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Cannabidiol as a Potential Treatment for Anxiety Disorders

Cannabidiol (CBD), a 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. The purpose of the current review is to determine CBD’s potential as a treatment for anxiety-related disorders, by assessing evidence from preclinical, human experimental, clinical, and epidemiological studies. 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.

Electronic supplementary material

The online version of this article (doi:10.1007/s13311-015-0387-1) contains supplementary material, which is available to authorized users.

Keywords: Cannabidiol, Endocannabinoids, Anxiety, Generalized anxiety disorder, Post-traumatic stress disorder

Introduction

Fear and anxiety are adaptive responses essential to coping with threats to survival. Yet excessive or persistent fear may be maladaptive, leading to disability. Symptoms arising from excessive fear and anxiety occur in a number of neuropsychiatric disorders, including generalized anxiety disorder (GAD), panic disorder (PD), post-traumatic stress disorder (PTSD), social anxiety disorder (SAD), and 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 associated with a diminished sense of well-being, elevated rates of unemployment and relationship breakdown, and elevated suicide risk [1–3]. Together, they have a lifetime prevalence in the USA of 29 % [4], the highest of any mental disorder, and constitute an immense social and economic burden [5, 6].

Currently available pharmacological treatments include serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, benzodiazepines, monoamine oxidase inhibitors, tricyclic antidepressant drugs, 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 and residual symptoms, particularly in PTSD, 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.

Cannabidiol (CBD) is a phytocannabinoid constituent of Cannabis sativa that lacks the psychoactive effects of ∆ 9- tetrahydrocannabinol (THC). CBD has broad therapeutic properties across a range of neuropsychiatric disorders, stemming from diverse central nervous system actions [11, 12]. 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.

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 2015, 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 “post-traumatic stress disorder” or “panic disorder” or “obsessive compulsive disorder”. 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. Epidemiological or clinical studies that assessed CBD’s effects on anxiety symptoms, or the potential protective effects of CBD on anxiety symptoms induced by cannabis use (where the CBD content of cannabis is inferred via a higher CBD:THC ratio), were included.

CBD Pharmacology Relevant to Anxiety

General Pharmacology and Therapeutic Profile

Cannabis sativa, a 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, analgesic, neuroprotective, anticonvulsant, antiemetic, antioxidant, anti-inflammatory, antiarthritic, and antineoplastic properties (see [11, 12, 16–19] for reviews). A review of potential side effects in humans found that CBD was well tolerated across a wide dose range, up to 1500 mg/day (orally), with no reported psychomotor slowing, negative mood effects, or vital sign abnormalities noted [20].

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 (CB1R), the serotonin 5-HT1A receptor, and the transient receptor potential (TRP) vanilloid type 1 (TRPV1) receptor [11, 12, 19, 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 [11, 12, 19, 21]. In the current review of primary studies, the following receptor-specific actions were found to have been investigated as potential mediators of CBD’s anxiolytic action: CB1R, TRPV1 receptors, and 5-HT1A receptors. Pharmacology relevant to these actions is detailed below.

The Endocannabinoid System

Following cloning of the endogenous receptor for THC, namely the CB1R, endogenous CB1R ligands, or “endocannabinoids” (eCBs) were discovered, namely anandamide (AEA) and 2-arachidonoylglycerol (reviewed in [22]). The CB1R is an inhibitory Gi/o protein-coupled receptor that is mainly localized to nerve terminals, and is expressed on both γ-aminobutryic acid-ergic and glutamatergic neurons. eCBs are fatty acid derivatives that are synthesized on demand in response to neuronal depolarization and Ca 2+ influx, via cleavage of membrane phospholipids. The primary mechanism by which eCBs regulate synaptic function is retrograde signaling, wherein eCBs produced by depolarization of the postsynaptic neuron activate presynaptic CB1Rs, leading to inhibition of neurotransmitter release [23]. The “eCB system” includes AEA and 2-arachidonoylglycerol; their respective degradative enzymes fatty acid amide hydroxylase (FAAH) and monoacylglycerol lipase; the CB1R and related CB2 receptor (the latter expressed mainly in the periphery); as well as several other receptors activated by eCBs, including the TRPV1 receptor, peroxisome proliferator-activated receptor-γ, and G protein-coupled 55 receptor, which functionally interact with CB1R signaling (reviewed in [21, 24]). Interactions with the TRPV1 receptor, in particular, appear 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 [26, 27].

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 [29, 30]. Activation of CB1Rs 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 CB1R activation is complex: CB1R activation may enhance or reduce fear expression, depending on brain locus and the eCB ligand [34]; however, CB1R activation potently enhances fear extinction [35], and can prevent fear reconsolidation. Genetic manipulations that impede CB1R 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–CB1R signaling in the amygdala mediates the anxiogenic effects of corticotropin-releasing hormone [37], and CB1R activation is essential to negative feedback of the neuroendocrine stress response, and protects against the adverse effects of chronic stress [38, 39]. Finally, chronic stress impairs eCB signaling in the hippocampus and amygdala, leading to anxiety [40, 41], and people with PTSD show elevated CB1R availability and reduced peripheral AEA, suggestive of reduced eCB tone [42].

Accordingly, CB1R activation has been suggested as a target for anxiolytic drug development [15, 43, 44]. Proposed agents for enhancing CB1R activation include THC, which is a potent and direct agonist; synthetic CB1R 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 CB1R, it functions as an indirect agonist, potentially via augmentation of CB1R 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 CB1R-activating agents to serve as anxiolytic drugs. First, CB1R 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 [33, 45]). This biphasic profile may stem from the capacity of CB1R agonists to also activate TRPV1 receptors when administered at a high, but not low dose, as demonstrated for AEA [46]. 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 [27, 47]. 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 CB1R agonists also depends on dynamic factors, including environmental stressors [33, 49].

