psyc265: exam 2

ethyl alcohol

alcholism, alcohol abuse, binge drinking, underage drinking - public health issues 

ethanol - psychoactice sedative hypnotic; recreational

crosses blood brain and placental barriers 

absorption and distribution of alcohol

• 20% absorbed in stomach, 80% absorbed in intestines

• food in stomach slows absorption

• peak BAC: 15-60 minutes post drinking 

• evenly distributed, crosses membranes easily

metabolism of alchohol

• liver metabolizes ~85%, 5% exhaled/unchanged

• 3 steps: alcohol → acetaldehyde (ADH) → acetic acid → CO2 +h20

sex differences - alchohol

women: lower gastric adh → higher bac - more body fat, less dilution

men: higher muscle to fat ratio, lower bac

alcohol substitutes

alcosynth: synthetic alcohol like substance, no hangover liver damage

palcohol: powdered alcohol - 10% abv, limited legal approval

neurotransmitter systems affected by alcohol

glutamate: inhibits NMDA → memory impairment 

GABA: enhances inhibition → sedation

opiods: influence reward, blocked by naltrexone

serotonin: chronic use rises activity, SSRIs help 

cannabinoids: chronic use lowers receptors, withdrawal → craving

behavioral and physiological effects of alcohol

acute: cns depression, slowed reaction, impaired judgement, blackouts possible

withdrawal: hyperexcitability, seizures

long term: nutritional, liver, nerve, cancer risks

inhalants of abuse - alcohol

definition: volatile vapors inhaled for psychoactive effects (aerosols, adhesives, solvents, nitrites

acute: hypoxia, cardiac arrhythmia, similar to depressants

chronic: CNS/liver damage, dementia, toluene neurotoxicity, fetal solvent syndrome

treatment: oxygen therapy, prevention best approach

caffeine basics

most widely used psychoactive drug - over 80% consumption by US adults daily 

stimulates CNS, heart, kidneys, relaxes smooth muscle 

caffeine regulation

fda: safe below .02% in beverages, or ~400 mg/day

caffeine powder unregulated

not a DEA controlled substance

pharmokinetics of caffeine

absorption: 99% within 45 minutes, crosses placenta and BBB

elimination half life: 2.5-10 hours

metabolized by CYP1A2 → paraxanthine, theophylline, theobromine 

SSRIs can inhibit metabolism 

genetic factors: CYP1A2: fast vs slow metabolizers; ADORA2A: alters adenosine receptor sensitivity 

beneficial effects of caffeine

cardiovascular: headache relief, lower CVD risk

metabolic: improved insulin secretion, lower diabetes risk

cancer: reduced liver, cancer risk

neurological: possible protection vs parkinsons, ms

cognitive: better alertness, reduced depression

other: bronchial relaxation, increased urination

pharmocodynamic and behavioral effects of caffeine

normal dose: 100-200mg, alertness, focus, less fatigue, coordination errors

high dose: anxiety, tremors, insomnia

toxic dose: spinal cord stimulation, arrhythmias

lethal dose: ~100 cups of coffee

adverse effects of caffeine

sleep interference, false sense of sobriety when w/ alcohol

risky behaviors

energy drinks: unregulated, common cause of toxicity in children

caffeine poder: one tablespoon can be lethal

mechanism of action of caffeine

adenosine normally inhibits neurotransmission

caffeine blocks adenosine receptors (A1, A2A, A2B, A3) → NE, DA, Ach, glutamate, GaBA

promotes wakefulness and alertness through prefrontal dopamine (not nucleus accumbens)

reproductive effects of caffeine

75% of pregnant women consume caffeine 

linked to low birth weight, miscarriage (dose dependent)

recommends: <200mg/day during pregnance

tolerance/depdnence use for caffeine disorder

tolerance develops for BP, HR, andrenaline effects, not for alertness

caffeine use disorder (DSM-5)

