Dose-related modulation of event-related potentials to novel and target stimuli by intravenous Δ⁹-THC in humans.
D'Souza et al.·NeuropsychopharmacologyImpact 4.4
Klarer NutzenGRADEModerat96 Zitate
Stichproben = 26 Pat.
Dauerdrei Testtage
KontrollePlacebo
EndpunktP300-Amplitude
Verblindungdoppelblind
DesignRCT (Cross-over, IV THC, Gesunde Probanden)
Cannabinoidthc
”Kernaussage
Δ⁹-THC reduzierte dosisabhängig die P300a- und P300b-Amplituden, ohne Latenzen oder frühe sensorische Komponenten zu beeinflussen.
Zusammenfassung
Randomisierter Cross-over-Versuch (n=26), intravenöses Δ⁹-THC (Placebo, 0,015, 0,03 mg/kg): THC reduzierte dosisabhängig P300a- und P300b-Amplituden (p<0.05 jeweils) und induzierte dosisabhängig psychotomimetische Effekte sowie Wahrnehmungsveränderungen; die THC-induzierten P3b-Reduktionen korrelierten mit den Wahrnehmungsveränderungen. Befunde stützen CB1-Rezeptor-Beteiligung an Top-down-/Bottom-up-Informationsverarbeitung als neurobiologisches Substrat Cannabis-assoziierter Psychose-Vulnerabilität.
P
PopulationGesunde Probanden (Cannabis-Nutzer und Cannabis-Abstinente), n=26, Crossover-Design
I
InterventionIntravenöses Δ⁹-THC, zwei Dosisstufen: 0,015 mg/kg und 0,03 mg/kg
C
KontrollePlacebo (intravenös)
O
OutcomeΔ⁹-THC reduzierte dosisabhängig die Amplitude der P300b (Zielreiz) und P300a (Novelty); kein Effekt auf Latenzen von P300a/b oder frühe sensorische Komponente N100; P300b-Amplitudenreduktion korrelierte mit wahrnehmungsverändernden Effekten
Vertrauen in die Evidenz
Sehr niedrigNiedrigModeratHoch
Moderat
Dritte von vier GRADE-Stufen, die Effektschätzung ist wahrscheinlich verlässlich.
Herabgestuft wegen
Ungenauigkeit
Qualitätsprofil
Größe★★★★★
VerblindungDoppelblind
EffektstärkeKlarer Nutzen
Zitate / Jahr★★★★★
Autoren
D'Souza DC, Fridberg DJ, Skosnik PD, Williams A, Roach B, Singh N, Carbuto M, Elander J, Schnakenberg A, Pittman B, Sewell RA, Ranganathan M, Mathalon D.
Design: RCT (Cross-over, IV THC, Gesunde Probanden)
Teilen
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 (Δ⁹-THC) on psychophysiological indices of information processing in humans. Healthy subjects (n=26) completed three test days during which they received intravenous Δ⁹-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). Δ⁹-THC dose-dependently reduced the amplitude of both the target P300b and the novelty P300a. Δ⁹-THC did not have any effect on the latency of either the P300a or P300b, or on early sensory-evoked ERP components preceding the P300 (the N100). Concomitantly, Δ⁹-THC induced psychotomimetic effects, perceptual alterations, and subjective 'high' in a dose-dependent manner. Δ⁹-THC -induced reductions in P3b amplitude correlated with Δ⁹-THC-induced perceptual alterations. Lastly, exploratory analyses examining cannabis use status showed that whereas recent cannabis users had blunted behavioral effects to Δ(9)-THC, there were no dose-related effects of Δ⁹-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, Δ⁹-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.