Cannabidiol (CBD) is just one of over 85 scientifically-identified cannabinoids (or chemical compounds) derived from the flowering plant cannabis. Each of the cannabinoids within cannabis elicit unique neurophysiological effects. Most people are well-aware of THC (tetrahydrocannabinol), the predominant cannabinoid within cannabis that is ingested by upwards of 230 million people per year as a psychoactive euphoriant.
Although not as abundant as THC cannabinoid content, cannabidiol accounts for approximately 40% of all cannabinoids within cannabis extract. Unlike THC, cannabidiol is non-psychoactive and isn’t typically ingested with the intent to attain any sort of psychological euphoria. That said, the medicinal properties associated with cannabidiol (often administered in the format of “CBD oil”) are thought to far exceed those of THC.
Preliminary evidence suggests that CBD may act as an: anticonvulsant, antipsychotic, anti-inflammatory, and neuroprotective agent. Furthermore, some evidence suggests that CBD oil may be an effective intervention for the ongoing management of anxiety disorders. Those with anxiety disorders who fail to derive benefit from traditional pharmacology and/or who are unable to tolerate standard pharmacological treatments may want to consider administration of CBD oil on an ongoing or “as-needed” basis.
How CBD Oil Treats Anxiety (Mechanisms of Action)
Cannabidiol offers a novel pharmacodynamic profile as an anxiolytic agent. It is believed that administration of CBD (cannabidiol) modulates neurotransmission in a multitude of ways. Literature shows that cannabidiol alters 5-HT1A, GPR55, CB1/CB2, and mu/delta opioid receptor sites – while simultaneously enhances hippocampal neurogenesis. The combination of these neurophysiological effects likely contribute to its efficacy as a novel anxiolytic.
5-HT1A partial agonist: Modulation of neurotransmission at the 5-HT1A receptor is understood to provide anxiolytic, antidepressant, and neuroprotective effects. Research has demonstrated the effect of cannabidiol as a 5-HT1A receptor partial agonist, meaning it binds to the receptor site but only stimulates the receptor partially (relative to a full agonist). Studies with cloned human cell cultures note that cannabidiol displaces 5-HT1A agonists from 5-HT1A receptor sites in a dose-dependent manner.
In other words, the greater the amount of CBD oil administered following administration of a 5-HT1A agonist, the more significant the displacement. Researchers mention that this mechanism differs from THC which is incapable of displacing 5-HT1A agonists from the 5-HT1A receptor. Partial agonism of the 5-HT1A receptor site is associated with an array of therapeutic effects including: increased serotonin (or serotonergic effects), increased dopamine (in medial PFC, striatum, hippocampus), releasing acetylcholine, and hippocampal neurogenesis.
A study published in 2008 indicated that CBD injections into the dorsolateral periaqueductal gray area of rats reduced anxiety via 5-HT1A receptor interaction. Researchers noted that the 5-HT1A receptors were more involved than cannabinoid receptors (e.g. CB1) in reducing anxiety. The study concluded that cannabidiol interacts directly with 5-HT1A receptors to yield an anxiolytic response.
Although the 5-HT1A partial agonism exerted by CBD may not be an outright cure for anxiety, it is likely to help many individuals. Studies conducted on humans with panic disorder note impairments in 5-HT1A receptor function and poor 5-HT1A binding. The bottom line is that individuals with anxiety could have dysfunctional 5-HT1A activation and may resort to commercialized 5-HT1A partial agonists (e.g. Buspar) as treatments.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/16258853
- Source: https://www.ncbi.nlm.nih.gov/pubmed/15906386
- Source: http://www.ncbi.nlm.nih.gov/pubmed/14736842
- Source: http://www.ncbi.nlm.nih.gov/pubmed/1346719
- Source: http://www.ncbi.nlm.nih.gov/pubmed/18446323
Hippocampal neurogenesis: One hypothesized mechanism by which pharmaceutical anxiolytics may decrease anxiety is via hippocampal neurogenesis – or growth of new neurons within the hippocampus. It appears as though cannabidiol administration induces hippocampal neurogenesis in animal models, and for this reason, similar outcomes may occur in humans. A rat study involving the chronic administration of 5-HT1A partial agonist (tandospirone) increases the biomarker of doublecortin – indicating emergence of new neurons in the hippocampus.
Some researchers believe that hippocampal neurogenesis may play a critical role in attenuating symptoms of severe anxiety and/or depression. Although not all 5-HT1A partial agonists may induce hippocampal neurogenesis, there’s evidence to suggest that cannabidiol does. A study published in 2013 assessed the anxiolytic effects of CBD in mice exposed to chronic stress.
Results from the study indicated that CBD administration increased neuronal proliferation and neurogenesis in the hippocampal region. It is also thought that CBD’s modest affinity for cannabinoid receptors CB1 and CB2 may contribute to hippocampal neurogenesis. Stimulation of the CB1/CB2 receptor sites upregulates endocannabinoid signaling and leads to neuronal growth.
Regardless of how CBD oil induces hippocampal neurogenesis, the growth of new brain cells may be enough to decrease anxiety. A report published in 2015 documented that increasing adult neurogenesis (regardless of the modality) is sufficient enough to decrease anxiety. Therefore, it could be that CBD is an effective anxiolytic predominantly through mechanisms implicated in neurogenesis.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23298518
- Source: http://www.ncbi.nlm.nih.gov/pubmed/26000223
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25833129
CB1 + CB2 receptor (inverse agonist): Most evidence suggests that CBD oil has a low affinity for CB1 and CB2 receptor sites as an inverse agonist. In other words, it binds to the CB1 and CB2 receptors but exerts the pharmacologically opposite effect to an agonist. This differs from a CB1/CB2 antagonist which solely binds to these receptors and blocks stimulation from endocannabinoids.
It also is distinct from THC which acts as a CB1/CB2 partial agonist, thereby stimulating the receptor sites. If it acted the same as THC at the CB1/CB2 receptor sites, its therapeutic potential may be reduced. Moreover, since cannabidiol acts as an inverse agonist at the CB1/CB2 receptor sites, it doesn’t induce psychological euphoria and/or pleasure associated with downstream dopaminergic enhancement in the mesolimbic pathway (resulting from CB1/CB2 agonism).
