heroin and Cognition-Disorders

Over the past decade fatal opioid overdose has emerged as a major public health issue internationally. This paper examines the risk factors for overdose from a biomedical perspective. While significant risk factors for opioid overdose fatality are well recognized, the mechanism of fatal overdose remains unclear. Losses of tolerance and concomitant use of alcohol and other CNS depressants clearly play a major role in fatality; however, such risk factors do not account for the strong age and gender patterns observed consistently among victims of overdose. There is evidence that systemic disease may be more prevalent in users at greatest risk of overdose. We hypothesize that pulmonary and hepatic dysfunction resulting from such disease may increase susceptibility to both fatal and non-fatal overdose. Sequelae of non-fatal overdose are recognized in the clinical literature but few epidemiological data exist describing the burden of morbidity arising from such sequelae. The potential for overdose to cause persisting morbidity is reviewed.

Topics: Adolescent; Adult; Age Factors; Cognition Disorders; Drug Interactions; Drug Tolerance; Female; Hepatitis C, Chronic; Heroin; Heroin Dependence; Humans; Male; Pneumonia, Bacterial; Respiration; Respiratory Insufficiency; Risk Factors; Risk-Taking; Sex Factors; Smoking

Groups of subjects whose primary drug of abuse was amphetamine or heroin were compared, together with age- and IQ-matched control subjects. The study consisted of a neuropsychological test battery which included both conventional tests and also computerised tests of recognition memory, spatial working memory, planning, sequence generation, visual discrimination learning, and attentional set-shifting. Many of these tests have previously been shown to be sensitive to cortical damage (including selective lesions of the temporal or frontal lobes) and to cognitive deficits in dementia, basal ganglia disease, and neuropsychiatric disorder. Qualitative differences, as well as some commonalities, were found in the profile of cognitive impairment between the two groups. The chronic amphetamine abusers were significantly impaired in performance on the extra-dimensional shift task (a core component of the Wisconsin Card Sort Test) whereas in contrast, the heroin abusers were impaired in learning the normally easier intra-dimensional shift component. Both groups were impaired in some of tests of spatial working memory. However, the amphetamine group, unlike the heroin group, were not deficient in an index of strategic performance on this test. The heroin group failed to show significant improvement between two blocks of a sequence generation task after training and additionally exhibited more perseverative behavior on this task. The two groups were profoundly, but equivalently impaired on a test of pattern recognition memory sensitive to temporal lobe dysfunction. These results indicate that chronic drug use may lead to distinct patterns of cognitive impairment that may be associated with dysfunction of different components of cortico-striatal circuitry.

Topics: Adolescent; Adult; Amphetamine-Related Disorders; Amphetamines; Analysis of Variance; Attention; Chronic Disease; Cognition Disorders; Female; Heroin; Heroin Dependence; Humans; Language Tests; Male; Memory; Middle Aged; Neuropsychological Tests; Pattern Recognition, Visual; Reaction Time; Set, Psychology

A 29-year-old man was admitted for acute cognitive impairment. Three weeks earlier, he had been admitted for coma due to sniffed heroin abuse responsive to naloxone infusion. At admission, the patient presented with apraxia, severe memory impairment and anosognosia. Brain MRI revealed symmetric hyperintensities of supratentorial white matter, sparing brainstem and cerebellum, on FLAIR and B1000 sequences. Four months later, repeated neuropsychological assessment revealed dramatic improvement of global cognitive functions. Toxic leucoencephalopathy excluding the cerebellum and brainstem is a rare complication of heroin abuse, and seems to concern especially patients that use heroin by sniff or injection. In these patients, cognitive troubles are predominant, prognosis seems better and infratentorial brain structures can be spared. In conclusion, our observation emphasizes that heroin-induced encephalopathy can have a favourable outcome and that imaging and clinical patterns can indicate the mode of drug administration.

