Cannabidiol enhancement of exposure therapy in treatment refractory patients with phobias: study protocol of a randomized controlled trial (original) (raw)
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European Neuropsychopharmacology, 2022
Background: Phobic anxiety disorders are among the most prevalent psychiatric disorders and are burdensome in terms of loss of quality of life and work productivity. Evidence-based treatments are relatively successful in the majority of patients, especially exposure therapy. However, a substantial subset of patients fails to achieve or stay in remission. Preclinical and genetic research have yielded evidence that the cannabinoid system is involved in the extinction of fear, presumed to underlie the beneficial effects of exposure therapy in phobic disorders. A cannabinoid constituent that may enhance endocannabinoid signaling is cannabidiol (CBD), a non-psychoactive component of cannabis. Hence, the addition of CBD to exposure therapy is expected to strengthen effects of treatment. To determine the added benefit of CBD on exposure therapy, we conduct a randomized controlled trial, in which patients in whom previous treatment as usual has not yielded sufficient response receive either CBD or placebo preceding 8 exposure sessions in a double-blind fashion. A subsidiary aim is to explore which (combination of) clinical, behavioral and genetic profiles of patients are related to treatment response. Methods/design: This is an 8-week multicenter, randomized, double-blind, placebo-controlled trial. Seventy-two patients with social phobia or panic disorder with agoraphobia with incomplete response to earlier treatment will be included from outpatient clinics in the Netherlands. Patients are randomized to augmentation of exposure therapy with 300 mg CBD or placebo. The study medication is administered orally, 2 h preceding each of the eight 90 min exposure sessions. Measurements will take place at baseline, first administration of medication, every session, mid-treatment, last administration of medication, post-treatment and at 3 and 6 months' follow-up. The primary outcome measure is the score on the Fear Questionnaire (FQ). In addition, determinants of the expected treatment enhancing effect of CBD will be explored. Discussion: This is the first trial to investigate whether the addition of CBD to exposure therapy is effective in reducing phobic symptoms in treatment refractory patients with social phobia or panic disorder with agoraphobia.
Journal of Pharmacy Technology, 2023
Background: Anxiety is a condition for which current treatments are often limited by adverse events (AEs). Components of medicinal cannabis, cannabidiol (CBD) and tetrahydrocannabinol (THC), have been proposed as potential treatments for anxiety disorders, specifically posttraumatic stress disorder (PTSD). Objective: To evaluate quality-of-life outcomes after treatment with various cannabis formulations to determine the effectiveness and associated AEs. Methods: An interim analysis of data collected between September 2018 and June 2021 from the CA Clinics Observational Study. Patient-Reported Outcomes Measurement Information System-29 survey scores of 198 participants with an anxiety disorder were compared at baseline and after treatment with medicinal cannabis. The data of 568 anxiety participants were also analyzed to examine the AEs they experienced by the Medical Dictionary for Regulatory Activities organ system class. Results: The median doses taken were 50.0 mg/day for CBD and 4.4 mg/day for THC. The total participant sample reported significantly improved anxiety, depression, fatigue, and ability to take part in social roles and activities. Those who were diagnosed with PTSD (n = 57) reported significantly improved anxiety, depression, fatigue, and social abilities. The most common AEs reported across the whole participant cohort were dry mouth (32.6%), somnolence (31.3%), and fatigue (18.5%), but incidence varied with different cannabis formulations. The inclusion of THC in a formulation was significantly associated with experiencing gastrointestinal AEs; specifically dry mouth and nausea. Conclusions: Formulations of cannabis significantly improved anxiety, depression, fatigue, and the ability to participate in social activities in participants with anxiety disorders. The AEs experienced by participants are consistent with those in other studies.
