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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

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.

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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.

What is the Best CBD Oil for Anxiety?

A growing number of people are considering taking CBD oil for anxiety. But what’s all the hype about? The answers lie in cannabidiol, the main ingredient extracted from hemp, a subspecies of the cannabis plant.

This article explains how and why CBD oil may help people who experience anxiety disorders, post-traumatic stress disorder or high stress levels and guides you through the top 10 CBD brands in USA.

Quick access

What does CBD oil do for anxiety?

Over the last 10 years, a number of studies have explored the potential effects of CBD on anxiety disorders, including social anxiety disorder and post-traumatic stress disorder.

While more study is needed to confirm, cannabidiol products are a safe and effective long-term treatment option for people who experience anxiety or stress, recent studies have provided positive preliminary results.

Like THC, CBD interacts with our bodies’ cannabinoid receptors, which signal our endocannabinoid system (ECS) to take action on a broad range of body functions, including:

  • Mood
  • Sleep
  • Stress
  • Appetite
  • Memory and learning
  • Immune system responses

However, studies still couldn’t pinpoint exactly how CBD acts on those receptors.

Still, the World Health Organization concluded that cannabidiol doesn’t appear to cause dependence or have abuse potential.

A study found that CBD can help people reduce their anxiety by conducting simulated public speaking experiments (2011 – DOI: 10.1038/npp.2011.6).

A review of 49 studies also provides evidence suggesting that CBD could have positive effects on post-traumatic stress disorder and other anxiety disorders (2015 – DOI: 10.1007/s13311-015-0387-1).

Another study showed mostly positive results of CBD for anxiety and sleep: 79% of the people observed experienced anxiety improvements in the first month (2019 – DOI: 10.7812/TPP/18-041).

Even though the latest studies provide promising results, the positive effects of cannabidiol still need more evidence.

Effectiveness may also vary from one body to another due to several factors.

Is CBD or hemp oil better for anxiety?

Hemp seed oil is extracted from the hemp plant’s seeds through cold-pressing, the same way we produce olive oil.

Its very high concentration of omegas and other polyunsaturated fatty acids provides numerous health benefits, including:

  • Skin health improvement
  • Reduction of blood pressure
  • Reduction of cholesterol levels
  • Inflammation and pain relief

The nutritional properties of hemp seed oil encourage people to include it in their daily meal ingredients.

On the other hand, experts agree that CBD oil may be a more effective treatment option to help with the conditions listed above because of its interaction with the endocannabinoid system (ECS).

What is the best CBD oil for anxiety?

Now that you have a better idea of why customers buy CBD oil for anxiety and panic attacks, let’s take a look at the different product types available on the market.

U.S. companies typically sell broad-spectrum and/or full-spectrum CBD oil:

  • Broad-spectrum means the product contains cannabidiol and other natural compounds found in the cannabis plant but has no THC.
  • Full-spectrum means the product contains cannabidiol and other natural compounds found in cannabis, including trace amounts of THC.

Because of the entourage effect, experts suggest that full-spectrum CBD oil may be the best product type for anxiety disorders and other conditions since the effects of cannabidiol are maximized by the synergy with other cannabinoids.

Its low level of THC (0.3% or less) also prevents users from “feeling high” and rules out the possibility of unwanted psychotropic effects.

How to use CBD oil for anxiety?

At this point, it’s important to note there’s no universal rule for the optimal dose.

Since each body is different, you should always ask your doctor about the right CBD oil dosage for anxiety according to your individual case.

Your health condition, body chemistry, and weight can all impact the relative effectiveness of each dose, along with the potential interactions with the medications and supplements you may already take.

Once you know how much is the right dose for you, you can choose to take CBD oil orally, sublingually (keeping the dose under your tongue for up to a minute before swallowing) or by adding the dose to your food or drink.

Some customers will prefer to ingest CBD gummies for anxiety. These products offer a wider range of flavors, but CBD oil remains the most popular form.

