Within the depths of our being lies an extraordinary ally—the endocannabinoid system (ECS). Often referred to as our body’s inner healer, the ECS orchestrates a symphony of balance, offering relaxation, appetite control, sound sleep, memory modulation, enhanced protection, neuroprotection, and neuroregeneration. In this enlightening blog post, we explore the wondrous capabilities of the ECS in the context of stress, burnout, PTSD, and CPTSD, understanding how it supports our mental and emotional well-being.
I learned about trauma-informed approach in the worst possible way. Working as a mental health professional for three decades, neither I nor any of my colleagues ever suspected that I was living with PTSD. It was only during my EMDR training that I came to this realization. Well, to be honest, it’s come up a few times in conversations with my partner lately, but to me, it’s been nothing more than a justification for my occasional verbal outbursts.
From the moment I realized this, I started studying everything I could. Hours of online training, dozens of articles read, and of course, the PTSD bible by Bessel van der Kolk – “The Body Keeps the Score.” On one hand, the newly charged knowledge helped me understand why I had lived on the edge of society for the last ten years and gave me the will to fight; at the same time, it opened new deep wounds in my soul. But most importantly, it gave meaning to this part of life that I thought was lost.
Some will consider it a coincidence, others synchronicity, and there will be those who see the finger of fate in it. Amidst the tough times of almost being without a home and job I suddenly had more time on my hands than I ever imagined.
This unexpected turn of events opened up a unique chance for me to dive deep into the world of cannabis and its impact on our health. It’s funny how challenges sometimes bring unexpected gifts, and for me, it was the gift of time and the chance to learn and explore in ways I hadn’t before. Over the years, I have devoted less and less time to the plant itself and more to understanding the role of the endocannabinoid system.
Despite being discovered thirty years ago and influencing the management of all body systems, it remains practically unknown to the majority of professionals as well as the general public. I will now leave aside the reasons why this is so, but focus on its importance and potential in the treatment of stress-related disorders, PTSD, and complex PTSD.
It’s astonishing that I have spent the last ten years studying something of fundamental importance to myself and all those suffering from similar problems.
Simultaneously, what struck me, without much surprise, was that throughout my intensive learning journey over the past three months—immersed in the realms of stress and trauma—I hadn’t encountered a single mention of the ECS among those engaged in the fields of education and therapy.
The age of this system exceeds 500 million years1, and its basic role is to ensure survival in an inhospitable environment, including dealing with stress and inflammation. Its name is quite misleading—it has nothing to do with cannabis.
It is a lipid signaling system whose receptors are the most abundant group of receptors in the CNS2. We are learning more about it every day, and due to its complexity and intertwining with other key elements such as the microbiome, I recently proposed renaming it the Master Homeostatic Regulatory System.
For this blog, however, we will stick to its five functions, which Vicenzo di Marzo proposed only six years after its discovery: ‘relax, eat, sleep, forget, and protect.3
The endocannabinoid system (ECS) assumes a vital role in governing the regulation of the stress response, encompassing its eventual cessation. In conditions of normal physiology, the ECS operates as a inherent stress modulator, aiding in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis—a fundamental player in our stress response. When confronted with stress, this triggers the ECS to initiate the synthesis and release of endocannabinoids, which subsequently bind to CB1 receptors situated in specific regions of the brain—comprising the amygdala, hippocampus, prefrontal cortex, and nucleus accumbens.
Through interaction with these CB1 receptors, the ECS orchestrates a reduction in the discharge of stress hormones like cortisol, originating from the adrenal glands. This process yields a promotion of relaxation and an infusion of tranquility, facilitating recuperation from stress-inducing circumstances.
Significantly, the ECS also undertakes the role of curtailing the stress response upon the resolution of the stressor. By resetting the HPA axis and curtailing the undue release of stress hormones, the ECS facilitates a return to a state of homeostasis marked by diminished anxiety.
