12,13 In the sensitivity analysis, co-use was associated with a higher rate of suicide attempts and overdose deaths compared to non-use. However, these findings should be interpreted cautiously, as this study did not capture concurrent co-use, typically defined as using both substances within the same 30-day period.44

The relationships between the use of cannabis and tobacco with suicide and overdose should be considered in the broader context of other comorbidities among Veterans prescribed opioid analgesics, including chronic pain, mental health disorders, and other substance use disorders (e.g., alcohol use disorder).24,45 Individuals who use cannabis and tobacco often have pre-existing mental health conditions and concurrently use multiple substances. Beyond recreational use purposes, Veterans may use cannabis as a self-medication for anxiety or PTSD, and tobacco as a self-medication for pain, which may worsen mental health symptoms over time. When used for the long term, cannabis and tobacco may exacerbate these health issues, further increasing the risk of suicide and overdose. Additional investigation into reasons for and long-term health effects of cannabis and tobacco use among Veterans with opioid therapy is warranted.

This study has implications for clinical practice and policy aimed at preventing suicide and overdose among Veterans prescribed opioid analgesics. Unlike tobacco, cannabis use is not universally screened in the VA healthcare system. Few primary care providers make referrals related to cannabis use, and clinical discussions related to the medical risks of cannabis use are uncommon among Veterans prescribed opioids.46 Given the mental health comorbidities and the increasing cannabis use, improving communication and education for Veterans about the risks associated with tobacco and cannabis use may mitigate addiction and related harms. This is particularly critical for Veterans prescribed opioids, as some organizations are advocating for medical use of cannabis to treat psychiatric conditions (e.g., PTSD), despite a lack of evidence supporting its efficacy.47 As tobacco use may also be a marker for heightened suicide and overdose risk in patients with opioid therapy, monitoring of cannabis use in conjunction with tobacco use among Veterans prescribed opioids is warranted. Future research should examine whether screening for cannabis use and brief intervention reduces risks in this population.

Limitations

The sample primarily consists of older male Veterans prescribed opioid analgesics, which may limit the study’s generalizability to other populations (e.g., women, younger individuals, and those not prescribed opioids). Patients receiving opioid prescriptions are subject to more frequent substance use screening than other populations. The cohort comprised Veterans receiving care within the VHA system, and it is unclear whether these findings are applicable to individuals receiving care in non-VA settings. The frequency of cannabis and tobacco use may have differential associations with health harms. However, this study did not collect data on the frequency of use. Thus, the dose-response relationship between cannabis and tobacco use frequency with suicide and overdose warrants further investigation. Cannabis use measure based on clinical encounters and coded diagnoses is a standard approach to assessing substance use in medical record research,48–52 but may be subject to misclassification and not fully capture recent or problematic use. As such, this measure might include occasional or non-problematic cannabis use that occurred far from an overdose or suicide event. Thus, the association between cannabis use and suicide or overdose should be interpreted cautiously. Additionally, the COVID-19 pandemic may have influenced the findings as the study period extended through 2021. Prior studies have reported mixed changes in tobacco and cannabis use, worsening mental health, and disruptions in healthcare access during the pandemic.53–55 These factors may have influenced suicide and overdose risk, as well as substance use documentation in clinical records. Accordingly, the pandemic-related behavioral and healthcare disruptions should be considered when interpreting the observed associations between tobacco and cannabis use and suicide and overdose outcomes.

CONCLUSIONS

This longitudinal study showed that cannabis use was associated with a higher likelihood of suicide attempts, and tobacco use was associated with a higher likelihood of suicide attempts, suicide deaths, and overdose deaths among Veterans prescribed opioid analgesics. The findings underscore a need for monitoring cannabis and tobacco use and follow-up mental health and substance use treatment for Veterans prescribed opioids.

Supplementary Material

Appendix Tables

Funding:

This work was supported by the VA Health Services Research and Development IIR grant 18-231-2 from the US Department of Veterans Affairs Health Services. Support for US Department of Veterans Affairs (VA) and Centers for Medicare & Medicaid Services data was provided by the VA, VA Health Services Research and Development Service, and VA Information Resource Center (project numbers SDR 02-237 and 98-004). Dr. Nguyen is also supported by the California Tobacco-Related Disease Research Program (T32KT5071), the NIH/National Institute on Drug Abuse (K01DA056693), and the Hellman Fellowship Program. Dr. Byers receives a Research Career Scientist award (IK6 CX002386) from the Department of Veterans Affairs. Support for the Mortality Data Repository (MDR) is provided by the VA Center of Excellence for Suicide Prevention; Department of Veterans Affairs, Office of Mental Health and Suicide Prevention; Joint Department of Veterans Affairs and Department of Defense Mortality Data Repository; Data compiled from the National Death Index. Support for the Consolidated Suicide Behavior and Overdose Report/Suicide Prevention Applications Network (SBOR/SPAN) is provided by the Office of Mental Health and Suicide Prevention. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs and the funding agencies.

Footnotes

Declaration of Interest: None declared.

The abstract was presented as a poster at the Society of Behavioral Medicine 2025 annual meeting.

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