Nicole Evans

How Cannabis Causes Paranoia: Using the Intravenous Administration of ∆9-Tetrahydrocannabinol (THC) to Identify Key Cognitive Mechanisms Leading to Paranoia

Paranoia is receiving increasing attention in its own right, since it is a central experience of psychotic disorders and a marker of the health of a society. Paranoia is associated with use of the most commonly taken illicit drug, cannabis. The objective was to determine whether the principal psychoactive ingredient of cannabis—∆9-tetrahydrocannabinol (THC)—causes paranoia and to use the drug as a probe to identify key cognitive mechanisms underlying paranoia. A randomized, placebo-controlled, between-groups test of the effects of intravenous THC was conducted. A total of 121 individuals with paranoid ideation were randomized to receive placebo, THC, or THC preceded by a cognitive awareness condition. Paranoia was assessed extensively via a real social situation, an immersive virtual reality experiment, and standard self-report and interviewer measures. Putative causal factors were assessed. Principal components analysis was used to create a composite paranoia score and composite causal variables to be tested in a mediation analysis. THC significantly increased paranoia, negative affect (anxiety, worry, depression, negative thoughts about the self), and a range of anomalous experiences, and reduced working memory capacity. The increase in negative affect and in anomalous experiences fully accounted for the increase in paranoia. Working memory changes did not lead to paranoia. Making participants aware of the effects of THC had little impact. In this largest study of intravenous THC, it was definitively demonstrated that the drug triggers paranoid thoughts in vulnerable individuals. The most likely mechanism of action causing paranoia was the generation of negative affect and anomalous experiences.

Height, social comparison, and paranoia: an immersive virtual reality experimental study.

Mistrust of others may build upon perceptions of the self as vulnerable, consistent with an association of paranoia with perceived lower social rank. Height is a marker of social status and authority. Therefore we tested the effect of manipulating height, as a proxy for social rank, on paranoia. Height was manipulated within an immersive virtual reality simulation. Sixty females who reported paranoia experienced a virtual reality train ride twice: at their normal and reduced height. Paranoia and social comparison were assessed. Reducing a persons height resulted in more negative views of the self in comparison with other people and increased levels of paranoia. The increase in paranoia was fully mediated by changes in social comparison. The study provides the first demonstration that reducing height in a social situation increases the occurrence of paranoia. The findings indicate that negative social comparison is a cause of mistrust.

An early Phase II randomised controlled trial testing the effect on persecutory delusions of using CBT to reduce negative cognitions about the self: the potential benefits of enhancing self confidence.

Background Research has shown that paranoia may directly build on negative ideas about the self. Feeling inferior can lead to ideas of vulnerability. The clinical prediction is that decreasing negative self cognitions will reduce paranoia. Method Thirty patients with persistent persecutory delusions were randomised to receive brief CBT in addition to standard care or to standard care (ISRCTN06118265). The six session intervention was designed to decrease negative, and increase positive, self cognitions. Assessments at baseline, 8 weeks (posttreatment) and 12 weeks were carried out by a rater blind to allocation. The primary outcomes were posttreatment scores for negative self beliefs and paranoia. Secondary outcomes were psychological well-being, positive beliefs about the self, persecutory delusions, social comparison, self-esteem, anxiety, and depression. Results Trial recruitment and retention were feasible and the intervention highly acceptable to the patients. All patients provided follow-up data. Posttreatment there was a small reduction in negative self beliefs (Cohens d = 0.24) and a moderate reduction in paranoia (d = 0.59), but these were not statistically significant. There were statistically significant improvements in psychological well-being (d = 1.16), positive beliefs about the self (d = 1.00), negative social comparison (d = 0.88), self-esteem (d = 0.62), and depression (d = 0.68). No improvements were maintained. No adverse events were associated with the intervention. Conclusions The intervention produced short-term gains consistent with the prediction that improving cognitions about the self will reduce persecutory delusions. The improvement in psychological well-being is important in its own right. We recommend that the different elements of the intervention are tested separately and that the treatment is lengthened.

