Motivation and emotion/Book/2022/Endocannabinoid system and emotion

Overview
The endocannabinoid system is critical in the emotional, cognitive and physical homeostasis within the human body. The endocannabinoid system is a widespread neuro-modulatory system that plays a significant role in central nervous system (CNS) development, synaptic plasticity and recognising endogenous and environmental stimuli (Lu & Mackie, 2015). Endocannabinoids and their receptors are densely packed together and located throughout the entirety of the human body; in the organs, connective tissues, in the brain, glands and in the immune systems cells (Alger, 2013; Kendall & Yudowski, 2016). Additionally, research into the endocannabinoid system and the pharmacology of endocannabinoids began in the late 1940s, several decades before cannabinoids were detected in cannabis (also known as marijuana) (Pertwee, 2006). Since the first discovery in the 1940s, endocannabinoids were quickly discovered to be very useful and efficient in pharmacological medicines in order to treat drug addictions, regulating anxiety, stress, and as a therapeutic tool to improve emotional regulation and processes (Litvin, Phan, Hill, Pfaff, & McEwen, 2013; Marco & Laviola, 2013). This chapter discusses the role of endocannabinoid system in emotion. Firstly, the endocannabinoid system is discussed, outlining the system's history, impacts and significance in the psychology field. Additionally, the chapter discusses the physiological processes of the endocannabinoid system and the main receptors involved. Next, the chapter delves into the significance of emotions, highlighting core emotions related to the endocannabinoid system and the impact on emotional processing and regulation of an individual. Lastly, the chapter outlines future directions of research.

Focus questions:
 * What is the endocannabinoid system?
 * What is emotion?
 * How does the endocannabinoid system and emotions interact?

What is the endocannabinoid system?
The endocannabinoid system is a complex cell signalling system that serves various protective roles in pathophysiological conditions (Chanda, Neumann, & Glatz, 2019). It encapsulates an efficient network of various immune responses, communication between cells, appetite, metabolism and memory to name a few. The endocannabinoid system is significant in relation to emotions across the human lifespan, emotional regulation and processing (Marco & Laviola, 2013).

Physiological processes of the endocannabinoid system<
The endogenous cannabinoid system or, the endocannabinoid system (ECS) is comprised of endogenous cannabinoids (endocannabinoids), cannabinoid receptors, and the enzymes responsible for the synthesis and degradation of (Lu & Mackie, 2015). Therefore, the endocannabinoid system is key in daily bodily functions such as exercise, eating, metabolism levels and stress-related behaviours. In relation to the physiological processes of the ECS to emotional processing and regulation, cannabinoids' effect of "bliss" on the human body can have a positive and cathartic feelings but also could also be contributing to anxiety, depression and psychosis states in individuals (Moreira & Lutz, 2008).

CB1 Receptors
CB1 receptors are densely located and packed in the neocortex, hippocampus, basal ganglia, amygdala, striatum, cerebellum, and hypothalamus. These major brain regions mediate a wide variety of high-order behavioural functions, including learning and memory, executive function decision making, sensory and motor responsiveness, and emotional reactions, as well as feeding and other homeostatic processes (Alger, 2013). CB1 receptors play a key role in the central nervous system and in flight, fight or freeze responses, anxiety and arousal levels in the human body which can be directly linked to emotion (Litvin et. al., 2013)

However, if a person is deficient in CB1 receptors in their body, the lack of receptors is directly associated with anhedonia, anxiety, and persistence of negative memory recall, which can affect an individual's physical and mental wellbeing. Conjunctively, CB1 receptor-endocannabinoid signalling is activated by stress and functions to buffer or dampen the behavioural and endocrine effects of acute stress (Hillard, 2016).

CB2 Receptors
CB2 receptors are mainly associated with the internal workings of the immune system and immune modulation (Alger, 2013; Christino, Bisogno & Di Marzo, 2020). Unlike CB1 receptors, CB2 receptors are less densely packed within the body and expressed in the microglia in conditions such as alzheimers (AD), multiple sclerosis (MS) and schizophrenia (Christino, Bisogno & Di Marzo, 2020). In comparison to the CB1 receptors, CB2 has an unclear link to emotional processing and regulation, however more research is needed in this area for a deeper understanding of how CB2 can be a therapeutic aid for neurological disorders in the future (Chanda, Neumann, & Glatz, 2019).