How long does CBD oil take to work for anxiety?

The effects may begin working within 30 to 120 minutes for orally or sublingually administered oil.

However, it may vary according to the concentration of your dose and your body chemistry.

CBD oil for anxiety: where to buy near me?

If you’re looking to use cannabidiol concentrates for the treatment of anxiety disorders, buying a product made by a reputable source and sold by a trusted brand is crucial and ensures safety and effectiveness.

Not every company offers third-party tested oils made with organic hemp and contain no more than 0.3% THC.

To help you choose among today’s best brands and products, here’s our suggested list of the top 10 CBD companies in USA offering high-quality CBD oil for anxiety.

1. Extract Labs

Extract Labs prides itself on providing award-winning, high-quality products and keeping every step of production in-house. It has all the ingredients for being an industry-leading brand.

This company, founded by a U.S. combat veteran, provides lab reports for every batch, an exhaustive glossary of terms and thousands of customer reviews.

Concentration: from 1000 to 2000 mg per bottle
Potency: from 33 to 66 mg/ml
Price: from $60

2. CBDfx

CBDfx offers high-quality products made with organic, non-GMO and pesticide-free hemp crops.

This California company uses CO2 extraction and tests every product to ensure maximum effectiveness and purity. Their commitment to quality is backed by a 60-day satisfaction guarantee.

The brand offers a wide range of concentration options to best suit your needs.

Concentration: from 500 to 6000 mg per bottle
Potency: from 16,67 to 200 mg/ml
Price: from $39.99

3. CBDistillery

CBDistillery is a Colorado-based company with over 2 million satisfied customers and a broad range of products that may help you with anxiety.

Their products’ packaging clearly indicates the concentration per serving and useful information.

You can subscribe to receive the product regularly and enjoy a discount & free shipping.

Concentration: from 500 to 5000 mg per bottle
Potency: from 16,67 to 166,67 mg/ml
Price: from $35

4. Koi CBD

Koi CBD provides one of the most consistent and finest oils on the market made with hemp grown and extracted in the USA.

Each batch has full traceability from plant to finished product, which explains Koi CBD’s ever-growing list of satisfied customer reviews. A wide range of flavors is available.

Concentration: from 250 to 5000 mg per bottle
Potency: from 8,33 to 166,67 mg/ml
Price: from $29.99

5. Cornbread Hemp

Cornbread Hemp is Kentucky’s first company with USDA Organic certified products.

The brand is committed to cannabis excellence by producing some of the best products. Cornbread Hemp also has reward & discount programs with exclusive referral perks.

An easy-to-read lab report is available for each product batch.

Concentration: from 375 to 1500 mg per bottle
Potency: from 25 to 50 mg/ml
Price: from $27.99

6. Pure Hemp Botanicals

With Pure Hemp Botanicals, you can earn and redeem “pure points” for discounts and learn everything you need to know about CBD, THC and the cannabis plant in their information-rich knowledge portal.

Their products are lab-tested and certified non-GMO, vegan and cruelty-free.

Concentration: from 300 to 3000 mg
Potency: from 10 to 100 mg per serving
Price: from $17.46

7. Zatural

Zatural was founded by a Naturopathic Doctor, mother of 8 and grandmother of 28.

This multi-awarded company offers great customer service with an extensive list of products sourced from trusted U.S. sources, organically grown and third-party tested.

U.S. orders over $5 are eligible for free shipping, and orders over $15 receive a free item.

Concentration: from 300 to 12000 mg
Potency: from 10 to 100 mg/ml
Price: from $27.50

8. Joy Organics

Joy Organics is a family-founded company that helps consumers access safe and effective CBD in different forms and flavors.

The brand’s website provides useful information and details its complete process from A to Z.

You can also find thousands of customer reviews and enjoy discounts upon subscription.

