Abstract
Dear Editor,
We read with great interest the article by Amoroso et al 1 examining the association between preoperative cannabis use and perioperative outcomes in patients undergoing spinal fusion. Their work contributes valuable data to an evolving clinical issue; however, the complex neurobiologic interface between cannabis exposure, anxiety, and nociceptive modulation may deserve deeper exploration. The authors reported higher preoperative pain and anxiety among cannabis users, yet no significant reduction in postoperative opioid use. This apparent paradox raises a fundamental question: does cannabis act as an analgesic adjuvant or a pro-nociceptive sensitizer under surgical stress? Experimental evidence suggests that chronic stimulation of cannabinoid receptor type 1 (CB1) may induce receptor downregulation and cross-desensitization with μ-opioid receptors, diminishing endogenous opioid tone and increasing pain perception.2,3 Thus, the elevated pain scores in cannabis users may not merely reflect preoperative anxiety, but rather neuroadaptive tolerance mechanisms within the endocannabinoid-opioid system.
Moreover, the coexistence of anxiety in this population invites a psychoneuroimmunologic perspective. Preoperative cannabis use has been associated with altered amygdalar reactivity, dysregulated hypothalamic–pituitary–adrenal (HPA) signaling, and increased proinflammatory cytokine release—all of which may amplify postoperative pain intensity and analgesic demand.4,5 Integrating these biologic dimensions could explain why cannabis users may experience heightened nociceptive sensitivity despite its reputed anxiolytic properties. Future studies incorporating neuroimaging, cytokine profiling, and quantitative sensory testing could clarify these bidirectional effects.
Clinically, this interplay holds important implications for perioperative management. Routine screening for cannabis use should not only quantify frequency and dosage but also assess for anxiety comorbidity and potential neuroadaptation. Tailored multimodal analgesia—incorporating non-opioid and anti-inflammatory strategies—may help mitigate hyperalgesic rebound phenomena associated with chronic cannabinoid exposure. As cannabis legalization expands, understanding its mechanistic influence on pain circuitry and stress response will be critical to optimizing enhanced recovery pathways in spine surgery.
Amoroso et al 1 have opened an essential discussion on this topic. Their study invites the field to move beyond prevalence estimation toward mechanistic and translational research that bridges neurobiology, behavior, and surgical outcomes.
Footnotes
Author Contributions
Tirayut Veerasatian 30% ideas, writing, analyzing, approval. Schawanya K. Rattanapitoon 30 % ideas, writing, approval. Nav La 20% writing, analyzing, approval. Nathkapach K. Rattanapitoon 20% writing, supervision, approval.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
AI Declaration
The authors used computational tool for language editing/checking in preparation of the article.