Virtual reality in the treatment of persecutory delusions: Randomised controlled experimental study testing how to reduce delusional conviction

Background Persecutory delusions may be unfounded threat beliefs maintained by safety-seeking behaviours that prevent disconfirmatory evidence being successfully processed. Use of virtual reality could facilitate new learning. Aims To test the hypothesis that enabling patients to test the threat predictions of persecutory delusions in virtual reality social environments with the dropping of safety-seeking behaviours (virtual reality cognitive therapy) would lead to greater delusion reduction than exposure alone (virtual reality exposure). Method Conviction in delusions and distress in a real-world situation were assessed in 30 patients with persecutory delusions. Patients were then randomised to virtual reality cognitive therapy or virtual reality exposure, both with 30 min in graded virtual reality social environments. Delusion conviction and real-world distress were then reassessed. Results In comparison with exposure, virtual reality cognitive therapy led to large reductions in delusional conviction (reduction 22.0%, P = 0.024, Cohens d = 1.3) and real-world distress (reduction 19.6%, P = 0.020, Cohens d = 0.8). Conclusion Cognitive therapy using virtual reality could prove highly effective in treating delusions.

Gut feelings, deliberative thought, and paranoid ideation: A study of experiential and rational reasoning

Rapid intuitive hunches or gut feelings may be a compelling source of evidence for paranoid ideas. Conversely, a failure to apply effortful analytic thinking may contribute to the persistence of such thoughts. Our main aim was to examine for the first time the associations of persecutory thinking with experiential and rational thinking styles. Five hundred individuals recruited from the general population completed self-report assessments of current persecutory ideation, general reasoning styles and personality traits. Persecutory ideation was independently associated with greater use of experiential reasoning and less use of rational reasoning. The correlations were small. Persecutory ideation was also positively associated with neuroticism and negatively correlated with extraversion, agreeableness and conscientiousness. There was no evidence of an interaction between neuroticism and experiential reasoning in the prediction of paranoia, but high experiential reasoning in the context of low rational reasoning was particularly associated with persecutory ideation. Overall, the study provides rare evidence of self-reported general reasoning styles being associated with delusional ideation. Perceived reliance on intuition is associated with paranoid thinking, while perceived reliance on deliberation is associated with fewer such thoughts. The dual process theory of reasoning may provide a framework to contribute to the understanding of paranoid thinking.

The patient experience of sleep problems and their treatment in the context of current delusions and hallucinations

Objectives There is increasing recognition that sleep problems are common in patients with psychosis, that they exacerbate delusions and hallucinations and should be a treatment target. The aim of this study was to gain a patient perspective on the nature of sleep problems in psychosis and experience of treatment. Design A qualitative, semi‐structured interview‐based study to explore patient accounts of sleep problems and associated psychological treatment. Methods Ten patients with recent delusions and hallucinations, who had experienced sleep problems and received psychological treatment during a clinical trial (the Better Sleep Trial), were interviewed. Responses were analysed using interpretative phenomenological analysis. Results Patients reported experiencing problems of getting to sleep, staying asleep, too much sleep, nightmares, and erratic sleep patterns. These sleep problems caused emotional distress, fatigue, and reduction in daytime activities. Worry and psychotic experiences disturbed sleep, while consequent tiredness meant that patients coped poorly with voices and persecutory fears. Treatment for sleep problems was viewed very positively and considered to have wide‐ranging impacts. Conclusions Sleep disturbance is a major problem for patients with psychosis, which should be treated more often in services using evidence‐based interventions. Practitioner points Psychological interventions for sleep problems are valued by patients with psychosis. Patients with current distressing psychotic experiences report wide‐ranging benefits from a brief psychological intervention for sleep problems.

Genetic moderation of the effects of cannabis: Catechol-O-methyltransferase (COMT) affects the impact of Δ9-tetrahydrocannabinol (THC) on working memory performance but not on the occurrence of psychotic experiences