• craving failed attempts to quite

• continued use despite harm

  • withdrawal (headaches, irritability, fatigue) 

nicotine overview

derived from tobacco

administration: inhalation, nasal, oral, patch

blood levels comparable across routes

one of three most used psychoactive drugs and leading preventable cause of death

nicotine pharmokinetics

~25% absorbed in avg cigarette

crosses placenta and in breast milk

metabolism: CYP2A6 → cotinine (marker for use)

half life: 2 hours

mechanism of action of nicotine

nicotinic acetylcholine receptor (nAChR) agonist → rises dopamine release in mesolimbic system (VTA - nucleus accumbens)

menthol reduces receptor activation, increases addiction and relapse risk 

pharmacological/behavioral effects of nicotine

brain: dopamine release correlates with craving relief

cognitive: improved attention and memory, low dose

accute effects: vasoconstriction, stomach suppression, bowel stimulation, increased blood sugar

tolerance: minimal, smokers self titrate

withdrawal: irritability, anxiety, restlessness, insomnia, weight gain

toxicity and health risk

chronic exposure: upregulation of nicotinic receptors

CNS: brain matter loss, enzyme changes

cardiovascular: increased arteriosclerosis, thrombosis, CVD risk

pulmonary: lung damage, reduced cilia

cancer: major cause of lung, mouth, throat, bladder, pancreatic 

endocrine: diabetes, cataracts, premature aging 

reproductive: fetal hypoxia, low birth weight 

passive smoke: causes SIDS, asthma, heart disease, 1% of global deaths

nicotine cessation and treatment

Goals: withdrawal management, reduce craving, prevent relapse.
Nicotine Replacement Therapies (NRT):
- Gum, lozenges, patches, nasal spray, inhaler.
- works by providing lower, controlled doses of nicotine
Non-NRT options:
- Bupropion (Wellbutrin), varenicline (Chantix).
Partial agonists: reduce craving, block nicotine.
Nicotine vaccines: limited success.
Success rate ~22% at 12 months; 90% relapse within 1 year.

psychostimulants

- Increase monoamine neurotransmitters (dopamine, norepinephrine, serotonin).
- Stimulate the sympathetic nervous system (sympathomimetic).
- Include: cocaine, amphetamines, methamphetamines, MDMA, and natural stimulants (khat, caffeine, nicotine).
- Produced legally (e.g., methylphenidate, dextroamphetamine) or illegally (e.g., meth, crack cocaine).

cocaine 

schedule 2 drug - limited medical use, high abuse potential 

forms: leaf, powder, freebase/crack

patterns of use for cocaine

social and binge use; with alcohol

middle class professionals, injecting users

pharmokinetics of cocaine

- Absorption: 20–30% snorted, nearly 100% inhaled or injected.
- Onset: seconds (smoked), 1 min (IV), 5–10 min (snorted).
- Half-life: ~50 minutes.
- Metabolites: benzoylecgonine (drug testing) and cocaethylene (forms when cocaine is combined with alcohol increasing toxicity).`

mechanisms of action for cocaine

- Blocks dopamine transporter (DAT) and vesicular transporter (VMAT), increasing dopamine in synaptic cleft.
- Also blocks reuptake of norepinephrine and serotonin.

effects of cocaine

- Low doses: euphoria, alertness, increased libido.
- High doses: paranoia, anxiety, hallucinations (“formication”), cardiac damage.
- Withdrawal: depression, fatigue, cravings.
- Long-term use: brain damage (gray matter loss), psychosis, reproductive/fetal harm.

amphetamines

used for fatigue, depression, ADHD, weight control; later restricted

pharmokinetics of amphetamines 

- Well absorbed; long half-life (hours).
- Longer duration than cocaine → higher abuse potential.
- 20–25% experience rapid onset (<60 min).

mechanism of action for amphetamines

- Stimulates dopamine and norepinephrine release from presynaptic terminals.
- Blocks reuptake and reverses dopamine transport.
- High doses inhibit monoamine oxidase (MAO), preventing breakdown

effects of amphetamines

- Low doses: increased energy, alertness, respiration, heart rate.
- Moderate/high doses: tremors, restlessness, anxiety, paranoia.
- Chronic use: stereotyped movements, weight loss, psychosis.
- Dependence: depression, fatigue, insomnia, suicidal ideation on withdrawal

methamphetamine 

- More potent than amphetamine; stronger dopamine release and BBB penetration.
- Longer duration (6–8 hrs vs 4–6 hrs).
- Half-life ~11 hrs; metabolized in liver.
- Neurotoxic: reduces gray matter, increases inflammation and ventricle size.
- Linked to aggression, psychosis, immune suppression.
- Prenatal exposure: low birth weight, developmental issues, later ADHD risk

nonamphetamine stimulants

·       Ephedrine/Pseudoephedrine: found in cold meds; used in meth production.

