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Euphoria

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Not to be confused with Euphorbia. Euphoric redirects here. For other uses, see Euphoria (disambiguation) and Euphoric (disambiguation)..
Playing can induce an intense state of happiness and contentment.

Euphoria (pronunciation: Listeni/juːˈfɔːriə/) is an affective state in which a person experiences pleasure or excitement and intense feelings of well-being and happiness.[1][2] Certain drugs, many of which are addictive, can cause euphoria, which at least partially motivates their recreational use.[3] Similarly, certain natural rewards and social activities, such as aerobic exercise, laughter, listening to emotionally arousing music, music-making, and dancing, can induce a state of euphoria.[4][5] Euphoria is also a symptom of certain neurological or neuropsychiatric disorders, such as mania.[6] Romantic love and components of the human sexual response cycle are also associated with the induction of euphoria.[7][8][9]

According to Kent Berridge, an affective neuroscientist, intense euphoria occurs from the simultaneous activation of every hedonic hotspot within the brain's reward system.[10]

Definition[edit]

The word "euphoria" is derived from the Ancient Greek terms εὐφορία: εὖ eu meaning "well" and φέρω pherō meaning "to bear".[11][12] It is semantically opposite to dysphoria.

A 1706 English dictionary defined euphoria as "the well bearing of the Operation of a Medicine, i.e., when the patient finds himself eas'd or reliev'd by it".[13]

In the 1860s, the English physician Thomas Laycock described euphoria as the feeling of bodily well-being and hopefulness; he noted its misplaced presentation in the final stage of some terminal illnesses and attributed such euphoria to neurological dysfunction.[14] Sigmund Freud's 1884 monograph Über Coca described (his own) consumption of cocaine producing "the normal euphoria of a healthy person",[15] while about 1890 the German neuropsychiatrist Carl Wernicke lectured about the "abnormal euphoria" in patients with mania.[16]

A 1903 article in The Boston Daily Globe refers to euphoria as "pleasant excitement" and "the sense of ease and well-being,".[17] In 1920 Popular Science magazine described euphoria as "a high sounding name" meaning "feeling fit": normally making life worth living, motivating drug use, and ill formed in certain mental illnesses.[18] In 1940 The Journal of Psychology defined euphoria as a "state of general well being ... and pleasantly toned feeling."[19] A decade later, finding ordinary feelings of well being difficult to evaluate, American addiction researcher Harris Isbell redefined euphoria as behavioral changes and objective signs typical of morphine.[20] However, in 1957 British pharmacologist D. A. Cahal did not regard opioid euphoria as medically undesirable but an affect which "enhance[s] the value of a major analgesic."[21] The 1977 edition of A Concise Encyclopaedia of Psychiatry called euphoria "a mood of contentment and well-being," with pathologic associations when used in a psychiatric context. As a sign of cerebral disease, it was described as bland and out of context, representing an inability to experience negative emotion.[22]

In the 21st century, euphoria is generally defined as a state of great happiness, well-being and excitement, which may be normal, or abnormal and inappropriate when associated with psychoactive drugs, manic states, or brain disease or injury.[23]

Types[edit]

Many different types of stimuli can induce euphoria, including psychoactive drugs, natural rewards, and social activities.[1][24][5][6] Affective disorders such as unipolar mania or bipolar disorder can involve euphoria as a symptom.[6]

Exercise-induced[edit]

Runners can experience a euphoric state often called a "runner's high".

Continuous physical exercise, particularly aerobic exercise, can induce a state of euphoria; for example, distance running is often associated with a "runner's high", which is a pronounced state of exercise-induced euphoria.[25] Exercise is known to affect dopamine signaling in the nucleus accumbens, producing euphoria as a result, through increased biosynthesis of three particular neurochemicals: anandamide (an endocannabinoid),[26] β-endorphin (an endogenous opioid),[27] and phenethylamine (a trace amine and amphetamine analog).[25][28][29]

Music euphoria[edit]

Euphoria can occur as a result of dancing to music, music-making, and listening to emotionally arousing music.[5][30][31] Neuroimaging studies have demonstrated that the reward system plays a central role in mediating music-induced pleasure.[31][32] Pleasurable emotionally arousing music strongly increases dopamine neurotransmission in the dopaminergic pathways that project to the striatum (i.e., the mesolimbic pathway and nigrostriatal pathway).[30][31][32] Approximately 5% of the population experiences a phenomenon termed "musical anhedonia", in which individuals do not experience pleasure from listening to emotionally arousing music despite having the ability to perceive the intended emotion that is conveyed in passages of music.[32]

Drug-induced[edit]

A large dose of methamphetamine causes a drug-induced euphoria.[33]
"Euphoriant" redirects here.

