Dose-related modulation of event-related potentials to novel and target stimuli by intravenous Δ⁹-THC in humans.
Deepak Cyril D'Souza, Daniel J Fridberg, Patrick D. Skosnik, Ashley H Williams, Brian J Roach, Nagendra S. Singh, Michelle Carbuto, Jacqueline Elander, Ashley Schnakenberg, Brian Pittman, R Andrew Sewell, Mohini Ranganathan, Daniel H. Mathalon
Neuropsychopharmacology June 2012 DOI: 10.1038/npp.2012.8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 26 |
| Population | Healthy subjects |
| Intervention | Delta-9-tetrahydrocannabinol (Δ⁹-THC) |
| Dose | placebo, 0.015 and 0.03 mg/kg |
| Measures | P300a, P300b, N100 |
| Topics | Cannabis |
| Key findings | Delta-9-THC dose-dependently reduced P300a and P300b amplitudes without changing their latency or the earlier N100 component, and induced dose-dependent psychotomimetic effects, perceptual alterations, and subjective high. Reductions in P3b amplitude correlated with perceptual alterations. The authors suggest cannabinoid agonists may disrupt cortical processes responsible for context updating and automatic orientation of attention while leaving processing speed and earlier sensory components intact. |
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.
Comparable studies
Other randomized controlled trials on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants | 2012 | Randomized controlled trial | n = 48 |
| Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... | 2009 | Double-blind, randomized, placebo-controlled crossover trial | n = 15 |
| Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects | 2012 | Randomized controlled trial | n = 16 |
| Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... | 2009 | Randomized controlled trial | n = 15 |
| Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Healthy volunteers with a history of light cannabis use | 2019 | Randomized, double-blind, within-subjects crossover | n = 14 |
Citations in the library
Cited by 26
- Traditional marijuana, high‐potency cannabis and synthetic cannabinoids: increasing risk for psychosis World Psychiatry September 22, 2016
- Gone to Pot – A Review of the Association between Cannabis and Psychosis Frontiers in Psychiatry May 22, 2014
- Neuropharmacology of New Psychoactive Substances (NPS): Focus on the Rewarding and Reinforcing Properties of Cannabimimetics and Amphetamine-Like Stimulants Frontiers in Neuroscience April 19, 2016
- Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia JAMA Network Open May 1, 2020
- Human Laboratory Studies on Cannabinoids and Psychosis. Biological Psychiatry April 1, 2016
and 21 more in the library
Cites 14
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids Behavioural Pharmacology September 1, 2005
- The safety of studies with intravenous Δ⁹-tetrahydrocannabinol in humans, with case histories. Psychopharmacology February 2012
- Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers Molecular Psychiatry July 12, 2011
- Association between a cannabinoid receptor gene (CNR1) polymorphism and cannabinoid-induced alterations of the auditory event-related P300 potential. Neuroscience Letters May 27, 2011
and 9 more in the library