Tag Archive: kokain


Inhaltsverzeichnis……………………………………………………………………………………………….1
Abbildungs- und Tabellenverzeichnis……………………………………………………………………1
1 Einleitung und Fragestellung…………………………………………………………………………3
2 Methodik…………………………………………………………………………………………………….3
2.1 Durchführung………………………………………………………………………………………4
2.2 Auswertung………………………………………………………………………………………….4
3 Ergebnisse…………………………………………………………………………………………………..4
3.1 Die Untersuchungsgruppe……………………………………………………………………..5
3.2 Gesundheit…………………………………………………………………………………………..9
3.3 Konsummuster……………………………………………………………………………………12
3.3.1 Prävalenz des Drogenkonsums………………………………………………………13
3.3.2 Applikationsformen……………………………………………………………………..15
3.3.3 Konsumentengruppen…………………………………………………………………..16
3.4 Risikoverhalten………………………………………………………………………………………..19
3.5 Hilfebedarf und Hilfenutzung……………………………………………………………….22
3.6 Konsum in Haft………………………………………………………………………………….31
4 Fazit…………………………………………………………………………………………………………32
Literatur………………………………………………………………………………………………………….36
Abbildungs- und Tabellenverzeichnis
Abbildung 1: Anzahl der Befragten pro Stadt…………………………………………………………5
Abbildung 2: Durchschnittalter nach Stadt…………………………………………………………….6
Abbildung 3: Migrationshintergrund nach Stadt……………………………………………………..6
Tabelle 1: Schulabschluss…………………………………………………………………………………….7
Abbildung 4: Arbeitssituation………………………………………………………………………………7
Tabelle 2: Wohnsituation…………………………………………………………………………………….7
Abbildung 5: Substituierte nach Stadt……………………………………………………………………8
Abbildung 6: HIV-Infektion nach Stadt…………………………………………………………………9
Abbildung 7: HCV-Infektion nach Stadt………………………………………………………………10
Tabelle 3: Körperlicher und psychischer Zustand………………………………………………….10
Abbildung 8: Einschätzung des körperlichen Zustands nach Stadt…………………………..10
Abbildung 9: Einschätzung des psychischen Zustands nach Stadt…………………………..11
1
Abbildung 10: Anzahl Krankheitssymptome nach Stadt………………………………………..11
Tabelle 4: Körperliche und psychische Probleme………………………………………………….12
Abbildung 11: Prävalenz Drogenkonsum…………………………………………………………….13
Abbildung 12: Konsummuster von Männern und Frauen……………………………………….14
Abbildung 13: Heroin-, Kokain- und Crackkonsum nach Städten……………………………14
Abbildung 14: Prävalenzen nicht-verschriebener Substitutionsmittel nach Städten……15
Abbildung 15: Konsumformen……………………………………………………………………………15
Abbildung 16: Konsumgruppen nach Clusteranalyse…………………………………………….16
Abbildung 17: Konsummustergruppen nach Stadt…………………………………………………17
Abbildung 18: Wichtigkeit der Hilfsangebote nach Konsumgruppen………………………18
Abbildung 19: Spritzen- oder Utensilien-Teilen nach Konsumgruppe……………………..19
Abbildung 20: Risikoverhalten……………………………………………………………………………20
Abbildung 21: Verwendungshäufigkeit von Spritzen nach Städten………………………….20
Abbildung 22: Gemeinsames Nutzen von Spritzen oder Utensilien…………………………21
Abbildung 23: Drogen aus einer Spritze mit anderen geteilt…………………………………..21
Abbildung 24: Gemeinsame Nutzung der Crackpfeife…………………………………………..22
Tabelle 5: Gründe für den Aufenthalt auf der Szene………………………………………………22
Abbildung 25: Gründe für Szeneaufenthalt nach Stadt…………………………………………..23
Abbildung 26: Wichtigkeit von Hilfeangeboten……………………………………………………24
Abbildung 27: Wichtigkeit von Hilfeangeboten nach Stadt…………………………………….24
Abbildung 28: Häufigkeit des Besuchs der Einrichtung…………………………………………25
Abbildung 29: Häufigkeit des Besuchs der Einrichtung nach Stadt…………………………25
Abbildung 30: Besuch anderer Einrichtungen………………………………………………………26
Abbildung 31: Nutzung der Hilfsangebote……………………………………………………………26
Abbildung 32: Nutzung von Beratung…………………………………………………………………27
Abbildung 33: Nutzung des Konsumraumes…………………………………………………………28
Abbildung 34: Besuch anderer Konsumräume nach Stadt………………………………………28
Abbildung 35: Nutzung von Konsumräumen durch Substituierte……………………………29
Abbildung 36: Orte des Konsums……………………………………………………………………….29
Abbildung 37: Gründe für öffentlichen Konsum…………………………………………………..30
Abbildung 38: Grund für öffentlichen Konsum nach Stadt…………………………………….31
Abbildung 39: Drogenkonsum in Haft…………………………………………………………………32

Meine geliebten Statistiken:AbschlussberichtSzenebefragung

quelle: INSTITUT FÜR INTERDISZIPLINÄRE SUCHT- UND DROGENFORSCHUNG – ISD, HAMBURG Träger: Förderverein interdisziplinärer Sucht-
und Drogenforschung (FISD) e.V.
http://www.isd-hamburg.de

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Die Regierung erlaubt die Präsenz von US-Truppen in costaricanischen Gewässern und im Luftraum. Angeblich sollen sie bei der Bekämpfung des Drogenschmuggels helfen. VON CECIBEL ROMERO

Kampfflugzeuge wie diese AV-8B Harrier dürfen demnächst über dem eigentlich entmilitarisierten Costa Rica kreisen. Foto: rts

SAN SALVADOR taz | Über 60 Jahre lang hat sich Costa Rica gerühmt, eines der friedlichsten Länder der Welt zu sein. 1948 wurde die Armee abgeschafft, das kleine Land in Zentralamerika war entmilitarisierte Zone. Das wird jetzt anders: Das Parlament hat mit den Stimmen der regierenden National-liberalen Partei (PLN) und der rechten „Libertären Erneuerungsbewegung Costa Ricas“ (RC) ein Dekret verabschiedet, das die massive Präsenz von US-Truppen in costaricanischen Gewässern und im Luftraum erlaubt. 46 Kriegsschiffe, 7.000 Marines, 200 Helikopter und 10 Kampfflugzeuge vom Typ AV-8B Harrier dürfen sich im Hoheitsgebiet des Landes tummeln. Ihr abgeblicher Auftrag: die Bekämpfung des Drogenhandels und ein bisschen humanitäre Hilfe. Die Erlaubnis gilt zunächst für sechs Monate.

