Abstract
BackgroundCannabis use can induce acute and long-lasting 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.MethodsTwenty-four healthy men participated in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject, ∆9-THC challenge study.ResultsCompared 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).DiscussionPrevious modest cannabis use blunts the acute behavioral and neurophysiological effects of ∆9-THC, which are more marked in people who have never used cannabis.
Highlights
Cannabis use can induce acute and long-lasting psychosis and cognitive dysfunction
We conducted a Cochrane meta-analysis to determine the effects of pharmacological interventions aimed at reduction or prevention of weight gain in schizophrenia
Reboxetine may be slightly effective in preventing weight gain (Weight: mean differences (MD) -2.09 kg, 95% CI -3.12 to -1.05; participants = 111; studies = 3; BMI: MD -0.70, 95% CI -1.03 to -0.36; participants = 111; studies = 3) and but the quality of evidence is low as the studies are small and have all been conducted by the same group
Summary
METH- or MK-801–induced hyperactivity in rats and MK-801–induced PPI deficits in mice. TAK-063 at 0.1 mg/kg did not affect plasma prolactin levels and cataleptic response induced by HAL or OLA in rats. Discussion: PDE10A inhibitors and HAL showed similar patterns of gene regulation in indirect pathway MSNs in mice. Combined treatment with TAK-063 and either HAL or OLA at subeffective doses produced significant antipsychotic-like effects but no augmentation of the plasma prolactin level and cataleptic response. Further preclinical and clinical studies will be needed, TAK-063 may provide a novel mechanism as a PDE10A inhibitor for use as combination therapy in schizophrenia. DELTA-9-TETRAHYDROCANNABINOL CHALLENGE IN CANNABIS USERS AND NONUSERS DIFFERENTIALLY AFFECTS BRAIN FUNCTION AND BEHAVIOR: AN FMRI STUDY OF DEVELOPMENT OF TOLERANCE. Marco Colizzi*,1, Philip McGuire, Vincent Giampietro, Steve Williams, Mick Brammer, Sagnik Bhattacharyya1 1Institute of Psychiatry, King’s College
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