For our COVID resources click here. Welcome to our full therapist resources site. Welcome to our resources site for clinicians who are intending to treat clients with PTSD, social anxiety disorder and/or panic disorder using the specialised cognitive therapies developed from our models of PTSD (Ehlers and Clark, ), social anxiety disorder (Clark and Wells, ), and panic disorder Mar 11, · Prevalence estimates are also provided for a mild classification of each disorder. Pooled prevalence estimates of depression and anxiety were highest in studies conducted in the Middle-East (%; %). Subgroup and meta-regression analyses were conducted across covariates, including sampling method and outcome measure Sep 04, · Methods. A search of MEDLINE (PubMed), PsycINFO, Web of Science Scopus, and the Cochrane Library databases was conducted for English-language papers published up to 1 January , using the search terms “cannabidiol” and “anxiety” or “fear” or “stress” or “anxiety disorder” or “generalized anxiety disorder” or “social anxiety disorder” or “social phobia” or
Try out PMC Labs and tell us what you think. Learn More. Cannabidiol CBDa Cannabis sativa constituent, is a pharmacologically broad-spectrum drug that in recent years has drawn increasing interest as a treatment for a range of neuropsychiatric disorders.
We found that existing preclinical evidence strongly supports CBD as a treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive—compulsive disorder, and post-traumatic stress disorder when administered acutely; however, few studies have investigated chronic CBD dosing.
Likewise, evidence from human studies supports an anxiolytic role of CBD, but is currently limited to acute dosing, also with few studies in clinical populations. Overall, current evidence indicates CBD has considerable potential as a treatment for multiple anxiety disorders, with need for further study of chronic and therapeutic effects in relevant clinical populations, anxiety disorder papers.
The online version of this article doi Fear and anxiety are adaptive responses essential to coping with threats to survival. Yet excessive or persistent fear may be maladaptive, leading to disability, anxiety disorder papers. Symptoms arising from anxiety disorder papers fear and anxiety occur in a number of neuropsychiatric disorders, including generalized anxiety disorder GADpanic disorder PDanxiety disorder papers, post-traumatic stress disorder PTSDsocial anxiety disorder SADand obsessive—compulsive disorder OCD.
Notably, PTSD and OCD are no longer classified as anxiety disorders in the recent revision of the Diagnostic and Statistical Manual of Mental Disorders-5; however, excessive anxiety is central to the symptomatology of both disorders. These anxiety-related disorders are anxiety disorder papers with a diminished sense of well-being, elevated rates of unemployment and relationship breakdown, and elevated suicide risk [ 1 — 3 ].
Currently available pharmacological treatments include serotonin reuptake inhibitors, serotonin—norepinephrine reuptake inhibitors, benzodiazepines, monoamine oxidase inhibitors, tricyclic antidepressant drugs, anxiety disorder papers, and partial 5-hydroxytryptamine 5-HT 1A receptor agonists. Anticonvulsants and atypical antipsychotics are also used to treat PTSD. These medications are associated with limited response rates anxiety disorder papers residual symptoms, particularly in PTSD, anxiety disorder papers, and adverse effects may also limit tolerability and adherence [ 7 — 10 ].
The substantial burden of anxiety-related disorders and the limitations of current treatments place a high priority on developing novel pharmaceutical treatments.
CBD has broad therapeutic properties across a range of neuropsychiatric disorders, stemming from diverse central nervous system actions [ 1112 ]. In recent years, CBD has attracted increasing interest as a potential anxiolytic treatment [ 13 — 15 ]. The purpose of this review is to assess evidence from current preclinical, clinical, and epidemiological studies pertaining to the potential risks and benefits of CBD as a treatment for anxiety disorders.
In total, 49 primary preclinical, clinical, or epidemiological studies were included. Neuroimaging studies that documented results from anxiety-related tasks, or resting neural activity, were included.
Cannabis sativaa species of the Cannabis genus of flowering plants, is one of the most frequently used illicit recreational substances in Western culture. The 2 major phyto- cannabinoid constituents with central nervous system activity are THC, responsible for the euphoric and mind-altering effects, and CBD, which lacks these psychoactive effects. Preclinical and clinical studies show CBD possesses a wide range of therapeutic properties, including antipsychotic, anxiety disorder papers, analgesic, neuroprotective, anticonvulsant, antiemetic, antioxidant, anti-inflammatory, antiarthritic, and antineoplastic properties see [ 111216 — 19 ] for reviews.