Concentration: from 450 to 900 mg
Potency: from 15 to 30 mg/ml
Price: from $44.95

9. JustCBD

Besides being a transparent and professional GMP-certified company, JustCBD offers a vast selection of third-party tested products made with organic locally grown hemp.

Its blog is filled with educational articles that will help you better understand cannabidiol products. U.S. orders over $35 receive free shipping, and the brand offers a 30-day satisfaction guarantee.

Concentration: from 50 to 5000 mg
Potency: from 1,67 to 83,33 mg per serving
Price: from $9.99

10. Prest Organics

Prest Organics is a passionate and innovative brand that delivers a premium quality product with enhanced potency and absorption, thanks to its patented Cold-Press technology.

Prest Organics’ product is also 100% free from solvents, additives, preservatives, alcohol and MCT oils.

Concentration: from 500 to 1500 mg per bottle
Potency: from 16,67 to 50 mg/ml
Price: from $79.89

Talk with a medical professional before taking CBD oil for anxiety or any other condition, especially if you take any medications or supplements.

Disclaimer: The statements made regarding these products have not been evaluated by the Food and Drug Administration. The efficacy of these products has not been confirmed by FDA-approved research. These products are not intended to diagnose, treat, cure or prevent any disease. All information presented here is not meant as a substitute for or alternative to information from health care practitioners. Please consult your health care professional about potential interactions or other possible complications before using any product.

Best CBD Oils for Anxiety – Reviews

About the CBD Oils
CBDfx is boasting a new line of CBD products that include blends with delta-9 THC and with mushrooms. Customers can’t get over how effective these are at easing the symptoms associated with anxiety related disorders.

Delta-9 THC Drops + CBD: Ultimate Chill Blend
This CBD oil takes its original calming tincture up a notch. So much so that it comes with a warning that you may experience psychotropic effects. This blend made from organic hemp perfectly matches up to its name because you’ll experience the ultimate chill with these blueberry-flavored drops. They contain full-spectrum CBD oil and 2.25 mg of CBD per serving. There’s another delta-9 THC product but that one is geared specifically for sleep (look for the “sweet dreams blend”). That one is also worth trying if anxiety is keeping you up at night!

Unwind Mushroom + CBD Drops: CBN Relax Blend
This broad-spectrum CBD oil contains a relaxing blend of CBN along with reishi for stress relief, maitake for wellness, and turkey tail for immunity. It’s organic, non-GMO, and vegan with antioxidant-rich elderberry on top of the naturally potent formula. There is a second mushroom-boosting formula that’s ideal for daytime use because it contains broad-spectrum CBD with CBG and cordyceps for energy. If you need something for the day that won’t chill you out too much, you may want to check it out.

CBD + CBN Oil Calming Tincture
Their original formula, this CBD oil contains full-spectrum CBD and CBN and is curated with a blend of calming terpenes. Choose between five potencies: 500 mg, 1000 mg, 2000 mg, 4000 mg, and 6000 mg. There’s a nice counterpart to this CBD oil too—it’s a sleep tincture that you can purchase separately. They also have an “all-day calm bundle” that includes their calming and wellness formulas.

What You Can Expect to Pay
CBDfx has a fresh promotion going all the time. They are currently providing a 25% discount when you purchase three or more items and use the coupon “chill”. Always look toward the top banner of the CBDfx website for discount coupons that can help you maximize value when you shop with them.

When you order $75 or more from CBDfx, you get free shipping. The relaxing tincture costs $69.99 for 1000 mg of CBD, while the maximum potency option costs $199.99 for 6000 mg of CBD. You can purchase the 1500 mg option for $84.99 or the 6000 mg option for $239.99 to test out the delta-9 THC drops with CBD. The mushroom and CBD calming blend costs $109.99 for a 2000 mg strength option or $179.99 for a 4000 mg strength option.