Seit die Armee Costa Ricas am 1. Dezember 1948 abgeschafft und das auch in der Verfassung verankert wurde, gab es – abgesehen von illegalen Lagern der rechten nicaraguanischen Contra in den 80er-Jahren – keine Militärs im Land. Das Dekret, das nun der US-Armee Eintritt verschafft, wird deshalb von der Opposition als Einladung zur Besetzung verstanden: „Das ist ein Blankoscheck“, sagt Luis Fishman von der konservativen „Sozial-christlichen Einheit“ (PUSC). Die linke „Partei der Bürgeraktion“ (PAC) spricht von einer „Invasion in die nationale Souveränität“. Beide Parteien haben eine Verfassungsklage angekündigt.

Bereits seit 1999 gibt es ein Abkommen über gemeinsame Patrouillen der zur Polizei gehörenden Küstenwache Costa Ricas mit US-amerikanischen Drogenfahndern. Das Kommando haben die Costaricaner. Die Hoheitsgewässer des kleinen Landes werden von den Schnellbooten kolumbianischer Kokainkartelle auf ihrem Weg nach Mexiko und in die Vereinigten Staaten genutzt, der Luftraum wird von den kleinen Propellermaschinen der Drogenkuriere gekreuzt. Die Opposition hat nichts gegen diese gemeinsamen Patrouillen. Jetzt aber gehe es um eine massive Streitmacht, mit Flugzeugträgern und allem Drum und Dran.

Mit demselben Argument der Bekämpfung des Drogenhandels haben die USA im vergangenen Jahr mit Kolumbien ein Abkommen über die Nutzung von sieben Militärbasen des südamerikanischen Landes abgeschlossen. Das benachbarte linksregierte Venezuela verstand diesen Vertrag als direkte Bedrohung und zog seinen Botschafter aus Bogotá zurück. Es folgte eine andauernde politische Verstimmung zwischen den Nachbarländern. Die Militärpräsenz in Costa Rica dürfte weiter für Unruhe in den zentralamerikanischen Ländern sorgen, vor allem im direkten Nachbarland Nicaragua, das über das Wirtschaftsbündnis Alba politisch eng mit Venezuela verbandelt ist.

Die Alba-Mitglieder sehen in der US-Militärpräsenz zur angeblichen Bekämpfung des Drogenhandels einen Vorwand. Das eigentliche Ziel sei die Durchsetzung der politischen und wirtschaftlichen Interessen Washingtons in Lateinamerika. Präsident Barack Obama unterscheide sich da nicht von seinem Vorgänger George W. Bush. Erst in der vergangenen Woche hatte der von Militärs gestürzte frühere Präsident von Honduras Manuel Zelaya gesagt, der Putsch gegen ihn sei von US-Militärs ausgeheckt worden. Das Außenministerium in Washington wies diese Erklärung als „lächerlich“ zurück.

Quelle:http://www.taz.de/1/politik/amerika/artikel/1/blanko-scheck-zur-invasion/

For years, there has been much discussion about the best strategy to rid Afghanistan of its poppies. Eradication, said the George W Bush administration. Interdiction and alternative livelihoods, retorted the Barack Obama administration. Licensing and production for medicinal purposes, suggests the influential Senlis Council.

The issues have been fiercely debated: Would there be enough demand for Afghanistan’s legal morphine? Is the government too corrupt to implement this or that scheme? To what extent will eradication alienate farmers? Which crops should we substitute for poppies?

These questions are not unimportant, but fundamentally, they do not address the primary source of Afghan drug production: the
West’s (and Russia’s) insatiable demand for drugs.

Afghanistan accounts for about 90% of global illicit opium production. Western Europe and Russia are its two largest markets in terms of quantities consumed and market value (the United States is not an important market for Afghan opiates, importing the drugs from Latin America instead). Western Europe (26%) and Russia (21%) together consume almost half (47%) the heroin produced in the world, with four countries accounting for 60% of the European market: the United Kingdom, Italy, France and Germany.

In economic terms, the world’s opiates market is valued at $65 billion, of which heroin accounts for $55 billion. Nearly half of the overall opiate market value is accounted for by Europe (some $20 billion) and Russia ($13 billion). Iran is also a large consumer of opium, with smaller amounts of heroin. The situation is similar for cocaine, for which the US and Europe are the two dominant markets (virtually all coca cultivation takes place in Colombia, Peru and Bolivia).

In short, it is the West that has a drug problem, not producer countries like Afghanistan (or Colombia): demand is king and drives the global industry.

How should we reduce opiate consumption and its negative consequences in the West and Russia? Drug policy research has typically offered four methods. There is a wide consensus among researchers that such methods should be ranked as follows, from most to least effective: 1) treatment of addicts, 2) prevention, 3) enforcement, and 4) overseas operations in producer countries. For example, 12 established analysts reached the following conclusions, published a few months ago:

Efforts by wealthy countries to curtail cultivation of drug-producing plants in poor countries have not reduced aggregate drug supply or use in downstream markets, and probably never will … it will fail even if current efforts are multiplied many times over.

A substantial expansion of [treatment] services, particularly for people dependent on opiates, is likely to produce the broadest range of benefits … yet, most societies invest in these services at a low level.

