Zaburzenie używania alkoholu
Patofizjologia i mechanizm

Zaburzenie używania alkoholu (ZUA) to przewlekłe zaburzenie mózgu charakteryzujące się kompulsywnym spożywaniem alkoholu, utratą kontroli nad jego używaniem oraz negatywnymi emocjami w przypadku abstynencji. Patofizjologia ZUA obejmuje dysregulację wielu systemów neuroprzekaźników, w tym opioidowego, GABA, glutaminianowego, serotoninowego i dopaminowego. Przewlekłe spożycie alkoholu prowadzi do neuroadaptacji, takich jak down-regulacja receptorów GABA i up-regulacja receptorów NMDA, co skutkuje zwiększoną pobudliwością OUN po odstawieniu. ZUA wiąże się z dysfunkcją obwodów motywacyjnych i wykonawczych, zwłaszcza w korze oczodołowo-czołowej i zakręcie obręczy, co prowadzi do przejścia od impulsowego do kompulsywnego picia. Genetyka odgrywa około 50% roli w podatności na ZUA, a przewlekłe spożycie alkoholu powoduje zmniejszenie objętości mózgu, szczególnie płatów czołowych, oraz zaburzenia neurogenezy w hipokampie. Metabolizm etanolu w wątrobie generuje toksyczny acetaldehyd i wolne rodniki, co przyczynia się do choroby wątroby związanej z alkoholem (ALD) oraz dysbiozy jelitowej, nasilającej stan zapalny i progresję uszkodzeń wątroby.

  1. Mechanizmy patogenetyczne zaburzenia używania alkoholu
    1. Neurobiologiczne podstawy zaburzenia używania alkoholu
    2. Wpływ alkoholu na neuroprzekaźniki
    3. Fazy rozwoju uzależnienia od alkoholu
    4. Genetyczne podłoże zaburzenia używania alkoholu
    5. Strukturalne i funkcjonalne zmiany w mózgu
  2. Mechanizmy metaboliczne w zaburzeniu używania alkoholu
    1. Metabolizm alkoholu i jego konsekwencje
    2. Stres oksydacyjny i stan zapalny
    3. Oś jelitowo-wątrobowa w patogenezie ZUA
  3. Mechanizmy leczenia farmakologicznego zaburzenia używania alkoholu
    1. Leki zatwierdzone w leczeniu ZUA
    2. Leki eksperymentalne i stosowane poza wskazaniami
    3. Strategie farmakoterapeutyczne
  4. Współwystępowanie z innymi zaburzeniami psychicznymi
    1. Zaburzenia lękowe i afektywne
    2. Mechanizmy radzenia sobie a zaburzenie używania alkoholu
    3. Zespół kaca i jego patogeneza
  5. Zaburzenia funkcji poznawczych w ZUA
    1. Funkcje wykonawcze i elastyczność poznawcza
    2. Objawy odstawienia alkoholu i zmiany neurobiologiczne
    3. Dysregulacja obwodów neuronalnych
    4. Kolejne rozdziały

Mechanizmy patogenetyczne zaburzenia używania alkoholu

Zaburzenie używania alkoholu (ZUA) jest przewlekłym zaburzeniem mózgu charakteryzującym się kompulsywnym spożywaniem alkoholu, utratą kontroli nad jego używaniem oraz występowaniem negatywnych emocji (np. stresu i gniewu) w przypadku braku dostępu do alkoholu.1 W przeciwieństwie do osób pijących towarzysko, pacjenci z ZUA mają trudności z kontrolowaniem lub ograniczaniem ilości wypijanego alkoholu, często doświadczają intensywnych głodów alkoholowych i zwykle nie są w stanie przewidzieć, ile wypiją i kiedy przestaną.2 Etiologia i patofizjologia ZUA ma złożony charakter i wynika z interakcji czynników genetycznych, wpływów rodzicielskich, norm społecznych, farmakologii oraz współwystępujących zaburzeń psychicznych.3

Neurobiologiczne podstawy zaburzenia używania alkoholu

ZUA rozwija się, gdy osoba pije tak dużo, że obwody nagrody w mózgu ulegają zmianie, tworząc asocjację między spożywaniem alkoholu a przyjemnością. Ta zmiana powoduje, że dana osoba pije więcej, nawet gdy uczucie przyjemności zanika.4 Alkohol wpływa na praktycznie każdy system narządów w organizmie, a w wysokich dawkach może powodować śpiączkę i śmierć. Oddziałuje na kilka systemów neuroprzekaźników w mózgu, w tym na opioidy endogenne, GABA, glutaminian, serotoninę i dopaminę.5

Zwiększony poziom opioidów endogennych pomaga wyjaśnić efekt euforyczny alkoholu, podczas gdy jego wpływ na GABA powoduje działanie przeciwlękowe i sedatywne.6 Alkohol hamuje również receptor glutaminianowy. Długotrwałe spożywanie prowadzi do syntezy większej liczby receptorów glutaminianowych. Gdy alkohol jest odstawiony, ośrodkowy układ nerwowy doświadcza zwiększonej pobudliwości.7 Receptory opioidowe są zwiększone w mózgach pacjentów niedawno abstynujących od alkoholu, a ich liczba koreluje z głodem alkoholowym.8

Wpływ alkoholu na neuroprzekaźniki

Etanol działa na wiele systemów neuroreceptorów w mózgu. Przewlekłe używanie alkoholu nie wpływa tylko na jeden neuroprzekaźnik, ale na prawie wszystkie systemy neuroprzekaźnictwa.9 Alkohol jest zarówno agonistą receptora GABA, jak i antagonistą receptora NMDA glutaminianowego.10 Po przewlekłej ekspozycji na alkohol, typowo występuje zjawisko down-regulacji systemu GABA-ergicznego i up-regulacji receptorów NMDA glutaminianergicznych.11 Normalizacja tej nierównowagi może być skuteczna w leczeniu uzależnienia od alkoholu.12

Spożycie alkoholu prowadzi do wzrostu poziomów dopaminy w ośrodkach nagrody w mózgu, co przyczynia się do uczucia przyjemności i euforii często doświadczanych podczas picia.13 Z czasem mózg może zacząć kojarzyć alkohol z tymi pozytywnymi odczuciami, potencjalnie prowadząc do uzależnienia.14 Badania neuroobrazowe pokazują, że osoby z ZUA mają zwiększone wydzielanie dopaminy i aktywację mózgu w regionach związanych z przetwarzaniem nagrody (np. w obszarze zwanym brzusznym prążkowiem) po ekspozycji na wskazówki związane z alkoholem.15

Fazy rozwoju uzależnienia od alkoholu

Uzależnienie to dynamiczna dysregulacja obwodów motywacyjnych w mózgu spowodowana przesadnym znaczeniem bodźców i tworzeniem nawyków, deficytami w funkcji nagrody prowadzącymi do zwiększonego stresu oraz zaburzoną funkcją wykonawczą.16 Podczas rozwoju uzależnienia, jednostki przechodzą od impulsywnego do kompulsywnego spożywania substancji, czemu towarzyszy przejście od pozytywnego do negatywnego wzmocnienia.17

Badania neuroobrazowe często wskazują na korę oczodołowo-czołową i przednią część zakrętu obręczy w późniejszych stadiach uzależnienia, pokazując aktywację tych regionów mózgu podczas intoksykacji, głodu i objadania się oraz ich inaktywację podczas odstawienia.18 Faza objadania się/intoksykacji uzależnienia skutkuje dysregulacją obwodów mózgowych zaangażowanych w zdolność mediowania wartości bodźców, prowadząc do rozwoju nadmiernych nawyków spożywania substancji z powodu zwiększenia transmisji dopaminergicznej podczas przyjmowania substancji.19

Faza odstawienia/negatywnego afektu charakteryzuje się zwiększeniem reakcji stresowych i lękowych wynikających z odstawienia substancji i może obejmować ból emocjonny, złe samopoczucie, dysforię i utratę motywacji do naturalnych nagród.20 Faza zaabsorbowania/antycypacji uzależnienia polega na powrocie do zachowań poszukiwania substancji po okresie abstynencji.21

Genetyczne podłoże zaburzenia używania alkoholu

Uzależnienie od alkoholu jest zaburzeniem wieloczynnikowym, które przebiega transgeneracyjnie.22 Genetyka ma ważny i krytyczny wkład w rozwój nadużywania alkoholu.23 Według badań bliźniąt i adopcyjnych, około 50% podatności jest genetyczna, a pozostałe 50% przypisuje się czynnikom środowiskowym.24 Prawdopodobnie rolę odgrywają również adaptacje neurobiologiczne i epigenetyczne, ale potrzebne są dalsze badania.25

Ogólnie, wyniki większości badań bliźniąt genetycznych potwierdzają istnienie znaczących czynników genetycznych, które predysponują jednostki do rozwoju problemów związanych z alkoholem.26 Przeprowadzono kilka badań rodzinnych dotyczących alkoholizmu, które dostarczyły ważnej wiedzy na temat dziedziczenia i predyspozycji do alkoholizmu przez pokolenia.27

Wśród zmiennych, które zwiększają ryzyko rozwoju alkoholizmu, geny odpowiedzialne za enzymy wątrobowe są uważane za związane ze zwiększonym ryzykiem uzależnienia od alkoholu.28 Badania genetyczne przeprowadzone w różnych grupach etnicznych potwierdziły, że pewne odmiany alleli ADH oferują silną ochronę przed uzależnieniem od alkoholu.29 Oprócz genów enzymatycznych, geny neuroprzekaźników zostały powiązane ze zwiększonym ryzykiem uzależnienia od alkoholu.30

Strukturalne i funkcjonalne zmiany w mózgu

Przewlekłe spożywanie alkoholu może prowadzić do zmian w strukturze mózgu, w tym do zmniejszenia objętości mózgu.31 To kurczenie się dotyka głównie płatów czołowych, które są odpowiedzialne za wyższe funkcje poznawcze, takie jak planowanie, regulacja emocji i kontrola impulsów.32

Długotrwałe używanie alkoholu może prowadzić do długoterminowych zmian w chemii mózgu.33 Regularna ekspozycja na alkohol może zmienić równowagę neuroprzekaźników, sprawiając, że mózg staje się mniej responsywny na alkohol i inne bodźce.34 Może to prowadzić do szeregu problemów, w tym zwiększonej tolerancji na alkohol, zależności i objawów odstawienia, gdy alkohol nie jest spożywany.35

Spożywanie alkoholu, szczególnie w dużych ilościach, może zaburzyć proces neurogenezy, tworzenia nowych neuronów, szczególnie w hipokampie.36 To zaburzenie może mieć długoterminowe implikacje dla uczenia się i pamięci.37 Wysokie poziomy spożycia alkoholu mogą być neurotoksyczne, prowadząc do śmierci komórek w pewnych obszarach mózgu.38

Mechanizmy metaboliczne w zaburzeniu używania alkoholu

Metabolizm alkoholu i jego konsekwencje

Alkohol jest wchłaniany do krwi głównie z jelita cienkiego, choć część jest wchłaniana z żołądka. Alkohol gromadzi się we krwi, ponieważ absorpcja jest szybsza niż utlenianie i eliminacja.39 Alkohol wywiera swoje działanie poprzez kilka mechanizmów – wiąże się bezpośrednio z receptorami kwasu gamma-aminomasłowego (GABA) w ośrodkowym układzie nerwowym, powodując sedację. Alkohol bezpośrednio wpływa również na tkankę sercową, wątrobową i tarczycową.40

Oksydacyjny metabolit etanolu, acetaldehyd, jest wysoce toksyczny i może łatwo ulegać krzyżowemu wiązaniu z DNA lub makromolekułami białkowymi w mitochondriach.41 Wiązanie acetaldehydu z glutationem (GSH) hamuje funkcję usuwania nadtlenku wodoru, tym samym zaostrzając stres oksydacyjny i peroksydację lipidów.42

Patogeneza choroby wątroby związanej ze spożywaniem alkoholu nie jest w pełni zrozumiała. Wiadomo, że niektórzy pacjenci z zaburzeniami używania alkoholu rozwijają chorobę wątroby, głównie dlatego, że wątroba metabolizuje większość spożytego etanolu. Ponadto metabolizm etanolu jest niezbędny do wystąpienia uszkodzeń wątroby, chociaż różnice w metabolizmie etanolu nie wyjaśniają całkowicie zmiennej podatności na chorobę wątroby związaną z alkoholem.43

Stres oksydacyjny i stan zapalny

Utlenianie etanolu prowadzi do zwiększonej produkcji wolnych rodników w wątrobie. Niekontrolowane reaktywne formy tlenu (ROS) są kluczowe dla obrzęku i apoptozy hepatocytów. Acetaldehyd może indukować produkcję ROS i prowadzić do choroby wątroby związanej z alkoholem (ALD).44

Stres azotylacyjny odnosi się do biochemicznego działania reaktywnych form azotu, gdzie tlenek azotu (NO) przyłącza się do reszty tyrozynowej, powodując generowanie wewnątrzkomórkowych białek niosących reszty 3-nitrotyrozyny (3-NT).45 Główne enzymy związane ze stresem azotylacyjnym to dwa podtypy syntazy tlenku azotu (NOS): śródbłonkowa NOS (eNOS) i indukowalna NOS (iNOS).46

Długotrwały stres w retikulum endoplazmatycznym (ER) może prowadzić do uszkodzenia komórek i tkanek.47 Etanol może wyzwalać odpowiedź stresu ER, po której następuje stymulacja ekspresji genów związanych z apoptozą, proliferacja komórek i zaburzenie równowagi apoptozy.48 Ekspresja SREBP-1 była również podwyższona przez stres ER indukowany etanolem.49

Oś jelitowo-wątrobowa w patogenezie ZUA

Wątroba i przewód pokarmowy są ściśle powiązane, a ich interakcje tworzą oś jelitowo-wątrobową. Translokacja bakterii lub produktów mikrobiologicznych z jelita do wątroby jest kluczowym czynnikiem zapalnym, który indukuje przejście od stłuszczenia alkoholowego do alkoholowego stłuszczeniowego zapalenia wątroby (ASH).50

Ekspozycja na etanol prowadzi do utraty komórek nabłonkowych na końcu kosmków jelitowych.51 Po długotrwałym spożyciu etanolu, struktura komórek nabłonka jelitowego u szczurów jest wyraźnie zmieniona, wykazując rozszerzenie mitochondriów i retikulum endoplazmatycznego.52 Stres oksydacyjny zapoczątkowany przez etanol prowadził do utlenienia mikrotubul cytoszkieletu i degradacji ścisłych połączeń (TJ).53

Fizyczna interakcja między etanolem a mikrobami jelitowymi może być kluczowym powodem zmian w zawartości flory jelitowej indukowanych etanolem.54 Zmiany w składzie mikroflory jelitowej mogą odgrywać ważną rolę w patogenezie zespołu kaca. Wykazano, że przewlekłe spożywanie alkoholu prowadzi do dysbiozy. Dysbioza indukowana alkoholem charakteryzuje się wzrostem liczby bakterii prozapalnych i zmniejszeniem liczby bakterii przeciwzapalnych.55

Mechanizmy leczenia farmakologicznego zaburzenia używania alkoholu

Leki zatwierdzone w leczeniu ZUA

Obecnie trzy leki są zatwierdzone przez amerykańską Agencję Żywności i Leków (FDA) do leczenia uzależnienia od alkoholu: disulfiram, akamprozat i naltrekson.56 Każdy z tych leków działa na odmienne mechanizmy w mózgu, które przyczyniają się do ZUA.

