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Dose-related modulation of event-related potentials to novel and target stimuli by intravenous Δ⁹-THC in humans.
Neuropsychopharmacology 2012; 37(7):1632-46N

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.

Authors+Show Affiliations

Psychiatry Service, VA Connecticut Healthcare System, West Haven, CT 06516, USA. deepak.dsouza@yale.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

22334121

Citation

D'Souza, Deepak Cyril, et al. "Dose-related Modulation of Event-related Potentials to Novel and Target Stimuli By Intravenous Δ⁹-THC in Humans." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 37, no. 7, 2012, pp. 1632-46.
D'Souza DC, Fridberg DJ, Skosnik PD, et al. Dose-related modulation of event-related potentials to novel and target stimuli by intravenous Δ⁹-THC in humans. Neuropsychopharmacology. 2012;37(7):1632-46.
D'Souza, D. C., Fridberg, D. J., Skosnik, P. D., Williams, A., Roach, B., Singh, N., ... Mathalon, D. (2012). Dose-related modulation of event-related potentials to novel and target stimuli by intravenous Δ⁹-THC in humans. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 37(7), pp. 1632-46. doi:10.1038/npp.2012.8.
D'Souza DC, et al. Dose-related Modulation of Event-related Potentials to Novel and Target Stimuli By Intravenous Δ⁹-THC in Humans. Neuropsychopharmacology. 2012;37(7):1632-46. PubMed PMID: 22334121.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dose-related modulation of event-related potentials to novel and target stimuli by intravenous Δ⁹-THC in humans. AU - D'Souza,Deepak Cyril, AU - Fridberg,Daniel J, AU - Skosnik,Patrick D, AU - Williams,Ashley, AU - Roach,Brian, AU - Singh,Nagendra, AU - Carbuto,Michelle, AU - Elander,Jacqueline, AU - Schnakenberg,Ashley, AU - Pittman,Brian, AU - Sewell,R Andrew, AU - Ranganathan,Mohini, AU - Mathalon,Daniel, Y1 - 2012/02/15/ PY - 2012/2/16/entrez PY - 2012/2/16/pubmed PY - 2012/9/22/medline SP - 1632 EP - 46 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 37 IS - 7 N2 - 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. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/22334121/Dose_related_modulation_of_event_related_potentials_to_novel_and_target_stimuli_by_intravenous_Δ⁹_THC_in_humans_ L2 - http://dx.doi.org/10.1038/npp.2012.8 DB - PRIME DP - Unbound Medicine ER -