Acute Effects of Delta-9-Tetrahydrocannabinol on Performance Monitoring in Healthy Volunteers

Rationale: The error-related negativity (ERN) is a negative event-related potential that occurs immediately after an erroneous response and is thought to reflect human performance monitoring. Delta-9-Tetrahydrocannabinol (THC) administration in healthy volunteers has been linked to impaired performance monitoring in behavioral studies, but to date no studies have examined the effects of cannabinoids on the ERN. Methods: EEG data from 10 healthy volunteers was recorded during execution of a speeded choice-reaction-time task (Flankers task) after administration of THC or placebo vapor in a double-blind randomized crossover design. Results: The findings of this study show that the ERN was significantly reduced after administration of THC. The behavioral outcomes on the Flankers task showed no indications of drug-induced impairments. Discussion: The diminished ERN reflects impairments in the process of performance monitoring. The task design was not optimized to find behavioral effects. The study shows that cannabinoids impair performance monitoring

Acute effects of MDMA (3,4-methylenedioxymethamphetamine) on EEG oscillations: alone and in combination with ethanol or THC (delta-9-tetrahydrocannabinol)

Item does not contain fulltextRATIONALE: Typical users of 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") are polydrug users, combining MDMA with alcohol or cannabis [most active compound: delta-9-tetrahydrocannabinol (THC)]. OBJECTIVES: The aim of the present study was to investigate whether co-administration of alcohol or THC with MDMA differentially affects ongoing electroencephalogram (EEG) oscillations compared to the administration of each drug alone. METHODS: In two separate experiments, 16 volunteers received four different drug conditions: (1) MDMA (100 mg); (2) alcohol clamp (blood alcohol concentration = 0.6 per thousand) or THC (inhalation of 4, 6 and 6 mg, interval of 1.5 h); (3) MDMA in combination with alcohol or THC; and (4) placebo. Before and after drug administration, electroencephalography was recorded during an eyes closed resting state. RESULTS: Theta and alpha power increased after alcohol intake compared to placebo and reduced after MDMA intake. No interaction between alcohol and MDMA was found. Significant MDMA x THC effects for theta and lower-1-alpha power indicated that the power attenuation after the combined intake of MDMA and THC was less than the sum of each drug alone. For the lower-2-alpha band, the intake of MDMA or THC alone did not significantly affect power, but the intake of combined MDMA and THC significantly decreased lower-2-alpha power. CONCLUSIONS: The present findings indicate that the combined intake of MDMA and THC, but not of MDMA and alcohol, affects ongoing EEG oscillations differently than the sum of either one drug alone. Changes in ongoing EEG oscillations may be related to the impaired task performance that has often been reported after drug intake

Effects of average reward rate on vigor as a function of individual variation in striatal dopamine

Rationale: We constantly need to decide not only which actions to perform, but also how vigorously to perform them. In agreement with an earlier theoretical model, it has been shown that a significant portion of the variance in our action vigor can be explained by the average rate of rewards received for that action. Moreover, this invigorating effect of average reward rate was shown to vary with within-subject changes in dopamine, both in human individuals and experimental rodents. Objectives: Here, we assessed whether individual differences in the effect of average reward rate on vigor are related to individual variation in a stable measure of striatal dopamine function in healthy, unmedicated participants.Methods: Forty-four participants performed a discrimination task to test the effect of average reward rate on response times to index vigor and completed an [18F]-DOPA PET scan to index striatal dopamine synthesis capacity. Results: We did not find an interaction between dopamine synthesis capacity and average reward rate across the entire group. However, a post-hoc analysis revealed that participants with higher striatal dopamine synthesis capacity, particularly in the nucleus accumbens, exhibited a stronger invigorating effect of average reward rate among the 30 slowest participants.Conclusions: Our findings provide converging evidence for a role of striatal dopamine in average reward rate signaling, thereby extending the current literature on the mechanistic link between average reward rate, vigor and dopamine

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

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

Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users with low activity DBH genotypes

The dopamine β-hydroxylase (DβH) enzyme transforms dopamine into noradrenaline. We hypothesized that individuals with low activity DBH genotypes (rs1611115 CT/TT) are more sensitive to the influence of cannabis and cocaine on cognitive impulse control and functional connectivity in the limbic ‘reward’ circuit because they experience a drug induced hyperdopaminergic state compared to individuals with high activity DBH genotypes (rs1611115 CC). Regular drug users (N = 122) received acute doses of cannabis (450 μg/kg THC), cocaine HCl 300 mg and placebo. Cognitive impulse control was assessed by means of the Matching Familiar Figures Test (MFFT). Resting state fMRI was measured in a subset of participants to determine functional connectivity between the nucleus accumbens (NAc) and (sub)cortical areas. The influence of cannabis and cocaine on impulsivity and functional connectivity significantly interacted with DBH genotype. Both drugs increased cognitive impulsivity in participants with CT/TT genotypes but not in CC participants. Both drugs also reduced functional connectivity between the NAc and the limbic lobe, prefrontal cortex, striatum and thalamus and primarily in individuals with CT/TT genotypes. Correlational analysis indicated a significant negative association between cognitive impulsivity and functional connectivity in subcortical areas of the brain. It is concluded that interference of cannabis and cocaine with cognitive impulse control and functional corticostriatal connectivity depends on DBH genotype. The present data provide a neural substrate and behavioral mechanism by which drug users can progress to drug seeking and may also offer a rationale for targeted pharmacotherapy in chronic drug users with high risk DBH genotypes

Group characteristics for the psychopathic, non-psychopathic and the control group.

<p>Group means are reported with their standard deviation between brackets. Significant Group differences are flagged.</p