Podstawowe działanie farmakologiczne disulfiramu polega na zaburzeniu normalnego metabolizmu alkoholu.57 Disulfiram działa poprzez blokowanie rozkładu alkoholu w organizmie, co prowadzi do nagromadzenia toksycznego związku, który może powodować złe samopoczucie u osób pijących alkohol podczas przyjmowania leku.58

Uważa się, że akamprozat normalizuje równowagę między szlakami pobudzającymi i hamującymi, które adaptują się do przewlekłego używania alkoholu, i łagodzi psychologiczny i fizjologiczny dyskomfort, który następuje po odstawieniu.59 Główny przeciwalkoholowy efekt neurochemiczny akamprozatu przypisuje się modulacji neurotransmisji glutaminianergicznej na receptorach metabotropowych-5 glutaminianowych.60 Akamprozat zmniejsza zależność mózgu od alkoholu poprzez zmienianie sposobu, w jaki produkuje i uwalnia neuroprzekaźniki.61

Naltrekson funkcjonuje jako konkurencyjny antagonista receptorów opioidowych.62 Naltrekson wywiera swoje główne działanie farmakologiczne poprzez blokadę receptora mu-opioidowego. Endogenne opioidy modulują wzmacniające działanie alkoholu.63 Naltrekson wiąże się z receptorami endorfinowymi w organizmie i blokuje działanie i odczucia związane z alkoholem.64

Lek Mechanizm działania Efekt terapeutyczny
Disulfiram Blokowanie rozkładu alkoholu w organizmie (inhibitor dehydrogenazy aldehydowej) Powoduje reakcję awersyjną po spożyciu alkoholu
Akamprozat Modulacja receptorów glutaminianergicznych, normalizacja równowagi między układami pobudzającymi i hamującymi Zmniejsza głód alkoholowy i ryzyko nawrotu
Naltrekson Antagonista receptorów opioidowych, blokuje endogenne opioidy Zmniejsza przyjemność z picia alkoholu i głód alkoholowy
Topiramat* Blokowanie kanałów sodowych zależnych od napięcia, modulacja układu GABA i antagonizm receptorów glutaminianowych Zmniejsza spożycie alkoholu i głód alkoholowy

* Lek stosowany poza wskazaniami (off-label)

Leki eksperymentalne i stosowane poza wskazaniami

Topiramat, lek przeciwdrgawkowy o właściwościach farmakologicznych obejmujących blokowanie kanałów sodowych zależnych od napięcia, nasilenie transmisji GABA-ergicznej i antagonizm receptorów glutaminianergicznych, został uznany za skuteczny w zmniejszaniu spożycia alkoholu u osób z zaburzeniem używania alkoholu.65 Badania mózgowe pokazują, że topiramat może działać poprzez zmniejszenie uwalniania dopaminy w regionach mózgu związanych z nagrodą, gdy alkohol jest spożywany lub gdy osoby są narażone na bodźce związane z alkoholem.66

Z czasem to zmniejszenie odpowiedzi mózgu na alkohol może działać na zmniejszenie wzmacniających/nagradzających efektów alkoholu, tym samym osłabiając wyuczone skojarzenie między alkoholem, wskazówkami alkoholowymi a nagrodą, i zmniejszając głód alkoholowy i motywację do picia.67

Ondansetron (Zofran) może zmniejszać spożycie alkoholu u pacjentów z ZUA. W trzech badaniach ondansetron (4 mcg na kg dwa razy dziennie) w połączeniu z terapią poznawczo-behawioralną zmniejszył spożycie alkoholu i głód oraz zwiększył abstynencję u młodych dorosłych z wczesnym ZUA.68

Psilocybina wydaje się obiecująca w leczeniu ZUA, gdyż niedawne badanie kliniczne z użyciem psilocybiny w połączeniu z psychoterapią wykazało znaczną redukcję dni intensywnego picia u pacjentów z ZUA.69 Behawioralne i terapeutyczne efekty psilocybiny są głównie przypisywane aktywacji receptora serotoninowego 2A (5-HT2AR) i jego modulacji przez inne szlaki, w tym fizyczną interakcję z mGluR2.70

Strategie farmakoterapeutyczne

Strategie farmakologiczne mające na celu zmniejszenie picia u pacjentów z ZUA mogą próbować korygować nierównowagę między ścieżkami pobudzającymi i hamującymi oraz łagodzić intensywny głód alkoholowy wywołany neuroadaptacją.71 Leczenie farmakologiczne zaburzenia używania alkoholu koncentruje się na zmianie wzmacniających efektów spożywania alkoholu. Rozwój leków skupił się na kilku systemach neuroprzekaźnikowych, które pośredniczą we wzmocnieniu, w tym systemach opioidowych, glutaminianergicznych, GABA-ergicznych i serotoninergicznych.72

Kilka leków może być stosowanych w leczeniu zaburzenia używania alkoholu, prowadząc do zmniejszenia intensywnego picia i zwiększenia dni abstynencji. Te wyniki prawdopodobnie zmniejszają ogólne ryzyko związane z zaburzeniem używania alkoholu, mimo że całkowita abstynencja nie zostaje osiągnięta.73

Współwystępowanie z innymi zaburzeniami psychicznymi

Zaburzenia lękowe i afektywne

Osoby z zaburzeniami psychicznymi mogą być bardziej skłonne do rozwoju alkoholizmu.74 Pożądane efekty spożycia alkoholu występują, ponieważ alkohol jest depresantem ośrodkowego układu nerwowego (OUN).75 Badania sugerują, że może istnieć dwukierunkowe połączenie między zaburzeniami lękowymi a ZUA.76 Osoby z ZUA mogą mieć wyższe ryzyko rozwoju zaburzenia lękowego, takiego jak uogólnione zaburzenie lękowe lub fobia społeczna.77

Narodowy Instytut ds. Nadużywania Alkoholu i Alkoholizmu (NIAAA) sugeruje, że ZUA i choroby psychiatryczne, takie jak zaburzenia lękowe, dzielą genetyczne i środowiskowe czynniki ryzyka. Może to wyjaśniać związek między nimi.78 W wielu przypadkach nie jest jasne, czy alkohol powoduje lęk, czy lęk czyni osobę bardziej skłonną do picia alkoholu.79 Według niektórych badań na zwierzętach, osoby pijące alkohol w młodości mogą być bardziej podatne na lęk w dorosłości, co mogłoby sugerować związek przyczynowy.80

Przeważność współwystępujących psychopatologii w różnych badaniach waha się od 15-70%, w tym depresji i zaburzeń lękowych.81 Mechanizmy radzenia sobie danej osoby odgrywają kluczową rolę w przypadku rozwoju zależności od alkoholu i różnych psychopatologii.82 Złożona interakcja psychopatologii, umiejętności radzenia sobie i używania alkoholu może wpływać na wynik uzależnienia od alkoholu.83

Mechanizmy radzenia sobie a zaburzenie używania alkoholu

Nadużywanie i uzależnienie od alkoholu często wynika z używania alkoholu jako mechanizmu radzenia sobie.84 Niestety, alkohol jest mechanizmem radzenia sobie, którego tymczasowe korzyści są często przeważane przez długoterminowe negatywne skutki dla zdrowia i relacji, złe podejmowanie decyzji pod wpływem, a także zwiększoną zależność.85 Alkohol działa, spowalniając ośrodkowy układ nerwowy, tworząc uczucie relaksacji. Zmniejsza również hamowanie, osąd i pamięć. Ze względu na te cechy, alkohol staje się sposobem na zdystansowanie się od stresorów lub wyzwań, z którymi dana osoba może się mierzyć.86

Osoby z historią alkoholizmu w rodzinie mogą być bardziej skłonne do używania alkoholu jako metody radzenia sobie, ponieważ alkohol mógł być używany przez rodziców lub krewnych. Ci, którzy używają alkoholu do radzenia sobie, mogą nie być wyposażeni w adaptacyjne umiejętności radzenia sobie.87

Przy braku zdrowych mechanizmów radzenia sobie, lęk, depresja i inne zaburzenia zdrowia psychicznego nie są rzadkością wśród osób, które używają alkoholu do radzenia sobie.88 Niezależnie od tego, czy nadużywanie substancji i/lub uzależnienie występuje w rodzinie, wszystkie osoby doświadczają zwiększonej tolerancji na alkohol, im więcej i dłużej piją. Więcej alkoholu jest wymagane, aby osiągnąć ten sam efekt.89

W skrajnych przypadkach fizycznej zależności od alkoholu, osoba może stać się tak uzależniona, że doświadcza objawów odstawienia bez substancji, takich jak drżenia, pocenie się, bezsenność, bóle głowy i więcej. Odstawienie alkoholu może być śmiertelne w ciężkich przypadkach.90

Zespół kaca i jego patogeneza

Pomimo znacznych szkód dla zdrowia i dużych strat ekonomicznych związanych z zespołem kaca (HS), patogeneza tego stanu nie jest dobrze zrozumiana. Jednocześnie zrozumienie mechanizmów patogenetycznych HS jest niezbędne do opracowania środków zapobiegania i leczenia tego stanu.91 Przypuszczalne mechanizmy patogenezy HS to: zaburzenia metaboliczne i endokrynologiczne indukowane alkoholem, stres oksydacyjny, stan zapalny, zaburzenia równowagi wodno-elektrolitowej i równowagi kwasowo-zasadowej.92

Szereg badań przedstawia dane wskazujące na zaangażowanie układu odpornościowego w patogenezę HS.93 Dodatkowymi mechanizmami patogenetycznymi HS mogą być odwodnienie (alkohol zwiększa diurezę), zaburzenia metabolizmu mineralnego (zmniejszenie poziomu wapnia i magnezu w osoczu krwi), alkoholowa kwasica mleczanowa i ketonowa (z powodu zwiększonego tworzenia octanu i kwasu beta-hydroksymasłowego).94 Niewystarczające zrozumienie mechanizmów patogenetycznych HS komplikuje opracowanie naukowo udowodnionych skutecznych środków jej zapobiegania i leczenia.95

Zaburzenia funkcji poznawczych w ZUA

Funkcje wykonawcze i elastyczność poznawcza

Funkcje wykonawcze (EF) zostały zaproponowane jako transdiagnostyczny czynnik ryzyka dla zaburzeń eksternalizacyjnych i zachowań, w tym zespołu nadpobudliwości psychoruchowej z deficytem uwagi (ADHD), agresji i używania alkoholu.96 EF wykazało znaczące związki przyczynowe z ADHD (P < 0,01), ZUA (P < 0,03) i spożyciem alkoholu (P < 0,01) w kilku metodach estymacji.97 Wyniki sugerują, że EF może być mechanizmem przyczynowym leżącym u podstaw niektórych zachowań eksternalizacyjnych, w tym ADHD i używania alkoholu, oraz że ADHD może również prowadzić do niższych wyników w zadaniach EF.98

Wykorzystując model zwierzęcy, Jun Wang, PhD, profesor nadzwyczajny w Departamencie Neuronauki i Terapeutyki Eksperymentalnej w Texas A&M University School of Medicine, i członkowie jego laboratorium zaobserwowali, że przewlekłe spożycie alkoholu i odstawienie zmniejszają elastyczność poznawczą jednostek.99 Ta zmniejszona elastyczność behawioralna jest głównie spowodowana zmniejszonymi wejściami wzgórzowymi do cholinergicznych interneuronów prążkowia grzbietowo-przyśrodkowego, spowodowanymi przewlekłym spożyciem alkoholu. Poprzez zaburzenie komunikacji między wzgórzem a prążkowiem, przewlekłe spożycie alkoholu zaburzyło elastyczność behawioralną zwierząt.100

Ten brak komunikacji powoduje zaburzoną elastyczność poznawczą, wskazywaną przez brak odwrócenia uczenia instrumentalnego.101 Co ważniejsze, gdy selektywnie zwiększono transmisję między cholinergicznymi interneuronami wzgórza i prążkowia grzbietowo-przyśrodkowego, używając narzędzi optogenetycznych, można było uratować indukowane alkoholem deficyty uczenia się odwrócenia u zwierząt.102

Objawy odstawienia alkoholu i zmiany neurobiologiczne

Fizyczna zależność towarzysząca tolerancji jest głęboka, a odstawienie alkoholu ma potencjalnie śmiertelne skutki uboczne.103 Kontinuum objawów i oznak hiperaktywności ośrodkowego układu nerwowego (w tym autonomicznego) może towarzyszyć zaprzestaniu spożywania alkoholu.104 Halucynoza alkoholowa następuje po nagłym zaprzestaniu długotrwałego, nadmiernego używania alkoholu, zwykle w ciągu 12 do 24 godzin.105 Majaczenie alkoholowe zwykle zaczyna się 48 do 72 godzin po odstawieniu alkoholu; ataki lęku, rosnące zamieszanie, zły sen (z przerażającymi snami lub nocnymi iluzjami), obfite pocenie się i ciężka depresja również występują.106

Majaczenie drżenne (delirium tremens) rozwija się najczęściej u osób z zaburzeniem używania alkoholu. Szacuje się, że 80% osób z uzależnieniem od alkoholu nie wchłania ani nie zatrzymuje wystarczającej ilości tiaminy.107 Najczęstszą przyczyną niedoboru tiaminy jest przewlekłe używanie alkoholu. Alkohol utrudnia organizmowi wchłanianie tiaminy i przechowywanie jej w wątrobie.108 Około 50% osób, u których rozwija się encefalopatia Wernickego, ostatecznie rozwija zespół Korsakowa. Liczba ta jest wyższa (80%) wśród osób z zaburzeniem używania alkoholu.109

Przewlekłe spożycie alkoholu, zwłaszcza w dużych ilościach, może zakłócać proces neurogenezy, tworzenia nowych neuronów, szczególnie w hipokampie. To zakłócenie może mieć długoterminowe implikacje dla uczenia się i pamięci.110 Wysokie poziomy spożycia alkoholu mogą być neurotoksyczne, prowadząc do śmierci komórek w pewnych obszarach mózgu.111

Dysregulacja obwodów neuronalnych

Przydatne biomarkery dotyczą mechanizmów kontroli czołowej, które są poważnie zaburzone w ZUA. Prowadzi to do zmniejszonej kontroli hamującej kompulsywnego zachowania i ostatecznie do nawrotu.112 Uzasadniliśmy tutaj, że dysfunkcja czołowa, która leży u podstaw podatności na nawrót, jest widoczna dzięki zmienionym podpisom neuroelektrycznym i powinna być przywrócona przez interwencje farmakologiczne, które specyficznie ukierunkowane są na dysfunkcję czołową.113

Zaburzenia elektrofizjologiczne u szczurów uzależnionych od alkoholu to zmniejszone amplitudy komponentów P1N1 i N1P2 oraz atenuowana aktywność oscylacyjna związana z wydarzenia.114 Ponadto, zwierzęta uzależnione od alkoholu wykazywały dominację w wyższych częstotliwościach beta wskazującą na stan nadpobudliwości, który jest podatny na nawrót, czemu szczególnie psilocybina była w stanie przeciwdziałać.115

Uznaje się, że opisane zaburzenia poznawcze i ograniczona kontrola behawioralna obserwowane w ZUA odnoszą się do zaburzeń przede wszystkim w sieciach przedczołowo-korowych.116 Jeden z celów terapeutycznych to metabotropowy receptor glutaminianowy 2 (mGluR2), kluczowy regulator uwalniania glutaminianu.117 W konsekwencji zaproponowano użycie agonistów mGluR2, takich jak LY379268, aby przeciwdziałać tej zmniejszonej funkcji czołowej, dostarczając przedklinicznych dowodów na jego potencjał do osłabienia poszukiwania alkoholu i zachowań podobnych do nawrotu.118

Zaburzenie używania alkoholu to głębokie zaburzenie psychiatryczne charakteryzujące się zaburzoną łącznością między rozproszonymi regionami mózgu, wskazującą na zaburzoną integrację funkcjonalną.119 Wcześniejsze badania konektomu wykorzystujące funkcjonalny rezonans magnetyczny (fMRI) koncentrowały się głównie na niekierunkowej łączności funkcjonalnej, podczas gdy specyficzne zmiany w kierunkowej łączności efektywnej (EC) związane z ZUA pozostają niejasne.120

Osoby z ZUA wykazywały zmniejszoną EC z lewej pre-SMA do prawego jądra ogoniastego, z prawego dACC do prawego jądra ogoniastego oraz z prawego LOFC do prawego NACC w porównaniu do zdrowych osób.121 Ponadto, siła EC z prawego NACC do lewej pre-SMA i z prawego dACC do prawego jądra ogoniastego mediowała związek między nasileniem uzależnienia (wyniki MAST) a miarami behawioralnymi (wyniki impulsywne i kompulsywne).122

Kolejne rozdziały

Zapraszamy do dalszego czytania naszego leksykonu.

Wybierz kolejny rozdział z menu poniżej, aby otworzyć nową podstronę kompedium wiedzy i uzyskać szczegółowe informację o leku, substancji lub chorobie.

