Dose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Δ9-THC in Humans

Abstract

Cannabinoids induce a host of perceptual alterations and cognitive deficits in humans. However, the neural correlates of these deficits have remained elusive. The current study examined the acute, dose-related effects of delta-9-tetrahydrocannabinol (D 9 -THC) on psychophysiological indices of information processing in humans. Healthy subjects (n ¼ 26) completed three test days during which they received intravenous D 9 -THC (placebo, 0.015 and 0.03 mg/kg) in a within-subject, double-blind, randomized, cross-over, and counterbalanced design. Psychophysiological data (electroencephalography) were collected before and after drug administration while subjects engaged in an event-related potential (ERP) task known to be a valid index of attention and cognition (a three-stimulus auditory 'oddball' P300 task). -THC-induced perceptual alterations. Lastly, exploratory analyses examining cannabis use status showed that whereas recent cannabis users had blunted behavioral effects to D 9 -THC, there were no dose-related effects of D 9 -THC on P300a/b amplitude between cannabis-free and recent cannabis users. Overall, these data suggest that at doses that produce behavioral and subjective effects consistent with the known properties of cannabis, D 9-THC reduced P300a and P300b amplitudes without altering the latency of these ERPs. Cannabinoid agonists may therefore disrupt cortical processes responsible for context updating and the automatic orientation of attention, while leaving processing speed and earlier sensory ERP components intact. Collectively, the findings suggest that CB1R systems modulate top-down and bottom-up processing.

GABA Deficits Enhance the Psychotomimetic Effects of Δ9-THC

“…Each outcome was assessed visually for normality using histograms and normal probability plots. As THC peak effects were captured 70 min after drug administration, and because at other timepoints there was little difference from the minimum score, each behavioral and subjective outcome was expressed as peak change from baseline using methods described elsewhere (D'Souza et al, 2012). The data were analyzed using linear mixed models with drug condition: (1) active iomazenil, placebo THC, (2) active iomazenil, active THC, (3) placebo iomazenil, active THC, and (4) placebo iomazenil, placebo THC as a within-subjects factor.…”

“…A three-stimulus auditory oddball task adapted from our previous study was used (D'Souza et al, 2012). Briefly, a random series of infrequent (8.33%) 'target' tones (1000 Hz sine wave), frequent (83.33%) 'standard' tones (20, 30, or 40 Hz click trains), and infrequent distractor sounds (8.33%) were presented with a 1250 interstimulus interval in three separate blocks.…”

“…The N100 was defined as the largest negative voltage peak between 50 and 150 ms after stimulus onset. For statistical analysis, data were used for each component where amplitude was largest as described previously (Pz for P300b; Cz for P300a; Cz for N100) (D'Souza et al, 2012). Processing and analysis of distractor stimuli will be reported elsewhere.…”

Brain Mapping-Based Model of Δ9-Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix

“…CB 1 receptor activations have been associated with several perceptual and cognitive effects. They include an inhibition of chronic inflammatory and neuropathic pain (Agarwal et al, 2007;Bishay et al, 2010), a modulation of sensory information processing (Dervaux et al, 2013;Tart, 1970), often described as taking on new qualities, including nociception (Walker and Huang, 2002), a disruption of filtering of non-salient information (D'Souza et al, 2012) and attentional salience processing (Bhattacharyya et al, 2012;Solowij et al, 1991), and an extinction of aversive memories (Marsicano et al, 2002).…”

Mariguana y sus efectos sobre el cerebro, la toma de decisiones y la inteligencia. Una revisión narrativa

“…sensación de bienestar y de "high" y cambios en la percepción. Además, se ha reportado que es el responsable del deterioro de la atención y la memoria, así como del aumento de la frecuencia cardiaca que el usuario prefiere no tener (Bossong et al, 2012;D'Souza et al, 2012;Hart, Van Gorp, Haney, Foltin, & Fischman, 2001). El Δ9-THC ejerce su acción principalmente sobre el sistema endocannabinoide (sECB), actuando sobre diversos receptores como el receptor a cannabinoides 1 (CB1) y el receptor a cannabinoides 2 (CB2); pero también tiene acción sobre otros receptores, v.gr.…”