Also, a widely cited 1994 RAND study concluded that targeting “source countries” is 23 times less cost effective than “treatment” for addicts domestically, the most effective method; “interdiction” was estimated to be 11 times less cost effective and “domestic enforcement” seven times. The problem is that the West’s drug policy strategy has for years emphasized enforcement, combined to overseas adventures, to the detriment of treatment and prevention. Also, Russia has been complaining about the suspension of eradication in Afghanistan, but it has a very poor record of offering treatment to its own addicts, rejecting widely accepted scientific evidence. Moscow has chosen a strategy that “serves the end of social control and enforcement,” just like the US: criminalization is emphasized and the largest share of public resources is directed to arrest, prosecute and incarcerate drug users, instead of offering them treatment. This worsens Russia’s HIV epidemic, the fastest growing in the world – with nearly one million HIV infections, some 80% of which related to the sharing of drug needles – while syringe availability remains very limited. For instance, methadone and buprenorphine remain prohibited by law in Russia, even if they are effective in reducing the drug problem by shifting addicts from illegal opiates to safer, legal alternatives. Accordingly, a just released New York University report states that “Nothing that happens in Afghanistan, for good or ill, would affect the Russian drug problem nearly as much as the adoption of methadone” in Russia – which would also help Afghanistan reduce poppy cultivation. Obama announced last year that the US would have access to seven military bases in Colombia under the pretext of fighting a war on terror and a war on drugs. Likewise, Russia recently announced that it would set up a second military base in Kyrgyzstan, to combat drug trafficking. Victor Ivanov, the Director of the Russian Federal Drug Control Service, explained how he was inspired by US drug war tactics in Latin America:

The United States‘ experience is certainly quite effective. The powerful flow of cocaine from Colombia into the United States prompted Washington to set up seven military bases in the Latin American nation in question. The US then used aircraft to destroy some 230,000 hectares of coca plantations … Russia suggests building its military base in Kyrgyzstan since it is the republic’s Osh region that is a center of sorts whence drugs are channeled throughout Central Asia.

Europe’s record on drug policy has improved over the last two decades, important advances having been made to bring harm reduction into the mainstream of drug policy, and rates of drug usage for each category of drugs are lower in the European Union (EU) than in states with a far more criminalized drug policy, such as the US, Canada and Australia. But there is still room for improvement. For example, although opioid substitution treatment and needle and syringe exchange programs now reach more addicts, “important differences between [European] countries continue to exist in scale and coverage”, a recent review of harm reduction policies in Europe concludes. In particular, “Overall provision of substitution treatment in the Baltic States and the central and south-east European regions, except in Slovenia, remains low despite some recent increases. An estimate from Estonia suggests that only 5% of heroin users in the four major urban centers are covered by substitution programs, and that this rate is as low as 1% at national level.“ Lack of funds is no excuse, as there is plenty of money available, for instance, out of the $300 billion Europeans spend every year on their militaries, to maintain among other things their more than 30,000 troops in Afghanistan. The UK was put in charge of counter-narcotics in Afghanistan. However, domestically, leading specialists Peter Reuter and Alex Stevens report that “Despite rhetorical commitments to the rebalancing of drug policy spending towards treatment… the bulk of public expenditure continues to be devoted to criminal justice measures… this emphasis on enforcement in drug control expenditures also holds for the most explicitly harm reduction-oriented country, the Netherlands.“ In the UK, over 1994-2005, “the number of prison cell years handed out in annual sentences has tripled“ (although significant increases have also been made towards treatment). “The prison population has increased rapidly in the past decade [and] the use of imprisonment has increased even more rapidly for drug offenders than other offenders… These increases have contributed significantly to the current prison overcrowding crisis.“ British enforcement costs taxpayers dearly, but the government does not regularly or publicly calculate those costs. Through a Freedom of Information request a document was released that “calculated the annual cost of enforcing drug laws – including police, probation, prison and court costs – at approximately ฃ2.19 billion, of which about ฃ581 million was spent on imprisoning drug offenders.“ All this said, there is one way in which Afghanistan does have a drug problem, namely, its increasing number of addicts. A recent report from the United Nations Office on Drugs and Crime (UNODC) estimated that drug use had increased dramatically over the last few years and that around one million Afghans now suffer from drug addiction, or 8% of the population – twice the global average. Since 2005, the number of regular opium users in Afghanistan has grown from 150,000 to 230,000 (a 53% increase) and for heroin, from 50,000 to 120,000 (a 140% increase). This spreads HIV/AIDS because most injecting drug users share needles. But treatment resources are very deficient. Only about 10% of addicts have ever received treatment, meaning that about 700,000 are left without it, which prompted UNODC chief Antonio Maria Costa to call for much greater resources for drug prevention and treatment in the country. The problem is that the Obama and Bush administrations could not care less: since 2005, the US has allocated less than $18 million to “demand reduction” activities in Afghanistan – less than 1% of the $2 billion they spent on eradication and interdiction. Clearly, US priorities have nothing to do with fighting a war on drugs.

source: http://www.atimes.com/atimes/South_Asia/LG01Df02.html

INHALT
Zusammenfassung
1. Einleitung
1.1. Zum Frühverlauf der Schizophrenie
1.2. Zur Komorbidität von Psychose und Sucht
1.2.1. Epidemiologie
1.2.2. Erklärungsansätze zur Komorbidität
1.2.3. Probleme in der Therapie komorbider Patienten
1.3. Fragestellungen dieser Arbeit
2. Material und Methoden
2.1. Untersuchungsrahmen
2.2. Art der Datenerhebung
2.3. Beschreibung der Gesamt-Stichprobe
2.4. Beschreibung der Stichprobe der berücksichtigten Patienten
2.5. Zusammenfassung
3. Ergebnisse
3.1. Psychopathologie im Verlauf
3.2. Bestimmung der Parallelisierungszeitpunkte
3.3. Das Konsummuster zwischen 1988 und 1997
3.4. Varianzanalyse zum Konsummuster
3.5. Das Konsummuster an den Parallelisierungszeitpunkten
3.6. Einfluß von subjektiver Symptomatik und Diagnose-Zeitpunkt
4. Diskussion
4.1. Methodische Fragen
4.2. Diskussion der Ergebnisse
4.3. Fazit und Ausblick

weiterlesen: PsychoseundSucht_Studie

Dies ist ein ziemlicher Brocken an Information (160 Seiten)

aber meiner wirklich ganz bescheidenen meinung nach lesenswert,

denn immerhin bildet sich das Bild ueber Drogen-User and Abuser

durch solche Artikel!