5-HT1A Receptors

The 5-HT1A receptor (5-HT1AR) is an established anxiolytic target. Buspirone and other 5-HT1AR agonists are approved for the treatment of GAD, with fair response rates [50]. In preclinical studies, 5-HT1AR agonists are anxiolytic in animal models of general anxiety [51], prevent the adverse effects of stress [52], and enhance fear extinction [53]. Both pre- and postsynaptic 5-HT1ARs are coupled to various members of the Gi/o protein family. They are expressed on serotonergic neurons in the raphe, where they exert autoinhibitory function, and various other brain areas involved in fear and anxiety [54, 55]. Mechanisms underlying the anxiolytic effects of 5-HT1AR 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-HT1AR agonist [57], in vivo studies are more consistent with CBD acting as an allosteric modulator, or facilitator of 5-HT1A signaling [58].

Preclinical Evaluations

Generalized Anxiety Models

Relevant studies in animal models are summarized in chronological order in Table ​ Table1. 1 . CBD has been studied in a wide range of animal models of general anxiety, including the elevated plus maze (EPM), the Vogel-conflict test (VCT), and the elevated T maze (ETM). See Table ​ Table1 1 for the anxiolytic effect specific to each paradigm. Initial studies of CBD in these models showed conflicting results: high (100 mg/kg) doses were ineffective, while low (10 mg/kg) doses were anxiolytic [59, 60]. When tested over a wide range of 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 [61, 90]. All further studies of acute systemic CBD without prior stress showed anxiolytic effects or no effect [62, 65], 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. [66] showed that in rat, CBD treatment for 21 days attenuated inhibitory avoidance acquisition [83]. Long et al. [69] showed that, in mouse, CBD produced moderate anxiolytic effects in some paradigms, with no effects in others.

Table 1

Study Animal Route Dose Model Effect Receptor Involvement
Silveira Filho et al. [59] WR i.p. 100 mg/kg,
acute
GSCT No effect NA
Zuardi et al. [60] WR i.p. 10 mg/kg,
acute
CER Anxiolytic NA
Onaivi et al. [61] ICR mice i.p. 0.01, 0.10, 0.50, 1.00, 2.50, 5.00, 10.00, 50.00, 100.00 mg/kg, acute EPM Anxiolytic Effects ↓ by IP flumazenil, unchanged by naloxone
Guimaraes et al. [61] WR i.p. 2.5, 5.0, 10.0 and 20.0 mg/kg, acute EPM Anxiolytic NA
Moreira et al. [62] WR i.p. 2.5, 5.0 and 10.0 mg/kg, acute VCT Anxiolytic Effect unchanged by IP flumazenil
Resstel et al. [63] WR i.p. 10 mg/kg, acute CFC Anxiolytic NA
Campos et al. [64] WR dlPAG 15.0, 30.0, 60.0 nmol/0.2 μl, acute EPM Anxiolytic Both effects ↓ by intra-dlPAG WAY100635 but not intra-dlPAG AM251
VCT Anxiolytic
Bitencourt et al. [65] WR i.c.v. 2.0 μg/μl
5 min before extinction, acute
CFC
extinction
Anxiolytic Extinction effect ↓ by SR141716A but not capsazepine
EPM before and 24 h after CFC No effect before CFC
Anxiolytic following CFC
Campos et al. [66] WR dlPAG 30, 60 mg/kg, acute EPM Anxiolytic Intra-dlPAG capsazepine renders 60 mg/kg anxiolytic
Resstel et al. [67] WR i.p. 1, 10 or 20 mg/kg, acute RS Anxiolytic,
↓ Pressor
↓ Tachycardia
All effects ↓ by systemic WAY100635
EPM 24 h
following RS
Anxiolytic
Soares et al. [68] WR dlPAG 15, 30 or 60 nmol, acute ETM Anxiolytic
Panicolytic
All effects ↓ by intra-dlPAG WAY100635 but not AM251
PAG E-stim Panicolytic
Long et al. [69] C57BL/6 J mice i.p. 1, 5, 10, 50 mg/kg, chronic, daily/21 d EPM No effect NA
L-DT 1 mg/kg
anxiolytic
SI No effect
OF 50 mg/kg anxiolytic
Lemos et al. [70] WR i.p.
PL
IL
10 mg/kg IP, 30 nmol intra-PL and intra-IL, acute CFC IP and PL anxiolytic IL anxiogenic NA
Casarotto et al. [71] C57BL/6 J mice i.p. 15, 30, and 60 mg/kg, acute, or subchronic, daily/7 d MBT Anticompulsive Effect ↓ by IP AM251 but not WAY100635
Gomes et al. [72] WR BNST 15, 30, and 60 nmol, acute EPM Anxiolytic Both effects ↓ by intra BNST WAY100635
VCT Anxiolytic
Granjeiro et a l. [73] WR Intracisternal 15, 30, and 60 nmol, acute RS Anxiolytic, ↓Pressor ↓Tachycardia NA
EPM 24 h after RS Anxiolytic
Deiana et al. [74] SM i.p.
Oral
120 mg/kg, acute MBT Anticompulsive NA
Uribe-Marino et al. [75] SM i.p. 0.3, 3.0, 30.0 mg/kg, acute PS Panicolytic NA
Stern et al. [76] WR i.p. 3, 10, 30 mg/kg
immediately after retrieval, acute
Reconsolidation blockade Anxiolytic
1 and 7 d old fear memories disrupted
Effect ↓ by AM251 but not WAY100635
Campos et al. [77] WR i.p. 5 mg/kg, subchronic, daily/7 d EPM following PS Anxiolytic Effects ↓ by IP WAY100635
Hsiao et al. [78] WR CeA 1 μg/μl REM sleep time ↓ REM sleep suppression NA
EPM Anxiolytic
OF Anxiolytic
Gomes et al. [79] WR BNST 15, 30, 60 nmol, acute CFC Anxiolytic Both effects ↓ by intra-BNST WAY100635
El Batsh et al. [80] LE-H R i.p. 10 mg/kg, chronic,
daily/14 d
CFC Anxiogenic NA
Campos et al. [81] C57BL/6 mice i.p. 30 mg/kg 2 h after CUS,
chronic daily/14 d
EPM Anxiolytic Both effects ↓ by AM251
NSF Anxiolytic
Do Monte et al. [82] L-E HR IL 1 μg or 0.4 μg/0.2 μl 5 min before extinction daily/4 d Extinction of CFC Anxiolytic Effect ↓ by IP rimonabant
Campos et al. [83] Rat i.p. 5 mg/kg, chronic, daily/21 d ETM Anxiolytic
Panicolytic
Panicolytic effect ↓ by intra-dlPAG WAY100635
Almeida et al. [84] Rat i.p. 1, 5, 15 mg/kg, acute SI Anxiolytic NA
Gomes et al. [85] WR BNST 30 and 60 nmol, acute RS Anxiogenic
↑ Tachydardia
Effect ↓ by WAY100635
Twardowschy et al. [86] SM i.p. 3 mg/kg, acute PS Panicolytic Effects ↓ by IP WAY100635
Focaga et al. [87] WR PL 15, 30, 60 nmol, acute EPM Anxiogenic All effects ↓ by intra PL WAY100635
Anxiolytic EPM effect post-RS ↓ by IP metyrapone
EPM after RS Anxiolytic
CFC Anxiolytic
Nardo et al. [88] SM i.p. 30 mg/kg, acute MBT Anticompulsive NA
da Silva et al. [89] WR SNpr 5 μg/0.2 μl GABAA blockade in dlSC Panicolytic Both effects ↓ by AM251
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Effective doses are in bold

