Euphoria ( // (listen)) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music, and dancing, can induce a state of euphoria. Euphoria is also a symptom of certain neurological or neuropsychiatric disorders, such as mania. Romantic love and components of the human sexual response cycle are also associated with the induction of euphoria. Certain drugs, many of which are addictive, can cause euphoria, which at least partially motivates their recreational use.
Hedonic hotspots – i.e., the pleasure centers of the brain – are functionally linked. Activation of one hotspot results in the recruitment of the others. Inhibition of one hotspot results in the blunting of the effects of activating another hotspot. Therefore, the simultaneous activation of every hedonic hotspot within the reward system is believed to be necessary for generating the sensation of an intense euphoria.
History of the term 
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. Sigmund Freud's 1884 monograph Über Coca described (his own) consumption of cocaine producing "the normal euphoria of a healthy person", while about 1890 the German neuropsychiatrist Carl Wernicke lectured about the "abnormal euphoria" in patients with mania.
A 1903 article in The Boston Daily Globe refers to euphoria as "pleasant excitement" and "the sense of ease and well-being". 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. Robert S. Woodworth's 1921 textbook Psychology: A study of mental life, describes euphoria as an organic state which is the opposite of fatigue, and "means about the same as feeling good."
In 1940 The Journal of Psychology defined euphoria as a "state of general well being ... and pleasantly toned feeling." 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. However, in 1957 British pharmacologist D. A. Cahal did not regard opioid euphoria as medically undesirable but an effect which "enhance[s] the value of a major analgesic." 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.
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.
Hedonic hotspots – i.e., the pleasure centers of the brain – are functionally linked. Activation of one hotspot results in the recruitment of the others. Inhibition of one hotspot results in the blunting of the effects of activating another hotspot. Therefore, the simultaneous activation of every hedonic hotspot within the reward system is believed to be necessary for generating the sensation of euphoria.
Many different types of stimuli can induce euphoria, including psychoactive drugs, natural rewards, and social activities. Affective disorders such as unipolar mania or bipolar disorder can involve euphoria as a symptom.
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. 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), β-endorphin (an endogenous opioid), and phenethylamine (a trace amine and amphetamine analog).
Euphoria can occur as a result of dancing to music, music-making, and listening to emotionally arousing music. Neuroimaging studies have demonstrated that the reward system plays a central role in mediating music-induced pleasure. 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). 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.
A clinical study from January 2019 that assessed the effect of a dopamine precursor (levodopa), dopamine antagonist (risperidone), and a placebo on reward responses to music – including the degree of pleasure experienced during musical chills, as measured by changes in electrodermal activity as well as subjective ratings – found that the manipulation of dopamine neurotransmission bidirectionally regulates pleasure cognition (specifically, the hedonic impact of music) in human subjects. This research suggests that increased dopamine neurotransmission acts as a sine qua non condition for pleasurable hedonic reactions to music in humans.
The various stages of copulation may also be described as inducing euphoria in some people. Various analysts have described either the entire act of copulation, the moments leading to orgasm, or the orgasm itself as the pinnacle of human pleasure or euphoria.
A euphoriant is a type of psychoactive drug which tends to induce euphoria. Most euphoriants are addictive drugs due to their reinforcing properties and ability to activate the brain's reward system.
Dopaminergic stimulants like amphetamine, methamphetamine, cocaine, MDMA, and methylphenidate are euphoriants. Nicotine is a parasympathetic stimulant that acts as a mild euphoriant in some people.
Chewing areca nut (seeds from the Areca catechu palm) with slaked lime (calcium hydroxide) – a common practice in South- and Southeast Asia – produces stimulant effects and euphoria. The major psychoactive ingredients – arecoline (a muscarinic receptor partial agonist) and arecaidine (a GABA reuptake inhibitor) – are responsible for the euphoric effect.
Some barbiturates and benzodiazepines may cause euphoria. Euphoriant effects are determined by the drug's speed of onset, increasing dose, and with intravenous administration. Barbiturates more likely to cause euphoria include amobarbital, secobarbital and pentobarbital. Benzodiazepines more likely to cause euphoria are flunitrazepam, alprazolam and clonazepam. Benzodiazepines also tend to enhance opioid-induced euphoria.