Research has shown that administration of cannabidiol actually inhibits agonist effects at the CB1/CB2 receptor sites. Although the effects of CB1 inverse agonism aren’t fully elucidated, many speculate that CB2 inverse agonism may contribute to cannabidiol’s anti-inflammatory effects. Due to the fact that neuroinflammation is associated with anxiety disorders, we could hypothesize that a decrease in inflammation may yield anxiolytic responses in a subset of CBD users.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/17245363/
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22814704
Opioid receptor modulator: Another possible mechanism by which CBD may alleviate symptoms of anxiety is through allosteric modulation of mu-opioid receptor (MOR) and delta-opioid receptor (DOR) sites. Though it is known that allosteric modulation of the MOR and DOR is capable of reducing anxiety, it isn’t fully understood how. Some speculate that MOR and DOR sites affect GABAergic and dopaminergic neurotransmission.
Certain individuals may be more prone to anxiety than others as a result of mu-opioid receptor expression and/or activation. Research indicates that mu-opioid receptors participate in the modulation of anxiety based on the specific region of the brain in which they are stimulated. What’s more, a report published in 2015 indicated that the neural circuitry associated with the DOR (delta opioid receptor) can induce OR inhibit anxiety.
Selective delta receptor agonists have been shown (in animal studies) to reduce anxiety-like behavior and block anxiogenic effects of stressors. Specifically, modulation of the DOR in the central amygdala may predict severity of an individual’s anxiety. There’s reason to believe that allosteric MOR and DOR modulation provided by CBD could reduce anxiety in a subset of individuals – especially when combined with aforestated 5-HT1A and CB1/CB2 effects.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/16489449
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16626794
- Source: http://www.ncbi.nlm.nih.gov/pubmed/20730419
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25444168
Other possible mechanisms of CBD Oil for anxiety…
Although the 5-HT1A receptor partial agonism is thought to facilitate a majority of CBD’s anxiolytic effects – hippocampal neurogenesis, opioidergic modulation, and CB1/CB2 inverse agonism likely also contribute. Lesser researched mechanisms of CBD that could also decrease anxiety include: FAAH inhibition, adenosine reuptake inhibition, GPR55 antagoism, intracellular calcium (Ca2+) increases, and PPAR agonism. Of these mechanisms, inhibition of FAAH may be most significant in regards to anxiety attenuation.
- Adenosine 2A receptor: Administration of CBD is thought to act upon the adenosine 2A receptor site, possibly contributing to its anxiolytic and anti-inflammatory effects. Adenosine receptors are known to influence cardiovascular processes (cardiac rhythm, circulation), immune function, sleep, pain regulation, and blood flow. The adenosine 2A receptor interacts with G proteins to alter cAMP (cyclic adenosine monophosphate). Dysfunction of the adenosine 2A receptor may disrupt neurotransmission of glutamate and dopamine, and simultaneously cause inflammation, neurodegeneration, and possibly anxiety.
- GPR55 antagonism: GPR55 (G-protein-coupled receptor 55) is a receptor expressed predominantly within the caudate nucleus and putamen. It is often referenced as an atypical cannabinoid receptor due to the fact that it is activated by cannabinoids. A study published in 2015 investigated the role of GPR55 function in anxiety. Researchers concluded that GPR55 may modulate anxiety-related behaviors in rats. In the study, it was discovered that GPR55 antagonists lead to increased anxiety. Cannabidiol is thought to act as a GPR55 antagonist which may improve bone health and decrease proliferation of cancer cells – but may not help anxiety.
- FAAH inhibitor: The anxiolytic efficacy of CBD may be a result of its ability to act as an enzymatic inhibitor of FAAH (fatty acid amide hydroxylase). FAAH is an enzyme responsible for metabolizing endocannabinoids such as anandamide, but when inhibited, these endocannabinoid concentrations are increased. Increased concentrations of endocannabinoids such as anandamide and 2-AG, both of which bind to peripheral CB1/CB2 receptor sites.
- PPAR agonism: Agonism of PPARs (peroxisome proliferator activated receptors) may have a variety of benefits including: anticancer, neuroprotective (via removal of beta-amyloid plaques), and antipsychotic effects. Cannabidiol bolsters PPAR-alpha signaling and simultaneously decreases inflammation. Although PPAR agonism may not directly foster an anxiolytic effect, it cannot be ruled out as a potential synergistic contributor.
- TRPV1 receptor: The TRPV1 (transient receptor potential cation channel subfamily V member 1) receptor is a “vanilloid receptor” associated mostly with the modulation of body temperature and nociception. Cannabidiol is believed to act as a TRPV1 receptor agonist, thereby stimulating the receptor which may reduce sensations of pain and lower inflammation. It is possible that the nociceptive effect associated with TRPV1 agonism also reduces anxiety.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/23108553
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25175973
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15219815
- Source: http://www.ncbi.nlm.nih.gov/pubmed/26360704
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25620584
Benefits of CBD Oil for Anxiety (Possibilities)
There are an array of speculative advantages associated with using CBD [oil] as a treatment for anxiety. The agent appears effective for reducing many different types of anxiety and stress when administered on an acute, single-dose basis. In addition to reducing anxiety, preliminary research suggests that CBD may enhance mood, reduce inflammation, improve sleep quality, and preserve healthy brain function. Compared to traditional anxiolytics, CBD isn’t associated with any significant side effects nor substantial contraindications, thereby making it an appealing investigational treatment.
- Acute “as needed” administration: Though studies haven’t examined the effects of chronic CBD administration in humans, most have documented the effects of acute administration. Acute administration is associated with a significant anxiolytic effect (as compared to a placebo). Unlike medications such as SSRIs, CBD provides fast-acting (nearly instantaneous) anxiety relief and doesn’t require daily administration for weeks/months to attenuate symptoms.
