Study register · detailRCT (Cross-over, IV THC, Gesunde Probanden) · Psychosis Risk · 2012
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
Clear benefitGRADEModerate96 citations
Samplen = 26 Pat.
Durationthree test days
ControlPlacebo
EndpointP300 amplitude
Blindingdoppelblind
DesignRCT (Cross-over, IV THC, Gesunde Probanden)
Cannabinoidthc
”Key finding
Δ⁹-THC dose-dependently reduced P300a and P300b amplitudes, without affecting latencies or early sensory components.
Summary
Randomized cross-over trial (n=26), intravenous Δ⁹-THC (placebo, 0,015, 0,03 mg/kg): THC reduced P300a and P300b amplitudes dose-dependently (p<0.05 each) and dose-dependently induced psychotomimetic effects as well as perceptual alterations; the THC-induced P3b reductions correlated with the perceptual alterations. Findings support CB1 receptor involvement in top-down/bottom-up information processing as a neurobiological substrate of cannabis-associated psychosis vulnerability.
P
PopulationHealthy volunteers (cannabis users and cannabis abstainers), n=26, crossover design
I
InterventionIntravenous Δ⁹-THC, two dose levels: 0,015 mg/kg and 0,03 mg/kg
C
ControlPlacebo (intravenous)
O
OutcomeΔ⁹-THC dose-dependently reduced the amplitude of P300b (target stimulus) and P300a (novelty); no effect on latencies of P300a/b or the early sensory component N100; P300b amplitude reduction correlated with perception-altering effects
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
Downgraded for
Imprecision
Quality profile
Sample size★★★★★
BlindingDouble-blind
Effect sizeClear benefit
Citations / year★★★★★
Authors
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)
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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.