  1. 10.04.2026
  2. www.leksykon.com.pl

Materiały źródłowe

  • #1 Alcohol Use Disorder: A Growing Public Health Crisis | Columbia University Department of Psychiatry
    https://www.columbiapsychiatry.org/news/alcohol-use-disorder-growing-public-health-crisis
    AUD is a chronic brain disorder resulting from compulsive alcohol consumption, loss of control over alcohol use, and negative emotions (e.g., stress and anger) when not drinking. […] Social drinkers dont have the same difficulty controlling or limiting what they drink, while those with AUD tend to struggle with intense cravings and are often unable to predict how much they will drink and when they will stop. […] There are three medications approved by the FDA for treating alcohol dependence: disulfiram, acamprosate, and naltrexone. Disulfiram works by blocking the breakdown of alcohol in the body, which leads to a buildup of a toxic compound that can cause people who drink alcohol while taking the medication to get sick. Naltrexone binds to the endorphin receptors in the body and blocks the effects and feelings of alcohol. Acamprosate reduces the brains dependence on alcohol by changing how it produces and releases neurotransmitters.
  • #2 Alcohol Use Disorder: A Growing Public Health Crisis | Columbia University Department of Psychiatry
    https://www.columbiapsychiatry.org/news/alcohol-use-disorder-growing-public-health-crisis
    AUD is a chronic brain disorder resulting from compulsive alcohol consumption, loss of control over alcohol use, and negative emotions (e.g., stress and anger) when not drinking. […] Social drinkers dont have the same difficulty controlling or limiting what they drink, while those with AUD tend to struggle with intense cravings and are often unable to predict how much they will drink and when they will stop. […] There are three medications approved by the FDA for treating alcohol dependence: disulfiram, acamprosate, and naltrexone. Disulfiram works by blocking the breakdown of alcohol in the body, which leads to a buildup of a toxic compound that can cause people who drink alcohol while taking the medication to get sick. Naltrexone binds to the endorphin receptors in the body and blocks the effects and feelings of alcohol. Acamprosate reduces the brains dependence on alcohol by changing how it produces and releases neurotransmitters.
  • #3 Alcohol Use Disorders: Aetiology and Pathophysiology (Chapter 6) – Seminars in Addiction Psychiatry
    https://www.cambridge.org/core/books/seminars-in-addiction-psychiatry/alcohol-use-disorders-aetiology-and-pathophysiology/8E5E87C9A5E0FD25DF7E69CEDA29A3C4
    The aetiology and pathophysiology of alcohol dependence are complex, derived from genetics, parenting, peer and societal norms and rules, pharmacology and mental health comorbidity. […] It explores the various aspects of family history that contribute to the heritability of alcohol use disorders, and summarises relevant social and psychological factors. […] It then provides a nuanced understanding of the pharmacological rationale underpinning withdrawal and relapse prevention treatment, including an understanding of the role of GABA, glutamate and opioid systems. […] The chapter concludes by highlighting the ways in which patients with psychiatric disorders may be at greater risk of alcohol use disorders.
  • #4 People Drink Alcohol as a Coping Mechanism – Pinelands Recovery
    https://www.pinelandsrecovery.com/why-people-drink-alcohol-as-a-coping-mechanism/
    The cause of alcohol use disorder (AUD) may range from various factors, including environmental factors, mental health disorders and more. […] However, through education, individuals can become aware of the potential risk factors of AUD and protect themselves and those they love. […] AUD forms when a person drinks so much that the brain’s reward circuit is altered to associate drinking alcohol with pleasure. This change causes individuals to drink more, even when the feelings of pleasure subside. […] Those who struggle with mental health disorders may often look for relief from their symptoms. Unfortunately, alcohol is commonly used to self-medicate and escape from these symptoms. […] If AUD runs in your family, you pose a higher risk of developing AUD yourself than someone that does not have a genetic history of AUD.
  • #5 Alcoholism: Practice Essentials, Background, Pathophysiology
    https://emedicine.medscape.com/article/285913-overview
    Alcohol affects virtually every organ system in the body and, in high doses, can cause coma and death. It affects several neurotransmitter systems in the brain, including opiates, GABA, glutamate, serotonin, and dopamine. Increased opiate levels help explain the euphoric effect of alcohol, while its effects on GABA cause anxiolytic and sedative effects. […] Alcohol inhibits the receptor for glutamate. Long-term ingestion results in the synthesis of more glutamate receptors. When alcohol is withdrawn, the central nervous system experiences increased excitability. Persons who abuse alcohol over the long term are more prone to alcohol withdrawal syndrome than persons who have been drinking for only short periods. Brain excitability caused by long-term alcohol ingestion can lead to cell death and cerebellar degeneration, Wernicke-Korsakoff syndrome, tremors, alcoholic hallucinosis, delirium tremens, and withdrawal seizures. Opiate receptors are increased in the brains of recently abstinent alcoholic patients, and the number of receptors correlates with cravings for alcohol.
  • #6 Alcoholism: Practice Essentials, Background, Pathophysiology
    https://emedicine.medscape.com/article/285913-overview
    Alcohol affects virtually every organ system in the body and, in high doses, can cause coma and death. It affects several neurotransmitter systems in the brain, including opiates, GABA, glutamate, serotonin, and dopamine. Increased opiate levels help explain the euphoric effect of alcohol, while its effects on GABA cause anxiolytic and sedative effects. […] Alcohol inhibits the receptor for glutamate. Long-term ingestion results in the synthesis of more glutamate receptors. When alcohol is withdrawn, the central nervous system experiences increased excitability. Persons who abuse alcohol over the long term are more prone to alcohol withdrawal syndrome than persons who have been drinking for only short periods. Brain excitability caused by long-term alcohol ingestion can lead to cell death and cerebellar degeneration, Wernicke-Korsakoff syndrome, tremors, alcoholic hallucinosis, delirium tremens, and withdrawal seizures. Opiate receptors are increased in the brains of recently abstinent alcoholic patients, and the number of receptors correlates with cravings for alcohol.
  • #7 Alcoholism: Practice Essentials, Background, Pathophysiology
    https://emedicine.medscape.com/article/285913-overview
    Alcohol affects virtually every organ system in the body and, in high doses, can cause coma and death. It affects several neurotransmitter systems in the brain, including opiates, GABA, glutamate, serotonin, and dopamine. Increased opiate levels help explain the euphoric effect of alcohol, while its effects on GABA cause anxiolytic and sedative effects. […] Alcohol inhibits the receptor for glutamate. Long-term ingestion results in the synthesis of more glutamate receptors. When alcohol is withdrawn, the central nervous system experiences increased excitability. Persons who abuse alcohol over the long term are more prone to alcohol withdrawal syndrome than persons who have been drinking for only short periods. Brain excitability caused by long-term alcohol ingestion can lead to cell death and cerebellar degeneration, Wernicke-Korsakoff syndrome, tremors, alcoholic hallucinosis, delirium tremens, and withdrawal seizures. Opiate receptors are increased in the brains of recently abstinent alcoholic patients, and the number of receptors correlates with cravings for alcohol.
  • #8 Alcoholism: Practice Essentials, Background, Pathophysiology
    https://emedicine.medscape.com/article/285913-overview
    Alcohol affects virtually every organ system in the body and, in high doses, can cause coma and death. It affects several neurotransmitter systems in the brain, including opiates, GABA, glutamate, serotonin, and dopamine. Increased opiate levels help explain the euphoric effect of alcohol, while its effects on GABA cause anxiolytic and sedative effects. […] Alcohol inhibits the receptor for glutamate. Long-term ingestion results in the synthesis of more glutamate receptors. When alcohol is withdrawn, the central nervous system experiences increased excitability. Persons who abuse alcohol over the long term are more prone to alcohol withdrawal syndrome than persons who have been drinking for only short periods. Brain excitability caused by long-term alcohol ingestion can lead to cell death and cerebellar degeneration, Wernicke-Korsakoff syndrome, tremors, alcoholic hallucinosis, delirium tremens, and withdrawal seizures. Opiate receptors are increased in the brains of recently abstinent alcoholic patients, and the number of receptors correlates with cravings for alcohol.
  • #9 A short review on the aetiology and pathophysiology of alcoholism | Annals of General Psychiatry | Full Text
    https://annals-general-psychiatry.biomedcentral.com/articles/10.1186/1744-859X-8-10
    Alcohol acts on many neuroreceptor systems and, as already mentioned, alcohol addiction differs from other addictions in that it has no known receptor system in the brain. […] Chronic alcohol use does not influence just one neurotransmitter but almost all neurotransmitter systems. […] Although we now know much more about the influence of alcohol on the central nervous system, the mechanisms of action remain under discussion. […] These influences are different if the quantity of alcohol consumed is large or small. […] In addition, psychological factors and mechanisms are in constant interaction with the biological background, the genetic influence and the sociocultural environment, creating new clinical results and various study areas.
  • #10 Pharmacology of Alcohol and Alcohol Use Disorder | SpringerLink
    https://link.springer.com/10.1007/978-3-030-62059-2_340
    Alcohol (ethanol) is a central nervous system (CNS) depressant drug that, depending on its blood concentration, can induce various manifestations such as relief from anxiety, disinhibition, ataxia, and general anesthesia. Chronic exposure to alcohol can cause persistent structural and functional changes in the brain. […] It is crucial that we understand the complex mechanism of action of alcohol to find better therapeutic alternatives. Alcohol acts on various neurotransmitters such as gamma-aminobutyric acid (GABA), glutamate, dopamine, serotonin, and endogenous opioids. Alcohol is both a GABA agonist and a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist. […] After chronic exposure, downregulation of GABAergic and upregulation of NMDA glutamatergic systems typically occur. Normalizing this imbalance might be effective in the treatment of alcohol dependence. Antagonism of the -opioid system also reduces the motivation to consume alcohol. […] New animal models of binge alcohol intake, such as the alcohol deprivation effect (ADE) and the Drinking-in-the-Dark technique, would help us to develop new treatment methods against alcohol dependence.
  • #11 Pharmacology of Alcohol and Alcohol Use Disorder | SpringerLink
    https://link.springer.com/10.1007/978-3-030-62059-2_340
    Alcohol (ethanol) is a central nervous system (CNS) depressant drug that, depending on its blood concentration, can induce various manifestations such as relief from anxiety, disinhibition, ataxia, and general anesthesia. Chronic exposure to alcohol can cause persistent structural and functional changes in the brain. […] It is crucial that we understand the complex mechanism of action of alcohol to find better therapeutic alternatives. Alcohol acts on various neurotransmitters such as gamma-aminobutyric acid (GABA), glutamate, dopamine, serotonin, and endogenous opioids. Alcohol is both a GABA agonist and a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist. […] After chronic exposure, downregulation of GABAergic and upregulation of NMDA glutamatergic systems typically occur. Normalizing this imbalance might be effective in the treatment of alcohol dependence. Antagonism of the -opioid system also reduces the motivation to consume alcohol. […] New animal models of binge alcohol intake, such as the alcohol deprivation effect (ADE) and the Drinking-in-the-Dark technique, would help us to develop new treatment methods against alcohol dependence.
  • #12 Pharmacology of Alcohol and Alcohol Use Disorder | SpringerLink
    https://link.springer.com/10.1007/978-3-030-62059-2_340
    Alcohol (ethanol) is a central nervous system (CNS) depressant drug that, depending on its blood concentration, can induce various manifestations such as relief from anxiety, disinhibition, ataxia, and general anesthesia. Chronic exposure to alcohol can cause persistent structural and functional changes in the brain. […] It is crucial that we understand the complex mechanism of action of alcohol to find better therapeutic alternatives. Alcohol acts on various neurotransmitters such as gamma-aminobutyric acid (GABA), glutamate, dopamine, serotonin, and endogenous opioids. Alcohol is both a GABA agonist and a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist. […] After chronic exposure, downregulation of GABAergic and upregulation of NMDA glutamatergic systems typically occur. Normalizing this imbalance might be effective in the treatment of alcohol dependence. Antagonism of the -opioid system also reduces the motivation to consume alcohol. […] New animal models of binge alcohol intake, such as the alcohol deprivation effect (ADE) and the Drinking-in-the-Dark technique, would help us to develop new treatment methods against alcohol dependence.
  • #13 The Science of Addiction: How Alcohol Affects the Brain
    https://boldhealthinc.com/the-science-of-addiction-how-alcohol-affects-the-brain-understanding-the-impact/
    Alcohol consumption leads to an increase in dopamine levels in the brain’s reward centers. […] This surge in dopamine contributes to the feelings of pleasure and euphoria often experienced during drinking. […] However, over time, the brain may start to associate alcohol with these positive feelings, potentially leading to addiction. […] Chronic alcohol consumption can lead to alterations in brain structure, including a reduction in brain volume. […] This shrinkage predominantly affects the frontal lobes, which are responsible for higher cognitive functions, such as planning, regulating emotions, and impulse control. […] Prolonged alcohol use can lead to long-term changes in brain chemistry. […] Regular exposure to alcohol can alter the balance of neurotransmitters, making the brain less responsive to alcohol and other stimuli.
  • #14 The Science of Addiction: How Alcohol Affects the Brain
    https://boldhealthinc.com/the-science-of-addiction-how-alcohol-affects-the-brain-understanding-the-impact/
    Alcohol consumption leads to an increase in dopamine levels in the brain’s reward centers. […] This surge in dopamine contributes to the feelings of pleasure and euphoria often experienced during drinking. […] However, over time, the brain may start to associate alcohol with these positive feelings, potentially leading to addiction. […] Chronic alcohol consumption can lead to alterations in brain structure, including a reduction in brain volume. […] This shrinkage predominantly affects the frontal lobes, which are responsible for higher cognitive functions, such as planning, regulating emotions, and impulse control. […] Prolonged alcohol use can lead to long-term changes in brain chemistry. […] Regular exposure to alcohol can alter the balance of neurotransmitters, making the brain less responsive to alcohol and other stimuli.
  • #15 How does topiramate work for alcohol use disorder? A look at the effects on brain activation in response to alcohol cues and relationship to alcohol craving and use – Recovery Research Institute
    https://www.recoveryanswers.org/research-post/topiramate-alcohol-use-disorder-effects-brain-activation-response-alcohol-cues-relationship-alcohol-craving-use/
    Topiramate is an anti-seizure medication that has been recently investigated for the treatment of alcohol use disorder. […] Investigating brain changes that occur in response to topiramate can provide insight into how the medication works and its utility in alcohol use disorder treatment and recovery. […] Brain imaging studies show that individuals with alcohol use disorder have enhanced dopamine release (brain chemical that plays a role in pleasure and reward) and brain activation in regions involved in reward processing (e.g., an area called the ventral striatum) when exposed to alcohol-related cues. […] It has been hypothesized that topiramate may work by reducing dopamine release in reward-related regions of the brain when alcohol is consumed, or individuals are exposed to alcohol cues.
  • #16 Alcohol Use Disorder: Neurobiology and Therapeutics
    https://www.mdpi.com/2227-9059/10/5/1192
    Addiction is a dynamic dysregulation of the motivational circuits within the brain caused by exaggerated incentive salience and habit formation, deficits in reward function leading to increased stress, and compromised executive functioning. […] During the development of addiction, individuals move from impulsive to compulsive drug taking, which is accompanied by a shift from positive to negative reinforcement. […] Neuroimaging studies have frequently implicated the orbitofrontal cortex and anterior cingulate gyrus in the later stages of addiction, showing activation of these brain regions during intoxication, craving, and bingeing, and their inactivation during withdrawal. […] The binge/intoxication stage of addiction results in the dysregulation of the brain circuits involved in the ability to mediate salience value, leading to the development of excessive drug-taking habits due to increases in DA neurotransmission during drug intake.
  • #17 Alcohol Use Disorder: Neurobiology and Therapeutics
    https://www.mdpi.com/2227-9059/10/5/1192
    Addiction is a dynamic dysregulation of the motivational circuits within the brain caused by exaggerated incentive salience and habit formation, deficits in reward function leading to increased stress, and compromised executive functioning. […] During the development of addiction, individuals move from impulsive to compulsive drug taking, which is accompanied by a shift from positive to negative reinforcement. […] Neuroimaging studies have frequently implicated the orbitofrontal cortex and anterior cingulate gyrus in the later stages of addiction, showing activation of these brain regions during intoxication, craving, and bingeing, and their inactivation during withdrawal. […] The binge/intoxication stage of addiction results in the dysregulation of the brain circuits involved in the ability to mediate salience value, leading to the development of excessive drug-taking habits due to increases in DA neurotransmission during drug intake.
  • #18 Alcohol Use Disorder: Neurobiology and Therapeutics
    https://www.mdpi.com/2227-9059/10/5/1192
    Addiction is a dynamic dysregulation of the motivational circuits within the brain caused by exaggerated incentive salience and habit formation, deficits in reward function leading to increased stress, and compromised executive functioning. […] During the development of addiction, individuals move from impulsive to compulsive drug taking, which is accompanied by a shift from positive to negative reinforcement. […] Neuroimaging studies have frequently implicated the orbitofrontal cortex and anterior cingulate gyrus in the later stages of addiction, showing activation of these brain regions during intoxication, craving, and bingeing, and their inactivation during withdrawal. […] The binge/intoxication stage of addiction results in the dysregulation of the brain circuits involved in the ability to mediate salience value, leading to the development of excessive drug-taking habits due to increases in DA neurotransmission during drug intake.
  • #19 Alcohol Use Disorder: Neurobiology and Therapeutics
    https://www.mdpi.com/2227-9059/10/5/1192
    Addiction is a dynamic dysregulation of the motivational circuits within the brain caused by exaggerated incentive salience and habit formation, deficits in reward function leading to increased stress, and compromised executive functioning. […] During the development of addiction, individuals move from impulsive to compulsive drug taking, which is accompanied by a shift from positive to negative reinforcement. […] Neuroimaging studies have frequently implicated the orbitofrontal cortex and anterior cingulate gyrus in the later stages of addiction, showing activation of these brain regions during intoxication, craving, and bingeing, and their inactivation during withdrawal. […] The binge/intoxication stage of addiction results in the dysregulation of the brain circuits involved in the ability to mediate salience value, leading to the development of excessive drug-taking habits due to increases in DA neurotransmission during drug intake.
