Towards virtual reality exposure therapy for cocaine use disorder: A feasibility study of inducing cocaine craving through virtual reality.

Background: Craving is a core symptom of cocaine use disorders (CUD). Inducing craving in exposure to substance cues is of relevant interest for numerous clinical applications. Virtual reality exposure (VRE) might be a promising candidate for improving cue-exposure paradigms but remains almost not studied for cocaine. This feasibility study's main aim is to assess whether VRE to cocaine cues is capable to induce cocaine craving compared with VRE to neutral cues. Methods: We conducted a within-subjects controlled trial in which cocaine users performed 3 consecutive 10 mins-tasks: VRE to neutral and cocaine cues, and a relaxation-based resting procedure. The primary outcome was the change in Cocaine Craving Questionnaire-Brief (CCQ-Brief) scores between VRE to neutral and cocaine cues. Secondary outcomes included between-tasks changes in scores of cocaine craving, pleasant/unpleasant emotions as well as self-efficacy to cope with craving. Results: We recruited 11 chronic cocaine users including mostly crack smokers (45 %), cocaine snorters (36 %) and injectors (18 %), with 73 % of participants meeting DSM-IV criteria for cocaine dependence and/or abuse. Non-parametrical sign tests indicated significant large increases of CCQ-Brief scores from neutral to cocaine cue-VRE (S(11) = 11, p < 0.01, Cliff's Δ = 0.65, 95 % CI: 0.17-0.88). Exploratory comparative analyses indicated significant changes after our post-cues VRE relaxation procedure, with cocaine craving and emotions restored to baseline. Conclusions: VRE to cocaine cues was feasible and capable to induce cocaine craving in cocaine users. This second VRE-based cue-reactivity study in cocaine paves the way for unexplored research on VRE clinical applications for CUD.

No harmful effect of propranolol administered prior to fear memory extinction in rats and humans.

Exposure therapy is an evidence-based treatment option for anxiety-related disorders. Many patients also take medication that could, in principle, affect exposure therapy efficacy. Clinical and laboratory evidence indeed suggests that benzodiazepines may have detrimental effects. Large clinical trials with propranolol, a common beta-blocker, are currently lacking, but several preclinical studies do indicate impaired establishment of safety memories. Here, we investigated the effects of propranolol given prior to extinction training in 9 rat studies (N = 215) and one human study (N = 72). A Bayesian meta-analysis of our rat studies provided strong evidence against propranolol-induced extinction memory impairment during a drug-free test, and the human study found no significant difference with placebo. Two of the rat studies actually suggested a small beneficial effect of propranolol. Lastly, two rat studies with a benzodiazepine (midazolam) group provided some evidence for a harmful effect on extinction memory, i.e., impaired extinction retention. In conclusion, our midazolam findings are in line with prior literature (i.e., an extinction retention impairment), but this is not the case for the 10 studies with propranolol. Our data thus support caution regarding the use of benzodiazepines during exposure therapy, but argue against a harmful effect of propranolol on extinction learning.

Effects of Narrative Exposure Therapy for Treating Depressive and Anxious Disorders: A Systematic Review and Meta-Analysis.

OBJECTIVE: Narrative exposure therapy (NET) has been used in various contexts for the treatment of the effects of trauma, with promising results in clinical trials. However, its effects on anxiety and depression are still unclear. The present study is a systematic review and meta-analysis of the effects of NET on depression and anxiety. METHODS: The Embase, Cumulative Index of Nursing and Allied Health Literature, PubMed, Web of Science core collection, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, and Wangfang databases were searched from the earliest records to March 2023. Two researchers independently screened the literature, extracted data, evaluated the risk of bias, and cross-checked the data. Meta-analysis was performed using the program RevMan 5.3. RESULTS: Eleven randomized controlled trials with a total of 754 participants were included in the study. The results showed that NET reduced both the depression (standard mean difference [SMD]=-0.51, 95% confidence interval [CI] -0.73--0.29, p<0.00001) and anxiety (SMD=-0.65, 95% CI -1.13--0.18, p=0.007) scores of the patients. Furthermore, NET was found to alleviate negative emotions associated with guilt (mean difference [MD]=-3.60, 95% CI -5.52--1.68, p=0.0005) and negative change (MD=-5.80, 95% CI -9.76--1.83, p=0.004). CONCLUSION: This analysis showed that NET can alleviate depression and anxiety. It may thus be used in clinical settings to alleviate patients' negative feelings and aid their overall recovery.

