Using saccadic eye movements as objective measures of tolerance in methadone dependent individuals during the hydromorphone challenge test.

Substitute methadone prescribing is one of the main modes of treatment for opiate dependence. This study examined the relationship between methadone dose (measured by daily dose and methadone's active (R)-enantiomer blood levels) and opiate receptor function. Nine subjects on substitute methadone (30 - 90 mg daily) received three subcutaneous injections 1.5 hours apart (saline, 5 mg and 10 mg hydromorphone, a short-acting opiate agonist) followed by measures of functional response in particular saccadic eye movements (SEMs), as well as self-report measures. Ten mg of hydromorphone significantly slowed SEM parameters (peak velocity by 15%, p < 0.005; peak acceleration by 20%, p < 0.025; peak deceleration by 26%, p < 0.025) and the SEM velocity changes correlated significantly with (R)-methadone levels (r = 0.844, p < 0.005) and with the oral dose of methadone being taken (r = 0.829, p < 0.005). Although a similar trend was observed for 5 mg, this was not significant. These finding suggest that, at higher methadone doses (resulting in higher plasma concentrations), there is significant tolerance to the action of agonists. Such studies may help in refining our understanding of the actions of methadone and the SEM measure could help in defining the degree of tolerance in individuals using street heroin.

Changes in regional cerebral blood flow elicited by craving memories in abstinent opiate-dependent subjects.

OBJECTIVE: The brain circuitry of opiate craving was investigated with positron emission tomography (PET) imaging of regional cerebral blood flow (rCBF). METHOD: Twelve abstinent opiate-dependent subjects listened to audiotaped autobiographical scripts of an episode of craving and a neutral episode while undergoing a PET scan with the tracer [(15)O]H(2)O. Statistical parametric mapping was used to analyze the PET images of rCBF changes. RESULTS: Comparison of the drug-related and neutral stimulus conditions revealed activation of rCBF in the left medial prefrontal and left anterior cingulate cortices and deactivation in the occipital cortex in response to the drug-related stimulus. A further statistical parametric mapping analysis with a subjective rating of craving as a covariate showed a positive association of between craving and rCBF in the left orbitofrontal cortex. CONCLUSIONS: The patterns of cerebral activation reflect the different brain regions mediating the salience of opiate-related stimuli and the subjective experience of craving for opiates.

The feasibility of abrupt methadone-buprenorphine transfer in British opiate addicts in an outpatient setting.

A study of 13 male opiate addicts was undertaken to investigate the feasibility of transferring abruptly from methadone maintenance treatment to buprenorphine in an outpatient setting. The mean age of subjects was 30 years (range 18-45) and all fulfilled DSM-III-R criteria for opioid dependence. All were maintained on a methadone dose of 20-30 mg mixture daily and were transferred for 3 days to 4 mg buprenorphine sublingually 24-26 hours after their last dose of methadone. On day 1 repeated measures of drug effects were performed, including agonist and withdrawal effects, and this was complemented by saccadic eye movements, a potential new measure of central opioid effects. These recordings were repeated once on days 2 and 3 and the subjects returned to their previous dose of methadone on day 4. Buprenorphine caused no detectable agonist effects or drug "high", but had "good" effects, was "liked" and well tolerated, suggesting that subjects would comply with buprenorphine treatment despite the lack of reinforcing effects. A mild increase in subjective withdrawal symptoms, which was not clinically significant, was seen in association with an increase in saccadic peak velocity on day 2 of the study but no withdrawal occurred on the other days, indicating that the abrupt transfer technique was acceptable.

Asthma in opiate addicts.

A case-note study of 2276 opiate addicts revealed that 112(5%) had a history of asthma and that in 31(1.4%) cases there appeared to be a definite temporal relationship between heroin abuse and the onset of asthma. This rarely-reported complication of heroin dependence has a higher incidence among female addicts (3.3%) than among male addicts (0.7%).