A euphoriant is a type of psychoactive drug which tends to induce euphoria.[34][35] Most euphoriants are addictive drugs due to their reinforcing properties and ability to activate the brain's reward system.[6]

Stimulants[edit]

Dopaminergic stimulants like amphetamine, methamphetamine, cocaine, MDMA, and methylphenidate are euphoriants.[1][6] Nicotine is a parasympathetic stimulant that acts as a mild euphoriant in some people.[6]

Depressants[edit]

Certain depressants can produce euphoria; some of the euphoriant drugs in this class include drinking alcohol (i.e., ethanol) in moderate doses,[36][37] γ-hydroxybutyric acid,[1] and ketamine.[1] Euphoria has also been noted to occur in a very small percentage of individuals who used pregabalin in controlled trials as a treatment for neuropathic pain associated with diabetic peripheral neuropathy.[38]

Some barbiturates and benzodiazepines may cause euphoria. Euphoriant effects are determined by the drug's speed of onset,[39] increasing dose,[40] and with intravenous administration.[41] Barbiturates more likely to cause euphoria include amobarbital, secobarbital and pentobarbital.[42][43] Benzodiazepines more likely to cause euphoria are flunitrazepam, alprazolam and clonazepam.[39][44][45] Benzodiazepines also tend to enhance opioid-induced euphoria.[46]

Opioids[edit]

µ-Opioid receptor agonists are a set of euphoriants[6] that include drugs such as heroin, morphine, codeine, oxycodone, and fentanyl. By contrast, κ-opioid receptor agonists, like the endogenous neuropeptide dynorphin, are known to cause dysphoria,[6] a mood state opposite to euphoria that involves feelings of profound discontent.

Cannabinoids[edit]

Cannabinoid receptor 1 agonists are a group of euphoriants that includes certain plant-based cannabinoids (e.g., THC from the cannabis plant), endogenous cannabinoids (e.g., anandamide), and synthetic cannabinoids.[6]

Inhalants[edit]

Certain gases, like nitrous oxide (N2O, aka "laughing gas"), can induce euphoria when inhaled.[6][47]

Glucocorticoids[edit]

Acute exogenous glucocorticoid administration is known to produce euphoria, but this effect is not observed with long-term exposure.[6]

Asphyxia-induced[edit]

Asphyxiation initially produces an extreme feeling of euphoria[48] leading some people to intentionally induce temporary asphyxiation. Erotic asphyxiation typically employs strangulation to produce euphoria which enhances masturbation and orgasm.[49] The choking game, prevalent in adolescents, uses brief hypoxia in the brain to achieve euphoria.[50][51] Strangulation, or hyperventilation followed by breath holding are commonly used to achieve the effects. Accidental deaths occur from both practices but are often mislabeled as suicide.[52][53][54]

Neuropsychiatric[edit]

Mania[edit]

Euphoria is also strongly associated with both hypomania and mania, mental states characterized by a pathological heightening of mood, which may be either euphoric or irritable, in addition to other symptoms, such as pressured speech, flight of ideas, and grandiosity.[55][56]

Although hypomania and mania are syndromes with multiple etiologies (that is, ones that may arise from any number of conditions), they are most commonly seen in bipolar disorder, a psychiatric illness characterized by alternating periods of mania and depression.[55][56]

Epilepsy[edit]

Brief euphoria may occur immediately before or during epileptic seizures originating in the temporal lobes or insulae.[57][58] This euphoria is symptomatic of a rare syndrome called ecstatic seizures, itself closely associated with religious and mystical experiences which are often euphoric.[59] Euphoria (or more commonly dysphoria) may also occur in periods between such seizures. This condition, interictal dysphoric disorder, is considered an atypical affective disorder.[60]