Receptor specific agents: AM251 = cannabinoid receptor type 1 (CB1R) inverse agonist; WAY100635 = 5-hydroxytryptamine 1A antagonist; SR141716A = CB1R antagonist; rimonabant = CB1R antagonist; capsazepine = transient receptor potential vanilloid type 1 antagonist; naloxone = opioid antagonist; flumazenil = GABAA receptor antagonist

Anxiolytic effects in models used: CER = reduced fear response; CFC = reduced conditioned freezing; CFC extinction = reduced freezing following extinction training; EPM = reduced % time in open arm; ETM = decreased inhibitory avoidance; L-DT = increased % time in light; VCT = increased licks indicating reduced conflict; NSF = reduced latency to feed; OF = increased % time in center; SI = increased social interaction

Anticomplusive effects: MBT = reduced burying

Panicolytic effects: ETM = decreased escape; GABAA blockade in dlSC = defensive immobility, and explosive escape; PAG-E-Stim = increased threshold for escape; PS = reduced explosive escape

WR = Wistar rats; SM = Swiss mice; L-E HR = Long–Evans hooded rats; i.p. = intraperitoneal; dlPAG = dorsolateral periaqueductal gray; i.c.v. = intracerebroventricular; PL = prelimbic; IL = infralimbic; BNST = bed nucleus of the stria terminalis; CeA = amygdala central nucleus; SNpr = substantia nigra pars reticularis; CUS = chronic unpredictable stress; GSCT = Geller–Seifter conflict test; CER = conditioned emotional response; EPM = elevated plus maze; VCT = Vogel conflict test; CFC = contextual fear conditioning; RS = restraint stress; ETM = elevated T maze; PAG E-stim = electrical stimulation of the dlPAG; L-DT = light–dark test; SI = social interaction; OF = open field; MBT = marble-burying test; PS = predator stress; NSF = novelty suppressed feeding test; GABAA = γ-aminobutyric acid receptor A; dlSC = deep layers superior colliculus; REM = rapid eye movement; NA = not applicable

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-HT1ARs but not by CB1Rs [65, 68]. The bed nucleus of 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 on 5-HT1AR 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, CBD was anxiogenic in the EPM, partially via 5-HT1AR receptor activation; however, following acute restraint stress, CBD was anxiolytic [87]. Finally, the anxiolytic effects of systemic CBD partially depended on GABAA receptor activation in the EPM model but not in the VCT model [61, 62].

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 TRPV1 receptors in the DPAG rendered a previously ineffective high dose of CBD as anxiolytic in the EPM [66]. Given TRPV1 receptors have anxiogenic effects, this may indicate that at higher doses, CBD’s interaction with TRPV1 receptors to some extent impedes anxiolytic actions, although was notably not sufficient to produce anxiogenic effects.

Stress-induced Anxiety Models

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-HT1AR activation [67, 73]. However intra-BNST microinjection of CBD augmented stress-induced heart rate increase, also partially via 5-HT1AR 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-HT1AR 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 CB1R activation and hippocampal neurogenesis, as demonstrated by genetic ablation techniques [81]. Prior stress also appears to modulate CBD’s anxiogenic effects: microinjection of CBD into the prelimbic cortex of unstressed animals was anxiogenic in the EPM but following restraint stress was found to be anxiolytic [87]. Likewise, systemic CBD was anxiolytic in the EPM following but not prior to stress [65].

PD and Compulsive Behavior Models

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-HT1AR activation but were not affected by CB1R blockade. CBD was also panicolytic in the predator–prey model, which assesses explosive escape and defensive immobility in response to a boa constrictor snake, also partially via 5-HT1AR activation; however, more consistent with an anxiogenic effect, CBD was also noted to decrease time spent outside the burrow and increase defensive attention (not shown in Table ​ Table1) 1 ) [75, 86] . Finally, CBD, partially via CB1Rs, decreased defensive immobility and explosive escape caused by bicuculline-induced neuronal activation in the superior colliculus [89]. Anticompulsive effects of CBD were investigated in marble-burying behavior, conceptualized to model OCD [96]. Acute systemic CBD reduced marble-burying behavior for up to 7 days, with no attenuation in effect up to high (120 mg/kg) doses, and effect shown to depend on CB1Rs but not 5-HT1ARs [71, 74, 88].

Contextual Fear Conditioning, Fear Extinction, and Reconsolidation Blockade

Several studies assessed CBD using contextual fear conditioning. Briefly, this paradigm involves pairing a neutral context, the conditioned stimulus (CS), with an aversive unconditioned stimulus (US), a 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. 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-HT1AR activation [79]. Similarly, CBD in the prelimbic cortex reduced conditioned freezing [70], an effect prevented by 5-HT1AR blockade [87]. By contrast, CBD microinjection in the infralimbic cortex enhanced conditioned freezing [70]. Finally, El Batsh et al. [80] reported that repeated CBD doses over 21 days, that is chronic as opposed to acute treatment, facilitated conditioned freezing. 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 extinction 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 CB1R activation, without involvement of TRPV1 receptors [65]. Further studies showed CB1Rs in the infralimbic cortex may be involved in this effect [82].

