CBD Medical Uses Health Science

CBD Effects On Anxiety: Social Anxiety

CBD’s effects on anxiety are well-documented and expansive. As one of the most popular medical benefits of CBD, CBD for anxiety has generated huge buzz in the health and wellness communities as a natural alternative to side effect-ridden pharmaceuticals that alter your personality and can even make anxiety worse for some. Those with social phobia know that it’s not just something you can get over; it’s a very real, gripping sensation that can impair work, school, and even family relationships. The use of CBD oil for anxiety is rapidly gaining popularity for one simple reason: it works. 1, 4, 6

What is Social Anxiety?

Social anxiety disorder (SAD), or social phobia, is a condition characterized by apprehension and avoidance of social situations, especially those which make one the center of group attention. It affects over 3 million Americans, and it’s different than stage fright or a fear of public speaking in that even non-threatening social interactions produce a fear response that can lead to dysfunction and a quantifiable decrease in quality of life.5

An interesting statistic that sheds light on the nature of this condition is that, while only about 1% of the general US population has social anxiety, 6% of 13-18 year olds exhibit the symptoms of diagnosable social phobia. The essential characteristic that separates social anxiety from general anxiety is that social anxiety specifically refers to a fear of judgment or ostracization by a group of peers. Many kids experience judgement and even bullying in school, by their peers. For some people that may be more neurologically prone, an irrational fear response becomes associated with social interactions of any kind, and when this gets reinforced over and over, the chemistry and structure of neurons actually begins to change.8, 12

The emotions of anxiety and fear are closely related. Fear can be thought of as an acute response to some immediate threat. Anxiety, on the other hand, is a conditioned response formed after repeated negative experiences associated with a certain stimulus. Anxiety can be thought of as “learned fear”. When our brains learn to fear, and therefore avoid, something that isn’t truly threatening such as homework or social interactions, that fear isn’t functional, but rather it impairs our ability to operate normally.

The cannabinoid receptors in mammalian brains control the release and reuptake of glutamate, the brain’s primary excitatory neurotransmitter. It also suppresses GABA, the primary inhibitory neurotransmitter. This is how the endocannabinoid system modulates homeostasis, and whenever it fails to balance out the converse activity of these two signallers, CBD can act as a buffer, helping to rein in any outlying signalling.

A study from 2003 showed a strong correlation between social exclusion and activity in the ACC (anterior cingulate cortex which mediates our emotional response to physical pain. They used fMRI imaging to measure brain activity while experiencing various models of social exclusion. It activated the same pathway which associates a negative emotion with physical pain. The function is to motivate corrective measures and to protect the injured body part; activity here during social “injury” suggests a similar function of impetus to repair damage to social connections.9

Why do people use CBD oil for anxiety?

While there are many diverse benefits of CBD, CBD for anxiety and mood disorders stands out. The cannabidiol molecule is one of the most biologically active substances ever discovered in nature. In the human brain, it has over 30 different effects. In the rest of the body, estimates range from 70 to over 300 different biological targets for the activity of CBD. Moreover, CB1 receptors, the cannabinoid receptors found in the  brain, are more numerous than all of the other receptors combined. However, as a result of their behind-the-scenes role, scientific understanding of the CB1 receptors in our brain and the CB2 receptors in the rest of our body is still in its infancy relative to other systems.

CBD has shown the ability to reduce acute fear responses, to disrupt negative reconsolidation of a memory, and to enhance extinction of useless memories. Each time we recall a memory, we “reconsolidate it”, meaning we remember the last time we remembered it, not the first time we encoded the memory. By disrupting negative consolidation, CBD helps to enable us to reorganize the emotional makeup of once-negative memories. This is highly useful in combination with cognitive therapy, which has this specific end goal. In addition to cannabinoid receptors, CBD also activates serotonin 5-HT1a receptors, TRPV-1 vanilloid pain receptors, and several other enzymatic targets.3, 7, 9

CBD for social anxiety: cannabinoid receptor pathways

Cannabinoid receptors are retrograde inhibitory receptors, meaning they mediate negative feedback loops in the brain. Anandamide (AEA) and 2-AG  are the brain’s endogenous cannabinoid signals. Their distinct functions aren’t entirely understood, but in general, their activity is correlated with social activity. Further, when AEA decreases, the fear response associated with adrenal activity increases; this means AEA reduces neuroendocrine stress. The benefits of CBD are centralized around its ability to reduce the activity of the enzyme FAAH (fatty acid amide hydrolase). This enzyme degrades AEA, so CBD’s inhibition of it actually increases the amounts of AEA present in the brain.2, 3, 5

Social interest versus social motivation is also associated with cannabinoid receptor activity. Motivation is associated with greater emotional activity in the amygdala versus interest, which will fade unless it is reinforced by motivation. AEA is directly correlated with increased amygdala activity, and also dopamine production in the nucleus accumbens and dorsal striatum (both heavily involved in reward-motivation circuits from higher cognition to motor control). 2-AG has the same effect, but isolated only to the nucleus accumbens.5

