Protein kinase B (AKT1) genotype mediates sensitivity to cannabis-induced impairments in psychomotor control

2014 ◽  
Vol 44 (15) ◽  
pp. 3315-3328 ◽  
Author(s):  
S. Bhattacharyya ◽  
C. Iyegbe ◽  
Z. Atakan ◽  
R. Martin-Santos ◽  
J. A. Crippa ◽  
...  

Background.What determines inter-individual variability to impairments in behavioural control that may underlie road-traffic accidents, and impulsive and violent behaviours occurring under the influence of cannabis, the most widely used illicit drug worldwide?Method.Employing a double-blind, repeated-measures design, we investigated the genetic and neural basis of variable sensitivity to cannabis-induced behavioural dyscontrol in healthy occasional cannabis users. Acute oral challenge with placebo or Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, was combined with functional magnetic resonance imaging, while participants performed a response inhibition task that involved inhibiting a pre-potent motor response. They were genotyped for rs1130233 single nucleotide polymorphisms (SNPs) of the protein kinase B (AKT1) gene.Results.Errors of inhibition were significantly (p = 0.008) increased following administration of THC in carriers of the A allele, but not in G allele homozygotes of theAKT1rs1130233 SNP. The A allele carriers also displayed attenuation of left inferior frontal response with THC evident in the sample as a whole, while there was a modest enhancement of inferior frontal activation in the G homozygotes. There was a direct relationship (r = − 0.327,p = 0.045) between the behavioural effect of THC and its physiological effect in the inferior frontal gyrus, whereAKT1genotype modulated the effect of THC.Conclusions.These results require independent replication and show that differing vulnerability to acute psychomotor impairments induced by cannabis depends on variation in a gene that influences dopamine function, and is mediated through modulation of the effect of cannabis on the inferior frontal cortex, that is rich in dopaminergic innervation and critical for psychomotor control.

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3629 ◽  
Author(s):  
Jan Mieszkowski ◽  
Błażej Stankiewicz ◽  
Andrzej Kochanowicz ◽  
Bartłomiej Niespodziński ◽  
Tomasz Kowalik ◽  
...  

Purpose: While an increasing number of studies demonstrate the importance of vitamin D for athletic performance, the effects of any type of exercise on vitamin D metabolism are poorly characterized. We aimed to identify the responses of some vitamin D metabolites to ultra-marathon runs. Methods: A repeated-measures design was implemented, in which 27 amateur runners were assigned into two groups: those who received a single dose of vitamin D3 (150,000 IU) 24 h before the start of the marathon (n = 13) and those (n = 14) who received a placebo. Blood samples were collected 24 h before, immediately after, and 24 h after the run. Results: In both groups of runners, serum 25(OH)D3, 24,25(OH)2D3, and 3-epi-25(OH)D3 levels significantly increased by 83%, 63%, and 182% after the ultra-marathon, respectively. The increase was most pronounced in the vitamin D group. Body mass and fat mass significantly decreased after the run in both groups. Conclusions: Ultra-marathon induces the mobilization of vitamin D into the blood. Furthermore, the 24,25(OH)2D3 and 3-epi-25(OH)D3 increases imply that the exercise stimulates vitamin D metabolism.


2018 ◽  
Vol 48 (16) ◽  
pp. 2748-2756 ◽  
Author(s):  
Sagnik Bhattacharyya ◽  
Thomas Sainsbury ◽  
Paul Allen ◽  
Chiara Nosarti ◽  
Zerrin Atakan ◽  
...  

AbstractBackgroundCannabis and its main psychoactive ingredient δ-9-tetrahydrocannibidiol (THC) can induce transient psychotic symptoms in healthy individuals and exacerbate them in those with established psychosis. However, not everyone experience these effects, suggesting that certain individuals are particularly susceptible. The neural basis of this sensitivity to the psychotomimetic effects of THC is unclear.MethodsWe investigated whether individuals who are sensitive to the psychotomimetic effects of THC (TP) under experimental conditions would show differential hippocampal activation compared with those who are not (NP). We studied 36 healthy males under identical conditions under the influence of placebo or THC (10 mg) given orally, on two separate occasions, in a pseudo-randomized, double-blind, repeated measures, within-subject, cross-over design, using psychopathological assessments and functional MRI while they performed a verbal learning task. They were classified into those who experienced transient psychotic symptoms (TP; n = 14) following THC administration and those who did not (NP; n = 22).ResultsUnder placebo conditions, there was significantly greater engagement of the left hippocampus (p < 0.001) in the TP group compared with the NP group during verbal encoding, which survived leave-one-out analysis. The level of hippocampal activation was directly correlated (Spearman's ρ = 0.44, p = 0.008) with the severity of transient psychotic symptoms induced by THC. This difference was not present when we compared two subgroups from the same sample that were defined by sensitivity to anxiogenic effects of THC.ConclusionsThese results suggest that altered hippocampal activation during verbal encoding may serve as a marker of sensitivity to the acute psychotomimetic effects of THC.


