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PubMed1986

Investigation of the abuse liability of buspirone in alcohol-dependent patients.

By use of the Addiction Research Center Inventory, the Amphetamine Self-Rating Scale, the Single-Dose Questionnaire, and selected physiologic measures (blood pressure, pulse and respiratory rates, oral temperature, and pupil diameter), the abuse liability of buspirone (10, 20, and 40 mg) was compared with that of diazepam (10 and 20 mg) and placebo in 19 subjects who were hospitalized for the treatment of alcohol dependency. Each treatment was given as a single dose at intervals of at least three days according to a double-blind, six-period, crossover Latin square design. Neither buspirone nor diazepam had any effect on blood pressure, pulse and respiratory rates, or body temperature. A small, transient pupillary constriction was evident in the 20- and 40-mg buspirone groups, but it dissipated within two hours after dosing. Both buspirone and diazepam had only a small stimulating effect on appetite. On the Pentobarbital-Chlorpromazine-Alcohol Group and Sedation subscales of the Addiction Research Center Inventory, the 40-mg dose of buspirone yielded effects suggestive of a mild sedative-type drug. Only the 20-mg dose produced a significant effect on the Euphoria scale. Diazepam appeared to be more active as a sedative-hypnotic type of drug, by virtue of its effects on both the Amphetamine and Euphoria subscales and its greater effects on the Morphine-Benzedrine Group, Pentobarbital-Chlorpromazine-Alcohol Group, and Sedation subscales, suggesting euphoria. Not only does the lack of effect of buspirone on the Amphetamine and Morphine-Benzedrine Group subscales indicate lack of a euphorigenic property, but the score on the Lysergic Acid Diethylamide subscale, especially in the 40-mg group, suggests a dysphorigenic property at high doses. On the Amphetamine Self-Rating Scale, buspirone and diazepam affected only the sleep factor and only the 40-mg buspirone dose was distinguishable from placebo. On the Single-Dose Questionnaire, both buspirone and diazepam tended to be rated more as sedative-type drugs, but buspirone was generally less well liked than diazepam. Overall, the results, which suggest a lack of euphoria and the presence of dysphoria at high doses, indicate that buspirone has only limited, if any, abuse liability.

Administration, Oral↗
PubMedDate not supplied

[Mood and insulin-dependent diabetes. Value of the Von Zerssen test].

At the end of a week of education, 120 diabetics (I.D.D.M.) checked the list of items from the Von Zerssen's test. This self evaluation test classifies the mood in to depression (13%), anxiety (27%), normal (39%) and euphoria (21%). The ages of the patients and the duration of their diabetes were irrelevant to the results. But, according the type of diabetes, the results become: discovery of I.D.D.M.: depression (4%), anxiety (35%), normal (35%), euphoria (26%); I.D.D.M. (former N.I.D.D.M.): depression (16%), anxiety (28%), normal (31%), euphoria (25%); I.D.D.M. ancient: depression (15%), anxiety (23%), normal (45%), euphoria (17%).

Adolescent↗
PubMed2004

Correlating brain atrophy with cognitive dysfunction, mood disturbances, and personality disorder in multiple sclerosis.

Neuropsychological impairment is a common feature of multiple sclerosis. Affected patients often have deficits in information-processing speed and memory and exhibit psychopathological states such as depression. A minority of patients have rarer affect/mood disorders such as euphoria sclerotica and pathological laughter/crying. Neuropsychological impairment is a major predictor of low quality of life, unemployment, and caregiver distress. Studies evaluating correlations between neuropsychological impairment and findings on magnetic resonance imaging show that neuropsychological dysfunction is associated with lesion burden and diffuse disease in normal-appearing brain tissue. However, measures of tissue atrophy including whole-brain and central atrophy are especially well correlated with and predictive of cognitive impairment. Moreover, recent studies have shown that conventional measures of brain atrophy explain more variance in neuropsychological dysfunction than do measures of lesion burden. In particular, neuropsychological outcomes correspond highly with linear measures of subcortical atrophy such as ventricle enlargement. Within the domain of emotional dysfunction, both lesion burden and atrophy are related to major depressive disorder. Brain atrophy also predicts euphoria and disinhibition. The preliminary data suggest that although lesion burden primarily predicts depressive disorder, both lesion burden and atrophy predict the presence of euphoria. Euphoria and disinhibition likely represent personality change associated with worsening cognition as the disease progresses. Taken together, this growing body of data on magnetic resonance imaging to neuropsychological correlations supports the clinical relevance and validity of brain atrophy as a measure of disease progression in multiple sclerosis. Continuing research focuses on the possible relationship between measures of regional brain atrophy and cognitive and emotional impairment.

