Treatment of pain in methadone-maintained patients.

Patients with opioid dependency experience trauma, acute medical illness and chronic diseases, and may have to undergo surgery to the same extent as other individuals. They need to be treated for relief of symptoms, including pain. Undertreatment or inadequate treatment of pain for these individuals is a particular problem because of opioid dependency and/or methadone maintenance treatment. The guiding principles governing treatment of these patients are to maintain the methadone treatment and to use short-acting narcotics administered at higher doses, and to do so as often as necessary, preferably on a fixed schedule, to relieve the pain. Supplemental analgesic medication may also be employed, except that opiate antagonists must be avoided.

Three oral formulations of methadone. A clinical and pharmacodynamic comparison.

This study was done to determine whether there were any differences in subjective symptoms of opiate withdrawal or methadone pharmacodynamics among patients as they were switched between three different oral formulations of methadone. Patients enrolled in a three-way double-blind crossover trial of three methadone formulations. Subjective symptoms and pharmacodynamic measures were assessed throughout the study period. Eighteen patients were enrolled the study. No statistically significant differences in any of the pharmacodynamic parameters studied were found among the three methadone preparations. There was no significant difference among preparations in the rate and extent of rise and fall in plasma methadone levels during a 24-hour intensive sampling period. Subjective symptoms also did not correlate with methadone formulation. Intolerance to changes in methadone formulation, often observed clinically, do not appear to have a pharmacodynamic basis. Our findings support the notion that such change intolerance reflects factors other than the pharmacologic properties of the different formulations of methadone.

Conditioned place preference induced by delta 9-tetrahydrocannabinol: comparison with cocaine, morphine, and food reward.

The rewarding property of delta 9-tetrahydrocannabinol (THC), the psychoactive constituent of marijuana and hashish, was studied using the conditioned place preference paradigm, and compared to that of cocaine, morphine, and food reward. The results of Experiment 1 demonstrated that 2.0 and 4.0 mg/kg doses produced a reliable shift in preference for the THC-paired compartment. The THC place preference observed at 2.0 and 4.0 mg/kg was nearly equivalent to that produced by low doses of cocaine (5.0 mg/kg), morphine (4.0 mg/kg), and food in non food-deprived animals. The second experiment used a different conditioning procedure that included a washout period for THC. The results of Experiment 2 demonstrated that a THC place preference could be obtained using a lower dose of THC (1.0 mg/kg), and that this THC place preference was equivalent to that produced by 10 mg/kg cocaine. At higher doses (2.0 and 4.0 mg/kg), THC produced a dose-dependent place aversion. These results suggest that THC's action on brain reward substrates, previously demonstrated by electrical brain stimulation reward, in vivo brain microdialysis, and in vivo brain electrochemistry studies, reflects itself behaviorally in increased appetitive motivational value for environmental stimuli associated with ingestion of marijuana and hashish.

Marijuana's interaction with brain reward systems: update 1991.

The most pervasive commonality amongst noncannabinoid drugs of abuse is that they enhance electrical brain stimulation reward and act as direct or indirect dopamine agonists in the reward relevant dopaminergic projections of the medial forebrain bundle (MFB). These dopaminergic projections constitute a crucial drug sensitive link in the brain's reward circuitry, and abused drugs derive significant abuse liability from enhancing these circuits. Marijuana and other cannabinoids were long considered "anomalous" drugs of abuse, lacking pharmacological interaction with these brain reward substrates. It is now clear, however, that delta 9-tetrahydrocannabinol (delta 9-THC), marijuana's principal psychoactive constituent, acts on these brain reward substrates in strikingly similar fashion to noncannabinoid drugs of abuse. Specifically, delta 9-THC enhances MFB electrical brain stimulation reward, and enhances both basal and stimulated dopamine release in reward relevant MFB projection loci. Furthermore, delta 9-THC's actions on these mechanisms is naloxone blockable, and delta 9-THC modulates brain mu and delta opioid receptors. This paper reviews these data, suggests that marijuana's interaction with brain reward systems is fundamentally similar to that of other abused drugs, and proposes a specific neural model of that interaction.