Multiple sclerosis[edit]

Euphoria sometimes occurs in persons with multiple sclerosis as the illness progresses. This euphoria is part of a syndrome originally called euphoria sclerotica, which typically includes disinhibition and other symptoms of cognitive and behavioral dysfunction.[61][62][63]

See also[edit]

References[edit]

  1. ^ a b c d e Bearn J, O'Brien M (2015). ""Addicted to Euphoria": The History, Clinical Presentation, and Management of Party Drug Misuse". Int. Rev. Neurobiol. 120: 205–33. doi:10.1016/bs.irn.2015.02.005. PMID 26070759. Eating, drinking, sexual activity, and parenting invoke pleasure, an emotion that promotes repetition of these behaviors, are essential for survival. Euphoria, a feeling or state of intense excitement and happiness, is an amplification of pleasure, aspired to one's essential biological needs that are satisfied. People use party drugs as a shortcut to euphoria. Ecstasy (3,4-methylenedioxymethamphetamine), γ-hydroxybutyric acid, and ketamine fall under the umbrella of the term "party drugs," each with differing neuropharmacological and physiological actions. 
  2. ^ Alcaro A, Panksepp J (2011). "The SEEKING mind: primal neuro-affective substrates for appetitive incentive states and their pathological dynamics in addictions and depression". Neuroscience and Biobehavioral Reviews. 35 (9): 1805–1820. doi:10.1016/j.neubiorev.2011.03.002. PMID 21396397. Recent human data have demonstrated that the SEEKING brain circuitry, as predicted, is involved in the emergence of a characteristic appetitive affective state, which may be described as “enthusiastic positive excitement” or “euphoria” (Drevets et al., 2001; Volkow and Swanson, 2003) and that do not resemble any kind of sensory pleasure (Heath, 1996; Panksepp et al., 1985) ... However, in our view, cognitive processes, are only one “slice of the pie”, and gamma oscillations may be more globally viewed as the overall emotional–motivational neurodynamics through which the SEEKING disposition is expressed, accompanied by a feeling of excitement/eurphoria (not ‘pleasure’) that is evolutionarily designed to achieve a diversity of useful outcomes 
  3. ^ Johnson BA (2010). Addiction Medicine: Science and Practice. Springer Science & Business Media. p. 133. ISBN 9781441903389. It has been observed that drugs of abuse as diverse as alcohol, barbiturates, opiates, and psychomotor stimulants all share a profile of psychoactive effects characterized as euphoria. It is generally accepted that euphoria is at least a partial explanation why these drugs are abused. 
  4. ^ "Key DSM-IV Mental Status Exam Phrases". Gateway Psychiatric Services. Mood and Affect. Archived from the original on 2013-11-13. Retrieved 2014-02-17. 
  5. ^ a b c Cohen EE, Ejsmond-Frey R, Knight N, Dunbar RI (2010). "Rowers' high: behavioural synchrony is correlated with elevated pain thresholds". Biol. Lett. 6 (1): 106–8. doi:10.1098/rsbl.2009.0670. PMC 2817271Freely accessible. PMID 19755532. This heightened effect from synchronized activity may explain the sense of euphoria experienced during other social activities (such as laughter, music-making and dancing) that are involved in social bonding in humans and possibly other vertebrates. 
  6. ^ a b c d e f g h i j k Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY, eds. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 191, 350–351, 367–368, 371–375. ISBN 9780071481274. Changes in appetite and energy may reflect abnormalities in various hypothalamic nuclei. Depressed mood and anhedonia (lack of interest in pleasurable activities) in depressed individuals, and euphoria and increased involvement in goal-directed activities in patients, who experience mania, may reflect opposing abnormalities in the nucleus accumbens, medial prefrontal cortex, amygdala, or other structures. ... Although short-term administration of glucocorticoids often produces euphoria and increased energy, the impact of long-lasting increases in endogenous glucocorticoids produced during depression can involve complex adaptations such as those that occur in Cushing syndrome (Chapter 10). ... Exposure to addictive chemicals not only produces extreme euphoric states that may initially motivate drug use, but also causes equally extreme adaptations in reinforcement mechanisms and motivated behavior that eventually lead to compulsive use. Accordingly, the evolutionary design of human and animal brains that has helped to promote our survival also has made us vulnerable to addiction. 
  7. ^ Georgiadis JR, Kringelbach ML (July 2012). "The human sexual response cycle: brain imaging evidence linking sex to other pleasures" (PDF). Prog. Neurobiol. 98 (1): 49–81. doi:10.1016/j.pneurobio.2012.05.004. PMID 22609047. Strong feelings of pleasure and euphoria, as well as marked alterations in cognitive processing, self-referential thought, and physiological arousal are defining features of sexual consummation, especially during orgasm (Mah and Binik, 2001). 
