Summary: A 2021 systematic review of 7 double-blind placebo-controlled clinical studies (and 1 pre-clinical study) on Cannabidiol (CBD) for stress reveals that CBD is as effective as pharmaceuticals like benzodiazepines and antidepressants at significantly reducing the stress response and its manifestations (anxiety, depression, burnout, fear).

The research underscores the potential of dietary interventions to address the rising rates of urgent stress-related illnesses, which account for up to 90% of the global disease burden. By highlighting cannabidiol (CBD) as a promising intervention, the study offers a potential solution to mitigate the adverse effects of stress on physical and mental health, and the burden that poses to our societies.

Through robust preclinical and clinical evidence, CBD emerges as an effective regulator of the stress response, holding promise for reducing anxiety, fear, depression, and burnout. This research sets the stage for further exploration of CBD's therapeutic potential in tackling the pervasive impact of stress-related morbidities worldwide.

  • CBD's Efficacy for Stress Reduction:

    A comprehensive analysis of seven double-blind placebo-controlled clinical trials shows that CBD is extremely effective at significantly reducing stress and its associated symptoms, such as anxiety, depression, burnout, and fear.

  • Superior to Pharmaceuticals:

    The review reveals that CBD performs comparably to pharmaceutical interventions like benzodiazepines and antidepressants, highlighting its potential as a viable alternative for stress management. Unlike traditional pharmaceuticals, CBD targets the root cause of stress response dysfunction by enhancing and supporting the Endocannabinoid System, which regulates your stress response and maintains homeostasis.

  • Promising Avenues for Mental and Physical Health:

    Supported by both clinical trials and mechanistic evidence, CBD's ability to modulate stress response pathways offers promising avenues for developing novel therapeutic strategies targeting stress-related disorders. Because of its high tolerability and minimal (if any) side effects, CBD may be invaluable for reducing the cost of stress on our minds, bodies, and societies, as well as our global burden of disease.

A 2021 systematic review led by Jeremy D. Henson, a postdoctoral researcher at the Cancer Cell Immortality group in the Adult Cancer Program at the Prince of Wales Clinical School, and researchers from the University of Sydney and Medlab Clinical Ltd. presents novel findings on the efficacy of cannabidiol (CBD) in significantly reducing stress and its manifestations, providing a promising alternative to traditional pharmaceutical treatments—and potentially addressing a global health crisis where chronic stress is implicated in up to 90% of all illnesses and diseases.

CBD and the stress response.

Stress is a pervasive issue linked to a significant number of health problems worldwide, accounting for up to 90% of illnesses and diseases. Traditional treatments like benzodiazepines and antidepressants are only effective for approximately 1/3 of people, take some time to work, are only effective as long as you're taking them, and come with a host of undesirable side effects and risks of dependency. This study posits that CBD, a major non-psychoactive component of cannabis, offers a safer alternative.

Read: Cannabidiol (CBD): Side Effects and Possible Interactions

The 2021 systematic review led by Jeremy D. Henson and colleagues delves into the efficacy of Cannabidiol (CBD) in mitigating stress-related conditions like anxiety, depression, burnout, and trauma, offering a nuanced understanding of its potential therapeutic role.

Through a meticulous analysis of seven double-blind placebo-controlled clinical trials alongside preclinical evidence, the study demonstrates CBD's ability to significantly alleviate stress responses and associated manifestations, such as anxiety, depression, and burnout. This comprehensive examination provides substantial evidence supporting the effectiveness of CBD as a stress management tool, presenting a promising alternative to conventional pharmaceutical treatments.

The researchers highlight that CBD's influence on the Endocannabinoid System (ECS) emerges as a critical mechanism underpinning its stress-alleviating properties. By enhancing signaling through CB1 and CB2 receptors and inhibiting the degradation of anandamide (AEA), CBD reduces stress responses and promotes a sense of calm. Additionally, CBD's interactions with serotonin receptors and other pathways contribute to its anxiety-reducing, neuroprotective, and anti-inflammatory effects, offering a multifaceted approach to stress management and mental health.

How CBD Works in the Body

CBD exerts its effects by influencing the Endocannabinoid System (ECS), a biological system that regulates homeostasis (chemical and biological balance). It does this is by boosting the activity of receptors in the ECS known as CB1 and CB2 receptors, leading to an increase of a compound called anandamide (AEA), which helps regulate mood and stress.

CBD also lightly interacts with a number of other pathways and systems, like serotonin and TRPV1 receptors, further adding to its ability to reduce anxiety and inflammation.

Mechanistically, CBD’s role in increasing AEA levels, activating serotonin receptors, and desensitizing TRPV1 receptors is crucial. These actions collectively reduce anxiety, neuroinflammation, and stress-induced gastrointestinal dysfunctions, while improving mental clarity, memory, and brain health.

This CBD's multi-targeted approach to supporting overall health and well-being, which could offer advantages over single-target pharmaceuticals.

The researchers explored one pre-clinical study, and seven double-blind placebo-controlled clinical trials on CBD for stress.

The preclinical studies on rodents demonstrate CBD’s efficacy in mitigating both acute and chronic stress effects. These studies show that CBD not only prevents stress-induced anxiety but also promotes the growth of new brain cells (neurogenesis) and enhances the brain's ability to adapt and learn (synaptic plasticity), which could lead to improved mood, cognition, and overall mental well-being in daily life.

