The Analgesic Efficacy of Perioperative Δ9-THC (Namisol®) in Patients Undergoing Major Abdominal Surgery: A Randomized, Double Blinded, Placebo-controlled, Parallel Design

Rationale: Early postsurgical pain is a consequence of tissue trauma during surgery, which can lead to hyperalgesia or allodynia. Adequate management of postsurgical pain leads to earlier mobilization, shortened hospital stay, reduced costs, and increased patient satisfaction. Treatment usually involves the use of opioids, which have many side effects. Besides the problem of acute surgical pain, surgery may lead to the development of persistent postsurgical pain.

Based on preclinical research, it is hypothesized that Δ9-THC may improve outcomes of early postsurgical pain due to pain modulatory effects and may lower the incidence of persistent postsurgical pain through modulation of central pain processing, e.g. reduction of central sensitization. From clinical studies, evidence for the value of Δ9-THC in this context is, to date, scarce. Indeed, research in a patient group with a major nociceptive load - i.e. major abdominal surgery - and an extended perioperative treatment schedule has not been performed so far. Both a major nociceptive load and an extended perioperative treatment schedule are necessary for adequate assessment of the analgesic efficacy of Δ9-THC in this context. Thus, the question regarding the perioperative analgesic efficacy of Δ9-THC in major abdominal surgery remains unresolved.

Objectives: The primary aim of this study is to investigate the analgesic effect of perioperatively administered Namisol® to reduce postsurgical pain on the day of major abdominal surgery and in the first five days after major abdominal surgery. A secondary aim is to investigate the effect of perioperatively administered Namisol® on the incidence of persistent postsurgical pain in the first 12 postoperative weeks.

Study design: A randomized, double-blind, placebo-controlled, parallel-group study design with an perioperative add-on treatment of Namisol or placebo and a follow-up period of 24 weeks.

Study population: Forty patients will be recruited from the outpatient clinic of the department of surgery of the Radboud University Nijmegen Medical Center. Patients will have persistent or intermittent abdominal pain, due to underlying intra-abdominal pathology including diverticulitis, Crohn's disease, chronic pancreatitis, ulcerative colitis, endometriosis, or abdominal adhesions. Other intra-abdominal pathology may be included if causing pain and if judged appropriate by the investigator. Patients will be planned to undergo elective, open abdominal surgery with planned use of an epidural catheter for perioperative analgesia. The surgical procedure will have an estimated duration of at least two hours, excluding the time to induce anesthesia.