Long-Term Pharmacotherapy for Opiate (Primarily Heroin) Addiction: Opioid Agonists

Altered HPA Axis Responsivity to Metyrapone Testing in Methadone Maintained Former Heroin Addicts with Ongoing Cocaine Addiction

“…Our group has demonstrated normalization of HPA axis function during stabilization in long-term methadone-maintenance treatment. Basal ACTH and cortisol levels were found to be within normal limits, and metyrapone testing causes HPA axis activation comparable to that observed in normal volunteers (Kreek 1972(Kreek , 1973(Kreek , 1992(Kreek , 1996Kreek et al 1983Kreek et al , 1984. Although opiates have been shown to suppress HPA axis activity in humans acutely, and opiate withdrawal is as- sociated with HPA axis activation, acute cocaine administration is associated with HPA axis activation (Mendelson et al 1992a).…”

“…Our group and others have hypothesized that alterations in responsivity to stress, reflected in and perhaps driven by, abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis, are integral to the vulnerability to, acquisition and maintenance of, relapse to, and treatment of heroin and cocaine addictions (Kreek 1972(Kreek , 1973(Kreek , 1992(Kreek , 1996Cushman and Kreek 1994, Kreek et al 1983, 1984. Alterations in HPA axis function can be assessed using a number of probes, alone or in combination, to stimulate or inhibit activity at different control points of the axis.…”

“…In the most common pattern of active heroin addiction, addicts administer several daily doses of this relatively short-acting opiate, resulting in multiple steep peaks in brain opiate levels. Metyrapone testing in active heroin users has demonstrated reduced HPA axis activation, with flattened or reduced circadian rhythms of adrenocorticotropin hormone (ACTH) and cortisol, and lowered basal levels (Kreek 1972(Kreek , 1973(Kreek , 1992(Kreek , 1996Cushman and Kreek 1974). Using the metyrapone test as an indicator of HPA axis responsivity in cocaine addicts during early and protracted abstinence, our group reported an increased responsivity, observed both in patients dependent on cocaine alone and in those who were also opiate-dependent former heroin addicts in long-term methadone maintenance treatment (Schluger et al 1997).…”

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

“…Opioids, especially heroin and morphine, can produce severe changes in the immune system and can possess a two-step action in the production of cytokines with phases of stimulation and inhibition (Kreek 1996;Pacifici et al 2000;Neri et al 2002). It was demonstrated in some studies that long-term methadone treatment can progressively restore the immune system and increase cytokine production (Kreek 1996;Pacifici et al 2000;Neri et al 2002).…”

“…Buprenorphine possesses a unique receptor profile and may be a useful alternative option to methadone as it has fewer disadvantages and still achieves successful treatment; results from many trials (Kreek 1996;Vidal-Trevan et al 2003;O'Connor and Fiellin 2000;Obadia et al 2001;Krook et al 2002;Kakko et al 2003) indicate the relative safety and efficacy of buprenorphine because this drug can reduce the risk of overdose and can be used to suppress heroin craving and antagonize heroin effects. Buprenorphine has high affinity for opiate receptors but low intrinsic efficacy, so higher doses saturate the receptors longer but give only minimal additional opiate effect, making it safer in overdose than full opiate agonists.…”