  • #20 Alcohol Use Disorder: Neurobiology and Therapeutics
    https://www.mdpi.com/2227-9059/10/5/1192
    The withdrawal/negative affect stage is characterized by increases in stress and anxiety-like responses resulting from withdrawal from drugs and may involve emotional pain, malaise, dysphoria, and loss of motivation for natural rewards. […] The preoccupation/anticipation stage of addiction consists of the return to drug-seeking behaviours after a period of abstinence. […] In summary, addictive drugs act on multiple circuits within the brain, including those responsible for executive control, motivation, and reward, leading to a loss of inhibitory control, deficits in decision making, changes to reward and motivation, and increased activity of stress response systems.
  • #21 Alcohol Use Disorder: Neurobiology and Therapeutics
    https://www.mdpi.com/2227-9059/10/5/1192
    The withdrawal/negative affect stage is characterized by increases in stress and anxiety-like responses resulting from withdrawal from drugs and may involve emotional pain, malaise, dysphoria, and loss of motivation for natural rewards. […] The preoccupation/anticipation stage of addiction consists of the return to drug-seeking behaviours after a period of abstinence. […] In summary, addictive drugs act on multiple circuits within the brain, including those responsible for executive control, motivation, and reward, leading to a loss of inhibitory control, deficits in decision making, changes to reward and motivation, and increased activity of stress response systems.
  • #22 A short review on the aetiology and pathophysiology of alcoholism | Annals of General Psychiatry | Full Text
    https://annals-general-psychiatry.biomedcentral.com/articles/10.1186/1744-859X-8-10
    Alcoholism is a chronic remitting and relapsing condition; its aetiology and pathophysiology remains largely obscure despite recent advances. […] This review summarises the current knowledge about the causation (biological or psychological) of alcohol addiction. This involves heredity, candidate genes, alcohol metabolism regulation and the influence of alcohol in the pathophysiology of the different neurotransmitter systems. Alcohol addiction is a multifactorial phenomenon where personality structure, individual state of mind and social influences are in constant interaction with brain neurobiology and pathophysiology. […] Alcohol addiction is a multifactorial disorder that runs transgenerationally. […] Genetics have an important and critical contribution in the development of alcohol abuse.
  • #23 A short review on the aetiology and pathophysiology of alcoholism | Annals of General Psychiatry | Full Text
    https://annals-general-psychiatry.biomedcentral.com/articles/10.1186/1744-859X-8-10
    Alcoholism is a chronic remitting and relapsing condition; its aetiology and pathophysiology remains largely obscure despite recent advances. […] This review summarises the current knowledge about the causation (biological or psychological) of alcohol addiction. This involves heredity, candidate genes, alcohol metabolism regulation and the influence of alcohol in the pathophysiology of the different neurotransmitter systems. Alcohol addiction is a multifactorial phenomenon where personality structure, individual state of mind and social influences are in constant interaction with brain neurobiology and pathophysiology. […] Alcohol addiction is a multifactorial disorder that runs transgenerationally. […] Genetics have an important and critical contribution in the development of alcohol abuse.
  • #24 Alcohol Use Disorder – StatPearls – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK436003/
    Although the exact etiology of alcohol use disorder remains unknown, susceptibility to the disorder is likely multifactorial. According to twin and adoption studies, approximately 50% of the liability is genetic, with the remaining 50% attributed to environmental factors. Neurobiological and epigenetic adaptations likely play a role in the development of AUD, but further research is needed.
  • #25 Alcohol Use Disorder – StatPearls – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK436003/
    Although the exact etiology of alcohol use disorder remains unknown, susceptibility to the disorder is likely multifactorial. According to twin and adoption studies, approximately 50% of the liability is genetic, with the remaining 50% attributed to environmental factors. Neurobiological and epigenetic adaptations likely play a role in the development of AUD, but further research is needed.
  • #26 A short review on the aetiology and pathophysiology of alcoholism | Annals of General Psychiatry | Full Text
    https://annals-general-psychiatry.biomedcentral.com/articles/10.1186/1744-859X-8-10
    Overall, the results of the majority of twin genetic studies support the existence of significant genetic factors that predispose individuals to the development of alcohol related problems. […] There have been several family studies on alcoholism that have provided important knowledge about the inheritance and the predisposition to alcoholism through the generations. […] Amongst the variables that enhance the risk of developing alcoholism, the genes responsible for the liver enzymes are believed to be related to an increased risk for alcohol dependence. […] Genetic studies conducted in various ethnic groups have confirmed that certain allele variations of ADH offer strong protection against alcohol addiction. […] In addition to the enzyme genes, neurotransmitter genes have been associated with increased risk for alcohol dependence.
  • #27 A short review on the aetiology and pathophysiology of alcoholism | Annals of General Psychiatry | Full Text
    https://annals-general-psychiatry.biomedcentral.com/articles/10.1186/1744-859X-8-10
    Overall, the results of the majority of twin genetic studies support the existence of significant genetic factors that predispose individuals to the development of alcohol related problems. […] There have been several family studies on alcoholism that have provided important knowledge about the inheritance and the predisposition to alcoholism through the generations. […] Amongst the variables that enhance the risk of developing alcoholism, the genes responsible for the liver enzymes are believed to be related to an increased risk for alcohol dependence. […] Genetic studies conducted in various ethnic groups have confirmed that certain allele variations of ADH offer strong protection against alcohol addiction. […] In addition to the enzyme genes, neurotransmitter genes have been associated with increased risk for alcohol dependence.
  • #28 A short review on the aetiology and pathophysiology of alcoholism | Annals of General Psychiatry | Full Text
    https://annals-general-psychiatry.biomedcentral.com/articles/10.1186/1744-859X-8-10
    Overall, the results of the majority of twin genetic studies support the existence of significant genetic factors that predispose individuals to the development of alcohol related problems. […] There have been several family studies on alcoholism that have provided important knowledge about the inheritance and the predisposition to alcoholism through the generations. […] Amongst the variables that enhance the risk of developing alcoholism, the genes responsible for the liver enzymes are believed to be related to an increased risk for alcohol dependence. […] Genetic studies conducted in various ethnic groups have confirmed that certain allele variations of ADH offer strong protection against alcohol addiction. […] In addition to the enzyme genes, neurotransmitter genes have been associated with increased risk for alcohol dependence.
  • #29 A short review on the aetiology and pathophysiology of alcoholism | Annals of General Psychiatry | Full Text
    https://annals-general-psychiatry.biomedcentral.com/articles/10.1186/1744-859X-8-10
    Overall, the results of the majority of twin genetic studies support the existence of significant genetic factors that predispose individuals to the development of alcohol related problems. […] There have been several family studies on alcoholism that have provided important knowledge about the inheritance and the predisposition to alcoholism through the generations. […] Amongst the variables that enhance the risk of developing alcoholism, the genes responsible for the liver enzymes are believed to be related to an increased risk for alcohol dependence. […] Genetic studies conducted in various ethnic groups have confirmed that certain allele variations of ADH offer strong protection against alcohol addiction. […] In addition to the enzyme genes, neurotransmitter genes have been associated with increased risk for alcohol dependence.
  • #30 A short review on the aetiology and pathophysiology of alcoholism | Annals of General Psychiatry | Full Text
    https://annals-general-psychiatry.biomedcentral.com/articles/10.1186/1744-859X-8-10
    Overall, the results of the majority of twin genetic studies support the existence of significant genetic factors that predispose individuals to the development of alcohol related problems. […] There have been several family studies on alcoholism that have provided important knowledge about the inheritance and the predisposition to alcoholism through the generations. […] Amongst the variables that enhance the risk of developing alcoholism, the genes responsible for the liver enzymes are believed to be related to an increased risk for alcohol dependence. […] Genetic studies conducted in various ethnic groups have confirmed that certain allele variations of ADH offer strong protection against alcohol addiction. […] In addition to the enzyme genes, neurotransmitter genes have been associated with increased risk for alcohol dependence.
  • #31 The Science of Addiction: How Alcohol Affects the Brain
    https://boldhealthinc.com/the-science-of-addiction-how-alcohol-affects-the-brain-understanding-the-impact/
    Alcohol consumption leads to an increase in dopamine levels in the brain’s reward centers. […] This surge in dopamine contributes to the feelings of pleasure and euphoria often experienced during drinking. […] However, over time, the brain may start to associate alcohol with these positive feelings, potentially leading to addiction. […] Chronic alcohol consumption can lead to alterations in brain structure, including a reduction in brain volume. […] This shrinkage predominantly affects the frontal lobes, which are responsible for higher cognitive functions, such as planning, regulating emotions, and impulse control. […] Prolonged alcohol use can lead to long-term changes in brain chemistry. […] Regular exposure to alcohol can alter the balance of neurotransmitters, making the brain less responsive to alcohol and other stimuli.
  • #32 The Science of Addiction: How Alcohol Affects the Brain
    https://boldhealthinc.com/the-science-of-addiction-how-alcohol-affects-the-brain-understanding-the-impact/
    Alcohol consumption leads to an increase in dopamine levels in the brain’s reward centers. […] This surge in dopamine contributes to the feelings of pleasure and euphoria often experienced during drinking. […] However, over time, the brain may start to associate alcohol with these positive feelings, potentially leading to addiction. […] Chronic alcohol consumption can lead to alterations in brain structure, including a reduction in brain volume. […] This shrinkage predominantly affects the frontal lobes, which are responsible for higher cognitive functions, such as planning, regulating emotions, and impulse control. […] Prolonged alcohol use can lead to long-term changes in brain chemistry. […] Regular exposure to alcohol can alter the balance of neurotransmitters, making the brain less responsive to alcohol and other stimuli.
  • #33 The Science of Addiction: How Alcohol Affects the Brain
    https://boldhealthinc.com/the-science-of-addiction-how-alcohol-affects-the-brain-understanding-the-impact/
    Alcohol consumption leads to an increase in dopamine levels in the brain’s reward centers. […] This surge in dopamine contributes to the feelings of pleasure and euphoria often experienced during drinking. […] However, over time, the brain may start to associate alcohol with these positive feelings, potentially leading to addiction. […] Chronic alcohol consumption can lead to alterations in brain structure, including a reduction in brain volume. […] This shrinkage predominantly affects the frontal lobes, which are responsible for higher cognitive functions, such as planning, regulating emotions, and impulse control. […] Prolonged alcohol use can lead to long-term changes in brain chemistry. […] Regular exposure to alcohol can alter the balance of neurotransmitters, making the brain less responsive to alcohol and other stimuli.
  • #34 The Science of Addiction: How Alcohol Affects the Brain
    https://boldhealthinc.com/the-science-of-addiction-how-alcohol-affects-the-brain-understanding-the-impact/
    Alcohol consumption leads to an increase in dopamine levels in the brain’s reward centers. […] This surge in dopamine contributes to the feelings of pleasure and euphoria often experienced during drinking. […] However, over time, the brain may start to associate alcohol with these positive feelings, potentially leading to addiction. […] Chronic alcohol consumption can lead to alterations in brain structure, including a reduction in brain volume. […] This shrinkage predominantly affects the frontal lobes, which are responsible for higher cognitive functions, such as planning, regulating emotions, and impulse control. […] Prolonged alcohol use can lead to long-term changes in brain chemistry. […] Regular exposure to alcohol can alter the balance of neurotransmitters, making the brain less responsive to alcohol and other stimuli.
  • #35 The Science of Addiction: How Alcohol Affects the Brain
    https://boldhealthinc.com/the-science-of-addiction-how-alcohol-affects-the-brain-understanding-the-impact/
    This can lead to a range of issues, including increased tolerance to alcohol, dependence, and withdrawal symptoms when not consuming alcohol. […] Alcohol consumption, especially in large quantities, can disrupt the process of neurogenesis, the creation of new neurons, particularly in the hippocampus. […] This disruption can have long-term implications for learning and memory. […] High levels of alcohol consumption can be neurotoxic, leading to cell death in certain areas of the brain. […] Alcohol enhances the effect of GABA, leading to a slowing down of brain activity. […] However, chronic alcohol use can disrupt the normal functioning of GABA, contributing to dependence and withdrawal symptoms. […] Alcohol inhibits glutamate’s action at the NMDA receptors, leading to a decrease in brain activity.
  • #36 The Science of Addiction: How Alcohol Affects the Brain
    https://boldhealthinc.com/the-science-of-addiction-how-alcohol-affects-the-brain-understanding-the-impact/
    This can lead to a range of issues, including increased tolerance to alcohol, dependence, and withdrawal symptoms when not consuming alcohol. […] Alcohol consumption, especially in large quantities, can disrupt the process of neurogenesis, the creation of new neurons, particularly in the hippocampus. […] This disruption can have long-term implications for learning and memory. […] High levels of alcohol consumption can be neurotoxic, leading to cell death in certain areas of the brain. […] Alcohol enhances the effect of GABA, leading to a slowing down of brain activity. […] However, chronic alcohol use can disrupt the normal functioning of GABA, contributing to dependence and withdrawal symptoms. […] Alcohol inhibits glutamate’s action at the NMDA receptors, leading to a decrease in brain activity.
  • #37 The Science of Addiction: How Alcohol Affects the Brain
    https://boldhealthinc.com/the-science-of-addiction-how-alcohol-affects-the-brain-understanding-the-impact/
    This can lead to a range of issues, including increased tolerance to alcohol, dependence, and withdrawal symptoms when not consuming alcohol. […] Alcohol consumption, especially in large quantities, can disrupt the process of neurogenesis, the creation of new neurons, particularly in the hippocampus. […] This disruption can have long-term implications for learning and memory. […] High levels of alcohol consumption can be neurotoxic, leading to cell death in certain areas of the brain. […] Alcohol enhances the effect of GABA, leading to a slowing down of brain activity. […] However, chronic alcohol use can disrupt the normal functioning of GABA, contributing to dependence and withdrawal symptoms. […] Alcohol inhibits glutamate’s action at the NMDA receptors, leading to a decrease in brain activity.
  • #38 The Science of Addiction: How Alcohol Affects the Brain
    https://boldhealthinc.com/the-science-of-addiction-how-alcohol-affects-the-brain-understanding-the-impact/
    This can lead to a range of issues, including increased tolerance to alcohol, dependence, and withdrawal symptoms when not consuming alcohol. […] Alcohol consumption, especially in large quantities, can disrupt the process of neurogenesis, the creation of new neurons, particularly in the hippocampus. […] This disruption can have long-term implications for learning and memory. […] High levels of alcohol consumption can be neurotoxic, leading to cell death in certain areas of the brain. […] Alcohol enhances the effect of GABA, leading to a slowing down of brain activity. […] However, chronic alcohol use can disrupt the normal functioning of GABA, contributing to dependence and withdrawal symptoms. […] Alcohol inhibits glutamate’s action at the NMDA receptors, leading to a decrease in brain activity.
  • #39 Alcohol Toxicity and Withdrawal – Special Subjects – MSD Manual Professional Edition
    https://www.msdmanuals.com/professional/special-subjects/illicit-drugs-and-intoxicants/alcohol-toxicity-and-withdrawal
    Alcohol is absorbed into the blood mainly from the small bowel, although some is absorbed from the stomach. Alcohol accumulates in blood because absorption is more rapid than oxidation and elimination. Alcohol exerts its effects by several mechanisms. Alcohol binds directly to gamma-aminobutyric acid (GABA) receptors in the central nervous system, causing sedation. Alcohol also directly affects cardiac, hepatic, and thyroid tissue. […] The physical dependence accompanying tolerance is profound, and alcohol withdrawal has potentially fatal adverse effects. […] A continuum of symptoms and signs of central nervous system (including autonomic) hyperactivity may accompany cessation of alcohol intake. […] Alcoholic hallucinosis follows abrupt cessation from prolonged, excessive alcohol use, usually within 12 to 24 hours. […] Delirium tremens usually begins 48 to 72 hours after alcohol withdrawal; anxiety attacks, increasing confusion, poor sleep (with frightening dreams or nocturnal illusions), profuse sweating, and severe depression also occur.
  • #40 Alcohol Toxicity and Withdrawal – Special Subjects – MSD Manual Professional Edition
    https://www.msdmanuals.com/professional/special-subjects/illicit-drugs-and-intoxicants/alcohol-toxicity-and-withdrawal
    Alcohol is absorbed into the blood mainly from the small bowel, although some is absorbed from the stomach. Alcohol accumulates in blood because absorption is more rapid than oxidation and elimination. Alcohol exerts its effects by several mechanisms. Alcohol binds directly to gamma-aminobutyric acid (GABA) receptors in the central nervous system, causing sedation. Alcohol also directly affects cardiac, hepatic, and thyroid tissue. […] The physical dependence accompanying tolerance is profound, and alcohol withdrawal has potentially fatal adverse effects. […] A continuum of symptoms and signs of central nervous system (including autonomic) hyperactivity may accompany cessation of alcohol intake. […] Alcoholic hallucinosis follows abrupt cessation from prolonged, excessive alcohol use, usually within 12 to 24 hours. […] Delirium tremens usually begins 48 to 72 hours after alcohol withdrawal; anxiety attacks, increasing confusion, poor sleep (with frightening dreams or nocturnal illusions), profuse sweating, and severe depression also occur.
  • #41 Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease | Journal of Translational Medicine | Full Text
    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04166-8