- Adjunctive option: Many speculate that CBD could bolster anxiolytic effects of various first-line pharmaceutical agents. Since likelihood of CBD interacting with other agents is minimal, it may serve as a novel adjunctive option for those with severe anxiety. In other words, someone who fails to derive sufficient benefit from a first-line option may find that addition of CBD (on an “as needed” basis) fully attenuates anxious symptoms.
- Antipsychotic: Those suffering from anxiety as a result of a condition like schizophrenia may benefit from utilization of CBD oil. While the phytocannabinoid THC may exacerbate positive symptoms of schizophrenia (due to its psychotomimetic properties), CBD is understood to have antipsychotic properties. It isn’t fully elucidated as to how CBD reduces psychotic symptoms, but some believe its indirect modulation of dopaminergic transmission plays a role.
- Anti-inflammatory: Many individuals with neuropsychiatric disorders have severe inflammation, particularly neuroinflammation. Neuroinflammation is associated with many causative underpinnings including: air pollution, brain injuries, viruses, and even standard aging. This increase in inflammation can lead to glial cell and cytokine abnormalities, each of which could contribute to anxiety disorders. CBD has been shown to reduce neuroinflammation, which in turn may directly improve anxiety, as well as cognitive function and mood.
- Doesn’t affect cognition: A major drawback associated with anxiolytics is that many affect cognitive function. Sure it helps to take a pill and have less anxiety, but what if it compromises your cognitive abilities (e.g. critical thinking, problem solving, planning, etc.)? Agents such as benzodiazepines are linked to memory problems and generally impair functionality despite reducing anxiety. Research has highlighted CBD’s ability to reduce anxiety without impairing cognitive function.
- Few interactions: Most evidence indicates that CBD is unlikely to interact with pharmaceutical drugs. However, when taken at a reasonable dosage, CBD is understood to inhibit CYP450 isoenzymes in the liver. This may alter the pharmacokinetics of other drugs such as Warfarin which are metabolized by similar enzymes. That said, the pharmacokinetic and pharmacodynamic contraindications associated with CBD appear minimal.
- Efficacy: While it is impossible to confirm that CBD will effectively reduce anxiety in all users, most evidence indicates that it is likely to provide benefit when ingested at a sufficient dosage (600 mg – orally) on an acute basis. In other words, most people seeking immediate relief from anxiety will likely feel significantly less anxious after using CBD than if they had ingested a placebo. Placebo-controlled studies have already documented the efficacy of acute CBD administration for anxiety.
- General health improvement: Intermittent usage of CBD oil on an “as-needed” basis is understood to provide numerous general health benefits. Research suggests that CBD oil may offer anticancer, analgesic, and antiemetic properties. There’s evidence noting that it may boost immune function, slow the growth of bacteria, reduce muscle spasms, and modulate blood sugar levels. Literature indicates that cannabidiol may be conducive to general health.
- Mood enhancement: While CBD isn’t known for provoking a euphoric high, there’s some evidence to suggest that it may enhance mood. Research in animal models notes that CBD yields a combination of anxiolytic and antidepressant effects. That said, this research cannot be generalize to humans. If you’re severely depressed, don’t expect CBD to treat your depression. However, the fact that the drug targets the 5-HT1A receptor and CB1/CB2 receptors suggests that it could improve mood in certain individuals.
- Multiple types of anxiety: A limitation associated with CBD research is that it hasn’t been tested extensively among patients with a specific diagnostic subtype of anxiety (e.g. generalized anxiety). That said, studies note that CBD is likely efficacious in treating symptoms of many different types of anxiety including: social phobia, PTSD, panic disorder, OCD, and generalized anxiety disorder. Therefore, individuals may derive anxiolytic benefit from CBD – regardless of their specific type of anxiety.
- Neuroprotective properties: There’s some evidence to suggest that CBD may act as a neuroprotective agent. In other words, it may prevent brain cell death and/or damage resulting from hypoxic-ischemic encephalopathy. Those with hypoxic-ischemic encephalopathy tend to incur damage as a result of inadequate brain oxygenation. Studies in pigs indicate that CBD protects the brain from hypoxic-ischemic damage.
- Nervous system reset: When we experience a freeze-fight-flight response, activity in the autonomic nervous system (ANS) is altered. Anxiety and fear-inducing situations skew activation of the ANS so that the sympathetic branch is more active than the parasympathetic branch. Administration of CBD has been shown to prevent overactivity in the sympathetic branch via 5-HT1A partial agonism. This means that administration of CBD prior to or after a highly stressful event may prevent a full-blown nervous breakdown.
- Public speaking: Those who have difficulty with public speaking due to anxiety will likely benefit from CBD. Cannabidiol administration approximately 1.5 hours prior to a simulated public speaking engagement significantly reduced anxiety compared to a placebo. Those with social anxiety were found to derive the most benefit from its administration. However, it is likely that cannabidiol would benefit even those without social phobia if anxiety is experienced during a public speaking task.
- Safety: As of current, there’s zero evidence to suggest that cannabidiol is unsafe and/or intolerable. While certain individuals may experience adverse effects from its administration, these adverse effects are not common and may be a result of: poor sourcing, formatting, addition of other unwanted chemicals or cannabinoids, or contamination. Most research indicates CBD is just as safe and well-tolerated as a placebo.
- Side effects: There appear to be no significant unwanted side effects associated with CBD compared to a placebo. Many anxiolytics carry severe side effects such as: brain fog, drowsiness, inability to retrieve memories, impaired learning, sexual dysfunction, etc. Individuals taking CBD are unlikely to experience severe unwanted side effects.
- Sleep enhancement: Many individuals with anxiety disorders struggle to get proper sleep. Anxiety often causes insomnia and insomnia often causes anxiety – leading to a vicious cycle of back-and-forth reinforcement that is seemingly inescapable. Administration of CBD has been shown to restore normal REM sleep and is thought to improve sleep quality of certain individuals.
Drawbacks of CBD Oil for Anxiety (Possibilities)
There may be some drawbacks associated with using CBD oil for anxiety, especially over a long-term. Hypothetical drawbacks could result from CBD usage include: deleterious epigenetic and/or neurophysiological effects, increased anxiety, tolerance onset (with decreased efficacy over time), and/or withdrawal symptoms. Keep in mind that many of these drawbacks are merely speculative and cannot be confirmed.