CBD has a broad pharmacological profile, including interactions with several receptors known to regulate fear and anxiety-related behaviors, specifically the cannabinoid type 1 receptor CB 1 Rthe serotonin 5-HT 1A receptor, and the transient receptor potential TRP vanilloid type 1 TRPV1 receptor [ 111219anxiety disorder papers, 21 ].
In addition, CBD may also regulate, directly or indirectly, the peroxisome proliferator-activated receptor-γ, the orphan G-protein-coupled receptor 55, the equilibrative nucleoside transporter, the adenosine transporter, additional TRP channels, and glycine receptors [ 11121921 ]. Pharmacology anxiety disorder papers to these actions is detailed below. The primary mechanism by which eCBs regulate synaptic function is retrograde signaling, wherein eCBs produced by depolarization of the postsynaptic neuron activate presynaptic CB 1 Rs, leading to inhibition of neurotransmitter release [ 23 ].
Interactions with the TRPV1 receptor, in particular, anxiety disorder papers to be critical in regulating the extent to which eCB release leads to inhibition or facilitation of presynaptic neurotransmitter release [ 25 ].
The TRPV1 receptor is a postsynaptic cation channel that underlies sensation of noxious heat in the periphery, with capsacin hot chili as an exogenous ligand. TRPV1 receptors are also expressed in the brain, including the amygdala, periaqueductal grey, hippocampus, and other areas [ 2627 ]. The eCB system regulates diverse physiological functions, including caloric energy balance and immune function [ 28 ].
The eCB system is also integral to regulation of emotional behavior, being essential to forms of synaptic plasticity that determine learning and response to emotionally salient, particularly highly aversive events [ 29anxiety disorder papers, 30 ]. Activation of CB 1 Rs produces anxiolytic effects in various models of unconditioned fear, relevant to multiple anxiety disorder symptom domains reviewed in [ 30 — 33 ].
Regarding conditioned fear, the effect of CB 1 R activation is complex: CB 1 R activation may enhance or reduce fear expression, depending on brain locus and the eCB ligand [ 34 ]; however, Anxiety disorder papers 1 R activation potently enhances fear extinction [ 35 ], and can prevent fear reconsolidation.
Genetic manipulations that impede CB 1 R activation are anxiogenic [ 35 ], and individuals with eCB system gene polymorphisms that reduce eCB tone—for example, FAAH gene polymorphisms—exhibit physiological, psychological, and neuroimaging features consistent with impaired fear regulation [ 36 ].
Reduction of AEA—CB 1 R signaling in the amygdala mediates the anxiogenic effects of corticotropin-releasing hormone [ 37 ], and CB 1 R activation is essential to negative feedback of the neuroendocrine stress response, and protects against the adverse effects of chronic stress [ 3839 ].
Finally, chronic stress impairs eCB signaling in the hippocampus and amygdala, leading to anxiety anxiety disorder papers 4041 ], anxiety disorder papers, and people anxiety disorder papers PTSD show elevated CB 1 R availability and reduced peripheral AEA, suggestive of reduced eCB tone [ 42 ].
Accordingly, CB 1 R activation has been suggested as a target for anxiolytic anxiety disorder papers development [ 154344 ]. Proposed agents for enhancing CB 1 R activation include THC, which is a potent and direct agonist; synthetic CB 1 R agonists; FAAH inhibitors and other agents that increase eCB availability, as well as nonpsychoactive cannabis phytocannabinoids, including CBD. While CBD has low affinity for the CB 1 R, it functions as an indirect agonist, potentially via augmentation of CB 1 R constitutional activity, or via increasing AEA through FAAH inhibition reviewed in [ 21 ].
Several complexities of the eCB system may impact upon the potential of CBD and other CB 1 R-activating agents to serve as anxiolytic drugs. First, anxiety disorder papers, CB 1 R agonists, including THC and AEA, have a biphasic effect: low doses are anxiolytic, but higher doses are ineffective or anxiogenic, in both preclinical models in and humans reviewed in [ 3345 ].
This biphasic profile may stem from the capacity of CB 1 R agonists to also activate TRPV1 receptors when administered at anxiety disorder papers high, but not low dose, as demonstrated for AEA [ 46 ], anxiety disorder papers. Activation of TRPV1 receptors is predominantly anxiogenic, and thus a critical balance of eCB levels, determining CB1 versus TRPV1 activation, is proposed to govern emotional behavior [ 2747 ].
