What can research tell us about CBD’s impact on chronic stress, anxiety, and sleep?

Can-i-Sleep

Cannabidiol (CBD) is a well researched, non-psychoactive cannabinoid resulting from CBDA degradation, known for its varied range of therapeutic and medical applications.  Though CBD was first discovered by Roger Adams and his team at the University of Illinois in 1940, it wasn’t until 1963 that Cannabidiol’s structure was fully uncovered by Raphael Mechoulam and his team at the Hebrew University of Jerusalem in Israel, leading the way to more focused research into this cannabinoid and cannabis as a whole.   

Mechanisms of Action

To date, researchers have identified about 60 different molecular pathways through which CBD can affect various aspects of our health.  Perhaps surprisingly, most of CBD’s “mechanisms of action” do not involve cannabinoid receptors type 1 or type 2 (CB1 or CB2) as research confirms CBD’s low interaction rate with CB1 and CB2 which is limited to inhibiting the uptake of THC at CB1.  Cannabidiol’s blocking or inhibitory action at CB1 makes CBD a negative allosteric modulator as it actually changes the shape of CB1 receptors in a way that inhibits the receptors’ ability to bind with THC (this process is also responsible for reducing the THC high).  

As CBD hasn’t been shown to significantly activate CB1 or CB2 receptors, its other mechanisms of action include activating several non cannabinoid receptors and multiple receptor-independent channels, such as Vanilloid receptor TRPV1, known to mediate pain perception, inflammation and body temperature, as well as G‐protein coupled receptors (GPR55) and Peroxisome proliferator‐activated receptors (PPARs).  

At high concentrations, CBD directly activates the 5-HT1A (hydroxytryptamine) serotonin receptor which contributes to CBD’s anti-anxiety effects. Serotonin receptors are implicated in a range of biological and neurological processes, including anxiety, addiction, appetite, sleep, pain perception, nausea and vomiting, hence CBD’s role has been implicated in all of these areas and continues to be investigated.

As a further mechanism of anxiety reduction, CBD has been shown to change the shape of the GABA-A receptor in a way that amplifies the natural calming effect of GABA (the main inhibitory neurotransmitter in the mammalian central nervous system).  This is another example of CBD’s allosteric receptor modulator function, except in this case CBD enhances GABA by changing the shape of that receptor.

But beyond the molecular level, what can research tell us about CBD’s role in helping individuals cope with stress, anxiety, and sleeplessness?  

Anxiolytic (Anxiety Reducing) Effects of CBD

Meta-analyses, research reviews and cross-sectional CBD user studies suggest a calming, anxiolytic effect of CBD, supporting what has previously been observed in animal studies.  Cannabidiol users often cite relief of symptoms related to anxiety, depression, insomnia, PTSD, and headaches among other conditions, many of which are supported by varying levels of research.  Specifically, CBD has been shown to reduce symptoms of social anxiety in humans (Social Anxiety Disorder) and has been particularly effective in diminishing levels of stress and anxiety associated with public speaking.  

One such double-blind, randomized design study of previously never treated participants with Social Anxiety Disorder, administered 600mg of CBD to participants 1.5 hrs prior to a public speaking test.  The study found that pretreatment with CBD significantly reduced anxiety, cognitive impairment and discomfort in speech performance whereas the placebo group presented higher anxiety, cognitive impairment, discomfort, and alert levels when compared with the control group.  An additionally interesting finding was that the pretreatment group of SAD participants who received CBD performed comparably to a control group of participants who had never suffered from Social Anxiety Disorder.

Another study published in 2017 compared the anxiety levels of participants who were randomly assigned to one of five groups, each receiving either a placebo, clonazepam (1 mg), or pure, isolated CBD (100mg, 300mg, and 900mg).  Interestingly, the results confirmed that administration of CBD (150 mins prior to public speaking) reduced anxiety but in a dose-dependent inverted U-shaped curve in healthy subjects: anxiety measures were greatly reduced with CBD 300mg, but not with CBD 100mg and 900mg, in the post-speech phase.  Other research has also noted the importance of observing the dose-dependent inverted U-shape or biphasic effect of using pure, isolated Cannabidiol (this response has not yet been reported with whole spectrum CBD).  

General anxiety reduction findings have more recently been supported by research conducted at a Colorado mental health clinic which found anxiety scores decreased within the first month in 79% of patients and remained reduced in the second month in 78% of patients when oral doses of 25mg - 75mg CBD per day (morning) were administered.  

Novel research involving participants with other types of anxiety disorders, such as panic and obsessive-compulsive, is ongoing and aims to further investigate the specific implications of CBD for specific conditions.  Cannabidiol has also been shown to effectively reduce the anxiety and psychotic symptoms brought on by high doses of THC in some individuals.

Post Traumatic Stress Disorder & CBD

Related to Cannabidiol’s anxiety reducing effects is research that explores CBD’s role in relieving symptoms of post-traumatic stress disorder (PTSD).  Recent research involving PTSD patients who consented to treatment with CBD in addition to routine psychiatric treatments at an outpatient mental health clinic, found that 91% of patients experienced a decrease in the severity of their symptoms after 8 weeks of CBD administration when compared to their baselines of standard psychiatric drugs alone.  Specifically, participants experienced a reduction in nightmares related to their traumatic event (50%) and improvement in quality of sleep (38%) when given 25mg-100mg of CBD daily by capsule and/or oral spray combination.  

