Modulation of acute effects of delta-9-tetrahydrocannabinol on psychotomimetic effects, cognition and brain function by previous cannabis exposure

TY - JOUR

T1 - Modulation of acute effects of delta-9-tetrahydrocannabinol on psychotomimetic effects, cognition and brain function by previous cannabis exposure

AU - Colizzi, Marco

AU - McGuire, Philip

AU - Giampietro, Vincent

AU - Williams, Steve

AU - Brammer, Mick

AU - Bhattacharyya, Sagnik

PY - 2018/6/21

Y1 - 2018/6/21

N2 - Cannabis use has been associated with psychosis and cognitive dysfunction. Some evidence suggests that the acute behavioral and neurocognitive effects of the main active ingredient in cannabis, (−)-trans-Δ9-tetrahydrocannabinol (∆9-THC), might be modulated by previous cannabis exposure. However, this has not been investigated either using a control group of non-users, or following abstinence in modest cannabis users, who represent the majority of recreational users. Twenty-four healthy men participated in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject, ∆9-THC challenge study. Compared to non-users (N=12; <5 lifetime cannabis joints smoked), abstinent modest cannabis users (N=12; 24.5±9 lifetime cannabis joints smoked) showed worse performance and stronger right hemispheric activation during cognitive processing, independent of the acute challenge (all P≤0.047). Acute ∆9-THC administration produced transient anxiety and psychotomimetic symptoms (all P≤0.02), the latter being greater in non-users compared to users (P=0.040). Non-users under placebo (control group) activated specific brain areas to perform the tasks, while deactivating others. An opposite pattern was found under acute (∆9-THC challenge in non-users) as well as residual (cannabis users under placebo) effect of ∆9-THC. Under ∆9-THC, cannabis users showed brain activity patterns intermediate between those in non-users under placebo (control group), and non-users under ∆9-THC (acute effect) and cannabis users under placebo (residual effect). In non-users, the more severe the ∆9-THC-induced psychotomimetic symptoms and cognitive impairments, the more pronounced was the neurophysiological alteration (all P≤0.036). Previous modest cannabis use blunts the acute behavioral and neurophysiological effects of ∆9-THC, which are more marked in people who have never used cannabis.

AB - Cannabis use has been associated with psychosis and cognitive dysfunction. Some evidence suggests that the acute behavioral and neurocognitive effects of the main active ingredient in cannabis, (−)-trans-Δ9-tetrahydrocannabinol (∆9-THC), might be modulated by previous cannabis exposure. However, this has not been investigated either using a control group of non-users, or following abstinence in modest cannabis users, who represent the majority of recreational users. Twenty-four healthy men participated in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject, ∆9-THC challenge study. Compared to non-users (N=12; <5 lifetime cannabis joints smoked), abstinent modest cannabis users (N=12; 24.5±9 lifetime cannabis joints smoked) showed worse performance and stronger right hemispheric activation during cognitive processing, independent of the acute challenge (all P≤0.047). Acute ∆9-THC administration produced transient anxiety and psychotomimetic symptoms (all P≤0.02), the latter being greater in non-users compared to users (P=0.040). Non-users under placebo (control group) activated specific brain areas to perform the tasks, while deactivating others. An opposite pattern was found under acute (∆9-THC challenge in non-users) as well as residual (cannabis users under placebo) effect of ∆9-THC. Under ∆9-THC, cannabis users showed brain activity patterns intermediate between those in non-users under placebo (control group), and non-users under ∆9-THC (acute effect) and cannabis users under placebo (residual effect). In non-users, the more severe the ∆9-THC-induced psychotomimetic symptoms and cognitive impairments, the more pronounced was the neurophysiological alteration (all P≤0.036). Previous modest cannabis use blunts the acute behavioral and neurophysiological effects of ∆9-THC, which are more marked in people who have never used cannabis.

KW - Cannabis use

KW - Cognitive functioning

KW - Delta-9-tetrahydrocannabinol

KW - Functional Magnetic Resonance Imaging

KW - Psychosis

KW - Tolerance

UR - http://www.scopus.com/inward/record.url?scp=85048800456&partnerID=8YFLogxK

U2 - 10.1016/j.euroneuro.2018.04.003

DO - 10.1016/j.euroneuro.2018.04.003

M3 - Article

AN - SCOPUS:85048800456

SN - 0924-977X

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

ER -