CBD acts as a TRPV1 agonist at high concentrations, potentially by interfering with AEA inactivation [ 48 ]. In addition to dose-dependent activation of TRPV1 channels, the anxiogenic versus anxiolytic balance of CB 1 R agonists also depends on dynamic factors, including environmental stressors [ 3349 ].
The 5-HT 1A receptor 5-HT 1A R is an established anxiolytic target. Buspirone and other 5-HT 1A R agonists are approved for the treatment of GAD, with fair response rates [ 50 ]. In preclinical studies, 5-HT 1A R agonists are anxiolytic in animal models of general anxiety [ 51 ], prevent the adverse effects of stress [ 52 ], and enhance fear extinction [ 53 ]. They are expressed on serotonergic neurons in the raphe, where they exert autoinhibitory function, and various other brain areas involved in fear and anxiety [ 5455 ].
Mechanisms underlying the anxiolytic effects of 5-HT 1A R activation are complex, varying between both brain region, and pre- versus postsynaptic locus, and are not fully established [ 56 ]. While in vitro studies suggest CBD acts as a direct 5-HT 1A R agonist [ 57 ], in vivo studies are more consistent with CBD acting as an allosteric modulator, or facilitator of 5-HT 1A signaling [ 58 ].
CBD has been studied in a wide range of animal models of general anxiety, including the elevated plus maze EPMthe Vogel-conflict test VCTand the elevated T maze ETM. When tested over a wide range anxiety disorder papers doses in further studies, the anxiolytic effects of CBD presented a bell-shaped dose—response curve, with anxiolytic effects observed at moderate but not higher doses [ 61anxiety disorder papers, 90 ].
All further studies of acute systemic CBD without prior stress showed anxiolytic effects or no effect [ 6265 ], the latter study involving intracerebroventricular rather than the intraperitoneal route. No anxiogenic effects of acute systemic CBD dosing in models of general anxiety have yet been reported. As yet, few studies have examined chronic dosing effects of CBD in models of generalized anxiety. Campos et al. Long et al. Anxiolytic effects of CBD in models of generalized anxiety have been linked to specific receptor mechanisms and brain regions.
The midbrain dorsal periaqueductal gray DPAG is integral to anxiety, orchestrating autonomic and behavioral responses to threat [ 91 ], and DPAG stimulation in humans produces feelings of intense distress and dread [ 92 ]. Microinjection of CBD into the DPAG produced anxiolytic effects in the EPM, VGC, and ETM that were partially mediated by activation of 5-HT 1A Rs but not by CB 1 Rs [ 6568 ].
The bed nucleus anxiety disorder papers the stria terminalis BNST serves as a principal output structure of the amygdaloid complex to coordinate sustained fear responses, relevant to anxiety [ 93 ]. Anxiolytic effects of CBD in the EPM and VCT occurred upon microinjection into the BNST, where they depended anxiety disorder papers 5-HT 1A R activation [ 79 ], and also upon microinjection into the central nucleus of the amygdala [ 78 ]. In the prelimbic cortex, which drives expression of fear responses via connections with the amygdala [ 94 ], CBD had more complex effects: in unstressed rats, anxiety disorder papers, CBD was anxiogenic in the EPM, partially via 5-HT 1A R receptor activation; however, following acute restraint stress, CBD was anxiolytic [ 87 ].
Finally, the anxiolytic effects of systemic CBD partially depended on GABA A receptor activation in the EPM model but not in the VCT model [ 61anxiety disorder papers ].
As noted, CBD has been found to have a bell-shaped response curve, with higher doses being ineffective. This may reflect activation of TRPV1 receptors at higher dose, as blockade of Anxiety disorder papers receptors in the DPAG rendered a previously ineffective high dose of CBD as anxiolytic in the EPM [ 66 ].
Stress is an important contributor to anxiety disorders, and traumatic stress exposure is essential to the development of PTSD. Systemically administered CBD reduced acute increases in heart rate and blood pressure induced by restraint stress, as well as the delayed 24 h anxiogenic effects of stress in the EPM, partially by 5-HT 1A R activation [ 6773 ].
However intra-BNST microinjection of CBD augmented stress-induced heart rate increase, also partially via 5-HT 1A R activation [ 85 ]. In a subchronic study, CBD administered daily 1 h after predator stress a proposed model of PTSD reduced the long-lasting anxiogenic effects of chronic predator stress, partially via 5-HT 1A R activation [ 77 ].
In a chronic study, systemic CBD prevented increased anxiety produced by chronic unpredictable stress, in addition to increasing hippocampal AEA; these anxiolytic effects depended upon CB 1 R activation and hippocampal neurogenesis, as demonstrated by genetic ablation techniques [ 81 ]. Likewise, systemic CBD was anxiolytic in the EPM following but not prior to stress [ 65 ].