CBD also blocked reconsolidation of aversive memories in rat [76]. Briefly, fear memories, when reactivated by re-exposure (retrieval), enter 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. 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 CB1R activation but not 5-HT1AR activation [76].

Summary and Clinical Relevance

Overall, existing preclinical evidence strongly supports the 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-HT1ARs appears to mediate anxiolytic and panicolytic effects, in addition to reducing conditioned fear expression, although CB1R activation may play a limited role. By contrast, CB1R activation appears to mediate CBD’s anticompulsive effects, enhancement of fear extinction, reconsolidation blockade, and capacity to prevent the long-term anxiogenic consequences of stress, with involvement of hippocampal neurogenesis.

While CBD predominantly has acute anxiolytic effects, some species discrepancies are apparent. In addition, effects may be contingent on prior stress and vary according to brain region. A notable contrast between CBD and other agents that target the eCB system, including THC, direct CB1R agonists and FAAH inhibitors, is a lack of anxiogenic effects at a higher dose. Further receptor-specific studies may elucidate the receptor specific basis of this distinct dose response profile. Further studies are also required to establish the efficacy of CBD when administered in chronic dosing, as relatively few relevant studies exist, with mixed results, including both anxiolytic and anxiogenic outcomes.

Overall, preclinical evidence supports systemic CBD as an acute treatment of GAD, SAD, PD, OCD, and PTSD, and suggests that CBD has the advantage of not producing anxiogenic effects at higher dose, as distinct from other agents that enhance CB1R activation. In particular, results show potential for the treatment of multiple PTSD symptom domains, including reducing arousal and avoidance, preventing the long-term adverse effects of stress, as well as enhancing the extinction and blocking the reconsolidation of persistent fear memories.

Human Experimental and Clinical Studies

Evidence from Acute Psychological Studies

Relevant studies are summarized in Table ​ Table2. 2 . The anxiolytic effects of CBD in humans were first demonstrated in the context of reversing the anxiogenic effects of THC. CBD reduced THC-induced anxiety when administered simultaneously with this agent, but had no effect on baseline anxiety when administered alone [99, 100]. Further studies using higher doses supported a lack of anxiolytic effects at baseline [101, 107]. By contrast, CBD potently reduces experimentally induced anxiety or fear. CBD reduced anxiety associated with a simulated public speaking test in healthy subjects, and in subjects with SAD, showing a comparable efficacy to ipsapirone (a 5-HT1AR agonist) or diazepam [98, 105]. CBD also reduced the presumed anticipatory anxiety associated with undergoing a single-photon emission computed tomography (SPECT) imaging procedure, in both healthy and SAD subjects [102, 104]. Finally, CBD enhanced extinction of fear memories in healthy volunteers: specifically, inhaled CBD administered prior to or after extinction training in a contextual fear conditioning paradigm led to a trend-level enhancement in the reduction of skin conductance response during reinstatement, and a significant reduction in expectancy (of shock) ratings during reinstatement [106].

Table 2

Human psychological studies

Study Subjects,
design
CBD route,
dose
Measure Effect
Karniol et al. [99] HV,
DBP
Oral, 15, 30, 60 mg, alone or with THC,
acute, at 55, 95, 155, and 185 min
Anxiety and pulse rate after THC and at baseline ↓ THC-induced increases in subjective anxiety and pulse rate
No effect at baseline
Zuardi et al., [100] HV,
DBP
Oral 1 mg/kg alone or with THC, acute, 80 min STAI score after THC ↓ THC-induced increases in STAI scores
Zuardi et al. [98] HV,
DBP
Oral 300 mg,
acute, 80 min
VAMS, STAI and BP following SPST ↓ STAI scores
↓ VAMS scores
↓ BP
Martin-Santos et al. [101] HV,
DBP
Oral 600 mg,
acute, 1, 2, 3 h
Baseline anxiety and pulse rate No effect
Crippa et al. [102] 10 HV,
DBP
Oral 400 mg,
acute, 60 and 75 min
VAMS before SPECT
SPECT
↓ VAMS scores
Bhattacharyya et al. [103] 15 HV
DBP
Oral 600 mg,
acute, 1, 2, 3 h
STAI scores
VAMS scores
↓ STAI scores
↓ VAMS scores
Crippa et al. [104] SAD and HC
DBP
Oral 400 mg,
acute, 75 and 140 min
VAMS before SPECT
SPECT
↓ VAMS scores
Bergamaschi et al. [105] SAD and HC DBP Oral 600 mg, acute, 1, 2, 3 h VAMS, SSPS-N, cognitive impairment, SCR, HR after SPST ↓ VAMS, SSPS-N and cognitive impairment, no effect on SCR or HR
Das et al. [106] HV
DBP
Inhaled, 32 mg, acute, immediately following, before, after extinction SCR and shock expectancy following extinction CBD after extinction training produced trend level reduction in SCR and decreased shock expectancy
Hindocha et al. [107] Varying in schizotypy and cannabis use, DBP Inhaled, 16 mg, acute Baseline VAS anxiety No significant effect of CBD
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HV = healthy volunteers; DBP = double-blind placebo; SAD = social anxiety disorder; HC = healthy controls; THC = Δ 9-tetrahydrocannabinol; STAI = Spielberger’s state trait anxiety inventory; VAMS = visual analog mood scale; BP = blood pressure; SPST = simulated public speaking test; SCR = skin conductance response; SPECT = single-photon emission computed tomography; SSPS-N = negative self-evaluation subscale; HR = heart rate; VAS = visual analog scale, CBD = cannabidiol

Evidence from Neuroimaging Studies

Relevant studies are summarized in Table ​ Table3. 3 . In a SPECT study of resting cerebral blood flow (rCBF) in normal subjects, CBD reduced rCBF in left medial temporal areas, including the amygdala and hippocampus, as well as the hypothalamus and left posterior cingulate gyrus, but increased rCBF in the left parahippocampal gyrus. These rCBF changes were not correlated with anxiolytic effects [102]. In a SPECT study, by the same authors, in patients with SAD, CBD reduced rCBF in overlapping, but distinct, limbic and paralimbic areas; again, with no correlations to anxiolytic effects [104].

