Investigating Cannabis Use Parameters on Anesthesia and Inflammation in Lumbar Spinal Surgeries

Cannabis is the most commonly used illicit drug in the United States with reported rates of use increasing from approximately 50 million in 2020 to 61.8 million in 2023 among individuals aged 12 or older. This rise can be attributed to a combination of growing social acceptance and expanding legalization for recreational and medical use of cannabis. Consequently, this has led to increased commercially available cannabis products with heterogeneous concentrations of cannabinoids (i.e., THC:CBD ratios) and new methods of administration becoming more available (e.g., vaping and gummies). Taken together, this rapidly shifting landscape further contributes to the significant variability in individual use patterns (i.e., frequency, duration, and route of administration) resulting in diverse clinical responses, which poses significant challenges for anesthetic management. Recent systematic reviews and meta-analysis have quantitatively demonstrated that cannabis users require higher dosages during anesthesia induction, experience greater hemodynamic instability, and report higher opioid consumption and pain scores post-operatively. These findings have led to the prevailing notion that cannabis exposure adversely affect anesthetic management. Yet, key cannabis exposure parameters in individual use patterns (i.e., variations in THC:CBD ratios, route of administration, frequency, and duration of use) remain poorly characterized and could confound observed clinical effects in relation to their effects on pain modulation and anesthetic requirements. Current perioperative assessments do not account for these critical variables, creating a gap that limits the development of more accurate and personalized anesthetic protocols. Failure to account for individual cannabis exposure parameters may lead to inappropriate anesthetic dosing - where underdosing could result in intraoperative awareness, pain, or patient movement, while overdosing might cause cardiovascular depression, respiratory failure, or prolonged recovery from anesthesia. Concomitantly, researchers have discovered that cannabis consumption modulates immune function such that early life exposure to cannabis produces a long-lasting and persistent inflammatory state characterized by reduced serum levels of IL-6, TNF-α, and IL-2. In contrast, recent research demonstrates that cannabinoid exposure improves skin healing in patients with cutaneous disorders. However, the effects of altered inflammatory responses, and the diverse actions of various cannabinoids on postoperative wound healing remain largely unexplored. Our long-term goal is to elucidate the mechanistic impact of chronic cannabis use parameters on anesthetic and analgesic requirements, thereby enabling the development of personalized, evidence-based perioperative management strategies. The investigators hypothesize that chronic cannabis exposure leads to impaired endogenous pain and immune modulation, resulting in increased intraoperative anesthetic dosing, heightened hemodynamic variability, and elevated postoperative pain and inflammation.

Study Overview

• Status: Enrolling by invitation
• Conditions: Cannabis Use

Detailed Description

Cannabis is the most commonly used illicit drug in the United States with reported rates of use increasing from approximately 50 million in 2020 to 61.8 million in 2023 among individuals aged 12 or older. This rise can be attributed to a combination of growing social acceptance and expanding legalization for recreational and medical use of cannabis. Consequently, this has led to increased commercially available cannabis products with heterogeneous concentrations of cannabinoids (i.e., THC:CBD ratios) and new methods of administration becoming more available (e.g., vaping and gummies). Taken together, this rapidly shifting landscape further contributes to the significant variability in individual use patterns (i.e., frequency, duration, and route of administration) resulting in diverse clinical responses, which poses significant challenges for anesthetic management. Recent systematic reviews and meta-analysis have quantitatively demonstrated that cannabis users require higher dosages during anesthesia induction, experience greater hemodynamic instability, and report higher opioid consumption and pain scores post-operatively. These findings have led to the prevailing notion that cannabis exposure adversely affect anesthetic management. Yet, key cannabis exposure parameters in individual use patterns (i.e., variations in THC:CBD ratios, route of administration, frequency, and duration of use) remain poorly characterized and could confound observed clinical effects in relation to their effects on pain modulation and anesthetic requirements. Current perioperative assessments do not account for these critical variables, creating a gap that limits the development of more accurate and personalized anesthetic protocols. Failure to account for individual cannabis exposure parameters may lead to inappropriate anesthetic dosing - where underdosing could result in intraoperative awareness, pain, or patient movement, while overdosing might cause cardiovascular depression, respiratory failure, or prolonged recovery from anesthesia. Concomitantly, researchers have discovered that cannabis consumption modulates immune function such that early life exposure to cannabis produces a long-lasting and persistent inflammatory state characterized by reduced serum levels of IL-6, TNF-α, and IL-2. In contrast, recent research demonstrates that cannabinoid exposure improves skin healing in patients with cutaneous disorders. However, the effects of altered inflammatory responses, and the diverse actions of various cannabinoids on postoperative wound healing remain largely unexplored. Our long-term goal is to elucidate the mechanistic impact of chronic cannabis use parameters on anesthetic and analgesic requirements, thereby enabling the development of personalized, evidence-based perioperative management strategies. The investigators hypothesize that chronic cannabis exposure leads to impaired endogenous pain and immune modulation, resulting in increased intraoperative anesthetic dosing, heightened hemodynamic variability, and elevated postoperative pain and inflammation. To test this hypothesis, the investigators propose the following specific aims: Specific aim 1: Assess cannabis use parameters of individual use patterns in relation to anesthetic and analgesic requirements during elective spine surgeries. The investigators will conduct a prospective study in patients undergoing ambulatory or short-stay lumbar spine surgery asking them to fill out a survey detailing their individual cannabis use patterns (e.g., frequency, duration, and method of use) and attach pictures of their products (to obtain variations in THC:CBD ratios and product type). The investigators will compare intraoperative anesthetic dosing (e.g., propofol and opioid anesthetics) and evaluate hemodynamic parameters (e.g., blood pressure fluctuations and vasopressor requirements), and assess postoperative pain intensity and analgesic needs between cannabis users and non-users. This aim will provide direct clinical evidence linking specific chronic cannabis exposure parameters to intraoperative anesthetic and analgesic requirements, thereby laying the groundwork for tailored anesthetic protocols to reduce complications during surgery. Specific aim 2: Determine the inflammatory mechanisms by which chronic cannabis use alters pain processing and wound repair. The investigators will measure serum biomarkers of inflammation, including IL-6, TNF-α, IL-2, and CRP before and after surgery, and again at 2- and 6-week follow-up, to assess how chronic cannabis exposure modulates immune responses and wound healing in elective spine surgeries. In parallel, the investigators will obtain subjective pain assessments using validated scales and correlate these with intraoperative anesthetic dosing and inflammatory biomarker levels, thereby elucidating the interplay between cannabis-induced immune modulation in altering pain processing and wound healing. Impact: If successful, these studies will fill critical gaps in our understanding by: • Precisely characterizing how individual cannabis exposure parameters affect perioperative anesthetic and analgesic needs, thereby enabling personalized dosing protocols that reduce the risk of intraoperative awareness, cardiovascular instability, and prolonged recovery. • Defining the immunologic alterations associated with chronic cannabis use and their relationship to wound healing and postoperative pain, which may pave the way for novel interventions to optimize surgical outcomes. This integrative approach will advance the fields of anesthesiology, and surgical perioperative patient care and addiction research.

