Biomedical subjects

J H Jaffe

Publications and source records attributed to J H Jaffe.

At least 37 records · Page 2Linked to original sources

PubMed1991

Effects of nifedipine pretreatment on subjective and cardiovascular responses to intravenous cocaine in humans.

The effects of oral nifedipine pretreatment on subjective and cardiovascular responses to intravenous cocaine infusions were studied in cocaine-using volunteers. Nifedipine, 10 mg or placebo, was administered 20-25 min before placebo, 20 mg, or 40 mg cocaine, using a repeated measures randomized double-blind design. The variables measured were self-reported subjective effects, general behavior rated by two observers, blood pressure and heart rate. Cocaine produced the expected dose-related effects on subjective and cardiovascular measures. Nifedipine pretreatment attenuated some subjective effects of cocaine. Nifedipine directly reduced blood pressure but did not antagonize the effects of cocaine on blood pressure. These findings suggest that dihydropyridine calcium channel modulators may be useful compounds in the clinical management of cocaine users.

Adult↗

PubMed1991

Induction of phencyclidine-like behavior in rats by dextrorphan but not dextromethorphan.

The behavioral effects of dextromethorphan (DM), dextrorphan (DO) and phencyclidine (PCP) were compared in rats. DO (15-120 mg/kg) was similar to PCP (1.25-20 mg/kg) in inducing dose-dependent locomotor hyperactivity, stereotypy and ataxia. DM (15-120 mg/kg) induced moderate hyperactivity only at the higher doses about 45 min after treatment. DM and DO modified the locomotor facilitation induced by 10 mg/kg PCP in opposite directions. Pretreatment with DO facilitated, whereas DM dose-dependently inhibited PCP-elicited hyperactivity. Although the metabolism of DM in rats is unknown, the recently reported abuse of DM in humans may occur by its conversion to DO in the organism, i.e., to a metabolite which produces PCP-like effects.

Animals↗

PubMed1991

The partial opioid agonist, buprenorphine, protects against lethal effects of cocaine.

Buprenorphine (0.3-3.0 mg/kg) produced dose-dependent protection against the lethal effects of cocaine in mice. The (+)-enantiomer of buprenorphine did not protect up to doses over 100 times greater than the lowest effective dose of its (-)-enantiomer. The protective effects were also produced by the opioid agonists morphine and methadone, but not by the opioid antagonist, naltrexone. Low doses of naltrexone (0.3-1.0 mg/kg) blocked the protective effects of buprenorphine. Protection conferred by buprenorphine was not observed in CXBK mice, a recombinant inbred strain relatively devoid of mu-opioid receptors. Thus, buprenorphine appears to protect against the lethal effects of cocaine by a process mediated by mu-opioid receptors. The present results should provide some additional safety assurance in future clinical trials with buprenorphine, especially in outpatient trials where cocaine abuse may continue along with treatment.

Animals↗

PubMed1991

Comparison of amantadine and desipramine combined with psychotherapy for treatment of cocaine dependence.

We conducted a single-blind, random assignment, placebo-controlled, 12-week comparison of desipramine hydrochloride and amantadine hydrochloride as adjunctive treatments to counseling for cocaine dependence. Subjects were 54 outpatients who met DSM III-R criteria for active cocaine dependence and who completed a minimum of 2 weeks of treatment. Subjects treated with fixed doses of 200 mg/day desipramine (N = 17), 400 mg/day amantadine-placebo (N = 16), and placebo (N = 21) did not differ for lifetime cocaine use, lifetime histories of psychopathology, admission scores on psychometric assessments, and sociodemographics. All treatment groups demonstrated dramatic and persistent decreases in cocaine use, craving for cocaine, and psychiatric symptoms consequent to treatment. Although there was a trend for more dropouts by subjects taking desipramine, there were no significant differences among treatment groups regarding retention in treatment, craving for cocaine, and decreased cocaine use confirmed by urine toxicology. There was a trend for subjects treated with desipramine to maintain longer periods of cocaine abstinence. Mean plasma concentration of desipramine in a subsample of our subjects was less than that recommended for treatment of depression, thus the dosage of desipramine may have been subtherapeutic.