- Bioavailability: The bioavailability of orally-administered CBD is considered extremely low (around 6%). If you smoke cannabidiol, the bioavailability increases to over 30% and if you utilize an intranasal preparation, bioavailability may reach nearly 50%. However, since many people are using oral preparations of CBD, the bioavailability is low and will require a high dose.
- Chronic administration: There’s minor evidence suggesting that chronic administration of CBD may be deleterious to neurophysiological health. This evidence didn’t come from a human study, but discovered that chronic CBD administration (10 mg/kg, intraperitoneal injections) for 14 days reduced BDNF expression in various regions of the brain. It also altered protein expression of TrkB and phospho-ERK1/2 – indicating (potentially) unwanted epigenetic changes.
- Cost: For high quality, unadulterated CBD – you’re going to pay a hefty price. Assuming you don’t want a product with pesticides, herbicides, fertilizers, and/or other chemical additives, you’ll likely end up paying a significant amount for just a few doses. Until scientists figure out a way to enhance CBD’s bioavailability, regular users of oral CBD may feel as if the supplement is too costly. Fortunately, there are other ways to administer cannabidiol such as vaporizing the oil – which will likely save consumers money.
- Increased anxiety: Rodents administered cannabidiol daily for 14 days exhibited anxiogenic behaviors. In other words, the cannabidiol may increase anxiety when used too regularly. Although this effect cannot be confirmed in humans, it is logical to assume that a person’s neurophysiology will adapt to the effects of CBD when used regularly, possibly blunting its efficacy.
- Tolerance: It is possible that someone who uses CBD oil often could become tolerant to its effects. This is because no drug is capable of bypassing the endogenous homeostatic mechanisms of the human body. If something were capable of doing so, people could remain on an anxiolytic and/or antidepressant for an indefinite period of time without any decreased efficacy. Unfortunately, it is likely that if used too frequently, tolerance will ensue and an individual will require greater doses to maintain a therapeutically anxiolytic effect.
- Unknown long-term: The long-term effects of cannabidiol aren’t well understood. In just the past few years, the substance has received more mainstream attention and is increasing in popularity. As more scientific studies support its safety and efficacy as a treatment for medical conditions, more data will be gathered from long-term users. As of now, we aren’t sure whether there could be any detrimental long-term effects of cannabidiol – especially when used by minors.
- Withdrawal: It is unclear as to whether there are any withdrawal symptoms ensuing following discontinuation of chronic CBD oil administration. It is apparent that there are marijuana withdrawal symptoms – it took years for these to receive legitimate scientific attention in the literature. Though most would speculate that CBD is unlikely to cause discontinuation effects, withdrawal symptoms cannot be ruled out among long-term, chronic users.
Cannabidiol (CBD Oil) For Anxiety (Review of Evidence)
Below is a synopsis of the literature investigating cannabidiol (CBD) for the treatment of anxiety. Understand that there may be limitations associated with the research in regards to study designs and/or lack of participants. That said, preliminary evidence indicates that CBD may be a safe, effective pharmacological treatment for anxiety.
2016: Neural correlates of interactions between cannabidiol and Δ(9) -tetrahydrocannabinol in mice: implications for medical cannabis.
A study conducted by Todd and Arnold (2016) elucidated the neural correlates associated with CBD and THC interactions in mice. The researchers administered CBD, THC, or a combination of CBD/THC to mice and examined anxiety-related behaviors – as well as other neurophysiological markers. Results indicated that THC suppressed locomotor activity and was anxiogenic in that it increased anxiety.
Administration of CBD reduced the anxiogenic effects of THC, suggesting that it is capable of decreasing anxiety in animal models. It was also documented that standalone CBD treatment reduced expression of c-Fos in the central nucleus of the amygdala. Reduction in c-Fos is understood to yield anxiolytic effects – possibly another mechanism by which cannabidiol attenuates symptoms of anxiety.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/26377899
- Source: http://www.ncbi.nlm.nih.gov/pubmed/7621504
2015: Cannabidiol as a Potential Treatment for Anxiety Disorders.
A study published by Blessing et al. (2015) evaluated the therapeutic efficacy of cannabidiol in the treatment of anxiety disorders. Researchers compiled and assessed evidence from preclinical, experimental, clinical, and epidemiological publications. This report concluded that preclinical evidence supports the usage of CBD as a potential intervention for anxiety disorders.
Authors noted that CBD is capable of reducing anxiety, panic, and obsessive tendencies. It appears to reduce autonomic arousal and conditioned fear expression, and impairs anxiogenic effects associated with stress. What’s more, it enhances fear extinction and appears to induce a blockade of traumatic memory “reconsolidation”– reducing the frequency at which persistent traumatic memories resurface.
Evidence indicates that CBD is an effective intervention for neuropsychiatric anxiety disorders such as: generalized anxiety disorder, social phobia, panic disorder, PTSD, and OCD. Researchers believe that its anxiolytic effects are principally a result of its affinity for 5-HT1A and CB1 receptors. While further research is warranted regarding long-term use of CBD oil for anxiety, authors note that it does not increase anxiety, has minimal sedation, and is extremely safe when used over a short-term.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/26341731
2014: Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa.
A study published by de Mello Schier et al. (2014) reviewed the literature involving administration of CBD to animal models of anxiety. The studies reviewed by researchers assessed animal performance with measures such as: forced swimming tests (FST), elevated plus mazes (EPM), and Vogel conflict tests (VCT). In all cases, administration of CBD to animal models reduced anxiety and improved mood – as evidenced by behavioral performance.
Interestingly, researchers noted that cannabinoid receptor sites CB1 and CB2 remained inactive after CBD administration. This suggested that anxiolytic benefits were attained likely through binding to the 5-HT1A receptor. Nonetheless, research in animal models indicates that CBD appears efficacious as an anxiolytic.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24923339
2012: Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug.