• Study Type: Observational
• Enrollment (Estimated): 210

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University Hospital
    • Columbia, Missouri, United States, 65211
      • Missouri Orthopaedic Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Ambulatory and short-stay lumbar spine surgery patients

Description

Inclusion Criteria for both cannabis users and non-users:

• Undergoing ambulatory or short-stay lumbar spine surgery.
• English speaking.
• Ability to consent for themselves.
• Aged 18 years and above.
• Access to a smartphone or computer/laptop (to be determined on the day of consent).

Inclusion criteria for cannabis users:

• Any lifetime use of cannabis products irrespective of the strain, CBD/THC content, or frequency of use.

Exclusion Criteria:

• Non-English speaking.
• Inability to consent for themselves.
• Actively pregnant (SOC) or planning to become pregnant in the next 2 months (research only). Urine testing will be done as SOC prior to undergoing surgery.
• Active or past severe psychiatric instability (e.g., active psychosis, acute suicidality)
• Active, uncontrolled use of illicit drugs use such as methamphetamine, cocaine, opioids, etc., as listed in their clinical charts.
• History of major neurological illnesses.
• Presence of an untreated illness or serious medical condition.
• Any other concern that in the investigator's opinion would impact participant safety, study instruction compliance, or confound the interpretation of the study results.
• No access to a smartphone or computer/laptop.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Never users; Patients who have never used cannabis products
Current users; Individuals who have used cannabis products in the last 30 days
Past users; Individuals who have used cannabis products in the past but not in the last 30 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative Propofol dose (mg/kg/hr)	Our primary outcome is intraoperative anesthetic dose (i.e., propofol mg/kg/hr), which will be extracted from anesthesia records and entered into each patient's individual REDCap record by the study personnel.	Duration of surgery
Change in serum inflammatory biomarker IL-2 (pg/mL)	The investigators will measure serum biomarker of inflammation IL-2 (pg/mL) before and after surgery, and again at 2- and 6-week follow-ups, to assess how cannabis exposure modulates immune responses.	From enrollment to 6 week post-surgery
Change in serum inflammatory biomarker IL-6 (pg/mL)	The investigators will measure serum biomarker of inflammation IL-6 (pg/mL) before and after surgery, and again at 2- and 6-week follow-ups, to assess how cannabis exposure modulates immune responses.	From enrollment to 6 week post-surgery
Change in serum inflammatory biomarker TNF-α (pg/mL)	The investigators will measure serum biomarker of inflammation TNF-α (pg/mL) before and after surgery, and again at 2- and 6-week follow-ups, to assess how cannabis exposure modulates immune responses.	From enrollment to 6 week post-surgery
Change in serum inflammatory biomarker CRP (pg/mL)	The investigators will measure serum biomarker of inflammation CRP (pg/mL) before and after surgery, and again at 2- and 6-week follow-ups, to assess how cannabis exposure modulates immune responses.	From enrollment to 6 week post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative opioid dose (MME)	Intraoperative opioid dose (MME) will be extracted from anesthesia records and entered into each patient's individual REDCap record by the study personnel.	Duration of surgery
Wound healing (cm^2)	Wound healing will be assessed with the aid of the surgical team using the elliptical method, estimating area as (π × length × width)/4 from standardized incision measurements. The investigators will obtain these with the help of the surgical team in the operating room, and then remeasure at follow-up visits.	From end of surgery to 6 week post-surgery
Postoperative pain scores (0-10)	Postoperative pain scores will be assessed with the participant using a visual analog scale 0-10, with 0 as no pain and 10 as the greatest amount of pain imaginable. The pain score will be obtained by nurses at 6 hour intervals after surgery till discharge. The data will be extracted from patient health records and entered into their respective records on REDCap.	Post-operative day 0