CBD inhibited escape responses in the ETM and increased DPAG escape electrical threshold [ 68 ], both proposed models of panic attacks [ 95 ]. These effects partially depended on 5-HT 1A R activation but were not affected by CB 1 R blockade.
Finally, anxiety disorder papers, CBD, partially via CB 1 Rs, decreased defensive immobility and explosive escape caused by bicuculline-induced neuronal activation in the superior colliculus [ 89 ], anxiety disorder papers. Anticompulsive effects of CBD were investigated in marble-burying behavior, conceptualized to model OCD [ 96 ]. Anxiety disorder papers studies assessed CBD using contextual fear conditioning. Briefly, this paradigm involves pairing a neutral context, the conditioned stimulus CSwith an aversive unconditioned stimulus USa mild foot shock.
After repeated pairings, the subject learns that the CS predicts the US, and subsequent CS presentation elicits freezing and other physiological responses, anxiety disorder papers. Systemic administration of CBD prior to CS re-exposure reduced conditioned cardiovascular responses [ 63 ], an effect reproduced by microinjection of CBD into the BNST, and partially mediated by 5-HT 1A R activation [ 79 ]. Similarly, CBD in the prelimbic cortex reduced conditioned freezing [ 70 ], anxiety disorder papers, an effect prevented by 5-HT 1A R blockade [ 87 ].
By contrast, CBD microinjection in the infralimbic cortex enhanced conditioned freezing [ 70 ]. Finally, El Batsh et al. In this study, CBD was administered prior to conditioning rather than prior to re-exposure as in acute studies, thus further directly comparable studies are required.
CBD has also been shown to enhance anxiety disorder papers of contextually conditioned fear responses. Extinction training involves repeated CS exposure in the absence of the US, leading to the formation of a new memory that inhibits fear responses and a decline in freezing over subsequent training sessions. Systemic CBD administration immediately before training markedly enhanced extinction, and this effect depended on CB 1 R activation, without involvement of TRPV1 receptors [ 65 ].
Further studies showed CB 1 Rs in the infralimbic cortex may be involved in this effect [ 82 ]. CBD also blocked reconsolidation of aversive memories in rat [ 76 ].
Briefly, anxiety disorder papers, fear memories, when reactivated by re-exposure retrievalenter into a labile state in which the memory trace may either be reconsolidated or extinguished [ 97 ], and this process may be pharmacologically modulated to achieve reconsolidation blockade or extinction, anxiety disorder papers.
When administered immediately following retrieval, CBD prevented freezing to the conditioned context upon further re-exposure, and no reinstatement or spontaneous recovery was observed over 3 weeks, consistent with reconsolidation blockade rather than extinction [ 76 ].
This effect depended on CB 1 R activation but not 5-HT 1A R activation [ 76 ]. Overall, existing preclinical evidence strongly supports anxiety disorder papers potential of CBD as a treatment for anxiety disorders. CBD exhibits a broad range of actions, relevant to multiple symptom domains, including anxiolytic, panicolytic, and anticompulsive actions, as well as a decrease in autonomic arousal, a decrease in conditioned fear expression, enhancement of fear extinction, reconsolidation blockade, and prevention of the long-term anxiogenic effects of stress.
Activation of 5-HT 1A Rs appears to mediate anxiolytic and panicolytic effects, anxiety disorder papers, in addition to reducing conditioned fear expression, although CB 1 R activation may play a limited role. While CBD predominantly has acute anxiolytic effects, anxiety disorder papers, some anxiety disorder papers discrepancies are apparent.
Abnormal Psychology- Lecture 8: Anxiety Disorders
, time: 50:59
Apr 21, · Social anxiety, which is also referred to as social anxiety disorder or social phobia, is a mental illness in which a person has a fear of or worry concerning social situations that does not go away Panic disorder usually begins in adulthood (after age 20), but children can also have panic disorder and many children experience panic-like symptoms (“fearful spells”). About % of Americans experience panic disorder in a given year and it is twice as common in women than in men For our COVID resources click here. Welcome to our full therapist resources site. Welcome to our resources site for clinicians who are intending to treat clients with PTSD, social anxiety disorder and/or panic disorder using the specialised cognitive therapies developed from our models of PTSD (Ehlers and Clark, ), social anxiety disorder (Clark and Wells, ), and panic disorder
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