Research conducted by Schier et al. (2012) aimed to review the literature of cannabidiol (CBD) as an anxiolytic due to the fact that it is non-psychotomimetic. Researchers gathered scientific publications from English, Portuguese, and Spanish databases. All compiled articles analyzed the anxiolytic effects of cannabidiol from both human and animal model studies.
The review of evidence documented an anxiolytic-like effect of CBD in both healthy volunteers and animal models. What’s more, CBD significantly reduced feelings of anxiety among those diagnosed with social anxiety disorder (SAD). Although the specific anxiolytic mechanisms of CBD aren’t fully elucidated, researchers recommend additional trials of CBD for panic disorder, OCD, social phobia, and PTSD.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22729452
2012: Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers.
A study conducted by Martin-Santos et al. (2012) aimed to compare the acute effects of two notable cannabinoids: CBD (cannabidiol) and THC (tetrahydrocannabinol). Researchers recruited 16 healthy males and set up a randomized, placebo-controlled, double-blind, cross-over trial. The 16 participants received three consecutive single-dose agents administered 1-month apart in the following order: 10 mg THC (oral) – first month, 600 mg CBD (oral) – second month, or a placebo – third month.
To determine the effects of each substance, physiological measures were collected along with symptom ratings approximately 1, 2, and 3 hours post-administration. Post-trial assessment of physiological measures indicated that compared to placebo and CBD, administration of THC caused anxiety, dysphoria, positive psychotic symptoms, neurophysiological sedation, and elevated heart rate. Strikingly, there appeared to be no significant differences between CBD and placebo on physiological or symptomatic measures.
From this study we can conclude that the acute effects of THC (e.g. increased anxiety) are unfavorable. Evidence suggests that CBD appears well-tolerated and safe, with no adverse physiological reactions compared to a placebo. However, since the physiological effects of CBD (600 mg) were of no statistically significant difference from the placebo, it is unclear if CBD elicits any therapeutic effect – even at a seemingly reasonable dose.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22716148
2011: Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients.
Researchers Bergamaschi et al. (2011) highlighted previous literature regarding CBDs anxiolytic properties and lack of psychotomimetic effects. For this reason, they wanted to test its efficacy for the treatment of anxiety among 24 individuals with social phobia. It should be noted that all 24 of these individuals had never received any sort of prior treatment (e.g. SSRIs) as an intervention for their social anxiety and were considered “treatment-naïve.”
The 24 individuals were divided evenly into groups of 12 and randomly assigned to receive either CBD (600 mg) or a placebo – prior to a stimulated public speaking test (SPST). As a comparison, researchers also recruited 12 healthy individuals without any neuropsychiatric diagnosis to serve as a control – this group received no CBD. The CBD and placebo were administered 1.5 hours prior to the simulated public speaking test.
Throughout the SPST, researchers utilized the Visual Analogue Mood Scale (VAMS), Negative Self-Statement scale (SSPS-N), and physiological measures (blood pressure, heart rate, skin conductance) to determine the anxiolytic efficacy of CBD. Results indicated that those receiving the CBD exhibited significantly less anxiety, cognitive deficits, speech discomfort, and decreased alertness on the VAMS measure. Contrastingly, the individuals receiving the placebo exhibited high anxiety, cognitive deficits, high alertness, and overall discomfort on the VAMS.
The SPSS-N revealed substantial increases among those receiving the placebo, whereas those receiving the CBD did not differ from the healthy controls in this measure. This study indicates that those with social phobia experience significant increases in anxiety during a public speaking task. However, administration of single-dose CBD (600 mg) ~1.5 hours before speaking significantly attenuates anxiety and improves performance.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21307846
2011: Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report.
Crippa et al. (2011) published a study investigating the effects of CBD on neural activation among those with social anxiety disorders. For the study, researchers recruited 10 treatment-naïve patients with social anxiety disorders. To determine how CBD influenced neural activity, they utilized functional neuroimaging to assess regional cerebral blood flow at rest with a SPECT scan incorporating an L-ethylcysteinate dimer (ECD) tracer.
In the primary session, participants were assigned to receive either CBD (400 mg) or a placebo in double-blinded framework. Thereafter in a second session, participants received the agent that they hadn’t received in the first session; those that received the placebo first received the CBD – and vice-versa. Measures indicated that after receiving CBD (400 mg), subjective measures of anxiety significantly decreased compared to the placebo.
There were distinct changes in neural activation associated with the significant anxiolytic effects provided by CBD. When compared to the placebo, administration of CBD significantly: increased ECD tracer uptake in the right posterior cingulate gyrus and decreased ECD tracer uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus. Researchers concluded that reductions in social anxiety from CBD are related to modulation of neural activity in the limbic and paralimbic regions.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/20829306
2009: 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioral and cardiovascular responses to acute restraint stress in rats.
An animal study involving male Wistar rats conducted by Resstel et al. (2009) examined the effect of CBD on restraint stress (RS). Previous research had demonstrated that the phytocannabinoid cannabidiol (CBD) yielded anxiolytic and antipsychotic properties in animal models. For this reason, they investigated whether CBD facilitates adaptation to scenarios of inescapable stress and whether this response is mediated by 5-HT1A receptors.
In an initial experiment, the male Wistar rats received injections of CBD and were exposed to 60 minutes of restraint stress – with cardiovascular responses recorded. In a second experiment designed to determine effects of CBD on the 5-HT1A receptor, researchers administered a 5-HT1A antagonist prior to the CBD. Precisely 24 hours after CBD administration, the Wistar rats were tested in an elevated plus-maze to gauge anxiety.
All exposure to restraint stress resulted in increased blood pressure and heart rate, thereby significantly increasing anxiety in the elevated plus-maze 24 hour. However, administration of CBD alleviated the anxiety associated with the elevated plus-maze. Prior administration of the 5-HT1A antagonist inhibited the therapeutic effects of the cannabidiol.