Mean arterial pressure (MAP) variability minutes	Intraoperative mean arterial pressure (MAP) variability will be measured as the number of minutes the MAP falls under 65 mmHg (i.e., hypotensive) during the surgery. The data will be extracted from patient electronic records and entered into their respective records on REDCap.	Duration of surgery
Heart rate (HR) variability in minutes	Intraoperative heart rate (HR) variability will be measured as the number of minutes the HR falls under 65 bpm (i.e., bradycardia) or goes above 110 bpm (i.e., tachycardia) during the surgery. The data will be extracted from patient electronic records and entered into their respective records on REDCap.	During surgery
Total intraoperative vasopressor use (microgram/kg/min)	Intraoperative vasopressor can be administered using multiple different drugs, so the investigators will sum all amounts used into a unified total amount adjusted to micrograms/kg/min. The information will be extracted from anesthesia records and entered into each patient's individual REDCap record by the study personnel.	During surgery
Postoperative opioid consumption (MME) during hospital stay	Postoperative opioid consumption (MME) will be extracted patient electronic records and entered into their respective records on REDCap by study personnel.	Post-operative day 0
Pain assessment following discharge	The investigators will use ecological momentary assessments (EMAs) to administered questions remotely in two phases: phase 1 will have EMAs sent once daily for the 1st week following discharge from surgery, and phase 2 will have EMAs sent once weekly between the 2-week and 6-week follow-up sessions. The EMAs will ask patients about pain assessment using the same visual analog scale of 0-10, with 0 as no pain and 10 as the greatest amount of pain imaginable.	Post-operative day 0 to 6 week post-surgery
Opioid consumption (MME) following discharge	The investigators will use ecological momentary assessments (EMAs) to administered questions remotely in two phases: phase 1 will have EMAs sent once daily for the 1st week following discharge from surgery, and phase 2 will have EMAs sent once weekly between the 2-week and 6-week follow-up sessions. The EMAs will ask patients about medication adherence, patients will be asked to indicate if they took more than their prescribed amount of discharge opiate/analgesic medications and how much (measured in MME).	Post-operative day 0 to 6 week post-surgery
Cannabis use following discharge	The investigators will use ecological momentary assessments (EMAs) to administered questions remotely in two phases: phase 1 will have EMAs sent once daily for the 1st week following discharge from surgery, and phase 2 will have EMAs sent once weekly between the 2-week and 6-week follow-up sessions. The EMAs will ask participants about if and how much cannabis the participant used (measured in mg) going back 24 hours for phase 1, and 1 week for phase 2.	Post-operative day 0 to 6 week post-surgery
Cannabis cravings following discharge	The investigators will use ecological momentary assessments (EMAs) to administered questions remotely in two phases: phase 1 will have EMAs sent once daily for the 1st week following discharge from surgery, and phase 2 will have EMAs sent once weekly between the 2-week and 6-week follow-up sessions. The EMAs will ask participants about cannabis cravings with a 4-item Craving Questionnaire going back 24 hours for phase 1, and 1 week for phase 2. The craving questionnaire will ask the participants about intensity, frequency, and length of time of cravings on a scale of 0-4 (0 = None at all; 1= Slight; 2 = Moderate; 3 = Considerable; 4 = Extreme). The fourth question will ask about the total number of times the participants had cravings in the last 24 hours.	Post-operative day 0 to 6 week post-surgery

Collaborators and Investigators

• Sponsor: University of Missouri-Columbia
• Investigators: Study Director: Antoinette Burger, PhD, University of Missouri-Columbia; Study Director: Randi Foraker, PhD, University of Missouri-Columbia

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): May 30, 2027

Study Registration Dates

• First Submitted: June 9, 2025
• First Submitted That Met QC Criteria: January 14, 2026
• First Posted (Actual): January 21, 2026

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: anesthesia; cannabis; inflammation; cytokines
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Substance-Related Disorders; Chemically-Induced Disorders; Pathological Conditions, Signs and Symptoms; Inflammation; Marijuana Abuse
• Other Study ID Numbers: 2128606

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No