Uncontrolled eating in healthy women has limited influence on food cue reactivity and food-related inhibitory control.

Uncontrolled eating-in the general population-is characterized by overeating, hedonic hunger and being drawn towards palatable foods. Theoretically, it is the result of a strong food reward signal in relation to a poor ability to exert inhibitory control. How food consumption influences inhibitory control and food cue sensitivity, and how this relates to the continued urge to eat, remains unclear. We used fMRI in order to investigate the neural mechanism underlying food cue reactivity and food-specific response inhibition (go-nogo task), by comparing women reporting high (n = 21) versus low/average (n = 19) uncontrolled eating across two sessions: during an inter-meal state and after consumption of a high-caloric snack. We found no effects of individual differences in uncontrolled eating, food consumption, nor their interaction on food cue reactivity. Differences in uncontrolled eating and food consumption did interact in modulating activity in an occipital-parietal network, extending from left lateral superior occipital cortex to visual cortex, cuneal cortex, and precuneus during response inhibition of non-food stimuli, areas previously associated with successful nogo-vs. go-trials. Yet, behavioural performance on the go-nogo task was not modulated by uncontrolled eating nor food consumption. Women with a low/average tendency for uncontrolled eating may need more cognitive resources to support successful response inhibition of non-food stimuli during food 'go' blocks in an inter-meal state, whereas women with a high tendency for uncontrolled eating showed this after food consumption. However, considering current and previous findings, it seems that individual differences in uncontrolled eating in healthy women have only limited influence on food cue reactivity and food-related inhibitory control.

Beneficial Effect of Sodium Nitrite on EEG Ischaemic Markers in Patients with Subarachnoid Haemorrhage.

Subarachnoid haemorrhage (SAH) is associated with long-term disability, serious reduction in quality of life and significant mortality. Early brain injury (EBI) refers to the pathological changes in cerebral metabolism and blood flow that happen in the first few days after ictus and may lead on to delayed cerebral ischaemia (DCI). A disruption of the nitric oxide (NO) pathway is hypothesised as a key mechanism underlying EBI. A decrease in the alpha-delta power ratio (ADR) of the electroencephalogram has been related to cerebral ischaemia. In an experimental medicine study, we tested the hypothesis that intravenous sodium nitrite, an NO donor, would lead to increases in ADR. We studied 33 patients with acute aneurysmal SAH in the EBI phase. Participants were randomised to either sodium nitrite or saline infusion for 1 h. EEG measurements were taken before the start of and during the infusion. Twenty-eight patients did not develop DCI and five patients developed DCI. In the patients who did not develop DCI, we found an increase in ADR during sodium nitrite versus saline infusion. In the five patients who developed DCI, we did not observe a consistent pattern of ADR changes. We suggest that ADR power changes in response to nitrite infusion reflect a NO-mediated reduction in cerebral ischaemia and increase in perfusion, adding further evidence to the role of the NO pathway in EBI after SAH. Our findings provide the basis for future clinical trials employing NO donors after SAH.

Opposite effects of cannabis and cocaine on performance monitoring.

Drug use is often associated with risky and unsafe behavior. However, the acute effects of cocaine and cannabis on performance monitoring processes have not been systematically investigated. The aim of the current study was to investigate how administration of these drugs alters performance monitoring processes, as reflected in the error-related negativity (ERN), the error positivity (Pe) and post-error slowing. A double-blind placebo-controlled randomized three-way crossover design was used. Sixty-one subjects completed a Flanker task while EEG measures were obtained. Subjects showed diminished ERN and Pe amplitudes after cannabis administration and increased ERN and Pe amplitudes after administration of cocaine. Neither drug affected post-error slowing. These results demonstrate diametrically opposing effects on the early and late phases of performance monitoring of the two most commonly used illicit drugs of abuse. Conversely, the behavioral adaptation phase of performance monitoring remained unaltered by the drugs.

Acute effects of cocaine and cannabis on reversal learning as a function of COMT and DRD2 genotype.

