Methadone doses upon multiple readmissions to inpatient detoxification: Clinical evidence for very moderate opioid tolerance

Abstract

Escalation of drug use by addicts has traditionally been interpreted as tolerance to the drug's effects. On the basis of animal behavioral data, several groups have recently proposed alternative explanations, i.e., that such an escalation of drug dose might not be based on tolerance but rather be indicative of (i) sensitization to the reinforcing effect or the incentive salience of the drug of abuse or (ii) shifts in baseline mood, i.e., allostasis. In the present study, the emergence of opioid tolerance or sensitization during the progression of opioid dependence was assessed by comparing the methadone doses that were initially required to alleviate the opioid withdrawal symptoms of intravenous opioid users who presented for detoxification upon 3-7 consecutive admissions over the course of up to 84 months. Upon the second admission, the 48 surveyed male patients needed 115 +/- 6% (p = 0.012) and the 32 female patients needed 121 +/- 12% (p = 0.01) of the methadone dose required upon the first admission. Upon the third admission, the respective values were 121 +/- 8% (males; p = 0.013) and 111 +/- 12% (females; n.s.), and upon the fourth admission, 125 +/- 14% (males; p = 0.026) and 131 +/- 14 (females; p = 0.01). Inter-admission intervals averaged 14 +/- 1 months (n = 135) for males and 13 +/- 1 months (n = 91) for females and were not significantly different across consecutive admissions, suggesting that tolerance did not develop faster upon repetition of abuse-withdrawal cycles. In conclusion, the intravenous opioid users surveyed in the present study developed only very moderate tolerance during the repeated abuse-detoxification cycles that were typical for their disease progression. The present data do not support the notion that sensitization to the opioids' reinforcing effects occurred in this naturalistic clinical sample.