Author(s):  
Adam U. Upshaw ◽  
Tiffany S. Wong ◽  
Arash Bandegan ◽  
Peter W.R. Lemon

Postexercise chocolate milk ingestion has been shown to enhance both glycogen resynthesis and subsequent exercise performance. To assess whether nondairy chocolate beverage ingestion post–glycogen-lowering exercise can enhance 20-km cycling time trial performance 4 hr later, eight healthy trained male cyclists (21.8 ± 2.3y, VO2max = 61.2 ± 1.4 ml·kg-1·min-1; M ± SD) completed a series of intense cycling intervals designed to lower muscle glycogen (Jentjens & Jeukendrup, 2003) followed by 4 hr of recovery and a subsequent 20-km cycling time trial. During the first 2 hr of recovery, participants ingested chocolate dairy milk (DAIRYCHOC), chocolate soy beverage (SOYCHOC), chocolate hemp beverage (HEMPCHOC), low-fat dairy milk (MILK), or a low-energy artificially sweetened, flavored beverage (PLACEBO) at 30-min intervals in a double-blind, counterbalanced repeated-measures design. All drinks, except the PLACEBO (247 kJ) were isoenergetic (2,107 kJ), and all chocolate-flavored drinks provided 1-g CHO·kg body mass-1·h-1. Fluid intake across treatments was equalized (2,262 ± 148 ml) by ingesting appropriate quantities of water based on drink intake. The CHO:PRO ratio was 4:1, 1.5:1, 4:1, and 6:1 for DAIRYCHOC, MILK, SOYCHOC, and HEMPCHOC, respectively. One-way analysis of variance with repeated measures showed time trial performance (DAIRYCHOC = 34.58 ± 2.5 min, SOYCHOC = 34.83 ± 2.2 min, HEMPCHOC = 34.88 ± 1.1 min, MILK = 34.47 ± 1.7 min) was enhanced similarly vs PLACEBO (37.85 ± 2.1) for all treatments (p = .019) These data suggest that postexercise macronutrient and total energy intake are more important for same-day 20-km cycling time trial performance after glycogen-lowering exercise than protein type or protein-to-carbohydrate ratio.


2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
S. Bhattacharyya ◽  
P. Fusar-Poli ◽  
S. Borgwardt ◽  
R. Martin-Santos ◽  
C. Carroll ◽  
...  

There is considerable interest in the therapeutic potential of Cannabidiol (CBD), the second most abundant component of Cannabis. While delta-9-THC, the main psychoactive ingredient of cannabis, impairs memory and induces anxiety and psychotic symptoms acutely and increases the risk of psychotic disorders in regular cannabis users, CBD does not impair memory, may have anxiolytic and possibly antipsychotic effects. Hence, we compared directly the acute neural effects of these two active ingredients of cannabis, by combining pharmacological challenge with fMRI. Using a double-blind, repeated measures design and oral challenge with 10mg of delta-9-THC, 600mg of CBD or placebo in 15 healthy volunteers, we examined whether delta-9-THC and CBD have opposing effects on the neural substrates of verbal memory and fear processing and whether they also have opposing effects on the neural substrates of anxiety and psychotic symptoms induced by delta-9-THC. Delta-9-THC induced anxiety and psychotic symptoms acutely while there was a trend for a reduction in anxiety but no change in psychotic symptoms with CBD. During the memory task, delta-9-THC attenuated and CBD increased activation in the striatum bilaterally. Effect of delta-9-THC on striatal activation was inversely correlated with the psychotic symptoms induced by it concomitantly. During the processing of fearful faces, delta-9-THC increased and CBD attenuated activation in the amygdala and these effects correlated with their anxiogenic and anxiolytic effects respectively. These opposing effects of CBD on the key neural substrates for psychotic symptoms and anxiety induced by delta-9-THC may suggest its possible therapeutic role in countering these conditions.


Biorheology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Xiaotong Zhu ◽  
Keying Zhang ◽  
Li He ◽  
Fuyuan Liao ◽  
Yuanchun Ren ◽  
...  