  8. ^ Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, Oscar-Berman M, Gold M (March 2012). "Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms". J. Psychoactive Drugs. 44 (1): 38–55. doi:10.1080/02791072.2012.662112. PMC 4040958Freely accessible. PMID 22641964. Early-stage romantic love can induce euphoria, is a cross-cultural phenomenon, and is possibly a developed form of a mammalian drive to pursue preferred mates. ... Under normal conditions, it is not surprising that sexual activity is physiologically regulated by the reward circuitry of the brain, specifically by dopaminergic pathways (see Figure 1). Moreover, the early stages of a new, romantic relationship can be a powerful and absorbing experience. Individuals in new romantic relationships report feeling euphoric and energetic. They also become emotionally dependent on, desire closeness with, and have highly focused attention on their partner (Reynaud et al. 2010; Young 2009). Human neuroimaging studies have shown that feelings experienced during the early stages of a romantic relationship are associated with neural activations in several reward-system and affect-processing regions of the brain (Young 2009; Aron et al. 2005; Bartels & Zeki 2000; Mashek, Aron & Fisher 2000). 
  9. ^ Jankowiak, William; Paladino, Thomas (2013). "Chapter 1. Desiring Sex, Longing for Love: A Tripartite Conundrum". In Jankowiak, William R. Intimacies: Love and Sex Across Cultures. Columbia University Press. p. 13. ISBN 9780231508766. These emotional states may also be manifested behaviorally as "labile psychophysical responses to the loved person, including exhilaration, euphoria, buoyancy, spiritual feelings, increased energy, sleeplessness, loss of appetite, shyness, awkwardness ... in the presence of the loved person" (Fisher 1998:32). The presence of similar neurological mechanisms and brain patterns may account for the ability to readily identify when someone is romantically involved or erotically excited (Fisher 1998:32; Fisher 1995). 
  10. ^ Kringelbach ML, Berridge KC (2013). "The Joyful Mind". From Abuse to Recovery: Understanding Addiction. Macmillan. pp. 199–207. ISBN 9781466842557. Retrieved 8 April 2016. Intense euphoria is harder to come by than everyday pleasures. The reason may be that strong enhancement of pleasure—like the chemically induced pleasure bump we produced in lab animals—seems to require activation of the entire network at once. 
  11. ^ Euphoria, Henry George Liddell, Robert Scott, A Greek-English Lexicon, at Perseus
  12. ^ Online Etymology Dictionary
  13. ^ Kersey J, Phillips E (1706). The new world of words: or, Universal English dictionary. London: Printed for J. Phillips. pp. EU–EU. 
  14. ^ Laycock T (4 January 1862). The Medical Times & Gazette. London: John Churchill. p. 1. Not unfrequently, indeed, the appearance of the patient is more diagnostic than his feelings. This is the case in some very grave diseases, in which that portion of the nervous system which subserves to the feeling of bodily well-being,—termed, in psychological phrase, euphoria—is morbidly modified as to function. 
      Laycock T (17 May 1864). The Medical Times & Gazette. London: John Churchill. p. 500. The morbid hopefulness of phthisis, physiologically termed euphoria, is seen more particularily in this class of patients. I have often called attention to it at the bedside, and shown that it ushers in the last stage. It is really a disease of the nervous system of a low type, a sort of insanity, and is of the worst significance. 
  15. ^ Freud S (1884). Über Coca. , cited in, NIDA Research Monograph #13 Siegel RK (1977). "Chapter VI Cocaine: Recreational Use and Intoxication". In Petersen RC, Stillman RC. NIDA Research Monograph #13 (PDF). U.S. Government Printing Office. p. 130. The psychic effect (of cocaine) consists of exhilaration and lasting euphoria, which does not differ in any way from the normal euphoria of a healthy person.... One senses an increase of self-control and feels more vigorous and more capable of work; on the other hand, if one works, one misses the heightening of the mental powers which alcohol, tea, or coffee induce. One is simply normal, and soon finds it difficult to believe that one is under the influence of any drug at all. 
  16. ^ Miller R, Dennison J (2015). "Lecture 31". An Outline of Psychiatry in Clinical Lectures: The Lectures of Carl Wernicke Check |url= value (help). Springer. p. 216. ISBN 9783319180519 – via Google books. [R]ational judgment of actual ability is lost, and a feeling of increased capacity arises, … it induces feelings of happiness, to the point of abnormal euphoria; but here too, assuming that some degree of psychic ability prevails, self-awareness of the change in personality may be enabled—an autopsychic paraesthesia in the above sense. Consequently, the Affective state of abnormal euphoria which determines the clinical picture often shows up as transitions to autopsychic disarray. 
