Short-term effects of cannabis consumption on cognitive performance in medical cannabis patients.

This observational study examined the acute cognitive effects of cannabis. We hypothesized that cognitive performance would be negatively affected by acute cannabis intoxication. Twenty-two medical cannabis patients from Southwestern Ontario completed the study. The majority (n = 13) were male. Mean age was 36.0 years, and mean level of education was 13.7 years. Participants were administered the same brief neurocognitive battery three times during a six-hour period: at baseline ("Baseline"), once after they consumed a 20% THC cannabis product ("THC"), and once again several hours later ("Recovery"). The average self-reported level of cannabis intoxication prior to the second assessment (i.e., during THC) was 5.1 out of 10. Contrary to expectations, performance on neuropsychological tests remained stable or even improved during the acute intoxication stage (THC; d: .49-.65, medium effect), and continued to increase during Recovery (d: .45-.77, medium-large effect). Interestingly, the failure rate on performance validity indicators increased during THC. Contrary to our hypothesis, there was no psychometric evidence for a decline in cognitive ability following THC intoxication. There are several possible explanations for this finding but, in the absence of a control group, no definitive conclusion can be reached at this time.

Introducing a forced choice recognition trial to the Hopkins Verbal Learning Test - Revised.

OBJECTIVE: This study was designed to replicate previous research on embedded validity indicators (EVIs) in the Hopkins Verbal Learning Test - Revised (HVLT-R) and introduce a new forced choice recognition trial (FCR). METHOD: Undergraduate research volunteers were randomly assigned (MAge = 21.7; MEducation = 14.5 years, 85% female) to either the control or experimental malingering condition, and were administered a brief battery of neuropsychological tests. RESULTS: Recognition memory based EVIs (both existing and newly introduced) effectively discriminated credible and non-credible response sets. An FCR ≤11 produced .59 sensitivity and perfect specificity to invalid responding. A Recognition Discrimination (RD) score ≤8 also produced a good combination of sensitivity (.35) and specificity (.96). The FCR trial made unique contributions to performance validity assessment above and beyond previously published EVIs. CONCLUSIONS: RD achieved ≥.90 specificity at higher cutoffs than previously reported. The newly introduced FCR trial has the potential to enhance the existing arsenal of EVIs within the HVLT-R. However, it must demonstrate its ability to differentiate genuine impairment from non-credible responding before it can be recommended for clinical use.

Prospective Analysis of the Effects of Maternal Immune Activation on Rat Cytokines during Pregnancy and Behavior of the Male Offspring Relevant to Schizophrenia.

Influenza during pregnancy is associated with the development of psychopathology in the offspring. We sought to determine whether maternal cytokines produced following administration of viral mimetic polyinosinic-polycytidylic acid (polyI:C) to pregnant rats were predictive of behavioral abnormalities in the adult offspring. Timed-pregnant Sprague Dawley rats received a single intravenous injection of 4-mg/kg polyI:C or saline on gestational day (GD)15. Blood was collected 3 h later for serum analysis of cytokine levels with ELISA. Male offspring were tested in a battery of behavioral tests during adulthood and behavior was correlated with maternal cytokine levels. Maternal serum levels of CXCL1 and interleukin (IL)-6, but not tumor necrosis factor (TNF)-α or CXCL2, were elevated in polyI:C-treated dams. PolyI:C-treated dams experienced post-treatment weight loss and polyI:C pups were smaller than controls at postnatal day (PND)1. Various behavior alterations were seen in the polyI:C-treated offspring. Male polyI:C offspring had enhanced MK-801-induced locomotion, and reduced sociability. PolyI:C offspring failed to display crossmodal and visual memory, and oddity preference was also impaired. Set-shifting, assessed with a lever-based operant conditioning task, was facilitated while touchscreen-based reversal learning was impaired. Correlations were found between maternal serum concentrations of CXCL1, acute maternal temperature and body weight changes, neonatal pup mass, and odd object discrimination and social behavior. Overall, while the offspring of polyI:C-treated rats displayed behavior abnormalities, maternal serum cytokines were not related to the long-term behavior changes in the offspring. Maternal sickness effects and neonatal pup size may be better indicators of later effects of maternal inflammation in the offspring.

The D-KEFS Trails as performance validity tests.

