Lecture 74 - Pathophysiology of Substance Use Disorder Flashcards
Stimulants
Cocaine
Amphetamine
Meth
Bath salts
Ecstasy
Nicotine
Depressants
Opioids
Alcohol
Cannabis
GHB
Inhalants
Psychedelics
LSD
Psilocybin
PCP
Mescaline
Ketamine
CONTROLLED SUBSTANCE ACT - DRUG CLASSIFICATION
Schedule I-V
Schedule I
No medical use, high abuse potential. Safety not guaranteed
Heroin, Marijuana, THC, LSD, GHB, psilocybin, MDMA
Schedule II
Medical use, high abuse potential, large risk of dependence
Morphine, fentanyl, cocaine, ritalin, PCP, barbiturates, oxycodone, hydropmorphone, Vicodin (hydrocodone+tylenol) , Percocet (oxycodone +tylenol), nabilone (synthetic cannabinoid)
Schedule III
Medical use, moderate abuse and dependence Ketamine, buprenorphine, Marinol (THC in oil capsule)
Schedule IV
Medical use, low abuse and dependence Benzodiazepine
Schedule V
lower risk relative to IV
Cough suppressants with small amount of codeine; Lomotil (antidiarrheal opioid with atropine)
“SEMI LEGAL” HIGHS – ON THE BORDER OF LEGALITY
Some are legal: Fuel, glue
Some were legal: Spice, K2 (synthetic THC mimics), Bath salts, Banned, updated by DEA
- Case by case, Blanket ruling
Some are still legal: New designer drugs - “Not for consumption”, Until DEA catches up
Some are illegal: But hard to enforce - Mushrooms
SUBSTANCES OF ABUSE THAT ACT DIRECTLY ON G PROTEIN-COUPLED RECEPTORS
Opioids (heroin, prescription meds): Opioid receptors (mu)
LSD, Mushrooms (psilocybin, psilocin): Serotonin receptor (5-HT2A, 5-HT2C)
Marijuana, K2, spice: Cannabinoid receptors (CB1)
Gamma Hydroxy Butyric acid: GABAB
Caffeine: Adenosine receptors
SUBSTANCES OF ABUSE THAT ACT INDIRECTLY ON G PROTEIN-COUPLED RECEPTORS
Cocaine, amphetamine: Dopamine transporter (dopamine receptors); Noradrenaline, serotonin transporters; Release dopamine, noradrenaline, serotonin -> GPCRs
MDMA/Ecstasy: Monamine transporters
- dopamine, serotonin
Alcohol: GABA channels, 5HT3, NMDAR, nAchR, KiR3; Causes release of endogenous opioids -> GPCRs
SUBSTANCES OF ABUSE THAT ACT ON ION CHANNELS
Nicotine: Ionotropic acetylcholine receptors (Na+), agonist
PCP, ketamine: Ionotropic NMDA receptor (Ca2+, Na+ - K+), Antagonist
Benzodiazepines, barbiturates: Ionotropic GABAA receptors (Cl-); positive allosteric modulators
Frontal cortex
decision making, impulsivity
Striatum
reward/value
Nucleus accumbens
pleasure, valuation
VTA
source of dopamine
Hippocampus
memory, learning
STIMULANTS, DEPRESSANTS AND PSYCHEDELICS ALL ACT ON THE
mesolimbic system
THE DOPAMINE HYPOTHESIS OF ADDICTION
“Pleasurable events” release dopamine
Parkinson patients only develop addiction during treatment
Dopamine important for assigning value to reward prediction error: Value provides the drug with an incentive salience; Salience = state or quality of an item that stands out relative to neighboring items
LIMITS OF DOPAMINE HYPOTHESIS
Dopamine not required for reward learning: Dissociation between liking (direct effect)
and wanting (motivation) - “You don’t always like what you want”
Tolerance to pleasurable effect (↓ liking), enhanced craving
Dopamine does not encode liking, but involved in making reward predictions and learning from
the outcome/error
THE GLUTAMATE HYPOTHESIS OF ADDICTION
Glutamate can increase dopamine activity in NAcc: Glutamate projection to VTA; Destruction of this pathway reduces cocaine/morphine reward; NMDA antagonist blocks acquisition of reinforcement learning; Intra NAcc AMPA injection causes relapse
Dopamine controls glutamate activity in amygdala
DRUG USE INDUCES LONG TERM CHANGES IN NEURONAL PLASTICITY
Rewarding substances cause relative increase in glutamatergic AMPA receptors
Drug abuse
The use of a drug for a nontherapeutic effect
Drug misuse
Inappropriate, illegal, or excessive use of a prescription or nonprescription drug: Taking more/more frequent then prescribed; Taking it for different indication; Taking someone else’s medication
SUBSTANCE USE DISORDER CRITERIA
Previously substance abuse and substance dependence
Mild (2-3), moderate (4-5) or severe (>6): taking substance in larger amounts for for longer; unable to stop; preoccupied; cravings; distracted; problems in relationships; giving up; put yourself in danger; against better judgement; tolerance; withdrawal
PHYSICAL VERSUS PSYCHOLOGICAL DEPENDENCE
Physical dependence: Body needs more drug – tolerance - Cellular adaptations upon repeated activation of receptors; Body withdraws without the drug
Psychological dependence (≈addiction): Mental urge to take drug to function; Compulsive need/craving; Even in absence of withdrawal
TYPES OF WITHDRAWAL SYMPTOMS
emotional
physical
dangerous
Emotional Withdrawal Symptoms
Anxiety, depression
Restlessness, insomnia
Irritability
Headaches
Poor concentration
Physical Withdrawal Symptoms
Sweating
Racing heart
Goose bumps = Cold turkey
Muscle spasms = kicking the habit
Tremors
Nausea, vomiting, diarrhea
Dangerous Withdrawal Symptoms
Alcohol and tranquilizers
Grand mal seizures (also tramadol)
Heart attacks, Strokes
Hallucinations, Delirium tremens (DTs)
DRUG REWARD AND ITS RELATION TO POSITIVE AND NEGATIVE REINFORCEMENT
Drug is “rewarding” or produces positive reinforcement when the user feels pleasure/satisfaction: Of value, strengthen behavior to repeat; Just liking isn’t enough
Negative reinforcement: reward by escaping negative/painful stimulus or event (NOT same as punishment)
WHAT ARE RISKS OF DRUG BINGES AND MULTI DRUG USE
Use depressant together with stimulant to numb the crash of stimulant: Speedball (heroin + cocaine)
Risk of overdose (not aware of some signs): More difficult to treat overdose
PHYSIOLOGICAL RESPONSES THAT MAY LEAD TO FATAL OVERDOSE
Respiratory depression: opioids, alcohol
Cardiac arrhythmias, Brain hemorrhage, stroke: Stimulants
Fatal seizures: Choke on own vomit, Also risk during withdrawal