·       Modafinil: non-amphetamine stimulants for narcolepsy, sleep disorders.

Methylphenidate (Ritalin): blocks dopamine transporters; ADHD treatment

psychedelic drugs

·       Psychedelic drugs alter perception, mood, and cognition by acting on CNS

Major classes include anticholinergic, monoaminergic (catecholamine-like and serotonin-like), glutamatergic NMDA antagonists, and kappa-opioid receptor agonists

anticholinergic psychedelics

• Examples: scopolamine, atropine, and l-hyoscyamine.

• Found in plants such as belladonna, mandrake, and datura.

• They are competitive antagonists at muscarinic acetylcholine receptors.
  Effects: dry mouth, blurred vision, amnesia, delirium, drowsiness, hallucinations. Historically associated with witchcraft and sorcery.

• Medical uses include motion sickness treatment.

Tolerance is modest; toxicity mainly results from accidents or suicide rather than overdose

monoaminergic psychedelics

·       Drugs resemble monoamine neurotransmitters (serotonin, dopamine, norepinephrine).

·       Rapid tolerance & cross-tolerance occurs among similar drugs.

·       Examples include mescaline (peyote cactus) and MDMA.

·       Effects include stimulant and hallucinogenic activity, euphoria, empathy, and sensory intensification.

·       MDMA acts as a serotonin and dopamine releaser/reuptake inhibitor but is neurotoxic with chronic use.

serotonergic psychedelics

• Includes LSD, DMT, and psilocybin.

• Compounds act as agonists at 5-HT2A receptors.

• LSD is potent (active at 25–300 μg), produces vivid visual hallucinations, altered time perception, and emotional shifts. Physiological effects include increased heart rate, blood pressure, and temperature.

• Psilocybin (from mushrooms) less potent than LSD; effects last 6–10 hours.

• DMT is short-acting (30 minutes) and present in ayahuasca.

• Rapid tolerance and cross-tolerance occur among serotonergic psychedelics but little physical dependence.

Possible use for depression, PTSD, OCD, and end-of-life anxiety

glutanminergic NMDA antagonists 

·       Drugs: PCP (phencyclidine) and ketamine. - block the NMDA receptor ion channel, causing analgesia and sensory distortions without loss of consciousness.

·       High doses produce psychotic symptoms resembling schizophrenia.

·       Ketamine has therapeutic potential as a rapid-acting antidepressant. Side effects include agitation, hypertension, and urinary tract damage.

kappa -opiod psychedelics

·       Salvinorin A (from Salvia divinorum) is a kappa-opioid receptor agonist, not acting on serotonin receptors.

·       Produces short-lasting visual hallucinations and dissociative experiences.

·       Potential therapeutic effects include antidepressant and anxiolytic benefits.

therapeutic potential

·       Research suggests LSD, psilocybin, and MDMA may help treat mood disorders, PTSD, and addiction when combined with psychotherapy.

·       Psychedelics may promote neuroplasticity and emotional processing, although safety, regulation, and potential abuse remain key concerns.

cannabis 

·       Cannabis (marijuana) - derived from the Cannabis sativa, indica, and ruderalis species.

·       The main psychoactive component is tetrahydrocannabinol (THC), with cannabidiol (CBD) contributing nonpsychoactive, therapeutic effects.

·       Produces stimulant, sedative, analgesic, and hallucinatory effects.

·       Legalization, social attitudes, and synthetic derivatives have greatly influenced current research and policy trends.

history and legalization of cannabis

·       Use dates back to ancient China (4000 BCE) and India (1500 BCE); spread through trade and colonial expansion.

·       U.S. laws evolved from early prohibitions (1906–1937) to the Controlled Substances Act (1970).

·       Modern shifts include medical and recreational legalization in many states, though federal law still classifies cannabis as Schedule I.

·       Research is limited due to regulatory barriers, including reliance on NIDA-supplied cannabis.

cannabis plant composition and forms 

·       Cannabis plants contain varying THC (higher in Sativa) and CBD (higher in Indica) ratios depending on strain.

THC concentration has increased overtime

mechanism of action, endocannabinoid system of cannabis

·       Cannabinoid receptors (CB1 in CNS, CB2 in immune and peripheral tissues) are G-protein-coupled receptors.

·       THC is a partial agonist at CB1 and CB2, increasing dopamine in the short term but reducing it with chronic use.