Ich poste dennoch solch dinge weil es keine 100% Wahrheit beim Thema Sucht und Drogen geben kann/ wird!

Der Artikel ist Deutsch-Sprachig!

Hier klicken und lesen: SuchtmedReihe_Drogen

A) ALLGEMEINE GRUNDLAGEN 2
1. Verhaltensbiologie 2
2. Das Gehirn – Strukturen, Prozesse und Funktionen 3
2.1 Anatomie (Makroanatomie) 3
2.2 Struktur hirnlokaler Netzwerke (Mikroanatomie,
Histologie) 9
2.3 Die Nervenzelle und ihre Verknüpfungen 11
2.4 Die Nervenzelle – chemische Impulse 15
2.5 Innerzelluläre molekulare Signalketten 17
2.6 Neurophilosophie – das „Gehirn-Geist“-Problem
und das „Mikro-Makro“-Problem 19
B) NEUROBIOLOGIE DER SUCHT 20
3. Drogen 20
4. Neurochemische Dynamik 24
5. Neuroanatomie der Sucht 28
5.1 Die zentrale Rolle des Dopamin-Systems 28
5.2 Das Gesamtbild der funktionellen Architektur des
süchtigen Gehirns 30
5.3 Hirn-Schädigungen als Konsumfolge 31
C) LITERATUR 32

Weiter lesen: 001_070402_BAS_Skript_Neurobiologie_der_Sucht_Tretter

Most definitions of drug addiction or substance dependence include (i) descriptions of „overwhelming involvement with the use of a drug (compulsive use)“ (1) and (ii) a number of symptoms or criteria that reflect a loss of control over drug intake and a narrowing of the number of different behavioral responses toward drug-seeking (2). Drug addiction can be equated with substance dependence as defined by the American Psychiatric Association (3). However, it is important to distinguish between what is termed substance use, substance abuse, and substance dependence (addiction) (4).

In humans, most drug users do not become drug abusers or drug-dependent (4). Similarly, stable drug intake can be observed in animals without pronounced signs of dependence, even with intravenous drug administration under limited-access situations. Many factors such as availability (route of administration), genetics, history of drug use, stress, and life events contribute to the transition from drug use to drug addiction. The current challenge is to discover what neurobiological elements convey the individual differences in vulnerability to this transition to drug addiction.

In this article we will draw from recent formulations in behavioral neuroscience and other disciplines to construct a framework to view addiction as a continuous process of hedonic homeostatic dysregulation. Multiple sources of reinforcement are identified in the spiralling cycle of addiction, and the symptoms of this hedonic dysregulation form the well-known criteria for substance dependence or addiction (2, 3). Critical neurotransmitters, hormones, and neurobiological sites have been identified that may mediate the hedonic dysregulation and may provide the substrates that convey both vulnerability to, and protection against, drug addiction (5) (Fig. 1).


Fig. 1. Diagram describing the spiralling distress-addiction cycle from four conceptual perspectives: social psychological, psychiatric, dysadaptational, and neurobiological. (A) The three major components of the addiction cycle, preoccupation-anticipation, binge-intoxication, and withdrawal-negative affect, and some of the sources of potential self-regulation failure in the form of underregulation and misregulation. (B) The same three major components of the addiction cycle with the different criteria for substance dependence from DSM-IV incorporated. (C) The places of emphasis for the theoretical constructs of sensitization and counteradaptation. (D) The hypothetical role of different neurochemical and endocrine systems in the addiction cycle. Small arrows refer to increased functional activity. DA, dopamine, CRF, corticotropin-releasing factor. Note that the addiction cycle is conceptualized as a spiral that increases in amplitude with repeated experience, ultimately resulting in the pathological state known as addiction. (fuer groesseres Bild unten gucken!)


Spiralling Distress and the Addiction Cycle

Important elements that may be involved in the failure to self-regulate drug use, as well as other behaviors such as compulsive gambling and binge eating, have derived from social psychology (6). It is of interest to conceptualize how these regulation failures ultimately lead to addiction in the case of drug use or an addiction-like pattern with nondrug behaviors. Lapse-activated causal patterns, that is, patterns of behavior that contribute to the transition from an initial lapse in self-regulation to a large-scale breakdown in self-regulation, can lead to spiralling distress (6). Spiralling distress describes how, in some cases, the first self-regulation failure can lead to emotional distress, which sets up a cycle of repeated failures to self-regulate, and where each violation brings additional negative affect (6). For example, a failure of strength may lead to initial drug use or relapse, and other self-regulation failures can be recruited to prevent an exit from the addiction cycle. Here, spiralling distress will be used to describe the progressive dysregulation of the brain reward system within the context of repeated addiction cycles (Fig. 1A).

Psychiatry and experimental psychology, in effect, address the same addiction cycle (Fig. 1B), and neurobiology has begun to identify the neurobiological elements that contribute to the break with hedonic homeostasis, known as addiction. Although animal models provide a critical part of the study of the neurobiology of addiction, no animal models incorporate all the elements of addiction. Alternatively, animal models can be established and validated for different symptoms or constructs associated with addiction (7). There is much evidence for valid animal models of many of the criteria in the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (3) and the sources of reinforcement associated with addiction (7).

Neurobiology of Drug Reinforcement

The focus for the neurobiological mechanism for the positive-reinforcing effects of drugs of abuse has been the mesocorticolimbic dopamine system and its connections in the basal forebrain (8, 9). For cocaine, amphetamine, and nicotine, the facilitation of dopamine neurotransmission in the mesocorticolimbic dopamine system appears to be critical for the acute reinforcing actions of these drugs [for reviews, see (8, 9)]. Multiple dopamine receptors including D-1, D-2, and D-3 have been implicated in this reinforcing action (10, 11). Neuropharmacological studies support both a dopamine-dependent and a dopamine-independent contribution to the positive-reinforcing effects of opiates such as heroin (8, 9, 12). Ethanol appears to interact with ethanol-sensitive elements in multiple neurotransmitter receptor systems, and these interactions may contribute to ethanol’s positive-reinforcing actions (13). The neurotransmitters and receptor systems implicated include actions on the gamma -aminobutyric acid (GABA), glutamate, dopamine, serotonin, and opioid peptide systems, all of which are within the mesocorticolimbic dopamine system and its connections to the nucleus accumbens and amygdala (13). Limited study has implicated the release of dopamine in the nucleus accumbens in the positive-reinforcing actions of tetrahydrocannabinol (THC) (14).

