Motivation and emotion/Book/2020/Endocannabinoid system and emotion

Overview


Increasingly, the endocannabinoid system is recognised as central to health maintenance. Endocannabinoids and their receptors can be found throughout the body: the brain; organs; tissues; glands; and the immune system (Alger, 2013). Research exploring the endocannabinoid system began in the 1940s. This was several years before the presence of cannabinoids were found to be in the plant that lead to the discovery of the system, cannabis sativa (Pertwee, 2006). Since then, research has found that the endocannabinoid system can be useful for pharmaceutical medicines, the treatment of drug addictions (Chye, Christensen, Sololowji and Yucel, 2019) as well as emotional processing in terms of fear, anxiety and stress (Lutz, Marsicano, Maldonado and Hillard, 2015).

This chapter discusses the endocannabinoid system. It will be beginning by exploring an understanding of emotion. It will then draw attention to emotional responses to fear, stress, and their connection to anxiety. Finally it will discuss the endocannabinoid system, its physiological aspects, and its role in emotional processing.

Focus questions:
 * What are emotions?
 * What is the endocannabinoid system?
 * What is the effect of the endocannabinoid system on emotion?

What are emotions?
While there is extensive literature on the study of emotion there is a lack of consensus on a clear definition (Cabanac, 2002). However, Reeves (2018) defined emotions in a simplified form. Emotions are "short-lived, feeling-purpose-expressive-bodily responses that help us adapt to the opportunities and challenges we face during important life events”.

The basic emotions
Basic emotions are easy to identify and are a part of every individual’s emotions. Basic emotions produce behavioural, cognitive and social effects in an individual (Reeves, 2018). The basic emotions are fear, anger, disgust, sadness, joy and interest (Reeves, 2018). {Which emotion arises in the presence of an obstacle to an individuals goals? - Joy - Anger - Sadness - Disgust - Fear - Contempt - Interest
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Focus emotion: Fear
The emotion most relevant to the functioning of the endocannabinoid system is fear, and its close ally of anxiety (Reeves, 2018). Despite popular belief, fear is not triggered by a conscious feeling of being afraid or the behavioural response of running away. Certainly this may be evidence of fear, but fear is is actually caused by a specific external stimuli (Adolphs, 2013).

Fear is mostly about perceived vulnerability to a threat or danger. In this way, fear is a response that motivates protection (Reeves, 2018). Significantly, fear is a contributing mechanism to the ‘flight’ aspect of the fight and flight response (Reeves, 2018). The body can either flee through physical distance or freeze by being quiet or still to protect itself from the stimuli causing the fear response (Reeves, 2018). So, while fear gives an individual notice of vulnerability, it also teaches the body how to cope with the adverse response (Reeves, 2018).

Physiological studies of fear have shown that it is recognised and expressed in the amygdala of the brain. Importantly, research has identified that the amygdala is not only activated during unpleasant stimuli, but it is also activated in in the presents of anxiety and phobia provoking stimuli (Adolphs, 2013). As such, one can note the significant relationship between anxiety and fear. (Reeves, 2018). This connection is considered in further detail below.

The endocannabinoid system
The endogenous cannabinoid System, or the endocannabinoid system (ECS) was named after the plant, cannabis, which led to its discovery (Alger, 2013). In the last 25 years it has been found to be essential within the physiological systems that maintain human health (Sharkey and Wiley, 2016). Endocannabinoids and their receptors are found throughout the body including within the brain, organs, tissues, glands and immune cells. It{{what} contributes to the complex workings of the nervous and immune system (Alger, 2013). Research spanning recent decades has consistently acknowledged its essentialness within physiological systems and thus the maintenance of human health (Sharkey and Wiley, 2016).

The physiology of the endocannabinoid system
The endocannabinoid system plays an important role in the central nervous system and in an individual’s response to environmental stimuli. It is comprised of cannabinoid receptors, endocannabinoids, and enzymes responsible for the synthesis and degradation of the endocannabinoids (Lu and Mackie, 2016).

CB1 Receptors


The most prevalent form of receptor in the endocannabinoid system is the CB1 receptor and is most abundant in the central nervous system (Lu and Mackie, 2016). Their role is to control the physiological actions of the endocannabinoid system in the central nervous system (Martin, Ledent, Patmentier, Maldonado, 2002). Interestingly, these receptors can be found in the central amygdala and the hypothalamus in the brain which are both responsible for the fear and stress response. Further, they have been noted to active the hypothalamic-pituitary-adrenal axis which is involved in the responses to emotional stress (Martin, Ledent, Patmentier, Maldonado, 2002).

CB2 Receptors
In comparison to CB1 receptors, CB2 receptors are expressed at a lower level in the central nervous system. The CB2 receptor appear to be expressed in conditions such as nerve injury. Further, research shows a link between CB2 receptor and an increased risk for psychological conditions such as schizophrenia (Lu and Mackie, 2016). The CB2 receptor has also been found to be a significant factor in immune response (Alger, 2012). Significant but limited research has also noted its contribution to emotional regulation (Alger, 2012). {Which endocannabinoid receptor is responsible for the fear and stress response? - CB1 receptors - CB2 receptors
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Runners high and the endocannabinoid system (Ashton and Moore, 2011):

A specific example of how the endocannabinoid system can affect emotion is found in a psychological phenomenon known as the ‘runners high’. The ‘runners high’ has been described as giving an individual’s pure happiness, endless peacefulness and decreased anxiety. Previously, researchers agreed that it was the realize of endorphins during exercise that increased these feelings in the body. However, endorphins do not pass the blood brain barrier. Later, research found that exercise heightened the blood levels of anandamide. This is a neurotransmitter that does cross the blood-brain barrier. The demands of exercise on the body cause the realise of anandamide in the brain. Similarly, the emotions experience in during a ‘runners high’ are extremely similar to the emotions produce by the CB1 receptor agonists THC, found in the plant cannabis. This research strongly suggests that it is the endocannabinoids, rather that endorphins, that are important in emotional regulations in phenomenon such as the ‘runner high’.

