cbd oil dosage for anxiety

The Ultimate Guide to CBD Oil For Anxiety: Science, Benefits & Dosage

CBD has a range of health benefits and can be taken as part of a healthy lifestyle to alleviate the symptoms of anxiety. This guide takes you through everything you need to know about CBD oil for anxiety.

What is CBD?

CBD is an active cannabinoid found in cannabis, otherwise referred to as marijuana or hemp. It stands for Cannabidoil and is a completely natural chemical that can be extracted for human use to relieve anxiety.

CBD can be taken in either the full spectrum (containing other cannabinoids) or isolate (solely CBD) varieties depending on your preference.

Becoming increasingly popular as a health product in the UK, North America and globally, it is different from THC, another cannabinoid found in hemp. This is Tetrahydrocannabinol and is the chemical that ‘gets you high’. CBD products for anxiety contain only trace amounts of THC which will have no effect. The legal amount permitted in the UK is less than 0.2% THC.

What is CBD oil?

CBD oil is the CBD compound extracted from the cannabis plant by a variety of methods, most commonly CO2 extraction and steam distillation, dissolved in an oil. It is taken orally, added to food or drink or by putting drops under the tongue.

In the UK CBD must legally contain less than 0.2% THC. As a result, you cannot get high or experience psychological effects from CBD oil. Now there are patented technologies that allow the human body to better absorb CBD – these have created water soluble CBD oils and are changing the face of CBD as a health supplement.

With water soluble CBD oils, you know exactly what you’re getting as absorption rates are up to 99%, as opposed to 5% for non-water soluble products.

What types of anxiety can CBD help with?

Current scientific knowledge points to CBD oil helping with the following anxiety conditions and symptoms:

  • Generalised anxiety disorder (GAD)
  • Social anxiety disorder (SAD)
  • Post-traumatic stress disorder (PTSD)
  • Obsessive compulsive disorder (OCD)
  • Panic disorder and panic attacks
  • Anxiety induced insomnia

Studies include a 2016 US study on the effects on PTSD including insomnia and a 2015 study on various types of anxiety, including generalised anxiety disorder.

Another good resource for reading more about scientific studies is on Project CBD.

The benefits of CBD for anxiety

It’s important to differentiate that CBD is not a cure for anxiety or depression and won’t root out the exact cause, but can be used to improve its symptoms.

Typically, the main benefit users can experience is this reduction in symptoms of anxiety, alleviation of stress, depression and an improvement in general well-being. When used alongside other methods such as counselling, it can be a great source of extra support to get the results you’re looking for.

It’s also very easy to incorporate into your daily and weekly routine as simple to use pipette bottles are the standard for CBD oils, letting you accurately control your dosage.

How does CBD work to alleviate symptoms?

CBD (a cannabinoid) is absorbed into the bloodstream and helps to regulate the existing endocannabinoids produced by our bodies which naturally impact on mood, appetite, sleep and the sensation of pain.

The endocannabinoids target receptors in the brain and help to bind the chemical serotonin to the receptors to improve mood and reduce stress. Through modulating and enhancing how serotonin binds and works with the receptors, it can improve the potential effects of serotonin.

The best CBD for anxiety

If you suffer from anxiety and are looking for a cost effective solution with better results, the best CBD available will be water soluble CBD.

  • Up to 99% absorption rates
  • Stronger and faster effects on anxiety
  • Easy and discreet to take with water or fruit juice

Water soluble CBD has a high bioavailability and is optimised to be absorbed by the human body. This ensures faster and better results and also means you benefit from up to 99% of the CBD you’re buying, without losing the majority of it before it enters your bloodstream.

Patented micelle technology delivers CBD efficiently and effectively to your body and if you’ve been using traditional hemp oil in the past, you should see a huge improvement if you make the switch.

Micelle technology

Micelle technology is the solution to CBD oils that deliver low absorption rates. Questions have been asked in recent years about how well the human body absorbs CBD and how this can be increased for health benefits. A Swiss scientific process, micelle technology enables CBD to pass the mucous membrane (which is 90-95% water) and enter the bloodstream almost instantly.

In comparison, non-water soluble oils will see CBD be largely wasted by the body as it will enter the stomach and be destroyed by acid and enzymes in the liver before it is absorbed. It’s estimated that on average only 5-10% of these oil types are ingested by the human body.