Pregabalin induces dose-dependent euphoria. Occurring in a small percentage of individuals at recommended doses, euphoria is increasingly frequent at supratherapeutic doses (or with intravenous- or nasal administration). At doses five times the maximum recommended, intense euphoria is reported. Another GABA analogue, gabapentin, may induce euphoria. Characterized as opioid-like but less intense, it may occur at supratherapeutic doses, or in combination with other drugs, such as opioids or alcohol. Ethosuximide and perampanel can also produce euphoria at therapeutic doses.
µ-Opioid receptor agonists are a set of euphoriants 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, a mood state opposite to euphoria that involves feelings of profound discontent.
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.
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.
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.
Euphoria may occur during auras of seizures typically originating in the temporal lobe, but affecting the anterior insular cortex. This euphoria is symptomatic of a rare syndrome called ecstatic seizures, often also involving mystical experiences. Euphoria (or more commonly dysphoria) may also occur in periods between epileptic seizures. This condition, interictal dysphoric disorder, is considered an atypical affective disorder. Persons who experience feelings of depression or anxiety between or before seizures occasionally experience euphoria afterwards.
Some persons experience euphoria in the prodrome – hours to days before the onset – of a migraine headache. Similarly, a euphoric state occurs in some persons following the migraine episode.
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.
- Bearn J, O'Brien M (2015). "Addicted to Euphoria": The History, Clinical Presentation, and Management of Party Drug Misuse. Int. Rev. Neurobiol. International Review of Neurobiology. 120. pp. 205–33. doi:10.1016/bs.irn.2015.02.005. ISBN 9780128029787. 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.
- 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
- "Key DSM-IV Mental Status Exam Phrases". Gateway Psychiatric Services. Mood and Affect. Archived from the original on 13 November 2013. Retrieved 17 February 2014.
- 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 2817271. 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.
- 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.
- 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. Archived (PDF) from the original on 13 August 2016. Retrieved 13 November 2016.
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).
- 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". Journal of Psychoactive Drugs. 44 (1): 38–55. doi:10.1080/02791072.2012.662112. PMC 4040958. 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).
- Jankowiak, William; Paladino, Thomas (2013). "Chapter 1. Desiring Sex, Longing for Love: A Tripartite Conundrum". In Jankowiak, William R. (ed.). 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).
- 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.
- Berridge KC, Kringelbach ML (May 2015). "Pleasure systems in the brain". Neuron. 86 (3): 646–664. doi:10.1016/j.neuron.2015.02.018. PMC 4425246. PMID 25950633.
- Castro, DC; Berridge, KC (24 October 2017). "Opioid and orexin hedonic hotspots in rat orbitofrontal cortex and insula". Proceedings of the National Academy of Sciences of the United States of America. 114 (43): E9125–E9134. doi:10.1073/pnas.1705753114. PMC 5664503. PMID 29073109.
- Kringelbach ML, Berridge KC (2012). "The Joyful Mind" (PDF). Scientific American. 307 (2): 44–45. Bibcode:2012SciAm.307b..40K. doi:10.1038/scientificamerican0812-40. PMID 22844850. Archived from the original (PDF) on 29 March 2017. Retrieved 17 January 2017.
So it makes sense that the real pleasure centers in the brain – those directly responsible for generating pleasurable sensations – turn out to lie within some of the structures previously identified as part of the reward circuit. One of these so-called hedonic hotspots lies in a subregion of the nucleus accumbens called the medial shell. A second is found within the ventral pallidum, a deep-seated structure near the base of the forebrain that receives most of its signals from the nucleus accumbens. ...
On the other hand, 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. Defection of any single component dampens the high.
Whether the pleasure circuit – and in particular, the ventral pallidum – works the same way in humans is unclear.
- Euphoria, Henry George Liddell, Robert Scott, A Greek-English Lexicon, at Perseus
- "Online Etymology Dictionary". Archived from the original on 21 December 2008. Retrieved 11 May 2008.
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- Laycock T (4 January 1862). The Medical Times & Gazette. London: John Churchill. pp. 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. pp. 500.