Fear, anxiety and the endocannabinoid system
The endocannabinoid system has a significant effect on one particular aspect of human emotion. Studies have shown the system has been linked to the perception of the external and internal stimuli that influence behavioural outcomes. Specifically, the system seems to be related to emotional responses such as fear, anxiety and stress. It is also, however, related to coping, a means through which an individual is able to adapt to their environment (Lutz, Marsicano, Maldonado and Hillard, 2015).

In order to understand the endocannabinoids system in relation to emotional fear, it is important, to recognise the connection between fear and anxiety. Fear and anxiety are both cognitive and behavioural responses that signal danger, threat, or motivational conflict, in order to trigger an adaptive response in the body (Steimer, 2002). While fear is a focused response to known environmental danger, anxiety is a more general response to an unknown threat or internal conflict (Steimer, 2002). Although fear and anxiety may be separated in terms of emotional state, this does not mean that they do not cross over in terms of brain and behavioural response (Steimer, 2002). Arguably, anxiety may even be a more intense form of fear, providing an individual with an increased capacity to respond to fear (Steimer, 2002). Research, as explained in detail in the following section, shows the endocannabinoid system as one of the key regulators in anxiety behaviour. (Ruehle, Rey, Remmers and Lutz, 2012).

The endocannabinoids systems contributions to emotional processing
While the function of the endocannabinoid system appears to have positive effects on disorders such as anxiety, research has also shown the opposite effect. It has only been in recent years that the mechanisms of this complex system have been discovered (Lutz, Marsicaro, Maldono and Hillard, 2015). As such, only limited literature attempts to explain how the endocannabinoid system effects fear and anxiety in humans.

Positive effects of the Endocannabinoid System on Anxiety
The connection between the endocannabinoid system to anxiety behaviour has been linked with the recreational use of cannabis, its euphoric effects are seen to lower anxiety as well as seen to increase people’s sociability (Ruhle, Rey, Remmers and Lutz, 2012). When the majority of people are asked why they use cannabis, the majority of responses are found to be that it makes them feel relaxed (Lutz, Marsicaro, Maldono and Hillard, 2015). This strongly indicates that the endocannabinoid system in the body has an important role in the control of fear, stress and anxiety.

Some studies have shown that the endocannabinoid system appears to decrease anxiety like behaviour (Zanettini et al., 2011). Other research has shown that the endocannabinoid system is present in areas of the brain related to the regulation of the fear response (Lutz, Marsicaro, Maldono and Hillard, 2015). A study by Bossong et al (2013) showed how the endocannabinoid system is involved in emotional processing. The study involved participants being administered THC, a chemical found in the cannabis plant, in order to activate the endocannabinoid system. Results showed that when the endocannabinoid system was activated, participants showed a bias for the positive stimuli (happy faces) compared to the negative stimuli (fearful faces). These results suggested that the endocannabinoids system can reduce the perception of fear and anxiety in human studies. Similar results have been shown in animal studies where administration of THC to activate the endocannabinoid system has reduced anxiety like behaviour (Marco and Laviola, 2012). These studies indicate the positive effect of the endocannabinoid system on emotion processing, however, the following section explores studies that have outlined the negative effects of the endocannabinoid system on emotion processing.

Negative effects of the Endocannabinoid System and Anxiety
There have been some studies outlining how the endocannabinoid system, in relation to its CB1 receptors, actually contributes to the role of anxiety behaviour and fear response in mice. It has been shown that stress and anxiety related behaviour are consistent with the reduction of endocannabinoid levels in the brain regions that control anxiety and fear related behaviours (Lutz, Marsicaro, Maldono and Hillard, 2015). For example, mutant mice that lack the expression of the CB1 receptor have been found to exhibit anxiety-like symptoms, a sustained fear response, impaired stress coping, and impaired extinction of aversive memories (Ruehle, Rey, Remmers and Lutz, 2012). Significantly, such studies indicate that a disturbed endocannabinoid system can contribute to altered emotional behaviour that can, rather than alleviate, actually lead to the development of mood disorders such as anxiety and depression (Jenniches et al., 2016).

Conclusion
The endocannabinoid system appears to have a significant effect on how an individual comes to process their emotions. However, this chapter has demonstrated that the existing literature is limited, and perhaps more significantly, somewhat contradictory. Some research has found that the endocannabinoid system can be significant in guarding the fear response, anxiety and stress. Conversely, other research has demonstrated possibility that the same system can increase an individual’s fear response and impair the individual’s ability to cope with stress. Still, each study strengthens our understanding of this complex and important system and allows researchers a way forward in more clearly understanding both its role and impact in health and emotional processing (Lutz, Marsicano, Maldonado and Hillard, 2015).