One of the main problems with this is that clinical trials won’t be accurate based on dosage and CBD concentrations as the absorption rate is so low.

Water soluble vs non-water soluble CBD

When researching oils, look for ones labelled as water soluble for better results, and specifically ‘micellated CBD’.

The micelle technology also ensures that the active component of the CBD is released into cells in the body and is a 100% natural process, mimicking our own body’s micelle system.

Consideration Non-water soluble Water soluble
Absorption rate 5-10% (average) Up to 99%
Application Drops under the tongue In water or fruit juice
Cost Lower cost but most CBD is wasted in the stomach and liver Higher cost but you get the concentration you’ve paid for as it’s better absorbed
Results Poor Better, faster

Advice on dosage

There isn’t a ‘one dosage fits all’ when it comes to CBD; there are recommended drops for oils but each individual needs to find what works for them.

The ideal amount per person depends on a range of factors including:

  • Body chemistry
  • Body weight
  • CBD concentration in the chosen oil

Due to the variables, when you start taking CBD oil, discuss with your doctor and start with a low dose or whatever they recommend, before gradually increasing it over time.

As doses for each product depend on the concentration of CBD, start with a lower concentration oil and dose accordingly. Again, whilst it varies per person, it would be better to start on 20mg per day rather than 40mg when you don’t know how it will affect your body.

Oils will state their concentration in mg per ml, and from this you can calculate the dosage per drop when using a dropper bottle.

Generally, stick to the initial dose for a week or two before increasing and always seek medical help if you experience any side effects or are unsure about how you’re using CBD.

Tips on using CBD to treat anxiety

CBD may offer a number of benefits for you and your anxiety and it’s important to consider how to start using it from a number of angles. To help, here are some tips.

Research your oils

Ensure you choose CBD that is certified, has less than 0.2% THC. If you want to better understand the dosage and absorption rate from your CBD, pick water soluble oils where you absorb up to 99% rather than around 5% for non-water soluble options.

Keep a journal

Take notes in a journal of when you take your CBD and the number of drops you use throughout the day and over the course of at least the first couple of weeks. In addition, write about how you’re feeling and any changes you might experience in mood and symptoms. Over time you can review and better understand how it is working or not working for you.

Start with a low dose

Always start with a low dose. CBD oils should come with a recommended dosage; you can start with the minimum or even lower but generally (although it depends on the product) you can start with 1-2 drops a day before increasing.

Why is this important? There is a risk you could have negative results from taking it and you want to ensure this is minimised. If you have any negative experiences, stop immediately and consult medical advice.

Stay consistent

Day to day and week to week, keep your dose consistent for the best results once you have worked out what is right for you. Being consistent generally means that your results will be consistent as well.

How long does CBD take to work for anxiety?

Ultimately this will vary person to person and when you first start out it’s best to monitor the effects you experience based on a low starting dosage that you gradually increase over time until the desired effects are achieved.

As everyone will have different sensitivities to CBD, results can vary from a few hours, a few days or even two weeks. As a result, don’t get disheartened if you don’t immediately see results. If you initially keep a note of the dosage and the effects, you’ll be able to better judge the results and determine how well it works for you and your anxiety symptoms.

As explained, if you opt for water soluble CBD, you’ll likely reduce the amount of time it takes to work for you which can be an important consideration if stress and anxiety is having a negative impact on your wellbeing.

Can it be used as a standalone treatment?

The short answer is yes it can, but it depends on you and your individual experience with anxiety and the methods to relieve it that work for you. Other solutions can include cognitive behavioural therapy (CBT), counselling, prescribed antidepressant medication and exposure therapy.

If CBD is combined with other treatments, you may find that you deal with the root cause of your anxiety through therapy and other means, whilst easing the symptoms with use of the oil.

What are the possible side effects of CBD?

Studies suggest that CBD is generally safe and non-toxic for humans and most users will find they have no side effects when they introduce it to their lifestyle. However, there are possible side effects to higher doses that you should be aware of and watch out for.

  • Tiredness
  • Nausea and vomiting
  • Diarrhea
  • Appetite changes
  • A dry mouth
  • Drowsiness
  • Low blood pressure
  • Lightheadedness

Most likely these would be felt with higher doses, so to limit the risk always start with low dosages and consult your GP before you take CBD for the first time, especially if you are on existing medicines or dietary supplements that it could interact with in your system and make less effective. These can include but are not limited to blood thinners.

