Please use this link to access this publication. Abstract Δ9-Tetrahydrocannabinol (Δ9-THC), the principal psychoactive constituent of the Cannabis sativa plant, and other agonists at the central cannabinoid (CB1) receptor may induce characteristic psychomotor effects, psychotic reactions and cognitive impairment resembling schizophrenia. These effects of Δ9-THC can be reduced in animal and human models of psychopathology by two exogenous cannabinoids, cannabidiol (CBD) and SR141716. CBD is the second most abundant constituent of Cannabis sativa that has weak partial antagonistic properties at the CB1 receptor. CBD inhibits the reuptake and hydrolysis of anandamide, the most important endogenous CB1 receptor agonist, and exhibits neuroprotective antioxidant activity. SR141716 is a potent and selective CB1 receptor...

Abstract The main active ingredient in cannabis, delta-9-tetrahydrocannabinol (THC), can acutely induce psychotic symptoms and impair episodic and working memory. Another major constituent, cannabidiol (CBD), may attenuate these effects. This study aimed to determine the effects of THC and CBD, both alone and in combination on psychotic symptoms and memory function. A randomised, double-blind crossover design compared the effects of (i) placebo, (ii) THC 8 mg, (iii) CBD 16 mg and (iv) THC 8 mg + CBD 16 mg administered by inhalation through a vaporiser. Using an experimental medicine approach to predict treatment sensitivity, we selected 48 cannabis users from the community on the basis of (1) schizotypal personality questionnaire...

Abstract The pharmacological interventions available for individuals in the early stages of psychosis are extremely limited. For those at clinical high risk for psychosis, there is no licensed treatment available. For those with first-episode psychosis, all licensed antipsychotic medications act via dopamine D2 receptors. While treatment with antipsychotics is transformative in some patients, in others, it is ineffective. In addition, these medications can often cause adverse effects which make patients reluctant to take them. This is a particular problem in the early phases of psychosis, when patients are being treated for the first time, as unpleasant experiences may colour their future attitude towards treatment. Recent...

Please use this link to access this publication. Key Points Question  To what extent is the association between cannabis use and psychotic-like experiences attributable to predispositional (ie, shared genetic) or to individual-specific factors? Findings  This cross-sectional study of twin and nontwin sibling pairs analyzed a combined sample comprising 4674 individuals and found significant evidence for shared genetic factors between cannabis involvement and psychotic-like experiences. After accounting for genetic overlap, frequent users of cannabis were more likely to report psychotic-like experiences than relatives who used cannabis less frequently. Meaning  Although shared genetic influences are important, person-specific factors also appear to influence the association between cannabis involvement and psychotic-like...

Abstract Emotional dysregulation and anxiety are common in people at clinical high risk for psychosis (CHR) and are associated with altered neural responses to emotional stimuli in the striatum and medial temporal lobe. Using a randomised, double-blind, parallel-group design, 33 CHR patients were randomised to a single oral dose of CBD (600 mg) or placebo. Healthy controls (n = 19) were studied under identical conditions but did not receive any drug. Participants were scanned with functional magnetic resonance imaging (fMRI) during a fearful face-processing paradigm. Activation related to the CHR state and to the effects of CBD was examined using a region-of-interest approach. During fear processing, CHR...

Abstract   Rationale: Stress is a risk factor for psychosis and treatments which mitigate its harmful effects are needed. Cannabidiol (CBD) has antipsychotic and anxiolytic effects.   Objectives: We investigated whether CBD would normalise the neuroendocrine and anxiety responses to stress in clinical high risk for psychosis (CHR) patients.   Methods: Thirty-two CHR patients and 26 healthy controls (HC) took part in the Trier Social Stress Test (TSST) and their serum cortisol, anxiety and stress associated with public speaking were estimated. Half of the CHR participants were on 600 mg/day of CBD (CHR-CBD) and half were on placebo (CHR-P) for 1 week.   Results: One-way analysis of variance...