Strain-specific facilitation of dopamine efflux by delta 9-tetrahydrocannabinol in the nucleus accumbens of rat: an in vivo microdialysis study.

This study tests the hypothesis that delta 9-tetrahydrocannabinol (delta 9-THC) has a strain-specific facilitatory effect on dopamine (DA) efflux in rat nucleus accumbens, a crucial forebrain convergence of reward-relevant DA neural fibers that has been implicated as a focal brain locus mediating the euphorigenic properties of drugs of abuse. The dependent variable is presynaptic DA efflux measured by in vivo microdialysis in the nucleus accumbens. The independent variables are: (1) intraperitoneal injections of delta 9-THC at 0.0 (vehicle), 0.5 and 1.0 mg/kg; (2) Sprague-Dawley vs Lewis strain rat. Results show that delta 9-THC produces a dose-dependent, strain-specific enhancement of basal DA efflux in Lewis strain rats. These results suggest that genetic variation influences drug abuse vulnerability.

Delta 9-tetrahydrocannabinol enhances presynaptic dopamine efflux in medial prefrontal cortex.

Acute administration of 1.0-2.0 mg/kg delta 9-tetrahydrocannabinol (delta 9-THC) increased presynaptic dopamine (DA) efflux in the medial prefrontal cortex of rats, as measured by intracerebral microdialysis in awake, behaving rats. These data are congruent with suggestions that (1) marijuana's euphorigenic effects and abuse potential may be related to augmentation of presynaptic DA mechanisms, and (2) the medial prefrontal cortex may be an important site of action for drugs of abuse in general and for delta 9-THC in particular.

Changes in AIDS risk behavior among intravenous drug abusers in New York City.

Forty newly admitted patients to a methadone treatment clinic in New York City were interviewed to assess their patterns of intravenous (IV) drug abuse, sexual activity, and other risk behaviors for the acquired immunodeficiency syndrome (AIDS). The study revealed a marked decline in needle sharing since 1984 (46% to 14%), despite a concurrent doubling of the number of weekly IV drug injections per subject (10 to 21). High rates of promiscuous heterosexual activity were noted among men (80% said they were currently active with more than one woman), while the rates of condom use were low, as reported by both men and women (less than 30%). Recent reduction in weight were reported by 40% of subjects, and the average body mass of all individuals was subnormal. Thus, despite an apparent decline in needle sharing, high risk sexual behavior is apparently persisting, drug use is increasing, and nutritional deficits are prevalent among IV drug abusers. Synergism of these factors should be considered in the manifestation of HIV infection among IV drug abusers.

Delta 9-tetrahydrocannabinol produces naloxone-blockable enhancement of presynaptic basal dopamine efflux in nucleus accumbens of conscious, freely-moving rats as measured by intracerebral microdialysis.

This study examined the effects of acute administration of delta-9-tetrahydrocannabinol (delta 9-THC), the psychoactive ingredient in marijuana, on extracellular efflux of dopamine (DA) and its metabolites as measured by in vivo microdialysis in nucleus accumbens of conscious, freely-moving rats. delta 9-THC, at low doses (0.5-1.0 mg/kg), which significantly enhance brain stimulation reward (intracranial self-stimulation), significantly increased DA efflux in nucleus accumbens. Augmentation of DA efflux by delta 9-THC was abolished by removal of calcium (Ca++) ions from the perfusion fluid, indicating a Ca(++)-dependence of delta 9-THC's action. Augmentation of DA efflux by delta 9-THC was either totally blocked or significantly attenuated by doses of naloxone as low as 0.1 mg/kg. Given the postulated role of mesocorticolimbic DA circuits in mediating and/or modulating brain stimulation reward, the present data raise the possibility that marijuana's rewarding effects, and hence its euphorigenic effects and abuse potential, may be related to pharmacological augmentation of presynaptic DA mechanisms. Additionally, the DA mechanisms enhanced by marijuana appear to be modulated by an endogenous opioid peptide system.