The morbid hopefulness of phthisis, physiologically termed euphoria, is seen more particularly 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.
- Freud S (1884). Über Coca., cited in, NIDA Research Monograph #13 Siegel RK (1977). "Chapter VI Cocaine: Recreational Use and Intoxication" (PDF). In Petersen RC, Stillman RC (eds.). NIDA Research Monograph #13. 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.
- Miller R, Dennison J (2015). "Lecture 31". An Outline of Psychiatry in Clinical Lectures: The Lectures of Carl Wernicke. 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.
- "Paris Doctors Say That Scorching is Like Effects of Drugs". Paris Herald. 1903. reprinted in The Boston Daily Globe, 13 May 1903. p. 6
- "Have You Euphoria?". Popular Science. 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?
- Woodworth, RS (1921). "Chapter VII: Emotion: Various organic states, and the conscious states that go with them". Psychology, a study of mental life. New York: Henry Holt and Company. pp. 119–120. Retrieved 16 April 2017 – via Internet archive.
Something was said before about "organic states", under the general head of tendencies to reaction. Fatigue was an example. Now we could include fatigue under the term, "stirred-up state of the organism"; at least, if not precisely "stirred-up", it is uneasy. It is a deviation from the normal or neutral state. Also, it is often a conscious state, as when we speak of the "tired feeling"; not a purely cognitive state, either not simply a recognition of the fact that we are fatigued but a state of disinclination to work any longer. Though fatigue is thus so much like an emotion that it fits under our definition, it is not called an emotion, but a sensation or complex of sensations....
Many other organic states are akin to emotion in the same way. The opposite of fatigue, the "warmed-up" condition, brought on by a certain amount of activity after rest, is a case in point. It is a deviation from the average or neutral condition, in the direction of greater readiness for activity. The warmed-up person feels ready for business, full of "ginger" or "pep" in short, full of life. The name "euphoria", which means about the same as "feeling good", is given to this condition. Drowsiness is another of these emotion-like states; but hunger and thirst are as typical examples as any.
- Bousfield WA (1940). "The Relation of the Euphoric Attitude to the Quality of Sleep". The Journal of Psychology. 9 (2): 393–401. 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.
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[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.
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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.
- 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.).
- "definition of euphoria in English". Oxford Dictionaries. Archived from the original on 28 July 2016. Retrieved 16 December 2016.
a feeling or state of intense excitement and happiness
• "definition of euphoria". Dictionary.com. Archived from the original on 29 December 2016. 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. Archived from the original on 2 July 2017. Retrieved 29 December 2016.
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
- Schultz W (2015). "Neuronal reward and decision signals: from theories to data". Physiological Reviews. 95 (3): 853–951. doi:10.1152/physrev.00023.2014. PMC 4491543. PMID 26109341.
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).
- 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 1724404. 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.
- 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 . ... 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 , 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 ; (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 ; and (4) exercise increases eCB plasma levels [64–67].
- 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. 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.
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The pharmacology of TAs might also contribute to a molecular understanding of the well-recognized antidepressant effect of physical exercise . 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 , which mirrors increased β-PEA synthesis in view of its limited endogenous pool half-life of ~30 s [18,55].
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It has also been suggested that the antidepressant effects of exercise are due to an exercise-induced elevation of [phenethylamine] .
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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.
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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 . 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 . ... 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 .
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.
- Zatorre RJ (March 2015). "Musical pleasure and reward: mechanisms and dysfunction". Ann. N. Y. Acad. Sci. 1337 (1): 202–211. Bibcode:2015NYASA1337..202Z. doi:10.1111/nyas.12677. PMID 25773636.
Most people derive pleasure from music. Neuroimaging studies show that the reward system of the human brain is central to this experience. Specifically, the dorsal and ventral striatum release dopamine when listening to pleasurable music, and activity in these structures also codes the reward value of musical excerpts. Moreover, the striatum interacts with cortical mechanisms involved in perception and valuation of musical stimuli. ... Development of a questionnaire for music reward experiences has allowed the identification of separable factors associated with musical pleasure, described as music-seeking, emotion-evocation, mood regulation, sensorimotor, and social factors. Applying this questionnaire to a large sample uncovered approximately 5% of the population with low sensitivity to musical reward in the absence of generalized anhedonia or depression. Further study of this group revealed that there are individuals who respond normally both behaviorally and psychophysiologically to rewards other than music (e.g., monetary value) but do not experience pleasure from music despite normal music perception ability and preserved ability to identify intended emotions in musical passages.