Topics: Administration, Inhalation; Adult; Brain; Cognition Disorders; Heroin; Heroin Dependence; Humans; Leukoencephalopathies; Magnetic Resonance Imaging; Male; Narcotics; Neuropsychological Tests

Serious leukoencephalopathy can be related to heroin injection or inhalation.. We report the first case of leukoencephalopathy observed three weeks after a 46-year-old man sniffed heroin. The clinical presentation included cognitive and behaviour disorders, pyramidal irritation and slight gait instability. Blood and cerebrospinal fluid analyse were normal. Brain magnetic resonance imaging showed diffuse, symmetrical supratentorial white matter lesions producing high intense signals on FLAIR and b1000-weighted sequences. Proton spectroscopy revealed an increased rate of cholin, in favour of active demyelinated lesions. Brain biopsy showed intramyelinic oedema with reactive gliosis. After two and a half years, moderate attentional fluctuations and difficulties in initiating activities persisted. Repeated MRI showed a reduction of the leukoencephalopathy.. Heroin could be a cause more common than thought of leukoencephalopathy. The clinical and radiological expression and prognosis could be related to the mode of consummation (inhalation, intravenous injection, sniffing). This parameter may modulate severity and localization of brain lesions. More systematic use of MRI for patients with psychiatric symptoms after heroin intoxications could lead to a better evaluation of heroin-related neurotoxicity and potentially improve prevention.

Topics: Administration, Inhalation; Biopsy; Brain Chemistry; Brain Edema; Choline; Cognition Disorders; Demyelinating Diseases; Gliosis; Heroin; Heroin Dependence; Humans; Leukoencephalopathies; Magnetic Resonance Imaging; Male; Middle Aged; Narcotics; Prognosis

Cell therapies in animal models of neurobehavioral defects are normally derived from neural stem cells (NSC) of the developing cortex. However, the clinical feasibility of NSC therapies would be greatly improved by deriving transplanted cells and from a tissue culture source that is self-renewing, containing cells that potentially differentiate into the desired neuronal phenotypes. These cultures can be engineered to contain the appropriate factors to support their therapeutic action and likely evoke lesser immune reactions. In the current study, we employed our model of mice neurobehaviorally impaired via prenatal exposure to heroin, to test the therapeutic efficacy of NSC derived from murine embryonic stem cells culture (ESC). The culture contained elongated bipolar cells, 90% of which are positive for nestin, the intermediate filament protein found in neural precursors. After removal of growth factors, the NSC differentiated into neurons (34.0% +/- 3.8% NF-160 positive), including cholinergic cells (ChAT positive), oligodendrocytes (29.9% +/- 4.2% O(4)), and astrocytes (36.1% +/- 4.7% GFAP positive). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis confirmed the immunocytochemical findings. Mice made deficient in Morris maze behavior by prenatal heroin exposure (10 mg/kg heroin s.c. on gestational days 9-18) were transplanted into the hippocampus region on postnatal day 35 with the ES culture-derived NSC (ES-NSC) labeled with dialkylcarbocyanine (Dil) cell tracker. Dil+ and NF160+ cells were detected in the hippocampal region (50% +/- 8% survival). The transplantation completely restored maze performance to normal; e.g., on day 3, transplantation improved the behavior from the deficient level of 11.9-sec latency to the control of 5.6-sec latency (44.5% improvement).

Topics: Animals; Cell Differentiation; Cell Survival; Cognition Disorders; Disease Models, Animal; Embryonic Stem Cells; Female; Heroin; Male; Maze Learning; Mice; Narcotics; Neurogenesis; Neurons; Opioid-Related Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Stem Cell Transplantation; Stem Cells

Prescribing of injectable diacetylmorphine (DAM) for heroin dependence has raised concerns about its safety. In light of various reports by heroin-maintained patients of DAM-related adverse events, and previously established unwanted effects of opioids in pain management, we undertook a survey in February 2001 of a random sample of 132 (127 participated) of 1061 patients prescribed DAM in Switzerland at that time. The purpose was to document the prevalence rates of a list of unintended symptoms experienced and attributed to DAM by patients. To assess symptom complaints and other data, staff administered a six-page self-report questionnaire. The patients ascribed numerous symptoms to DAM, with the best-known being the most frequently reported (e.g. skin itching, sweating, constipation). Among potentially more problematic complaints ranged irregular menses, cognitive deficits, muscle twitches, labored breathing, pains in the cardiac region, and temporary paralysis of limbs. In the absence of a control group, however, these may also be due to other factors, such as expectation, co-medication, concomitant substance use or co-morbidity. This pilot study emphasizes the necessity of rigorous assessment of the true rates, types, severity and preventability of such complications, especially given the current efforts to establish heroin maintenance as an optional treatment for heroin dependence.