    The oxidative metabolite of ethanol, acetaldehyde, is highly toxic and can readily undergo crosslinking with DNA or protein macromolecules in mitochondria. […] Ethanol oxidation leads to an increase in free radical production in the liver. Uncontrolled ROS are critical to hepatocyte swelling and apoptosis. […] Acetaldehyde can induce ROS production and lead to ALD. […] Nitrification stress refers to the biochemical action of reactive nitrogen species, where nitric oxide (NO) is attached to a tyrosine residue, resulting in the generation of intracellular proteins carrying 3-nitrotyrosine (3-NT) residues. […] Sustained ER stress may lead to cell and tissue damage. […] Ethanol can trigger the ER stress response, which is followed by the stimulation of apoptosis-related gene expression, cell proliferation, and apoptosis imbalance.
  • #42 Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease | Journal of Translational Medicine | Full Text
    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04166-8
    Ethanol-induced liver injury mainly involves structural damage to liver cells, lipid accumulation, and inflammation. […] Ethanol can be alternatively metabolized via nonoxidative pathways. […] The binding of acetaldehyde to GSH inhibits the scavenging function of hydrogen peroxide, thereby exacerbating oxidative stress and lipid peroxidation. […] The main enzymes related to nitrification stress are two subtypes of NO synthase (NOS): endothelial NOS (eNOS) and inducible NOS (iNOS). […] The expression of SREBP-1 was also upregulated by ethanol-mediated ER stress. […] The oxidative metabolite of ethanol, acetaldehyde, is highly toxic and can readily undergo crosslinking with DNA or protein macromolecules in mitochondria. […] The binding of acetaldehyde to GSH inhibits the scavenging function of hydrogen peroxide, thereby exacerbating oxidative stress and lipid peroxidation.
  • #43 Pathogenesis of alcohol-associated liver disease – UpToDate
    https://www.uptodate.com/contents/pathogenesis-of-alcohol-associated-liver-disease
    The pathogenesis of liver disease associated with alcohol ingestion is incompletely understood. What is known is that some patients with alcohol use disorder develop liver disease, primarily because the liver metabolizes the majority of ingested ethanol. Furthermore, the metabolism of ethanol is required for hepatic injury to occur, although variations in ethanol metabolism do not completely explain the variable susceptibility to alcohol-associated liver disease. […] This topic will focus on the following issues related to risk of alcohol-associated liver disease: […] Mechanisms that may be responsible for the development of liver disease.
  • #44 Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease | Journal of Translational Medicine | Full Text
    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04166-8
    The oxidative metabolite of ethanol, acetaldehyde, is highly toxic and can readily undergo crosslinking with DNA or protein macromolecules in mitochondria. […] Ethanol oxidation leads to an increase in free radical production in the liver. Uncontrolled ROS are critical to hepatocyte swelling and apoptosis. […] Acetaldehyde can induce ROS production and lead to ALD. […] Nitrification stress refers to the biochemical action of reactive nitrogen species, where nitric oxide (NO) is attached to a tyrosine residue, resulting in the generation of intracellular proteins carrying 3-nitrotyrosine (3-NT) residues. […] Sustained ER stress may lead to cell and tissue damage. […] Ethanol can trigger the ER stress response, which is followed by the stimulation of apoptosis-related gene expression, cell proliferation, and apoptosis imbalance.
  • #45 Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease | Journal of Translational Medicine | Full Text
    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04166-8
    The oxidative metabolite of ethanol, acetaldehyde, is highly toxic and can readily undergo crosslinking with DNA or protein macromolecules in mitochondria. […] Ethanol oxidation leads to an increase in free radical production in the liver. Uncontrolled ROS are critical to hepatocyte swelling and apoptosis. […] Acetaldehyde can induce ROS production and lead to ALD. […] Nitrification stress refers to the biochemical action of reactive nitrogen species, where nitric oxide (NO) is attached to a tyrosine residue, resulting in the generation of intracellular proteins carrying 3-nitrotyrosine (3-NT) residues. […] Sustained ER stress may lead to cell and tissue damage. […] Ethanol can trigger the ER stress response, which is followed by the stimulation of apoptosis-related gene expression, cell proliferation, and apoptosis imbalance.
  • #46 Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease | Journal of Translational Medicine | Full Text
    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04166-8
    Ethanol-induced liver injury mainly involves structural damage to liver cells, lipid accumulation, and inflammation. […] Ethanol can be alternatively metabolized via nonoxidative pathways. […] The binding of acetaldehyde to GSH inhibits the scavenging function of hydrogen peroxide, thereby exacerbating oxidative stress and lipid peroxidation. […] The main enzymes related to nitrification stress are two subtypes of NO synthase (NOS): endothelial NOS (eNOS) and inducible NOS (iNOS). […] The expression of SREBP-1 was also upregulated by ethanol-mediated ER stress. […] The oxidative metabolite of ethanol, acetaldehyde, is highly toxic and can readily undergo crosslinking with DNA or protein macromolecules in mitochondria. […] The binding of acetaldehyde to GSH inhibits the scavenging function of hydrogen peroxide, thereby exacerbating oxidative stress and lipid peroxidation.
  • #47 Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease | Journal of Translational Medicine | Full Text
    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04166-8
    The oxidative metabolite of ethanol, acetaldehyde, is highly toxic and can readily undergo crosslinking with DNA or protein macromolecules in mitochondria. […] Ethanol oxidation leads to an increase in free radical production in the liver. Uncontrolled ROS are critical to hepatocyte swelling and apoptosis. […] Acetaldehyde can induce ROS production and lead to ALD. […] Nitrification stress refers to the biochemical action of reactive nitrogen species, where nitric oxide (NO) is attached to a tyrosine residue, resulting in the generation of intracellular proteins carrying 3-nitrotyrosine (3-NT) residues. […] Sustained ER stress may lead to cell and tissue damage. […] Ethanol can trigger the ER stress response, which is followed by the stimulation of apoptosis-related gene expression, cell proliferation, and apoptosis imbalance.
  • #48 Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease | Journal of Translational Medicine | Full Text
    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04166-8
    The oxidative metabolite of ethanol, acetaldehyde, is highly toxic and can readily undergo crosslinking with DNA or protein macromolecules in mitochondria. […] Ethanol oxidation leads to an increase in free radical production in the liver. Uncontrolled ROS are critical to hepatocyte swelling and apoptosis. […] Acetaldehyde can induce ROS production and lead to ALD. […] Nitrification stress refers to the biochemical action of reactive nitrogen species, where nitric oxide (NO) is attached to a tyrosine residue, resulting in the generation of intracellular proteins carrying 3-nitrotyrosine (3-NT) residues. […] Sustained ER stress may lead to cell and tissue damage. […] Ethanol can trigger the ER stress response, which is followed by the stimulation of apoptosis-related gene expression, cell proliferation, and apoptosis imbalance.
  • #49 Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease | Journal of Translational Medicine | Full Text
    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04166-8
    Ethanol-induced liver injury mainly involves structural damage to liver cells, lipid accumulation, and inflammation. […] Ethanol can be alternatively metabolized via nonoxidative pathways. […] The binding of acetaldehyde to GSH inhibits the scavenging function of hydrogen peroxide, thereby exacerbating oxidative stress and lipid peroxidation. […] The main enzymes related to nitrification stress are two subtypes of NO synthase (NOS): endothelial NOS (eNOS) and inducible NOS (iNOS). […] The expression of SREBP-1 was also upregulated by ethanol-mediated ER stress. […] The oxidative metabolite of ethanol, acetaldehyde, is highly toxic and can readily undergo crosslinking with DNA or protein macromolecules in mitochondria. […] The binding of acetaldehyde to GSH inhibits the scavenging function of hydrogen peroxide, thereby exacerbating oxidative stress and lipid peroxidation.
  • #50 Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease | Journal of Translational Medicine | Full Text
    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04166-8
    The intake of a large amount of ethanol induces the expression of ASS, which enzymatically activates the nitrification stress response and apoptosis in liver cells. […] The liver and digestive tract are closely associated and their interactions form the gut-liver axis. The translocation of bacterial or microbial products from the intestine to the liver is a key inflammatory factor that induces the transition from alcoholic steatosis to ASH. […] Ethanol exposure results in the loss of epithelial cells at the tip of intestinal villi. […] After long-term ethanol intake, the intestinal epithelial cell structure in rats is markedly changed, exhibiting mitochondrial and endoplasmic reticulum dilation. […] The oxidative stress initiated by ethanol led to the oxidation of cytoskeletal microtubules and TJ decomposition.
  • #51 Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease | Journal of Translational Medicine | Full Text
    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04166-8
    The intake of a large amount of ethanol induces the expression of ASS, which enzymatically activates the nitrification stress response and apoptosis in liver cells. […] The liver and digestive tract are closely associated and their interactions form the gut-liver axis. The translocation of bacterial or microbial products from the intestine to the liver is a key inflammatory factor that induces the transition from alcoholic steatosis to ASH. […] Ethanol exposure results in the loss of epithelial cells at the tip of intestinal villi. […] After long-term ethanol intake, the intestinal epithelial cell structure in rats is markedly changed, exhibiting mitochondrial and endoplasmic reticulum dilation. […] The oxidative stress initiated by ethanol led to the oxidation of cytoskeletal microtubules and TJ decomposition.
  • #52 Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease | Journal of Translational Medicine | Full Text
    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04166-8
    The intake of a large amount of ethanol induces the expression of ASS, which enzymatically activates the nitrification stress response and apoptosis in liver cells. […] The liver and digestive tract are closely associated and their interactions form the gut-liver axis. The translocation of bacterial or microbial products from the intestine to the liver is a key inflammatory factor that induces the transition from alcoholic steatosis to ASH. […] Ethanol exposure results in the loss of epithelial cells at the tip of intestinal villi. […] After long-term ethanol intake, the intestinal epithelial cell structure in rats is markedly changed, exhibiting mitochondrial and endoplasmic reticulum dilation. […] The oxidative stress initiated by ethanol led to the oxidation of cytoskeletal microtubules and TJ decomposition.
  • #53 Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease | Journal of Translational Medicine | Full Text
    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04166-8
    The intake of a large amount of ethanol induces the expression of ASS, which enzymatically activates the nitrification stress response and apoptosis in liver cells. […] The liver and digestive tract are closely associated and their interactions form the gut-liver axis. The translocation of bacterial or microbial products from the intestine to the liver is a key inflammatory factor that induces the transition from alcoholic steatosis to ASH. […] Ethanol exposure results in the loss of epithelial cells at the tip of intestinal villi. […] After long-term ethanol intake, the intestinal epithelial cell structure in rats is markedly changed, exhibiting mitochondrial and endoplasmic reticulum dilation. […] The oxidative stress initiated by ethanol led to the oxidation of cytoskeletal microtubules and TJ decomposition.
  • #54 Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease | Journal of Translational Medicine | Full Text
    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04166-8
    The physical interaction between ethanol and intestinal microbes may be a key reason for the ethanol-driven alteration in the intestinal flora contents. […] The association of MyD88 with interleukin (IL)-1 receptor-associated kinases 14 leads to the activation of the tumour necrosis factor receptor-associated factor 6/transforming growth factor -activated kinase 1 complex, which activates mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), P38, and extracellular signal-regulated protein kinase (ERK), resulting in inflammation and apoptosis. […] Ethanol consumption can result in nuclear factor-kappaB (NF-B) translocation to the nucleus via the phosphorylation of inhibitory B (IB) and to the release of inflammatory cytokines. […] Ethanol alters signalling cascades, such as the Wnt/-catenin signalling pathway.
  • #55 Hangover Syndrome: Pathogenesis and Treatment
    https://clinmedjournals.org/articles/iasar/international-archives-of-substance-abuse-and-rehabilitation-iasar-3-009.php?jid=iasar
    Changes in the composition of the intestinal microflora may play an important role in the pathogenesis of hangover syndrome. It has been shown that chronic alcohol consumption leads to dysbiosis. Alcohol-induced dysbiosis is characterized by an increase in the number of pro-inflammatory and a decrease in the number of anti-inflammatory bacteria. […] A number of studies have presented data indicating the involvement of the immune system in the pathogenesis of HS. […] Additional pathogenic mechanisms of HS can be dehydration (alcohol increases diuresis), impaired mineral metabolism (a decrease in the level of calcium and magnesium in the blood plasma), alcoholic lactate and ketoacidosis (due to increased formation of acetoacetate and beta-hydroxybutyric acid). […] Insufficient understanding of the pathogenetic mechanisms of HS complicates the development of scientifically proven effective means of its prevention and treatment.
  • #56 Alcohol Use Disorder: A Growing Public Health Crisis | Columbia University Department of Psychiatry
    https://www.columbiapsychiatry.org/news/alcohol-use-disorder-growing-public-health-crisis
    AUD is a chronic brain disorder resulting from compulsive alcohol consumption, loss of control over alcohol use, and negative emotions (e.g., stress and anger) when not drinking. […] Social drinkers dont have the same difficulty controlling or limiting what they drink, while those with AUD tend to struggle with intense cravings and are often unable to predict how much they will drink and when they will stop. […] There are three medications approved by the FDA for treating alcohol dependence: disulfiram, acamprosate, and naltrexone. Disulfiram works by blocking the breakdown of alcohol in the body, which leads to a buildup of a toxic compound that can cause people who drink alcohol while taking the medication to get sick. Naltrexone binds to the endorphin receptors in the body and blocks the effects and feelings of alcohol. Acamprosate reduces the brains dependence on alcohol by changing how it produces and releases neurotransmitters.
  • #57 Alcohol use disorder: pathophysiology, effects, and pharmacologic options for treatment
    https://pmc.ncbi.nlm.nih.gov/articles/PMC3931699/
    The primary pharmacologic action of disulfiram involves the disruption of normal alcohol metabolism. […] Acamprosate is believed to normalize the balance between excitatory and inhibitory pathways that become adapted to chronic alcohol use and alleviate psychological and physiological discomfort that follows withdrawal. […] Naltrexone functions as a competitive antagonist at opioid receptors. […] Pharmacologic strategies to reduce drinking in patients with AUD may attempt to correct the imbalance between excitatory and inhibitory pathways, and relieve the intense craving for alcohol brought about by neuroadaptation.
  • #58 Alcohol Use Disorder: A Growing Public Health Crisis | Columbia University Department of Psychiatry
    https://www.columbiapsychiatry.org/news/alcohol-use-disorder-growing-public-health-crisis
    AUD is a chronic brain disorder resulting from compulsive alcohol consumption, loss of control over alcohol use, and negative emotions (e.g., stress and anger) when not drinking. […] Social drinkers dont have the same difficulty controlling or limiting what they drink, while those with AUD tend to struggle with intense cravings and are often unable to predict how much they will drink and when they will stop. […] There are three medications approved by the FDA for treating alcohol dependence: disulfiram, acamprosate, and naltrexone. Disulfiram works by blocking the breakdown of alcohol in the body, which leads to a buildup of a toxic compound that can cause people who drink alcohol while taking the medication to get sick. Naltrexone binds to the endorphin receptors in the body and blocks the effects and feelings of alcohol. Acamprosate reduces the brains dependence on alcohol by changing how it produces and releases neurotransmitters.
  • #59 Alcohol use disorder: pathophysiology, effects, and pharmacologic options for treatment
    https://pmc.ncbi.nlm.nih.gov/articles/PMC3931699/
    The primary pharmacologic action of disulfiram involves the disruption of normal alcohol metabolism. […] Acamprosate is believed to normalize the balance between excitatory and inhibitory pathways that become adapted to chronic alcohol use and alleviate psychological and physiological discomfort that follows withdrawal. […] Naltrexone functions as a competitive antagonist at opioid receptors. […] Pharmacologic strategies to reduce drinking in patients with AUD may attempt to correct the imbalance between excitatory and inhibitory pathways, and relieve the intense craving for alcohol brought about by neuroadaptation.
  • #60 Alcohol use disorder: Pharmacologic management – UpToDate
    https://www.uptodate.com/contents/alcohol-use-disorder-pharmacologic-management
    Pharmacologic treatment of alcohol use disorder has focused on altering the reinforcing effects of alcohol use. Medication development has focused on several neurotransmitter systems that mediate reinforcement including opioid, glutamate, gamma-aminobutyric acid, and serotonin systems. […] Several medications can be used to treat alcohol use disorder, leading to reduced heavy drinking and increased days of abstinence. These outcomes likely reduce the overall risk associated with alcohol use disorder despite total abstinence not being achieved. […] Acamprosate’s principal antidrinking neurochemical effect has been attributed to the modulation of glutamate neurotransmission at metabotropic-5 glutamate receptors. […] Naltrexone exerts its principal pharmacologic effects through blockade of the mu-opioid receptor. Endogenous opioids modulate alcohol’s reinforcing effects.
  • #61 Alcohol Use Disorder: A Growing Public Health Crisis | Columbia University Department of Psychiatry
    https://www.columbiapsychiatry.org/news/alcohol-use-disorder-growing-public-health-crisis
    AUD is a chronic brain disorder resulting from compulsive alcohol consumption, loss of control over alcohol use, and negative emotions (e.g., stress and anger) when not drinking. […] Social drinkers dont have the same difficulty controlling or limiting what they drink, while those with AUD tend to struggle with intense cravings and are often unable to predict how much they will drink and when they will stop. […] There are three medications approved by the FDA for treating alcohol dependence: disulfiram, acamprosate, and naltrexone. Disulfiram works by blocking the breakdown of alcohol in the body, which leads to a buildup of a toxic compound that can cause people who drink alcohol while taking the medication to get sick. Naltrexone binds to the endorphin receptors in the body and blocks the effects and feelings of alcohol. Acamprosate reduces the brains dependence on alcohol by changing how it produces and releases neurotransmitters.
  • #62 Alcohol use disorder: pathophysiology, effects, and pharmacologic options for treatment
    https://pmc.ncbi.nlm.nih.gov/articles/PMC3931699/
