Patterns of craving and pharmacokinetics in long-term opiate addicts in methadone maintenance therapy

Results are presented and discussed of a clinical study of 20 long-term opiate addicts currently enrolled in Methadone Maintenance Therapy (MMT) and hospitalized in the Jellinek Clinic in Amsterdam. The purpose of this study was to better understand the craving and pharmacokinetics associated with difficulties in determining an optimal dosage schedule in MMT. Plasma methadone concentrations were determined using a newly developed HPLC (high pressure liquid chromatography) procedure. Drug craving was measured using the Experience Sampling Method (ESM), a new technique for measuring craving in MMT which provides data not previously reported in methadone literature. Within the subjects medicated in the normal therapeutic dosage range of MMT (10-90 mg/day), a significant relationship was found between higher methadone dose and higher craving levels, a finding that counters much of the accepted knowledge on MMT. Supporting this finding, some subjects showed high plasma methadone trough levels and high craving levels. At the group level. no significant relationships were found between craving and kinetic parameters, such as plasma methadone trough level and half-life. Three specific craving patterns were identified that related to daily fluctuations: high peak of the craving score just before the patients receive methadone around 9 am; an elevation in craving at around noon and a clear group difference of those subjects which show an increase in craving level between 2 pm and 10 pm and those which show a decrease. The results suggest that factors other than pharmacokinetics such as anticipatory conditional response and/or circadian influences might also be affecting craving.