Stress Relief Without Harmful Side Effects: CBD Proves as Effective as Pharma Drugs in Multiple Clinical Trials

Stress Relief Without Harmful Side Effects: CBD Proves as Effective as Pharma Drugs in Multiple Clinical Trials

This 2021 scientific review that looked into the current research on cannabidiol (CBD) and its potential to reduce the harmful effects of stress showed promising results. CBD is an endocannabinoid system regulator and enhancer that can modulate the primary regulator of the stress response, the endocannabinoid system. The level of endocannabinoid tone can increase or decrease how much stress one feels, and CBD has been shown to reduce stress by modulating the system.

Chronic deficiency in endocannabinoid tone is associated with the pathological complications of chronic stress, which is today referred to as clinical endocannabnoid deficiency. Therefore, CBD may be a valuable solution for maladaptive stress responses and the endocannabinoid system, which deserve more attention from clinicians and researchers alike.

The review yielded promising results, with several clinical trials demonstrating that CBD is just as effective as pharmaceutical drugs in reducing stress-related symptoms. This 2021 scientific review focuses on the results of seven double-blind, placebo-controlled clinical trials of CBD for stress, involving a total of 232 participants, and one partially controlled study on 120 participants, all of which showed that CBD significantly reduced stress response and was non-inferior to pharmaceutical comparators. 

Stress is a prevalent issue that can cause a range of physical and mental health problems, and current treatments often fall short; however, this highlights the potential for CBD as a valuable solution to address maladaptive stress responses and the endocannabinoid system, both of which require greater attention from clinicians and researchers.

Several double-blind, placebo-controlled clinical trials have demonstrated that CBD can significantly reduce the stress response and its manifestations, including anxiety, fear, depression, and burnout. Two of these clinical trials even included a comparator arm with benzodiazepines and/or 5HT1A (Serotonin 1A) receptor agonists, and both showed that the CBD effect were comparable to that of the pharmaceutical drug. This means that CBD could be a safe and effective alternative to conventional medications for individuals experiencing stress-related symptoms.

In the UK, more than 10% of adults have tried CBD, while in the USA, there were over 6 million online searches for CBD in just a month. A significant number of people in the UK, USA, Denmark, and New Zealand who use CBD for medicinal purposes use it for stress relief, with estimates ranging between 35% and 65%. Moreover, over 90% of people who have tried CBD for stress relief report feeling less stressed, with no one reporting an increase in stress levels.

Cannabis has been used for centuries to reduce the physiological and psychological effects of stress, and cannabidiol (CBD) appears to be the component responsible for these effects. CBD is commonly used around the world to treat stress, anxiety, and insomnia. Unlike THC, CBD does not act as a competitive inhibitor of the endocannabinoid system and may be more effective and safer for constraining the stress response. CBD acts on several targets, making it more effective and safer than molecules targeting specific receptors.

The stress response is a normal physiological function activated by life events, such as the "fight or flight" reaction, which mobilizes glucose and increases blood flow to the muscles. Fear, anxiety, and depressive behaviors are normal physiological aspects of the stress response that can enhance mental functions.

However, if stress is excessive or chronic, it can cause harm and increase the risk of somatic and mental health disorders, including inflammation, pain, gastrointestinal dysfunction, and mental illnesses such as anxiety disorders and depression. Chronic stress is especially harmful and can lead to neurodegenerative diseases, osteoporosis, and suppression of the immune response. Habituation or adaptation of the stress response is important for minimizing the adverse effects from repeated stress.

Occupational stress is a significant contributor to the overall impact of stress, causing a range of negative outcomes including decreased productivity and increased accidents. Treatment options for stress include pharmacological and psychological approaches such as beta blockers, benzodiazepines, meditation, relaxation, biofeedback, and cognitive and behavioral therapy, but many medications have adverse effects and potential for addiction.

Reviews of 49 clinical trials of CBD, including intravenous, inhalation, and oral routes of administration and oral dose ranges of 10–1500 mg per day, found that CBD was well tolerated with a good safety profile. CBD has also been shown to have no potential for abuse or dependence in humans.

The endocannabinoid system is the key regulator of the stress response and is important for returning the body to a non-stressed state. The endocannabinoid system directly inhibits stress-related processes such as fear, anxiety, depressive behaviors, inflammation, and hyperalgesia while promoting behaviors such as feeding and sleep.