This evidence supports the idea that CBD decreases autonomic stress responses (e.g. increased blood pressure, faster heart rate, etc.) associated with stress in animal models. Additionally, the reduction in stress associated with CBD is induced predominantly via its binding to the 5-HT1A receptor sites. Based on the results, we could speculate that CBD may be equally therapeutic in attenuating exaggerated autonomic stress responses in humans.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19133999
2004: Effects of cannabidiol (CBD) on regional cerebral blood flow.
A study by Crippa et al. (2004) attempted to elucidate alterations in neural activity as induced by cannabidiol. For the study, researchers recruited 10 healthy volunteers and divided them into two groups of 5. These two groups were then assigned to receive CBD (400 mg) or a placebo on separate occasions – one week apart.
Researchers utilized SPECT neuroimaging with an ECD tracer to assess regional cerebral blood flow of the participants ~90 minutes after CBD or placebo administration. They also administered the VAMS (Visual Analogue Mood Scale) to determine subjective mood of participants throughout the study. After each participant had been examined twice (once with the placebo, once with the CBD) – data was compared.
Results indicated that CBD significantly reduced subjective measures of anxiety as evidenced by changes in VAMS scores. Neuroimaging data revealed decreased ECD-tracer uptake when participants received the CBD compared to when they took the placebo. Particularly, activity in the left amygdala-hippocampal complex and the left posterior cingulate gyrus decreased following CBD administration.
Furthermore, there appeared to be increased activation within the left parahippocampal gyrus among those receiving the CBD. Authors concluded that CBD is capable of eliciting anxiolytic effects that are mediated by limbic and paralimbic brain areas. It should be noted that similar findings would be reported in a follow-up study published in 2011 – also conducted by Crippa.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/14583744
1993: Effects of ipsapirone and cannabidiol on human experimental anxiety.
A study published in 1993 by Zuardi et al. attempted to elucidate the effects of ipsapirone and cannabidiol among humans exposed to an experimental anxiety task. For the study, researchers recruited 40 healthy volunteers that were assigned to a simulated public speaking (SPS) test – designed to mimic the effects of public speaking. The 40 participants were divided into 4 groups of 10 – each of which was assigned randomly to receive: CBD (300 mg), Valium (10 mg), ipsapirone (5 mg), or a placebo.
In case you are unfamiliar, ipsapirone is classified as a 5-HT1A partial agonist that is understood to exert antidepressant and anxiolytic effects. Although it isn’t approved by the FDA to treat any conditions, it is commonly used as a research chemical. Additionally, the drug Valium is understood to be a potent benzodiazepine that acts as a positive allosteric modulator at GABAA receptors; it is FDA approved for acute anxiety.
To compare the efficacy of the aforestated agents in reducing anxiety associated with the simulated public speaking task, researchers collected measures using the VAMS (Visual Analogue Mood Scale) and State-Trait Anxiety Inventory (STAI). Comparatively, ipsapirone (5mg) reduced anxiety induced by the simulated public speaking task, whereas CBD (400 mg) only decreased anxiety after the task. Valium (10 mg) reduced anxiety before and after the simulated public speaking task, but didn’t decrease anxiety during the speaking.
Researchers reported that ipsapirone was the only agent that inhibited increases of systolic blood pressure resulting from the test. Administration of Valium resulted in substantial sedation. Investigators concluded that ipsapirone and CBD have anxiolytic effects among healthy humans exposed to a stressful situation.
It should be noted that ipsapirone and CBD may attenuate anxiety similarly by altering 5-HT1A receptor signaling. Perhaps a greater dose (than 400 mg) would’ve attenuated anxiety before, during, and after the simulated public speaking task. Furthermore, although Valium is an effective anxiolytic, it is clearly not optimal for public speaking as it increases sedation which may impair cognition and/or speech delivery.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22290374
1982: Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects.
One of the earliest researchers of CBD as an intervention for anxiety is Zuardi. In 1982, Zuardi et al. published a paper examining the effects of cannabidiol on anxiety induced by THC. They also wanted to elucidate whether the attenuation of THC-induced anxiety by CBD resulted from an inhibition of THC or through a distinct anxiolytic mechanism.
For the study, researchers recruited 8 volunteers and administered the following: THC (0.5 mg/kg), CBD (1 mg/kg), CBD/THC mix OR Valium (10 mg) or placebo (serving as controls). The volunteers each received the combinations in an order different from the others. Researchers were able to verify that CBD inhibited anxiety as induced by THC, but physiological data revealed it was not a result of direct THC inhibition.
Rather, it appeared as though CBD attenuated anxiety induced by THC via alternative mechanisms. It was noted that various effects resulting from CBD appeared to be opposite of those associated with THC. This study published in the early 1980s provided initial evidence that CBD (rather than THC) promotes relaxation and is capable of attenuating drug-induced anxiety.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/6285406/
Limitations associated with the research of CBD for anxiety
Although nearly all of the published studies found CBD effective for the attenuation of anxiety, there are some notable limitations associated with the research. Perhaps the most notable limitation is the fact that most CBD studies investigate the effect of acute, single-dose administration. The problem with this is that it remains unclear as to whether chronic or long-term CBD ingestion maintains therapeutic efficacy.
- Anxiety subtypes: While the literature confers therapeutic efficacy of CBD for anxiety disorders, it doesn’t mention whether CBD may be more effective for certain subtypes of anxiety compared to others. Although most types of anxiety share commonalities, not all are the same nor exhibit the same underlying neural abnormalities. Therefore, it is logical to assume that CBD may provide greater benefit to those diagnosed with one type of anxiety (e.g. social phobia) than another (e.g. OCD).
- Acute vs. Chronic: Most studies have examined the acute effects of CBD rather than effects associated with chronic, ongoing administration. It is possible that acute administration may attenuate anxiety, but chronic administration may not. Some individuals may become tolerant to the effects of CBD when administered chronically and/or may find that it worsens their anxiety.
- Designs: To accurately know whether CBD is an effective intervention for anxiety disorders, robust designs should be implemented in research. In other words, study designs should be placebo-controlled, double-blinded, randomized, and preferably with large sample sizes. Unfortunately, a majority of the published literature investigating the anxiolytic potential of CBD utilizes suboptimal designs, has limited numbers of participants, or both.