A major question still challenging drug abuse research, however, is whether the neurobiology of reward and drug reinforcement changes with chronic use and during the manifestation of an abstinence syndrome when the drug is no longer self-administered. Historically, substance dependence has focused on the manifestation of an abstinence syndrome upon abrupt cessation of drug administration that was characterized by physical signs such as the well-documented tremor and autonomic hyperactivity of ethanol withdrawal and the discomfort and pain associated with opiate withdrawal. However, recent conceptualizations of abstinence symptoms have begun to focus on aspects of abstinence that are common to all drugs of abuse and may be considered more motivational in nature and perhaps are best described as a negative affective state (5, 15, 16). These symptoms include various negative emotions such as dysphoria, depression, irritability, and anxiety (3, 15, 16).

Consistent with these clinical observations, animal studies in which intracranial self-stimulation was used as a measure of reward function have revealed pronounced decreases in reward (or increases in the reward threshold) associated with withdrawal from all major drugs of abuse tested to date (Fig. 2). These effects vary with dose and duration of exposure to the drug, but can last as long as 96 hours after withdrawal from the drug in rodent models (15, 16).


Fig. 2. Changes in reward threshold associated with chronic administration of three major drugs of abuse. Reward thresholds were determined by a rate-independent discrete trials threshold procedure for intracranial self-stimulation (ICSS) of the medial forebrain bundle. (A) Rats equipped with intravenous catheters were allowed to self-administer cocaine for 12 hours before withdrawal and reward threshold determinations. Elevations in threshold were dose-dependent with longer bouts of cocaine self-administration yielding larger and longer-lasting elevations in reward thresholds (51). Asterisks refer to significant differences between treatment and control values. Values are mean ± SEM. (B) Elevations in reward thresholds with the same ICSS technique after chronic exposure to ethanol of about 200 mg% in ethanol vapor chambers (52). (C) Elevations in reward thresholds measured with the same ICSS technique after administration of very low doses (in milligrams per kilogram of body weight) of the opiate antagonist naloxone to animals made dependent on morphine with two, 75-mg morphine (base) pellets implanted subcutaneously (53). (fuer groesseres Bild unten gucken!)


The significance of drug abstinence syndromes remains controversial as a basis for compulsive use (1, 7), but increasing evidence both in animal and human studies suggests that the presence of a negative affective state may not only signal the beginning of the development of dependence (17), but may contribute to vulnerability to relapse and may also have motivational significance. Rats made dependent on opiates and ethanol show increases in drug self-administration (18). Thus, exposure to sufficient amounts of drug to produce dependence as measured by elevations in reward thresholds can increase the motivation for a drug. This increase could result from additive or even synergistic sources of positive and negative reinforcement (19) and may contribute to the addiction cycle.

Neural Substrates for Sensitization and Counteradaptation of Reward

At the neurobiologial level, two neuroadaptive models have been conceptualized to explain the changes in motivation for drug-seeking that reflect compulsive use: counteradaptation and sensitization. Counteradaptation hypotheses (20) were intimately linked to the development of hedonic tolerance by the formulation known as opponent process theory (21). In contrast, sensitization, a progressive increase in a drug’s effect with repeated administration, has been conceptualized to be a shift in an incentive-salience state (21).

Both of these conceptual positions focus on neurobiological changes at the molecular, cellular, and system levels, and both may involve what have been described as „within-system“ and „between-system“ changes (8). At the neurochemical level, changes associated with the same neurotransmitters implicated in the acute reinforcing effects of drugs that are altered during the development of substance dependence would be examples of within-system changes.

Counteradaptive, within-system neurochemical events include decreases in dopaminergic and serotonergic neurotransmission in the nucleus accumbens during drug withdrawal (22). At the molecular and cellular levels, changes in opiate receptor function during withdrawal from chronic opiates and decreased GABAergic and increased glutamatergic transmission during ethanol withdrawal have been observed [(23), and Nestler and Aghajanian (24) in this issue)]. Sensitization to the locomotor stimulant effects of psychomotor stimulants and opiates also appears to involve within-system activation of the mesolimbic dopamine system. There appears to be a time-dependent chain of adaptations within the mesolimbic dopamine system that leads to the long-lasting changes produced by sensitization (25).

Changes in other neurotransmitter systems that are not linked to the acute reinforcing effects of the drug but are recruited during chronic drug administration have been conceptualized as between-system adaptations. Examples of between-system counteradaptations include increases in dynorphin function in the nucleus accumbens during chronic cocaine administration, increases in anti-opioid peptides associated with chronic opioid administration, and augmentation of brain stress systems such as corticotropin-releasing factor (CRF) associated with cocaine, opiates, ethanol, and THC (15, 16, 26).

Recent neuroanatomical, neurochemical, and neuropharmacological observations have provided support for a distinct brain circuit within the basal forebrain that may mediate both the within-system and between-system neurochemical changes associated with drug reward. The extended amygdala (27) is a hypothesized macrostructure consisting of several basal forebrain structures that share similarities in morphology, neurochemistry, and connectivity (27). Support for the role of the extended amygdala in the acute reinforcing effects of drugs of abuse can be found in a series of in vivo microdialysis and neuropharmacological studies that showed selective activation of dopamine in the shell of the nucleus accumbens by most of the major drugs of abuse (28). In addition, GABAergic and opioidergic mechanisms in the central nucleus of the amygdala may participate in the acute reinforcing actions of ethanol (29). Also, the central nucleus of the amygdala may function in counteradaptation of the brain reward system during the development of drug dependence. Chronic administration of drugs can alter both CRF and proopiomelanocortin gene expression in the amygdala (30). An increased CRF response in the central nucleus of the amygdala is associated with acute withdrawal from ethanol, opiates, cocaine, and THC (31).