    The primary pharmacologic action of disulfiram involves the disruption of normal alcohol metabolism. […] Acamprosate is believed to normalize the balance between excitatory and inhibitory pathways that become adapted to chronic alcohol use and alleviate psychological and physiological discomfort that follows withdrawal. […] Naltrexone functions as a competitive antagonist at opioid receptors. […] Pharmacologic strategies to reduce drinking in patients with AUD may attempt to correct the imbalance between excitatory and inhibitory pathways, and relieve the intense craving for alcohol brought about by neuroadaptation.
  • #63 Alcohol use disorder: Pharmacologic management – UpToDate
    https://www.uptodate.com/contents/alcohol-use-disorder-pharmacologic-management
    Pharmacologic treatment of alcohol use disorder has focused on altering the reinforcing effects of alcohol use. Medication development has focused on several neurotransmitter systems that mediate reinforcement including opioid, glutamate, gamma-aminobutyric acid, and serotonin systems. […] Several medications can be used to treat alcohol use disorder, leading to reduced heavy drinking and increased days of abstinence. These outcomes likely reduce the overall risk associated with alcohol use disorder despite total abstinence not being achieved. […] Acamprosate’s principal antidrinking neurochemical effect has been attributed to the modulation of glutamate neurotransmission at metabotropic-5 glutamate receptors. […] Naltrexone exerts its principal pharmacologic effects through blockade of the mu-opioid receptor. Endogenous opioids modulate alcohol’s reinforcing effects.
  • #64 Alcohol Use Disorder: A Growing Public Health Crisis | Columbia University Department of Psychiatry
    https://www.columbiapsychiatry.org/news/alcohol-use-disorder-growing-public-health-crisis
    AUD is a chronic brain disorder resulting from compulsive alcohol consumption, loss of control over alcohol use, and negative emotions (e.g., stress and anger) when not drinking. […] Social drinkers dont have the same difficulty controlling or limiting what they drink, while those with AUD tend to struggle with intense cravings and are often unable to predict how much they will drink and when they will stop. […] There are three medications approved by the FDA for treating alcohol dependence: disulfiram, acamprosate, and naltrexone. Disulfiram works by blocking the breakdown of alcohol in the body, which leads to a buildup of a toxic compound that can cause people who drink alcohol while taking the medication to get sick. Naltrexone binds to the endorphin receptors in the body and blocks the effects and feelings of alcohol. Acamprosate reduces the brains dependence on alcohol by changing how it produces and releases neurotransmitters.
  • #65 Alcohol use disorder: Pharmacologic management – UpToDate
    https://www.uptodate.com/contents/alcohol-use-disorder-pharmacologic-management
    Topiramate, an anticonvulsant medication with pharmacologic properties including blocking of voltage-dependent sodium channels, potentiation of gamma-aminobutyric acid mediated transmission and antagonism of glutamate receptors, has been found to decrease alcohol use in individuals with alcohol use disorder.
  • #66 How does topiramate work for alcohol use disorder? A look at the effects on brain activation in response to alcohol cues and relationship to alcohol craving and use – Recovery Research Institute
    https://www.recoveryanswers.org/research-post/topiramate-alcohol-use-disorder-effects-brain-activation-response-alcohol-cues-relationship-alcohol-craving-use/
    Topiramate is an anti-seizure medication that has been recently investigated for the treatment of alcohol use disorder. […] Investigating brain changes that occur in response to topiramate can provide insight into how the medication works and its utility in alcohol use disorder treatment and recovery. […] Brain imaging studies show that individuals with alcohol use disorder have enhanced dopamine release (brain chemical that plays a role in pleasure and reward) and brain activation in regions involved in reward processing (e.g., an area called the ventral striatum) when exposed to alcohol-related cues. […] It has been hypothesized that topiramate may work by reducing dopamine release in reward-related regions of the brain when alcohol is consumed, or individuals are exposed to alcohol cues.
  • #67 How does topiramate work for alcohol use disorder? A look at the effects on brain activation in response to alcohol cues and relationship to alcohol craving and use – Recovery Research Institute
    https://www.recoveryanswers.org/research-post/topiramate-alcohol-use-disorder-effects-brain-activation-response-alcohol-cues-relationship-alcohol-craving-use/
    Over time, this decrease in the brain’s response to alcohol might act to decrease the reinforcing/rewarding effects of alcohol, thereby weakening the learned association between alcohol, alcohol cues, and reward, and reducing alcohol cravings and the motivation to drink. […] Characterizing the effects of topiramate on the brain and its relationship to alcohol-related behaviors can help further our understanding of how this medication, traditionally used for epilepsy, works for alcohol use disorder. […] Given that topiramate patients had reduced activity in these two brain regions in response to alcohol cues, topiramate might act to reduce the importance of alcohol cues and the motivation to consume alcohol by reducing the perceived value (i.e., salience) of alcohol cues and, in turn weakening the learned association between alcohol cues and reward.
  • #68 Medications for Alcohol Use Disorder | AAFP
    https://www.aafp.org/pubs/afp/issues/2016/0315/p457.html
    A Cochrane review that included 50 randomized trials and 7,793 patients found that oral naltrexone decreased heavy drinking (NNT = 10) and slightly decreased daily drinking (NNT = 25). The number of heavy drinking days and the amount of alcohol consumed also decreased. […] Topiramate appears to decrease alcohol consumption. The AHRQ review concluded that there is moderate evidence that topiramate decreases number of drinking days, heavy drinking days, and drinks per day based on two randomized trials. […] Ondansetron (Zofran) may decrease alcohol consumption in patients with AUD. In three studies, ondansetron (4 mcg per kg twice per day) combined with cognitive behavior therapy decreased alcohol consumption and cravings and increased abstinence in young adults with early AUD.
  • #69 Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction | Translational Psychiatry
    https://www.nature.com/articles/s41398-024-03189-z
    Psilocybin seems promising in treating AUD since a recent clinical trial using psilocybin in combination with psychotherapy demonstrated a significant reduction of heavy drinking days in AUD patients. […] The behavioral and therapeutic effects of psilocybin are primarily attributed to the activation of the serotonin 2A receptor (5-HT2AR) and its modulation by other pathways, including the physical interaction with the mGluR2. […] Both mGluR2 and 5-HT2AR are enriched in prefrontal areas. This supports our hypothesis that their activation can restore altered ERPs and neural oscillations in alcohol-dependent rats, thereby improving cognitive functioning and reducing the risk of relapse.
  • #70 Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction | Translational Psychiatry
    https://www.nature.com/articles/s41398-024-03189-z
    Psilocybin seems promising in treating AUD since a recent clinical trial using psilocybin in combination with psychotherapy demonstrated a significant reduction of heavy drinking days in AUD patients. […] The behavioral and therapeutic effects of psilocybin are primarily attributed to the activation of the serotonin 2A receptor (5-HT2AR) and its modulation by other pathways, including the physical interaction with the mGluR2. […] Both mGluR2 and 5-HT2AR are enriched in prefrontal areas. This supports our hypothesis that their activation can restore altered ERPs and neural oscillations in alcohol-dependent rats, thereby improving cognitive functioning and reducing the risk of relapse.
  • #71 Alcohol use disorder: pathophysiology, effects, and pharmacologic options for treatment
    https://pmc.ncbi.nlm.nih.gov/articles/PMC3931699/
    The primary pharmacologic action of disulfiram involves the disruption of normal alcohol metabolism. […] Acamprosate is believed to normalize the balance between excitatory and inhibitory pathways that become adapted to chronic alcohol use and alleviate psychological and physiological discomfort that follows withdrawal. […] Naltrexone functions as a competitive antagonist at opioid receptors. […] Pharmacologic strategies to reduce drinking in patients with AUD may attempt to correct the imbalance between excitatory and inhibitory pathways, and relieve the intense craving for alcohol brought about by neuroadaptation.
  • #72 Alcohol use disorder: Pharmacologic management – UpToDate
    https://www.uptodate.com/contents/alcohol-use-disorder-pharmacologic-management
    Pharmacologic treatment of alcohol use disorder has focused on altering the reinforcing effects of alcohol use. Medication development has focused on several neurotransmitter systems that mediate reinforcement including opioid, glutamate, gamma-aminobutyric acid, and serotonin systems. […] Several medications can be used to treat alcohol use disorder, leading to reduced heavy drinking and increased days of abstinence. These outcomes likely reduce the overall risk associated with alcohol use disorder despite total abstinence not being achieved. […] Acamprosate’s principal antidrinking neurochemical effect has been attributed to the modulation of glutamate neurotransmission at metabotropic-5 glutamate receptors. […] Naltrexone exerts its principal pharmacologic effects through blockade of the mu-opioid receptor. Endogenous opioids modulate alcohol’s reinforcing effects.
  • #73 Alcohol use disorder: Pharmacologic management – UpToDate
    https://www.uptodate.com/contents/alcohol-use-disorder-pharmacologic-management
    Pharmacologic treatment of alcohol use disorder has focused on altering the reinforcing effects of alcohol use. Medication development has focused on several neurotransmitter systems that mediate reinforcement including opioid, glutamate, gamma-aminobutyric acid, and serotonin systems. […] Several medications can be used to treat alcohol use disorder, leading to reduced heavy drinking and increased days of abstinence. These outcomes likely reduce the overall risk associated with alcohol use disorder despite total abstinence not being achieved. […] Acamprosate’s principal antidrinking neurochemical effect has been attributed to the modulation of glutamate neurotransmission at metabotropic-5 glutamate receptors. […] Naltrexone exerts its principal pharmacologic effects through blockade of the mu-opioid receptor. Endogenous opioids modulate alcohol’s reinforcing effects.
  • #74 How Alcohol Affects People With Schizophrenia – Alcohol Help
    https://www.alcoholhelp.com/resources/dual-diagnosis/alcohol-and-schizophrenia/
    People with any mental health disorder can be more likely to develop alcoholism. […] The desired effects of alcohol use occur because alcohol is a central nervous system (CNS) depressant. […] Not only does this dull many symptoms of schizophrenia, giving the sufferer break from what they normally experience, but studies show that alcohol can have a greater euphoric effect on them than people without the disorder. […] The increased consumption makes schizophrenics more susceptible to develop an alcohol use disorder (AUD). […] An alcohol use disorder will affect a schizophrenic in every way it would affect someone without the disorder, straining their relationships and health. […] Additionally, the symptoms of withdrawal can make their hallucinations worse, adding additional pain to what they are seeing and hearing.
  • #75 How Alcohol Affects People With Schizophrenia – Alcohol Help
    https://www.alcoholhelp.com/resources/dual-diagnosis/alcohol-and-schizophrenia/
    People with any mental health disorder can be more likely to develop alcoholism. […] The desired effects of alcohol use occur because alcohol is a central nervous system (CNS) depressant. […] Not only does this dull many symptoms of schizophrenia, giving the sufferer break from what they normally experience, but studies show that alcohol can have a greater euphoric effect on them than people without the disorder. […] The increased consumption makes schizophrenics more susceptible to develop an alcohol use disorder (AUD). […] An alcohol use disorder will affect a schizophrenic in every way it would affect someone without the disorder, straining their relationships and health. […] Additionally, the symptoms of withdrawal can make their hallucinations worse, adding additional pain to what they are seeing and hearing.
  • #76 Alcohol and anxiety: Causes, risks, and treatment
    https://www.medicalnewstoday.com/articles/326597
    People with anxiety disorders may use alcohol as a coping mechanism, which could lead to alcohol use disorder (AUD). […] Research suggests there may be a bidirectional connection between anxiety disorders and AUD. […] People with AUD may have a higher risk of developing an anxiety disorder, such as generalized anxiety disorder or social anxiety. […] The National Institute on Alcohol Abuse and Alcoholism (NIAAA) suggests AUD and psychiatric conditions such as anxiety disorders share genetic and environmental risk factors. This may explain the link between them. […] In many cases, it is unclear whether alcohol causes anxiety or if anxiety makes a person more likely to drink alcohol. […] According to some animal research, those who drink alcohol in their youth may be more prone to anxiety in adulthood, which might suggest a causal relationship.
  • #77 Alcohol and anxiety: Causes, risks, and treatment
    https://www.medicalnewstoday.com/articles/326597
    People with anxiety disorders may use alcohol as a coping mechanism, which could lead to alcohol use disorder (AUD). […] Research suggests there may be a bidirectional connection between anxiety disorders and AUD. […] People with AUD may have a higher risk of developing an anxiety disorder, such as generalized anxiety disorder or social anxiety. […] The National Institute on Alcohol Abuse and Alcoholism (NIAAA) suggests AUD and psychiatric conditions such as anxiety disorders share genetic and environmental risk factors. This may explain the link between them. […] In many cases, it is unclear whether alcohol causes anxiety or if anxiety makes a person more likely to drink alcohol. […] According to some animal research, those who drink alcohol in their youth may be more prone to anxiety in adulthood, which might suggest a causal relationship.
  • #78 Alcohol and anxiety: Causes, risks, and treatment
    https://www.medicalnewstoday.com/articles/326597
    People with anxiety disorders may use alcohol as a coping mechanism, which could lead to alcohol use disorder (AUD). […] Research suggests there may be a bidirectional connection between anxiety disorders and AUD. […] People with AUD may have a higher risk of developing an anxiety disorder, such as generalized anxiety disorder or social anxiety. […] The National Institute on Alcohol Abuse and Alcoholism (NIAAA) suggests AUD and psychiatric conditions such as anxiety disorders share genetic and environmental risk factors. This may explain the link between them. […] In many cases, it is unclear whether alcohol causes anxiety or if anxiety makes a person more likely to drink alcohol. […] According to some animal research, those who drink alcohol in their youth may be more prone to anxiety in adulthood, which might suggest a causal relationship.
  • #79 Alcohol and anxiety: Causes, risks, and treatment
    https://www.medicalnewstoday.com/articles/326597
    People with anxiety disorders may use alcohol as a coping mechanism, which could lead to alcohol use disorder (AUD). […] Research suggests there may be a bidirectional connection between anxiety disorders and AUD. […] People with AUD may have a higher risk of developing an anxiety disorder, such as generalized anxiety disorder or social anxiety. […] The National Institute on Alcohol Abuse and Alcoholism (NIAAA) suggests AUD and psychiatric conditions such as anxiety disorders share genetic and environmental risk factors. This may explain the link between them. […] In many cases, it is unclear whether alcohol causes anxiety or if anxiety makes a person more likely to drink alcohol. […] According to some animal research, those who drink alcohol in their youth may be more prone to anxiety in adulthood, which might suggest a causal relationship.
  • #80 Alcohol and anxiety: Causes, risks, and treatment
    https://www.medicalnewstoday.com/articles/326597
    People with anxiety disorders may use alcohol as a coping mechanism, which could lead to alcohol use disorder (AUD). […] Research suggests there may be a bidirectional connection between anxiety disorders and AUD. […] People with AUD may have a higher risk of developing an anxiety disorder, such as generalized anxiety disorder or social anxiety. […] The National Institute on Alcohol Abuse and Alcoholism (NIAAA) suggests AUD and psychiatric conditions such as anxiety disorders share genetic and environmental risk factors. This may explain the link between them. […] In many cases, it is unclear whether alcohol causes anxiety or if anxiety makes a person more likely to drink alcohol. […] According to some animal research, those who drink alcohol in their youth may be more prone to anxiety in adulthood, which might suggest a causal relationship.
  • #81
    https://www.ijmedicine.com/index.php/ijam/article/view/434
    Alcohol use disorder is a common and challenging problem in India. In various studies the prevalence of co-morbid psychopathologies ranges from 15-70% including depression anxiety disorders. Coping mechanisms of individual play vital role in case of developing alcohol dependence and various psychopathologies. A complex interaction of psychopathologies, coping skills, and alcohol use can influence the outcome of alcohol dependence. […] Problem focussed coping mechanism such as problem solving is associated with better outcome in terms of lesser anxiety and later age of first drink as well as developing dependence. Passivity, which is an emotion focussed coping mechanism, is associated with earlier first drink and higher depression score in patient suggesting poor outcome. […] Co-morbid psychopathologies like anxiety and depression are common in alcohol dependence individuals and thus, screening for these symptoms is essential for early interventions and better outcomes.
  • #82
    https://www.ijmedicine.com/index.php/ijam/article/view/434
    Alcohol use disorder is a common and challenging problem in India. In various studies the prevalence of co-morbid psychopathologies ranges from 15-70% including depression anxiety disorders. Coping mechanisms of individual play vital role in case of developing alcohol dependence and various psychopathologies. A complex interaction of psychopathologies, coping skills, and alcohol use can influence the outcome of alcohol dependence. […] Problem focussed coping mechanism such as problem solving is associated with better outcome in terms of lesser anxiety and later age of first drink as well as developing dependence. Passivity, which is an emotion focussed coping mechanism, is associated with earlier first drink and higher depression score in patient suggesting poor outcome. […] Co-morbid psychopathologies like anxiety and depression are common in alcohol dependence individuals and thus, screening for these symptoms is essential for early interventions and better outcomes.
  • #83
    https://www.ijmedicine.com/index.php/ijam/article/view/434
    Alcohol use disorder is a common and challenging problem in India. In various studies the prevalence of co-morbid psychopathologies ranges from 15-70% including depression anxiety disorders. Coping mechanisms of individual play vital role in case of developing alcohol dependence and various psychopathologies. A complex interaction of psychopathologies, coping skills, and alcohol use can influence the outcome of alcohol dependence. […] Problem focussed coping mechanism such as problem solving is associated with better outcome in terms of lesser anxiety and later age of first drink as well as developing dependence. Passivity, which is an emotion focussed coping mechanism, is associated with earlier first drink and higher depression score in patient suggesting poor outcome. […] Co-morbid psychopathologies like anxiety and depression are common in alcohol dependence individuals and thus, screening for these symptoms is essential for early interventions and better outcomes.
  • #84 Alcohol Use as a Coping Mechanism | Sandstone Care