Why Buy from CBDfx
CBDfx has recently expanded its line of CBD oils to include wellness-boosting mushroom formulas, demonstrating its commitment to developing and providing items that benefit its consumers’ health. They didn’t just come up with one product and settle. They continue to innovate, to meet their customer’s demands for product variety, and to do so with expert care. They are confident you’ll love their formulations and offer you a 60-day satisfaction guarantee on all CBD products. Plus, CBDfx is always willing to offer incentives to purchase from them—letting you save up to 25% off when you stock up on their items.

2. Green Roads – Runner Up

Pros:

  • Over 30k 5-star reviews
  • Award-winning products
  • Cruelty-free formulas
  • Independent lab tested

Cons:

  • Only the broad-spectrum CBD oil is available in multiple flavors

About the CBD Oils
Green Roads offers pharmacist-formulated CBD oils that contain a premium blend of hemp cannabis plant extracts. There are some flavored options if you prefer a little splash of sweetness or a blast of mint.

Full-Spectrum CBD
Packed with full-spectrum CBD, this formula also incorporates at least six other ingredients to make it easier for your body to absorb. Try the mild dose at 300 mg of CBD per bottle, or move into the mighty dose of 1500 mg of CBD per bottle.

Broad-Spectrum CBD
This formula helps you better manage your everyday stressors. The CBD oil has a natural flavor that tastes a bit like caramel and it’s also available in other options, like apple kiwi bliss and mint breeze. For sleep support, you can try their “sweet sleep oil” which contains both broad-spectrum CBD and CBN.

What You Can Expect to Pay
Free shipping is offered from Green Roads in two ways: either you spend $100 or more, or you subscribe for regular deliveries and get free shipping on every order. The 50 mg/mL concentration of full-spectrum CBD oil costs $149.99, whereas the 10 mg/mL concentration costs only $44.99.

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The 50 mg/mL concentration of the broad-spectrum option is also $149.99, while the 10 mg/mL concentration is $44.99. The rates are the same whether you choose the original taste, apple kiwi bliss, or mint breeze. The easiest way to get a great deal is to subscribe, which will give you 30% off your first order and 15% off all subsequent orders.

Why Buy from Green Roads
Because it was manufactured by a qualified compounding pharmacist, Green Roads is a fantastic brand. The creator took a risk while pursuing a personal vision, which is reflected in the way Green Roads operates now. Because of the quality and performance of their CBD products, they’ve received accolades and are well-known in the CBD business.

3. CBDistillery – Honorable Mention

Pros:

  • Natural farming practices
  • Try different CBD oil flavors
  • 0% THC and full-spectrum CBD
  • Wide range of potencies

Cons:

  • Some items may sell out due to their popularity

About the CBD Oils
CBDistillery has several CBD oil tinctures available for purchase. Their primary tincture is the Relief & Relax formula available in pure CBD isolate, full-spectrum and broad-spectrum oils, but you can also find gummies, flavored tinctures, and a sleep formula available on their website.

Relief & Relax Full-Spectrum CBD Oil Tincture
Select from three different strengths, including 500 mg, 1000 mg, and 2500 mg of CBD per 30 mL bottle. This range allows you to select what’s best for you, whether you’re new to CBD or accustomed to taking it and are just trying a new brand. To add a little more flavor to your CBD doses, you can purchase a full-spectrum mango tincture or see if they still have the limited edition, peppermint flavor, in stock!

What You Can Expect to Pay
The original full-spectrum CBD tincture, which contains 1000 mg of CBD per 30 mL, costs $60 for a single purchase. The lowest amount, 500 mg, is only $35 for a one-time purchase, while the greatest concentration, 2500 mg, is $130. If you prefer CBD with more flavor, no problem! Flavored alternatives aren’t an additional cost. And remember, when you choose the subscribe and save option on any of their CBD products, you save 20% and get free shipping.