CBD for social anxiety increases the levels of these two signals in all of these areas, and it also potentiates their receptors by making them more selective and responsive inside the neuron once activated. Multiple studies have shown that high doses of CBD (600mg) reduced 3 key neurophysiological signs of anxiety after exposure to fearful facial expressions. CBD caused a significant reduction in amygdala activity on fMRI, self-reported subjective anxiety, and skin conductance. The researchers hypothesized that CBD weakens the negative emotional response to the “pain” associated with a negative social experience. 3, 6, 9

CBD for social anxiety: serotonin receptor pathways

CBD’s activity on the serotonin system has been known for some time now, but its exact mechanisms are still under investigation. One of the medical benefits of CBD is the ability to directly bind to serotonin receptors, thus mimicking the activity of serotonin. Studies have also demonstrated its effect in increasing baseline serotonin levels, either by upregulating receptor counts, or by preventing their enzymatic degradation, similar to its effect on the endocannabinoids.3, 4

Serotonin is an inhibitory neurotransmitter, meaning that when it is released, the neuron that it binds to becomes less active. This is useful in the amygdala, where serotonin tonic signalling (consistent, low-level signalling) keeps the amygdala operating at the perfect rate. In anxiety, this baseline serotonin activity decreases or disappears altogether, producing consistent anonymous anxiety. By upregulating general serotonin activity, CBD has the subtle effect of reducing anxiety without creating any psychoactive feelings.

As more research is carried out, a clearer understanding of the various impacts of CBD on anxiety will be cultivated. It is currently understood that the broad-spectrum activity of this molecule has a balancing effect on itself by acting on opposite features of the same systems, as a sort of buffer. This is a sophisticated domain of biological activity, and we still don’t understand the multidimensional circuitry of our bodies; research into the endocannabinoid system will allow us to keep learning more.

References:

  1. Zuardi, A. W., Rodrigues, N. P., Silva, A. L., Bernardo, S. A., Hallak, J. E. C., Guimarães, F. S., & Crippa, J. A. S. (2017). Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life. Frontiers in Pharmacology8, 259. http://doi.org/10.3389/fphar.2017.00259
  2. Karhson, D. S., Hardan, A. Y., & Parker, K. J. (2016). Endocannabinoid signaling in social functioning: an RDoC perspective. Translational Psychiatry6(9), e905–. http://doi.org/10.1038/tp.2016.169
  3. Miller, M. A., Bershad, A. K., & de Wit, H. (2015). Drug effects on responses to emotional facial expressions: recent findings. Behavioural Pharmacology26(6), 571–579. http://doi.org/10.1097/FBP.0000000000000164
  4. Jurkus, R., Day, H. L. L., Guimarães, F. S., Lee, J. L. C., Bertoglio, L. J., & Stevenson, C. W. (2016). Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders. Frontiers in Pharmacology7, 454. http://doi.org/10.3389/fphar.2016.00454
  5. Merikangas KR, He J, Burstein M, Swanson SA, Avenevoli S, Cui L, Benjet C, Georgiades K, Swendsen J. Lifetime prevalence of mental disorders in U.S. adolescents: Results from the National Comorbidity StudyAdolescent Supplement (NCS-A). J Am Acad Child Adolesc Psychiatry. 2010 Oct;49(10):980-989.
  6. Keifer, O. P., Hurt, R. C., Ressler, K. J., & Marvar, P. J. (2015). The Physiology of Fear: Reconceptualizing the Role of the Central Amygdala in Fear Learning. Physiology30(5), 389–401. http://doi.org/10.1152/physiol.00058.2014
  7. Eisenberger, N. I., Lieberman, M. D., & Williams, K. D. (2003, October 10). Does Rejection Hurt? An fMRI Study of Social Exclusion. Retrieved November 08, 2017
  8. Norris C, Loureiro M, Kramar C, et al. Cannabidiol Modulates Fear Memory Formation Through Interactions with Serotonergic Transmission in the Mesolimbic System. Neuropsychopharmacology. 2016;41(12):2839-2850. doi:10.1038/npp.2016.93.
  9. Shannon, S., & Opila-Lehman, J. (2016). Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report. The Permanente Journal20(4), 108–111. http://doi.org/10.7812/TPP/16-005
  10. Robinson OJ, Krimsky M, Lieberman L, Allen P, Vytal K, Grillon C. Towards a mechanistic understanding of pathological anxiety: the dorsal medial prefrontal-amygdala “aversive amplification” circuit in unmedicated generalized and social anxiety disorders. The Lancet Psychiatry. 2014;1(4):294-302. doi:10.1016/S2215-0366(14)70305-0.
  11. Blessing EM, Steenkamp MM, Manzanares J, Marmar CR. Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics. 2015;12(4):825-836. doi:10.1007/s13311-015-0387-1.
  12. Campos AC, Moreira FA, Gomes FV, Del Bel EA, Guimarães FS. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philosophical Transactions of the Royal Society B: Biological Sciences. 2012;367(1607):3364-3378. doi:10.1098/rstb.2011.0389.

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