Adult↗

PubMed1991

Amyl nitrite alters human in vitro immune function.

Effects on the human immune system of volatile nitrite inhalation were studied in 18 male volunteers. While nitrite inhalation decreased the absolute number of CD3+ T lymphocytes during the period of inhalation, cell numbers returned to pre-treatment levels within one week after cessation of the drug. Nitrite inhalation did not alter the percentage of CD3+, CD4+, CD8+ or CD19+ lymphocytes. Natural killer (NK) cell activity against K562 target cells was depressed by nitrite administration but returned to pre-inhalation or greater levels after nitrite discontinuation. Cell proliferation following cell activation by PHA, ConA and PWM was unaffected by amyl nitrite inhalation. We conclude that in humans inhalation of volatile nitrites causes cycles of modest immunosuppression, particularly in NK activity, followed by gradual recovery when the drug is not inhaled for several days.

Adult↗

PubMed1990

Cocaine-induced reduction of glucose utilization in human brain. A study using positron emission tomography and [fluorine 18]-fluorodeoxyglucose.

We examined the effects of cocaine hydrochloride (40 mg intravenously) on regional cerebral metabolic rates for glucose and on subjective self-reports of eight polydrug abusers in a double-blind, placebo-controlled, crossover study. The regional cerebral metabolic rate for glucose was measured by the [fluorine 18]-fluorodeoxyglucose method, using positron emission tomography. With eyes covered, subjects listened to a tape that presented white noise, "beep" prompts, and questions about subjective effects of cocaine or saline. Cocaine produced euphoria and reduced glucose utilization globally (mean reduction, 14%). Twenty-six of 29 brain regions (all neocortical areas, basal ganglia, portions of the hippocampal formation, thalamus, and midbrain) showed significant decrements (5% to 26%) in the regional cerebral metabolic rate for glucose. No significant effects of cocaine were observed in the pons, the cerebellar cortex, or the vermis. Right-greater-than-left hemispheric asymmetry of regional cerebral metabolic rates for glucose occurred in the lateral thalamus. The findings demonstrate that reduced cerebral metabolism is associated with cocaine-induced euphoria.

Adult↗

PubMed1990

The relationship between a diagnosis of antisocial personality and hostility: development of an Antisocial Hostility scale.

An antisocial hostility scale was developed by correlating items of the Buss-Durkee Hostility Inventory with a diagnosis of antisocial personality (ASP) as determined by a computerized version of the DSM-III. Fifty-two male volunteers for drug-related studies at the Addiction Research Center were used for a preliminary test development sample. The scale developed thereby was related significantly to a diagnosis of antisocial personality in a cross-validation sample of 28 drug abusers. A final scale was developed by obtaining correlations between ASP and Buss-Durkee items using the subjects from both of these preliminary samples. Items that comprise the scale were predominantly behaviorally oriented hostility items covered by the Assault scale rather than affective items such as those in the Resentment scale. In a 122 cross-validation sample the scale was related significantly to a diagnosis of antisocial personality. The study confirms the generality of the criterion of overt aggression as a condition for meeting DSM-III criteria for antisocial personality.

Adult↗

PubMed1990

Self-report vs. laboratory measures of aggression as predictors of substance abuse.

Measures of aggressive behavior, antisocial personality, criminality, and impulsivity were obtained on a sample of 85 drug abusing volunteers for studies at the Addiction Research Center in Baltimore. Measures included the Buss-Durkee Hostility Inventory, Diagnostic Interview Schedule Antisocial Personality Disorder diagnosis, Elliott-Huizinga Lifetime Events Scale, Eysenck's Impulsiveness-Venturesomeness-Empathy scales, and a laboratory measure of aggression patterned after the Buss 'aggression machine'. All of the self-report measures of aggression and antisocial personality were moderately correlated with each other, but did not correlate with the laboratory aggression measure. This laboratory measure, nevertheless, made a significant contribution to the prediction of certain substance abuse diagnoses over and above the contributions of the other measures.