Atrophy↗
PubMed1975

Attenuation of the euphoriant and activating effects of d- and l-amphetamine by lithium carbonate treatment.

Seven of nine depressed patients experienced a 4.3-fold increase in rated euphoria and activation following 30 mg d-amphetamine in a replicated dose, double blind study. d-Amphetamine was 2 to 2.3-fold more effective in producing activation, euphoria, and antidepressant effects than the same dose of l-amphetamine. Co-treatment with lithium carbonate produced a 60% (P less than 0.001) attenuation of the activation and euphoria responses to d-amphetamine. The responses to l-amphetamine were almost completely abolished by lithium. This study raises the possibility of lithium carbonate use as an adjunct in the treatment of amphetamine addiction.

Adult↗
PubMed1993

Subjective and behavioral effects of diazepam depend on its rate of onset.

This study addressed the assumption that rate of onset affects the euphorigenic effects of drugs. Drugs with rapid onset are commonly thought to be more euphorigenic than drugs with slower onset, but this idea has rarely been studied directly. Nine healthy male social drinkers, with no history of drug- or alcohol-related problems, participated in three sessions. On each session they received oral doses of placebo (PLAC), diazepam in a rapid onset condition (FAST), or diazepam in a slow onset condition (SLOW). In the FAST condition, they received a single 20 mg dose, whereas in the SLOW condition they received six 4 mg doses administered at 30-min intervals. Plasma levels of diazepam and desmethyldiazepam, subjective effects (including measures of euphoria), psychomotor performance and vital signs were monitored throughout each session. Although the FAST and SLOW conditions led to similar peak plasma levels of drug, the peak was attained earlier in the FAST condition (61 min versus 220 min). Subjects' scores on a measure of euphoria (MBG scale of the ARCI) were significantly higher in the FAST condition compared to the SLOW and PLAC conditions. Subjects exhibited significantly more behavioral signs of intoxication and greater psychomotor impairment in the FAST condition. Sedative effects of the drug were similar in magnitude, but the effects lasted slightly longer in the FAST condition. On several measures diazepam produced similar effects in the two conditions (e.g., ratings of strength of drug effect). These data provide limited support for the notion that a faster rate of onset of drug effects is associated with greater euphoria.

Adult↗
PubMed1986

Evaluation of mixtures of morphine and d-amphetamine for subjective and physiological effects.

Combinations of morphine and d-amphetamine have been shown to be more effective in relieving pathological and experimental pain with fewer side effects than morphine alone. Subjective, physiological and behavioral effects of the combination were assessed in the present study to determine whether the abuse liability of the combination might also be enhanced. Single intramuscular doses of morphine and d-amphetamine alone and in combination were tested under double-blind conditions in 10 adult, male, non-dependent substance abusers. Morphine and amphetamine alone increased scores on subjective effect measures including the Morphine-Benzedrine Group (MBG) (euphoria) and liking scales. In general, the combination produced greater euphoria than that produced by either drug alone. In contrast, many physiological effects of the drugs were mutually antagonized. Thus, the combination of morphine and d-amphetamine has a greater potential to be abused because of the additive euphoria and a lessening of side effects.