This study was designed to examine the potential of the Delis-Kaplan Executive System (D-KEFS) version of the Trail Making Test (TMT) as a performance validity test (PVT). Data were collected from a mixed clinical sample of 157 consecutively referred outpatients (49% male, MAge = 47.1, MEducation = 13.6) undergoing neuropsychological assessment at an academic medical center in the northeastern United States. Sensitivity and specificity of the D-KEFS Trails to psychometrically defined invalid responding was calculated across various cutoffs and criterion PVTs. The D-KEFS Trails produced classification accuracy comparable to the original version of the TMT, hovering around the "Larrabee limit" (.50 sensitivity at .90 specificity). Different cutoffs (age-corrected scaled score ≤5 on Trails 1-3, ≤4 on Trails 4 and ≤8 on Trails 5) were needed to achieve the same classification accuracy across the five trials. Combining multiple cutoffs improved the signal detection performance. The study provides preliminary evidence of the utility of D-KEFS Trails as a PVT. Embedded PVTs are valuable, because they make a multivariate approach to validity assessment feasible. Combining validity indicators is superior to relying on single cutoffs. (PsycINFO Database Record

Medial prefrontal cortex and dorsomedial striatum are necessary for the trial-unique, delayed nonmatching-to-location (TUNL) task in rats: role of NMDA receptors.

The trial-unique, delayed nonmatching-to-location (TUNL) task is a recently developed behavioral task that measures spatial working memory and a form of pattern separation in touchscreen-equipped operant conditioning chambers. Limited information exists regarding the neurotransmitters and neural substrates involved in the task. The present experiments tested the effects of systemic and intracranial injections of NMDA receptor antagonists on the TUNL task. After training, male Long Evans rats systemically injected with the competitive NMDA receptor antagonist CPP (10 mg/kg) had impaired accuracy regardless of the degree of stimuli separation or length of delay between the sample and test phases. Injections of Ro 25-6981 (6 or 10 mg/kg), an antagonist selective for GluN2B subunit-containing NMDA receptors, did not affect accuracy on the task. Direct infusion of the competitive NMDA receptor antagonist AP5 into mPFC or dmSTR reduced overall accuracy on the TUNL task. These results demonstrate that TUNL task performance depends on NMDA receptors within the mPFC and dmSTR.

MK-801-induced impairments on the trial-unique, delayed nonmatching-to-location task in rats: effects of acute sodium nitroprusside.

RATIONALE: The cognitive symptoms observed in schizophrenia are not consistently alleviated by conventional antipsychotics. Following a recent pilot study, sodium nitroprusside (SNP) has been identified as a promising adjunct treatment to reduce the working memory impairments experienced by schizophrenia patients. OBJECTIVE: The present experiments were designed to explore the effects of SNP on the highly translatable trial-unique, delayed nonmatching-to-location (TUNL) task in rats with and without acute MK-801 treatment. METHODS: SNP (0.5, 1.0, 2.0, 4.0, and 5.0 mg/kg) and MK-801 (0.05, 0.075, and 0.1 mg/kg) were acutely administered to rats trained on the TUNL task. RESULTS: Acute MK-801 treatment impaired TUNL task accuracy. Administration of SNP (2.0 mg/kg) with MK-801 (0.1 mg/kg) failed to rescue performance on TUNL. SNP (5.0 mg/kg) administration nearly 4 h prior to MK-801 (0.05 mg/kg) treatment had no preventative effect on performance impairments. SNP (2.0 mg/kg) improved performance on a subset of trials. CONCLUSION: These results suggest that SNP may possess intrinsic cognitive-enhancing properties but is unable to block the effects of acute MK-801 treatment on the TUNL task. These results are inconsistent with the effectiveness of SNP as an adjunct therapy for working memory impairments in schizophrenia patients. Future studies in rodents that assess SNP as an adjunct therapy will be valuable in understanding the mechanisms underlying the effectiveness of SNP as a treatment for schizophrenia.

Effects of stress on behavioral flexibility in rodents.

Cognitive flexibility is the ability to switch between different rules or concepts and behavioral flexibility is the overt physical manifestation of these shifts. Behavioral flexibility is essential for adaptive responses and commonly measured by reversal learning and set-shifting performance in rodents. Both tasks have demonstrated vulnerability to stress with effects dependent upon stressor type and number of repetitions. This review compares the effects of stress on reversal learning and set-shifting to provide insight into the differential effect of stress on cognition. Acute and short-term repetition of stress appears to facilitate reversal learning whereas the longer term repetition of stress impairs reversal learning. Stress facilitated intradimensional set-shifting within a single, short-term stress protocol but otherwise generally impaired set-shifting performance in acute and repeated stress paradigms. Chronic unpredictable stress impairs reversal learning and set-shifting whereas repeated cold intermittent stress selectively impairs reversal learning and has no effect on set-shifting. In considering the mechanisms underlying the effects of stress on behavioral flexibility, pharmacological manipulations performed in conjunction with stress are also reviewed. Blocking corticosterone receptors does not affect the facilitation of reversal learning following acute stress but the prevention of corticosterone synthesis rescues repeated stress-induced set-shifting impairment. Enhancing post-synaptic norepinephrine function, serotonin availability, and dopamine receptor activation rescues and/or prevents behavioral flexibility performance following stress. While this review highlights a lack of a standardization of stress paradigms, some consistent effects are apparent. Future studies are necessary to specify the mechanisms underlying the stress-induced impairments of behavioral flexibility, which will aid in alleviating these symptoms in patients with some psychiatric disorders.