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PubMed1975

Clinical pharmacology of nabilone, a cannabinol derivative.

Nabilone is a modified cannabinol derivative with central nervous system activity. Administration of nabilone in single doses of 1 to 5 mg results in dose-related pharmacologic effects in man. One and 2.5 mg doses of nabilone induced relaxant and sedative effects in all subjects. No euphoria, dry mouth, tachycardia, or postural hypotension was seen after 1 mg, minimal effects were seen after 2.5 mg, and marked effects were seen after 5 mg. Effects were evident within 60 to 90 min and persisted for 8 to 12 hr. Nabilone produced no significant tachycardia. There were no changes in supine blood pressure; however, marked postural hypotension occurred after the 5-mg dose. The administration of nabilone at doses of 1 mg or 2 mg two times daily resulted in euphoria and dry mouth during the first two days of drug; thereafter tolerance developed to these effects but there was no apparent decrease in relaxation. Subjects challenged with a single 5-mg dose of nabilone showed a 66% reduction in symptoms and signs after the 7-day drug period compared to that of the same dose after 1 wk of placebo. Comparison of nabilone with other cannabinol derivatives suggests that some of the undesirable pharmacologic effects can be separated within the group.

Adult↗
PubMed1986

Instrumental analysis of ethanol-induced intoxication in human males.

A study was conducted to assess subjective reports of intoxication during the ascending phase of the plasma ethanol curve. Eighteen male social drinkers were divided into three groups and were given either placebo, 0.347 g/kg ethanol or 0.694 g/kg ethanol under double-blind conditions. Subjects reported levels of intoxication both instrumentally, by moving a joystick device, and verbally using an 11-point self-rating scale. Compared to placebo, ethanol produced significantly higher verbal self-rating scores, but there were no differences in the scores between the low- and high-dose ethanol groups. Instrumental responses of ethanol effects did, however, distinguish between the two ethanol treatments. All subjects who received ethanol reliably detected its effects when plasma ethanol levels reached 32 mg/dl, but only the subjects who received the high dose reported episodes of intense well-being or euphoria. Ethanol-induced euphoria occurred while plasma ethanol levels were rapidly rising, and was characterized by multiple, paroxysmal episodes that typically lasted about 3 min each. This study demonstrated that a continuously available instrumental response provided sensitive and reliable measures of rapidly changing behavioral states associated with ethanol-induced intoxication.

Adult↗
PubMed1996

Subjective responses to d-amphetamine alone and after pimozide pretreatment in normal, healthy volunteers.

The role of dopamine in d-amphetamine-induced euphoria has not been systematically examined in normal volunteers. Therefore, we examined the effects of the dopamine antagonist, pimozide, on responses to d-amphetamine in healthy volunteers, using a within-subjects, double-blind design. Ten subjects received single oral doses of d-amphetamine (0, 10, 20 mg) 2 hours following pretreatment with pimozide (0, 1, 2 mg). Subjective, behavioral, and physiological effects were assessed predrug and for 3 hours after d-amphetamine administration. d-Amphetamine alone produced prototypic effects on a variety of measures, including euphoria and drug liking. Pimozide did not produce any effects when administered alone and produced inconsistent effects on responses to d-amphetamine. Although higher doses of pimozide may be needed to antagonize the euphorigenic effects of d-amphetamine, these results raise the possibility that the role of dopamine in the subjective effects of stimulants may be more complex than initially appreciated.

Adult↗
PubMed1982

Circulating opioids: possible physiological roles in central nervous function.

Evidence is reviewed regarding the release of endorphins by such diverse conditions as stress, long distance running, acupuncture, sexual activity, suggestion and ritualistic dancing ceremonies. Additional evidence is cited regarding possible physiological roles of endorphins in antinociception, socialization, euphoria, some mental disorders, drive states and vegetative functions. The concentration of this latter type of evidence is on conditions during which endorphins seem to be exerting effects on a number of different systems together (for example, euphoria is almost always accompanied by analgesia), and the possibility is suggested that the activation of a number of functions together may be due to a global activation of opiate receptors throughout the CNS. A possible basis for this global activation arises from results from this laboratory indicating the presence of a blood-borne opioid hormone, secreted by the pituitary or by an endocrine gland under pituitary control, which is capable of passing from the blood into the CNS. This diffuse endorphinergic system, which is complementary to the well-established endorphinergic neuronal systems in the CNS, thus derives its property of global action on opiate receptors by the diffuse means by which the hormone reaches its target sites, i.e., by passing through the blood brain barrier. Thus, while each specific endorphin-mediated function can be activated by the activation of its respective neural pathway, it is proposed that the hormonal endorphinergic mechanism is activated to produce a global response provoked by conditions to which a more generalized response, including physiological and behavioural changes, is most appropriate.