- Ferreri L, Mas-Herrero E, Zatorre RJ, Ripollés P, Gomez-Andres A, Alicart H, Olivé G, Marco-Pallarés J, Antonijoan RM, Valle M, Riba J, Rodriguez-Fornells A (January 2019). "Dopamine modulates the reward experiences elicited by music". Proceedings of the National Academy of Sciences of the United States of America. 116 (9): 3793–3798. doi:10.1073/pnas.1811878116. PMC 6397525. PMID 30670642. Lay summary – Neuroscience News (24 January 2019).
Listening to pleasurable music is often accompanied by measurable bodily reactions such as goose bumps or shivers down the spine, commonly called “chills” or “frissons.” ... Overall, our results straightforwardly revealed that pharmacological interventions bidirectionally modulated the reward responses elicited by music. In particular, we found that risperidone impaired participants’ ability to experience musical pleasure, whereas levodopa enhanced it. ... Here, in contrast, studying responses to abstract rewards in human subjects, we show that manipulation of dopaminergic transmission affects both the pleasure (i.e., amount of time reporting chills and emotional arousal measured by EDA) and the motivational components of musical reward (money willing to spend). These findings suggest that dopaminergic signaling is a sine qua non condition not only for motivational responses, as has been shown with primary and secondary rewards, but also for hedonic reactions to music. This result supports recent findings showing that dopamine also mediates the perceived pleasantness attained by other types of abstract rewards (37) and challenges previous findings in animal models on primary rewards, such as food (42, 43).
- Goupil L, Aucouturier JJ (February 2019). "Musical pleasure and musical emotions". Proceedings of the National Academy of Sciences of the United States of America. 116 (9): 3364–3366. doi:10.1073/pnas.1900369116. PMC 6397567. PMID 30770455.
In a pharmacological study published in PNAS, Ferreri et al. (1) present evidence that enhancing or inhibiting dopamine signaling using levodopa or risperidone modulates the pleasure experienced while listening to music. ... In a final salvo to establish not only the correlational but also the causal implication of dopamine in musical pleasure, the authors have turned to directly manipulating dopaminergic signaling in the striatum, first by applying excitatory and inhibitory transcranial magnetic stimulation over their participants’ left dorsolateral prefrontal cortex, a region known to modulate striatal function (5), and finally, in the current study, by administrating pharmaceutical agents able to alter dopamine synaptic availability (1), both of which influenced perceived pleasure, physiological measures of arousal, and the monetary value assigned to music in the predicted direction. ... While the question of the musical expression of emotion has a long history of investigation, including in PNAS (6), and the 1990s psychophysiological strand of research had already established that musical pleasure could activate the autonomic nervous system (7), the authors’ demonstration of the implication of the reward system in musical emotions was taken as inaugural proof that these were veridical emotions whose study has full legitimacy to inform the neurobiology of our everyday cognitive, social, and affective functions (8). Incidentally, this line of work, culminating in the article by Ferreri et al. (1), has plausibly done more to attract research funding for the field of music sciences than any other in this community.
The evidence of Ferreri et al. (1) provides the latest support for a compelling neurobiological model in which musical pleasure arises from the interaction of ancient reward/valuation systems (striatal–limbic–paralimbic) with more phylogenetically advanced perception/predictions systems (temporofrontal).
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The areca nut is the fourth most used drug after nicotine, alcohol, and caffeine. The effects are described as pleasurable and generally stimulating, inducing a sense of well-being, euphoria, heightened alertness, a warm sensation throughout the body, and an increased capacity to work.
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It is one of the most widely consumed addictive substances in the world after nicotine, ethanol and caffeine, and is consumed by approximately 10% of the world's population.... The users of areca nut believe that it is helpful for the digestive system and has mild euphoric effects. ...
