Talk to the Veterans Crisis Line now
U.S. flag
An official website of the United States government

VA Health Systems Research

Go to the VA ORD website
Go to the QUERI website

IIR 18-231 – HSR Study

IIR 18-231
Risks of Cannabis Use Among Veterans on Long-term Opioid Therapy
Salomeh Keyhani, MD MPH
San Francisco VA Medical Center, San Francisco, CA
San Francisco, CA
Funding Period: December 2019 - May 2024


Background: Despite increasing cannabis use among the general population, very little data exists on potential harms associated with use. In randomized controlled trials examining the effect of THC-based pharmaceuticals on the management of pain, adverse events included dizziness, sedation, confusion, loss of balance, nausea, vomiting, and hallucination. These side effects suggest that cannabis used in combination with opioids—which also cause, dizziness, sedation, confusion, respiratory depression, nausea, vomiting and constipation—may be particularly harmful. Older Veterans, and those with underlying respiratory and cardiac conditions, may be at higher risk of adverse effects from combined opioid and cannabis use. On the other hand, several ecological studies suggest that state-based recreational legalization may be associated with a decrease in opioid related deaths. Thus, it is plausible that cannabis use, by reducing the use of opioids, reduces respiratory depression and the risk of overdose. However, ecological studies examining the effect of legalization on opioid related deaths do not inform our understanding of the effects of combined use of cannabis and opioids on individual health. Understanding the effects of the combined use of cannabis and opioids on individual patient outcomes is critically important. No evidence base is currently available to inform VA guidelines on cannabis use among chronic pain patients who receive opiates. Significance: Although cannabis use is common among Veterans with chronic pain, the risk or benefits of cannabis use among Veterans on long-term opioid therapy (LTOT) is unknown. This proposal is directly responsive to research gaps identified by VA practice guidelines and the HSR&D priority area focused on “Studying safety and efficacy issues related to long-term opioid therapy among aging Veterans and Veterans with mental health (non-pain) conditions”. Our proposal is also responsive to the HSR&D priority area: “Assessing the feasibility of LTOT cohort studies using data-mining strategies.” Innovation: To address the gaps in the literature on the potential harms (or benefits) of cannabis use among patients on long-term opioid therapy, we propose an innovative approach to cohort construction using a combination of urine drug screen data, text processing algorithms (developed by our team), and national VA and Medicare data to categorize exposure status (concomitant cannabis plus opioid vs. opioid without cannabis) to address the following aims: Specific Aims: Aim 1: To examine the association of cannabis use on the outcome of all-cause mortality among Veterans ≥18 years-old who use long-term opioids. Aim 2: To examine the association of cannabis use on the primary outcome of all-cause mortality and the secondary outcomes of hospitalization among Veterans ≥65 years-old on LTOT with chronic obstructive lung disease, congestive heart failure or sleep apnea. Aim 3: To examine the association of cannabis on the primary outcome of all-cause mortality and the secondary outcomes of any hospitalization, fall-related injury, any injury, and hospitalization for mood disorders among Veterans ≥65 years-old on LTOT. Methodology: We will leverage VA data sources and use data extracted from progress notes, urine toxicology data, and national VA and Medicare administrative data to answer a clinically relevant question. We will use propensity score methods to compare one-year outcomes among cannabis users and non-users. Next Steps: Next steps include dissemination of the findings to VA researchers and clinical and operational leaders. Study findings will be informative to VA guidelines and clinical practice.

External Links for this Project

NIH Reporter

Grant Number: I01HX002737-01A1

Dimensions for VA

Dimensions for VA is a web-based tool available to VA staff that enables detailed searches of published research and research projects.

Learn more about Dimensions for VA.

VA staff not currently on the VA network can access Dimensions by registering for an account using their VA email address.
    Search Dimensions for this project


Journal Articles

  1. Zaman T, Bravata DM, Byers A, Krebs E, Leonard S, Austin C, Sandbrink F, Hasin DS, Keyhani S. A national study of clinical discussions about cannabis use among Veteran patients prescribed opioids. Journal of cannabis research. 2024 Mar 16; 6(1):12. [view]
  2. Keyhani S, Leonard S, Byers AL, Zaman T, Krebs E, Austin PC, Moss-Vazquez T, Austin C, Sandbrink F, Bravata DM. Association of a Positive Drug Screening for Cannabis With Mortality and Hospital Visits Among Veterans Affairs Enrollees Prescribed Opioids. JAMA Network Open. 2022 Dec 1; 5(12):e2247201. [view]
  3. Rubin JB, Lai JC, Leonard S, Seal K, Hoggatt KJ, Keyhani S. Long-Term Opioid Use Among Veterans with Cirrhosis: High-Dose Prescriptions in an Exceedingly High-Risk Population. Journal of general internal medicine. 2022 Sep 1; 37(12):3205-3207. [view]

DRA: Mental, Cognitive and Behavioral Disorders, Substance Use Disorders, Other Conditions
DRE: Epidemiology, Treatment - Observational, TRL - Applied/Translational
Keywords: Complementary and Alternative Practices, Pain
MeSH Terms: None at this time.

Questions about the HSR website? Email the Web Team

Any health information on this website is strictly for informational purposes and is not intended as medical advice. It should not be used to diagnose or treat any condition.