ADDICTION AND DRUG ABUSE Flashcards
TWO TYPES OF ADDICTION?
Physiological addiction
Psychological addiction
DIFFERENCE BETWEEN ADDICTION AND HABIT?
Habit – repeated behaviour in which the repetition may be unconscious
Compulsion – if the habit occurs by compulsion and considerable discomfort is experienced if the behaviour is not performed, then the repetition or habit is considered an addiction
WHAT ARE THE TYPES OF ADDICTION
Money addictions
Compulsive gambling
Compulsive shopping and borrowing
Work addiction
Exercise:
Addictive exercisers
Muscle dysmorphia
Internet
Sexual
Multiple
THE INDICATION OF ADDICTION IS DESCRIBED AS HAVING 4 OR MORE SERVERE SYMPTOMS SUCH AS:
Tolerance 🡺 Larger doses needed; lower dosage does not produce typical effect
Withdrawal 🡺 Negative physical and psychological effects from stopping usage
Using more than intended amounts
Trying unsuccessfully to stop
Having physical or psychological problems made worse by drug
Experience problematic relationships
DSM-5 SUBSTANCE USE DISORDERS ARE CATEGORISED BY SPECIFIC SUBSTANCES SUCH AS?
Alcohol
Caffeine
Cannabis (e.g., marijuana)
Hallucinogens
Inhalants
Opioid (e.g., heroin)
Sedatives, Hypnotics, or Anxiolytics (e.g., diazepam)
Stimulants (cocaine, methamphetamine)
Tobacco
Neurobiology of Drug Addiction:
An endpoint of a series of transitions from
initial drug use—drug is voluntarily taken because it has reinforcing (REWARDING OR WITHDRAWAL) effects
through loss of control over this behaviour
becomes habitual and ultimately compulsive
addiction is an endpoint of a series of ____________________
addiction is an endpoint of a series of CHANGES within brain STRUCTURE AND FUNCTION
WHAT ARE THE TWO THEORIES OF DRUG ADDICTION?
Negative Reinforcement Models
Positive Reinforcement Models
DESCRIBE NEGATIVE REINFORCEMENTS MODELS?
Physical dependence (withdrawal) theory 🡺 opiates, barbiturates, alcohol
Distinguished by TOLERANCE and PHYSICAL DEPENDENCE 🡺 need the drug
DESCRIBE Positive Reinforcement Models
Positive incentive (reward) theory 🡺 cocaine, amphetamine, nicotine
Distinguished by REWARD and REINFORCEMENT 🡺 want the drug
Drug Addiction BEHAVIOUR IS CORRELATED WITH:
Brain regions
Brain pathways
Neurotransmitter systems
STATE FACTS ABOUT THE REWARD PATHWAY?
There is a axonal network in the brain labeled the ‘reward pathway’
This reward pathway is activated by:
Food, water and sex, activities (such as sky diving, paragliding etc) and exercise
This reward pathway is also activated by drugs
and alcohol
WHAT ARE THE NEUROTRANSMITTERS INVOLVED IN THE acute reinforcing effects of drugs of abuse?
DOPAMINE
GABA
GLUTAMATE
OPIOID PEPTIDES
WHAT ARE THE ANATOMICALSITES INVOLVED WITH DOPAMINE?
Ventral tegmental area, nucleus accumbens
WHAT ARE THE ANATOMICALSITES INVOLVED WITH OPIOID PEPTIDES
Nucleus accumbens, amygdala, ventral tegmental area
WHAT ARE THE ANATOMICALSITES INVOLVED WITH GLUTAMATE?
Nucleus accumbens
WHAT ARE THE ANATOMICALSITES INVOLVED WITH GABA?
Amygdala, bed nucleus
of stria terminalis
WHAT ARE THE NEUROTRANSMITTERS THAT ACT ON THE REWARD PATHWAY?