Why Buy from CBDistillery
CBDistillery is ranked third on this list because of the way they treat their client relationships. You’ll want to understand everything you can about CBD before investing in a good product, especially if you’re new to it. CBDistillery makes it simple to discover more about CBD and which mixes might be the best fit for your requirements. There is a “learn more” link at the top of their website where you can find their blog, answers to frequently asked questions, a CBD user guide, and their podcast! Seriously, they’ve got you covered, no matter how obscure your question might be. Their customer service team is top-notch, and they’re always happy to guide you, easing your stress along the way, so you can get the perfect product for your needs.

4. Batch CBD – Newly Discovered

Pros:

  • Save 25% off when you subscribe
  • Hand-crafted in small batches
  • Original and calm formulas
  • Formulas rooted in scientific research

Cons:

  • Product descriptions are a bit barebones, identifying only a few pieces of information

About the CBD Oils
Batch CBD’s original tincture was the starting point for its success. They developed several other, more specialized compositions based on this original mix, including their calm CBD oil tincture. Each bottle contains 30 mL, and the calm CBD version is available in strengths ranging from 1000 mg to 3000 mg, or you can try their original recipe, which comes in four distinct concentrations: 500 mg, 1000 mg, 2000 mg, and 3000 mg of CBD.

What You Can Expect to Pay
The Batch original recipe at 500 mg costs $44.99 one-time, whereas the highest concentration at 3000 mg of CBD costs $129.99. The subscribe and save option helps bring the total cost down to $97.49 if you subscribe for delivery every 30 or 60 days.

If you buy the 1000 mg strength of the calm CBD tincture once, it costs $74.99. The total for the 3000 mg concentration is $129.99. Again, subscribing will save you an additional 25% discount, bringing your total down to $97.49.

Batch offers free shipping on all orders over $15, which is one of their best features. That ensures that even if you buy their original formula at the lowest concentration, you’ll acquire free shipping.

Why Buy from Batch CBD
Batch is one of our favorite bands since they haven’t forgotten their beginnings. They just have one purpose in mind: to help you feel better. They are led by a group of individuals that grew up in the Milwaukee area of Wisconsin. They cultivated their spirit of entrepreneurship by deciding to launch a CBD product line that is transparent, real, and effective. Rather than mass-producing their items, they chose instead to handcraft each batch, ensuring the highest level of quality for you.

5. Extract Labs – Award-Winning

Pros:

  • Full-spectrum CBD oil
  • Original and extra strength CBD oil options
  • Some flavored options
  • CO2 extracted CBD oil

Cons:

  • Your order must exceed $75 to obtain free shipping

About the CBD Oils
You’ll find several targeted formulations on the Extract Labs website, including for cognitive support, relief, and nighttime support. Their two daily support formulas include:

Daily Support CBD Tincture – Full-Spectrum
This is a long-standing customer favorite formula. Its former name was “original tincture”, but they’ve rebranded it to daily support to better suit the way it supports their customers. This flagship formula is the most potent on the market and you can always double your dose with the extra strength option, which contains 66 mg of CBD per mL. If you prefer a flavored product, try their full-spectrum raspberry or lemon CBD tinctures.

Daily Support CBD Tincture – CBD Isolate
Always a brand to ensure all their customers feel accounted for, Extract Labs offers a daily support formula with pure CBD isolate. It’s powerful at 66 mg of CBD per mL but with zero THC.

What You Can Expect to Pay
The tincture is $50 in the standard strength and $85 for the extra strength option. If you order $75 or more, you’ll get free domestic delivery, and if you choose the extra strength option, the shipping fees will be deducted at checkout because it meets the minimum. Any orders under $75 will be charged a shipping fee, which you may determine at the time of checkout. Simply exchange your email and join Extract Labs’ biweekly newsletter mailing list to receive 15% off your whole order. You’ll immediately receive a promo code in your inbox for savings!