Improving Exposure Therapy: Rationale and Design of an International Consortium.

The Exposure Therapy Consortium (ETC) was established to advance the science and practice of exposure therapy. To encourage participation from researchers and clinicians, this article describes the organizational structure and activities of the ETC. Initial research working group experiences and a proof-of-principle study underscore the potential of team science and larger-scale collaborative research in this area. Clinical working groups have begun to identify opportunities to enhance access to helpful resources for implementing exposure therapy effectively. This article discusses directions for expanding the consortium's activities and its impact on a global scale.

The effect of social anxiety on threat acquisition and extinction: a systematic review and meta-analysis.

Although exposure-based therapy has been found to be effective at alleviating symptoms of social anxiety disorder, it often does not lead to full remission, and relapse after treatment is common. Exposure therapy is based on theoretical principles of extinction of conditioned fear responses. However, there are inconsistencies in findings across experiments that have investigated the effect of social anxiety on threat conditioning and extinction processes. This systematic review and meta-analysis aimed to examine whether elevated levels of social anxiety are associated with abnormalities in threat conditioning and extinction processes. A second aim was to examine the sensitivity of various study designs and characteristics to detect social anxiety-related differences in threat conditioning and extinction. A systematic search was conducted, which identified twenty-three experiments for inclusion in the review. The findings did not demonstrate compelling evidence that high levels of social anxiety are associated with atypical threat conditioning or extinction. Further, when systematically examining the data, there was no convincing support that the use of a particular psychophysiological measure, subjective rating, or experimental parameter yields more consistent associations between social anxiety and conditioning processes during threat acquisition or extinction. Meta-analyses demonstrated that during threat extinction, the use of anxiety ratings as a dependent variable, socially relevant unconditioned stimuli, and a higher reinforcement schedule produced more detectable effects of social anxiety on compromised extinction processes compared to any other dependent variable (subjective or physiological) or experimental parameter. Overall, the results of this study suggest that social anxiety is not reliably related to deficits in conditioning and extinction processes in the context of laboratory-based Pavlovian conditioning paradigms.

Spaced conditioned stimulus presentation facilitates the extinction of strong fear memory in mice.

Inducing fear memory extinction by re-presenting a conditioned stimulus (CS) is the foundation of exposure therapy for post-traumatic stress disorder (PTSD). Investigating differences in the ability of different CS presentation patterns to induce extinction learning is crucial for improving this type of therapy. Using a trace fear conditioning paradigm in mice, we demonstrate that spaced presentation of the CS facilitated the extinction of a strong fear memory to a greater extent than continuous CS presentation. These results lay the groundwork for developing more effective exposure therapy techniques for PTSD.

Implementation and Preliminary Outcomes of an Exposure-Based Summer Camp for Pediatric OCD and Anxiety.

Despite the high prevalence of anxiety disorders in children and adolescents and the existence of effective evidence-based treatments for them, access to psychological care remains a major public health concern. Summer camps may provide an effective treatment avenue for youth who might not otherwise have access to care. This study describes the design and implementation of Fear Facers, a semistructured, 5-day, daytime exposure-therapy-based summer camp designed for youth with a primary diagnosis of obsessive-compulsive disorder (OCD), social anxiety, separation anxiety, or a specific phobia. Preliminary data regarding feasibility and patient outcomes is also reported. Among 52 children and adolescents aged 7 to 16 who attended one of six camp sessions between 2018 and 2021, significant reductions in anxiety (d = 0.54) and OCD symptoms (d = 0.57) were observed from pre-camp to immediately post-camp. A subset of campers who were followed for an additional 3 months post-camp (n = 22) showed maintenance of treatment gains. Retention rates for the intervention were high. Our investigation provides further support for the use of a camp-based design for cognitive-behavioral approaches, and may provide a unique setting to maximize elements of inhibitory learning in exposures. We also discuss a number of elements regarding feasibility that need consideration for those hoping to develop similar interventions.