RATIONALE: Long-term cannabis and cocaine use has been associated with impairments in reversal learning. However, how acute cannabis and cocaine administration affect reversal learning in humans is not known. OBJECTIVE: In this study, we aimed to establish the acute effects of administration of cannabis and cocaine on valence-dependent reversal learning as a function of DRD2 Taq1A (rs1800497) and COMT Val108/158Met (rs4680) genotype. METHODS: A double-blind placebo-controlled randomized 3-way crossover design was used. Sixty-one regular poly-drug users completed a deterministic reversal learning task under the influence of cocaine, cannabis, and placebo that enabled assessment of both reward- and punishment-based reversal learning. RESULTS: Proportion correct on the reversal learning task was increased by cocaine, but decreased by cannabis. Effects of cocaine depended on the DRD2 genotype, as increases in proportion correct were seen only in the A1 carriers, and not in the A2/A2 homozygotes. COMT genotype did not modulate drug-induced effects on reversal learning. CONCLUSIONS: These data indicate that acute administration of cannabis and cocaine has opposite effects on reversal learning. The effects of cocaine, but not cannabis, depend on interindividual genetic differences in the dopamine D2 receptor gene.

Acute effects of cocaine and cannabis on response inhibition in humans: an ERP investigation.

Substance abuse has often been associated with alterations in response inhibition in humans. Not much research has examined how the acute effects of drugs modify the neurophysiological correlates of response inhibition, or how these effects interact with individual variation in trait levels of impulsivity and novelty seeking. This study investigated the effects of cocaine and cannabis on behavioural and event-related potential (ERP) correlates of response inhibition in 38 healthy drug using volunteers. A double-blind placebo-controlled randomized three-way crossover design was used. All subjects completed a standard Go/NoGo task after administration of the drugs. Compared with a placebo, cocaine yielded improved accuracy, quicker reaction times and an increased prefrontal NoGo-P3 ERP. Cannabis produced opposing results; slower reaction times, impaired accuracy and a reduction in the amplitude of the prefrontal NoGo-P3. Cannabis in addition decreased the amplitude of the parietally recorded P3, while cocaine did not affect this. Neither drugs specifically affected the N2 component, suggesting that pre-motor response inhibitory processes remain unaffected. Neither trait impulsivity nor novelty seeking interacted with drug-induced effects on measures of response inhibition. We conclude that acute drug effects on response inhibition seem to be specific to the later, evaluative stages of response inhibition. The acute effects of cannabis appeared less specific to response inhibition than those of cocaine. Together, the results show that the behavioural effects on response inhibition are reflected in electrophysiological correlates. This study did not support a substantial role of vulnerability personality traits in the acute intoxication stage.

MDMA, cannabis, and cocaine produce acute dissociative symptoms.

Some drugs of abuse may produce dissociative symptoms, but this aspect has been understudied. We explored the dissociative potential of three recreational drugs (3,4-methylenedioxymethamphetamine (MDMA), cannabis, and cocaine) during intoxication and compared their effects to literature reports of dissociative states in various samples. Two placebo-controlled studies were conducted. In Study 1 (N=16), participants received single doses of 25, 50, and 100 mg of MDMA, and placebo. In Study 2 (N=21), cannabis (THC 300 µg/kg), cocaine (HCl 300 mg), and placebo were administered. Dissociative symptoms as measured with the Clinician-Administered Dissociative States Scale (CADSS) significantly increased under the influence of MDMA and cannabis. To a lesser extent, this was also true for cocaine. Dissociative symptoms following MDMA and cannabis largely exceeded those observed in schizophrenia patients, were comparable with those observed in Special Forces soldiers undergoing survival training, but were lower compared with ketamine-induced dissociation. Cocaine produced dissociative symptoms that were comparable with those observed in schizophrenia patients, but markedly less than those in Special Forces soldiers and ketamine users. Thus, MDMA and cannabis can produce dissociative symptoms that resemble dissociative pathology. The study of drug induced dissociation is important, because it may shed light on the mechanisms involved in dissociative psychopathology.

Characterizing the cognitive effects of cocaine: a comprehensive review.

Understanding the cognitive sequela of repeated cocaine use is a growing area of research and is crucial to the development of cognitive models of addiction. We systematically reviewed all available placebo-controlled and case-controlled studies on the acute and long-term effects of cocaine on cognitive functioning. In order to compare the magnitude of cognitive effects across cognitive domains we conducted several meta-analyses on a subset of data from long-term effect studies. Studies on acute cocaine administration suggest enhancement of response inhibition and psychomotor speed, while all other domains appear to be unaffected or not investigated adequately. Long-term effects of cocaine show a wide array of deteriorated cognitive functions, indicating that long term cocaine use is characterized by a general cognitive impairment across functions, rather than by specific cognitive deficits. Literature on long-term cocaine effects is more substantial than literature on acute effects. This comprehensive review outlines possible dissociations and similarities of acute vs. long-term cocaine effects in the human brain. Atherosclerosis after cocaine exposure may underlie cognitive dysfunction, suggesting involvement of multiple brain areas. Acute drug studies are important to the future development of addiction models.