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Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: A preliminary report

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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.
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... For example, anxiety is at least twice as prevalent in those with chronic neck or back pain [34]. Both CBD and THC are both thought to have anxiolytic effects, however clinical studies to date have been limited and of low quality [32,[35][36][37]. The relationship between anxiety and CP is complex and bidirectional, as described by the biopsychosocial model of pain, in which anxiety is both a cause and consequence of CP [38,39]. ...
... However, anxiety marginally increased in the no anxiety cohort. The reduction in anxiety in the anxiety cohort is consistent with the clinical studies also showing reductions in anxiety following CBMP treatment, however these limited studies focused on only social anxiety and used different PROMs compared to this study, so direct comparison is difficult [35,37]. Moreover, it may be expected for anxiety to have decreased for over 50% of the participants who were illicit cannabis users through accessing legal CBMP treatment, due to a reduction in the potential stress and stigma analogous with illicit drug use [21,97,98]. ...
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Introduction There is growing evidence on the efficacy of cannabis-based medicinal products (CBMPs) for chronic pain(CP). Due to the complex interaction between chronic pain and anxiety, and the potential impact of CBMPs on both anxiety and chronic pain, this article aimed to compare the outcomes of CP patients with and without co-morbid anxiety following CBMP treatment. Methods Participants were prospectively enrolled in this cohort study and categorized by baseline General Anxiety Disorder-7(GAD-7) scores, into ‘no anxiety’(GAD-7<5) and ‘anxiety’(GAD-7≥5) cohorts. Primary outcomes were changes in Brief Pain Inventory Short-Form, Short-form McGill Pain Questionnaire-2, Pain Visual Analogue Scale, Sleep Quality Scale (SQS), GAD-7 and EQ-5D-5L index values at 1, 3 and 6 months compared to baseline. Results 1254 patients (anxiety=711; no anxiety=543) met inclusion criteria. Significant improvements in all primary outcomes were observed in both cohorts at all timepoints (p<0.050), except GAD-7 in the no anxiety group(p>0.050). The anxiety cohort reported greater improvements in EQ-5D-5L index values, SQS and GAD-7(p<0.050), but there were no consistent differences in pain outcomes. Conclusion A potential association between CBMPs and improvements in pain and health-related quality of life (HRQoL) in CP patients was identified. CP patients with co-morbid anxiety achieved greater improvements in general HRQoL, but not pain-specific outcomes.
... Clinical studies (i.e., placebo-controlled, case-control studies) have shown that CBD is able to decrease social anxiety symptoms and sedation [176] and anxiety and cognitive impairment during speech performance [177], as well as symptoms (i.e., anxiety and cognitive impairments) in post-traumatic stress disorder (PTSD) patients [178][179][180][181]. A recent clinical trial reported significant improvements in anxiety, mood, sleep, and executive functions in patients with moderate-severe anxiety treated with high-CBD/low-THC sublingual solutions (CBD: 9.97 mg/mL, THC: 0.23 mg/mL, 4 weeks). ...
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Cannabis is the most used drug of abuse worldwide. It is well established that the most abundant phytocannabinoids in this plant are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). These two compounds have remarkably similar chemical structures yet vastly different effects in the brain. By binding to the same receptors, THC is psychoactive, while CBD has anxiolytic and antipsychotic properties. Lately, a variety of hemp-based products, including CBD and THC, have become widely available in the food and health industry, and medical and recreational use of cannabis has been legalized in many states/countries. As a result, people, including youths, are consuming CBD because it is considered “safe”. An extensive literature exists evaluating the harmful effects of THC in both adults and adolescents, but little is known about the long-term effects of CBD exposure, especially in adolescence. The aim of this review is to collect preclinical and clinical evidence about the effects of cannabidiol.
... The copyright holder for this preprint this version posted March 5, 2023. ; https://doi.org/10.1101/2023.03.02.23286709 doi: medRxiv preprint anxiogenic effects 28-32 of delta-9-tetrahydrocannabinol, the main intoxicating cannabinoid in cannabis, CBD is non-intoxicating and has anxiolytic 33,34 and antipsychotic properties. [35][36][37] CBD modulates brain activation in response to cognitive and emotional fMRI tasks, particularly in medial temporal cortex and striatal regions, in both healthy and established psychosis cohorts. ...
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... One trial [61] reported a greater improvement in anxiety, assessed by VAS for mood with 600 mg cannabidiol compared with placebo in 24 patients. In another small double-blinded crossover study, CBD resulted in significantly lower anxiety in 10 patients with SAD [62]. However, these studies were limited by small sample sizes. ...
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... In Parkinson's patients, CBD ameliorated the motor symptoms and also improved the quality of life of these patients [205]. CBD also decreases anxiety in socially anxious individuals [206,207]. In sum, based on the accumulated data so far, CBD seems to have great therapeutic potential without the significant adverse psychoactive effects associated with THC and this is likely due to its multiple mechanisms of action. ...
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... Cannabinoids' increased prevalence in consumer products makes them ideal analytes to facilitate student engagement. 29 From their benefit as medical treatments 30,31 to their legalization for recreational use, public interest in cannabis spans diverse student backgrounds and majors. 32 Both cannabidiol (CBD) and tetrahydrocannabinoid (THC) are linked to various topics in pharmacology, toxicology, and forensics. ...
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