Charlotte's Web Basics

Charlotte's Web Basics

“Can CBD help with my anxiety?” is probably a question you’re wondering about even more now, during this strange and unprecedented time we face as a result of pandemic and unrest. At the best of times there is a definite link between ongoing stress and everyday mild anxiety(1) and now, more than ever, it helps to have options in our toolkit to help us better cope with the effects of everyday anxiety and stress 

In general, feeling anxious can be an understandable response to many of the stressful events life throws at us. The results of stress can have effects on the body as well, including headaches, muscle tension, and difficulty sleeping.

Mild, everyday anxiety is complex and there isn’t a one-size fits all solution, but an increasing number of early-phase studies of cannabidiol (CBD) bode extremely well for its use as a supplement for people dealing with everyday stress and anxiety. 

So far, most of the research on CBD and anxiety in humans has looked at social anxiety disorder (SAD), but we can learn a great deal from the research literature that helps support the idea of using CBD to manage the stress of occasional anxiety, which is what this article is about.  

 

Why Is CBD Helpful for Anxiety? 

Our very own endocannabinoid system (ECS) plays a critical role in modulating how we respond to anxiety and fear, and in how we manage stress.(2) In fact, the ECS appears to be like a conductor, overseeing and directing many of the other physiological systems in our body so they work in harmony to maintain a dynamic, optimal balance.  

Prolonged exposure to stresshowever, can have a detrimental effect on the ECSOver time, prolonged stress will impair the activity of CB1 receptors that are involved in how we process emotions.(3) It will also increase levels of the enzyme fatty acid amide hydrolase (FAAH), which breaks down the endocannabinoid anandamide, so we have less of this natural helpful substance in our system.(4)  

When the ECS is not working optimally, it can result in us feeling anxious, and unable to let go of negative memories or experience pleasure. One study even found an inverse relationship between levels of anandamide and severity of anxiety; namely, the lower the levels, the worse the anxiety.(5) It’s not such a big leap then to think that raising low anandamide levels could potentially help us feel less anxious. This was shown to be the case, at least in an animal study, where researchers found that blocking FAAH in mice whose anandamide levels were depleted due to stress-induced anxiety, reversed the deficiency and reduced anxious behaviors.(6) Our friend CBD has been shown to keep anandamide around in our system longer using similar mechanisms.(7) 

The more that is known about the ECS, the more far-reaching its importance seems to be. The ECS not only works via activation of its CB1 and CB2 cannabinoid receptor sites, it may also interact, in potentially helpful ways with other neurotransmitter systems. For example, low levels of the neurotransmitter serotonin are associated with both depression and anxiety.(8) And research suggests that CBD  interacts with receptors that support normal serotonin levels.(9) Furthermore, a study in mice shows that anandamide works closely with oxytocin, the natural substance known to reinforce our propensity for participation and social bonding, which are behaviors that are often unimaginable when we feel anxious.(10)  

 

While CBD is useful to help everyday common stress, it is not intended to diagnose, treat, cure or prevent any disease. 

 

Tell Me More About the Research on CBD for Anxiety! 

CBD has been studied for its effects on anxiety for several years. Most studies are pre-clinical or animal studies, but human studies of CBD and anxiety have greatly increased in recent years, and the evidence is positive.(11)

A scientific review in 2015 concluded that CBD has considerable potential to help with every day or occasional anxiety.(12) The amygdala is an area of the brain known to be crucial in processing intense experiences that trigger our fight or flight response. Sometimes we’re not able to fully process frightening experiences that happened in the past, and we may become more vulnerable to having anxious feelings in the future even in the absence of any obvious trigger. One study demonstrated that increasing anandamide levels in the amygdala of mice helped them to forget frightening events.(13) What’s more, CBD had that same effect in humans in study of 48 volunteers.(14) 

CBD’s potential to help with anxiety extends beyond the endocannabinoid system itself. Animal studies indicate that CBD interacts in various ways with the serotonin neurotransmitter system and has been shown to block the negative effects of fearful memories through that mechanism as well.(15,16) In one study, CBD also supported normal heart rate and reduced stress levels of rats put under stressful conditions ((17) This led researchers to suggest that there’s substantial evidence to consider using CBD as an adjunct support for anxiety and everyday stress in humans.(18,19) 