CB1 (Cannabinoid 1) and CB2 (Cannabinoid 2) receptors play an important role in regulating the stress response in the body. CB1 receptors are primarily found in the central nervous system and are involved in reducing anxiety and constraining the stress response via the HPA (Hypothalamic Pituitary Adrenal) axis and the sympathetic nervous system. CB2 receptors are mostly located in immune cells and modulate immune cell migration and cytokine release. Impairments in CB1 and CB2 signaling can lead to long-term complications of chronic stress, including learning and memory deficits, anxiety disorders, depression, and pain syndromes. Acute exposure to stress decreases the inhibitory tone of CB1 signaling, while increased cortisol levels stimulate production of the endocannabinoid 2-AG, increasing CB1 signaling and applying negative-feedback inhibition of the stress response. Repeated exposure to stress increases 2-AG levels and habituates the stress response. Chronic stress decreases CB1 expression in stress centers of the brain, leading to less feedback inhibition on the HPA axis and continued high levels of cortisol. Medications such as FAAH (Fatty Acid Amide Hydrolase) inhibitors or endocannabinoid reuptake inhibitors have been shown to prevent adverse effects of chronic stress. CBD increases signaling through CB1 and CB2 receptors by increasing levels of anandamide (AEA), an endocannabinoid that affects mood and stress response. CBD also activates other receptors such as 5-HT1A and PPARγ to reduce stress.

Preclinical studies using animal models (rodents) have shown that CBD can reduce the effects of acute and chronic stress by increasing CB1 and CB2 signaling and facilitating 5-HT1A receptor-mediated neurotransmission. FAAH inhibition by CBD also plays a role in these effects. CBD has been shown to prevent stress-associated anxiety behaviors, decrease in hippocampal neurogenesis, and prevent the persistence of fear. These effects were only seen in stressed animals, indicating that CBD induces anti-stress rather than anxiolytic effects. CBD also acts on 5-HT1A receptors to reduce stress-associated anxiety behaviors, heart rate, blood pressure, and fear expression.

Clinical trials have shown that CBD can reduce the stress response and its behavioral manifestations, such as anxiety, fear, and burnout syndrome. Studies have shown that a single dose of CBD ranging from 15-60 mg can significantly reduce THC-induced anxiety and tachycardia, which are part of the stress response.

CBD has also been shown to reduce stress-response-associated anxiety caused by public speaking and radiological tests, and its actions were stress-specific with no effect seen on anxiety measures before the stress response.

In addition, CBD may be helpful in normalizing abnormal stress responses. A clinical trial with burnout syndrome patients found that 150 mg of CBD twice a day for 14 days provided significant decreases in emotional exhaustion and associated symptoms of anxiety and depression.

Two clinical trials of CBD in social anxiety disorder (SAD) have shown that CBD significantly reduced subjective symptoms of anxiety, cognitive impairment, and performance discomfort. Furthermore, a recent double-blind study on teenagers with SAD and avoidant personality disorder showed that 300 mg/day of CBD for four weeks significantly decreased anxiety compared to placebo. A clinical trial of CBD for patients with any anxiety disorder found 25 mg/day of CBD to be effective.

In healthy volunteers, a single dose of 15-60 mg CBD reduced THC-induced anxiety, while doses of 30-60 mg significantly reduced THC-induced tachycardia. CBD also significantly lowered stress-induced anxiety caused by simulated public speaking tests, radiological tests, and the Trier Social Stress Test in healthy participants. In individuals with burnout syndrome, 150 mg CBD twice a day significantly decreased emotional exhaustion, symptoms of anxiety and depression, and had a medium effect size for treating burnout syndrome. CBD has also been studied in individuals with social anxiety disorder and found to reduce subjective symptoms of anxiety, cognitive impairment, and performance discomfort. A recent double-blind study showed that 300mg/day CBD for four weeks significantly decreased anxiety in teenagers with SAD and avoidant personality disorder. Low-dose CBD at 25 mg/day has also been found to be effective in treating any anxiety disorder.

In conclusion, there is a need for a safe and effective treatment for the stress response. The stress response is a pervasive issue that affects millions of people worldwide and can lead to a range of negative health outcomes. CBD has been shown in multiple clinical trials to be safe and effective in reducing the stress response and its associated symptoms, including anxiety, fear, depression, and burnout. Two clinical trials also showed that CBD was as effective when compared to pharmaceutical drugs in reducing stress. CBD's effectiveness is supported by its widespread use and established mechanism of action. Both maladaptive stress responses and the endocannabinoid system as a therapeutic target deserve further attention, and CBD may be a promising solution to both.

Study Title: Enhancing Endocannabinoid Control of Stress with Cannabidiol
Study Link:

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