Practices geared towards the stress management and the fostering of well-being—examples encompass mindfulness, autogenic training, singing, dancing, and various stress-alleviating activities—emerge as instrumental in reinstating ECS homeostasis. These methodologies exhibit a capacity to induce positive impacts on the ECS, thereby contributing to its peak functionality. The engagement in such activities finds support in the innate capability of the ECS to manage stress, bolster emotional well-being, and augment resilience in the face of demanding scenarios4.
In the realm of human behavior, the allure of hedonic eating often surpasses mere sustenance. Striking a balance between eating for energy and indulging in delight carries significant implications. Researchers delve into the puzzle of why we’re drawn to hedonic eating, even when it may not be healthy.
At the core of this exploration is dopamine, a neurotransmitter linked to pleasure. This interplay of chemicals intersects with hormones like leptin, ghrelin, and insulin, which regulate appetite. Alongside this, the endocannabinoid system (ECS) comes into play—a complex network governing our emotional and cognitive functions. The palatable foods we favor can impact these chemicals, sometimes leading us to overeat.
Central to this narrative is the lateral hypothalamus—a region where signals of hunger and taste converge. Working with endocannabinoids, ghrelin, and other factors, it molds our inclinations, potentially leading to overindulgence and specific food cravings.
In the backdrop, stress emerges as a significant influencer. When stress mounts, our bodies release endocannabinoids, driving us towards comfort foods. These chemicals also intertwine with the brain’s reward system, intensifying our desire for such comforts5.
Now, let’s focus on the endocannabinoid system itself. Beyond just encoding pleasure, it also shapes our stress responses. The interplay between the ECS and stress is evident in areas like substance misuse, spanning substances like drugs or alcohol. Scientists examine genetics linked to the ECS, investigating how prolonged cannabis use affects our responses to rewards.
Tools like functional magnetic resonance imaging (fMRI) provide insight into the brain’s response to rewards. For individuals closely tied to cannabis, genetics like CNR1, along with past and present stress, influence reactions to cannabis-related cues. Meanwhile, in those unaffected by cannabis, the FAAH gene and stress levels affect responses to rewards.
Navigating the intricate interplay of the ECS and stress reveals diverse responses to rewards. From cannabis-related triggers to natural pleasures, these interactions form a complex landscape. Researchers seek to decode this landscape, offering support to those grappling with substance misuse, particularly involving cannabis6.
Embedded in the Homeostatic approach is a strategy to stabilize the ECS, curbing cravings and steering towards wholesome rewards. Here, the Mediterranean diet emerges as an exemplar—a dietary path that extends beyond nourishment, guiding individuals towards holistic well-being.
Sleep functions as a natural reset button for our brain, inducing reduced awareness and responsiveness. Its various stages encompass REM (rapid eye movement) sleep and non-REM sleep, further divided into slow wave sleep (SWS) and lighter sleep. During the later nocturnal hours, REM sleep prevails, characterized by desynchronized brain regions and the activation of unique brain waves—ponto-geniculo-occipital (PGO) waves and theta activity. This REM phase intertwines with memory enhancement processes, contributing to effective information retention.
Within the realm of research, scientists embarked on injecting endocannabinoid anandamide (AEA) directly into the hippocampus—a brain region. This intervention yielded increased occurrences of REM sleep, albeit not prolonged, especially when administered during the “active” phase of the 12-hour light/dark cycle. Acknowledging the fluctuating levels of specific brain compounds across the day, they probed into how these elements influence sleep patterns during different timeframes. The hypothesis centered on the CB1 receptor, a specialized receptor in the brain, and its potential contribution to instigating REM sleep. Exploiting this avenue might hold promise for addressing sleep challenges like insomnia.
Interestingly, investigations unveiled that compounds targeting the CB1 receptor could potentially diminish REM sleep duration, possibly due to their role in reducing brain activity. In a contrasting effect, these compounds exhibited an augmentation of overall sleep duration. Consequently, blocking CB1 receptors led to increased instances of awakening.
The endocannabinoid system (ECS), pivotal in maintaining brain equilibrium, also assumes the role of shaping connections—either strengthening or weakening them. Strikingly, this process mirrors the actions transpiring during REM sleep. During specific sleep stages, endocannabinoids modify brain wave patterns, influencing memory.