Animals↗
PubMed1986

Simulation of gambling responses on the Addiction Research Center Inventory.

The present study investigated possible commonalities between compulsive gambling and abuse of psychoactive drugs. Nineteen volunteers with histories of compulsive gambling were tested twice using the Addiction Research Center Inventory (ARCI): Once answering items as they felt at the time of the test, the other time simulating how they felt while winning at gambling. The main findings were that, as measured on the ARCI, "simulated winning at gambling" produced a euphoria similar to the euphoria induced by the psychoactive drugs of abuse, particularly psychomotor stimulants; secondly, that as a group, the pathological gamblers, demonstrated elevated psychopathy scale scores similar to psychopathy scores found among persons with histories of drug dependence.

Adult↗
PubMed1986

Comparison of intravenously administered methadone, morphine and heroin.

Data from previously reported studies suggest that methadone may be more euphorigenic than other morphine-like drugs. To determine whether methadone is more potent in producing euphoria relative to its other opiate-like effects, single doses of intravenously administered methadone, morphine, heroin and placebo were compared in non-dependent post-addict volunteers. Morphine-like physiologic, subjective and behavioral effects were measured periodically for 24 h after drug administration. Under the conditions of the experiment methadone produced a profile of effects which was indistinguishable from that of morphine and heroin. Only the time course of miosis, which was longer lasting following methadone, differentiated among the three compounds. The relative potencies of methadone, morphine and heroin for the initial 5 h of effect were constant over all opiate-like effects, including measures of euphoria. Thus, methadone was not a selective euphoriant.

Adult↗
PubMedDate not supplied

Single-dose ritanserin and alcohol in healthy volunteers: a placebo-controlled trial.

A double blind cross-over design trial was carried out to investigate the effect of simultaneous administration of alcohol (0.5 g/kg) and ritanserin (10 mg) on biological and behavioral functioning. Twenty healthy volunteers were selected to participate in the study. To assess the effect of treatments the following evaluations were performed: psychomotor tests, vital signs, intoxication, euphoria, and mood. In addition, ritanserin and alcohol plasma concentration were measured. Psychomotor performance and vital signs during the ritanserin session did not differ significantly from the placebo session. Similar results were obtained in regard to alcohol intoxication, euphoria, and mood, except for tiredness and alertness, which were significantly different compared to placebo. Differences in blood alcohol concentration between the ritanserin and the placebo sessions did not attain significance. Plasma ritanserin concentration was 143 ng/ml 1 h after alcohol administration and decayed to 53 ng/ml 6 h after alcohol consumption in the active treatment session. Our findings tend to indicate that ritanserin neither enhances the central nervous system depressant effect of alcohol nor produces a pharmacokinetic interaction during acute alcohol ingestion.

Adult↗
PubMed1996

The serial measurement of mood in two brothers, renal transplant recipient and donor.

The object of this study was to demonstrate the importance of serial rather than single mood measurement in patients with fluctuating moods. We serially measured anxiety, sadness, and euphoria in two brothers, renal transplant recipient and donor, for 5 months postoperatively, using the Zung State Depression Scale, the Spielberger State Anxiety Scale, and a composite scale measuring euphoria. The results were plotted in an affect chart. The affect chart of the transplant recipient who had a postoperative mixed mood disorder, showed a widely fluctuating pattern. The affect chart of his brother, who had an affectively quiet postoperative course, showed a more stable pattern. Single mood measures in complex and fluctuating affective states give an incomplete picture, which may account for some confusion in the literature. Serial mood measurement more accurately describes complex affective states. This methodology may be useful in consultation-liaison research where the affective pattern itself is being used as an outcome measure.

Affect↗
PubMed2000

Increased CSF volumes are associated with diminished subjective responses to cocaine infusion.

We evaluated the hypothesis that ventricular and cortical CSF volume increases are associated with reductions in the magnitude of euphoric effects produced by intravenous IV cocaine infusion in cocaine dependent (CD) individuals. Eleven CD patients participating in a cocaine-infusion study and eleven control subjects underwent magnetic resonance imaging (MRI). Two CSF regions of interest (lateral ventricles and frontal cortex CSF) and two comparison regions (third ventricle and posterior cortex CSF) were measured. Self-reported ratings of the intensity of euphoric response ("high") were obtained from the CD subjects at 3, 10, and 30 minutes after IV administration of cocaine. A significant negative correlation was observed between the volume of the lateral ventricles and subjective ratings of the "high" experienced at 3 minutes, but not at 10 and 30 minutes after cocaine infusion. In contrast, a significant negative correlation between frontal cortex CSF volume and the intensity of euphoric response was observed at 30 minutes after IV cocaine. No significant associations were observed between the volumes of the two comparison regions and any subjective ratings of "high." No significant volume differences were observed between the CD and control groups in any region. The results suggest larger lateral ventricular volumes are associated with a decrease in immediate euphoria while larger frontal cortex CSF volumes are associated with a decrease in the duration of the euphoria induced by cocaine infusion. The age-related brain volume reductions underlying the volume increase in these two CSF spaces may be the neurobiological basis of the age-related reduction in the rates of addiction.