BACKGROUND: Local vibration has been shown promise in improving skin blood flow and wound healing. However, the underlying mechanism of local vibration as a preconditioning intervention to alter plantar skin blood flow after walking is unclear. OBJECTIVE: The objective was to use wavelet analysis of skin blood flow oscillations to investigate the effect of preconditioning local vibration on plantar tissues after walking. METHODS: A double-blind, repeated measures design was tested in 10 healthy participants. The protocol included 10-min baseline, 10-min local vibrations (100Hz or sham), 10-min walking, and 10-min recovery periods. Skin blood flow was measured over the first metatarsal head of the right foot during the baseline and recovery periods. Wavelet amplitudes after walking were expressed as the ratio of the wavelet amplitude before walking. RESULTS: The results showed the significant difference in the metabolic (vibration 10.06 ± 1.97, sham 5.78 ± 1.53, p < 0.01) and neurogenic (vibration 7.45 ± 1.54, sham 4.78 ± 1.22, p < 0.01) controls. There were no significant differences in the myogenic, respiratory and cardiac controls between the preconditioning local vibration and sham conditions. CONCLUSIONS: Our results showed that preconditioning local vibration altered the normalization rates of plantar skin blood flow after walking by stimulating the metabolic and neurogenic controls.


2014 ◽  
Vol 26 (2) ◽  
pp. 168-176 ◽  
Author(s):  
J. Bradley Jordan ◽  
Ajit Korgaokar ◽  
Richard S. Farley ◽  
John M. Coons ◽  
Jennifer L. Caputo

This study examined the effects of caffeine supplementation (6 mg·kg−1) on performance of a reactive agility test (RAT) in 17 elite, male, youth (M = 14 y) soccer players. Using a double-blind, repeated-measures design, players completed 4 days of testing on the RAT after a standardized warm-up. On day 1, anthropometric measurements were taken and players were accommodated to the RAT. On day 2, baseline performance was established. Caffeine or placebo conditions were randomly assigned on day 3 and the condition was reversed on day 4. Players completed 3 randomized trials of the RAT on days 2, 3, and 4 with at least 1 trial to the players’ dominant and nondominant sides. There were no significant differences among conditions in reaction time (RT) to the dominant side, heart rates at any point of measurement, or ratings of perceived exertion (RPE) after completion of the warm-up. Caffeine produced faster RT to the nondominant side (P = .041) and higher RPE at the conclusion of the RAT (P = .013). The effect on the total time (TT) to complete the agility test to the nondominant side approached significance (P = .051). Sprint time and TT to either side did not differ. Caffeine supplementation may provide ergogenic benefit to elite, male, youth soccer players.


2010 ◽  
Vol 20 (2) ◽  
pp. 104-114 ◽  
Author(s):  
Matthew S. Ganio ◽  
Jennifer F. Klau ◽  
Elaine C. Lee ◽  
Susan W. Yeargin ◽  
Brendon P. McDermott ◽  
...  

The purpose of this study was to compare the effects of a carbohydrate-electrolyte plus caffeine, carnitine, taurine, and B vitamins solution (CE+) and a carbohydrate-electrolyte-only solution (CE) vs. a placebo solution (PLA) on cycling performance and maximal voluntary contraction (MVC). In a randomized, double-blind, crossover, repeated-measures design, 14 male cyclists (M ± SD age 27 ± 6 yr, VO2max 60.4 ± 6.8 ml · kg−1 · min−1) cycled for 120 min submaximally (alternating 61% ± 5% and 75% ± 5% VO2max) and then completed a 15-min performance trial (PT). Participants ingested CE+, CE, or PLA before (6 ml/kg) and every 15 min during exercise (3 ml/kg). MVC was measured as a single-leg isometric extension (70° knee flexion) before (pre) and after (post) exercise. Rating of perceived exertion (RPE) was measured throughout. Total work accumulated (KJ) during PT was greater (p < .05) in CE+ (233 ± 34) than PLA (205 ± 52) but not in CE (225 ± 39) vs. PLA. MVC (N) declined (p < .001) from pre to post in PLA (988 ± 213 to 851 ± 191) and CE (970 ± 172 to 870 ± 163) but not in CE+ (953 ± 171 to 904 ± 208). At Minutes 60, 90, 105, and 120 RPE was lower in CE+ (14 ± 2, 14 ± 2, 12 ± 1, 15 ± 2) than in PLA (14 ± 2, 15 ± 2, 14 ± 2, 16 ± 2; p < .001). CE+ resulted in greater total work than PLA. CE+, but not PLA or CE, attenuated pre-to-post MVC declines. Performance increases during CE+ may have been influenced by lower RPE and greater preservation of leg strength during exercise in part as a result of the hypothesized effects of CE+ on the central nervous system and skeletal muscle.