Dopamine
Serotonin
Opioid peptides (Endorphins, Enkephalins)
Cannabinoids
WHAT IS THE REWARD PATHWAY OF DOPAIMINE?
Receptors: D1, D2
Function: pleasure, euphoria, mood, motor function
WHAT IS THE REWARD PATHWAY OF Serotonin
Receptors: 5HT3
Function: mood, impulsivity, anxiety, sleep, cognition
WHAT IS THE REWARD PATHWAY OF Cannabinoids
Receptors: CB1, CB2
Function: Pain, appetite, memory
WHAT IS THE REWARD PATHWAY OF Opioid peptides (Endorphins, Enkephalins)
Receptors: Kappa, Mu, Delta
Function: pain
In all rewards, ________ is the final activation chemical
In all rewards, dopamine is the final activation chemical
WHAT ARE NARCOTICS?
OPIATES
(morphine
Heroin)
OPIOIDS
(oxycodone
hydrocodone
codeine
Fentanyl
WHAT ARE HALLUCINOGENS?
LSD
PSILOCYBIN
MDMA
MESCALINE
PCP
MARIJUANA
WHAT ARE DEPRESSANTS?
Alcohol
Benzodiazepines
WHAT ARE STIMULANTS?
DEXEDRINE
CAFFEINE
METHEDRINE
AMPHETAMINE
COCAINE
NARCOTICS ARE _______ADDICTING?
PHYSICALLY
HALLUCINOGENS ARE _____ ADDICTING?
Psychologically
Addicting
DEPRESSANTS ARE _________ ADDICTING?
Physically Addicting
STIMULANTS ARE ___________ADDICTING?
Physically &
Psychologically
Addicting
DESCRIBE DIRECT DRUG ACTION IN ADDICTION?
Drugs of abuse may work via direct action on a DA receptor or DA transporter
🡺 increased DA receptor activation eg cocaine
DESCRIBE INDIRECT DRUG ACTION IN DRUG ADDICTION?
Drugs of abuse may modulate dopamine via other receptor system and neurotransmitters that then modulate a different system
Downstream effects on dopamine from above systems
e.g. Alcohol
MECHANISM OF ACTION DURING INDIRECT DRUG ACTION WHEN TAKING ALCOHOL?
ALCOHOL Binds to subreceptors GABAA: Dopaminergic activity is eventually increased in the VTA by inhibiting GABAergic interneurons
Also binds to NMDA, endorphins, activates secondary messages and has direct serotonergic effects
MECHANISM OF ACTION FOR ALCOHOL
Inhibit GABAergic neurons that project to dopaminergic neurons in the VTA
MECHANISM OF ACTION FOR HEROIN
Binds to opioid receptors that inhibit GABAergic neurons that project to dopaminergic neurons in the VTA
MECHANISM OF ACTION FOR COCAINE?
Blocks the function of DAT (by binding to the DAT and slowing transport)
MECHANISM OF ACTION FOR NICOTINE
Activates cholinergic neurons that project to dopaminergic neurons of the VTA
WITHDRAWAL SYNDROME INVOLVES?
AND WHAT DOES IT LEAD TO?
activation of the thalamus
release of corticotrophin releasing hormone (CRH)
activation of the noradrenergic nucleus locus coeruleus (LC)
Results in the stress response
Increased discomfort/anxiety during withdrawal as well as other negative effects
Can lead to further consumption and thus relapse
WHAT ARE THE INTOXICATION EFFECTS FOR THESE NEURO TRANSMITTERS?
DOPAMINE
OPIOID PEPTIDES
SEROTONIN
GABA
Dopamine: euphoria
Opioid Peptides: analgesia, relaxation
Serotonin: elevated mood
GABA: decreased anxiety, less panic, relaxation
WHAT ARE THE WITHDRAWAL EFFECTS INVOLVED WITH THESE NEUROTRANSMITTERS?