- Dosage: It is relatively difficult to determine the optimal dosage of CBD for anxiety. CBD is thought to have an extremely low bioavailability when administered orally as a standalone agent. The standard dosage used in research is around 600 mg for anxiolytic effects, but this is in an oral format which has a bioavailability of around 6%. Perhaps even higher dosages and/or cofactors are necessary to improve oral absorption. (Source: www.mdpi.com/1424-8247/5/5/529/pdf).
- Formatting: When smoked, the bioavailability of cannabidiol is around 31% – indicating that only about one-third of an actual dose is being absorbed. Researchers should attempt to determine whether alternative CBD formats such as intranasal or transdermal CBD exhibit superior bioavailability to oral preparations. Preliminary evidence suggests that intranasal bioavailability may reach 46%. (Source: http://www.ncbi.nlm.nih.gov/pubmed/20545522).
- Interactions: CBD, especially when ingested at high doses, may interact with other pharmacological agents, including prescription drugs. Cannabidiol inhibits CYP450 isoenzymes in the liver which means it may be contraindicated with drugs like Warfarin. Researchers should attempt to understand the full-spectrum of CBD interactions and refine usage guidelines for those taking other medications.
- Long-term outcomes: There are zero long-term studies investigating the safety, efficacy, and long-term effects of CBD as a treatment for anxiety. Data from animal model studies suggests that chronic CBD usage could yield deleterious epigenetic and/or neuropsychiatric effects. However, it is unclear as to whether administration of CBD at a normative (non-chronic) frequency would maintain therapeutic efficacy over a long-term.
- Sample sizes: As was already mentioned, the sample sizes used to test the effects of CBD for anxiety were relatively small-scale. Although the results from these small-scale studies may be accurate, larger-scale trials (with larger sample sizes) are warranted to confirm preliminary outcomes. A therapeutic effect found in just 10-20 patients may not hold up in a group of several hundred.
- Sourcing: In addition to formatting of CBD, the sourcing may make a difference in terms of quality. The modality of CBD extraction used to isolate the CBD may affect its quality and efficacy. Examples of some common extraction techniques include: carrier-oil extraction, CO2 extraction, and alcohol extraction. Implications of sourcing and extraction techniques should be considered by researchers.
- Worsening of anxiety: Though most research indicates that cannabidiol is likely to decrease anxiety in humans and animal models, contrasting evidence necessitates consideration. A study published in 2012 by ElBatsh et al. examined the effects of CBD administration on rodent behavior and protein expression. Notably, CBD decreased frontal and hippocampal BDNF and reduced TrkB and phosphor-ERK1/2 expression. This suggests that when used frequently, CBD may exacerbate underlying anxiety. (Source: https://www.ncbi.nlm.nih.gov/pubmed/22083592).
Is CBD (cannabidiol) an effective treatment for anxiety disorders?
Based on the existing scientific literature, it is impossible to conclude whether CBD is therapeutically effective as a treatment for anxiety disorders – especially when administered chronically and/or over a long-term. However, considerable evidence supports the efficacy of CBD when administered acutely for: social phobia, public speaking anxiety, and environmental stress. Acute administration of CBD appears to improve subjective, physiological, and objective measures of anxiety in stressful situations.
Additionally, CBD is also thought to inhibit reconsolidation of traumatic memories, which may have therapeutic implications for those with PTSD. What’s more, CBD appears to effectively reduce anxiety among healthy individuals without preexisting anxiety disorders. Though the mechanisms by which CBD attenuates anxiety aren’t fully deciphered, 5-HT1A partial agonism and modulation of limbic/paralimbic function likely plays a role.
Given the current state of evidence, it is important to avoid assuming CBD is a sustainable long-term intervention for anxiety disorders. As further research is conducted with larger-scale, longer-term, robustly designed trials – we will better understand the anxiolytic capacity of CBD. Those with refractory cases of anxiety in search of an alternative pharmacological intervention may want to discuss the feasibility of “as-needed” CBD administration with a medical professional.
What is the optimal dose of CBD oil for anxiety?
It is unclear as to what the optimal dosage of CBD is for anxiety disorders. Most literature suggests that a single 600 mg dose of CBD is sufficient to alleviate anxiety. However, the source from which you attain your CBD may make a major difference. Various companies are selling CBD formatted with nanotechnology and/or co-factors (to maximize bioavailability) and a significantly lesser dose may be required than agents without specialized formatting.
Therefore, it is important to realize that potency of CBD oil that you attain will be subject to variation based on the sourcing and its formatting. Additionally, there’s no way to recommend an “optimal” universal dose for all types of anxiety as different dosages may be necessary based on the specific subtype of anxiety disorder. For example, a person with PTSD may require a slightly different dose than someone with social phobia.
Responsiveness to certain dosages may be subject to individual variation based on factors such as: body size, whether you take other medications, liver health, etc. For this reason, it is necessary to always review the safety and efficacy of a hypothesized dosage with a medical professional. Also understand that CBD is not guaranteed to reduce anxiety for every user, and therefore some individuals may derive zero benefit from any dose (even if extremely high).
Personal Anecdotes: Taking CBD Oil for Anxiety
On multiple occasions I’ve taken orally formatted CBD as a test to determine whether it would lower my anxiety. The first occasion involved utilizing an extremely low dose which yielded a slightly noticeable psychological relaxation effect. The second time I administered CBD, I ingested a substantially greater dosage than the first occasion, but was also stressed prior to taking it.
I should preface this segment by documenting the specific type of CBD that I ingested. I purchased the supplement BioCBD+, a product that received solid customer feedback online and appears to have high-quality manufacturing standards. What’s more is that the product incorporates Hybrid-NanoEngineering technology which is thought to increase the bioavailability of orally administered CBD by 10-fold.
Whether the claim of 10-fold bioavailability of nano-engineered CBD can be scientifically verified isn’t known, however, preliminary testing from the company suggests that 10 mg of their product is equivalent to 100 mg of others. Assuming the nano-engineering is effectively increasing bioavailability by 10-fold, each BioCBD+ capsule I’ve taken (with 10 mg CBD) is delivering the equivalent of 100 mg standard CBD.