Limited data suggest a specific role for parts of the extended amygdala in sensitization. The mesolimbic dopamine system is clearly involved, but no specific subregion has been delineated. Glucocorticoids can activate the mesolimbic dopamine system by increasing dopamine synthesis, decreasing dopamine metabolism, and decreasing catecholamine uptake (5). The participation of a specific subprojection of the mesolimbic system in sensitization is under investigation.

Relapse: Neural Substrates and Vulnerability

Relapse and vulnerability to relapse are key elements in the maintenance of a chronic relapsing disorder such as addiction [see O’Brien (32), this issue]. Animal models predictive of relapse are being developed. Studies suggest that stresslike stimuli and neuropharmacological agents that activate the mesocorticolimbic dopamine system can rapidly reinstate intravenous drug self-administration that has been previously extinguished (33), and drugs that modulate dopamine receptors can block reinstatement of cocaine self-administration in rats (11). Naltrexone and acamprosate decrease relapse rates in alcoholics (34) and can modify excessive drinking in rodents in various models (35). Thus, a rich source for study of the neurobiological mechanisms of relapse will be the same neurotransmitters and neurocircuitry implicated in the within- and between-system adaptations of sensitization and counteradaptation.

The vulnerability to relapse will have both genetic and environmental bases resulting in a susceptible host, from a medical perspective (36). Animal studies have begun to address both these contributions. While genetic vulnerability is beyond the scope of this review, there are rodent strains that show preferences for drinking ethanol, and there is mounting evidence of alterations in the same reward neurotransmitters that may form the basis of such preferences (37). In addition, new techniques such as quantitative trait loci analysis and the study of knock-out and transgenic mice are revealing potential genetic sites associated with vulnerability (38).

Environmental factors involved in vulnerability have largely focused on the role of stress. An atypical responsivity to stress in former opiate- and cocaine-dependent subjects has been well documented and hypothesized to be linked to chronic relapse (39). Exposure to repeated stressors also increases the propensity to develop initial intravenous drug self-administration (acquisition) (40) and can facilitate reinstatement of drug self-administration after extinction (relapse) (33). These effects appear to be directly linked to activation of the hypothalamic pituitary adrenal axis. Suppression of stress-induced corticosterone secretion abolishes the enhanced behavioral responsiveness to amphetamine and morphine produced by different stressors (41). Consistent with these observations, repeated administration of corticosterone can substitute for stress and increase the behavioral effects of psychostimulants (41). It is hypothesized that glucocorticoid hormones function in the long-term maintenance of the sensitized state and may even represent a within-system change (41). In addition, vulnerability to drug-taking may be influenced by a history of drug experience and the presence of competing nondrug reinforcers altering the response to drug reinforcers (42).

The combination of genetic and environmental factors can dramatically change an animal’s response to drugs. A comparison of rats that show a high and low locomotor response to forced exposure in a novel environment revealed that high responders (HRs) show a greater propensity to develop intravenous drug self-administration compared with low responders (LRs) (43). This greater sensitivity to drugs in HRs shows a correlation with dysregulation of the hypothalamic pituitary adrenal axis (a prolonged secretion of corticosterone in response to stress) and with a higher sensitivity to the behavioral and dopamine-activating effects of glucocorticoids (41) (Fig. 3). Indeed, stress has been hypothesized to cause HR rats to express enhanced responses to drugs (43, 44). What is largely unknown is how these genetic and environmental factors combine to contribute to the development of what constitutes substance dependence (addiction) in humans. In addition, identification of the vulnerability for different parts of the addiction cycle using animal models will provide clues to relapse vulnerability in human addicts. With the use of animal models, studies of the interaction of genetics, of stress, and of the initial response to drugs on various features of the addiction cycle other than drug-taking will be informative.


Fig. 3. (A) The effects of adrenalectomy on cocaine self-administration in rats. Animals were trained to self-administer cocaine by nose-poking and subjected to a dose-effect function. Adrenalectomy produced a flattening of the dose-effect function, with decreases of cocaine intake at all the doses (54). (B) Corticosterone-induced changes in extracellular concentrations of dopamine in high-responding (HR) and low-responding (LR) animals. HR animals that drank the corticosterone solution (100 mg/ml) in the dark period showed a faster and higher increase in accumbens dopamine than LR animals (55). (fuer groesseres Bild unten gucken!)


Homeostasis of Reward, Self-Regulation, and „Natural“ Addictions

The concept of homeostasis contends that an organism maintains equilibrium in all of its systems, including the brain reward system, that is, the organism uses physiological and cognitive or behavioral capabilities to function within the appropriate limits of physiology with the help of its own resources. Environmental factors that challenge homeostasis are met with counter actions. Allostasis refers to the concept of physiology where an organism must vary all of the parameters of its internal milieu and match them appropriately to perceived and anticipated environmental demands in order to maintain stability (45). If the threats to the system continue to produce disequilibrium, the process of allostasis continues to regulate where the organism must mobilize enormous amounts of energy to maintain apparent stability at a now pathological „set point.“ The system is at the limit of its capability, and thus a small challenge can lead to breakdown (45). This is the beginning of spiralling distress and the addiction cycle. When the organism has reached a state of dysregulation so severe that it cannot recover by mobilizing its own resources, allostasis has reached the point of what is normally considered illness. The state of dysregulation of the reward system may produce loss of control over drug intake, compulsive use, or drug addiction. The mechanisms that contribute to this allostasis are normal mechanisms for homeostatic regulation of reward that have spun out of the physiological range (that is, sensitization and counteradaptation).

Addiction Cycle: Sensitization and Counteradaptation

The role of sensitization in dependence has been elaborated where a shift in an incentive-salience state, described as „wanting,“ progressively increases with repeated exposure to drugs of abuse (21). This shift is largely attributed to a pathological overactivity of mesolimbic dopamine function and, as such, represents a break with homeostasis. Other factors such as increased secretion of glucocorticoids may function in the long-term maintenance of this sensitized state (41).

