Dr Abdullah AbuAdas Addictionis a Conflict Between Desire and Will Congress

7/31/2019 Dr Abdullah AbuAdas Addictionis a Conflict Between Desire and Will Congress

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Dr. Abdullah AbuAdas

Presented by dr abdullah abuadas

http://medicsindex.ning.com/profile/drabdu

llahabuadas
http://medicsindex.ning.com/profile/drabdullahabuadashttp://medicsindex.ning.com/profile/drabdullahabuadashttp://medicsindex.ning.com/profile/drabdullahabuadashttp://medicsindex.ning.com/profile/drabdullahabuadas


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Compulsive DrugUse

IntensiveDrugUse

CasualDrugUse

ExperimentalDrug Use

Circumstanti

al Drug Use

MotivationalStrength

MotivationalToxicity

From Bozarth (1990); terms

described on the continuum weresuggested by Jaffe (1975).
http://www.jordanmedicslive.com/


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Accidents / injury Poisoning / hangovers Absenteeism

High-risk behaviour

Health Finances

Relationships Child neglect

Impaired controlDrug-centred behaviourIsolation / social problemsWithdrawal symptoms and psychiatric

problems

Health problems


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Drugs of abuse (including alcohol) are inherentlyrewarding, which is why they are consumed byhumans or self-administered by laboratoryanimals . Only a small percentage of individualsexposed to drugs will become addicted, that is,shift from controlled drug use to compulsivedrug use with loss of control over intake despiteadverse consequences, however . Factors thatdetermine who becomes addicted include genetic

(50% of risk), developmental (risk is higher inadolescence), and environmental (e.g., drugaccess, stress) factors .


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While psychological theoriesaccount for a largeproportion of thebehaviours related to druguse, other factors are alsoimportant

It is increasingly recognisedthat genes play animportant role in anindividuals response todrugs and the propensity forthe development ofdependence


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A range of environmental factors impact on druguse, including price and availability of both licitand illicit drugs

Other environmental factors include prenatalproblems, early childhood experiences, familyrelationship and bonding, and early educationalopportunities.

Cultural norms around drug use also act aspowerful determinants of the use of both licitand illicit substances


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: The reward pathway produces feelings of pleasure in response tonaturally enjoyable stimuli, such as food andsex.

Connected to other brain regions, includingmemory storage, the pathway motivates us to

repeat activities that perpetuate the species.


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Drinking or doingdrugs hijacks the reward pathway.

But in genetically vulnerable people, thisaltered state leads to an addiction that theyare, on their own, powerless to overcome.

Someone with an addiction cant talk herselfout of the compulsion any more than

someone can talk herself out of depression.


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Schick Shadel Hospital, 2009


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All drugs that can lead to addiction increase DA in NAc,which is achieved through their interaction with differentmolecular targets by the various drug classes . In humans,PET studies have shown that several drugs [stimulants ,nicotine , alcohol , and marijuana increase DA in dorsaland ventral striatum (where NAc is located). These studies

used a radiotracer that binds to DA D2 receptors (D2Rs)but only when these are not occupied by DA . Bycomparing binding after placebo and after the drug, thesestudies estimate the decreases in D2R availability inducedby the drug, which are proportional to DA increases. Moststudies have reported that participants who display thegreatest DA increases with the drug also report the mostintense high or euphoria ).


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PET studies have also shown that the speed with which a drugenters and leaves the brain (pharmacokinetic profile) is crucialfor its reinforcing effects. Specifically, PET studies of brainpharmacokinetics of drugs labeled with positron emitters showthat peak levels in human brain are reached within 10 min afteri.v. administration and that this fast drug uptake is associatedwith the high . Indeed, for an equivalent level of cocaine reaching

the brain (assessed as equivalent level of DA transporterblockade), when cocaine entered the brain rapidly (smoked andi.v. administration), it elicited a more intense high than when itentered the brain more slowly (snorted) . This is consistent withpreclinical studies showing that the faster the drug's entry intothe brain, the stronger are its reinforcing effects . This probablyreflects the fact that abrupt and large DA increases triggered by

drugs mimic the fast and large DA increases associated withphasic DA firing that are associated in the brain with conveyinginformation about reward and saliency .


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Imaginingthe brain on

drugs

Volkow (2004) Nat Rev.

Reduced D2Ravailability & blood flowcorrelate with addiction


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Source: Di Chiara et al.

FOOD

Source: Fiorino and Phillips

SEX

Natural rewards elevate dopaminelevels


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Drive

OFCSaliency

NAc

Memory

Amygdala

Control

CG

Non-AddictedBrain

AddictedBrain

STOP

GO

Drive

Memory

Saliency

Control

Drive

Memory

Saliency

Adapted from: Volkow et al.,J Clin Invest 111(10):1444-1451, 2003.