Neuropsychopharmacology, 2011
Generalized Social Anxiety Disorder (SAD) is one of the most common anxiety conditions with impairment in social life. Cannabidiol (CBD), one major non-psychotomimetic compound of the cannabis sativa plant, has shown anxiolytic effects both in humans and in animals. This preliminary study aimed to compare the effects of a simulation public speaking test (SPST) on healthy control (HC) patients and treatment-naïve SAD patients who received a single dose of CBD or placebo. A total of 24 never-treated patients with SAD were allocated to receive either CBD (600 mg; n ¼ 12) or placebo (placebo; n ¼ 12) in a double-blind randomized design 1 h and a half before the test. The same number of HC (n ¼ 12) performed the SPST without receiving any medication. Each volunteer participated in only one experimental session in a double-blind procedure. Subjective ratings on the Visual Analogue Mood Scale (VAMS) and Negative Self-Statement scale (SSPS-N) and physiological measures (blood pressure, heart rate, and skin conductance) were measured at six different time points during the SPST. The results were submitted to a repeated-measures analysis of variance. Pretreatment with CBD significantly reduced anxiety, cognitive impairment and discomfort in their speech performance, and significantly decreased alert in their anticipatory speech. The placebo group presented higher anxiety, cognitive impairment, discomfort, and alert levels when compared with the control group as assessed with the VAMS. The SSPS-N scores evidenced significant increases during the testing of placebo group that was almost abolished in the CBD group. No significant differences were observed between CBD and HC in SSPS-N scores or in the cognitive impairment, discomfort, and alert factors of VAMS. The increase in anxiety induced by the SPST on subjects with SAD was reduced with the use of CBD, resulting in a similar response as the HC. Neuropsychopharmacology advance online publication, 9 February 2011;
Rich evidence has shown that cannabis products exert a broad gamut of effects on emotional regulation. The main psychoactive ingredient of hemp, Δ 9-tetrahydrocannabinol (THC), and its synthetic cannabinoid analogs have been reported to either attenuate or exacerbate anxiety and fear-related behaviors in humans and experimental animals. The heterogeneity of cannabisinduced psychological outcomes reflects a complex network of molecular interactions between the key neurobiological substrates of anxiety and fear and the endogenous cannabinoid system, mainly consisting of the arachidonic acid derivatives anandamide and 2-arachidonoylglycerol (2-AG) and two receptors, respectively termed CB 1 and CB 2. The high degree of interindividual variability in the responses to cannabis is contributed by a wide spectrum of factors, including genetic and environmental determinants, as well as differences in the relative concentrations of THC and other alkaloids (such as cannabidiol) within the plant itself. The present article reviews the currently available knowledge on the herbal, synthetic and endogenous cannabinoids with respect to the modulation of anxiety responses, and highlights the challenges that should be overcome to harness the therapeutic potential of some of these compounds, all the while limiting the side effects associated with cannabis consumption.
Could Cannabidiol Be a Treatment for Coronavirus Disease-19-Related Anxiety Disorders?
Cannabis and Cannabinoid Research
Coronavirus disease-19 (COVID-19)-related anxiety and post-traumatic stress symptoms (PTSS) or post-traumatic stress disorder (PTSD) are likely to be a significant long-term issue emerging from the current pandemic. We hypothesize that cannabidiol (CBD), a chemical isolated from Cannabis sativa with reported anxiolytic properties, could be a therapeutic option for the treatment of COVID-19-related anxiety disorders. In the global over-thecounter CBD market, anxiety, stress, depression, and sleep disorders are consistently the top reasons people use CBD. In small randomized controlled clinical trials, CBD (300-800 mg) reduces anxiety in healthy volunteers, patients with social anxiety disorder, those at clinical high risk of psychosis, in patients with Parkinson's disease, and in individuals with heroin use disorder. Observational studies and case reports support these findings, extending to patients with anxiety and sleep disorders, Crohn's disease, depression, and in PTSD. Larger ongoing trials in this area continue to add to this evidence base with relevant patient cohorts, sample sizes, and clinical end-points. Pre-clinical studies reveal the molecular targets of CBD in these indications as the cannabinoid receptor type 1 and cannabinoid receptor type 2 (mainly in fear memory processing), serotonin 1A receptor (mainly in anxiolysis) and peroxisome proliferator-activated receptor gamma (mainly in the underpinning antiinflammatory/antioxidant effects). Observational and pre-clinical data also support CBD's therapeutic value in improving sleep (increased sleep duration/quality and reduction in nightmares) and depression, which are often comorbid with anxiety. Together these features of CBD make it an attractive novel therapeutic option in COVID-related PTSS that merits investigation and testing through appropriately designed randomized controlled trials.
Current Treatment Options in Psychiatry, 2022
Purpose of review Anxiety is a prevalent mental health condition which manifests as a disproportionate response of fear to a perceived threat. Different types of anxiety disorders vary in their pathophysiology, symptoms and treatments. The causes of anxiety disorders are complex and largely unknown; however, it has been suggested that a number of brain mechanisms and neurotransmitters are involved in the development of these conditions. While there are non-pharmacological treatments for anxiety, many patients are prescribed medications such as selective serotonin reuptake inhibitors, serotonin and noradrenaline reuptake inhibitors and/or benzodiazepines. Unfortunately, these medications have issues with efficacy and safety, and therefore, there is a continuing need for newer medicines. The cannabis constituents of tetrahydrocannabinol (THC), cannabidiol (CBD) and terpenes have been proposed as a potential treatment for anxiety conditions. Recent findings Medicinal cannabis constituents act on the endocannabinoid system (ECS) and other targets. The ECS affects several physiological functions through modulation of the central nervous system and inflammatory pathways. In particular, CBD has been suggested to exhibit anxiolytic properties, whereas THC can either have an anxiogenic or anxiolytic effect, depending on the dose, route of administration and individual genetic
Journal of Psychopharmacology, 2011
Animal and human studies indicate that cannabidiol (CBD), a major constituent of cannabis, has anxiolytic properties. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the present study was to investigate this in patients with generalized social anxiety disorder (SAD) using functional neuroimaging. Regional cerebral blood flow (rCBF) at rest was measured twice using (99m)Tc-ECD SPECT in 10 treatment-naïve patients with SAD. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping. Relative to placebo, CBD was associated with significantly decreased subjective anxiety (p < 0.001), reduced ECD uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus (p < 0.001, uncorrected), and increased ECD uptake in the right posterior cingulate gyrus (p < 0.001, uncorrected). These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.
