PSY290 - Drugs and Drug Addiction

drug

drug

a chemical substance that produces a biological effect

• can be a naturally-occurring substance or created in lab

routes of administration

determines onset and duration of effect

good drugs

potential therapeutic applications that are permitted in societies

bad drugs

significant drawbacks and perceived risks tend to be more tightly regulated/illegal

desired effect

therapeutic effect like anxiety relief with anxiolytics

unwanted effects

side effects like respiratory depression with anxiolytics

drug response

related to dosage (amount of drug administrated at one time), as it increase the likelihood of the effect and magnitude increase

Effective dose 50 (ED50)

dose at which 50% of the population shows the desired effect

what is the ideal ratio for desired and undesired effects with dosage?

low dose for desired effects and high dose for unwanted effects

therapeutic index

measure of the difference between the dose-response curves for desired and undesired effects

what TI window size is preferred?

wide

what is situated within the TI window?

the therapeutic dose, where desired effects are maximal and unwanted effects are minimal

routes of administration

• oral

• intravenous

• intramuscular

• subcutaneous

blood brain barrier

controls entry of substances via astrocytes

cannabis

positive responses to early use is correlated with future dependence that is related to different genes

ALDH and ADH

associated with poor alcohol tolerance and reduced risk of alcholism

CYP2D6

key involvement in metabolizing drugs and genes for it are correlated with effects

Agonist

binds to receptor for drug action to take effect

antagonist

binds to receptor so that no drug action or effect takes place

how is THC an agonist?

it partially bind to cannabinoid receptors

how is naloxone an antagonist?

blocks the effects of opioids at their receptors and can stop overdoses from occurring

how does cocaine affect transporters?

blocks dopamine transporter activity, keeping dopamine at the synapse for longer

psychoactive drugs

alter mood, though and behavior, can be used to manage neuropsychological illness and can be abused

what are the 5 subclasses of psychoactive drugs?

• antianxiety agents and sedative-hypnotics

• antipsychotic agents

• antidepressant and mood stabilizers

• opioid analgesics

• psychotropics

antianxiety agents and sedative-hypnotics

typically act on GABAa receptors

• benzodiazepines, barbiturates, alcohol, gamma-hydroxybutyrate, ketamine, etc

antipsychotic agents

treat psychosis like in schizophrenia and bipolar, antipsychotics

• block dopamine receptors

first generation antipsychotic agents

chlorpromazine and haloperidol

second generation antipsychotics

clozapine (affects other targets not just dopamine)

antidepressants

used to treat mood disorders

• MAOis, TCAs and SSRIs

mood stabilizers

used to treat bipolar disorder (lithium)

MAOis

prevent the breakdown of monoamine transmitters like serotonin and noradrenaline

SSRIs

prevent reuptake of serotonin by transporters

opioid analgesics

target opiate receptors (includes morphine and heroin)

opiate receptors

involved in the body’s ability to regulate the experience of pain

opioids

have a strong analgesic effect but high potential for tolerance, addiction and withdrawal

analgesic

pain relieving

psychotropics

drugs that affect a person’s mental state that have pleasurable effects making them attractive for recreational use, though many carry significant risk

• includes, amphetamine, nicotine, caffeine, hallucinogens

new perspective of psychedelics

microdosing and potential for therapeutic use

tolerance

decline in drug response as the body adapts to the drug

• related to frequency of use and environment

• can be reversible

metabolic tolerance

change in metabolic pathways

pharmacodynamic tolerance

change in how cells respond to the drug (most common)

Behavioral tolerance

people compensating for the effects of a drug

cross tolerance

when tolerance develops to one drug, the response to other drugs may be affected because both drugs have the same target

contingent tolerance

tolerance only develops to effects that are experienced

conditioned drug tolerance

tolerance expressed based on cues

sensitization

increase in drug response with repeated use like in amphetamines and cocaine

addiction

complex brain disease in which there is a compulsive engagement in behavior despite knowledge of harmful consequences

brain disease

perspective where impaired brain function is critically involved

• preferred term by DSM5 is substance use disorder

addiction risk factors

• stability of home

• early use and peer groups

• education

• employment

• genetics

• gender

• mental health status

gender

usage/dependence rates higher in men for most drugs and overdose rates higher in women for others

neural basis of dysfunction

addiction might involve dysfunction in systems governing mood effect, personality, reward, cognitive control

PFC and amygdala

mood, affect and personality

PFC, striatum and DA neurons

key in reward center

OFC in the PFC

cognitive control

reward system

neural structures implicated in the attribution of reward include the mesolimbic pathway

ventral tegmental area to nucleus accumbens in addiction

DA release in the pathway related to reward strength and craving a

contributes to habit formation which may dysfunction impulse control

DA hypothesis

stimulation of VTA neurons using implanted electrodes is reinforcing so lesion of DA projections prevents this

self administration tests

gauges addictive potential by number of times the mouse presses the bar

conditioned place preference tests

gauge preference for drug tests by evaluating time spend in drug change versus the other

DA antagonistic animal models

self administration and conditioned place preference test

DA signaling in addiction

more cravings which is a symptom of addiction is associated with lower DA receptor availability

• reduced striatal DA release too

DA hypothesis evidence

• stimulation of DA neurons is reinforcing

• antagonism of DA receptors can prevent self administration of substances

• rewards and cravings accompanied by DA release

• abnormalities in DA transmission common

• Gene variation in DA system

what are the issues associated with the DA hypothesis?

• studies in humans are correlational

• best evidence comes from drugs that affect the DA system

• DA release associated with a drug doesn’t predict its addictive properties

frontal cortex

organization, initiation and inhibition of behavior

• hypo frontality/low D2 and reduce gray matter density is associated with addiction in the frontal lobe

• reduced OFC activity = reduced ability to assess value and control behavior

limitations with animal models

• animals are not interacting with a community so disregards the social network risk factor

• environments are low quality

rat park study

• rats given access to an enriched environement with opportunity for social interaction used less morphine (controversial)

choice perspective

emphasis on personal accountability

• idea that it would lead to more effect in abstaining

Disease perspective

perspective acknowledges deficits in biological systems

physical dependence theories

take the drug to avoid withdrawal

positive incentive theories

take the drug for pleasurable effects

instrumental drug use/self medication theories

take the drug for a particular benefit

personality based theories

traits are correlated with drug use (OCEAN

what traits are associated with higher drug use?

neuroticism and openness to experience

what traits are associated with lower drug use?

agreeableness and conscientiousness