Morgan CJA, Curran HV. Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis. Br J Psychiatry 192: 306-307

Clinical Psychopharmacology Unit, Sub-Department of Clinical Health Psychology, University College London, London, UK.
The British Journal of Psychiatry (Impact Factor: 7.99). 05/2008; 192(4):306-7. DOI: 10.1192/bjp.bp.107.046649
Source: PubMed


Cannabis contains various cannabinoids, two of which have almost opposing actions: Delta9-tetrahydrocannabinol (Delta9-THC) is psychotomimetic, whereas cannabidiol (CBD) has antipsychotic effects. Hair samples were analysed to examine levels of Delta9-THC and CBD in 140 individuals. Three clear groups emerged: ;THC only', ;THC+CBD' and those with no cannabinoid in hair. The THC only group showed higher levels of positive schizophrenia-like symptoms compared with the no cannabinoid and THC+CBD groups, and higher levels of delusions compared with the no cannabinoid group. This provides evidence of the divergent properties of cannabinoids and has important implications for research into the link between cannabis use and psychosis.

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Available from: Celia Morgan, Sep 30, 2014
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    • "Neuroimaging studies suggest a correlation between higher CBD content and both better neuronal integrity in the striatum as indicated by NAA/tCR ratios and lower hippocampal volume and grey matter density. However, whereas the association between CBD content and the experience of psychosis-like symptoms later in life has repeatedly and independently been demonstrated (Morgan and Curran, 2008; Schubart et al., 2011; Morgan et al., 2012), other findings need confirmation in new cohorts. Finally, the only study that examined the impact of CBD/THC ratios in cannabis on acute behavioural and cognitive effects used a naturalistic approach, and remarkably did not find significant differences on psychotomimetic effects between groups smoking cannabis with low and high CBD (Morgan et al., 2010). "
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    ABSTRACT: Despite extensive study over the past decades, available treatments for schizophrenia are only modestly effective and cause serious metabolic and neurological side effects. Therefore, there is an urgent need for novel therapeutic targets for the treatment of schizophrenia. A highly promising new pharmacological target in the context of schizophrenia is the endocannabinoid system. Modulation of this system by the main psychoactive component in cannabis, Δ9-tetrahydrocannabinol (THC), induces acute psychotic effects and cognitive impairment. However, the non-psychotropic, plant-derived cannabinoid agent cannabidiol (CBD) may have antipsychotic properties, and thus may be a promising new agent in the treatment of schizophrenia. Here we review studies that investigated the antipsychotic properties of CBD in human subjects. Results show the ability of CBD to counteract psychotic symptoms and cognitive impairment associated with cannabis use as well as with acute THC administration. In addition, CBD may lower the risk for developing psychosis that is related to cannabis use. These effects are possibly mediated by opposite effects of CBD and THC on brain activity patterns in key regions implicated in the pathophysiology of schizophrenia, such as the striatum, hippocampus and prefrontal cortex. The first small-scale clinical studies with CBD treatment of patients with psychotic symptoms further confirm the potential of CBD as an effective, safe and well-tolerated antipsychotic compound, although large randomised clinical trials will be needed before this novel therapy can be introduced into clinical practice. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Feb 2015 · Schizophrenia Research
    • "Delta-9-tetrahydrocannabiol (delta-9- THC), the main psychoactive ingredient, is responsible for inducing transient psychotic and anxiety symptoms (Bhattacharyya et al, 2009a; D'Souza et al, 2004). In contrast, Cannabidiol (CBD), another major ingredient may have anxiolytic (Crippa et al, 2009; Fusar-Poli et al, 2009) and antipsychoticlike effects (Zuardi et al, 2009) and may oppose the neural effects of delta-9-THC (Bhattacharyya et al, 2010) and block the psychotogenic (Bhattacharyya et al, 2010; Morgan and Curran, 2008) and cognitive (Morgan et al, 2010a, 2010b) effects of delta-9-THC. We have recently reported that the induction of psychotic symptoms by delta-9-THC may be related to its effects on the striatum and prefrontal cortex, integral components of a network of brain areas involved in processing of salient information (Bhattacharyya et al, 2012c), consistent with emerging evidence regarding the role of aberrant salience attribution in psychosis (Jensen and Kapur, 2009; Palaniyappan and Liddle, 2012). "
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    ABSTRACT: There is now considerable evidence to support the hypothesis that psychotic symptoms are the result of abnormal salience attribution, and that the attribution of salience is largely mediated through the prefrontal cortex, striatum and hippocampus. Although these areas show differential activation under the influence of delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD), the two major derivatives of cannabis sativa, little is known about the effects of these cannabinoids on the functional connectivity between these regions. We investigated this in healthy occasional cannabis users by employing event-related fMRI following oral administration of delta-9-THC, CBD or a placebo capsule. Employing a seed cluster based functional connectivity analysis that involved using the average time-series from each seed cluster for a whole-brain correlational analysis, we investigated the effect of drug condition on functional connectivity between the seed clusters and the rest of the brain during an oddball salience processing task. Relative to the placebo condition, delta-9-THC and CBD had opposite effects on the functional connectivity between the dorsal striatum, prefrontal cortex, and hippocampus. Delta-9-THC reduced fronto-striatal connectivity, which was related to its effect on task performance, whereas this connection was enhanced by CBD. Conversely mediotemporal-prefrontal connectivity was enhanced by delta-9-THC and reduced by CBD. Our results suggest that the functional integration of brain regions involved in salience processing is differentially modulated by single doses of delta-9-THC and CBD and that this relates to the processing of salient stimuli.Neuropsychopharmacology accepted article preview online, 24 September 2014. doi:10.1038/npp.2014.258.
    No preview · Article · Sep 2014 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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    • "[19,87] Its anti-psychotic potential has subsequently been repeatedly demonstrated in dopamine and glutamate models of psychosis in both animals and humans. [88] [89] [90] The presence of significant amounts of CBD in street cannabis (an increasingly uncommon phenomenon) has been shown to protect users against both psychotic symptoms [21] and memory impairment. [20] Studies in humans using functional magnetic resonance imaging of the brain have demonstrated that these effects are related to the oppositional effects of THC and CBD in key areas of interest for schizophrenia including the striatum, prefrontal cortex and hippocampus. "
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    ABSTRACT: Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines. The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology. In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders. Copyright © 2013 John Wiley & Sons, Ltd.
    Preview · Article · Feb 2014 · Drug Testing and Analysis
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