This interface between the ECS and memory assumes significance, particularly in the context of post-traumatic stress disorder (PTSD). In cases of PTSD, traumatic memories often disrupt daily functioning. The ECS’s involvement in memory consolidation, wherein short-term memories morph into enduring ones, offers a glimpse into addressing memory-associated symptoms within PTSD. The intricate interplay of the ECS and sleep in molding memory processes might unlock avenues to address memory-related challenges across diverse scenarios, including conditions like PTSD7.
Anxiety and trauma-related disorders, such as post-traumatic stress disorder (PTSD), are mental health conditions that can significantly affect a person’s life and incur substantial societal costs. Examining how memories form and how we respond to fear can enhance our comprehension of how our brains process distressing memories and how we can address conditions like PTSD.
The brain circuitry governing learned fear and its attenuation through a process known as “extinction” is intricate. It involves the collaboration of different brain regions, each employing distinct chemicals for communication. Among these chemicals are endocannabinoids and norepinephrine, both individually associated with the processing of traumatic memories and the management of PTSD. Nevertheless, little research has explored the potential synergy between these two systems in fear extinction.
Interestingly, the brain regions influenced by these chemicals host both endocannabinoid and noradrenaline receptors. Consequently, activation of these receptors can aid in overcoming fear. In fact, the combined operation of both systems within these brain areas can enhance our capacity to surmount fear. Additionally, endocannabinoids can impact neurons that produce noradrenaline and influence their communication with another brain region known as the medial prefrontal cortex—a key area for dispelling alarming memories.
Of note, interactions between the endocannabinoid and noradrenergic systems may influence the way we remember fearful experiences. This suggests that the interplay between these two systems may partially shape our responses to fear. By amalgamating this information, we can posit that the endocannabinoid and noradrenergic systems might collaboratively facilitate fear alleviation. This holds vital implications for comprehending the mechanisms of PTSD within the brain and devising improved treatment strategies for the future8.
Let’s delve into some studies that elucidate how our brain’s endocannabinoid (eCB) system influences our ability to manage fear. Researchers scrutinized various brain regions and their response to the eCB system. In specific brain areas like the basolateral amygdala (BLA), heightened activity of the CB1R receptor facilitated the attenuation of distressing memories. Conversely, introducing substances lowering CB1R activity to the same region rendered it more challenging for mice to forget fear.
This narrative extends to other brain areas. For instance, in the dorsal hippocampus (DH), compounds increasing endocannabinoid activity enhanced mice’s ability to forget fearful memories. However, employing a substance with oposite effect actually impeded the mice’s fear extinction. Similar patterns emerged in regions such as the prelimbic cortex (PL) and infralimbic cortex (IL).
Remarkably, these studies imply that activating the CB1R receptor in different brain regions can aid in dispelling fear.
These findings aren’t limited to mice; they also extend to humans. Researchers have investigated the potential linkage between genes related to the eCB system and anxiety disorders, including PTSD. In individuals with PTSD, specific endocannabinoid levels in their bodies undergo alterations. Some studies administered a compound called dronabinol to individuals before they attempted to forget distressing experiences, resulting in enhanced memory of safety. This phenomenon correlated with increased brain activity in specific regions during memory retrieval.
In summary, these studies collectively underscore that heightened activity of the eCB system facilitates the attenuation of distressing memories. The eCB system collaborates with other neurotransmitters in our brain to achieve this. One such neurotransmitter is norepinephrine (NA), which also plays a pivotal role in fear extinction. While we recognize that the eCB and NA systems interact in other contexts, our understanding of how they synergize to aid in overcoming fear is still evolving8.
In the context of PTSD (post-traumatic stress disorder), the endocannabinoid system (ECS) plays a significant role in nerve protection and regeneration, which can have implications for understanding and treating the disorder.
Individuals with PTSD often experience heightened stress responses, which can lead to chronic neuroinflammation and oxidative stress, contributing to nerve cell damage. The ECS’s neuroprotective effects can help mitigate these harmful effects, potentially reducing the impact of chronic stress on nerve cells. By activating cannabinoid receptors, endocannabinoids can counteract the negative consequences of stress on neurons, promoting their survival and function.