2010 ◽  
Vol 25 (12) ◽  
pp. 1614-1622 ◽  
Author(s):  
Valérie Guille ◽  
Andrea Gogos ◽  
Pradeep J Nathan ◽  
Rodney J Croft ◽  
Maarten van den Buuse

Estrogen may be involved in schizophrenia by inhibiting serotonin-1A (5-HT1A) receptor function. We examined the effects of estrogen pre-treatment on modulation of loudness dependence of the auditory evoked potential (LDAEP) and mismatch negativity by the 5-HT1A receptor partial agonist, buspirone. Using a double-blind, placebo-controlled, repeated-measures design in healthy female volunteers, we observed that buspirone treatment significantly increased LDAEP slope. Estrogen increased LDAEP slope on its own, and a further LDAEP increase by buspirone was not seen after estrogen pre-treatment. Similar results were observed for mismatch negativity, where buspirone caused a small increase of latency, although not amplitude, after placebo but not estrogen pre-treatment, which enhanced mismatch negativity latency on its own. These results are in line with our previous findings on prepulse inhibition showing an inhibitory effect of estrogen on the action of buspirone. Taken together, these data suggest that estrogen may inhibit 5-HT1A receptor-mediated disruptions of auditory processing.


2018 ◽  
Vol 21 (6) ◽  
pp. 755-763 ◽  
Author(s):  
Bader Chaarani ◽  
Philip A Spechler ◽  
Alexandra Ivanciu ◽  
Mitchell Snowe ◽  
Joshua P Nickerson ◽  
...  

Abstract Introduction Research on cigarette smokers suggests cognitive and behavioral impairments. However, much remains unclear how the functional neurobiology of smokers is influenced by nicotine state. Therefore, we sought to determine which state, be it acute nicotine abstinence or satiety, would yield the most robust differences compared with nonsmokers when assessing neurobiological markers of nicotine dependence. Methods Smokers (N = 15) and sociodemographically matched nonsmokers (N = 15) were scanned twice using a repeated-measures design. Smokers were scanned after a 24-hour nicotine abstinence and immediately after smoking their usual brand cigarette. The neuroimaging battery included a stop-signal task of response inhibition and pseudocontinuous arterial spin labeling to measure cerebral blood flow (CBF). Whole-brain voxel-wise analyses of covariance were carried out on stop success and stop fail Stop-Signal Task contrasts and CBF maps to assess differences among nonsmokers, abstinent smokers, and satiated smokers. Cluster correction was performed using AFNI’s 3dClustSim to achieve a significance of p &lt; .05. Results Smokers exhibited higher brain activation in bilateral inferior frontal gyrus, a brain region known to be involved in inhibitory control, during successful response inhibitions relative to nonsmokers. This effect was significantly higher during nicotine abstinence relative to satiety. Smokers also exhibited lower CBF in the bilateral inferior frontal gyrus than nonsmokers. These hypoperfusions were not different between abstinence and satiety. Conclusions These findings converge on alterations in smokers in prefrontal circuits known to be critical for inhibitory control. These effects are present, even when smokers are satiated, but the neural activity required to achieve performance equal to controls is increased when smokers are in acute abstinence. Implications Our multimodal neuroimaging study gives neurobiological insights into the cognitive demands of maintaining abstinence and suggests targets for assessing the efficacy of therapeutic interventions.


2017 ◽  
Vol 95 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Grace E. Giles ◽  
Caroline R. Mahoney ◽  
Tad T. Brunyé ◽  
Holly A. Taylor ◽  
Robin B. Kanarek

Tea is perceived as more relaxing than coffee, even though both contain caffeine. L-theanine in tea may account for the difference. Consumed together, caffeine and theanine exert similar cognitive effects to that of caffeine alone, but exert opposite effects on arousal, in that caffeine accentuates and theanine mitigates physiological and felt stress responses. We evaluated whether caffeine and theanine influenced cognition under emotional arousal. Using a double-blind, repeated-measures design, 36 participants received 4 treatments (200 mg caffeine + 0 mg theanine, 0 mg caffeine + 200 mg theanine, 200 mg caffeine + 200 mg theanine, 0 mg caffeine + 0 mg theanine) on separate days. Emotional arousal was induced by highly arousing negative film clips and pictures. Mood, salivary cortisol, and visual attention were evaluated. Caffeine accentuated global processing of visual attention on the hierarchical shape task (p < 0.05), theanine accentuated local processing (p < 0.05), and the combination did not differ from placebo. Caffeine reduced flanker conflict difference scores on the Attention Network Test (p < 0.05), theanine increased difference scores (p < 0.05), and the combination did not differ from placebo. Thus, under emotional arousal, caffeine and theanine exert opposite effects on certain attentional processes, but when consumed together, they counteract the effects of each other.


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