DOPAMINE
SEROTONIN
OPIOID PEPTIDES
GABA
NPY
NE
GLUTAMATE
CRF
DYNORPHIN
Dopamine: dysphoria
Dynorphin: dysphoria
Serotonin: dysphoria
CRF: stress
Opioid Peptides: increased pain
GABA: anxiety, panic attacks
Norepinephrine: stress
NPY: anti-stress
Glutamate: hyperexcitability
WHAT IS THE NOVEL TREATMENT FOR?
Nicotine gum/patch: activate nicotinic receptors
PSYCHOSTYMULANT DEPENDENCE NOVEL TREATMENT?
Rimonabant: blocks cannabinoid receptors (CB1)
GIVE A BRIEF SUMMARY OF THE Neurobiology of Addiction
Anatomical areas of the brain involved in the reward pathway include the nucleus accumbens, ventral tegmental area and the prefrontal cortex
Dopaminergic activity is the final chemical action in most behaviors relating to reward
Drugs of abuse may work with receptors and transporters to directly or indirectly influence dopaminergic activity
Withdrawal occurs following an abrupt cessation of drug of abuse following changes to the nervous system
Addiction is the result of and results in lasting changes to neurocircuitry, cellular and molecular mechanisms
WHAT ARE THE 3 WAYS TO MANAGE ADDICTION?
Medical intervention
Pharmacotherapy
Psychosocial treatment.
WHAT ARE THE PAHRMACOLOGICAL STRATEGIES AIMED AT?
treating acute withdrawal symptoms
preventing relapse
substitution therapy
WHAT IS THE MA OF ALCOHOL?
Has its own binding site on the GABA-A receptor complex to enhance the effects of GABA.
Acts as an indirect antagonist at glutamate NMDA receptors 🡺 blocks ion channel associated with the glutamate NMDA receptor
Chronic blockade of glutamate NMDA receptors by alcohol 🡺 upregulation of these receptors.
Consequences of the upregulation of glutamate NMDA receptors include tolerance to the effects of alcohol 🡺 increase the risk of seizures during withdrawal.
NALTREXONE FACTS IN RESPECT TO
RECEPTOR IT WORKS ON OR MA
CLINICAL TRIALS
ADVERSE EFFECTS
USUAL DOSE
𝜇-opioid receptor antagonist that blocks the reinforcing effects of alcohol on the opioid system and reduce craving for alcohol
Clinical trials show that naltrexone is effective in reducing alcohol intake and in preventing relapse.
Naltrexone is usually taken orally in doses of 50 mg/d for up to 12 weeks or given as an intramuscular injection in the gluteus muscle at a dose of 380 mg every four weeks.
The main adverse effects are nausea, vomiting, loss of appetite, abdominal pain, dizziness, anxiety and dysphoria.
FACTS ABOUT DISULFRAM IN RESPECT TO
MA OF ETHANOL
MA OF DISULFRAM
USUAL DOSE
EFFECTIVENESS AND WHO IT SHOULD BE PRESCRIBED TO?
Ethanol 🡺 metabolised to acetaldehyde by the enzyme alcohol dehydrogenase 🡺 to acetic acid by the enzyme acetaldehyde dehydrogenase 🡺 the acetic acid enters the Krebs cycle 🡺 broken down into water and carbon dioxide.
Disulfiram 🡺 blocks the oxidation of ethanol at the aldehyde stage by inhibiting the enzyme aldehyde dehydrogenase 🡺 accumulation of acetaldehyde produce palpitations, throbbing headaches, hypotension, nausea, emesis, flushing, dizziness, chest pains and thirst.
Taken orally at a dose of 500 mg per day for 2 weeks and then maintained at a dose of 250 mg per day.
When taken daily, disulfiram is effective in preventing relapse in some people, but not all. It is recommended that disulfiram be prescribed to motivated patients as an adjunct to cognitive behavioural therapy and abstinence-based rehabilitation programmes.