Virtual reality-based cognitive-behavioural therapy for the treatment of anxiety in patients with acute myocardial infarction: a randomised clinical trial.

Background: The presence of mental health conditions is pervasive in patients who experienced acute myocardial infarction (AMI), significantly disrupting their recovery. Providing timely and easily accessible psychological interventions using virtual reality-based cognitive-behavioural therapy (VR-CBT) could potentially improve both acute and long-term symptoms affecting their mental health. Aims: We aim to examine the effectiveness of VR-CBT on anxiety symptoms in patients with AMI who were admitted to the intensive care unit (ICU) during the acute stage of their illness. Methods: In this single-blind randomised clinical trial, participants with anxiety symptoms who were admitted to the ICU due to AMI were continuously recruited from December 2022 to February 2023. Patients who were Han Chinese aged 18-75 years were randomly assigned (1:1) via block randomisation to either the VR-CBT group to receive VR-CBT in addition to standard mental health support, or the control group to receive standard mental health support only. VR-CBT consisted of four modules and was delivered at the bedside over a 1-week period. Assessments were done at baseline, immediately after treatment and at 3-month follow-up. The intention-to-treat analysis began in June 2023. The primary outcome measure was the changes in anxiety symptoms as assessed by the Hamilton Anxiety Rating Scale (HAM-A). Results: Among 148 randomised participants, 70 were assigned to the VR-CBT group and 78 to the control group. The 1-week VR-CBT intervention plus standard mental health support significantly reduced the anxiety symptoms compared with standard mental health support alone in terms of HAM-A scores at both post intervention (Cohen's d=-1.27 (95% confidence interval (CI): -1.64 to -0.90, p<0.001) and 3-month follow-up (Cohen's d=-0.37 (95% CI: -0.72 to -0.01, p=0.024). Of the 70 participants who received VR-CBT, 62 (88.6%) completed the entire intervention. Cybersickness was the main reported adverse event (n=5). Conclusions: Our results indicate that VR-CBT can significantly reduce post-AMI anxiety at the acute stage of the illness; the improvement was maintained at the 3-month follow-up. Trial registration number: The trial was registered at www.chictr.org.cn with the identifier: ChiCTR2200066435.

Specific Phobia, Fear, and the Autism Spectrum in Children and Adolescents: Adapting OST for ASD.

Fears and phobias are a common mental health concern for youth, and particularly for autistic youth. The following review briefly summarizes the extant literature on specific phobias and specific phobias in autistic youth. The evidence base is briefly highlighted pointing to the strong base behind behavioral and cognitive-behavioral treatments and techniques. A broad discussion of key evidence-based treatment findings is presented, leading up to the impactful work of Thomas H. Ollendick in researching Öst's One-Session Treatment (OST) with children and adolescents. OST for child specific phobias is discussed, and particular emphasis is given to this treatment's ongoing adaptation for use with youth on the autism spectrum.

Correspondence to Antici et al. Salivary CRP predicts treatment response to virtual reality exposure therapy for social anxiety disorder.

The study by Antici et al. (2024) investigates the effects of virtual reality exposure therapy on social anxiety disorder (SAD), focusing on the relationship between C-reactive protein (CRP) levels in saliva and therapy outcomes. Findings indicate that this therapy not only reduces SAD symptoms and discomfort but also correlates with decreased systemic inflammation, as evidenced by lowered CRP levels. Remarkably, higher baseline CRP levels predicted a greater reduction in anxiety symptoms, suggesting a unique response pattern in SAD compared to other psychological disorders. This study highlights systemic inflammation's significance in SAD and the promise of non-invasive biomarkers like salivary CRP for managing psychological disorders. It calls for more research to understand the underlying mechanisms and validate these initial findings.