Body Temperature↗
PubMedDate not supplied

[Differences in the subjective effects of drugs in patients with a first psychotic episode. Preliminary results].

INTRODUCTION: The study of the subjective effects of abuse substances may facilitate comprehension of the high prevalence of substance abuse in psychosis. OBJECTIVE: To assess the subjective effects of psychoactive substances in psychotic patients with substance use disorder in a prospective open study with a 6 month evaluation. METHODS: Thirty patients consecutively admitted for the first time to a psychiatric hospital because of a psychotic disorder (DSM-IV) were included. Sociodemographic data, substance use history, drug urine test, and severity of psychotic symptoms measured by BPRS, SANS and SAPS were evaluated. The subjective effects of drugs were assessed with the short form of the ARCI questionnaire. Patients were re-assessed at six months followup. RESULTS: Sixty-three percent of patients were male, mean age 29.2 years. A total of 46.6% presented at least one substance use disorder. Differences between substance users group and non-substance users group were only related to sex (more male in substance user group), and no other sociodemographic and clinical differences were found. The main abuse drugs found were: 86% cannabis, 17% cocaine, 17% alcohol, 3% heroin and 3% hypnosedatives. Fifty percent only consumed cannabis. The psychotic patients with substance use disorder showed higher punctuation in MBG scale (euphoria scale); no differences in other ARCI scales were found. At six months follow-up, 83.3% patients were re-assessed and no differences were found. CONCLUSIONS: The psychotic patients with substance use disorder showed a higher subjective effect of euphoria than non-substance user psychotics, suggesting that drug use is mainly related to obtaining euphoria-like effects than sedatives in this group.

Adult↗
PubMed1987

[Intellectual and mood disorders in multiple sclerosis].

Reports of frequency and interpretation of intellectual and mood disorders differ in multiple sclerosis (MS). Forty-one patients with MS defined according to MacAlpine's criteria were evaluated by psychometric tests (WAIS) and neuropsychologic examinations (study of language, gnosic and praxic activities, dynamic gestural organization, memory and learning) together with, in 24 of them, the AMDP psychopathologic rating scale. Intellectual disorders were noted in 65 p. 100 of patients. Although more frequent in severe and chronic forms they were nevertheless of early onset since more than a half of the patients with onset of disease less than 5 years ago were affected. Their semiology was fairly homogeneous, combining disturbances of dynamic gestural organization (decomposition or simplification) and memory and learning deficiencies without anomalies of instrumental functions or usual psychometric mental deterioration. Application of the AMDP scale failed to reveal any psychotic type of disorders. Mood disturbances were predominant, affecting 60 p. 100 of the subpopulation studied (24 cases) and combining, in an unexpected manner: dysphoria, euphoria and depression. Only euphoria appeared to be correlated with intellectual disorders. Frequency of both intellectual and mood disorders was similar to that reported in other series published. The relative homogeneity of semiology, seen by the correlation between the different disturbances (decomposition and simplification, plateau learning curve and euphoria) and the unusual grouping of these effects, is suggestive of their organic basis. In addition, signs and symptoms resemble the neuropsychological expression of frontal lobe lesions and certain lesions of central grey nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1997

Effects of meta-chlorophenylpiperazine infusions in patients with seasonal affective disorder and healthy control subjects. Diurnal responses and nocturnal regulatory mechanisms.