Topics: Adult; Cognition Disorders; Drug Prescriptions; Female; Health Status; Heroin; Heroin Dependence; Humans; Male; Myoclonus; Narcotics; Substance-Related Disorders; Surveys and Questionnaires; Time Factors

Chronic exposure to heroin is known to cause cognitive deficits. However, little is known about the underlying molecular mechanisms. It has been suggested that opiate-induced neurotoxicity as well as impaired plasticity and regeneration may be relevant. One of the target regions where regeneration still can be observed in the adult brain is the hippocampus. Since polysialic acid neural cell adhesion molecule is regarded as one of the key players involved in plasticity and regeneration of neural tissue, we analyzed polysialic acid neural cell adhesion molecule expression in the fascia dentate hilus of the human hippocampus of 29 lethally intoxicated heroin addicts and matched controls. Immunohistochemistry with an antibody directed against polysialic acid neural cell adhesion molecule revealed its expression in differently sized cells which could be identified as neurons and glial cells. We observed an increase in the percentage of polysialic acid neural cell adhesion molecule positive neurons in hippocampal hilus of heroin addicts compared with controls (P = 0.001).Interestingly, we also observed polysialic acid neural cell adhesion molecule expression in glial cells as evidenced by double immunofluorescence with glial fibrillary acidic protein and polysialic acid neural cell adhesion molecule using confocal laser scanning microscopy. The fraction of polysialic acid neural cell adhesion molecule positive glial cells was also higher in heroin addicts compared with controls (P = 0.009). In addition, within the group of addicts morphine blood concentrations showed a positive correlation with the percentage of polysialic acid neural cell adhesion molecule positive neurons (P = 0.04; r = 0.547). In conclusion, we observed an increase in polysialic acid neural cell adhesion molecule positive neurons and glial cells in hippocampi of heroin addicts. This might reflect an attempt to repair cell damage due to heroin exposure.

Topics: Adolescent; Adult; Biomarkers; Cognition Disorders; Dose-Response Relationship, Drug; Female; Glial Fibrillary Acidic Protein; Heroin; Heroin Dependence; Hippocampus; Humans; Male; Narcotics; Nerve Regeneration; Neural Cell Adhesion Molecule L1; Neuroglia; Neuronal Plasticity; Neurons; Sialic Acids; Up-Regulation

Recent studies provide evidence for specific aspects of cue processing in addictive disorders.. The present study employs event related potentials (ERPs) to investigate heroin related visual information processing.. Neutral and heroin related pictures were presented to 19 male abstinent heroin dependent patients and 14 male healthy controls.. Patients exhibited larger slow positive wave (SPW) components of the ERP on heroin related pictures than on neutral pictures. Within healthy control subjects there was no difference on the SPW between neutral and heroin pictures. Within heroin dependent patients, mean SPW response to heroin pictures was correlated with post-experiment craving.. This study provides neurophysiological evidence that information processing of drug-related information is abnormal in heroin dependent patients. The results provide further evidence for the cognitive and neurobiological accounts of substance dependence such as the incentive-sensitization theory.