For more information, check the NHS website for their advice on taking CBD.

Is there a chance CBD can increase the symptoms of anxiety?

Marjuana itself or ‘weed’ when smoked as a recreational drug can make a person more prone to being anxious when under the influence. However, as CBD oil only contains trace amounts of THC and is extracted CBD dissolved in an oil, either as an isolate or as full spectrum, it doesn’t work in the same way.

It is generally believed that CBD does not cause anxiety in users and will conversely reduce the symptoms, but as always, take note of your personal experience once you start and see how it affects you. If you have any concerns, stop taking it immediately and seek medical help.

How to buy CBD

CBD is legal in the UK and can be bought on the high street in various forms. You don’t need a prescription or medical note, although if you are concerned about the best steps forward for you and anxiety, it is best to consult a GP.

In the UK it isn’t very common to be prescribed CBD and to get it on prescription, but it may be given as treatment for epilepsy, vomiting and nausea caused by chemotherapy and muscle stiffness caused by MS.

Likely, the best option is to carry out your own research and buy water soluble CBD online. Be sure to check the CBD content (% and MG) in any product, as well as the THC amount before purchasing. It’s also recommended to pay close attention to the stated dosage on each individual product as it will vary depending on the CBD concentration.

The shelf life of CBD is generally between 12 and 24 months, so you can invest in larger sizes for use over a long period of time.

Can children take CBD oil for anxiety?

Parents are known to give their children medicinal CBD and CBD oil for a range of symptoms including anxiety, stress and insomnia, and the condition epilepsy. There are few scientific studies on the effects of CBD use by children and the safe dosage levels, however it is a growing area for research.

In the US the FDA approved a CBD based drug, Epidiolex. At this stage, any medication or the addition of CBD to a children’s treatment for a range of symptoms requires deep thought, consideration and the advice of medical professionals.

It is also worth noting that any CBD for children, and adults, should be certified with an accurate concentration of CBD to keep doses consistent.


CBD could be the solution you’re looking for to reduce your symptoms of anxiety disorders and stress. As a natural health supplement, cbd oils can have a positive impact to your lifestyle when used correctly and if trying it out for the first time, consult your doctor, start with a low dosage and take note of the effects.

Whichever product you choose, ensure you check the CBD concentration, THC amount and the certificate of analysis from the manufacturer.

For more information, get in touch with our experts at [email protected]

Always check with your GP if you have any health concerns. We do not sell CBD products as a medicinal product and they are in no way intended to be used to diagnose, cure, prevent or treat disease. They are sold here purely as food and health supplements. Always consult your health professional before taking any food supplements.

How Does CBD Affect Women? WHRY Fills Gaps in the Science of an Exploding Market

Google the three-letter acronym “CBD,” and you will receive 177 million results. For comparison, a search for “FBI” produces 213 million hits, “IBM,” 305 million, and “FDR,” just 51.3 million. Do you know what CBD is? More important, do you know what it does?

CBD is short for cannabidiol, a seemingly non-intoxicating compound of the cannabis plant, as opposed to tetrahydrocannabinol (THC), the major psychoactive component responsible for the drug’s euphoric effect.

CBD is the main active ingredient in a growing category of products sold in all 50 states with little regulation. The substance can be found in nasal sprays, food supplement powders, skin patches, suppositories, capsules, chocolates, coffee, beer, gummies, lollipops, macaroni and cheese, hummus, honey, jelly beans, cereal, gum, popcorn, peanut butter, massage oil, lotions, face masks, deodorant, pet treats, and bath bombs.

In 2019, more than 64 million Americans reported trying CBD, the majority of whom are female.

Manufacturers of these products have claimed they can help alleviate anxiety and pain, promote sleep, and treat depression, post-traumatic stress disorder, and more. But there is little research to support these claims or the safety of regularly using such products over time. Currently, the U.S. Food and Drug Administration has only approved the use of CBD to treat two rare, severe forms of epilepsy.

Now, with a grant from Women’s Health Research at Yale, Dr. Sarah Lichenstein is leading a study on how CBD may affect behavior and the brain to determine how it affects women and if it affects women and men differently.