A Novel Intervention to Reduce Fear of Progression and Trauma Symptoms in Advanced Cancer Using Written Exposure to Worst-Case Scenarios.

Background: Adults with advanced cancer experience profound future uncertainty, reflected in elevated fear of cancer progression (FoP) and cancer-related trauma symptoms. These symptoms are associated with physical symptom burden and poorer quality of life, and few interventions exist to manage them. Objective: To develop and pilot a written exposure-based coping intervention (EASE) focused on worst-case scenarios among adults with advanced cancer reporting elevated cancer-related trauma symptoms or FoP. Design: A single-arm intervention development and pilot trial. Participants: The trial enrolled 29 U.S. adults with stage III or stage IV solid tumor cancer (n = 24) or incurable or higher-risk blood cancer (n = 5) reporting elevated cancer-related trauma symptoms or FoP. Among those screened, 74% were eligible, with an eligible-to-enrolled rate of 85%. Design/Measurements: EASE was delivered over five 1:1 videoconferencing sessions. Feasibility and acceptability were evaluated via attendance, surveys, and exit interviews. Outcomes were assessed at five time points through 3-month (FU1, main assessment of interest) and 4.5-month (FU2) follow-up. Results: Participant and interventionist feedback was used to iteratively refine EASE. Among participants, 86% (25/29) completed all five sessions and FU1; surveys and exit interviews indicated high acceptability. Primary outcomes of cancer-related trauma symptoms and FoP improved significantly from pre to both follow-ups by predominantly large effect sizes. Secondary outcomes of anxiety, depression, hopelessness, fear of death/dying, and fatigue, and most process measures improved significantly by FU1 or FU2. Conclusions: EASE, a novel adaptation of written exposure therapy, is a promising approach to reducing FoP and cancer-related trauma symptoms among adults with advanced cancer that warrants further study.

Shared and distinct effect mediators in exposure-based and traditional cognitive behavior therapy for fibromyalgia: Secondary analysis of a randomized controlled trial.

Fibromyalgia is a chronic pain condition associated with substantial suffering and societal costs. Traditional cognitive behavior therapy (T-CBT) is the most evaluated psychological treatment, but exposure therapy (Exp-CBT) has shown promise with a pronounced focus on the reduction of pain-related avoidance behaviors. In a recent randomized controlled trial (N = 274), we found that Exp-CBT was not superior to T-CBT (d = -0.10) in reducing overall fibromyalgia severity. This study investigated pain-related avoidance behaviors, pain catastrophizing, hypervigilance, pacing, overdoing and physical activity as potential mediators of the treatment effect. Mediation analyses were based on parallel process growth models fitted on 11 weekly measurement points, and week-by-week time-lagged effects were tested using random intercepts cross-lagged panel models. Results indicated that a reduction in avoidance behaviors, pain catastrophizing, and hypervigilance were significant mediators of change in both treatments. An increase in pacing and a reduction in overdoing were significant mediators in T-CBT only. Physical activity was not a mediator. In the time-lagged analyses, an unequivocal effect on subsequent fibromyalgia severity was seen of avoidance and catastrophizing in Exp-CBT, and of overdoing in T-CBT. Exposure-based and traditional CBT for fibromyalgia appear to share common treatment mediators, namely pain-related avoidance behavior, catastrophizing and hypervigilance.

Determinants of Exposure Therapy Implementation in Clinical Practice for the Treatment of Anxiety, OCD, and PTSD: A Systematic Review.