Cannabis use can induce cognitive impairments and psychotic experiences. A functional polymorphism in the catechol-O-methyltransferase (COMT) gene (Val158Met) appears to influence the immediate cognitive and psychotic effects of cannabis, or ∆9-tetrahydrocannabinol (THC), its primary psychoactive ingredient. This study investigated the moderation of the impact of experimentally administered THC by COMT. Cognitive performance and psychotic experiences were studied in participants without a psychiatric diagnosis, using a between-subjects design (THC vs. placebo). The effect of COMT Val158Met genotype on the cognitive and psychotic effects of THC, administered intravenously in a double-blind, placebo-controlled manner to 78 participants who were vulnerable to paranoia, was examined. The results showed interactive effects of genotype and drug group (THC or placebo) on working memory, assayed using the Digit Span Backwards task. Specifically, THC impaired performance in COMT Val/Val, but not Met, carriers. In contrast, the effect of THC on psychotic experiences, measured using the Community Assessment of Psychic Experiences (CAPE) positive dimension, was unaffected by COMT genotype. This study is the largest to date examining the impact of COMT genotype on response to experimentally administered THC, and the first using a purely non-clinical cohort. The data suggest that COMT genotype moderates the cognitive, but not the psychotic, effects of acutely administered THC.

Self-Confidence and Paranoia: An Experimental Study Using an Immersive Virtual Reality Social Situation.

BACKGROUND Paranoia may build directly upon negative thoughts about the self. There have been few direct experimental tests of this hypothesis. AIMS The aim of the study was to test the immediate effects of manipulating self-esteem in individuals vulnerable to paranoia. METHOD A two condition cross-over experimental test was conducted. The participants were 26 males reporting paranoid ideation in the past month. Each participant experienced a neutral immersive virtual reality (VR) social environment twice. Before VR participants received a low self-confidence manipulation or a high self-confidence manipulation. The order of manipulation type was randomized. Paranoia about the VR avatars was assessed. RESULTS The low self-confidence manipulation, relative to the high self-confidence manipulation, led to significantly more negative social comparison in virtual reality and higher levels of paranoia. CONCLUSIONS Level of self-confidence affects the occurrence of paranoia in vulnerable individuals. The clinical implication is that interventions designed to improve self-confidence may reduce persecutory ideation.

Targeting Recovery in Persistent Persecutory Delusions: A Proof of Principle Study of a New Translational Psychological Treatment (the Feeling Safe Programme)

Background: Many patients do not respond adequately to current pharmacological or psychological treatments for psychosis. Persistent persecutory delusions are common in clinical services, and cause considerable patient distress and impairment. Our aim has been to build a new translational personalized treatment, with the potential for wide use, that leads to high rates of recovery in persistent persecutory delusions. We have been developing, and evaluating individually, brief modular interventions, each targeting a key causal factor identified from our cognitive model. These modules are now combined in “The Feeling Safe Programme”. Aims: To test the feasibility of a new translational modular treatment for persistent persecutory delusions and provide initial efficacy data. Method: 12 patients with persistent persecutory delusions in the context of non-affective psychosis were offered the 6-month Feeling Safe Programme. After assessment, patients chose from a personalized menu of treatment options. Four weekly baseline assessments were carried out, followed by monthly assessments. Recovery in the delusion was defined as conviction falling below 50% (greater doubt than certainty). Results: 11 patients completed the intervention. One patient withdrew before the first monthly assessment due to physical health problems. An average of 20 sessions (SD = 4.4) were received. Posttreatment, 7 out of 11 (64%) patients had recovery in their persistent delusions. Satisfaction ratings were high. Conclusions: The Feeling Safe Programme is feasible to use and was associated with large clinical benefits. To our knowledge this is the first treatment report focused on delusion recovery. The treatment will be tested in a randomized controlled trial.

Persecutory ideation and a history of cannabis use.

BACKGROUND Cannabis use is associated with the occurrence of psychotic experiences. However there are multiple distinct psychotic experiences, each likely to occur as quantitative traits in the general population. In this study we tested for an association of cannabis use with a dimensional assessment of persecutory ideation. METHOD A total of 1714 individuals from the general population completed a dimensional measure of current persecutory ideation and reported on whether they had ever taken cannabis. RESULTS Of all participants, 648 (38%) reported a history of cannabis use. These individuals reported significantly higher current levels of persecutory ideation. The amount of variance in paranoia scores explained was low. Individuals with a history of cannabis use had almost twice the odds of reporting any paranoid ideation in the past month compared with individuals who had never taken cannabis. CONCLUSIONS Using a state of the art assessment, the study adds to findings of an association of persecutory ideation with cannabis use.