Adult↗

PubMed1990

Use of buprenorphine in the treatment of opioid addiction. II. Physiologic and behavioral effects of daily and alternate-day administration and abrupt withdrawal.

Nineteen heroin-dependent male volunteers were administered buprenorphine sublingually, in ascending daily doses of 2, 4, and 8 mg. They were maintained on 8 mg daily through study day 18. On study days 19 through 36, subjects in group 1 continued to receive burprenorphine daily; subjects in group 2 received buprenorphine or placebo on alternate days. On days 37 through 52, all subjects received placebo. Subjects receiving buprenorphine on alternate days reported significantly greater urge for an opioid, increased dysphoria scores, and pupillary dilation on placebo days. After abrupt termination of buprenorphine, no withdrawal signs were detected with the Himmelsbach scale. However, subjects reported mild-to-moderate opioid withdrawal symptoms, peaking at 3 to 5 and lasting for 8 to 10 days. Daily administration of buprenorphine provided greater control of subtle opioid withdrawal symptoms, but subjects could tolerate a between-dose interval of 48 hours.

Adult↗

PubMed1990

Ibogaine fails to reduce naloxone-precipitated withdrawal in the morphine-dependent rat.

Because of anecdotal reports in which ibogaine eliminates opioid withdrawal symptoms in humans, we studied this phenomenon in the rat model. Ibogaine (5, 10, 20 and 40 mg kg-1, s.c.) was administered 15 min before naloxone (0.5 mg kg-1, s.c.) in morphine dependent rats (3 days after the s.c. implantation of a 75 mg morphine pellet). Of the 12 withdrawal signs scored, the only significant changes observed after ibogaine (compared with vehicle control) was a decrease in grooming (10 mg kg-1) and an increase in teeth chatter (5 mg kg-1). In spite of ibogaine's apparent interaction with several neurotransmitter receptor systems, it does not alleviate opioid withdrawal in this animal model at non-tremorigenic (5 and 10 mg kg-1) or tremorigenic (20 and 40 mg kg-1) doses.

Animals↗

PubMed1990

Trivializing dependence.

There are a number of repetitive behaviors which have in common what appears to be a decrease in an individual's capacity to choose to discontinue them. The taxonomy we select to categorize these behaviors depends on our objectives. Broad definition which label as 'addictions' both repetitive use of drugs and repetitive behaviors not related to drug use call attention to the loss of flexibility that the behaviors have in common. However, such broad definitions may overemphasize the value of general behavioral approaches to change and obscure the fact that seemingly similar behaviors can be dramatically changed by very different specific interventions; (for example, nicotine gum for cigarette smoking, clomipramine for obsessive compulsive disorder.) It is also possible that calling both compulsive hair-pulling and daily heroin use 'addictive disorders' may trivialize the concept of addiction and lead to an erosion of public support for research and intervention in the chemical addictions.

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PubMed1990

Intravenous pharmacokinetics of 2-hydroxyimipramine in alcoholics and normal controls.

Fifteen subjects (seven recently abstinent, male, chronic alcoholics and eight, age- and weight-matched male controls) were administered 10 mg 2-hydroxyimipramine (2-OHIMI) by intravenous infusion. Pharmacokinetic parameters were determined from multiple blood samples drawn over 60 hours. Total body clearance of unbound drug, as calculated from the plasma concentration versus time data, was significantly increased in the alcoholic group as compared to the control group (3.12 vs 1.51 L/hr/kg). Terminal elimination half-life was decreased in the alcoholics (7.07 vs 10.12 hr). The fraction of the drug unbound to plasma protein was determined by equilibrium dialysis and was found to be decreased in the alcoholic group over that found in the controls (29.8 vs 36.4%). All subjects were monitored by EKG during the first 4 hours of sampling. Although there was a small mean decrease in heart rate following infusion, it did not achieve statistical significance. Alcoholics had a greater mean increase in P-R but not QTc intervals than control subjects, a difference that was significant at 45 minutes and 1 hour postinfusion. There were no significant differences in the percentage of subjects with abnormal P-R or QTc intervals between the alcoholic and control groups.

Adult↗

PubMed1990