Table 3

Study Subjects, design CBD route, dose, timing Measure Effect of CBD
Crippa et al. [102] 10 HV,
DBP
Oral 400 mg,
acute, 60 and 75 min
SPECT, resting (rCBF) ↓ rCBF in left medial temporal cluster, including amygdala and HPC, also ↓ rCBF in the HYP and posterior cingulate gyrus
↑ rCBF in left PHG
Borgwardt et al. [108] 15 HV,
DBP
Oral 600 mg,
acute, 1–2 h
fMRI during oddball and go/no-go task ↓ Activation in left insula, STG and MTG
Fusar-Poli et al. [109] 15 HV,
DBP
Oral 600 mg,
acute, 1–2 h
fMRI activation during fearful faces task ↓ Activation in left medial temporal region, including amygdala and anterior PHG, and in right ACC and PCC
Fusar-Poli et al. [110] 15 HV,
DBP
Oral 600 mg,
acute, 1–2 h
fMRI functional connectivity during fearful faces task ↓ Functional connectivity between L) AMY and ACC
Crippa et al. [104] SAD and HC
DBP
Oral 400 mg,
acute, 75 and 140 min
SPECT, resting (rCBF) ↓ rCBF in the left PHG, HPC and ITG.
↑ rCBF in the right posterior cingulate gyrus

CBD = cannabidiol; HV = healthy controls; DBP = double-blind placebo; SAD = social anxiety disorder; HC = healthy controls; SPECT = single-photo emission computed tomography; rCBF = regional cerebral blood flow; fMRI = functional magnetic resonance imaging; HPC = hippocampus; HYP = hypothalamus; PHG = parahippocampal gyrus; STG = superior temporal gyrus; MTG = medial temporal gyrus; ACC = anterior cingulate cortex; PCC = posterior cingulate cortex

In a series of placebo-controlled studies involving 15 healthy volunteers, Fusar-Poli et al. investigated the effects of CBD and THC on task-related blood-oxygen-level dependent functional magnetic resonance imaging activation, specifically the go/no-go and fearful faces tasks [109, 110]. The go/no-go task measures response inhibition, and is associated with activation of medial prefrontal, dorsolateral prefrontal, and parietal areas [111]. Response activation is diminished in PTSD and other anxiety disorders, and increased activation predicts response to treatment [112]. CBD produced no changes in predicted areas (relative to placebo) but reduced activation in the left insula, superior temporal gyrus, and transverse temporal gyrus. The fearful faces task activates the amygdala, and other medial temporal areas involved in emotion processing, and heightened amygdala response activation has been reported in anxiety disorders, including GAD and PTSD [113, 114]. CBD attenuated blood-oxygen-level dependent activation in the left amygdala, and the anterior and posterior cingulate cortex in response to intensely fearful faces, and also reduced amplitude in skin conductance fluctuation, which was highly correlated with amygdala activation [109]. Dynamic causal modeling analysis in this data set further showed CBD reduced forward functional connectivity between the amygdala and anterior cingulate cortex [110].

Evidence from Epidemiological and Chronic Studies

Epidemiological studies of various neuropsychiatric disorders indicate that a higher CBD content in chronically consumed cannabis may protect against adverse effects of THC, including psychotic symptoms, drug cravings, memory loss, and hippocampal gray matter loss [115–118] (reviewed in [119]). As THC acutely induces anxiety, this pattern may also be evident for chronic anxiety symptoms. Two studies were identified, including an uncontrolled retrospective study in civilian patients with PTSD patients [120], and a case study in a patient with severe sexual abuse-related PTSD [121], which showed that chronic cannabis use significantly reduces PTSD symptoms; however, these studies did not include data on the THC:CBD ratio. Thus, overall, no outcome data are currently available regarding the chronic effects of CBD in the treatment of anxiety symptoms, nor do any data exist regarding the potential protective effects of CBD on anxiety potentially induced by chronic THC use.

Summary and Clinical Relevance

Evidence from human studies strongly supports the potential for CBD as a treatment for anxiety disorders: at oral doses ranging from 300 to 600 mg, CBD reduces experimentally induced anxiety in healthy controls, without affecting baseline anxiety levels, and reduces anxiety in patients with SAD. Limited results in healthy subjects also support the efficacy of CBD in acutely enhancing fear extinction, suggesting potential for the treatment of PTSD, or for enhancing cognitive behavioral therapy. Neuroimaging findings provide evidence of neurobiological targets that may underlie CBD’s anxiolytic effects, including reduced amygdala activation and altered medial prefrontal amygdala connectivity, although current findings are limited by small sample sizes, and a lack of independent replication. Further studies are also required to establish whether chronic, in addition to acute CBD dosing is anxiolytic in human. Also, clinical findings are currently limited to SAD, whereas preclinical evidence suggests CBD’s potential to treat multiple symptom domains relevant to GAD, PD, and, particularly, PTSD.

Conclusions

Preclinical evidence conclusively demonstrates CBD’s efficacy in reducing anxiety behaviors relevant to multiple disorders, including PTSD, GAD, PD, OCD, and SAD, with a notable lack of anxiogenic effects. CBD’s anxiolytic actions appear to depend upon CB1Rs and 5-HT1ARs in several brain regions; however, investigation of additional receptor actions may reveal further mechanisms. Human experimental findings support preclinical findings, and also suggest a lack of anxiogenic effects, minimal sedative effects, and an excellent safety profile. Current preclinical and human findings mostly involve acute CBD dosing in healthy subjects, so further studies are required to establish whether chronic dosing of CBD has similar effects in relevant clinical populations. Overall, this review emphasizes the potential value and need for further study of CBD in the treatment of anxiety disorders.

Best CBD Oil for Anxiety and Depression in 2022: Top 5 CBD Oil Brands

CBD’s capacity to help us cope with stress and anxiety is one of the most researched and scientifically validated benefits. CBD has been demonstrated to affect serotonin levels in the body and appears to replicate many of the effects of antidepressants, but without the adverse side effects.

As a result, CBD oil has become very popular, and it may be the best option for your anxiety problems. However, CBD products are widely available on the market, which could make it difficult to choose the right one for your needs.

As a result, we have compiled a list of the best CBD oils for anxiety from the top brands in the industry.