Adult↗
PubMed1983

Abuse potential of halazepam and of diazepam in patients recently treated for acute alcohol withdrawal.

Thirty men recently treated for alcohol withdrawal were enrolled in a three-way crossover double-blind study with a balanced incomplete block design. Patients received single doses of three of the following: halazepam, 320 mg; halazepam, 160 mg; diazepam, 40 mg; diazepam, 20 mg; and placebo. The doses of the drugs were approximately equivalent in anxiolytic effect. Patients rated themselves at baseline, 30 min after, and 1, 2, 3, 4, 6, and 8 hr after drug on the following: euphoria, sedation, "drug-liking," "feeling the drug," and drug identification. By 30 min both diazepam groups reported increases in euphoria, sedation, and feeling and liking the drug; halazepam groups reported little subjective change at 30 min, and at 1 hr subjective effects did not differ from placebo on any scale. At 2 and 3 hr, both halazepam doses induced subjective effects on several scales, but peak effects were lower than peak effects of high diazepam doses. Unlike diazepam, the higher halazepam dose did not appear to induce greater effects than the lower dose. At peak, more of the diazepam group correctly identified the drug than those in the halazepam groups. More in the halazepam groups identified it as placebo than either diazepam group. To the degree that abuse potential is related to peak intensity and to time of onset of those subjective effects described as pleasant or likable, halazepam should have a lower potential for abuse than diazepam.

Adult↗
PubMedDate not supplied

Cortical gray matter volumes are associated with subjective responses to cocaine infusion.

We analyzed the relationship between cocaine-induced euphoria and measures of frontal and temporal gray matter volumes in eleven cocaine-dependent (CD) patients who underwent magnetic resonance imaging (MRI). Self-reported ratings of the intensity of euphoric response to cocaine infusion were obtained from the CD subjects at 3, 10, and 30 minutes after cocaine infusion. Significant positive correlation between frontal and temporal cortical gray matter volume and the intensity of euphoria was observed at 10 minutes after IV cocaine. The data suggest that frontal and temporal lobe gray matter volume is associated with some of the reinforcing effects of cocaine. Given the well-established negative linear relationship between cortical gray matter volume and age, cortical gray matter volume may be a marker for the neurobiological substrate of the age-related reduction in addiction rates.

Adult↗
PubMed2005

Early carbon monoxide intoxication: happy to be poisoned?

Carbon monoxide poisoning is the commonest cause of death by poisoning in the UK and chronic exposure is thought to be a frequently missed diagnosis. Early recognition of carbon monoxide poisoning is vital to institute prompt treatment and to prevent exposure to others. An incident of mass exposure to carbon monoxide is presented where euphoria, lasting several hours, was the only symptom reported in approximately one quarter of the casualties. This has not been reported previously and we believe that mild carbon monoxide intoxication should be included in the list of differential diagnoses of inappropriate euphoria.

Adolescent↗
PubMed1982

Analgesic and euphoric effects of high dose diazepam in schizophrenia.

Schizophrenics treated with high doses of diazepam (150-200 mg/day) showed marked analgesia besides certain antipsychotic effects. Euphoria was noticed in some of the patients. We hypothesized that influence on the endorphin metabolism might contribute to these clinical effects. Therefore, we measured pain threshold by three different methods before and during diazepam treatment. All patients exhibited a 1.5- to 2-fold increase of pain perception. Further, using a double-blind design, the opiate antagonist naloxone (30 mg i.v.) was administered. A significant decrease but not a complete block of the euphoric state and of analgesia was achieved. It is, therefore, concluded that other pharmacological properties of diazepam might be involved in the diazepam-induced euphoria and analgesia in man.

Adult↗
PubMed1990

Addictiveness of central stimulants.