Exposure therapy (ET) forms a vital part of effective psychotherapy for anxiety-related presentations including anxiety disorders, obsessive-compulsive disorder (OCD), and post-traumatic stress disorder (PTSD), and is often underutilised in clinical practice. Using the Theoretical Domains Framework (TDF), this systematic review synthesised existing literature on the determinants of ET implementation for anxiety-related presentations and examined differences across presentations and developmental subgroups. Fifty-two eligible studies were assessed using the Mixed Methods Appraisal Tool, with 389 results (99%) mapped onto the TDF. Results suggested that clinicians' negative beliefs about the consequences of ET were commonly associated with reduced implementation. It also appeared that whilst broad unspecified ET training may be related to improved implementation for anxiety disorders; greater implementation for complex presentations (i.e., PTSD) likely requires more specialised training involving practical components. A subset of domains (e.g., social/professional role and identity) accounted for most results, whilst some remain unexplored (i.e., optimism; reinforcement; memory, attention, and decision processes) or underexplored (i.e., behavioural regulation). Likewise, specific presentations and developmental subgroups (i.e., PTSD and adults) represented a greater proportion of results in the literature than others (i.e., OCD and youth). Future research exploring ET implementation, across specific presentations and developmental subgroups, would benefit from integrating implementation science frameworks to guide the development of targeted, comprehensive strategies to close the research-practice gap of ET for the treatment of anxiety-related presentations.

The efficacy of augmented reality exposure therapy in the treatment of spider phobia-a randomized controlled trial.

The evidence for the use of Augmented Reality (AR) in treating specific phobias has been growing. However, issues of accessibility persist, especially in developing countries. The current study examined a novel, but relatively simple therapist guided smartphone-based AR Exposure Treatment (ARET) of spider phobia. Participants who reported symptoms of Arachnophobia were randomized into one of three comparison groups: ARET (n = 20), traditional in vivo exposure therapy (IVET; n = 18) and a waitlist control group (n = 17). Behavioral approach, subjective symptom measures, and galvanic skin response were assessed pre- and post-treatment. The study was concluded with a one-month follow up assessment. Results indicated that both treatment groups showed statistically significant and clinically meaningful improvements in behavioral approach at post-test that were maintained at 1 month follow- up, compared to the wait-listed group. Moreover, the treatment groups demonstrated significant improvements in subjective symptom report at 1-month follow up. Given its utility and potential accessibility, our findings suggest that future AR evaluation research could be conducted in therapy settings with minimal resources.

EFFects of Exposure and Cognitive behavioral Therapy for chronic BACK pain ("EFFECT-BACK"): study protocol for a randomized controlled trial.

INTRODUCTION: Chronic back pain is a widespread medical condition associated with high socioeconomic costs and increasing prevalence. Despite the advanced implementation of multidisciplinary approaches, providing a satisfactory treatment offer for those affected is often not possible. Exposure therapy (EXP) promises to be an effective and economical form of treatment and in a previous pilot study showed to be superior to cognitive behavioral therapy (CBT) in reducing perceived limitations of movement. The current study aims to further compare the efficacy of both treatment methods and identify those patient groups that particularly benefit from EXP. METHODS: The general objective of this randomized multicenter clinical trial (targeted N = 380) is to improve and expand the range of treatments available to patients with chronic back pain. As the primary objective of the study, two different psychological treatments (EXP and CBT) will be compared. The primary outcome measure is a clinically significant improvement in pain-related impairment, measured by the QPBDS, from baseline to 6-month follow-up. Secondary outcome measures are absolute changes and clinically significant improvements in variables coping, psychological flexibility, depressiveness, catastrophizing, exercise avoidance and fear of exercise, and intensity of pain. Participants are recruited in five psychological and medical centers in Germany and receive ten sessions of manualized therapy by trained licensed CBT therapists or clinical psychologists, who are currently in their post-gradual CBT training. Potential predictors of each treatment's efficacy will be explored with a focus on avoidance and coping behavior. CONCLUSION: This study will be the first RCT to compare CBT and EXP in chronic back pain in a large sample, including patients from different care structures due to psychological and medical recruitment centers. By identifying and exploring potential predictors of symptom improvement in each treatment group, this study will contribute to enable a more individualized assignment to treatment modalities and thus improves the care situation for chronic back pain and helps to create a customized treatment program for subgroups of pain patients. If our findings confirm EXP to be an efficacious and efficient treatment concept, it should gain more attention and be further disseminated. TRIAL REGISTRATION: ClinicalTrials.gov NCT05294081. Registered on 02 March 2022.