After reading this article, you will be armed with a plethora of useful information, and you will be able to choose the best CBD oil for anxiety comfortably.

Top 5 Best CBD Oil & Tinctures In 2022:

    : Overall Best CBD Oil for Anxiety & Depression; Editor’s Choice Most Potent CBD Oil for Anxiety : Preferred CBD Oil Dosage for Anxiety : CBD Oil & Tincture for Stress Relief : Highly Rated CBD Oil for Depression

Here are the detailed reviews of our top picks:

#1. Exhale Wellness: Overall Best CBD Oil for Anxiety & Depression; Editor’s Choice

Exhale Wellness is our top recommendation, as it is a well-known CBD brand that is available on a variety of platforms. Overall, it seeks to improve people’s lifestyles by providing high-quality CBD products. So, if you are looking to acquire the best CBD oil, Exhale is the place to go.

Its headquarters are in Los Angeles, California, and it has extensive experience in this industry. Some of the top CBD products on the market are grown, extracted, and manufactured by this company. Moreover, Exhale’s products are designed to provide users with a healthier approach to living a better life and improving their well-being.

The company believes nature contains the secret to good health and wellness, and as such, it has become their philosophy in developing CBD products. As a result, we recommend their full-spectrum CBD oil as the most refined option for anxiety reduction. Furthermore, the oil contains a whole spectrum of cannabinoids.

The full-spectrum CBD oil comes in an easy-to-use glass dropper bottle and in two potency options — 600mg and 1,200mg. It can be readily purchased from their official website, and if you choose the subscribe and save option, you will receive a 25% discount.

Features

Premium-Grade Hemp

Exhale Wellness collaborates with Colorado farms to obtain organic hemp that is grown locally. The hemp used to make CBD extracts is of the highest quality and comes from an organically produced hemp plant that is grown under rigorous quality control norms and laws.

Advanced Extraction Method

The company obtains CBD extracts from full-spectrum hemp using the CO2 extraction process, which is the most advanced and the best method. The CBD oil is also subjected to stringent quality control procedures during the manufacturing process.

Pros

  • Third-party lab tested
  • 18-month shelf life
  • Transparent about manufacturing processes
  • U.S.-grown, organic hemp
  • Wide range of products
  • Free shipping on all orders
  • 30-day money-back guarantee

Cons

  • Only available for purchase online

Customer Experience

Our research and consumer feedback shows that Exhale’s CBD oil is the most potent in the market. Aside from its strength, the CBD oil has quick-acting effects, making the brand number one on our list.
Customers will find it easy to make purchases on the site because it is incredibly user-friendly. The company also employs industry-standard production procedures and testing to assure quality and safety, along with offering user-friendly policies to all customers.

#2. BudPop: Most Potent CBD Oil for Anxiety

BudPop is now one of the most well-known brands on the market. The company has released several high-quality CBD products, and customers have reacted positively. Moreover, BudPop’s CBD oil is pure, as it contains no unnecessary ingredients.

This CBD oil is offered in two flavors — Peppermint and Natural — and it comes in a glass bottle dropper with a 30ml capacity. Each bottle contains 1,500mg of CBD, and each serving contains 50mg of CBD. The oil’s contents are listed on the packaging, and all of the ingredients are natural and organic.

Furthermore, BudPop’s products are sent to a third-party lab, which checks them for toxins and additives. As a result, customers receive the best goods of the finest quality. You can also get discounts on the products if you bundle them with other BudPop products.

Features

Brand Reputation

BudPop’s high-quality products have received glowing reviews from customers online, on social media, and in several high-profile publications.

In addition, BudPop’s lab-tested goods adhere to all authorized manufacturing methods, including federal requirements that ensure safe and pure lab-tested products produced entirely of non-GMO, vegan, and organic components.

Shipping & Customer Service

BudPop is quickly establishing a reputation for providing excellent customer service and a high level of client satisfaction. When a product refund is required, they provide it quickly and contact their consumers in a courteous, friendly, and prompt manner. Moreover, free shipping is available on all orders.

Pros

  • Third-party lab tested
  • Superior quality CBD oil
  • Easily available lab reports
  • 30-day money-back guarantee
  • Free shipping

Cons

  • Only available on the official website

Customer Experience

Many individuals have compared BudPop’s CBD oil to other brands and found it superior. BudPop’s CBD oils are said to have unrivaled taste and effectiveness. Furthermore, several users have stated that the top CBD oils have aided them in dealing with daily stress.

After using this product, one customer even claimed he could now tell the difference between highly potent and less effective CBD oils, and as a result, he is now a regular customer at BudPop.

#3. Hollyweed CBD: Preferred CBD Oil Dosage for Anxiety

Hollyweed’s staff consists of wellness-oriented individuals with extensive experience in the medical cannabinoid sector. These individuals believe in the beneficial properties of hemp and are working to develop products that reflect their beliefs. When it comes to CBD oil, Hollyweed is our third recommendation for you to consider.

Hollyweed’s CBD oil is made using an ultra-clean CO2 extraction technique. After extracting the full-spectrum CBD, they combine it with pure hemp seed oil. As a result, you get a soothing and tranquil CBD boost by putting a few drops on your tongue or by combining it with food and drink.

Hollyweed’s oil has been lab tested and is kept in a glass dropper bottle. Because it contains less than 0.3% delta-9 THC, it does not provide a psychoactive effect. Moreover, this CBD oil is both safe and effective, as natural, organic, and non-GMO ingredients are used in every recipe.

Because most brands lack consistency and transparency, Hollyweed has used various methods to gain each customer’s trust by ensuring their entire satisfaction and general wellness. If one thing sets them apart, it is their sincerity. Each product is made with carefully chosen ingredients that reflect the brand’s work ethic and credibility.

Features

Relieves Discomfort

Hollyweed CBD oil provides a calming and relaxing effect on the central nervous system, which may encourage deeper, more natural sleep. Furthermore, it may also lessen the symptoms of anxiety and stress.
CO2 Extraction Method

Hollyweed uses the cutting-edge and ultra-clean CO2 extraction technique to create CBD oil. Their team combines full-spectrum CBD oil with high-quality hemp seed oil to generate full-spectrum CBD oil.