Quiz
Time to test your learning so far! Click on the correct answer and then press submit to check your answers. {Are CB1 receptors densely packed in many regions of the brain? - No + Yes
 * type=""}

{Where are CB2 receptors expressed? + Microglia - Central Nervous System (CNS)
 * type=""}

{What symptoms are displayed when a person is deficient in CB1 receptors? } - Loss of vision, emotional outbursts and anxiety + Anhedonia, anxiety and persistence of negative memory recall - Improved motor functioning and emotional regulation



What is emotion?
Interestingly, there is no clear dictionary aligned definition of "emotion". The term is taken for granted in itself and, most often, emotion is defined with reference to a list: anger, disgust, fear, joy, sadness, and surprise (Cabanac, 2002). Additionally, Cabanac (2002) proposed that emotion is any mental experience with high intensity and high hedonic content (pleasure/displeasure) and later explores that emotion and the interrelated concept of consciousness in his 2009 research. Building on Cabanac's (2002) research, Orthony (2022) proposes that for decades the concept of basic emotions are "placed into lists and tables" as developed by psychological theorist, Ekman (1992). Despite decades of challenges to the idea that a small number of emotions enjoys the special status of "basic emotions, the idea continues to have considerable influence in psychology and other relevant fields of research. However, different theorists have proposed substantially different lists of basic emotions, which suggests that there exists no stable criterion of basicness. To some extent, the basic-emotions enterprise is bedeviled by an overreliance on English affective terms, but there also lurks a more serious problem—the lack of agreement as to what emotions are.

Importantly, modern emotion theories typically try to account for the observations that emotions are triggered by events of some significance or relevance to an organism. That emotions encompass a coordinated set of changes in brain and body, and that they appear adaptive in the sense that they are directed towards coping with whatever challenge was posed by the triggering event (Adolphs, 2010).

Focus emotions: Fear and anxiety
Fear is stated to be a core emotion in relation to the endocannabinoid system, as it is directly correlated with feelings of anxiety and a "flight response" within the human body (Moreira & Lutz, 2008). Fear is triggered by external, not internal stimuli and is triggered by the amygdala (a complex part of the temporal lobe of the brain) which is stated to access past fearful experiences in order to develop a fear response (Hyman, 1998). Fear and anxiety are demonstrated to be closely related as the amygdala is not only provoked when an external, unpleasant stimuli is presented and is also activated in the presence of anxiety and phobia related stimuli (Alger, 2013). Cannabinoid receptors are densely located in brain areas involved in emotional states, including amygdala, hippocampus and other limbic sites. The effects on anxiety are thought to be mediated mainly by CB1 receptors but possibly also by CB2 and GPR55 receptors (Ashton & Moore, 2011).

Endocannabinoid system and emotions
The interaction between the endocannabinoid system (ECS) and emotions is depicted to be closely related, especially in relation to CB1 receptors within the ECS. One widely viewed and accepted feature of the ECS is that it is "on demand" in functioning, meaning that endocannabinoids are synthesised and released when "it is needed" for a particular individual. In addition, the endocannabinoid system operates and acts as an undercurrent of brain activity below the level of consciousness. But the tone of the system, ‘endocannabinoid tone’, influences conscious perceptions and affects mood and behaviour and their physical accompaniments (Ashton & Moore, 2011).

The effect of fear and anxiety on the endocannabinoid system
By understanding the link between fear and anxiety in the human body, the better the understanding of how fear and anxiety function within the endocannabinoid system (ECS). In relation to fear and anxiety on the endocannabinoid system, Hyman (1998) proposes a relationship between the amygdala's effect on a fear response in an individual and how fear can increase anxiety, and how anxiety can increase a fear response in patients who have a lesion in their amygdala. Thus, those patients are more likely to experience stronger feelings of fear and anxiety to external stimuli.

The effect of fear and anxiety on the endocannabinoid system is related to an internal coping mechanism, in which an individual must adapt to their environment in order to survive. ECB signalling seems to determine the value of fear-evoking stimuli and to tune appropriate behavioural responses, which are essential for the organism’s long-term viability, homeostasis and stress resilience; and dysregulation of eCB signalling can lead to psychiatric disorders (Lutz, Marsicano, Maldonaldo, & Hillard, 2015). It is also important to note that ECB signalling in the amygdala and other brain regions is essential for several aspects of fear-memory processing, most prominently for extinction of fear responses in individuals. Research suggests that repeated re-exposure to a fear-related stimulus in the absence of the threat increasingly activates ECB signalling, contributing to habituation and/or extinction of specific fear responses which can then improve a persons mental and physical wellbeing (Christino, Bisogno & Di Marzo, 2020). Thus, the phobia/fear extinction will improve the functioning and adaptability of their endocannabinoid system.



Positive interaction of anxiety and the endocannabinoid system
The relationship between anxiety states and behaviours and the endocannabinoid system (ECS) is directly correlated to the use of cannabis. Cannabis is demonstrated to have "euphoric effects" and large "highs", which increases an individuals need for socialisation and connection, thus decreasing anxiety behaviours and cognitions (Lutz, Marsicano, Maldonaldo, & Hillard, 2015; Hillard, 2014). According to research, the effect of cannabis on individuals with generalised anxiety disorder (GAD) was demonstrated to have an overall positive effect on the clients mental wellbeing and anxiety-related thoughts, feelings and emotions after consumption, causing individuals to engage more with others and connect with people without feelings of anxiety and fearfulness. Whearas, the control group did not experience a reduction in their anxiety symptoms (Marco & Laviola, 2012; Moreira & Lutz, 2008).