Comorbid cannabis use and panic disorder: short term and long term follow-up study
Human Psychopharmacology: Clinical and Experimental, 2004
Objectives The aim of the study was to compare the treatment of panic disorder in patients with or without cannabis use according to response, relapse and side effects. Materials and Methods 66 panic disorder (PD) patients were included in our study. All the subjects met the DSM-IV diagnosis of panic disorder (n ¼ 45) or panic disorder with agoraphobia (n ¼ 21). Twenty four patients experienced their first panic attack within 48 h of cannabis use and then went on to develop PD. All the patients received pharmacologic treatment with paroxetine (gradually increased up to 40 mg/d). A masked rater that was blind to the group allocation, assessed patients in order to rate anxiety symptoms and medication side effects. Relapse was defined as the occurrence of a single panic attack after remission of panic symptoms. The instruments were administered at baseline and also at the 4, 8 and 12 weeks visits and at the 1 year visit. Results The two groups responded equally well to paroxetine treatment as measured at the 8 weeks and 12 months followup visits. There were no significant effects of age, sex and duration of illness as covariates with response rates between the two groups. Also PD or PDA diagnosis did not affect the treatment response in either group. There were no significant differences in weight gain, sexual side effects or relapse rates between patients according to gender or comorbid diagnosis. Summary Acute cannabis use can be associated with the onset of panic attacks and panic disorder, and panic disorder which develops after cannabis use is responsive to pharmacotherapy.
Communications Medicine
Background Evidence suggests cannabidiol (CBD) has anxiolytic properties, indicating potential for novel treatment strategies. However, few clinical trials of CBD-based products have been conducted, and none thus far have examined the impact of these products on cognition. Methods For the open-label stage of clinical trial NCT02548559, autoregressive linear modeling assessed efficacy and tolerability of four-weeks of 1 mL t.i.d. treatment with a full-spectrum, high-CBD sublingual solution (9.97 mg/mL CBD, 0.23 mg/mL Δ−9-tetrahydrocannabinol) in 14 outpatients with moderate-to-severe anxiety, defined as ≥16 on the Beck Anxiety Inventory (BAI) or ≥11 on the Overall Anxiety Severity and Impairment Scale (OASIS). Results Findings suggest significant improvement on primary outcomes measuring anxiety and secondary outcomes assessing mood, sleep, quality of life, and cognition (specifically executive function) following treatment. Anxiety is significantly reduced at week 4 relative to base...
Could Cannabidiol be a treatment for COVID-19-related anxiety disorders?
2020
COVID-19-related anxiety and post-traumatic stress symptoms (PTSS) or disorder (PTSD) are likely to be a significant longterm issue emerging from the current pandemic. We hypothesise that cannabidiol (CBD), a chemical isolated from Cannabis Sativa with reported anxiolytic properties, could be a therapeutic option for the treatment of COVID-19-related anxiety disorders. In the global over-the-counter CBD market, anxiety, stress, depression and sleep disorders are consistently the top reasons people use CBD. In small randomised, controlled clinical trials, CBD reduces anxiety in healthy volunteers, patients with social anxiety disorder, those at clinical high risk of psychosis, in patients with Parkinson's disease, and in individuals with heroin use disorder. Case reports and series support these findings, extending to patients with anxiety and sleep disorders, Crohn's disease, depression and in PTSD. Preclinical studies reveal the molecular targets of CBD in these indications as the cannabinoid receptors type 1 and 2 (CB1 and CB2) receptors (mainly in fear memory processing), serotonin 5HT1a receptors (mainly in anxiolysis) and peroxisome proliferator-activated receptor gamma (PPARγ) (mainly in the underpinning anti-inflammatory/anti-oxidant effects). Observational and preclinical data also support CBD's therapeutic value in improving sleep (increased sleep duration/quality and reduction in nightmares) and depression, often comorbid with anxiety. Together these features of CBD to reduce anxiety and depression, and improve sleep disturbances, could be an attractive novel therapeutic option in relieving COVID-related post-traumatic stress symptoms.