Clinical trials support these findings, with seven double-blind placebo-controlled studies showing CBD’s effectiveness in reducing stress-related symptoms such as anxiety, depression, fear, and burnout. Notably, these studies compare CBD favorably against traditional treatments like benzodiazepines and 5-HT1A agonists, suggesting CBD’s comparable efficacy without the associated risks.

However, while the study presents compelling evidence for CBD's efficacy, it's essential to acknowledge potential limitations and areas for further exploration.

One notable consideration is the need for additional research to elucidate the long-term effects and optimal dosages of CBD in stress management. While the study highlights CBD's non-inferiority to conventional pharmaceutical treatments, questions remain regarding its sustained efficacy and safety profile over extended periods. Moreover, variations in study design and participant demographics across clinical trials underscore the importance of standardized protocols and larger sample sizes to ensure robust conclusions.

Read: CBD Dosage: How Much To Take (Plus A Chart & Calculator)

However, we think that reasonable assumptions can be made about the optimal dose of CBD, as well as whether it is safe and effective in the long-run.

For example, recent studies suggest that the optimal dosage of CBD isolate is 300mg of CBD daily, which has been observed to significantly reduce stress, anxiety, and burnout. However, CBD isolate is dose-dependent, and does not increase in efficacy after 300mg.

Studies also demonstrate that full-spectrum CBD is significantly more effective than CBD isolate. Full-spectrum CBD isn't dose-dependent, unlike CBD isolate, and its effects increase proportionally to the dose.

We also know that CBD helps target the root cause of stress response dysfunction by supporting our body's innate intelligence by enhancing the health and function of the ECS, among other pathways. We believe that, by helping this system work more robustly, the effects of CBD will be sustained even after discontinued use. The caveat here is that other stress management strategies should also be employed after returning to baseline.

Despite these challenges, the findings of this systematic review signal a significant advancement in our understanding of CBD's therapeutic potential in stress management. By bridging the gap between preclinical evidence and clinical outcomes, the study paves the way for future research exploring the broader applications of CBD in mental health and well-being.

As society grapples with escalating rates of stress-related morbidities, the optimism surrounding CBD's efficacy offers a beacon of hope for more holistic approaches to healthcare. Looking ahead, the integration of CBD and other plant-based remedies into mainstream medicine holds promise for addressing the root causes of stress-related conditions. By harnessing the therapeutic potential of natural compounds, healthcare practitioners can adopt a more holistic approach to patient care, prioritizing preventive strategies and personalized interventions.

As our understanding of the intricate interplay between stress, the endocannabinoid system, and therapeutic agents like CBD continues to evolve, the future of medicine shines brightly with possibilities for transformative healing.

Where to find high-quality CBD oils.

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Full Spectrum, our clinical-strength full-spectrum CBD oil, is your SPF (stress protection factor). Up to 50mg of Full Spectrum CBD oil twice daily helps reduce anxiety and alleviate the emotional, hormonal, psychological, and physical manifestations of stress.

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About this psychopharmacology research news.

Author: Jeremy D. Henson
Source: Prince of Wales Clinical School, University of NSW, Sydney
Contact:  Jeremy D. Henson – University of NSW
Original Research: Open access.
Enhancing Endocannabinoid Control of Stress with Cannabidiol" by Jeremy D. Henson et al. Journal of Clinical Medicine

Simple summary.

The 2021 systematic review led by Jeremy D. Henson highlights the effectiveness of Cannabidiol (CBD) in reducing stress and its related symptoms, such as anxiety, depression, and burnout. Through seven double-blind placebo-controlled clinical studies and one pre-clinical study, the review demonstrates that CBD is non-inferior to traditional pharmaceutical treatments like benzodiazepines and antidepressants. CBD achieves these effects by influencing the endocannabinoid system, particularly by enhancing signaling through CB1 and CB2 receptors, while also interacting with serotonin receptors and other pathways. These findings offer promising insights into the potential of CBD as a safe and effective treatment for stress-related conditions, paving the way for further research in this field.


The stress response is a well-defined physiological function activated frequently by life events. However, sometimes the stress response can be inappropriate, excessive, or prolonged; in which case, it can hinder rather than help in coping with the stressor, impair normal functioning, and increase the risk of somatic and mental health disorders. There is a need for a more effective and safe pharmacological treatment that can dampen maladaptive stress responses. The endocannabinoid system is one of the main regulators of the stress response. A basal endocannabinoid tone inhibits the stress response, modulation of this tone permits/curtails an active stress response, and chronic deficiency in the endocannabinoid tone is associated with the pathological complications of chronic stress. Cannabidiol is a safe exogenous cannabinoid enhancer of the endocannabinoid system that could be a useful treatment for stress. There have been seven double-blind placebo controlled clinical trials of CBD for stress on a combined total of 232 participants and one partially controlled study on 120 participants. All showed that CBD was effective in significantly reducing the stress response and was non-inferior to pharmaceutical comparators, when included. The clinical trial results are supported by the established mechanisms of action of CBD (including increased N-arachidonylethanolamine levels) and extensive real-world and preclinical evidence of the effectiveness of CBD for treating stress.

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