Why Buy from Extract Labs
Extract Labs offers new clients a 15% discount on their total order if they sign up for their bi-weekly newsletter. Additional discount codes are usually found under the top banner of their website, and their CBD products have become so popular, they sometimes sell out! They offer full-spectrum, THC-free, and extra-strength CBD products in a range of flavors and formulations to appeal to a wide range of customers.

6. Plant MD – Gummies

Pros:

  • Gummies with full-spectrum CBD oil
  • Formulated to enhance focus
  • Promotes calm and relaxation
  • 100% customer satisfaction guarantee

Cons:

  • Limited supply—act fast if interested in these yummy gummies!

About the CBD Oils
Plant MD has created a full-spectrum gummy that delivers 750 mg of CBD in a bottle with 30 gummies. This all-natural product is free of adverse effects and does not require a prescription. They make their gummies with cold-pressed, unprocessed CBD oil and employ an innovative CO2 extraction technique to deliver therapeutic benefits like anxiety relief. These concentrated CBD extracts aid with mood regulation, allowing you to cope better with worry and stress. You’ll also notice that with regular use, your sleep cycles will improve, which will have a great impact on your waking hours.

What You Can Expect to Pay
The Plant MD website does not provide a price for the gummy bottle. Before you can see the price and shipping fees, you must first input your information and request a “rush” order.

Why Buy from Plant MD
These full-spectrum gummies were created by Plant MD to provide psychological and neurological advantages to improve your overall physical and mental health. They are committed to increasing your overall health by assisting in the regulation of your mood patterns and providing you with a more stable baseline on a daily basis. These gummies can help raise your mood and give you the peace you need to recover every night if you’re suffering from tension related to anxiety and worry.

7. Charlotte’s Web – Highly Reputable

Pros:

  • THC-formula available
  • Purchase up to 100 mL at a time
  • Exclusive offers when you sign up
  • Try the original or max strength formula

Cons:

  • To obtain free domestic shipping, you must first spend at least $74

About the CBD Oils
Charlotte’s Web boasts a line of CBD products that include an original formula, an extra-strength formula, and a THC-free formula.

Original Formula
This formula started an entire industry. Get the natural olive oil flavor or try the mint chocolate for a splash of cool. This formula is available in a 30 mL or 100 mL bottle and if 50 mg of CBD per mL isn’t enough for you, upgrade to their strongest option, which contains 60 mg of CBD per mL.

THC-Free CBD
This formula is only available in one flavor (mint chocolate) and a 30 mL bottle. It’s perfect for CBD users who prefer THC-free products. It contains 25 mg of CBD per mL.

What You Can Expect to Pay
The original formula costs $119.99, but you can save 20% by subscribing, bringing the total down to $95.99. The 30 mL bottle of the maximum strength product is priced the same. You may check out with Sezzle, a payment solution partner that allows you to make four interest-free installments, to soften the impact of your purchase (perfect for when you’re stocking up!). Because there aren’t any clear discount coupons on the site, the subscribe and save option might be your best hope for getting 20% off your order.

Why Buy from Charlotte’s Web
Charlotte’s Web is one of our current favorites since it was founded with the goal of bringing happiness to people who needed it the most. They use hemp cultivated in the United States, and their THC-free extraction and processing technique allows them to deliver a wide range of phytocannabinoids, terpenes, flavonoids, and vital fatty acids to their growing consumer base. They include premium hemp cannabis plant extract, carrier oil, and flavor in their ingredient list, which is kept minimal.

How to Choose the Best CBD Oil for Anxiety?

First, you should be sure that you’re selecting a formula that’s geared toward anxiety relief. Some formulas incorporate more energizing ingredients, like CBG, that may not provide the calm and sense of relaxation you’re seeking. However, they could help get you through the day without frayed nerves. Also, consider if you prefer an unwind formula for decompressing at the end of the day and if you need an additional formula to help you sleep better through the night. Sometimes, all a person needs is some daily support.