Topics: Behavior, Addictive; Cognition Disorders; Cues; Electroencephalography; Electrooculography; Evoked Potentials, Visual; Heroin; Heroin Dependence; Humans; Male; Mental Processes; Photic Stimulation; Reaction Time

Few well-controlled studies have examined psychomotor and cognitive performance in methadone maintenance patients (MMP). In the present study, performance of 18 opioid-dependent MMP was evaluated relative to that of 21 control participants without substance abuse histories. The MMP and control groups were balanced with respect to gender, race, age, years of education, current employment status, current reading level, and estimated IQ score. Recent drug abstinence was verified by urine testing. Participants with a urine screen positive for benzodiazepines or a breathalyzer test positive for alcohol prior to performance testing were excluded. To avoid testing under conditions of acute heroin or cocaine intoxication, but without testing under conditions of acute withdrawal, participants with current use of heroin or cocaine were only required to abstain for 24 h prior to performance testing. MMP exhibited impairment relative to controls in psychomotor speed (digit symbol substitution and trail-making tests), working memory (two-back task), decision making (gambling task), and metamemory (confidence ratings on a recognition memory test); results also suggested possible impairment in inhibitory mechanisms (Stroop color-word paradigm). MMP did not exhibit impairment in time estimation, conceptual flexibility or long-term memory. The wide range of impaired functions is striking, and may have important implications for daily functioning in MMP. Further research is necessary to determine the clinical significance of the impairments in laboratory-based tests for daily performance in the natural environment, as well as to differentiate impairments due to acute methadone dosing, chronic methadone maintenance, chronic poly-drug abuse, and other factors.

Topics: Adult; Cocaine; Cocaine-Related Disorders; Cognition Disorders; Concept Formation; Female; Heroin; Heroin Dependence; Humans; Male; Mental Recall; Methadone; Neuropsychological Tests; Problem Solving; Psychometrics; Psychomotor Performance; Reaction Time; Retention, Psychology; Risk Factors; Substance Abuse Detection; Time Perception

The present study examined differences in neuropsychological performance among chronic cocaine, alcohol, and polysubstance abusers. A comprehensive neuropsychological battery was completed by 355 incarcerated adult male felons who were classified by DSM-IV criteria into four subgroups: (1) alcohol dependence or abuse (ETOH) (n = 101), (2) cocaine dependence or abuse (COC) (n = 60), (3) polysubstance dependence or abuse (POLY (n = 56), and (4) a group of age and education matched adult male felons with no history of drug abuse (n = 138). Results showed no significant differences in neuropsychological performance between COC and control subjects. However, both the POLY and ETOH groups were found to perform significantly worse on nearly all measures compared to the COC and control groups. Further, analysis of neuropsychological domains showed the POLY group to perform significantly worse compared to the other groups in the areas of short-term memory, long-term memory and visual motor ability. Correlations between neuropsychological performance and length of abstinence from drug use showed the ETOH group to have made the greatest amount of improvement on individual measures and domains. The COC group showed the least amount of improvement, but their performance was not significantly different from controls. Results provide further support for the differential effects of drug use on neuropsychological functioning.

Topics: Adult; Alcohol Drinking; Alcohol-Related Disorders; Amphetamines; Chi-Square Distribution; Cocaine; Cocaine-Related Disorders; Cognition Disorders; Cross-Sectional Studies; Drug Interactions; Forensic Psychiatry; Heroin; Humans; Male; Multivariate Analysis; Neuropsychological Tests; Prisoners; Substance-Related Disorders; Time Factors

Topics: Administration, Inhalation; Adult; Brain; Cognition Disorders; Heroin; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Prion Diseases; Substance-Related Disorders

Twenty-five HIV-seropositive drug abusers (DA+HIV+) (groups II-III and IV [A, C2 and E] of the CDC classification) were evaluated by use of the WAIS scale to determine any possible involvement of cognitive functions in the not yet overt phases of AIDS. The results were compared with those obtained in two control populations composed of 19 seronegative drug abusers (DA+HIV-) and 24 healthy subjects (DA-HIV-) to evaluate, in addition to the disease, the possible effect of the use of alcohol and toxic substances on cognitive performance. In spite of the small number of subjects, the study indicated that drug abuse is the main factor, among those analyzed, in determining a decline in cognitive functions.

Topics: Acquired Immunodeficiency Syndrome; Adult; Brain; Cognition Disorders; Dementia; Ethanol; Female; Heroin; HIV Seropositivity; HIV-1; Humans; Italy; Male; Risk Factors; Severity of Illness Index; Substance Abuse, Intravenous; Substance-Related Disorders; Task Performance and Analysis; Wechsler Scales