Several studies show that CBD can support normal formation of new neurons in the hippocampus region of the brain, which is believed to further enhance its beneficial effects on anxiety.(20)

Findings from brain imaging studies corroborate that CBD supports areas of the brain that are associated with emotional and cognitive processes, and memory. Brain images of healthy subjects who were given CBD suggest that the sense of relaxation they reported correlated with activity in the limbic and paralimbic areas of the brain.(21) In another study, similar changes were observed on brain imaging in subjects with anxiety who were given CBD. They also reported significantly decreased symptoms of anxiety. Subjects receiving placebo did not show the same effects on brain imaging and did not report significant changes in occasional anxietyAgain, CBD was observed to influence the limbic and paralimbic regions of the brain.(22) 

randomized controlled study conducted in 2011 recreated a situation likely to induce anxiety in most people, namely public speaking. Participants were divided into a CBD or a placebo groupTheir situational anxiety levels were measured using subjective self-reported and objective physiological measures (e.g., heart rate and blood pressure). The group pretreated with CBD showed significantly less anxiety, cognitive impairment, and discomfort in performing public speaking compared to the placebo group.(23) 

 

How Much CBD Oil and How Often? 

Studies of CBD tend to use isolate forms. This makes translating the amounts used in research into something practical and applicable to full-spectrum hemp extracts high in CBD a little difficult. What is known is that much higher amounts of CBD isolates are required for the desired effect. This was verified in a meta-analysis of trials that looked at studies using extracts high in CBD versus CBD isolates. Results showed that patients successfully controlled their moments of stress with much lower amounts of CBD when the CBD is part of a full-spectrum hemp extract.(24)  

Animal studies have demonstrated significant benefit from CBD at a particular amount used, with litle benefit at either lower or higher amounts.(25) Stated more simply, this means that once you find the serving size that best serves you and your lifestyle needs, you don’t get much benefit from taking more or less than that amount.  We each have a personal “sweet spot based on our own body chemistry and finding that spot creates the foundation of a beneficial CBD wellness routine.   

 

Next Steps in Research on CBD for Anxiety 

A 2017 review of the pre-clinical and clinical trials that looked at CBD for various forms of situational anxiety confirmed how promising the evidence is, and also declared the need for further clinical trials.(26) Most clinical studies looking at CBD for situational or occasional anxiety have been small and short-term, but findings have been compelling enough to inspire more clinical trials. Currently, several of these studies are in the pipeline. One of them is looking at the effectiveness of using 25mg of CBD from a fullspectrum hemp extract in the form of soft gel capsules over a twelveweek period.(27) 

Another will evaluate the effects of CBD for occasional anxiety using a sublingual (under-the-tongue) tincture of whole plantderived CBD three times daily for four weeks.(28) In addition, a phase II clinical trial is going to look at CBD for social anxiety along with changes in endocannabinoid levels.(29)  

 

Summing It All Up 

Research on CBD for situational and occasional anxiety reinforces what has been known about the endocannabinoid system for some time, which is that one of its primary purposes is to maintain physiological balance by helping us recover from the effects of stress of all kinds.(30) Multiple studies show that the ECS communicates with regions of the brain that modulate mood, motivation, memory, and how we experience stress. CBD appears to support all of these activities. It also helps promote the optimal function of the ECS in several ways, including by influencing FAAH, the enzyme that breaks down anandamide, our own endocannabinoid, when our supply of this natural “feel good” substance has been depleted. Beyond the ECS, CBD supports the serotonin neurotransmitter system and activation of the “social-bonding” substance oxytocin. 

For all of these reasons, trying full-spectrum hemp extracts high in CBD for occasional anxiety can be an excellent approach to self-care, especially when its part of a comprehensive plan that includes a healthy diet, regular exercise, and practices to alleviate stress. 