Pros

  • Third-party lab tested
  • Excellent for calming and relaxing the mind
  • Non-GMO and gluten-free
  • Free of any additives
  • Full-spectrum oil
  • Long-lasting effects
  • High potency
  • Free shipping
  • 30-day money-back guarantee

Cons

  • Only available for purchase online

Customer Experience

We conducted extensive research and examined all social media reviews, as well as the leading review sites, to provide you with a comprehensive assessment of the brand’s overall rating.

We noticed a lot of positive feedback regarding the oil’s potency, with many customers stating they could feel the desired results in a short period. Customers also appreciate the products’ packaging and the brand’s comprehensive website detailing all of the products it sells.

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#4. Cheef Botanicals: CBD Oil & Tincture for Stress Relief

Cheef Botanicals sources and manufactures its products through a network of Colorado farmers. The company was founded because the owners saw a gap in California’s health-conscious, plant-based cannabis products.

The organization maintains stringent quality control at every level and uses organic procedures. Cheef Botanicals also has their products verified for quality and accuracy by third-party labs. Cheef Botanicals offers a collection of vegan-friendly, plant-based, one-of-a-kind organic items, which are non-GMO, gluten-free, cruelty-free, and dairy-free.

Artificial flavors and colors are not used in any of the products, and a 30-day money-back guarantee is also available from the company. Cheef Botanicals’ CBD oil comes in four distinct quantities, with 300mg being the smallest and 3,000mg being the largest. Aside from that, you can get the products as a bundle and save money.

Cheef Botanicals fills a need in plant-based medicine for health-conscious people. CBD products from Cheef Botanicals are legal in all 50 states across the United States, and all items are eligible for free shipping.

Features

Extraction Method

Cheef Botanicals’ CBD oil was created using a CO2 extraction technology that is entirely natural. They have developed the most potent concentrated oil that is simple to take and delivers rapid benefits. The drops have no flavor and are placed under the tongue for quick absorption into the bloodstream.
Safe

This product is composed entirely of natural ingredients and will not cause you to become inebriated. The CBD oil is non-GMO, organic, and free of chemicals and preservatives. The bottle comes in various sizes, including 300mg, 600mg, 1,200mg, and 3,000mg.

Furthermore, if you sign up for their newsletter, you will receive a 25% discount on your first purchase.

Pros

  • All-natural and organic
  • No additives or preservatives
  • Non-GMO and dairy-free
  • Four sizes available
  • Provides immediate effects
  • High potency
  • 30-day money-back guarantee
  • Free shipping

Cons

  • Larger bottles are more costly

Customer Experience

If you are looking for a natural CBD health supplement to help with anxiety, Cheef Botanicals’ CBD oil is your best alternative. It will perform significantly better than any other item due to its organic and natural structure.

You may notice a noticeable improvement in your overall health as well as the efficiency with which your body performs. This CBD oil may also help you sleep better, along with providing other beneficial effects.

#5. FAB CBD: Highly Rated CBD Oil for Depression

FAB CBD has been busy working since 2017, delivering clients high-quality, clean, and unique CBD products. In truth, the brand’s CBD oils for anxiety are powerful and outstanding. FAB CBD’s team has extensive experience in the health and wellness industry, which is one of the main reasons for the company’s success.

The brand’s objective has always been to offer the safest, most effective CBD products so customers can live a healthy lifestyle. When it comes to developing its award-winning CBD products, the brand has never strayed from its rigorous set of criteria.
FAB CBD offers full-spectrum CBD oils in various concentrations and natural tastes, and there are five different tastes and four different sizes to choose from. In addition, the hemp used by FAB CBD is all organic and produced and harvested in Colorado.

The brand’s pure and strong hemp extracts are extracted using the CO2 extraction method, which is widely used in the industry. This procedure ensures all extracts are pure and devoid of contaminants. As a result, the cannabinoids, terpenes, and phytonutrients in FAB CBD’s products are all healthy.

Features

Hemp Source

FAB CBD sources all of the organic hemp it utilizes in its high-quality products from Colorado. The hemp is cultivated and harvested utilizing cutting-edge cloning and growth technology, which ensures it is clean, potent, and devoid of pesticides, herbicides, and other toxic chemicals.

Third-Party Lab Testing

ProVerde Labs, an independent third-party lab, regularly tests every product that FAB CBD makes. Transparency is also important to the brand, which is why the brand posts each lab test report on its website for customers to view.

Pros

  • Top-notch, kind, and knowledgeable customer support
  • Third-party lab tested
  • Shipping is quick and secure
  • Free shipping on orders of $99 or more
  • 30-day money-back guarantee

Cons

  • No options for auto-ship or subscription

Customer Experience

Customers claim FAB has the greatest CBD oil on the market. They appreciate that this company offers flavored CBD oils, making them easier to swallow. Some users claimed to have received multiple benefits.

We also enjoy that the brand’s website contains a lot of information about the products, along with being simple to navigate. Many customers appreciate both the packaging and the potency of FAB CBD’s oil.

Factors to Consider While Buying CBD Oil for Anxiety

CBD oils are derived from hemp, as can be observed. But, for hemp to be effective and safe to use, it must be of high grade. As a result, it is critical to look for hemp products grown organically on farms in the United States. You should probably look for another brand if a company does not disclose information about the hemp they utilize.
It is also vital to inspect the oil’s complementing ingredients to ensure it is all-natural and does not contain any potentially harmful synthetic compounds. If you are searching for diversity, seek products that offer it, such as ones that come in various flavors.

The potency of a CBD oil is another key element to consider before purchasing it. The potency will tell you how much CBD is in the product and how many milliliters of oil it contains.

You should be aware that a higher potency does not necessarily imply that the oil will be more effective for you. Lower amounts have been shown to help some people; therefore, a 250mg CBD oil bottle may suffice for your pain.

As a beginner, you should start with a small dose and gradually raise it as your tolerance develops. However, keep in mind that dose varies depending on the person’s metabolism, tolerance level, and consumption mode. Each person is unique, and if you exceed your dosage limit, you may experience minor adverse effects.

CBD oil comes in both unflavored and flavored varieties. The unflavored version is the simpler of the two, and regardless of CBD or THC concentrations, natural CBD oils and hemp extracts have an earthy, musky flavor.

