Use of cannabidiol in anxiety and anxiety-related disorders

Skelley, Jessica W.; Deas, Crystal M.; Curren, Zachary; Ennis, Jonathan

doi:10.1016/j.japh.2019.11.008

Cited by 80 publications

(67 citation statements)

References 37 publications

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“…A recent systematic review identified six randomized pre-clinical studies in this area. 90 Most used doses of 300 mg or higher, and two examined a range of different doses. The first of these asked 60 healthy volunteers to complete a simulated public speaking test after pre-treatment with either CBD (100, 300 and 900 mg), clonazepam (1 mg) or placebo.…”

Section: Effects Of Cbd On Anxietymentioning

confidence: 99%

Lack of evidence for the effectiveness or safety of over-the-counter cannabidiol products

Chesney

McGuire

Freeman

et al. 2020

Therapeutic Advances in Psychopharmacology

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Over the past 5 years, public interest in the potential health benefits of cannabidiol (CBD) has increased exponentially, and a wide range of over-the-counter (OTC) preparations of CBD are now available. A substantial proportion of the population appears to have used these products, yet the extent to which they are effective or safe is unclear. We reviewed the evidence for whether CBD has significant pharmacological and symptomatic effects at the doses typically found in OTC preparations. We found that most of the evidence for beneficial effects is derived from studies of pure, pharmaceutical grade CBD at relatively high doses. Relatively few studies have examined the effect of OTC CBD preparations, or of CBD at low doses. Thus, at present, there is little evidence that OTC CBD products have health benefits, and their safety has not been investigated. Controlled trials of OTC and low-dose CBD preparations are needed to resolve these issues.

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Section: Effects Of Cbd On Anxietymentioning

confidence: 99%

Lack of evidence for the effectiveness or safety of over-the-counter cannabidiol products

Chesney

McGuire

Freeman

et al. 2020

Therapeutic Advances in Psychopharmacology

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“…CBD has weak affinity for endocannabinoid receptors and is not psychoactive (Pertwee 2005). It has been found to modulate the effects of THC and endocannabinoids and may be effective for symptomatic treatment of anxiety and psychosis and in treating some childhood epilepsy syndromes (Gofshteyn et al 2017;Bhattacharyya et al 2018;Skelley et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Origin and evolution of the cannabinoid oxidocyclase gene family

Velzen

Schranz

2020

Preprint

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Cannabis is an ancient crop representing a rapidly increasing legal market, especially for medicinal purposes. Medicinal and psychoactive effects of Cannabis rely on specific terpenophenolic ligands named cannabinoids. Recent whole-genome sequencing efforts have uncovered variation in multiple genes encoding the final steps in cannabinoid biosynthesis. However, the origin, evolution, and phylogenetic relationships of these cannabinoid oxidocyclase genes remain unclear. To elucidate these aspects we performed comparative genomic analyses of Cannabis, related genera within the Cannabaceae family, and selected outgroup species. Results show that cannabinoid oxidocyclase genes originated in the Cannabis lineage from within a larger gene expansion in the Cannabaceae family. Localization and divergence of oxidocyclase genes in the Cannabis genome revealed two main syntenic blocks, each comprising tandemly repeated cannabinoid oxidocyclase genes. By comparing these blocks with those in genomes from closely related species we propose an evolutionary model for the origin, neofunctionalization, duplication, and diversification of cannabinoid oxidocycloase genes. Based on phylogenetic meta-analyses, we propose a comprehensive classification of three main clades and seven subclades that is intended to aid unequivocal referencing and identification of cannabinoid oxidocyclase genes. Our data suggest that cannabinoid oxidocyclase gene copy number variation may have less functional relevance than previously thought. Instead, we propose that cannabinoid phenotype is primarily determined by presence/absence of single-copy genes. Increased sampling across Cannabis’ native geographic range is likely to uncover additional cannabinoid oxidocyclase gene sequence variation.Significance statementCannabis genome sequencing efforts have revealed extensive cannabinoid oxidocyclase gene variation. However, phylogenetic relationships and evolution of these genes remains unclear. Our meta analysis of currently available data reveals that these genes comprise three main clades and seven subclades that originated through Cannabis-specific gene duplication and divergence. Our new conceptual and evolutionary framework serves as a reference for future description and functional analyses of cannabinoid oxidocyclases.

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“…Similarly, our results suggest that CB1 receptor activity is also crucial to the expression of CBD's facilitation of stress-induced reinstatement of cocaine seeking. Given that CBD shows important molecular and behavioral anti-anxiety effects (Campos et al, 2017;Skelley et al, 2019), it is difficult to propose a possible mechanism underlying these results. However, the structural and functional ubiquity of CB1 receptors in the central nervous system (Busquets-Garcia et al, 2018) allows CBD to interfere in unexpected ways with different brain structures, in certain environmental situations leading to drug relapse.…”

Section: Discussionmentioning

confidence: 99%

The effects of cannabidiol on cue- and stress-induced reinstatement of cocaine seeking behavior in mice are reverted by the CB1 receptor antagonist AM4113

Luján

Alegre-Zurano

Martín‐Sánchez

et al. 2020

Preprint

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Cocaine addiction is a brain disorder characterized by the consumption of the drug despite harmful consequences, the loss of control over drug intake and increased risk of relapse. Albeit prolonged research efforts, there is no available medication approved for the treatment of cocaine addiction. In the last decade, cannabinoid-based compounds have drawn increased interest for its potential therapeutic applications in various psychiatric conditions. Cannabidiol, a non-psychotomimetic constituent of the C. sativa plant, shows promising results in rodent models of anxiety, schizophrenia, depression and drug addiction. However, the specific effects and mechanisms of action of cannabidiol in a rodent model of extinction-based abstinence and drug seeking relapse remain unclear. Here, we administered cannabidiol (20 mg/kg) to male CD-1 mice trained to self-administer cocaine (0.75 mg/kg/inf) during extinction training (8-12 days). Then, we evaluated the reinstatement of cocaine seeking induced by cues, stress and drug priming. To ascertain the participation of CB1 receptors in these behavioral responses, we systemically administered the neutral cannabinoid antagonist AM4113 (5 mg/kg) before each reinstatement session. The results document that cannabidiol (20 mg/kg) does not modulate extinction training but attenuates 'extinction burst' responding after one cannabidiol injection. Furthermore, cannabidiol specifically blocked the reinstatement of cocaine seeking triggered by a cue presentation, an effect prevented by AM4113 (5 mg/kg). Unexpectedly, cannabidiol facilitated stress-induced reinstatement of cocaine seeking behavior, also by a CB1-dependent mechanism.Finally, cannabidiol did not affect cocaine-primed (10 mg/kg) precipitation of cocaine seeking. Our results reveal a series of complex changes induced by cannabidiol treatment with opposite implications for the reinstatement of cocaine seeking behavior that may limit therapeutic opportunities. The activity of CB1 receptors seems to play a 3 crucial role in the expression of cannabidiol-induced neuroplasticity underlying both the desirable and undesirable reinstatement effects here detailed.

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Use of cannabidiol in anxiety and anxiety-related disorders

Cited by 80 publications

References 37 publications

Lack of evidence for the effectiveness or safety of over-the-counter cannabidiol products

Lack of evidence for the effectiveness or safety of over-the-counter cannabidiol products

Origin and evolution of the cannabinoid oxidocyclase gene family

The effects of cannabidiol on cue- and stress-induced reinstatement of cocaine seeking behavior in mice are reverted by the CB1 receptor antagonist AM4113

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