  17. ^ "Paris Doctors Say That Scorching is Like Effects of Drugs". Paris Herald. 1903 – via newspaperarchive.com.  reprinted in The Boston Daily Globe, 13 May 1903. p. 6 free to read
  18. ^ "Have You Euphoria?". Popular Science. New York: Modern Publishing Company. 97 (6): 79. December 1920 – via Google books. It takes a doctor to give a high-sounding name to a well known phenomenon. "Euphoria" means "feeling fit." It is as much a physiological fact as scarlet fever.
         Nature makes it worth while to be alive simply through euphoria. The joy of making a good tennis stroke, the delight that a Woodsman gets in the open air, the artist’s rhapsody—all are due to euphoria. Why do we drink alcohol—when we can get it or smoke tobacco? To affect euphoria. When a lunatic thinks that he is Napoleon and demands the homage due an emperor; he has euphoria in its worst form.
         Too little is known about euphoria. Since it can be affected by drugs and chemicals, who knows but it may have its seat in some gland?
      open access publication - free to read
  19. ^ Bousfield WA (1940). "The Relation of the Euphoric Attitude to the Quality of Sleep". The Journal of Psychology. 9 (2): 393. doi:10.1080/00223980.1940.9917707. Euphoria is a term aptly denoting the state of general well being, and while it involves a relatively enduring and pleasantly toned feeling, its psychological significance derives primarily from its being a semi-emotional attitude of considerable determining power. 
  20. ^ Keats AS, Beecher HK (1952). "Analgesic activity and toxic effects of acetylmethadol isomers in man". The Journal of Pharmacology and Experimental Therapeutics. 105 (2): 210–215. ISSN 0022-3565. PMID 14928223. Retrieved 17 September 2016. [Footnote 3] Since matters of some interest hang upon the definition of 'euphoria', direct enquiry of Dr. Isbell brought the following comment (letter of November 1, 1951). 'I think it would be wise to exercise a certain degree of care in our use of the term "euphoria". We use it here in the sense of a train of effects similar to those seen after the administration of morphine. These effects include changes in behavior and objective signs, such as constriction of the pupil, depression of the respiratory rate and volume, drop in rectal temperature, etc. We do not use it in the sense of "feeling of well-being", as this is something that I have been utterly unable to evaluate.' The present authors prefer to limit the definition of euphoria to 'a sense of well-being'. 
      Isbell H, Vogel VH (1949). "The addiction liability of methadon (amidone, dolophine, 10820) and its use in the treatment of the morphine abstinence syndrome". The American Journal of Psychiatry. 105 (12): 909–914. doi:10.1176/ajp.105.12.909. ISSN 0002-953X. PMID 18127077. Retrieved 17 September 2016. 
      Jaffe JH, Jaffe FK (1989). "4. Historical Perspectives on the Use of Subjective Effects Measures in Assessing the Abuse Potential of Drugs". In Fischman MW, Mello NK. Testing for Abuse Liability of Drugs in Humans. National Institute on Drug Abuse Research Monograph Series. 92. Rockville, MD: National Institute on Drug Abuse. 
  21. ^ Cahal DA (1957). "Analgesic activity of dipipanone hydrochloride in student volunteers" (PDF). British Journal of Pharmacology and Chemotherapy. 12 (1): 97–99. doi:10.1111/j.1476-5381.1957.tb01368.x. ISSN 0366-0826. PMC 1509651Freely accessible. PMID 13413158. Retrieved 17 September 2016. Not all of these effects can be regarded as undesirable. Drowsiness, euphoria, sleep, and 'detachment,' for instance, are effects which enhance the value of a major analgesic. 
  22. ^ Leigh D, Pare CM, Marks J (1977). A Concise Encyclopaedia of Psychiatry. Springer Science & Business Media. p. 152. ISBN 9789401159135 – via Google books. A mood of contentment and wellbeing. Euphoria in psychiatric terms always has a pathological connotation and is often an important early sign of organic cerebral disease. It differs from elation in subtle but important ways. It has no infectious quality and no element of gaiety, for its bland contentment is based on lack of awareness and inability to experience sadness or anxiety rather than on anything positive.
         It may be seen in any condition involving extensive cerebral damage, particularly if the frontal lobes are involved. It occurs sooner or later in senile and arteriosclerotic dementias (q.v.), in disseminated sclerosis and in Huntington’s chorea (q.v.) and is often seen also after severe head injury and old-fashioned forms of leucotomy (q.v.). Euphoria is sometimes seen in Addison's disease (q.v.).
     