BACKGROUND: Multiple lines of evidence suggest that brain serotonergic systems may be disturbed in seasonal affective disorder (SAD). Previously, we found that the serotonergic agent meta-chlorophenylpiperazine (m-CPP) produced increases in activation and euphoria in depressed patients with SAD, but not in patients with SAD following light treatment or in the summer, nor in healthy control subjects in any condition. In the present study, we attempted to replicate and extend this finding using better methods. METHODS: Seventeen outpatients with SAD and 15 control subjects underwent successive 3-week periods of bright light treatment and light avoidance in a randomized order. During the third week of each condition, on 2 different occasions, subjects were admitted to the hospital for a night of sleep (core temperatures were recorded), followed by infusions of m-CPP (0.08 mg/kg) or placebo the next morning. Dependent measures included the 24-item National Institute of Mental Health Self-Rating Scale, plasma corticotropin, cortisol, prolactin, growth hormone, and norepinephrine concentrations, and core temperatures. RESULTS: Meta-chlorophenylpiperazine produced (1) significant increases in "activation-euphoria" ratings only in depressed patients with SAD in the untreated condition and (2) blunted corticotropin and norepinephrine responses in patients with SAD compared with controls across both light treatment conditions. In both groups, light treatment was associated with significant reductions in nocturnal core temperatures, which were correlated with similarly significant reductions in mean diurnal growth hormone concentrations. In patients with SAD, (1) the reductions in nocturnal core temperatures also were correlated with the reductions in baseline depression ratings and (2) the reductions in mean growth hormone concentrations were significantly smaller compared with controls. CONCLUSIONS: The abnormal m-CPP-induced activation-euphoria responses represent a replicated state marker of winter depression in patients with SAD. The blunted m-CPP-induced responsiveness of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system may represent traitlike abnormalities. The improvements in mood following light treatment in patients with SAD seem to be associated with the lowering of nocturnal core temperatures. The findings, although not easily explained based on a uniform abnormality of serotonin receptors, are nonetheless compatible with the notion that selected regions of the central nervous system are deficient in serotonin transmission during winter depression.

Adrenocorticotropic Hormone↗
PubMed2005

Comparative and interactive human psychopharmacologic effects of ketamine and amphetamine: implications for glutamatergic and dopaminergic model psychoses and cognitive function.

BACKGROUND: In healthy individuals, ketamine hydrochloride and amphetamine sulfate produce cognitive, behavioral, and subjective effects resembling endogenous psychoses. Studying the comparative and interactive effects of these agents may provide insights into the roles of the glutamate and monoamine systems in psychosis and cognition. OBJECTIVES: To directly compare the effects of ketamine and amphetamine and to explore their interactive effects within individuals. DESIGN: Placebo-controlled, randomized, double-blind psychopharmacologic trial. SETTING AND PARTICIPANTS: Forty-one healthy individuals recruited from the community who completed up to 4 test days. MAIN OUTCOME MEASURES: On each test day, participants received amphetamine (a 1-minute infusion of amphetamine sulfate, 0.25 mg/kg, or saline) and ketamine (a 1-minute intravenous infusion of ketamine, 0.23 mg/kg, followed by a 1-hour infusion of 0.5 mg/kg or an identical saline bolus and infusion). The order of amphetamine and ketamine infusions was randomized. RESULTS: At the doses studied, ketamine and amphetamine produced positive symptoms and euphoria. However, perceptual changes were produced only by ketamine, and hostility, grandiosity, and somatic concern were stimulated only by amphetamine. Amphetamine and ketamine produced conceptual disorganization, but only ketamine produced concrete ideation and unusual mannerisms. Ketamine produced negative symptoms and disrupted delayed recall. Ketamine and amphetamine showed 3 types of interactive effects: (1) amphetamine attenuated the impairment of working memory produced by ketamine; (2) amphetamine and ketamine had additive effects on thought disorder, arousal, and euphoria; and (3) amphetamine and ketamine had less-than-additive effects on psychosis. CONCLUSIONS: These findings implicate N-methyl-D-aspartate glutamate receptors and dopamine systems in psychosis. However, glutamate and dopamine may differentially contribute to psychosis, thought disorder, and euphoria. Regarding medication development for cognitive dysfunction, the pattern of the interactive effects of ketamine and amphetamine is consistent with the hypothesis that facilitation of prefrontal cortical dopamine levels would attenuate some cognitive impairments associated with deficits in N-methyl-D-aspartate receptor function.

Amphetamine↗
PubMed2001

Neuropsychiatric assessment of Gilles de la Tourette patients: comparative study with other hyperkinetic and hypokinetic movement disorders.