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ec s o rugs on opam ne


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COCAINE

NICOTINE

Source: Shoblock and Sullivan; Di Chiara and Imperato

ec s o rugs on opam neRelease

ETHANOL

METHAMPHETAMINE


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Operating through different mechanisms drugs of

abuse have a final common pathway by which theyincrease dopamine levels within the core structures ofthe so called brain reward system which includes

the VTA and NA. A balance between the negativeeffects of the drug and positive feelings associatedwith stimulation of the brain reward systemdetermine if an individual will enjoy and continueusing the substance or not. Generally the positive

effects or high of using a drug occur immediately orshortly after use, by the action of increasingdopamine.


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The closer positive and negative effects are tothe actual time of drug use, the more likely weare to associate these effects with the drug.Unfortunately, the negative consequences of

drug use often come much later and moreunpredictably compared to the immediate pairingof drug administration and reward. For example,the later potential negative consequences of

chronic drinking (such as liver disease) may notbe as important as the immediate rewardingpositive effects of drinking.


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Some approaches to treatment attempt toconsistently pair the negative consequences ofdrug administration with drug administration. Ifone is taking disulfiram (Antabuse), the action ofdrinking will immediately cause a negative

consequence (extreme illness). The immediatenegative consequence of drinking now competeswith the normally immediate positive reward ofdrinking to combat illness. By changing the timecourse of positive and negative drug effectsthrough behavioral interventions orpharmaceutical interventions, we may be able tobetter treat addictions in the future.


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Pharmacotherapeutic interventions have been

developed to decrease drug use by influencingthe brain reward system. General strategies for

pharmacological treatment of drug addictioninclude creating aversion to the addicted drug,bringing consequences or punishment closer tothe reinforcement of drug use, modification of

neurotransmitters to decrease drug intake, andlong-term substitution with a less addictive andcross-tolerant medication .


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Increasing the negative or aversive effects of a drug is

one effective treatment used for alcohol addiction.Disulfiram (Antabuse), metronidazole, or calciumcarbimide is used to create negative effects with the

ingestion of alcohol . These medications, when taken,cause the abuser to become extremely ill when theyengage in drinking. Instead of experiencing thenegative effects of alcohol the next day (hangover) oryears later (liver disease), they experience unpleasant

effects such as nausea, vomiting, and flushing incloser proximity to ingestion which opposes thenormally immediate positive reward of the drug .


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By manipulating neurotransmitters in the reward pathway,

we can potentially modify cravings for drugs of abuse.This can be accomplished , by giving drug antagonists, ordrugs that block the addicting effects of the dopaminereward system. For example, dopamine blocking agents

have been shown to diminish intake of all drugs of abusein animal studies . However, application in humans hasbeen less promising. In humans, the euphoria induced byamphetamine administration is attenuated by dopamineblocking agents. Thus, when the drug no longer increasesdopamine levels and causes feelings of well being, the

desire for the drug may diminish. Bupropion, a dopamineagonist, has been shown in nicotine addiction but has notbeen shown to be effective in cocaine addiction.


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anhedonia craving

Chronichypodopaminergicactivity

Transitoryhyperdopaminergicactivity

Motivational ToxicityDependent Relapse


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By substituting one substance that stimulates

the brain reward pathway with another lessaddictive/ less harmful substance, we may

aid in relapse prevention. One example is theuse of methadone to treat heroin addiction.Methadone does not have the euphoriceffects that heroin does; however, it doesadequately stimulate the brain reward systemand provides a safer alternative to heroin use.


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W N d t T t th


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We Need to Treat the

Whole Person and the WholeVillage!

In the Social Context

Educate the Community, theChildren, the HealthcareProviders

Increased PrescriptionMonitoring Working inConjunction with Law

Enforcement


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Ongoing Funded Projects

Active and passive immunization using anti-cocaineantibodies and anti-cocaine catalytic antibodies

Cocaine vaccine (Xenova, UK)

Passive immunization using anti-PCP monoclonalAntibodies.

Passive immunization using anti-cocaine monoclonalantibodies .

Passive immunization using anti-methamphetaminemonoclonal antibodies .

Development of immunotherapies using:

Nicotine vaccine .


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Dr. Abdullah AbuAdas

Presented by dr abdullah abuadashttp://medicsindex.ning.com/profile/drabdullahabuadas

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Dr Abdullah AbuAdas Addictionis a Conflict Between Desire and Will Congress