In correlation to the postive interaction of cannabis and anxiety on the endocannabinoid system (ECS), a case study carried out by Walkaden (2019) was about 88 year old, Cynthia, and her journey of using medicinal cannabis to improve her anxiety symptoms and overall functioning of her endocannabinoid system. Throughout this section of the book chapter, Cynthia's case will be referred to to explain the positive interaction that medicinal cannabis use has on anxiety and the functioning of the endocannabinoid system as a whole.


 * Case study

Cynthia came to seek help from professionals regarding her psychological and emotional wellbeing. Her symptoms included managing generalised anxiety disorder (GAD) and symptoms of vertigo, causing extreme nausea, excessive worrying and loss of balance in her day to day functioning. Cynthia constantly experiences low mood and energy as she is grieving the loss of her husband, five years prior and expressed that she was losing control of her life. Cynthia has also expressed her concerns about going on Xanax again (anti-depressant) due to her vertigo issues and excessive shaking, she is not sure what her options are to help her wellbeing in her later years of life.

Cynthia engaged in taking medicinal doses of cannabis to ease her anxiety symptoms and improve her overall quality of life. Walkaden (2019) succeeded in Cynthia's case as after 5 weeks of taking a micro-dose of cannabis each morning, she reported to "not feel wonky" anymore and that she was energised and felt less anxious overall, with a 70% decrease in vertigo experiences. After 10 weeks when the research concluded, Cynthia had reported to the medical team that she "felt as if my life has changed ... I have never felt better". Therefore, a positive interaction between anxiety and the endocannabinoid system can be linked back to the medicinal and therapeutic use of cannabis.

Negative interaction of anxiety and the endocannabinoid system
In opposing studies, it was found that anxiety behaviour and thought patterns can be actually increased in a maladaptive manner through using cannabis as an aid for the endocannabinoid system (ECS). Jenneriches et al., (2016) findings are significant as it was found that a disruption of the endocannabinoid system through pharmacological or genetic invalidation of cannabinoid CB1 receptors has been linked to depression in humans and depression-like behaviors in mice. A disruption within the endocannabinoid system can cause stress-related reponses, feelings of anxiety and depression, low metabolism, panic attacks and distorted perceptions of reality if engaging in cannabis use regularly (Jenneriches et al., 2016; Lu & Mackie, 2015).

However, it should be noted that Jenneriches' et al. (2016) research may not be generalisable as most of the experiments were performed on mice. Nonetheless, the research is still important to understand the negative interaction of anxiety and cannabis and its impact on the endocannabinoid system. It should also be noted that more research into the negative interaction of anxiety and the endocannabinoid system is needed to further understand the reasons behind maladaptive functioning of the ECS due to cannabis use particularly.

Role of endocannabinoid system in emotional regulation and processing
Acute emotional processing is vital to interpersonal relationships and daily social interactions with others. Without strong emotional processing skills, individuals are more likely to inherit or become subject to major depressive disorder (MPD), bipolar disorder (BPD) and schizophrenia (Bossong et al., 2013). In terms of the role of the endocannabinoid system in emotional regulation and processing, there is a strong correlation that is linked to improved physical and psychological wellbeing. The endocannabinoid system (ECS) acts as an emotional buffer that moderates the effect of environmental stimuli and stress on cognitive processes which has a significant impact on individuals psychological wellbeing (Hillard, 2014; Walkaden, 2019).

Future research and practical applications
In relation to new directions of research, the endocannabinoid system and cannabis as a therapeutic tool for anxiety-related disorders is still a new topic in scope, with limited research in implementing cannabinoids as an aid for reducing anxiety in particular (Alger, 2013). The endocannabinoid system appears to play a pivotal role in the regulation of emotional states and may constitute a novel pharmacological target for anti-anxiety therapy, cognitive behavioural therapy (CBT), and talk therapy (Lu & Mackie, 2015; Moreira & Lutz, 2008).

Through the medicinal use of cannabis to aid anxiety-related disorders and issues, individuals lives and mindsets can be shifted for the better, in a practical manner over 3-10 week periods of micro-dosing and regular check ups from health care professionals throughout the process to tailor for the individuals specific needs and to improve the functioning of their ECS.

Conclusion
The role of the endocannabinoid system (ECS) in emotion is significant and steers towards a positive direction of future research in the field. Through understanding the physiological processes of the endocannabinoid system (particularly CB1 and CB2 receptors) and the complexity of human emotions (highlighting fear and anxiety), it is clear that the interaction between the system and emotion are strongly correlated towards each other, however more research is needed in the area. By exploring the medicinal use of cannabis to treat anxiety-related behaviours and disorders, a new wave of therapeutic and pharmacological tools have been unlocked to improve the functioning of the endocannabinoid system and decrease fearful and anxiety ridden behaviours in individuals.