The role of the basal ganglia in conditions with co-occurring movement disorders and neuropsychiatric symptoms is not well known. It has been hypothesized that hyperkinesia -disinhibited behaviors and hypokinesia-inhibited behaviors result from an imbalance between the direct and indirect striatal output pathways, and that differential involvement of these pathways could account for the concurrent abnormalities in movement and behavior observed in these disorders. This study aimed to evaluate whether the pattern and the extent of the neuropsychiatric manifestations of patients with GTS, a hyperkinetic movement disorder of basal ganglia origin, differs from that of patients with other basal ganglia hyperkinetic (e.g., HD) or hypokinetic (e.g., PSP) movement disorders, and to determine whether patients with GTS show a greater frequency of hyperactive behaviors (e.g., agitation, irritability, euphoria, or anxiety) than PSP patients, and are comparable to patients with HD. The Neuropsychiatric Inventory (NPI), a scale with established validity and reliability, was administered to 26 patients with GTS (mean age, 30.2 +/- 2.2 years), and the results were compared with that of 29 patients with HD (mean age, 43.8 +/- 2 years) and 34 with PSP (mean +/- S.D. age, 66.6 +/- 1.2 years). There was no difference between the groups in the total NPI scores. However, there was a double dissociation in behaviors: patients with hyperkinetic disorders (HD and GTS) exhibited significantly more agitation, irritability, anxiety, euphoria, and hyperkinesia, whereas hypokinetic patients (PSP) exhibited more apathy. Patients with GTS showed greater scores than HD patients in all those scores differentiating HD and GTS from PSP patients (e.g., agitation, irritability, anxiety and euphoria), and were differentiated in a logistic regression analysis from both HD and PSP patients in having significantly more anxiety. We found that patients with GTS manifested predominantly hyperactive behaviors similar but more pronounced than those presented by patients with HD, while those with PSP manifested hypoactive behaviors. Based on our findings and the proposed models of basal ganglia dysfunction in these disorders, we suggest that the hyperactive behaviors in GTS are comparable to those observed in HD, being both secondary to an excitatory subcortical output through the medial and orbitofrontal cortical circuits, while in PSP the hypoactive behaviors are secondary to hypostimulation of these circuits. Abnormalities of other brain structures (e.g., amygdala, brainstem nuclei) may account for the significantly higher anxiety scores differentiating GTS from HD patients.

Adult↗
PubMed1996

Neurochemical bases of locomotion and ethanol stimulant effects.

The locomotor stimulant effect produced by alcohol (ethanol) is one of a large number of measurable ethanol effects. Ethanol-induced euphoria in humans and locomotor stimulation in rodents, a potential animal model of human euphoria, have long been recognized and the latter has been extensively characterized. Since the euphoria produced by ethanol may influence the development of uncontrolled or excessive alcohol use, a solid understanding of the neurochemical substrates underlying such effects is important. Such an understanding for spontaneous locomotion and for ethanol's stimulant effects is beginning to emerge. Herein we review what is known about three neurochemical substrates of locomotion and of ethanol's locomotor stimulant effects. Several lines of research have implicated dopaminergic, GABAergic, and glutamatergic neurotransmitter systems in determining these behaviors. A large collection of work is cited, which strongly implicates the above-mentioned neurotransmitter substances in the control of spontaneous locomotion. A smaller, but persuasive, body of evidence suggests that central nervous system processes utilizing these transmitters are involved in determining the effects of ethanol on locomotion. Particular emphasis has been placed on the mesolimbic ventral tegmental area to nucleus accumbens dopaminergic pathway, and on the ventral pallidum/substantia innominata, where GABA and glutamate have been found to play a role in altering the activity of this dopaminergic pathway. Research on ethanol and drug locomotor sensitization, increased responsiveness to the substance with repeated administration, is also reviewed as a process that may be important in the development of drug addiction.

