Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration-effect relations using the IB-de-risk tool

BACKGROUND: Preclinical research suggests that cannabidiol (CBD) may have therapeutic potential in pathological anxiety. Dosing guidelines to inform future human studies are however lacking. AIM: We aimed to predict the therapeutic window for anxiety-reducing effects of CBD in humans based on preclinical models. METHODS: We conducted two systematic searches in PubMed and Embase up to August 2021, into pharmacokinetic (PK) and pharmacodynamic (PD) data of systemic CBD exposure in humans and animals, which includes anxiety-reducing and potential side effects. Risk of bias was assessed with SYRCLE's RoB tool and Cochrane RoB 2.0. A control group was an inclusion criterion in outcome studies. In human outcome studies, randomisation was required. We excluded studies that co-administered other substances. We used the IB-de-risk tool for a translational integration of outcomes. RESULTS: We synthesised data from 87 studies. For most observations (70.3%), CBD had no effect on anxiety outcomes. There was no identifiable relation between anxiety outcomes and drug levels across species. In all species (humans, mice, rats), anxiety-reducing effects seemed to be clustered in certain concentration ranges, which differed between species. DISCUSSION: A straightforward dosing recommendation was not possible, given variable concentration-effect relations across species, and no consistent linear effect of CBD on anxiety reduction. Currently, these results raise questions about the broad use as a drug for anxiety. Meta-analytic studies are needed to quantitatively investigate drug efficacy, including aspects of anxiety symptomatology. Acute and (sub)chronic dosing studies with integrated PK and PD outcomes are required for substantiated dose recommendations

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration-effect relations using the IB-de-risk tool

BACKGROUND: Preclinical research suggests that cannabidiol (CBD) may have therapeutic potential in pathological anxiety. Dosing guidelines to inform future human studies are however lacking. AIM: We aimed to predict the therapeutic window for anxiety-reducing effects of CBD in humans based on preclinical models. METHODS: We conducted two systematic searches in PubMed and Embase up to August 2021, into pharmacokinetic (PK) and pharmacodynamic (PD) data of systemic CBD exposure in humans and animals, which includes anxiety-reducing and potential side effects. Risk of bias was assessed with SYRCLE's RoB tool and Cochrane RoB 2.0. A control group was an inclusion criterion in outcome studies. In human outcome studies, randomisation was required. We excluded studies that co-administered other substances. We used the IB-de-risk tool for a translational integration of outcomes. RESULTS: We synthesised data from 87 studies. For most observations (70.3%), CBD had no effect on anxiety outcomes. There was no identifiable relation between anxiety outcomes and drug levels across species. In all species (humans, mice, rats), anxiety-reducing effects seemed to be clustered in certain concentration ranges, which differed between species. DISCUSSION: A straightforward dosing recommendation was not possible, given variable concentration-effect relations across species, and no consistent linear effect of CBD on anxiety reduction. Currently, these results raise questions about the broad use as a drug for anxiety. Meta-analytic studies are needed to quantitatively investigate drug efficacy, including aspects of anxiety symptomatology. Acute and (sub)chronic dosing studies with integrated PK and PD outcomes are required for substantiated dose recommendations

sj-xlsx-7-jop-10.1177_02698811221124792 – Supplemental material for Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool

Supplemental material, sj-xlsx-7-jop-10.1177_02698811221124792 for Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool by Caroline MB Kwee, Joop MA van Gerven, Fleur LP Bongaerts, Danielle C Cath, Gabriël Jacobs, Johanna MP Baas and Lucianne Groenink in Journal of Psychopharmacolog

sj-xlsx-10-jop-10.1177_02698811221124792 – Supplemental material for Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool

Supplemental material, sj-xlsx-10-jop-10.1177_02698811221124792 for Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool by Caroline MB Kwee, Joop MA van Gerven, Fleur LP Bongaerts, Danielle C Cath, Gabriël Jacobs, Johanna MP Baas and Lucianne Groenink in Journal of Psychopharmacolog

sj-xlsx-5-jop-10.1177_02698811221124792 – Supplemental material for Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool

Supplemental material, sj-xlsx-5-jop-10.1177_02698811221124792 for Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool by Caroline MB Kwee, Joop MA van Gerven, Fleur LP Bongaerts, Danielle C Cath, Gabriël Jacobs, Johanna MP Baas and Lucianne Groenink in Journal of Psychopharmacolog

sj-xlsx-9-jop-10.1177_02698811221124792 – Supplemental material for Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool

Supplemental material, sj-xlsx-9-jop-10.1177_02698811221124792 for Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool by Caroline MB Kwee, Joop MA van Gerven, Fleur LP Bongaerts, Danielle C Cath, Gabriël Jacobs, Johanna MP Baas and Lucianne Groenink in Journal of Psychopharmacolog

sj-xlsx-6-jop-10.1177_02698811221124792 – Supplemental material for Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool

Supplemental material, sj-xlsx-6-jop-10.1177_02698811221124792 for Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool by Caroline MB Kwee, Joop MA van Gerven, Fleur LP Bongaerts, Danielle C Cath, Gabriël Jacobs, Johanna MP Baas and Lucianne Groenink in Journal of Psychopharmacolog

sj-xlsx-8-jop-10.1177_02698811221124792 – Supplemental material for Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool

Supplemental material, sj-xlsx-8-jop-10.1177_02698811221124792 for Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool by Caroline MB Kwee, Joop MA van Gerven, Fleur LP Bongaerts, Danielle C Cath, Gabriël Jacobs, Johanna MP Baas and Lucianne Groenink in Journal of Psychopharmacolog

Skull base surgery during the Covid-19 pandemic: The Italian skull base society recommendations

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (Covid-19), is highly contagious with devastating impacts for healthcare systems worldwide. Medical staff are at high risk of viral contamination and it is imperative to know what personal protective equipment is appropriate for each situation. Furthermore, elective clinics and operations have been reduced in order to mobilize manpower to the acute specialties combatting the outbreak; appropriate differentiation between patients who require immediate care and those who can receive telephone consultation or whose treatment might viably be postponed is therefore crucial. Italy was one of the earliest and hardest-hit European countries and therefore the Italian Skull Base Society board has promulgated specific recommendations based on consensus best practices and the literature, where available. Only urgent surgical operations are recommended and all patients should be tested at least twice (on days 4 and 2 prior to surgery). For positive patients, procedures should be postponed until after swab test negativization. If the procedure is vital to the survival of the patient, FFP3 and/or PAPRs devices, goggles, full-face visor, double gloves, water-resistant gowns and protective caps, are mandatory. For negative patients, use of at least FFP2 mask is recommended. In all cases the use of drills, which promote the aerosolization of potentially infected mucous particles, should be avoided. Given the potential neurotropism of SARS-CoV-2, dura handling should be minimized. It is only through widely-agreed protocols and teamwork that we will be able to deal with the evolving and complex implications of this new pandemic. This article is protected by copyright. All rights reserved