The treatment of alcoholic methadone patients: a review.

Alcoholism is a major problem among methadone maintenance patients. Although alcoholism in the methadone patient is recognized as a problem, few treatment studies have been conducted. Treatment studies have examined abstinence oriented and controlled drinking therapies, voluntary disulfiram treatment, and combined behavioral-pharmacological treatment. The first three treatments were shown to be ineffective in impacting alcohol consumption. The ineffectiveness reported by these studies was attributed to patients' lack of motivation. However, the combined behavioral-pharmacological treatment, which made methadone treatment contingent on antabuse consumption, resulted in decreases in both alcohol consumption and arrests, with increases occurring in employment. Future research should examine the generality of the findings from combined treatment as well as examine whether other contingency management procedures may reduce alcohol consumption in the alcoholic methadone patient.

Issues of transference in methadone maintenance treatment.

Methadone maintenance treatment involves a great deal of governmental regulations and controls which have to be enforced by the clinician, thus having important transferential implications for therapy. This issue is explored on the basis of a case example, and recommendations are made to detach rule enforcement from therapy.

Locus of control and initiation of detoxification among male methadone maintenance patients.

Two hypotheses were derived linking locus of control to voluntary, "completion of treatment" detoxification from methadone maintenance: (1) methadone maintenance patients with an internal locus of control will be more likely to indicate a willingness to begin detoxification, and (2) among patients indicating a willingness to begin, those with an internal locus of control would be more likely to actually begin. Subjects were 115 male methadone patients. A nonsignificant trend was found in support of the first hypothesis, while the second was reversed at a statistically significant level (r = -.30, p less than .012).

Rehabilitation of the Puerto Rican addict: a cultural perspective.

Drug addiction has assumed major proportions in the Hispanic population. This paper questions whether treatment programs in Puerto Rican communities adequately relate their rehabilitative services to the realities of Hispanic culture. The experience of a clinic in the South Bronx is reviewed, and it is suggested that programs need to be aware of cultural differences, provide Hispanic staff to treat Hispanic patients, and build up acknowledged strengths, values, and folkways.

Methadone treatment and physical complaints: a clinical analysis.

In this study 102 male patients on the Harlem Hospital Methadone Maintenance Treatment Program were asked about physical complaints which they attributed to taking methadone. The most common complaints were sweating, constipation, drowsiness, sexual problems, and aches in bones and joints. There were no statistically significant differences between new patients and long-term patients, but long-term patients appear more likely to be bothered by sweating than new patients, and constipation occurs most frequently during the initial stages of treatment. Complaints were found, in general, to be minor and did not constitute a barrier to patient retention in treatment.

The narcotic-dependent mother: fetal and neonatal consequences.

During the years 1971--1974, 230 infants born to drug-dependent women and 33 infants born to ex-addicts were studied. Heroin abuse declined while methadone usage increased during those years. Compared to heroin abuse, methadone maintenance treatment during pregnancy was associated with more consistent prenatal care, more normal fetal growth and reduced fetal mortality. Meconium staining of amniotic fluid was increased in the heroin and heroin-methadone groups; this was not associated, however, with an increase in meconium aspiration or a reduction in Apgar scores. Of special note was the equally severe intrauterine growth retardation of infants of former heroin addicts who were free of narcotic use during pregnancy. Neonatal withdrawal from methadone appeared to be more severe than from heroin, as judged by amount of medication required to control symptoms and duration of treatment. In all groups, central nervous system signs were the most common manifestations of withdrawal. Severity of withdrawal did not correlate with late pregnancy maternal methadone dosage. Neonatal seizures occurred in 1.5% of the heroin group and 10% of the methadone group. Discharge of an infant to a parent rather than to an alternate care-taker was more likely if the mother was enrolled in a methadone treatment program. Methadone maintenance programs appear to offer significant therapeutic benefits, balancing the untoward effects of the drug on the newborn infant.