  23. ^ "definition of euphoria in English". Oxford Dictionaries. Retrieved 16 December 2016. a feeling or state of intense excitement and happiness 
      "definition of euphoria". Dictionary.com. Retrieved 16 December 2016. a state of intense happiness and self-confidence
         (psychology) a feeling of happiness, confidence, or well-being sometimes exaggerated in pathological states as mania
     
      Sadock B, Sadock V (2009). Kaplan and Sadock's Comprehensive Textbook of Psychiatry (9th ed.). pp. 411–412, 923. Refers to a persistent and unrealistic sense of well-being, without the increased mental or motor rate of mania.
         Exaggerated feeling of well-being that is inappropriate to real events. Can occur with drugs such as opiates, amphetamines, and alcohol.
     
      Mosby's Medical Dictionary (8th ed.). 2009. 1. a feeling or state of well-being or elation.
         2. an exaggerated or abnormal sense of physical and emotional well-being not based on reality or truth, disproportionate to its cause, and inappropriate to the situation, as commonly seen in the manic stage of bipolar disorder, some forms of schizophrenia, organic mental disorders, and toxic and drug-induced states
     
  24. ^ Schultz W (2015). "Neuronal reward and decision signals: from theories to data" (PDF). Physiological Reviews. 95 (3): 853–951. doi:10.1152/physrev.00023.2014. Archived from the original (PDF) on 6 September 2015. Retrieved 24 September 2015. The feeling of high that is experienced by sports people during running or swimming, the lust evoked by encountering a ready mating partner, a sexual orgasm, the euphoria reported by drug users, and the parental affection to babies constitute different forms (qualities) rather than degrees of pleasure (quantities). 
  25. ^ a b Szabo A, Billett E, Turner J (2001). "Phenylethylamine, a possible link to the antidepressant effects of exercise?". Br J Sports Med. 35 (5): 342–343. doi:10.1136/bjsm.35.5.342. PMC 1724404Freely accessible. PMID 11579070. The 24 hour mean urinary concentration of phenylacetic acid was increased by 77% after exercise. ... These results show substantial increases in urinary phenylacetic acid levels 24 hours after moderate to high intensity aerobic exercise. As phenylacetic acid reflects phenylethylamine levels3 , and the latter has antidepressant effects, the antidepressant effects of exercise appear to be linked to increased phenylethylamine concentrations. Furthermore, considering the structural and pharmacological analogy between amphetamines and phenylethylamine, it is conceivable that phenylethylamine plays a role in the commonly reported "runners high" thought to be linked to cerebral β-endorphin activity. The substantial increase in phenylacetic acid excretion in this study implies that phenylethylamine levels are affected by exercise. ... A 30 minute bout of moderate to high intensity aerobic exercise increases phenylacetic acid levels in healthy regularly exercising men. The findings may be linked to the antidepressant effects of exercise. 