First experience: Low-dose, afternoon administration
The first time I decided to take BioCBD+ was on a whim. I had just finished work and didn’t have much to do the rest of the day. I had been reviewing the literature on cannabidiol and talked myself into trying an extremely low dose. I popped one capsule of BioCBD+ at 10 mg and continued on with some household chores including: dishes, cleaning, and folding laundry.
Subjectively, I’d say it took around 15 to 20 minutes before I noticed some sort of an effect; could’ve been shorter or longer (I didn’t have a timer out). I wasn’t stressed or anxious prior to taking the capsule, so there may not have been as much neurophysiological contrast. That said, I noticed that I felt psychologically more relaxed and as if I stopped thinking critically about every little thing.
Throughout the entire experience, my alertness, cognitive function, and energy did not suffer. I wouldn’t say I felt significantly more physically relaxed than prior to taking it, but I did feel slightly more relaxed mentally. If I had to rate this psychological relaxation on a scale from 1 to 10, I’d say it was about a 4; it was noticeable, but not substantial.
I couldn’t really tell when the effect of the CBD tapered off, but I had a relatively nice, mellow afternoon. I noticed slight changes in perception after taking the BioCBD+ to the extent that I knew the formulation had “kicked-in.” Whether these perceptual changes were a direct result of cannabidiol, the other herbal additives in the product, or a combination of both – isn’t clear.
Reflecting upon the experience, I also realize that it could’ve been nothing more than a placebo effect. The placebo effect creates significant neurochemical changes as well, so maybe by expecting the BioCBD+ to do something, it ended up provoking a neurophysiological response – who knows. The one thing that I remembered from the experience was that my brain felt as if it was being “massaged from the inside.”
This “massage effect” could’ve been a result of modulations in endocannabinoid system, changes in cerebral blood flow, reduced inflammation, or a combination of every neurophysiological effect. I also noticed that my mood was slightly subdued during the experience. Whether the slightly subdued mood resulted from the CBD remains unclear.
In any regard, the slight relaxation and mild perceptual change I experienced lingered for the remainder of the afternoon and evening. Overall, I’d say that my first experience with CBD was a favorable one. The effect wasn’t too significant, but it also was fairly noticeable and enjoyable.
Second experience: Higher-dose, evening administration
In my second experience with CBD, I decided that I needed to double up the dose to determine whether I could enhance the anxiolytic effect. Keep in mind that this was weeks after my first administration with zero CBD usage in between. This time I decided to take 2 capsules of the BioCBD+ in the evening at around 6:00 PM prior to grocery shopping.
Within 10 to 20 minutes, I noticed a significant perceptual change and felt extremely relaxed. I noticed a similar “head massage” as reported in my first experience and enjoyed it. I also noticed that my psychological relaxation significantly increased and I felt less inhibited.
A friend texted me to hang out while I was grocery shopping and I replied yeah (not something I normally would’ve done). On my drive to the grocery store I felt completely calm without a major change in alertness or vigilance of my environment. While I was at the store, I had a pleasant experience, but noticed that my emotions felt slightly subdued again – but the effect wasn’t extreme.
I had absolutely no problem chatting with the grocery store clerk at the cash register and actually found myself enjoying the chat (not something that usually occurs). Thereafter, I drove home and cooked myself dinner. My friend sent me a text to hang out at like 10:00 PM and I was feeling a bit anxious, so I decided to pop 2 more CBD capsules at around 9:30 PM.
This meant that overall, throughout the entire span of the night, I had ingested 2 doses of 2 BioCBD+ capsules for a cumulative dose of 40 mg (equivalent to 400 mg CBD). After my second set of capsules, I ended up going over to a friend’s house and an unexpected party was going on (which made me nervous – I don’t like big parties). I felt somewhat nervous because I didn’t know anyone and they wanted to drink (I didn’t want to) and thought about simply just leaving the party and going home.
Fortunately, the party stopped at my friends and most people left, leaving us to just hang out and chat for a bit (which is what I wanted). At some point during the night I was cajoled into drinking a couple of beers (not something I’d normally agree to), but was trying to live it up for once. Comparatively, I’d say that the beer helped more than the CBD in terms of taking the anxious “edge off.”
However, I’m thinking that there may have been some sort of synergistic effect between the CBD and beer. The combination of CBD plus beer worked extremely well for my anxiety – but obviously the beer is not a sustainable nor healthy long-term option. Reflecting on the experience, it’s difficult to determine how well the CBD worked because I was exposed to a lot more anxiety than the first situation.
The second scenario involved anxiety associated with socializing, unknown strangers, a party going on, etc. I also had been experiencing anxiety related to a health issue that’s been plaguing me for awhile and has yet to get corrected. The health anxiety prompted me to run the second CBD experiment, and I went extra crazy with the dosing when the friend asked me to hang out.
If I had to rate the efficacy of the second dosing option for anxiety on a scale of 1 to 10, I’d rate it about a 6. Meaning, it was noticeably more effective than the first low-dose at even just 20 mg. Perhaps in the future I’ll press my luck with an even greater dose of around 60 mg, which is equivalent to 600 mg CBD and the dosage that has been documented as effective for anxiety in clinical research.
Have you tried CBD oil for anxiety?
If you have been diagnosed with an anxiety disorder and/or are dealing with significant stress, have you tested CBD oil as an intervention? Assuming you have tried CBD oil, share your experience in the comments section below. To help others get a better understanding of your situation, include details such as: type of anxiety you have (e.g. social phobia), the dosage of CBD you took, and how effective it was for attenuating your anxiety (on a scale of 1 to 10).
Also mention the specific source from which you attained your CBD (e.g. the company), how you administered it (e.g. orally, sublingually, vaporization, etc.), whether you noticed any unwanted side effects, and whether you use other medications and/or supplements along with it. Understand that CBD appears effective and safe when used for anxiety, but warrants further investigation – especially when used long-term and/or chronically. When used on a situational basis, a single oral dose of 600 mg appears to significantly decrease symptoms of anxiety.