Early theories of counteradaptation with chronic drug administration were based on the concept of homeostasis (20) and later extended to hedonic processes in opponent process theory (21) (Fig. 4). This theory may explain the affective withdrawal component of the addiction cycle and also may explain how repeated drug-taking can lead to spiralling distress. Indeed, the onset of a negative affective state can be used to define addiction (17). In addition, the negative affective state may have motivating properties in maintaining drug-seeking behavior, not only by direct negative reinforcement (that is, the drug is taken to relieve the negative state) but also by changing the set point for the efficacy of reinforcers and thus add motivational effectiveness to both positive drug effects and conditioned positive drug effects (7, 15, 16, 21). At least two common neurochemical elements, activation of limbic CRF systems and a decrease in mesolimbic DA function, are common neurochemical correlates of the early parts of drug withdrawal (15, 16, 31).


Fig. 4. Diagram illustrating an extension of Solomon and Corbit’s opponent-process model of motivation to incorporate the conceptual framework of this article (21). All panels represent the affective response to the presentation of the stimuli (that is, drug administration). (A) The original description of the affective stimulus, which was argued to be a sum of both an a-process and a b-process and represents the initial experience with no prior drug history. (B) The same affective stimulus in an individual with an intermittent history of drug use that may result in sensitized response. The shaded line illustrates the sametrace of the initial experience in (A). The dotted line represents the sensitized response. (C) Change in the affective stimulus hypothesized to exist in the heavily dependent individual (that is, after chronic exposure) where there is a major change in the hedonic set point. This represents a change sufficient to be considered a major break with hedonic homeostasis. The light dotted line represents the sensitized response observed in (B). (D) The hypothesized state of protracted abstinence and enhanced vulnerability to relapse with a history of chronic continuous experience. The change in this panel reflects the change in the affective response in an organism with a history of depen-dence where there is both a change in set point that is long-lasting and a residual sensitization. The bar to the right of each diagram illustrates the total peak-to-peak contrast between the lowest point in negative affect to the highest point in positive mood produced by a drug at any point in the addiction cycle. An alternative hypothesis still under consideration is that even during an intermittent sensitization pattern of drugtaking, the affective after-reaction (b-process) also may get progressively larger and larger (21). „On“ refers to the „time on“ of the hedonic stimulus, in this case the drug action. „Off“ refers to the „offset“ of the drug action. (fuer groesseres Bild unten gucken!)


At first glance, the two processes of sensitization and counteradaptation may appear to make opposite predictions about the course of drug dependence and the neurobiology of drug dependence. However, if drug dependence is viewed in the context of spiralling distress, then it is possible that both processes are active, although perhaps not concurrently, at different parts of the cycle (Figs. 1 and 4). The neurobiology of a heavily dependent person (Fig. 4C) will be very different from that of a nondependent person (Fig. 4A) and may reflect a state of severe allostasis (with a change in set point) and the part of the addiction cycle associated with negative affect and spiralling distress (Fig. 1C). For example, enhanced dopaminergic and opioidergic neurotransmission may be involved in the preoccupation-anticipation stage and result in sensitization (Figs. 1C and 4B), but compromised dopamine, serotonin, and opioidergic neurotransmission, as well as increases in stress neurotransmitters, may be responsible for the negative affective state of withdrawal (Figs. 1D and 4C). The combination of a change in hedonic set point produced by repeated counteradaptation and a separate mechanism for sensitization would provide a dramatic motivational force for continuing drug dependence (Fig. 4, C and D).

This view is similar to that of incentive motivational theory (46) and incorporates some aspects of incentive-salience theory (21). Under the current formulation, counteradaptation creates a need state that may or may not easily be labeled by subjective responses but, rather, reflects a chronic break with homeostasis such as a decrease in hedonic set point. Sensitization, in contrast, creates a facilitated incentive motivation or incentive salience that reflects enhanced responses to drug incentive stimuli (that is, wanting or craving).

According to this formulation, sensitization is assigned a relatively minor role in the ongoing process of spiralling distress, but a more important role in triggering the beginning of instability (vulnerability to drug-taking, as in the form of cross-sensitization to stress) or retriggering of instability as in the process of relapse (reentrance into the cycle of spiralling distress). Indeed, a dependent person is almost by definition already sensitized. However, there is little evidence of sensitization in drug-dependent people, and most clinical evidence points to tolerance, not sensitization. Human addicts consume enormous amounts of ethanol, opiates, and even stimulants that would easily be toxic to nonaddicted individuals (47). In addition, most of the animal studies of sensitization have focused either on locomotor activity as a dependent variable or in the drug reward domain on acquisition of drug self-administration (21). If sensitization is to gain a role as extensive as that outlined herein, more data will be required to show a link between these measures of enhanced sensitivity to drugs of abuse (locomotor activity and acquisition of drug self-administration) and other measures of dependence.

Implications for the Concept of Addiction and Treatment

The present conceptualization of addiction has important implications for the treatment of drug addiction. The social psychological components of failure to self-regulate may impact on different parts of the addiction cycle (Fig. 1A), and these different components may be reflected in changes in different components of reward neurocircuitry (Fig. 1D). For example, failure of strength may reflect increases in stress system activity, whereas failure of monitoring or attention may reflect cognitive changes that are influenced by the widely distributed brain monoamine systems.

The present conceptualization also provides a framework for studying the components of addiction most often neglected in animal studies. The role of neurobiology in different processes, such as social psychological self-regulation failures, positive and negative reinforcement, sensitization, and counteradaptation, changes dramatically over the course of transition from drug use to abuse to addiction. In addition, different drugs may act differentially on parts of the spiralling distress-addiction cycle. Young, type II alcoholics (48) may be more involved in the preoccupation-anticipation and binge components than terminal alcoholics, where a major need state has usurped most other sources of motivation. In contrast, users of opiates and nicotine may assume this need-state component at a much earlier stage (49). Studies of the neurobiology of such differences will be critical for future interventions at both the prevention and treatment levels.