Salivary CRP predicts treatment response to virtual reality exposure therapy for social anxiety disorder.

BACKGROUND: Social anxiety disorder (SAD) places a profound burden on public health and individual wellbeing. Systemic inflammation may be important to the onset and maintenance of SAD, and anti-inflammatory treatments have shown promise in relieving symptoms of SAD. In the present study, we conducted secondary analyses on data from a randomized clinical trial to determine whether C-reactive protein (CRP) concentrations and social anxiety symptoms decreased over the course of virtual reality exposure therapy, and whether changes in social anxiety symptoms as a function of treatment varied as a function of CRP. METHOD: Adult participants (N = 78) with a diagnosis of SAD (59 % female) were randomized to receive exposure therapy alone, or exposure therapy supplemented with scopolamine. Social anxiety symptoms, salivary CRP, and subjective units of distress were measured across three exposure therapy sessions, at a post-treatment extinction retest, and at a 1-month follow-up. RESULTS: CRP decreased over the course of treatment, b = -0.03 (SE = 0.01), p =.02 95 %CI [-0.06, -0.004], as did all social anxiety symptom domains and subjective distress. Higher CRP was associated with greater decreases from pre-treatment to 1-month follow-up in fear, b = -0.45 (SE = 0.15), p =.004 95 %CI [-0.74, -0.15], and avoidance, b = -0.62 (SE = 0.19), p =.002 95 %CI [-1.01, -0.23], and in-session subjective distress from pre-treatment to post-treatment, b = -0.42 (SE = 0.21), p =.05 95 %CI [-0.83, -0.001]. However, declines in CRP were not correlated with declines in fear, r = -0.07, p =.61, or avoidance, r = -0.10, p =.49, within-persons. CONCLUSIONS: Virtual reality exposure therapy may be associated with an improvement in systemic inflammation in patients with severe SAD. Pre-treatment CRP may also be of value in predicting which patients stand to benefit the most from this treatment.

An investigation of the role of estradiol in fear reduction during a single session of exposure therapy.

Research suggests that estradiol may moderate fear extinction. It is unclear whether these results generalize to exposure therapy. The aim of the current study was to determine whether estradiol moderates outcomes in exposure therapy among women with anxiety disorders. Participants were 35 women with a primary diagnosis of an anxiety disorder who participated in the study as part of routine care at an anxiety specialty clinic. Endogenous estradiol was assessed via saliva. They provided subjective distress ratings before (pre) and after (post) an exposure session, as well as after a brief delay (recall). Contrary to predictions, there were no significant differences in exposure outcomes between the high and low estradiol groups. However, among participants with primary obsessive-compulsive disorder (OCD), results were partially consistent with the hypotheses. Women with lower estradiol initially demonstrated more improvement in subjective distress from pre- to post-exposure, but after the delay, significantly greater distress (attenuated extinction recall). Results suggest that women with lower estradiol may respond less favorably to exposure therapy for OCD relative to women with higher estradiol. These findings await replication in larger samples with longer recall delays. Should replication occur, these results may inform the use of estradiol to augment exposure therapy.

Written exposure therapy for veterans with co-occurring substance use disorders and PTSD: Study design of a randomized clinical trial.

