PubMed · 15712977
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Alan M Levine, Richard K Burdick. Controlled-release oxycodone.. https://doi.org/10.5435/00124635-200501000-00001
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Presently, there is a considerable interest in heroin-assisted treatment: co-prescription of heroin to certain subgroups of chronic, treatment-resistant, opioid dependent patients. In 2002, nine countries had planned (Australia, Belgium, Canada, France, Spain) or ongoing (Germany, The Netherlands, Switzerland, United Kingdom) clinical trials on this subject. These trials (and the routine heroin-assisted treatment programs that might result) will need pharmaceutical heroin (diacetylmorphine) to prescribe to the patients. Research into the development of pharmaceutical forms of heroin for prescription to addicts can benefit from the large amount of knowledge that already exists regarding this substance. Therefore, in this paper we review the physicochemical and pharmaceutical properties of diacetylmorphine and the clinically investigated routes of administration, as well as routes of administration utilised on the street in the context of developing pharmaceutical heroin formulations for prescription to addicts. Patient acceptability of the formulation is essential, because heroin-assisted treatment is aimed at treatment-resistant addicts, who often have to be encouraged to participate (or to maintain participation) in a treatment program. This means that the most suitable products would have pharmacokinetic profiles mimicking that of diacetylmorphine for injection, with rapid peak concentrations of diacetylmorphine and 6-acetylmorphine, ensuring the 'rush effect' and the sustained presence of morphine(-6-glucuronide) creating the prolonged euphoria. Diacetylmorphine for inhalation after volatilisation (via 'chasing the dragon') seems to be a suitable candidate, while intranasal and oral diacetylmorphine are currently thought to be unsuitable. However, oral and intranasal delivery systems might be improved and become suitable for use by heroin dependent patients.
RATIONALE: Evidence indicates that social and environmental enrichment can influence the functional maturation of the central nervous system and may affect an organism's sensitivity to centrally acting drugs. OBJECTIVE: The purpose of the present study was to examine the effects of social and environmental enrichment on sensitivity to mu-opioids possessing a range of relative efficacies at the mu-receptor. METHODS: Rats were obtained at weaning (21 days) and divided into two groups immediately upon arrival. Isolated rats were housed individually in opaque laboratory cages with no visual or tactile contact with other rats; enriched rats were housed socially in groups of four in large cages and given various novel objects on a daily basis. After 6 weeks under these conditions, the effects of morphine, levorphanol, buprenorphine, butorphanol, and nalbuphine were examined in the warm-water, tail-withdrawal procedure and the place-conditioning procedure. RESULTS: In the tail-withdrawal procedure, isolated and enriched rats did not differ in sensitivity to morphine (1.0-30 mg/kg) and levorphanol (0.3-10 mg/kg), but enriched rats were more sensitive to buprenorphine (0.03-3.0 mg/kg), butorphanol (0.3-30 mg/kg), and nalbuphine (0.3-30 mg/kg). In drug combination tests, butorphanol and nalbuphine antagonized the effects of morphine in isolated rats under conditions in which they produced high levels of antinociception in enriched rats. In the place-conditioning procedure, doses of 10 morphine and 3.0 levorphanol established a place preference in both groups of rats, whereas doses of 0.3 buprenorphine, 3.0 butorphanol, and 10 nalbuphine established a place preference only in enriched rats. CONCLUSIONS: These findings may be taken as evidence that enriched rats are more sensitive than isolated rats to the effects of lower-efficacy mu-opioids and that social and environmental enrichment leads to functional alterations in opioid receptor populations.
RATIONALE: In previous studies, we have demonstrated that mice of the inbred strain C57BL/6J (C57) are more susceptible to amphetamine-induced conditioned place preference (CPP) than DBA/2J (DBA) mice. Moreover, we also observed parallel strain differences for the locomotor-stimulant effects of the drug. However, other studies have reported either no difference or opposite strain differences for cocaine- and morphine-induced CPP as well as for the locomotor effects of these drugs, suggesting that amphetamine-related behavioral phenotypes might depend on a specific pharmacological action of the psychostimulant. OBJECTIVES: This study was aimed at testing strain differences for cocaine- and morphine-related behavioral phenotypes in the same experimental protocol and conditions previously used for amphetamine. METHODS: C57 and DBA mice were tested for CPP induced by cocaine (0, 5, 10, and 20 mg/kg) and morphine (0, 5, 7.5, and 10 mg/kg). Locomotor activity data were simultaneously obtained by measuring distance moved during all different CPP phases and unconditioned locomotor activity, behavioral sensitization and conditioned hyperactivity were measured together with CPP. RESULTS: (a) Either cocaine or morphine promoted significant CPP at lower doses in C57 than in DBA mice; (b) only drug-trained C57 mice showed a significant CPP compared with the control group; and (c) only C57 mice showed dose-dependent effects of cocaine on CPP. Moreover, there was no relationship between drug-induced CPP and locomotion. CONCLUSIONS: The results demonstrate that C57 and DBA mice differ in their sensitivity to cocaine- and morphine-induced CPP and suggest that the two strains differ in sensitivity to the positive incentive properties of drugs of abuse.