References 

  1. Arnsten, A. Stress signalling pathways that impair prefrontal cortex structure and function. Nature Reviews Neuroscience.10, 410–422(2009) 
  2. Lutz, B et al. The endocannabinoid system in guarding against fear, anxiety and stress. Nat Rev Neurosci. 2015;16(12):705‐718 
  3. Hillard CJ Stress regulates endocannabinoid-CB1 receptor signaling. Seminars in immunology, 26(5), 2014, 380–388 
  4. Hill, MN et al. Suppression of amygdalar endocannabinoid signaling by stress contributes to activation of the hypothalamic-pituitary-adrenal axis. Neuropsychopharmacology 34,13 2009: 2733-45 
  5. Hill, M N et al. Serum endocannabinoid content is altered in females with depressive disorders: a preliminary report. Pharmacopsychiatry vol. 41,2, 2008: 48-53 
  6. Bluet, RJ et al. Central anandamide deficiency predicts stress-induced anxiety: behavioral reversal through endocannabinoid augmentation. Transl Psychiatry (2014) 4, e408; doi:10.1038/tp.2014.53 
  7. Bedse, Gaurav et al. Therapeutic endocannabinoid augmentation for mood and anxiety disorders: comparative profiling of FAAH, MAGL and dual inhibitors. Translational psychiatry vol. 8,1 92. 26 Apr. 2018 
  8. https://www.sciencedaily.com/releases/2008/02/080204094507.htm 
  9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161644/ 
  10. Wei, D et al. Endocannabinoid signaling mediates oxytocin-driven social reward. PNAS November 10, 2015 112 (45) 14084-14089; first published October 26, 2015 https://doi.org/10.1073/pnas.1509795112  
  11. Russo, EB et al. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res. 2005 Aug;30(8):1037-43 
  12. Blessing EM, et al. Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics 2015; 12:825-836 
  13. Gunduz-Cinar, O et al. Convergent translational evidence of a role for anandamide in amygdala-mediated fear extinction, threat processing and stress-reactivity. Molecular psychiatry vol. 18,7 2013, 813-23. doi:10.1038/mp.2012.72 
  14. Das RK, et al. Cannabidiol enhances consolidation of explicit fear extinction in humans. Psychopharmacology (Berl) 2013; 226:781-792 
  15. Campos A et al. Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: Possible involvement of 5HT1A receptors. Journal of Psychiatric Research 46 (2012) 1501e1510 
  16. Norris C et al. Cannabidiol Modulates Fear Memory Formation Through Interactions with Serotonergic Transmission in the Mesolimbic System. Neuropsychopharmacology (2016) 41, 2839–2850 
  17. Resstel, B M et al. 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. British journal of pharmacology vol. 156,1 (2009): 181-8 
  18. Bitencourt RM and Takahashi RN. Cannabidiol as a Therapeutic Alternative for Post-traumatic Stress Disorder: From Bench Research to Confirmation in Human Trials. Front. Neurosci. 12:502.doi: 10.3389/fnins.2018.0050 
  19. Chhatwa, J et al. Enhancing Cannabinoid Neurotransmission Augments the Extinction of Conditioned Fear. Neuropsychopharmacology (2005) 30, 516–524 
  20. Soares V and Campos A. Evidences for the anti-panic actions of cannabidiol. Curr Neuropharmacol 2017; 15:291-299 
  21. Crippa JA et al. Effects of cannabidiol (CBD) on regional cerebral blood flow. Neuropsychopharmacology 2004; 29:417-426 
  22. Crippa JA et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J Psychopharmacol 2011; 25:121-130 
  23. Bergamaschi, Mateus M et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology. 36,6, 2011, 1219-26 
  24. Pamplona, FA et al. Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis. Front Neurol. 2018 Sep 12;9:759 
  25. Gallily, R et al. Overcoming the Bell‐Shaped Dose‐Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol. Pharmacology & Pharmacy, 2015, 6, 75‐85 
  26. Lee, JLC et al. Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorders. Br J Pharmacol. 2017 Oct;174(19):3242-3256. doi: 10.1111/bph.13724. Epub 2017 Mar 9 
  27. https://clinicaltrials.gov/ct2/show/NCT03549819  
  28. https://clinicaltrials.gov/ct2/show/NCT02548559 
  29. https://clinicaltrials.gov/ct2/show/results/NCT04086342   
  30. Russo, E. Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes 2016 Jul 1. doi: 10.1089/can.2016.0009 

 

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