FACTS ABOUT ACAMPROSATE?
WITH RESPECT TO
MOA
SIDE EFFECT
EFFECTIVE NESS IN PERCENTAGES
WHAT COMBINATION THERAPY IS MOST EFFECTIVE?
An anti-craving drug that is used to sustain abstinence in alcoholics after detoxification.
MOA
Agonist activity at GABA-A receptors and antagonist activity at glutamate NMDA receptors 🡺 mimics the actions of alcohol at these receptors.
Oral dose
The main adverse effect is diarrhoea.
It reduces frequency of drinking by 30–50%.
Combining drug therapy with CBT and abstinence-based rehabilitation programmes has been found to reduce relapse rates further.
Administering acamprosate with naltrexone has greater beneficial effects than either of the drugs alone in attenuating the occurrence of relapse.
Alcoholics Anonymous (AA). IS A GROUP SUPPORT METHOD OF ACOHOL ABSTINENCE
STATE FACTS ABOUT IT?
The basic tenet of AA is that alcoholism is an incurable condition and the only way to manage the condition is life-long abstinence.
Alcoholics will attend regular meetings where they discuss the circumstances that lead them to abuse alcohol and become addicted.
Members of the group will give each other support to avoid relapse.
Such group therapy is effective in maintaining abstinence in a large number of alcoholics.
STATE FACTS ABOUT HEROIN
WITH RESPECT TO
MOA
HOW LONG IT TAKES TO DEVELOPE
DEPENDENCE AND TOLERANCE
WITHDRAWAL SYMPTOM
HOW ARE SOME OF THE WITHDRAWAL SYMPTOMS MANAGED?
Heroin is a 𝜇-opioid receptor agonist and mimics the reinforcing effects of naturally released enkephalins in the brain.
If heroin is taken regularly for a few weeks, tolerance and dependence develop.
People who are dependent on heroin will display withdrawal symptoms that include restlessness, spasms of agonizing pain, involuntary twitching of the leg muscles, fever and sweating followed by hypothermia, vomiting and diarrhoea.
Addicts who undergo withdrawal may be given medication to help with the withdrawal symptoms: loperamide for diarrhoea, metoclopramide for nausea and vomiting, ibuprofen for headache and lofexidine (an 𝛼-adrenoceptor agonist) for hypertension.
HOW IS HEROIN ADDICTION MANAGED?
METHADONE
BUPRENOPHINE
MOA OF METHADONE?
is a long-acting 𝜇-opioid receptor partial agonist that is administered as an oral solution once daily. The normal dose varies depending on the patient, but is in the range 15 to 40 mg. Methadone should be given eight hours after the discontinuation of heroin.
MOA OF BUPRENORPHINE?
Buprenorphine is a partial agonist at 𝜇-opioid receptor but also has antagonist activity at 𝜅 (kappa) opioid receptors. It is given as a sublingual tablet. Buprenorphine should be given 6–12 hours after the discontinuation of heroin. A combination preparation that contains buprenorphine and naloxone may be prescribed for addicts likely to inject the drug iv.
What are the dopamine pathways involved in addiction and drug abuse?
Answer: The dopamine pathways involved in addiction and drug abuse are the reward pathway, pleasure pathway, euphoria pathway, motor function pathway, and decision-making pathway.
Question: What region of the brain is involved in reward processing?
Answer: The nucleus accumbens is a region of the brain that is involved in reward processing.
Question: What is the role of serotonin in addiction and drug abuse?
Answer: Serotonin is involved in regulating mood, memory, sleep, and cognition. Chronic drug use can lead to changes in the serotonin pathways, leading to altered mood and anxiety levels.
Question: What can chronic cocaine use lead to in terms of serotonin levels and behavior?
Answer: Chronic cocaine use can lead to reduced serotonin levels in the prefrontal cortex, leading to increased impulsivity and risk-taking behavior. This can contribute to drug-seeking behavior and addiction.