Animals↗
PubMed2003

The dual factor structure of self-rated MDQ hypomania: energized-activity versus irritable-thought racing.

BACKGROUND: Bipolar II is diagnosed in a clinically depressed patient by documenting history of hypomania. Therefore, it is of great significance for both clinical and research purposes to characterize the factor structure of hypomania. METHODS: Among consecutive depressive outpatients-126 major depressives and 187 bipolar II-diagnosed by the Structured Clinical Interview for DSM-IV (Clinician Version), 181 who had clinically recovered from depression were administered the Mood Disorder Questionnaire (MDQ of. Am. J. Psychiatry 157, 1873). The MDQ is a newly developed, psychometrically validated self-report screening instrument for bipolar spectrum disorders. It screens for lifetime history of manic/hypomanic symptoms by including yes/no items covering all DSM-IV symptoms of mania/hypomania. The MDQ symptom interrelationships were studied by principal component analysis with varimax rotation. RESULTS: Hypomanic symptoms occurring in >50% were racing thoughts, increased energy and social activity, and irritability. Factor analysis revealed two factors: 'Energized-Activity' (eigenvalue=3.1) and 'Irritability-Racing Thoughts' (eigenvalue=1.5). LIMITATIONS: Cross-sectional assessment. CONCLUSIONS: Self-assessment of past hypomanic symptoms by patients, during clinical remission from depression, revealed two independent hypomanic factors, neither of which comprised euphoria. Hypomanic behavior appears to be more fundamental for the diagnosis of hypomania than elated mood accorded priority in DSM-IV; of hypomanic moods, irritability had greater significance than elation. It would appear that self-report of euphoria is less likely when hypomanias are brief (>or=2 vs. >or=4 days). The main implication for busy clinical practice is that energized activity and irritable mood associated with racing thoughts represent the modal experiences of hypomania among bipolar II outpatients; euphoria is neither sensitive, nor pathognomonic, in the diagnosis of these patients. These conclusions accord with recommendations made many years ago for the diagnosis of hypomania among cyclothymic patients [. Am. J. Psychiatry 134, 1227].

Bipolar Disorder↗
PubMed2005

Dopamine transporter gene associated with diminished subjective response to amphetamine.

Individual variability in responses to stimulant drugs may influence risk of stimulant abuse and treatment response. However, the genetic determinants of this variability have yet to be elucidated. The dopamine transporter is an important site of amphetamine action. Therefore, the dopamine transporter gene (DAT1) is a logical candidate gene to study. Using a drug challenge approach, we tested for association between DAT1 genotype and subjective responses to amphetamine in healthy adults. Volunteers participated in a double-blind, crossover design, randomly receiving placebo, 10 mg, and 20 mg oral D-amphetamine, and completed self-report measures on subjective effects including anxiety and euphoria. Subjects were genotyped for the DAT1 3'-untranslated region VNTR polymorphism and divided into groups based on genotype: homozygous for nine repeats (9/9, N=8), heterozygous (9/10, N=36) and homozygous for 10 repeats (10/10, N=52). The effects of amphetamine on ratings of Feel Drug, Anxiety, and Euphoria were examined with ANCOVA. In 9/10 and 10/10 subjects, amphetamine produced its expected effects of increased Euphoria, Anxiety, and Feel Drug (p<0.01). However, in 9/9 subjects, the effects of amphetamine were indistinguishable from placebo, suggesting that the 9/9 genotype has diminished subjective response to acute amphetamine. Interestingly, recent findings also implicate the 9/9 genotype in decreased therapeutic response to the stimulant methylphenidate in ADHD children. The current findings have important implications for understanding the genetic determinants of variability in stimulant response and risk of abuse.

3' Untranslated Regions↗
PubMed2000

Human pharmacology of 3,4-methylenedioxymethamphetamine ("ecstasy"): psychomotor performance and subjective effects.