  26. ^ Tantimonaco M, Ceci R, Sabatini S, Catani MV, Rossi A, Gasperi V, Maccarrone M (2014). "Physical activity and the endocannabinoid system: an overview". Cell. Mol. Life Sci. 71 (14): 2681–2698. doi:10.1007/s00018-014-1575-6. PMID 24526057. The traditional view that PA engages the monoaminergic and endorphinergic systems has been challenged by the discovery of the endocannabinoid system (ECS), composed of endogenous lipids, their target receptors, and metabolic enzymes. Indeed, direct and indirect evidence suggests that the ECS might mediate some of the PA-triggered effects throughout the body. ... the evidence that PA induces some of the psychotropic effects elicited by the Cannabis sativa active ingredient Δ9-tetrahydrocannabinol (Δ9-THC, Fig. 1), like bliss, euphoria, and peacefulness, strengthened the hypothesis that endocannabinoids (eCBs) might mediate, at least in part, the central and peripheral effects of exercise [14]. ... To our knowledge, the first experimental study aimed at investigating the influence of PA on ECS in humans was carried out in 2003 by Sparling and coworkers [63], who showed increased plasma AEA content after 45 min of moderate intensity exercise on a treadmill or cycle ergometer. Since then, other human studies have shown increased blood concentrations of AEA ... A dependence of the increase of AEA concentration on exercise intensity has also been documented. Plasma levels of AEA significantly increased upon 30 min of moderate exercise (heart rate of 72 and 83 %), but not at lower and significantly higher exercise intensities, where the age-adjusted maximal heart rate was 44 and 92 %, respectively ... Several experimental data support the hypothesis that ECS might, at least in part, explain PA effects on brain functions, because: (1) CB1 is the most abundant GPCR in the brain participating in neuronal plasticity [18]; (2) eCBs are involved in several brain responses that greatly overlap with the positive effects of exercise; (3) eCBs are able to cross the blood–brain barrier [95]; and (4) exercise increases eCB plasma levels [64–67]. 
  27. ^ Dinas PC, Koutedakis Y, Flouris AD (2011). "Effects of exercise and physical activity on depression". Ir J Med Sci. 180 (2): 319–325. doi:10.1007/s11845-010-0633-9. PMID 21076975. According to the 'endorphins hypothesis', exercise augments the secretion of endogenous opioid peptides in the brain, reducing pain and causing general euphoria. ... Based upon a large effect size, the results confirmed the endorphins hypothesis demonstrating that exercise leads to an increased secretion of endorphins which, in turn, improved mood states.
    β-Endorphin, an endogenous μ-opioid receptor selective ligand, has received much attention in the literature linking endorphins and depression or mood states. ... exercise of sufficient intensity and duration can increase circulating β-endorphin levels. ... Moreover, a recent study demonstrated that exercise and physical activity increased β-endorphin levels in plasma with positive effects on mood. Interestingly, the researchers reported that, independently of sex and age, dynamic anaerobic exercises increased β-endorphin, while resistance and aerobic exercises seem to only have small effects on β-endorphins. ... The results showed that mood tends to be higher in a day an individual exercises as well as that daily activity and exercise overall are strongly linked with mood states. In line with these findings, a recent study showed that exercise significantly improved mood states in non-exercises, recreational exercisers, as well as marathon runners. More importantly, the effects of exercise on mood were twofold in recreational exercisers and marathon runners.
     
