A randomized, double-blind, placebo-controlled, cross-over pilot study to assess the effects of long-term opioid drug consumption and subsequent abstinence in chronic noncancer pain patients receiving controlled-release morphine

Pain Med. Mar-Apr 2005;6(2):113-21. doi: 10.1111/j.1526-4637.2005.05020.x.


Objectives: The long-term use of strong opioid analgesics among chronic noncancer pain (CNCP) patients remains controversial because of concerns over problematic drug use. However, previous surveys suggest that this is not necessarily the case. Therefore, we designed a controlled study to generate evidence in support of these findings.

Patients/setting: Ten CNCP patients attending the pain clinic in a district general hospital had been taking an average daily dose of 40 mg controlled-release morphine sulphate (mean 40, range 10-90, SD 21 mg), for an average of 2 years (mean 2.175, range 2-2.25, SD 0.2 years).

Design: Randomized, double-blind, placebo controlled cross-over study. The study was based on the premise that abrupt cessation of opioid drugs is most likely to highlight problematic use and the consequent inability to stop using opioids. Morphine was substituted with placebo for 60-hour periods to compare the effects of abstinence with those of continued use. Assessment of morphine cessation and abstinence effects was through direct observation, physiological measurements, questionnaire responses, and Brief Pain Inventory scores.

Results: Following cessation and abstinence, there were no indications of psychological dependence or drug craving, but there was evidence of the detrimental effects of pain intensity on activity, mood, relationships, sleep, and enjoyment of life. Three patients (30%) reported opioid drug withdrawal symptoms. Pharmacokinetic data demonstrated compliance with abstinence by all patients.

Conclusion: The results suggest the existence of a group of CNCP patients whose long-term opioid consumption can be beneficial and remain moderate without them suffering from the consequences of problematic opioid drug use.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / adverse effects
  • Chronic Disease
  • Cross-Over Studies
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / adverse effects
  • Double-Blind Method
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Morphine / administration & dosage*
  • Morphine / adverse effects*
  • Neoplasms / complications
  • Pain / complications*
  • Pain / drug therapy*
  • Pain Measurement
  • Pilot Projects
  • Placebo Effect
  • Risk Assessment / methods*
  • Risk Factors
  • Severity of Illness Index
  • Substance Withdrawal Syndrome / diagnosis*
  • Substance Withdrawal Syndrome / etiology*
  • Substance Withdrawal Syndrome / prevention & control
  • Treatment Outcome


  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Morphine