    https://www.sandstonecare.com/blog/alcohol-use-as-a-coping-mechanism/
    Alcohol abuse and dependence can often arise from the use of alcohol as a coping mechanism. […] Unfortunately, alcohol is a coping mechanism, the temporary benefits of which are often outweighed by the long-term negative effects on health and relationships, poor decision-making under the influence, as well as increased dependency. […] Alcohol functions to slow down the central nervous system, creating feelings of relaxation. It also reduces inhibition, judgment, and memory. Because of these qualities, alcohol becomes a way to distance oneself from stressors or challenges an individual may be facing. […] Continued avoidance of life’s challenges and lack of healthy coping mechanisms can be direct facilitators of problematic drinking down the road. […] People with a family history of alcoholism may be more prone to using alcohol as a coping method because alcohol may have been used by parents or relatives. Those who use alcohol to cope may not be equipped with adaptive coping skills.
  • #85 Alcohol Use as a Coping Mechanism | Sandstone Care
    https://www.sandstonecare.com/blog/alcohol-use-as-a-coping-mechanism/
    Alcohol abuse and dependence can often arise from the use of alcohol as a coping mechanism. […] Unfortunately, alcohol is a coping mechanism, the temporary benefits of which are often outweighed by the long-term negative effects on health and relationships, poor decision-making under the influence, as well as increased dependency. […] Alcohol functions to slow down the central nervous system, creating feelings of relaxation. It also reduces inhibition, judgment, and memory. Because of these qualities, alcohol becomes a way to distance oneself from stressors or challenges an individual may be facing. […] Continued avoidance of life’s challenges and lack of healthy coping mechanisms can be direct facilitators of problematic drinking down the road. […] People with a family history of alcoholism may be more prone to using alcohol as a coping method because alcohol may have been used by parents or relatives. Those who use alcohol to cope may not be equipped with adaptive coping skills.
  • #86 Alcohol Use as a Coping Mechanism | Sandstone Care
    https://www.sandstonecare.com/blog/alcohol-use-as-a-coping-mechanism/
    Alcohol abuse and dependence can often arise from the use of alcohol as a coping mechanism. […] Unfortunately, alcohol is a coping mechanism, the temporary benefits of which are often outweighed by the long-term negative effects on health and relationships, poor decision-making under the influence, as well as increased dependency. […] Alcohol functions to slow down the central nervous system, creating feelings of relaxation. It also reduces inhibition, judgment, and memory. Because of these qualities, alcohol becomes a way to distance oneself from stressors or challenges an individual may be facing. […] Continued avoidance of life’s challenges and lack of healthy coping mechanisms can be direct facilitators of problematic drinking down the road. […] People with a family history of alcoholism may be more prone to using alcohol as a coping method because alcohol may have been used by parents or relatives. Those who use alcohol to cope may not be equipped with adaptive coping skills.
  • #87 Alcohol Use as a Coping Mechanism | Sandstone Care
    https://www.sandstonecare.com/blog/alcohol-use-as-a-coping-mechanism/
    Alcohol abuse and dependence can often arise from the use of alcohol as a coping mechanism. […] Unfortunately, alcohol is a coping mechanism, the temporary benefits of which are often outweighed by the long-term negative effects on health and relationships, poor decision-making under the influence, as well as increased dependency. […] Alcohol functions to slow down the central nervous system, creating feelings of relaxation. It also reduces inhibition, judgment, and memory. Because of these qualities, alcohol becomes a way to distance oneself from stressors or challenges an individual may be facing. […] Continued avoidance of life’s challenges and lack of healthy coping mechanisms can be direct facilitators of problematic drinking down the road. […] People with a family history of alcoholism may be more prone to using alcohol as a coping method because alcohol may have been used by parents or relatives. Those who use alcohol to cope may not be equipped with adaptive coping skills.
  • #88 Alcohol Use as a Coping Mechanism | Sandstone Care
    https://www.sandstonecare.com/blog/alcohol-use-as-a-coping-mechanism/
    With a lack of healthy coping mechanisms, anxiety, depression, and other mental health disorders are not uncommon among people who use alcohol to cope. […] Whether or not substance abuse and/or addiction run in your family, all people experience increased tolerance for alcohol the more and longer that they drink. More alcohol is required to achieve the same effect. […] In extreme cases of physical alcohol dependence, a person can become so addicted that they experience withdrawal symptoms without the substance, such as tremors, sweating, insomnia, headaches, and more. Alcohol withdrawal can be fatal in severe cases. […] Using alcohol as a coping mechanism tends to have consequences in relationships. At best, it tends to create distance between loved ones. At worst, it can contribute to anger, fighting, and irresponsible behavior in relationships.
  • #89 Alcohol Use as a Coping Mechanism | Sandstone Care
    https://www.sandstonecare.com/blog/alcohol-use-as-a-coping-mechanism/
    With a lack of healthy coping mechanisms, anxiety, depression, and other mental health disorders are not uncommon among people who use alcohol to cope. […] Whether or not substance abuse and/or addiction run in your family, all people experience increased tolerance for alcohol the more and longer that they drink. More alcohol is required to achieve the same effect. […] In extreme cases of physical alcohol dependence, a person can become so addicted that they experience withdrawal symptoms without the substance, such as tremors, sweating, insomnia, headaches, and more. Alcohol withdrawal can be fatal in severe cases. […] Using alcohol as a coping mechanism tends to have consequences in relationships. At best, it tends to create distance between loved ones. At worst, it can contribute to anger, fighting, and irresponsible behavior in relationships.
  • #90 Alcohol Use as a Coping Mechanism | Sandstone Care
    https://www.sandstonecare.com/blog/alcohol-use-as-a-coping-mechanism/
    With a lack of healthy coping mechanisms, anxiety, depression, and other mental health disorders are not uncommon among people who use alcohol to cope. […] Whether or not substance abuse and/or addiction run in your family, all people experience increased tolerance for alcohol the more and longer that they drink. More alcohol is required to achieve the same effect. […] In extreme cases of physical alcohol dependence, a person can become so addicted that they experience withdrawal symptoms without the substance, such as tremors, sweating, insomnia, headaches, and more. Alcohol withdrawal can be fatal in severe cases. […] Using alcohol as a coping mechanism tends to have consequences in relationships. At best, it tends to create distance between loved ones. At worst, it can contribute to anger, fighting, and irresponsible behavior in relationships.
  • #91 Hangover Syndrome: Pathogenesis and Treatment
    https://clinmedjournals.org/articles/iasar/international-archives-of-substance-abuse-and-rehabilitation-iasar-3-009.php?jid=iasar
    To discuss the state of art of pathogenesis and treatment of Hangover Syndrome (HS). […] It was shown, that there is a significant gap in the understanding of pathogenesis of HS, which hamper the elaboration of means of metabolic correction of this condition. The actual task of future research is the detailed investigation of pathogenic mechanisms of HS. This will allow elaborating the comprehensive medicine for HS treatment targeting all links of its pathogenesis. […] Despite the significant damage to health and large economic losses associated with HS, the pathogenesis of this condition is not well understood. At the same time, understanding the pathogenic mechanisms of HS is necessary for the development of means for the prevention and treatment of this condition. Presumptive mechanisms of HS pathogenesis are: Alcohol-induced metabolic and endocrine disorders, oxidative stress, inflammation, disturbances in water-electrolyte balance and acid-base balance.
  • #92 Hangover Syndrome: Pathogenesis and Treatment
    https://clinmedjournals.org/articles/iasar/international-archives-of-substance-abuse-and-rehabilitation-iasar-3-009.php?jid=iasar
    To discuss the state of art of pathogenesis and treatment of Hangover Syndrome (HS). […] It was shown, that there is a significant gap in the understanding of pathogenesis of HS, which hamper the elaboration of means of metabolic correction of this condition. The actual task of future research is the detailed investigation of pathogenic mechanisms of HS. This will allow elaborating the comprehensive medicine for HS treatment targeting all links of its pathogenesis. […] Despite the significant damage to health and large economic losses associated with HS, the pathogenesis of this condition is not well understood. At the same time, understanding the pathogenic mechanisms of HS is necessary for the development of means for the prevention and treatment of this condition. Presumptive mechanisms of HS pathogenesis are: Alcohol-induced metabolic and endocrine disorders, oxidative stress, inflammation, disturbances in water-electrolyte balance and acid-base balance.
  • #93 Hangover Syndrome: Pathogenesis and Treatment
    https://clinmedjournals.org/articles/iasar/international-archives-of-substance-abuse-and-rehabilitation-iasar-3-009.php?jid=iasar
    Changes in the composition of the intestinal microflora may play an important role in the pathogenesis of hangover syndrome. It has been shown that chronic alcohol consumption leads to dysbiosis. Alcohol-induced dysbiosis is characterized by an increase in the number of pro-inflammatory and a decrease in the number of anti-inflammatory bacteria. […] A number of studies have presented data indicating the involvement of the immune system in the pathogenesis of HS. […] Additional pathogenic mechanisms of HS can be dehydration (alcohol increases diuresis), impaired mineral metabolism (a decrease in the level of calcium and magnesium in the blood plasma), alcoholic lactate and ketoacidosis (due to increased formation of acetoacetate and beta-hydroxybutyric acid). […] Insufficient understanding of the pathogenetic mechanisms of HS complicates the development of scientifically proven effective means of its prevention and treatment.
  • #94 Hangover Syndrome: Pathogenesis and Treatment
    https://clinmedjournals.org/articles/iasar/international-archives-of-substance-abuse-and-rehabilitation-iasar-3-009.php?jid=iasar
    Changes in the composition of the intestinal microflora may play an important role in the pathogenesis of hangover syndrome. It has been shown that chronic alcohol consumption leads to dysbiosis. Alcohol-induced dysbiosis is characterized by an increase in the number of pro-inflammatory and a decrease in the number of anti-inflammatory bacteria. […] A number of studies have presented data indicating the involvement of the immune system in the pathogenesis of HS. […] Additional pathogenic mechanisms of HS can be dehydration (alcohol increases diuresis), impaired mineral metabolism (a decrease in the level of calcium and magnesium in the blood plasma), alcoholic lactate and ketoacidosis (due to increased formation of acetoacetate and beta-hydroxybutyric acid). […] Insufficient understanding of the pathogenetic mechanisms of HS complicates the development of scientifically proven effective means of its prevention and treatment.
  • #95 Hangover Syndrome: Pathogenesis and Treatment
    https://clinmedjournals.org/articles/iasar/international-archives-of-substance-abuse-and-rehabilitation-iasar-3-009.php?jid=iasar
    Changes in the composition of the intestinal microflora may play an important role in the pathogenesis of hangover syndrome. It has been shown that chronic alcohol consumption leads to dysbiosis. Alcohol-induced dysbiosis is characterized by an increase in the number of pro-inflammatory and a decrease in the number of anti-inflammatory bacteria. […] A number of studies have presented data indicating the involvement of the immune system in the pathogenesis of HS. […] Additional pathogenic mechanisms of HS can be dehydration (alcohol increases diuresis), impaired mineral metabolism (a decrease in the level of calcium and magnesium in the blood plasma), alcoholic lactate and ketoacidosis (due to increased formation of acetoacetate and beta-hydroxybutyric acid). […] Insufficient understanding of the pathogenetic mechanisms of HS complicates the development of scientifically proven effective means of its prevention and treatment.
  • #96 Executive Function as an Underlying Mechanism of Alcohol Use, Aggression, and ADHD | medRxiv
    https://www.medrxiv.org/content/10.1101/2024.06.10.24308620v1
    Executive functioning (EF) has been proposed as a transdiagnostic risk factor for externalizing disorders and behavior more broadly, including attention-deficit/hyperactivity disorder (ADHD), aggression, and alcohol use. […] The current study examined reciprocal causal associations between EF and several externalizing behaviors using a Mendelian randomization (MR) approach. […] Two-sample MR was conducted to test causal associations between EF and externalizing behaviors. […] Summary statistics from several genome-wide association studies (GWASs) were used in these analyses, including GWASs of EF, ADHD diagnostic status, drinks per week, aggressive behavior, and alcohol use disorder (AUD) diagnostic status. […] EF demonstrated significant causal relationships with ADHD (P 0.01), AUD (P 0.03), and alcohol consumption (P 0.01) across several estimation methods. […] Findings suggest that EF may be a causal mechanism underlying some externalizing behaviors, including ADHD and alcohol use, and that ADHD may also lead to lower performance on EF tasks.
  • #97 Executive Function as an Underlying Mechanism of Alcohol Use, Aggression, and ADHD | medRxiv
    https://www.medrxiv.org/content/10.1101/2024.06.10.24308620v1
    Executive functioning (EF) has been proposed as a transdiagnostic risk factor for externalizing disorders and behavior more broadly, including attention-deficit/hyperactivity disorder (ADHD), aggression, and alcohol use. […] The current study examined reciprocal causal associations between EF and several externalizing behaviors using a Mendelian randomization (MR) approach. […] Two-sample MR was conducted to test causal associations between EF and externalizing behaviors. […] Summary statistics from several genome-wide association studies (GWASs) were used in these analyses, including GWASs of EF, ADHD diagnostic status, drinks per week, aggressive behavior, and alcohol use disorder (AUD) diagnostic status. […] EF demonstrated significant causal relationships with ADHD (P 0.01), AUD (P 0.03), and alcohol consumption (P 0.01) across several estimation methods. […] Findings suggest that EF may be a causal mechanism underlying some externalizing behaviors, including ADHD and alcohol use, and that ADHD may also lead to lower performance on EF tasks.
  • #98 Executive Function as an Underlying Mechanism of Alcohol Use, Aggression, and ADHD | medRxiv
    https://www.medrxiv.org/content/10.1101/2024.06.10.24308620v1
    Executive functioning (EF) has been proposed as a transdiagnostic risk factor for externalizing disorders and behavior more broadly, including attention-deficit/hyperactivity disorder (ADHD), aggression, and alcohol use. […] The current study examined reciprocal causal associations between EF and several externalizing behaviors using a Mendelian randomization (MR) approach. […] Two-sample MR was conducted to test causal associations between EF and externalizing behaviors. […] Summary statistics from several genome-wide association studies (GWASs) were used in these analyses, including GWASs of EF, ADHD diagnostic status, drinks per week, aggressive behavior, and alcohol use disorder (AUD) diagnostic status. […] EF demonstrated significant causal relationships with ADHD (P 0.01), AUD (P 0.03), and alcohol consumption (P 0.01) across several estimation methods. […] Findings suggest that EF may be a causal mechanism underlying some externalizing behaviors, including ADHD and alcohol use, and that ADHD may also lead to lower performance on EF tasks.
  • #99 Researchers discover neural mechanism behind why chronic alcohol use impairs cognitive flexibility – Vital Record
    https://vitalrecord.tamu.edu/researchers-discover-neural-mechanism-behind-why-chronic-alcohol-use-impairs-cognitive-flexibility/
    Excessive alcohol drinking and its related problems have become a grave issue in the United States. Alcohol use disorder (AUD) is a chronic brain disorder that is characterized by the inability to stop drinking despite adverse consequences. […] Given the prevalence of AUD, researchers are working to understand its mechanisms and ultimately discover new therapeutic strategies to treat the disorder. […] Using an animal model, Jun Wang, PhD, associate professor in the Department of Neuroscience and Experimental Therapeutics at the Texas AM University School of Medicine, and members of his laboratory observed that chronic alcohol intake and withdrawal reduce individuals cognitive flexibility. […] This decreased behavioral flexibility is mainly due to the reduced thalamic inputs onto dorsomedial striatum cholinergic interneurons caused by chronic alcohol consumption, Wang said. By compromising the communication between the thalamus and striatum, chronic alcohol consumption impaired animals behavioral flexibility.
  • #100 Researchers discover neural mechanism behind why chronic alcohol use impairs cognitive flexibility – Vital Record
    https://vitalrecord.tamu.edu/researchers-discover-neural-mechanism-behind-why-chronic-alcohol-use-impairs-cognitive-flexibility/
    Excessive alcohol drinking and its related problems have become a grave issue in the United States. Alcohol use disorder (AUD) is a chronic brain disorder that is characterized by the inability to stop drinking despite adverse consequences. […] Given the prevalence of AUD, researchers are working to understand its mechanisms and ultimately discover new therapeutic strategies to treat the disorder. […] Using an animal model, Jun Wang, PhD, associate professor in the Department of Neuroscience and Experimental Therapeutics at the Texas AM University School of Medicine, and members of his laboratory observed that chronic alcohol intake and withdrawal reduce individuals cognitive flexibility. […] This decreased behavioral flexibility is mainly due to the reduced thalamic inputs onto dorsomedial striatum cholinergic interneurons caused by chronic alcohol consumption, Wang said. By compromising the communication between the thalamus and striatum, chronic alcohol consumption impaired animals behavioral flexibility.
  • #101 Researchers discover neural mechanism behind why chronic alcohol use impairs cognitive flexibility – Vital Record
    https://vitalrecord.tamu.edu/researchers-discover-neural-mechanism-behind-why-chronic-alcohol-use-impairs-cognitive-flexibility/
    This lack of communication then causes impaired cognitive flexibility, indicated by the lack of reversal of instrumental learning. […] More importantly, when we selectively increased the transmission between thalamus and dorsomedial striatum cholinergic interneurons using optogenetic tools, we were able to rescue alcohol-induced reversal learning deficits in animals, Wang added. […] Even though this optogenetic method is still far from clinical application, the insights gained from this study provide a base for developing new therapeutic strategies to enhance cognitive flexibility in patients with AUD.
  • #102 Researchers discover neural mechanism behind why chronic alcohol use impairs cognitive flexibility – Vital Record
    https://vitalrecord.tamu.edu/researchers-discover-neural-mechanism-behind-why-chronic-alcohol-use-impairs-cognitive-flexibility/
    This lack of communication then causes impaired cognitive flexibility, indicated by the lack of reversal of instrumental learning. […] More importantly, when we selectively increased the transmission between thalamus and dorsomedial striatum cholinergic interneurons using optogenetic tools, we were able to rescue alcohol-induced reversal learning deficits in animals, Wang added. […] Even though this optogenetic method is still far from clinical application, the insights gained from this study provide a base for developing new therapeutic strategies to enhance cognitive flexibility in patients with AUD.