“The majority of research on the neurological effects of CBD in healthy adults derives from a single small study conducted entirely on men,” said Lichenstein, Assistant Professor of Psychiatry at Yale School of Medicine. “If we are to make sure these products are safe and effective — and, if so, determine correct dosing — it is important to complement what has been done in men to understand how CBD affects the brain in women.”

In collaboration with Drs. Sarah Yip and Ayana Jordan, Dr. Lichenstein is focusing on CBD’s potential to treat anxiety disorders, the most common reason cited by CBD users for their interest in these products and a condition that is twice as prevalent among women than men. One in three women will meet the criteria for an anxiety or related disorder in their lifetime. In addition to direct negative impact on well-being, these disorders increase the risk of other significant harmful effects, including interpersonal difficulties, major depression, and suicide, as well as higher health care costs and higher rates of unemployment.

“We know that other substances used by women to manage anxiety, such as tobacco smoking, were once portrayed as non-addictive,” said WHRY Director Carolyn M. Mazure, Ph.D. “Yet smoking is in fact addictive and harder to quit for women compared to men.”

Currently, the most common medical treatment for anxiety disorders are benzodiazepines, medications which are twice as likely to be prescribed to women as men. These medications have been associated with a significant risk of abuse and fatal overdose when combined with alcohol or opioids.

“CBD presents a potentially promising alternative to benzodiazepines for treating anxiety, but there is a huge mismatch between the way these products are being marketed and the state of the science,” Lichenstein said. “We need to know much more about what CBD is doing, how it might operate in women, and if this is different in women and men — particularly as millions of Americans are already using it.”

Needed Research on CBD, Behavior, the Brain, and Women

Dr. Lichenstein’s study seeks to determine brain mechanisms behind how CBD affects the behavior of women, building on currently limited evidence showing that a single dose of CBD affects functional brain responses in healthy men and evidence that sex may influence how cannabis and its constituent compounds affect these responses.

“Most of what we know about how CBD acts on the brain comes from research on animals,” Lichenstein said. “There is evidence it acts on many different neural systems through diverse mechanisms of action, which makes it interesting to study. But also hard to pin down.”

Study participants will take either the FDA-approved CBD oral solution known commercially as Epidiolex or a similarly appearing and tasting but inert placebo. They will then undergo tasks proven to reliably induce low levels of stress in most healthy individuals while inside of a magnetic resonance imaging (MRI) scanner. Researchers will gather data on self-reported measures of anxiety and subjective and physiological effects following the administration of CBD or the placebo while observing and recording activation of the insula and amygdala, areas of the brain associated with stress and anxiety.

Crucially, all participants will be female, providing necessary data to compare with existing male data and to prepare applications for additional external funding for a larger study that can directly compare the effect of CBD on women and men.

Dr. Lichenstein anticipates that CBD’s effects on the insula and amygdala — and associated reduction in perceived anxiety — could be greater in women than in men.

“Women seem to have more exposure from the same dose of CBD,” Lichenstein said. “Preliminary data suggest that women reach peak concentrations more quickly and reach higher concentrations than men.”

However, it is also possible that greater exposure among women could interfere with CBD’s effects on anxiety based on preclinical studies suggesting that neurobiological channels may block the effects of CBD at higher doses and are modulated by the female sex hormone estradiol.

“If there is a point at which higher doses trigger a neurobiological mechanism that blocks the anti-anxiety effects of CBD, that could very likely lead to different effects for women and men,” Lichenstein said.

Such differences, if found in the brain and through an observed effect on anxiety reduction, would indicate the need to establish sex-specific dosing recommendations for CBD.

“We don’t know if or where a dosing cutoff exists for humans in terms of safety or reducing anxiety,” Lichenstein said. “We need research in people with anxiety disorders and research on dosing over long periods of time. But first, we need to take this initial, essential step toward understanding what exactly happens to the behavior and in the brains of women when using this popular but largely unexamined substance.”

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.


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.


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 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 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.

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 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 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].

Evidence from Neuroimaging Studies

Relevant studies are summarized in Table 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].

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.


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.


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New York University School of Medicine, New York, NY, USA

Esther M. Blessing, Maria M. Steenkamp, Jorge Manzanares & Charles R. Marmar

Instituto de Neurociencias de Alicante, Universidad Miguel Hernández and Consejo Superior de Investigaciones Científicas, Alicante, Spain