title: Tetrahydrocannabinol Does Not Reduce Pain in Patients With Chronic Abdominal Pain in a Phase 2 Placebo-controlled Study.
abstract: OBJECTIVE
  Delta-9-tetrahydrocannabinol (THC) is the most abundant cannabinoid from the plant Cannabis sativa. There is only equivocal evidence that THC has analgesic effects. We performed a phase 2 controlled trial to evaluate the analgesic efficacy, pharmacokinetics, safety, and tolerability of an oral tablet containing purified THC in patients with chronic abdominal pain.
  
  
  METHODS
  Sixty-five patients with chronic abdominal pain for 3 months or more (numeric rating scale scores of 3 or more) after surgery or because of chronic pancreatitis were randomly assigned to groups given the THC tablet or identical matching placebos for 50-52 days. Subjects in the THC group were given the tablet first in a step-up phase (3 mg 3 times daily for 5 days and then 5 mg 3 times daily for 5 days), followed by a stable dose phase (8 mg 3 times daily until days 50-52). Preceding and during the entire study period, patients were asked to continue taking their medications (including analgesics) according to prescription. Patients reported any additional pain medications in a diary. Efficacy and safety assessments were conducted preceding medication intake (day 1), after 15 days, and at 50-52 days. Plasma samples were collected on study days 1, 15, and 50-52; mean plasma concentration curves of THC and 11-OH-THC were plotted. The primary end point was pain relief, which was measured by a visual analogue scale (VAS) of the mean pain (VAS mean scores) on the basis of information from patient diaries. Secondary end points included pain and quality of life (determined from patient questionnaires), pharmacokinetics, and safety.
  
  
  RESULTS
  At days 50-52, VAS mean scores did not differ significantly between the THC and placebo groups (F1,46= 0.016; P = .901). Between the start and end of the study, VAS mean scores decreased by 1.6 points (40%) in the THC group compared with 1.9 points (37%) in the placebo group. No differences were observed in secondary outcomes. Oral THC was generally well-absorbed. Seven patients in the THC group stopped taking the tablets because of adverse events, compared with 2 patients in the placebo group. All (possibly) related adverse events were mild or moderate.
  
  
  CONCLUSIONS
  In a phase 2 study, we found no difference between a THC tablet and a placebo tablet in reducing pain measures in patients with chronic abdominal pain. THC, administered 3 times daily, was safe and well-tolerated during a 50-day to 52-day treatment period. ClinicalTrials.gov number: NCT01562483 and NCT01551511.
authors.affiliation: Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: marjan.devries@radboudumc.nl.
authors.forename: Marjan
authors.initials: M
authors.lastname: de Vries
authors.affiliation: Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Dagmar C M
authors.initials: DCM
authors.lastname: van Rijckevorsel
authors.affiliation: Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Kris C P
authors.initials: KCP
authors.lastname: Vissers
authors.affiliation: Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Centre for Sensory-Motor Interaction, Department of Health Sciences, Aalborg University, Aalborg, Denmark.
authors.forename: Oliver H G
authors.initials: OHG
authors.lastname: Wilder-Smith
authors.affiliation: Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D059350:Chronic Pain / Q000188:drug therapy*; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D010949:Plasma / Q000737:chemistry; D011788:Quality of Life / Q000523:psychology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D010919:Placebos; D013759:Dronabinol
keywords: AE; Chronic Pain; Marijuana; Randomized Controlled Trial