title: A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain management.
abstract: BACKGROUND
  Cannabinoids have dose-related antinociceptive effects in animals. This clinical study aimed to investigate whether a single oral dose of cannabis plant extract (Cannador; Institute for Clinical Research, IKF, Berlin, Germany) could provide pain relief with minimal side effects for postoperative pain.
  
  
  METHODS
  Patients (aged 18-75 yr) were recruited and consented before surgery if patient-controlled analgesia was planned for provision of postoperative pain relief. Each patient received a single dose of 5, 10, or 15 mg Cannador if he or she had at least moderate pain after stopping patient-controlled analgesia. Starting with 5 mg, dose escalation was based on the number of patients requesting rescue analgesia and adverse effects. Pain relief, pain intensity, and side effects were recorded over 6 h and analyzed using tests for trend with dose.
  
  
  RESULTS
  Rescue analgesia was requested by all 11 patients (100%) receiving 5 mg, 15 of 30 patient (50%) receiving 10 mg, and 6 of 24 patients (25%) receiving 15 mg Cannador (log rank test for trend in time to rescue analgesia with dose P < 0.001). There were also significant trends across the escalating dose groups for decreasing pain intensity at rest (P = 0.01), increasing sedation (P = 0.03), and more adverse events (P = 0.002). The number needed to treat to prevent one rescue analgesia request for the 10-mg and 15-mg doses, relative to 5 mg, were 2.0 (95% confidence interval, 1.5-3.1) and 1.3 (95% confidence interval, 1.1-1.7), respectively. The study was terminated because of a serious vasovagal adverse event in a patient receiving 15 mg.
  
  
  CONCLUSIONS
  These significant dose-related improvements in rescue analgesia requirements in the 10 mg and 15 mg groups provide a number needed to treat that is equivalent to many routinely used analgesics without frequent adverse effects.
authors.affiliation: Magill Department of Anaesthesia, Imperial College London and Chelsea and Westminster Hospital, London, United Kingdom. a.holdcroft@imperial.ac.uk
authors.forename: Anita
authors.initials: A
authors.lastname: Holdcroft
authors.forename: Mervyn
authors.initials: M
authors.lastname: Maze
authors.forename: Caroline
authors.initials: C
authors.lastname: Doré
authors.forename: Susan
authors.initials: S
authors.lastname: Tebbs
authors.forename: Simon
authors.initials: S
authors.lastname: Thompson
mesh_terms: D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects; D000368:Aged; D016058:Analgesia, Patient-Controlled; D000700:Analgesics / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D002188:Cannabis / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy*; D010936:Plant Extracts / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D020250:Postoperative Nausea and Vomiting / Q000188:drug therapy; D018401:Sample Size
chemical_list: D000700:Analgesics; D010936:Plant Extracts