If you plan to mix it with food or drinks, a product with flavoring may be preferable. Some manufacturers add a dash of lime, organic coconut oil, or berry juice for a delightful finish. Even a modest amount of flavor can dramatically improve the acceptability of CBD oil.

The fact that the products have been tested or not is a critical issue to consider as well. This is because third-party testing assures quality, safety, and potency.

You can also examine the hemp source, components utilized, oil strength, and other vital information if a manufacturer has given lab test findings on their website. It is not a good sign if a brand does not disclose lab testing reports on its website.

The manner of extraction is equally crucial, and CO2 extraction is the gold standard. It is utilized as a solvent to convert a solid state to a liquid by entering the plant and extracting the cannabinoids.

The CO2 will then disappear, leaving an oily, sticky extract behind. On the other hand, alternative extraction procedures include olive oil or alcohol.

If you want to understand if a product is worth buying, read the reviews first. One of the most crucial elements to consider is the customer experience. People are always willing to share their stories, and they are always brutally honest.

You can quickly assess whether a product is worth buying or not based on their statements. Each company’s website has a section for reviews, so scroll down and read what others have to say. If most of the comments are positive, the product is likely of great quality.

There will be negative feedback because the product will not work for everyone. You can base your decision on your requirements and previous customer experiences. The evaluations will also provide sufficient information about the company’s service, which is important for final decisions.

You can also ask friends who have tried the product for the most up-to-date information, and you can request that they let you test out their product to see if it works for you and whether or not it will be beneficial.

It is usually preferable to have fewer components in CBD oil, as it should only include CBD and a high-quality carrier oil. Some CBD oil companies additionally include natural flavors as a third ingredient.

If there are too many ingredients in the best CBD oils for anxiety, it is no longer pure and may not be as effective. Because some people dislike the flavor of hemp, improving the taste of CBD is beneficial. As a result, some brands turn to flavoring their CBD products.

There are hundreds of CBD natural extracts available, making it difficult to choose the ideal one for your anxiety or depression. Investing effort in researching ingredients can make a huge difference. To do so, you must first grasp the distinctions between CBD and hemp seed oils.

Both of these are made from hemp. The difference is that hemp oil is extracted from the seed and does not contain cannabidiol, whereas CBD oil is extracted from the leaves and contains a variety of cannabinoids. The amount of CBD in each extract varies, with broad-spectrum CBD being THC-free and full-spectrum CBD including trace quantities of THC.

Cannabinoids interact to create an entourage effect, which is one of the most critical advantages of full-spectrum CBD. It is thought that taking all industrial hemp plant parts together is more beneficial than taking them separately, and CBD with a broad spectrum of effects provides more targeted alleviation for specific depression and anxiety symptoms.

Other Benefits To Buy CBD Online:

CBD has been found in scientific research to help alleviate pain by interacting positively with the body’s endocannabinoid process to minimize inflammation.

  • Alleviate Cancer-Related Symptoms

CBD has been shown to help with cancer treatment side effects such as vomiting, discomfort, and nausea.

CBD has been demonstrated to be an effective treatment for neurological illnesses such as multiple sclerosis and epilepsy. It has also been shown to have neuroprotective properties.

CBD is also beneficial for one’s heart health. For example, nine healthy men were given 600mg CBD oil in one study, and researchers found their resting blood pressure lower.

Anxiety, sadness, coffee, medicine, medical ailments, and some environmental factors like loud noises or a bad mattress, for example, can all disrupt your sleep-wake pattern.

CBD improved sleep while also lowering anxiety disorders and social anxiety in a 2019 study. A total of 72 people were administered CBD every day for the duration of the study. 79.2% reported less anxiety in the first month, and 66.7% reported improved sleep.

FAQs: CBD Oil for Stress & Anxiety

Q1. Why should you use CBD oil instead of conventional medicine?

CBD oil is not designed to cure or treat anxiety, and it should not be used as a substitute for prescription medications or your existing treatment plan. Always consult with your doctor to identify the best course of action for your generalized social anxiety disorder and other diagnoses.

Many individuals appreciate CBD products because they help them relax, particularly during stressful situations, and also because they help them fall asleep sooner and remain asleep longer. Traditional drugs have a long list of adverse effects, and while they might help with generalized anxiety disorder, they can also make people feel disconnected and numb.

CBD helps alleviate the unpleasant feelings associated with anxiety disorders while also helping you stay present and enjoy the good things in life. Each person must select which form of assistance is best for them. Overall, CBD is gaining a good reputation, making it worthwhile for many to try.

Q2. What is the recommended dose of CBD oil for Post Traumatic Stress Disorder?

There is no one-size-fits-all solution for determining how much CBD oil to ingest. To begin with, everyone is unique. To attain the same potential advantages as someone twice their weight, a 150-pound individual needs substantially less CBD.

It is also crucial to think about CBD oil’s composition. Full-spectrum cannabidiol, for example, comprises a wide range of components that can have a stronger effect than broad-spectrum cannabidiol.

On the other hand, CBD isolate is a kind of pure cannabidiol that gives the best pound-for-pound outcomes. Therefore, you should only take a small quantity. Start with 5-10mg of CBD each serving as a general rule, and check the label if you are not sure how much that is. CBD products are labeled to indicate how much cannabidiol is in a single serving.

Q3. What is the difference between CBD oil and CBD tincture?

A tincture is often a solution made by steeping herbs in an ethanol solution to produce a concentrated liquid containing the herb’s active components. Oil is any liquid extract of a herb generally mixed with a carrier oil such as MCT oil. The terms tincture and oil are almost interchangeable in the CBD market for the most part.

Q4. Is CBD addictive?

According to the latest WHO studies, CBD does not cause habit-forming or addictive effects.

Conclusion:

Above, we discussed the best CBD oil for anxiety disorders that has proven to be effective in assisting people in overcoming their anxiety disorders. We believe that having this knowledge will aid you in determining which brand to purchase.
All of the brands we have featured have done exceptionally well in the CBD industry, and we are confident their CBD oil will not disappoint you. If you are unsure whether CBD oil should be added to your current supplement regimen, talk to your primary care doctor or a medical professional.

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