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

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.

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.

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.