PTSD is characterized by intrusive and distressing trauma-related memories. The ECS’s role in synaptic plasticity could have implications for memory processing and reconsolidation. Modulation of neurotransmitter release by endocannabinoids might affect the strength of synaptic connections related to traumatic memories. Understanding how the ECS influences synaptic plasticity could offer insights into memory reprocessing techniques used in PTSD therapies.
Neuroinflammation is linked to the persistent anxiety and hypervigilance seen in PTSD. The ECS’s anti-inflammatory properties could potentially mitigate the detrimental impact of neuroinflammation on nerve cells. By reducing inflammation, the ECS may contribute to restoring a more balanced neural environment, thereby enhancing the brain’s resilience to the effects of trauma.
Emerging research suggests that the ECS is involved in neurogenesis, which could have implications for healing the effects of trauma. Promoting the generation of new nerve cells, particularly in brain regions associated with emotional regulation and memory, may contribute to resilience and recovery in individuals with PTSD.
Incorporating our understanding of the ECS’s role in nerve protection, synaptic plasticity, neuroinflammation, and neurogenesis within the context of PTSD provides a broader perspective on the disorder’s underlying mechanisms. Targeting the ECS through pharmacological interventions or therapeutic strategies that support its natural function could offer innovative approaches to managing the symptoms of PTSD and enhancing overall mental well-being9.
- Sagheddu C, Muntoni AL, Pistis M, Melis M. Endocannabinoid Signaling in Motivation, Reward, and Addiction: Influences on Mesocorticolimbic Dopamine Function. Int Rev Neurobiol. 2015;125:257-302. doi: 10.1016/bs.irn.2015.10.004. Epub 2015 Nov 11. PMID: 26638769.
- Kendall DA, Yudowski GA. Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease. Front Cell Neurosci. 2017 Jan 4;10:294. doi: 10.3389/fncel.2016.00294. PMID: 28101004; PMCID: PMC5209363.
- Di Marzo V, Melck D, Bisogno T, De Petrocellis L. Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action. Trends Neurosci. 1998 Dec;21(12):521-8. doi: 10.1016/s0166-2236(98)01283-1. Erratum in: Trends Neurosci 1999 Feb;22(2):80. PMID: 9881850.
- Maldonado R, Cabañero D, Martín-García E. The endocannabinoid system in modulating fear, anxiety, and stress . Dialogues Clin Neurosci. 2020 Sep;22(3):229-239. doi: 10.31887/DCNS.2020.22.3/rmaldonado. PMID: 33162766; PMCID: PMC7605023.
- Coccurello R, Maccarrone M. Hedonic Eating and the “Delicious Circle”: From Lipid-Derived Mediators to Brain Dopamine and Back. Front Neurosci. 2018 Apr 24;12:271. doi: 10.3389/fnins.2018.00271. PMID: 29740277; PMCID: PMC5928395.
- Filbey FM, Beaton D, Prashad S. The contributions of the endocannabinoid system and stress on the neural processing of reward stimuli. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 2;106:110183. doi: 10.1016/j.pnpbp.2020.110183. Epub 2020 Nov 20. PMID: 33221340; PMCID: PMC8204292.
- Robledo-Menendez A, Vella M, Grandes P, Soria-Gomez E. Cannabinoid control of hippocampal functions: the where matters. FEBS J. 2022 Apr;289(8):2162-2175. doi: 10.1111/febs.15907. Epub 2021 May 19. PMID: 33977665.
- Warren WG, Papagianni EP, Stevenson CW, Stubbendorff C. In it together? The case for endocannabinoid-noradrenergic interactions in fear extinction. Eur J Neurosci. 2022 Feb;55(4):952-970. doi: 10.1111/ejn.15200. Epub 2021 Apr 5. PMID: 33759226.
- Heinbockel, T., Wang, Z.-J., Brown, E. A., & Austin, P. T. (2016). Endocannabinoid Signaling in Neural Circuits of the Olfactory and Limbic System. InTech. doi: 10.5772/63214