The major parasympathetic and muscarinic effects of areca nut are due to arecoline.
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Pilocarpine, arecoline and muscarine are rather selective parasympathetic agents; i.e., their cholinomimetic activity is exerted primarily at muscarinic sites with minimal nicotinic effects.
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Previous investigations indicated that the arecaidine and guvacine isolated from the A. catechu are effective antagonists of GABA, with IC50 values 122712 μM and 871 μM, respectively (Johnston et al., 1975; Lodge et al., 1977).
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The lime in the betel quid [areca nut, lime and Piper betle leaves] causes hydrolysis of arecoline to arecailide, a central nervous stimulant, which accounts, together with the essential oil of the betel pepper, for the eucphoric effects of chewing betel quid.
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Exceeding the therapeutic doses, pregabalin is described as an 'ideal psychotropic drug' for recreational purposes, including alcohol/GHB/benzodiazepine-like effects, euphoria, entactogenic feelings, and dissociation. ...
Up to 1200mg ... euphoria ... Over 1500mg ... intense euphoria
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Pregabalin is, in some cases, used for recreational purposes and it has incurred attention among drug abusers for causing euphoric and dissociative effects when taken in doses exceeding normal therapeutic dosages or used by alternative routes of administration, such as nasal insufflation or venous injection.
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Several case studies mentioned experiencing euphoria after gabapentin misuse that was reminiscent of, but not as strong as, opioids. This feeling was achieved in combination with other drugs (e.g., buprenorphine/naloxone, methadone, baclofen, quetiapine, alcohol) as well as by using gabapentin alone, in dosages ranging from 1500–12000 mg, though only three articles give actual amounts misused.
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[S]eizures themselves may be stimulating or may induce euphoria. Dostoyevsky describes his seizure experience as follows 'the air was filled with a big noise and I tried to move. I felt the heaven was going down upon the earth and that it had engulfed me. I have really touched God. He came into me myself. Yes, God exists. I cried, and I don't remember anything else. You all, healthy people ... can't imagine the happiness we epileptics feel during the second before our fit ... I don't know if this felicity lasts for seconds, hours, or months but believe me, for all the joys that life may bring, I would not exchange this one'.[emphasis added]
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The classic expression of an ictal psychiatric symptom is an "aura," presenting as feelings of fear, sadness, or euphoria.
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Patients who are aware of increased depression or tension prior to generalized tonic-clonic or limbic seizures occasionally report a feeling of euphoria or release during the postictal period....
[P]atients with interictal or preictal depression can report relief or euphoria postictally, which is consistent with the well-known beneficial effect of electroconvulsive shock therapy (ECT). Postictal hypomania can occur, particularly after repeated limbic seizures.
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More than 70% of migraineurs experience premonitory phenomena hours to days before headache onset. Psychological symptoms include anxiety, depression, euphoria, irritability, restlessness, mental slowness, hyperactivity, fatigue, and drowsiness.[emphasis added]
Following the headache, the patient may have impaired concentration or feel tired, washed out, irritable, and listless. Some people, however, feel unusually refreshed or euphoric after an attack.
- Green MW, Colman R (2015). "6. Complicated Migraine". In Diamond S (ed.). Headache and Migraine Biology and Management. Academic Press. p. 51. ISBN 9780128011621.
[P]remonitory symptoms can occur hours to a day or more prior to a migraine attack (with or without aura). Prodromal symptoms include various combinations of fatigue, stiff neck, sensitivity to light or sounds, difficulty in concentrating, depression or euphoria, cold hands and feet, blurred vision, yawning, nausea and pallor.[emphasis added]
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Patients in the 'classic' subgroup (approximately 20% of all migrainers) experience a characteristic aura before the onset of migraine head pain.... A much larger proportion of patients describe prodromal symptoms, which may be visceral, such as diarrhea or nausea, but are more commonly alterations in mood or behavior. Food cravings, mild euphoria (conversely, yawning), and heightened sensory perception, particularly of smell, are surprisingly common....[emphasis added]
The attack often terminates with sleep.... Many patients report a 'hangover' on waking after a migraine, but others report complete freedom from symptoms and a sense of euphoria.
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