Happiness has been viewed as a temporary emotional state (e.g., pleasure) and a relatively stable state of being happy (subjective happiness level). As previous studies demonstrated that individuals with high subjective happiness level rated their current affective states more positively when they experience positive events, these two aspects of happiness are interrelated. According to a recent neuroimaging study, the cytosine to thymine single-nucleotide polymorphism of the human cannabinoid receptor 1 gene is associated with sensitivity to positive emotional stimuli. Thus, we hypothesized that our genetic traits, such as the human cannabinoid receptor 1 genotypes, are closely related to the two aspects of happiness. In Experiment 1, 198 healthy volunteers were used to compare the subjective happiness level between cytosine allele carriers and thymine-thymine carriers of the human cannabinoid receptor 1 gene. In Experiment 2, we used positron emission tomography with 20 healthy participants to compare the brain responses to positive emotional stimuli of cytosine allele carriers to that of thymine-thymine carriers. Compared to thymine-thymine carriers, cytosine allele carriers have a higher subjective happiness level. Regression analysis indicated that the cytosine allele is significantly associated with subjective happiness level. The positive mood after watching a positive film was significantly higher for the cytosine allele carriers compared to the thymine-thymine carriers. Positive emotion-related brain region such as the medial prefrontal cortex was significantly activated when the cytosine allele carriers watched the positive film compared to the thymine-thymine carriers. Thus, the human cannabinoid receptor 1 genotypes are closely related to two aspects of happiness. Compared to thymine-thymine carriers, the cytosine allele carriers of the human cannabinoid receptor 1 gene, who are sensitive to positive emotional stimuli, exhibited greater magnitude positive emotions when they experienced positive events and had a higher subjective happiness level.

Introduction

Happiness is one of the most fundamental human goals, which has led researchers to examine the source of individual happiness. Happiness as a scientific construct has been viewed as a temporary emotional state (hedonia) and a relatively stable state of being happy (eudaimonia) [1]–[3]. Hedonia is usually experienced when we get the material objects and action opportunities we wish to possess or experience [4]–[8]. Therefore, at the least, hedonia corresponds to a psychological state of pleasure and is greatly influenced by life events or circumstances, such as health, human relationships, household income, and housing conditions [3]–[6]. In contrast, according to previous studies, there is a relatively stable state of being happy, which is related to the sum of one's recent levels of affect, one's satisfaction with life, and disposition/propensity [1]–[3]. Although eudaimonia may be more difficult to define scientifically, at the least, it corresponds to a subjective assessment of one's life lived well (e.g., subjective well-being or subjective happiness level) rather than to an emotional feeling [4]–[6], [9].

Although there is a conceptual distinction between pleasure and subjective happiness level, these two aspects of happiness are interrelated. According to previous studies, individuals with a high subjective happiness level rated their current affective states more positively when they experience positive events [4], [10], [11]. Conversely, consecutive experiences of positive events also increased their subjective happiness level [4], [7], [8]. Psychologists have established two psychological models that explain the relationship between these two aspects of happiness: a top-down and a bottom-up model [3], [4]. The top-down model assumes that individuals with a positive propensity, such as optimism, may evaluate their subjective happiness level and daily life events more positively than others who experience a similar number of positive life events [3], [4]. In contrast, the bottom-up model suggests that hedonic experience in each of the life domains (e.g., household income, housing conditions) influence subjective happiness level positively [3], [4]. Thus, the sum of positive life events may be important for constructing a subjective happiness level. However, previous epidemiological data have suggested a more complex interaction between these two happiness components; there is both top-down and bottom-up processes in happiness processing [3], [4]. Thus, researchers have proposed a third psychological model, the up-down model, which allows for bidirectional interactions between the two happiness components [3], [4].

Recent studies have suggested that the human endocannabinoid system is associated with positive emotional processing [12]. The endocannabinoid system refers to a group of neuromodulatory lipids [13]. The endocannabinoids such as anandamide and 2-arachidonoyl glycerol [14]–[16] bind to brain cannabinoid receptors, which are involved in several physiological processes including appetite, nociception, mood, and memory [13]. The function of cannabinoid receptor 1 (CB1) is well known. In the brain, CB1 inhibits γ-aminobutyric acid (GABA) transmission presynaptically [17], [18]. Recent studies have demonstrated a role for CB1 in modulating the brain reward system; in fact, CB1 activation may induce dopamine release in the striatum including the nucleus accumbens [19], [20]. The human CB1 receptor gene (CNR1) is located at chromosome 6q14–15 and there are multiple single-nucleotide polymorphisms (SNPs) in CNR1; however, its effects on CB1 receptor function are still unclear [21]. A recent study indicated that a cytosine to thymine (C/T) SNP of CNR1 (dbSNP number rs 806377), located in the untranslated exon 3, modulated striatal responses to happy faces [12]. The striatal activity in the cytosine (C) allele carriers was higher than that in individuals with a thymine-thymine (TT) genotype when happy faces were presented [12], suggesting that the C allele of the SNP of the CNR1 may enhance CB1 activity.

Based on these previous observations, our genetic traits, such as the CNR1 genotypes, are closely related to the two aspects of happiness. That is, compared to individuals with TT genotypes, C allele carriers of the SNP of CNR1, who are sensitive to positive emotional stimuli, may experience a higher magnitude pleasure response when they experience positive events and may have a higher subjective happiness level. In Experiment 1, to investigate the difference in subjective happiness level between C allele carriers and TT carriers, we assessed the subjective happiness level of 198 healthy participants. In Experiment 1, the participants were asked to evaluate their subjective happiness level using the Japanese version of the Subjective Happiness Scale (JSHS) [10], [11], [22], which included a subjective assessment of general happiness level and a subjective assessment of one's positive personal trait [9]. We predicted that subjective happiness level was higher in C allele carriers compared to TT carriers. Furthermore, in Experiment 2, we investigated the differences in brain responses and subjective ratings of temporal mood states between C allele carriers and TT carriers. To do so, we conducted a positron emission tomography (PET) study with an independent group of 20 healthy participants using the task of looking at one's favorite persons. Our previous PET study using the same task indicated that the act of looking at one's favorite persons evoked positive emotions [10]. Activation of the medial prefrontal cortex (mPFC) was positively correlated with the participants' self-rating of current positive mood states [10]. Thus, compared to TT carriers, we predicted that C allele carriers may evaluate their current mood state more positively and their mPFC may be activated to a greater degree when they looked at their favorite persons. Fortunately, the aim of this study was achieved through these experiments.