Central stimulants have been abused since their inception and we are currently in the midst of a cocaine epidemic that challenges our resources and capabilities. Through their actions on powerful endogenous reward centers, central stimulants produce intense euphoria that reinforces subsequent usage and eventual dependence. Considerable evidence indicates that the activation of dopamine circuits mediates stimulant reward. With regard to cocaine, it has been hypothesized that depletion of central dopamine leads to craving. Euphoria and craving, the key dynamics of stimulant addiction, may therefore result largely from neurochemical alterations of dopamine systems in the brain's reward center. Progressive deterioration of the stimulant addict involving medical, psychiatric, and psychosocial impairment occurs rapidly, underscoring the addiction potential of these agents. Tolerance, sensitization and withdrawal phenomena are discussed from clinical and neurochemical perspectives.

Amphetamines↗
PubMed1983

Methadone maintenance treatment: the other side of the coin.

The psychopharmacological rationale and clinical effectiveness of the methadone maintenance treatment program was subjected to critical theoretical and methodological analysis. It was concluded (1) that the MMTP constitutes and perpetuates an immature coping mechanism; i.e., "subliminal euphoria"--pervasive pharmacological shielding of addicts from the inevitable discomforts attending adaptation to the real world; (2) that it does not satisfy so-called tissue craving for florid euphoria because most "stabilized" clients actively seek and obtain same from heroin, methadone itself, and/or other potentially euphorogenic drugs; (3) that the source of this craving resides in the addict's personality rather than in his tissues; (4) that official evaluation studies of the MMTP grossly exaggerate its clinical effectiveness; and (5) that the MMTP has inadvertently created incomparably more primary methadone addicts than it has cured heroin addicts.

Drug Tolerance↗
PubMed1975

The effects of lithium carbonate upon subjective state changes induced by sodium pentobarbital.

Behavioral and mood changes were measured for 8 normal male subjects after oral administration of sodium pentobarbital (3 mg/kg body weight). This procedure was repeated on three occasions: firstly a drug-free condition; then a condition following two weeks of maintenance 0.7 to 1.2 MEQ/L lithium carbonate; and then another drug-free condition. Intial analyses indicated a lowering of the level of euphoria reached in the lithium pentobarbital condition below that achieved after pentobarbital alone. Examination of this effect showed that the reduction after pentobarbital plus lithium was mirrored by a reduction in the baseline for the same response items due to lithium alone. The lessening of euphoria appeared to result from a general lowering of affect due to lithium maintenance. More detailed analyses showed that the quantitative response to pentobarbital was in no case reduced by lithium condition. Certain reversal effects were also discovered in which lithium plus pentobarbital acted in the opposite direction from pentobarbital alone.

Adult↗
PubMed1992

Buprenorphine attenuates the effects of cocaine on adrenocorticotropin (ACTH) secretion and mood states in man.

Adrenocorticotropin (ACTH) levels in plasma increased rapidly to 105% above baseline within 5 minutes after intravenous injection of cocaine (30 mg) in cocaine-dependent men. The time course of ACTH stimulation paralleled increases in plasma cocaine levels and self-reports of salient drug effects on mood states and did not occur after placebo administration. An opioid mixed agonist-antagonist, buprenorphine (4 mg/day sublingually), suppressed the acute cocaine-induced stimulation of both ACTH and euphoria. Buprenorphine's suppression of postcocaine ACTH and euphoria were not related to differences in plasma cocaine levels or cocaine-induced alterations of cardiovascular function.

Adrenocorticotropic Hormone↗
PubMed1992

Vehicle injuries to joggers. Case report and review.

A medico-legal case is presented where a jogger was struck by a car while crossing an intersection and later sought major damages in a civil court. This incident is reviewed in the context of overall information on injury to joggers by vehicles, and the possibility (raised by the defendant's counsel) that the euphoria generated by prolonged exercise may have created a sense of "invincibility" that predisposed the jogger to reckless actions. The defendants argued that the young man concerned was taking an amount of exercise that could have led to a jogging addiction and alteration of consciousness in a susceptible individual, and a history of alcohol, drug and video addiction was advanced as evidence that he may indeed have been a susceptible person. During the actual incident, the jogger recognised that the driver of the vehicle had not seen him, but nevertheless he proceeded to enter a crosswalk that had already been 75% traversed by the car, leaving himself only 0.6 metres of space, a half of the lane width normally required by a runner. A calculation of the relative velocities of the car and the jogger suggests that the latter must have veered 1-2 metres onto the main highway in order to pass in front of the care and be hit from the side. The behaviour of the jogger was plainly reckless, but more information is needed on the relative incidence of traffic injuries in joggers and walkers, on the prevalence of jogging addiction, and on diagnostic criteria for this condition before the accident could be categorically attributed to a jogging-related euphoria.

Accidents, Traffic↗