Randomized clinical trial to compare the effects of methadone and buprenorphine on the immune system in drug abusers

Psychopharmacology (Berl). 2005 May;179(3):700-4. doi: 10.1007/s00213-005-2239-x. Epub 2005 Apr 2.


Rationale: Buprenorphine may be a useful alternative option to methadone in addicts. Opioids can produce severe changes in the immune system.

Objectives: The objectives of this study are to compare the effect of sublingual buprenorphine and methadone on the immune system and to compare the two substances on the drying-out program compliance.

Methods: We studied 62 randomized outpatients for a period of 12 months. Subjects (55 males and 7 females; mean age 25+/-4 years; average history of heroin abuse being 2 years) on maintenance treatment were assigned in two groups (A and B). Methadone chloride (medium dose 100 mg/day) was administered to group A, whereas group B received sublingual buprenorphine (32.40+/-2.8 mg/day). Urine toxicological screening, plasma levels of TNF-alpha interleukin-1, interleukin-beta, lymphocyte CD14 and a self-rating depression questionnaire were measured.

Results: Urine screening was negative for opiates in 17.6% of group A and in 10.7% of group B (p<0.001; r = 0.62). Depression score was 62+/-2 in group A and 55+/-3 in group B (p < 0.01). Cytokine and CD14 revealed higher concentrations both in groups A and B without significant differences (p > 0.05) between the two groups.

Conclusions: The effects of buprenorphine and methadone tested on the immune system were overlapping in our patients. The elevated cytokine levels observed may suggest that the two drugs stimulate immunologic hyperactivation of an immune system that was formerly inhibited by heroin. Furthermore, our data suggest that buprenorphine can be a valid alternative to methadone in maintenance treatment of chronic heroin abuse and referred a marked decline in depression.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Buprenorphine / therapeutic use*
  • Cytokines / immunology
  • Cytokines / metabolism
  • Female
  • Humans
  • Lipopolysaccharide Receptors / immunology
  • Lipopolysaccharide Receptors / metabolism
  • Male
  • Methadone / therapeutic use*
  • Substance-Related Disorders / drug therapy*
  • Substance-Related Disorders / immunology*
  • Substance-Related Disorders / metabolism


  • Cytokines
  • Lipopolysaccharide Receptors
  • Buprenorphine
  • Methadone