  • #103 Alcohol Toxicity and Withdrawal – Special Subjects – MSD Manual Professional Edition
    https://www.msdmanuals.com/professional/special-subjects/illicit-drugs-and-intoxicants/alcohol-toxicity-and-withdrawal
    Alcohol is absorbed into the blood mainly from the small bowel, although some is absorbed from the stomach. Alcohol accumulates in blood because absorption is more rapid than oxidation and elimination. Alcohol exerts its effects by several mechanisms. Alcohol binds directly to gamma-aminobutyric acid (GABA) receptors in the central nervous system, causing sedation. Alcohol also directly affects cardiac, hepatic, and thyroid tissue. […] The physical dependence accompanying tolerance is profound, and alcohol withdrawal has potentially fatal adverse effects. […] A continuum of symptoms and signs of central nervous system (including autonomic) hyperactivity may accompany cessation of alcohol intake. […] Alcoholic hallucinosis follows abrupt cessation from prolonged, excessive alcohol use, usually within 12 to 24 hours. […] Delirium tremens usually begins 48 to 72 hours after alcohol withdrawal; anxiety attacks, increasing confusion, poor sleep (with frightening dreams or nocturnal illusions), profuse sweating, and severe depression also occur.
  • #104 Alcohol Toxicity and Withdrawal – Special Subjects – MSD Manual Professional Edition
    https://www.msdmanuals.com/professional/special-subjects/illicit-drugs-and-intoxicants/alcohol-toxicity-and-withdrawal
    Alcohol is absorbed into the blood mainly from the small bowel, although some is absorbed from the stomach. Alcohol accumulates in blood because absorption is more rapid than oxidation and elimination. Alcohol exerts its effects by several mechanisms. Alcohol binds directly to gamma-aminobutyric acid (GABA) receptors in the central nervous system, causing sedation. Alcohol also directly affects cardiac, hepatic, and thyroid tissue. […] The physical dependence accompanying tolerance is profound, and alcohol withdrawal has potentially fatal adverse effects. […] A continuum of symptoms and signs of central nervous system (including autonomic) hyperactivity may accompany cessation of alcohol intake. […] Alcoholic hallucinosis follows abrupt cessation from prolonged, excessive alcohol use, usually within 12 to 24 hours. […] Delirium tremens usually begins 48 to 72 hours after alcohol withdrawal; anxiety attacks, increasing confusion, poor sleep (with frightening dreams or nocturnal illusions), profuse sweating, and severe depression also occur.
  • #105 Alcohol Toxicity and Withdrawal – Special Subjects – MSD Manual Professional Edition
    https://www.msdmanuals.com/professional/special-subjects/illicit-drugs-and-intoxicants/alcohol-toxicity-and-withdrawal
    Alcohol is absorbed into the blood mainly from the small bowel, although some is absorbed from the stomach. Alcohol accumulates in blood because absorption is more rapid than oxidation and elimination. Alcohol exerts its effects by several mechanisms. Alcohol binds directly to gamma-aminobutyric acid (GABA) receptors in the central nervous system, causing sedation. Alcohol also directly affects cardiac, hepatic, and thyroid tissue. […] The physical dependence accompanying tolerance is profound, and alcohol withdrawal has potentially fatal adverse effects. […] A continuum of symptoms and signs of central nervous system (including autonomic) hyperactivity may accompany cessation of alcohol intake. […] Alcoholic hallucinosis follows abrupt cessation from prolonged, excessive alcohol use, usually within 12 to 24 hours. […] Delirium tremens usually begins 48 to 72 hours after alcohol withdrawal; anxiety attacks, increasing confusion, poor sleep (with frightening dreams or nocturnal illusions), profuse sweating, and severe depression also occur.
  • #106 Alcohol Toxicity and Withdrawal – Special Subjects – MSD Manual Professional Edition
    https://www.msdmanuals.com/professional/special-subjects/illicit-drugs-and-intoxicants/alcohol-toxicity-and-withdrawal
    Alcohol is absorbed into the blood mainly from the small bowel, although some is absorbed from the stomach. Alcohol accumulates in blood because absorption is more rapid than oxidation and elimination. Alcohol exerts its effects by several mechanisms. Alcohol binds directly to gamma-aminobutyric acid (GABA) receptors in the central nervous system, causing sedation. Alcohol also directly affects cardiac, hepatic, and thyroid tissue. […] The physical dependence accompanying tolerance is profound, and alcohol withdrawal has potentially fatal adverse effects. […] A continuum of symptoms and signs of central nervous system (including autonomic) hyperactivity may accompany cessation of alcohol intake. […] Alcoholic hallucinosis follows abrupt cessation from prolonged, excessive alcohol use, usually within 12 to 24 hours. […] Delirium tremens usually begins 48 to 72 hours after alcohol withdrawal; anxiety attacks, increasing confusion, poor sleep (with frightening dreams or nocturnal illusions), profuse sweating, and severe depression also occur.
  • #107 Wernicke-Korsakoff Syndrome: Causes, Symptoms & Treatment
    https://my.clevelandclinic.org/health/diseases/22687-wernicke-korsakoff-syndrome
    Wernicke encephalopathy develops most often in people with alcohol use disorder. […] An estimated 80% of people with alcohol addiction dont absorb or retain enough thiamine. […] The most common cause of thiamine deficiency is chronic alcohol use. Alcohol makes it harder for your body to absorb thiamine and store it in your liver. […] About 50% of those who develop Wernicke encephalopathy eventually develop Korsakoff syndrome. The number is higher (80%) among those who have alcohol use disorder.
  • #108 Wernicke-Korsakoff Syndrome: Causes, Symptoms & Treatment
    https://my.clevelandclinic.org/health/diseases/22687-wernicke-korsakoff-syndrome
    Wernicke encephalopathy develops most often in people with alcohol use disorder. […] An estimated 80% of people with alcohol addiction dont absorb or retain enough thiamine. […] The most common cause of thiamine deficiency is chronic alcohol use. Alcohol makes it harder for your body to absorb thiamine and store it in your liver. […] About 50% of those who develop Wernicke encephalopathy eventually develop Korsakoff syndrome. The number is higher (80%) among those who have alcohol use disorder.
  • #109 Wernicke-Korsakoff Syndrome: Causes, Symptoms & Treatment
    https://my.clevelandclinic.org/health/diseases/22687-wernicke-korsakoff-syndrome
    Wernicke encephalopathy develops most often in people with alcohol use disorder. […] An estimated 80% of people with alcohol addiction dont absorb or retain enough thiamine. […] The most common cause of thiamine deficiency is chronic alcohol use. Alcohol makes it harder for your body to absorb thiamine and store it in your liver. […] About 50% of those who develop Wernicke encephalopathy eventually develop Korsakoff syndrome. The number is higher (80%) among those who have alcohol use disorder.
  • #110 The Science of Addiction: How Alcohol Affects the Brain
    https://boldhealthinc.com/the-science-of-addiction-how-alcohol-affects-the-brain-understanding-the-impact/
    This can lead to a range of issues, including increased tolerance to alcohol, dependence, and withdrawal symptoms when not consuming alcohol. […] Alcohol consumption, especially in large quantities, can disrupt the process of neurogenesis, the creation of new neurons, particularly in the hippocampus. […] This disruption can have long-term implications for learning and memory. […] High levels of alcohol consumption can be neurotoxic, leading to cell death in certain areas of the brain. […] Alcohol enhances the effect of GABA, leading to a slowing down of brain activity. […] However, chronic alcohol use can disrupt the normal functioning of GABA, contributing to dependence and withdrawal symptoms. […] Alcohol inhibits glutamate’s action at the NMDA receptors, leading to a decrease in brain activity.
  • #111 The Science of Addiction: How Alcohol Affects the Brain
    https://boldhealthinc.com/the-science-of-addiction-how-alcohol-affects-the-brain-understanding-the-impact/
    This can lead to a range of issues, including increased tolerance to alcohol, dependence, and withdrawal symptoms when not consuming alcohol. […] Alcohol consumption, especially in large quantities, can disrupt the process of neurogenesis, the creation of new neurons, particularly in the hippocampus. […] This disruption can have long-term implications for learning and memory. […] High levels of alcohol consumption can be neurotoxic, leading to cell death in certain areas of the brain. […] Alcohol enhances the effect of GABA, leading to a slowing down of brain activity. […] However, chronic alcohol use can disrupt the normal functioning of GABA, contributing to dependence and withdrawal symptoms. […] Alcohol inhibits glutamate’s action at the NMDA receptors, leading to a decrease in brain activity.
  • #112 Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction | Translational Psychiatry
    https://www.nature.com/articles/s41398-024-03189-z
    Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. […] Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced inhibitory control of compulsive behavior and, eventually, relapse. […] We reasoned here that prefrontal dysfunction, which underlies vulnerability to relapse, is evidenced by altered neuroelectric signatures and should be restored by pharmacological interventions that specifically target prefrontal dysfunction. […] Electrophysiological impairments in alcohol-dependent rats are reduced amplitudes of P1N1 and N1P2 components and attenuated event-related oscillatory activity. […] Furthermore, alcohol-dependent animals displayed a dominance in higher beta frequencies indicative of a state of hyperarousal that is prone to relapse, which particularly psilocybin was able to counteract.
  • #113 Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction | Translational Psychiatry
    https://www.nature.com/articles/s41398-024-03189-z
    Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. […] Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced inhibitory control of compulsive behavior and, eventually, relapse. […] We reasoned here that prefrontal dysfunction, which underlies vulnerability to relapse, is evidenced by altered neuroelectric signatures and should be restored by pharmacological interventions that specifically target prefrontal dysfunction. […] Electrophysiological impairments in alcohol-dependent rats are reduced amplitudes of P1N1 and N1P2 components and attenuated event-related oscillatory activity. […] Furthermore, alcohol-dependent animals displayed a dominance in higher beta frequencies indicative of a state of hyperarousal that is prone to relapse, which particularly psilocybin was able to counteract.
  • #114 Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction | Translational Psychiatry
    https://www.nature.com/articles/s41398-024-03189-z
    Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. […] Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced inhibitory control of compulsive behavior and, eventually, relapse. […] We reasoned here that prefrontal dysfunction, which underlies vulnerability to relapse, is evidenced by altered neuroelectric signatures and should be restored by pharmacological interventions that specifically target prefrontal dysfunction. […] Electrophysiological impairments in alcohol-dependent rats are reduced amplitudes of P1N1 and N1P2 components and attenuated event-related oscillatory activity. […] Furthermore, alcohol-dependent animals displayed a dominance in higher beta frequencies indicative of a state of hyperarousal that is prone to relapse, which particularly psilocybin was able to counteract.
  • #115 Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction | Translational Psychiatry
    https://www.nature.com/articles/s41398-024-03189-z
    Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. […] Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced inhibitory control of compulsive behavior and, eventually, relapse. […] We reasoned here that prefrontal dysfunction, which underlies vulnerability to relapse, is evidenced by altered neuroelectric signatures and should be restored by pharmacological interventions that specifically target prefrontal dysfunction. […] Electrophysiological impairments in alcohol-dependent rats are reduced amplitudes of P1N1 and N1P2 components and attenuated event-related oscillatory activity. […] Furthermore, alcohol-dependent animals displayed a dominance in higher beta frequencies indicative of a state of hyperarousal that is prone to relapse, which particularly psilocybin was able to counteract.
  • #116 Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction | Translational Psychiatry
    https://www.nature.com/articles/s41398-024-03189-z
    It is recognized that the described cognitive impairments and limited behavioral control observed in AUD relate to disturbances primarily within prefrontocortical networks. […] Thus, the present study builds on the assumption that (i) aberrant neuroelectric signatures in AUD represent impaired prefrontal function that underlies vulnerability to relapse, and (ii) pharmacological interventions that address such a vulnerable state can restore altered electrophysiological activity. […] One of the therapeutic targets is the metabotropic glutamate receptor 2 (mGluR2), a key regulator of glutamate release. […] Consequently, it has been proposed to use mGluR2 agonists such as LY379268 to counteract this diminished prefrontal function, providing preclinical evidence of its potential to attenuate alcohol-seeking and relapse-like behavior.
  • #117 Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction | Translational Psychiatry
    https://www.nature.com/articles/s41398-024-03189-z
    It is recognized that the described cognitive impairments and limited behavioral control observed in AUD relate to disturbances primarily within prefrontocortical networks. […] Thus, the present study builds on the assumption that (i) aberrant neuroelectric signatures in AUD represent impaired prefrontal function that underlies vulnerability to relapse, and (ii) pharmacological interventions that address such a vulnerable state can restore altered electrophysiological activity. […] One of the therapeutic targets is the metabotropic glutamate receptor 2 (mGluR2), a key regulator of glutamate release. […] Consequently, it has been proposed to use mGluR2 agonists such as LY379268 to counteract this diminished prefrontal function, providing preclinical evidence of its potential to attenuate alcohol-seeking and relapse-like behavior.
  • #118 Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction | Translational Psychiatry
    https://www.nature.com/articles/s41398-024-03189-z
    It is recognized that the described cognitive impairments and limited behavioral control observed in AUD relate to disturbances primarily within prefrontocortical networks. […] Thus, the present study builds on the assumption that (i) aberrant neuroelectric signatures in AUD represent impaired prefrontal function that underlies vulnerability to relapse, and (ii) pharmacological interventions that address such a vulnerable state can restore altered electrophysiological activity. […] One of the therapeutic targets is the metabotropic glutamate receptor 2 (mGluR2), a key regulator of glutamate release. […] Consequently, it has been proposed to use mGluR2 agonists such as LY379268 to counteract this diminished prefrontal function, providing preclinical evidence of its potential to attenuate alcohol-seeking and relapse-like behavior.
  • #119 Atypical effective connectivity from the frontal cortex to striatum in alcohol use disorder | Translational Psychiatry
    https://www.nature.com/articles/s41398-024-03083-8
    Alcohol use disorder (AUD) is a profound psychiatric condition marked by disrupted connectivity among distributed brain regions, indicating impaired functional integration. […] Previous connectome studies utilizing functional magnetic resonance imaging (fMRI) have predominantly focused on undirected functional connectivity, while the specific alterations in directed effective connectivity (EC) associated with AUD remain unclear. […] Our results indicated that the ReHo-based support vector classification (SVC) exhibits the highest accuracy in distinguishing individuals with AUD from HCs (classification accuracy: 98.57%). […] The results of spectral DCM analysis indicated that individuals with AUD exhibited decreased EC from the left pre-SMA to the right putamen, from the right dACC to the right putamen, and from the right LOFC to the right NACC compared to HCs.
  • #120 Atypical effective connectivity from the frontal cortex to striatum in alcohol use disorder | Translational Psychiatry
    https://www.nature.com/articles/s41398-024-03083-8
    Alcohol use disorder (AUD) is a profound psychiatric condition marked by disrupted connectivity among distributed brain regions, indicating impaired functional integration. […] Previous connectome studies utilizing functional magnetic resonance imaging (fMRI) have predominantly focused on undirected functional connectivity, while the specific alterations in directed effective connectivity (EC) associated with AUD remain unclear. […] Our results indicated that the ReHo-based support vector classification (SVC) exhibits the highest accuracy in distinguishing individuals with AUD from HCs (classification accuracy: 98.57%). […] The results of spectral DCM analysis indicated that individuals with AUD exhibited decreased EC from the left pre-SMA to the right putamen, from the right dACC to the right putamen, and from the right LOFC to the right NACC compared to HCs.
  • #121 Atypical effective connectivity from the frontal cortex to striatum in alcohol use disorder | Translational Psychiatry
    https://www.nature.com/articles/s41398-024-03083-8
    Alcohol use disorder (AUD) is a profound psychiatric condition marked by disrupted connectivity among distributed brain regions, indicating impaired functional integration. […] Previous connectome studies utilizing functional magnetic resonance imaging (fMRI) have predominantly focused on undirected functional connectivity, while the specific alterations in directed effective connectivity (EC) associated with AUD remain unclear. […] Our results indicated that the ReHo-based support vector classification (SVC) exhibits the highest accuracy in distinguishing individuals with AUD from HCs (classification accuracy: 98.57%). […] The results of spectral DCM analysis indicated that individuals with AUD exhibited decreased EC from the left pre-SMA to the right putamen, from the right dACC to the right putamen, and from the right LOFC to the right NACC compared to HCs.
  • #122 Atypical effective connectivity from the frontal cortex to striatum in alcohol use disorder | Translational Psychiatry
    https://www.nature.com/articles/s41398-024-03083-8
    Moreover, the EC strength from the right NACC to left pre-SMA and from the right dACC to right putamen mediated the relationship between addiction severity (MAST scores) and behavioral measures (impulsive and compulsive scores). […] These findings provide crucial evidence for the underlying mechanism of impaired self-control, risk assessment, and impulsive and compulsive alcohol consumption in individuals with AUD, providing novel causal insights into both diagnosis and treatment. […] The second purpose was to investigate the neural mechanisms underlying AUD and identify the potential clinical biomarkers associated with AUD by assessing the EC among the brain regions that provide the most information features for the classification. […] We hypothesized that individuals with AUD exhibit an atypical pattern of EC among brain regions implicated in executive control and reward/loss processing, and that these aberrant connectivities are associated with symptoms of both obsessive-compulsive behavior and impulsivity.

Zobacz więcej

mechanizm patogenetyczny kora oczodołowo-czołowa wydzielanie dopaminy encefalopatia Wernickego neurogeneza zespół Korsakowa stres oksydacyjny dysbioza funkcja wykonawcza receptor glutaminianowy oś jelitowo-wątrobowa głód alkoholowy zaburzenie używania alkoholu alkoholowe stłuszczeniowe zapalenie wątroby zaburzenie lękowe brzuszne prążkowie płat czołowy dehydrogenaza aldehydowa antagonista receptora NMDA receptor opioidowy fobia społeczna uogólnione zaburzenie lękowe neuroadaptacja elastyczność poznawcza nabłonek jelitowy majaczenie alkoholowe receptor NMDA reaktywne formy tlenu opioid endogenny neuroprzekaźnik mózgowy objaw odstawienia metabolizm alkoholu zakręt obręczy antagonista receptora opioidowego choroba wątroby alkoholowa ośrodkowy układ nerwowy delirium tremens niedobór tiaminy