3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a recreational drug of increasing use among youth because of its apparent entactogenic properties, such as euphoria, friendliness, closeness, and empathy. However, experimental studies have shown MDMA to be neurotoxic. Data on pharmacologic actions of MDMA in humans are limited. The authors conducted a randomized, double-blind, crossover, controlled trial to assess psychomotor performance and subjective effects in eight healthy male volunteers. MDMA was given in the same range of doses used for recreational purposes (75 and 125 mg). Amphetamine (40 mg) and placebo were used as reference compounds. For the digit-symbol substitution test (DSST), MDMA-125 produced a mild decrease in responses, and amphetamine produced a mild improvement. For the Maddox wing device, MDMA-125 induced esophoria compared with the other drug conditions. MDMA-125 and MDMA-75 produced increases in feelings of euphoria and well-being, as noted by increases in scores on the Addiction Research Center Inventory (ARCI) MBG and A scales, as well as scores of "stimulated," "good effects," "liking," and "high" on the visual analog scales. Amphetamine administration induced similar effects. At the same time, MDMA-125 enhanced sedation- and dysphoria-related effects (ARCI-PCAG and LSD, "confusion," "drunken," and Profile of Mood States Confusion scale). Mild changes in some body perception-related feelings were also reported after MDMA use, but hallucinations or psychoses were not present. In summary, the short-term administration of MDMA produced marked euphoria, a slight impairment in the performance of psychomotor tasks, and mild changes in body perceptions without hallucinations. These data support the abuse liability of MDMA.

Adult↗
PubMed2004

Duloxetine Treatment of Stress Urinary Incontinence in Women Does Not Induce Mania or Hypomania.

BACKGROUND: Mania is a rare but unwelcome side effect of treating depressed patients with antidepressants. This research sought to determine the risk of treatment-emergent mania or hypomania in women with stress urinary incontinence treated with duloxetine, a balanced dual serotonin-norepinephrine reuptake inhibitor currently under investigation for the treatment of both stress urinary incontinence and major depressive disorder. METHOD: Data were obtained from 4 double-blind, randomized, placebo-controlled studies involving 1913 women aged 22 to 83 years and 4 ongoing uncontrolled longer-term studies involving 1877 women aged 20 to 87 years. In all studies, women had the predominant symptom of stress urinary incontinence; in the active treatment arms, all women received duloxetine 80 mg/day. Women receiving antidepressants for major depressive disorder were excluded. In the placebo-controlled studies, 1 woman reported a history of bipolar disorder and 74 women reported a history of depression. In the uncontrolled longer-term studies, 1 woman reported a history of bipolar disorder and 69 reported a history of depression. RESULTS: In the placebo-controlled trials, 1 woman treated with duloxetine reported euphoria, while 1 reported mania and 1 reported euphoria when on placebo. In the uncontrolled longer-term studies, 1 woman reported mania; 1, euphoria; and 4, elevated moods. No women discontinued the study due to treatment-emergent mood elevation. CONCLUSION: These data suggest that duloxetine does not induce mania or hypomania in women with stress urinary incontinence in this population, in which few women had a history of bipolar disorder or depression and women on antidepressants were excluded.

Journal Article↗
PubMed2001

Abuse liability of diazepam through different routes.

Abuse liability of diazepam was examined among experienced drug users. The subjects, randomly divided into two groups, each having eight subjects, received diazepam, 15 mg intravenously (gr. 1) and 30 mg orally (gr. 2). Subjective states, drug liking, sedation and euphoria were assessed at pre-drug, 15 min, 120 min and 240 min post-drug administration. In addition, brief assessment to evaluate euphoria and sedation was carried out at 5 min and 45 min for subjects in gr. 1, and at 45 min and 150 min for those in gr. 2. Plasma diazepam level was also estimated. Results indicate those subjects in gr. 1 reported quicker and higher euphoria, drug liking, subjective effects and higher plasma level. The study suggests that route of administration of a compound which has faster onset of action is associated with more liability of abuse.

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↗