Researchers believe that CBD’s beneficial impact on some PTSD symptoms, such as nightmares, may be due to evidence that the endocannabinoid system has been shown to play an important role in the process of aversive memory extinction through the activity of CB1 receptors.  Cross-sectional research of CBD user experiences has also observed PTSD symptom reduction to be a to be a factor for many individuals who choose to use CBD products.

Chronic Stress & Cortisol Levels

Another mechanism by which high dose CBD may be able to help with chronic stress is through the reduction of elevated cortisol levels.  At least one small, double blind, experimental study has found high doses of 300mg and 600mg CBD to interfere with cortisol secretion in a sample of otherwise health volunteers.  Study participants also reported feeling a calming, sedating effect after ingesting 300mg and 600mg CBD--effects which are consistent with those of other research.  

CBD & the Sleep-Wake Cycle:  Alertness vs Relaxation

A key finding in the area of sleep and daytime alertness has been that CBD’s effects regarding sleep versus alertness are very dose dependent and research has reported a range of 10mg to up to 600mg CBD per day.  At moderate to high doses of 200mg to 600mg, CBD induces sleep promoting effects though it is technically not categorized as a potent sedative.  Cannabidiol’s calming and stress relieving effects have much to do with its ability to reduce anxiety, therefore enabling relaxation and sleep which is most often associated with CBD’s impact on serotonin and GABA receptors.  

Improved sleep quality was most often noted when sleeplessness was caused by excess anxiety or excess activation of the central nervous system. However, in very low doses CBD has been shown to activate the same adenosine receptors as caffeine acting to promote wakefulness, thereby preventing sleep, so using an appropriate dosage is key.  The exploration of CBD to improve sleep isn’t entirely new as earlier studies of Cannabidiol have supported its sleep enhancing action.

One CBD study of otherwise health volunteers suffering from insomnia compared doses of 40mg, 80mg, and 160mg CBD to a placebo and 5mg nitrazepam over a 30 day period.  Researchers found that participants who received 160mg CBD daily reported having slept significantly more than those receiving the placebo. Additionally, participants receiving all three doses of CBD reported significantly less dream recall than those receiving placebo which is a finding that is similar to the nightmare reduction experienced in other research.

A number of sleep experts have also reviewed the application of CBD for sleep related issues Most recently, a 2019 study publication from a Colorado mental health clinic noted the efficacy of CBD as a sleep aid in 67% of its patients based on sleep scores gathered in the first month at a dose of 25mg - 75mg of CBD in the evening.  The efficacy of CBD as a sleep aid did fluctuate to 56% of patients in the second month and researchers did note that higher dose CBD (300mg-600mg) has generally been reported in sleep related research, though they opted to investigate the therapeutic value of lower dose CBD.  At higher doses of 200mg to 600mg CBD, studies suggest a therapeutic effect for anxiety, insomnia, and epilepsy which is often accompanied by mental sedation.

Though CBD has been shown to be effective for insomnia that is associated with stress and anxiety, research suggests that additional sleep support may be achieved by including Cannabinol (CBN) in your evening routine.




LEARN MORE ABOUT CBD

Cannabinoid pharmacology: the first 66 years (2006)

How CBD Works

Cannabidiol as a Potential Treatment for Anxiety Disorders (2015)  

Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series (2018)

Cannabidiol as a Therapeutic Alternative for Post-traumatic Stress Disorder: From Bench Research to Confirmation in Human Trials  (2018)

The endogenous cannabinoid system controls extinction of aversive memories  (2002)

Cannabidiol in Anxiety and Sleep: A Large Case Series (2019)

Cannabidiol in Anxiety and Sleep: A Large Case Series (2019), Continued

Hypnotic and antiepileptic effects of cannabidiol  (1981)

Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age  (2018)

The Anxiolytic Effects of Cannabidiol (CBD): Chapter e13 in Handbook of Cannabis and Related Pathologies (2017)

Potential Effects of Cannabidiol as a Wake-Promoting Agent  (2014)

A Cross-Sectional Study of Cannabidiol Users (2018)

Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation? (2016)

Single Compound vs Whole Plant CBD (2015)

Cannabidiol in Humans—The Quest for Therapeutic Targets (2012)

Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report.

Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients (2011)

Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life (2017)

The Ultimate Guide to CBD and Sleep

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Cannabidiol, neuroprotection and neuropsychiatric disorders (2016)

Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels (2018)

An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies (2017)

Current Status and Prospects for Cannabidiol Preparations as New Therapeutic Agents (2016)

Cannabis and cannabinoid drug development: evaluating botanical versus single molecule approaches (2018)

Cannabis Therapeutics and the Future of Neurology (2018)

Effects of ipsapirone and cannabidiol on human experimental anxiety.

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The Health Effects of Cannabis & Cannabinoids: The Current State of Evidence and Recommendations for Research

Dr. Ethan Russo: CBD, the Entourage Effect and the Microbiome (video)

Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes

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