  28. ^ Lindemann L, Hoener MC (2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375. The pharmacology of TAs might also contribute to a molecular understanding of the well-recognized antidepressant effect of physical exercise [51]. In addition to the various beneficial effects for brain function mainly attributed to an upregulation of peptide growth factors [52,53], exercise induces a rapidly enhanced excretion of the main β-PEA metabolite β-phenylacetic acid (b-PAA) by on average 77%, compared with resting control subjects [54], which mirrors increased β-PEA synthesis in view of its limited endogenous pool half-life of ~30 s [18,55]. 
  29. ^ Berry MD (2007). "The potential of trace amines and their receptors for treating neurological and psychiatric diseases". Rev Recent Clin Trials. 2 (1): 3–19. doi:10.2174/157488707779318107. PMID 18473983. It has also been suggested that the antidepressant effects of exercise are due to an exercise-induced elevation of [phenethylamine] [151]. 
  30. ^ a b Salimpoor VN, Benovoy M, Larcher K, Dagher A, Zatorre RJ (2011). "Anatomically distinct dopamine release during anticipation and experience of peak emotion to music". Nat. Neurosci. 14 (2): 257–262. doi:10.1038/nn.2726. PMID 21217764. Music, an abstract stimulus, can arouse feelings of euphoria and craving, similar to tangible rewards that involve the striatal dopaminergic system. ... the caudate was more involved during the anticipation and the nucleus accumbens was more involved during the experience of peak emotional responses to music. ... Notably, the anticipation of an abstract reward can result in dopamine release in an anatomical pathway distinct from that associated with the peak pleasure itself. 
  31. ^ a b c Mavridis IN (March 2015). "Music and the nucleus accumbens". Surg Radiol Anat. 37 (2): 121–125. doi:10.1007/s00276-014-1360-0. PMID 25102783. The functional connectivity between brain regions mediating reward, autonomic and cognitive processing provides insight into understanding why listening to music is one of the most rewarding and pleasurable human experiences. Musical stimuli can significantly increase extracellular DA levels in the NA. NA DA and serotonin were found significantly higher in animals exposed to music. Finally, passive listening to unfamiliar although liked music showed activations in the NA. ... Music can arouse feelings of euphoria and craving, similar to tangible rewards that involve the striatal DAergic system [16]. Reward value for music can be coded by activity levels in the NA, whose functional connectivity with auditory and frontal areas increases as a function of increasing musical reward [19]. ... Listening to pleasant music induces a strong response and significant activation of the VTA-mediated interaction of the NA with the hypothalamus, insula and orbitofrontal cortex [1].
    Conclusions
    Listening to music strongly modulates activity in a network of mesolimbic structures involved in reward processing including the NA. Music, acting as a positive pleasant emotion, increases NA DAergic activity. Specifically the NA is more involved during the experience of peak emotional responses to music. Reward value of music can be predicted by increased functional connectivity of auditory cortices, amygdala and ventromedial prefrontal regions with the NA. Further research is needed to improve our understanding of the NA role in the influence of music in our lives.
     
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    Heightened well-being. One of the first mentioned features, in all patients, was the 'very pleasant filling of the whole body with a wave of warmth or well-being.' ...
    – '[…] a halo, something pleasant which fills my inner body, wrapping me, with a rapid crescendo. It is a well-being inside, a sensation of velvet, as if I were sheltered from anything negative.... Something has taken possession of my body, to feel really good…' ... – 'the sensation was a feeling of pleasure. I felt intensely well in my body.' – 'My inner body rises from an unalterable bliss.'
    Intense serenity and bliss. There is a feeling of great serenity and peace.
    – 'This led to a feeling of complete serenity, total peace, no worries; it felt beautiful, everything was great.' – 'The immense joy that fills me is above physical sensations.'
    Feeling of overload. Some patients reported that this feeling was evolving to a very strong intensity, causing a feeling of overload....
    – 'The sensation is certainly more intense than could be achieved with any drug.' – 'The pleasure goes crescendo until it reaches a peak.'
    Mystic/religious experience. Some patients reported strong religious or religious-like feelings:
    – 'Maybe the closest sensation that I know would be an orgasm, but what I felt was not at all sexual. I have no religious feeling, but it was almost religious.' – 'a wellbeing of almost spiritual consonance' – 'These experiences brought me confidence. They confirm that there is something that surpasses us.' – 'It is a big happening in your life to have these seizures. Thanks to these experiences, I do not fear death anymore. I see the world differently.' 
     
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      Filley CM, Filley CM (2011). Neurobehavioral Anatomy, Third Edition. University Press of Colorado. p. 167. ISBN 9781607320999 – via Google books. Rare cases of ictal euphoria have also been reported , and it has been suggested that Fyodor Dostoyevsky may have experienced this emotion as ecstatic seizures... 
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