There are high rates of posttraumatic stress disorder (PTSD) among treatment-seeking veterans with substance use disorders (SUD). While addiction programs traditionally do not address PTSD, there is evidence that trauma treatments for individuals with this comorbidity have improved PTSD and SUD outcomes. Written exposure therapy (WET), a five-session evidence-based psychotherapy (EBP) for PTSD, has high patient satisfaction, and lower dropout compared to other EBPs for PTSD. WET may be ideally suited for clinical settings that may not have the trauma expertise found in PTSD specialty clinics, given it requires less training time, treatment sessions, preparation time, and therapist involvement than existing EBPs, and no homework assignments. This paper describes the design, methodology, and protocol of a randomized clinical trial to evaluate whether treatment as usual (TAU) plus WET (n = 51) is superior to TAU plus a neutral topic writing condition (n = 51) on both PTSD and addiction outcomes for veterans in SUD treatment. The primary hypothesis is that participants assigned to TAU+WET, compared to those in TAU+ neutral topic writing, will report reduced symptoms of PTSD. The secondary hypothesis is that veterans receiving WET will have greater decreases in number of days of substance use compared to TAU+ neutral topic controls at follow-up. Assessments will take place at baseline, post-treatment, 8-week, and 12-week follow-up. Exploratory aims will examine the association between heart rate variability and treatment outcomes. If results prove promising, they will support WET as an effective brief, easy to disseminate, adjunct to current SUD treatment for veterans with comorbid PTSD. Trial registration: ClinicalTrials.gov ID NCT05327504.

Is disgust more resistant to extinction than fear? A meta-analytic review of laboratory paradigms.

Disgust can be acquired via evaluative conditioning; a process by which a neutral stimulus (conditioned stimulus; CS) comes to be evaluated as disgusting due to its pairing with an inherently disgusting stimulus (unconditioned stimulus; US). Research has shown that conditioned disgust responses are resistant to extinction which may have implications for disorders (i.e., contamination-based obsessive-compulsive disorder, specific phobias, and post-traumatic stress disorder) in which heightened disgust has been implicated. Importantly, extinction is the primary mechanism by which exposure therapies are thought to achieve symptom reduction for these disorders. Exposure therapies were originally modeled on fear extinction, whereas disgust extinction was largely overlooked until recently. Accordingly, differences in the degree to which learned disgust and fear can be attenuated via extinction learning remains unclear. The present investigation was a meta-analysis directly comparing the degree of extinction of conditioned disgust (n = 14) and conditioned fear (n = 14) in laboratory paradigms. Extinction was operationalized as the standardized mean difference (SMD) in evaluative ratings between the CS+ (the CS paired with the US) and CS- (the unpaired CS) after extinction training. Results of a subgroup analysis indicated that disgust (SMD = 0.52) was significantly more resistant to extinction than fear (SMD = 0.37). Additionally, a series of meta-regression analyses indicated that extinction was not influenced by important study characteristics (e.g., sex, age, number of conditioning and extinction trials). The findings suggest that extinction-based approaches may be less effective at attenuating learned disgust and research is needed to better optimize treatments for disgust-related disorders.

Enhancing massed prolonged exposure with cannabidiol to improve posttraumatic stress disorder: Design and methodology of a pilot randomized clinical trial.

Background: The impact of posttraumatic stress disorder (PTSD) is substantial and often results in pervasive functional impairments. Although evidence-based treatments for PTSD are established, there remains room for improvement as many individuals continue to meet diagnostic criteria even after successful treatment completion. Cannabidiol (CBD) has attracted considerable attention based on its potential to treat a myriad of health conditions. CBD may decrease anxiety and facilitate extinction learning processes, two critical targets of trauma-focused psychotherapies. We present the design and methods for a pilot randomized clinical trial to examine the combination of CBD and prolonged exposure for PTSD. Methods: Participants (n = 24) will be randomized to CBD or placebo for 18 days delivered in combination with ten daily prolonged exposure sessions over two weeks. The study medication will be Epidiolex® (250 mg BID). The PTSD Checklist for DSM-5 will be the primary outcome to assess PTSD severity at baseline, during treatment, and at 1-month follow-up. Blood, saliva, and heart rate will be collected during treatment to assess intervention effects on biological outcomes related to PTSD and the endocannabinoid system. Results: Consistent with the purpose of a pilot, our goals are to evaluate the feasibility of study procedures, safety of the intervention, and the preliminary effect of CBD to inform a larger trial. Descriptive and inferential statistics will be used to address study aims. Conclusion: Findings will inform decision making on combining CBD with behavioral interventions for PTSD to enhance outcomes and mitigate the morbidity of this debilitating condition.