We’ll also remind you to review the factors we considered when putting this list of best CBD oil for anxiety products together. Always double-check ingredients to make sure that the formula is clean and all-natural; broad-spectrum, full-spectrum as well as pure CBD isolate oils should include the appropriate cannabinoids, terpenes, etc., and products made from organic hemp cannabis plant crops should get high marks. Purchase your supplies only from reputable suppliers that have made a name for themselves in the CBD industry. We can’t stress that enough. That’s the best way you can ensure you’re getting a safe product that has been tested by an independent lab.

Also, consider the potency you’re seeking. How much CBD oil to take is always a moderate or mild dose if you’re new to CBD. If you already know how CBD interacts with your body, you may want to venture into higher doses, depending on the therapeutic benefits you’re seeking. Flavors are important too. If you don’t like the taste, you might dread taking it, which defeats the purpose of having a helpful supplement on hand. If you need a flavored option, choose something fruity or something minty to help it go down with ease.

Benefits of CBD Oil

CBD has so many amazing therapeutic benefits that it’s almost hard to list them all so we will keep it centered around anxiety. When you’re anxious, your heart rate shoots up, your breathing accelerates, and your body stays in a panic zone, even when there aren’t any perceptible dangers. CBD calms all these symptoms, which brings your body back into a state of balance, so you are not subdued by the intensity of your typical nervous system responses.

Especially with anxiety disorders like post-traumatic stress disorder (PTSD), the symptoms can be completely unpredictable. You might fall asleep feeling good but wake in a cold sweat after having a nightmare. At that point, your sleep may be ruined, and you may just lay in bed trying to calm down, reminding yourself you’re safe. CBD can help to alleviate the symptoms related to PTSD and create a sense of safety by altering how your brain works.

Whether it’s a nightmare that wakes you or you simply can’t go to sleep at night, CBD can feel like a complete godsend. If your anxiety tends to appear mostly at night when you’re trying to rest, you may benefit from a sleep formula that serves as a figurative lullaby and gets you feeling cradled enough to relax, release tension, and surrender to sleep.

How to Use CBD Oil for a Generalized Anxiety Disorder?

When using CBD for general anxiety disorders, you’ll have a starting dose. You may need to increase it or decrease it depending on how the CBD affects you. When you first receive your shipment, confirm the dosage is what you initially purchased. Next, shake the bottle well to ensure a good consistency, and measure out your dose.

It could be half a dropper full or a full dropper full depending on the brand and the strength you selected, so be mindful about double-checking that. Once you have your dose ready, go ahead and place it beneath your tongue. Make sure that you don’t touch the dropper to your mouth, otherwise you compromise the quality of the CBD oil when you place the dropper back inside the bottle.

Hold the oil underneath your tongue for a minimum of 30 seconds but it’s better if you can hold it there for at least a minute before you swallow. That’s pretty much all you have to do! Just give it at least 30 minutes for you to feel the calming effects of the CBD.

Safety and Side Effects

CBD is extremely safe to use which is one big reason why the US Farm Bill made CBD legal. Any side effects you may experience will be mild. Some people report experiencing drowsiness when they first start taking their CBD. Often, this is because they have administered a dose that is too high for their needs. At the end of a long day when you’re looking to unwind, that drowsy feeling may actually help you relax and be a good sensation that you appreciate. However, if you are feeling drowsy during the day, try lowering your dose.

Another side effect may be gastrointestinal upset. This could be an upset stomach or perhaps diarrhea. Diarrhea occurs because of the carrier oil that loads CBD into your system. If you take your CBD product on an empty stomach, that could be the reason why. Try pairing it with food next time or lowering your dose and slowly increasing it over time.

Conclusion

Anxiety disorders don’t have to stop you from living. You’re entitled to a full life—one with quality relationships, restful sleep, and lots of laughter. CBD can be the perfect complement for your treatment plan, helping you tackle the obstacles you face with both grace and resilience.

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