There is clearly a neurobiological basis for multiple sites of treatment intervention. Eliminating affective withdrawal and the reward need state are critical (such as methadone for opiate addiction), as well as eliminating the changes that lead to facilitated incentive salience (such as naltrexone for alcohol addiction). Various forms of behavioral therapies and psychotherapy have been shown to be effective in treating addiction, particularly in combination with pharmacotherapy [(34) and O’Brien (32), this issue]. These therapies ultimately act on the same dysregulated hedonic circuitry to help return and maintain it within homeostatic boundaries. In addition, vulnerability to addiction can be conveyed at any part of the spiralling distress of the addiction cycle and should not be simply relegated to initial drug responses.

Although beyond the scope of the present review, dysregulation of hedonic homeostasis can also occur with compulsive use of nondrug reinforcers. Similar patterns of spiralling distress-addiction cycles have been observed with pathological gambling, binge eating, compulsive exercise, compulsive sex, and others (6). The same neurobiological dysregulations and breaks with homeostasis may be occurring within the same neurocircuitry implicated in drug dependence. With the advent of more sophisticated measures of brain function in humans, such questions may be pursued.

The implications of this homeostatic view for everyday existence forces one to return to social psychology, but with a biological perspective. The brain hedonic system may be a limited resource (50). One can expend this resource rapidly in a binge of drug-taking or other compulsive behavior, but at a great risk for entrance into the spiralling dysregulation of the addiction cycle. Alternately, one can adopt a more regulated, „hedonic Calvinistic“ approach (51) where use of the reward system is restricted within the homeostatic boundary (that is, without the development of subsequent negative affect). Such an ascetic view may or may not fall within certain cultural norms, but probably makes biological sense.

REFERENCES AND NOTES

  1. J. H. Jaffe, in Goodman and Gilman’s The Pharmacological Basis of Therapeutics, A. G. Gilman, T. W. Rall, A. S. Nies, P. Taylor, Eds. (Pergamon, New York, ed. 8, 1990), pp. 522-573.
  2. World Health Organization, International Statistical Classification of Diseases and Related Health Problems (World Health Organization, Geneva, 10th revision, 1990).
  3. Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, Washington, DC, ed. 4, 1994).
  4. A recent Institute of Medicine report [Institute of Medicine, Pathways of Addiction (National Academy Press, Washington, DC, 1996)] used a three-stage conceptualization of drug-taking behavior that applies to all psychoactive drugs, whether licit or illicit: use, abuse, and dependence. „Use“ of drugs is the taking of drugs, in the narrow sense, to distinguish it from a more intensified pattern of use. „Abuse“ refers to any harmful use, regardless of whether the behavior constitutes a disorder in the DSM-IV of the American Psychiatric Association. „Dependence“ refers to „substance dependence“ as defined by DSM-IV or „addiction“ as defined by International Classification of Diseases (ICD 10).
  5. G. F. Koob and E. J. Nestler, J. Neuropsychiatry Clin. Neurosci. 9, 482 (1997) [Abstract/Free Full Text] ; P. V. Piazza and M. Le Moal, Brain Res. Rev., in press.
  6. Underregulation can be defined as a „failure to exert control over one’s self.“ Conflicting or inadequate standards would be a breakdown in the basis for self-regulation. Reduction in monitoring is a failure of a person to evaluate one’s self and actions against relevant standards. Inadequate strength is analogous to the common-sense concept of willpower and is a conflict between the power of impulse/tendency to act and the self-regulatory mechanism to interrupt that response and prevent action. Misregulation can be defined as „exerting control in a way that fails to bring about the desired result or leads to some alternative result.“ Misregulation probably most often involves some kind of deficiency in knowledge, especially self-knowledge. These knowledge deficiencies include false beliefs, distorted beliefs, overgeneralizations, and misdirected control efforts. Lapse-activated causal patterns are the patterns of behavior that translate an initial lapse (break in self-regulation) into a large-scale indulgence or major binge. Many factors contribute to these patterns of behavior, including underregulation, emotional responses, stress, zero-tolerance beliefs, spiralling distress, and others [R. F. Baumeister, T. F. Heatherton, D. M. Tice, Eds., Losing Control: How and Why People Fail at Self-Regulation (Academic Press, San Diego, 1994)].
  7. The use of animal models to characterize the neurobiology of specific aspects of human disorders is a reorientation to the „top-down“ approach. Here, specific behaviors are explored at the system level, the cellular level, and ultimately the molecular level, with hypothesis testing based on an understanding of the mechanism of the behavioral response [ A. Markou, et al., Psychopharmacology 112, 163 (1993) [CrossRef] [Medline] ; G. F. Koob, in Psychopharmacology: The Fourth Generation of Progress, F. E. Bloom and D. J. Kupfer, Eds. (Raven Press, New York, 1995), pp. 759-772; G. F. Koob et al., J. Psychopharmacol., in press].
  8. G. F. Koob and F. E. Bloom, Science 242, 715 (1988) [Abstract/Free Full Text] .
  9. R. A. Wise and P.-P. Rompre, Annu. Rev. Physiol. 40, 191 (1989) ; M. Le Moal and H. Simon, Physiol. Rev. 71, 155 (1991) [Free Full Text] ; G. F. Koob, Trends Pharmacol. Sci. 13, 177 (1992) [CrossRef] [Medline] ; F. E. Pontieri, G. Tanda, F. Orzi, G. Di Chiara, Nature 382, 255 (1996) [CrossRef] [Medline] .
  10. W. L. Woolverton, Pharmacol. Biochem. Behav. 24, 531 (1986) [CrossRef] [ISI] [Medline] ; G. F. Koob, H. T. Le, I. Creese, Neurosci. Lett. 79, 315 (1987) [CrossRef] [ISI] [Medline] ; J. Bergman, J. B. Kamien, R. D. Spealman, Behav. Pharmacol. 1, 355 (1990) [Medline]; S. B. Caine and G. F. Koob, Science 260, 1814 (1993) [Abstract/Free Full Text] .
  11. D. W. Self, W. J. Barnhart, D. A. Lehman, E. J. Nestler, Science 271, 1586 (1996) [Abstract] .
  12. G. Di Chiara and R. A. North, Trends Pharmacol. Sci. 13, 185 (1992) [CrossRef] [Medline] ; T. S. Shippenberg, A. Herz, R. Spanagel, R. Bals-Kubik, C. Stein, Ann. N. Y. Acad. Sci. 65