·       CBD is a partial antagonist at CB1 and a 5-HT1A agonist at high doses, countering THC’s psychotic potential.

·       Endogenous cannabinoids such as anandamide (AEA) and 2-AG act retrogradely on presynaptic neurons, regulating neurotransmitter release and homeostasis.

pharmokinetics of cannabis

·       Absorption: Smoking delivers 5–60% of THC; onset within minutes. Oral ingestion has delayed onset but prolonged duration of action due to first-pass metabolism.

·       Distribution: THC rapidly enters fat tissue; 25–30% retained for a week, creating reverse tolerance.

·       Metabolism: Main active metabolite is 11-hydroxy-THC; inactive metabolite THC-COOH used in urine tests.

·       Elimination half-life varies; chronic users may test positive for 7–21 days.

acute and chronic effects 

·       Acute physiological effects include bloodshot eyes, increased heart rate, and appetite stimulation.

·       Psychoactive effects: euphoria, relaxation, altered time perception, and anxiety relief. Impaired coordination, reaction time, and divided attention affect driving and work performance.

·       Chronic heavy use may reduce hippocampal CB1 density and impair learning, motivation, and executive function. Cognitive effects can persist, especially with early onset use.

therapeutic applications of cannabis

·       Dronabinol (Marinol) and Sativex: appetite stimulation in wasting disorders, nausea reduction in chemotherapy, and reduced spasticity in multiple sclerosis.

·       Experimental findings show neuroprotection and reduced inflammation but inconclusive results for Alzheimer’s, glaucoma, and anxiety disorders.

psychiatric and behavioral effects

·       THC can exacerbate psychosis and schizophrenia in vulnerable individuals.

·       Early and heavy use increases psychosis risk, possibly via dopaminergic dysregulation and high THC/low CBD strains.

·       Associations exist between chronic cannabis use and depression, anxiety, and bipolar relapse.

tolerance, withdrawal, dependence 

·       Tolerance results from CB1 receptor downregulation and desensitization.

·       Withdrawal symptoms include irritability, anxiety, insomnia, reduced appetite, and depressed mood, typically lasting 2–10 days.

opiods

·       Opioids are a class of drugs that bind to opioid receptors to produce analgesia, euphoria, and sedation.

·       They include

o   natural opiates (morphine, codeine)

o   semi-synthetic derivatives (heroin, oxycodone)

o   synthetic analogs (fentanyl, methadone).

·       Medical use centers on pain management, cough suppression, and diarrhea control.

·       High addiction potential and respiratory depression pose major health risks.

endogenous opioid system and receptors

Opioid receptors are G-protein-coupled receptors located throughout the brain and spinal cord. Major receptor subtypes include:
- Mu (μ): analgesia, euphoria, respiratory depression, dependence.
- Delta (δ): analgesia, mood regulation.
- Kappa (κ): dysphoria, hallucinations, spinal analgesia.
Endogenous ligands include endorphins, enkephalins, and dynorphins. These modulate pain perception, stress, and reward pathways. Activation inhibits adenylyl cyclase and decreases calcium influx, reducing neurotransmitter release.

opioid pharmokinetics 

·       Absorption: Rapid after oral, intravenous, or intranasal administration.

·       Distribution: Lipid solubility determines CNS penetration

o   heroin and fentanyl cross the blood-brain barrier quickly.

·       Metabolism occurs mainly in the liver (CYP2D6, CYP3A4). Morphine is converted to morphine-6-glucuronide (active), while codeine is metabolized to morphine.

·       Excretion occurs through urine, with half-lives ranging from 2 to 24 hours depending on the compound.

opioid mechanism of action and pharmocodynamics

Opioids bind to presynaptic and postsynaptic receptors in pain pathways (periaqueductal gray, thalamus, spinal cord). They hyperpolarize neurons by increasing potassium efflux and decreasing calcium influx, inhibiting neurotransmitter release. Rewarding effects result from inhibition of GABAergic neurons in the ventral tegmental area (VTA), which disinhibits dopamine release in the nucleus accumbens. This underlies both analgesic and reinforcing properties.

opioid therapeutic uses

Opioids are used for acute and chronic pain, cough suppression (codeine, dextromethorphan), diarrhea, and anesthesia (fentanyl).

opioid tolerance/dependence/withdrawal 

·       Tolerance develops to euphoria and analgesia but less to respiratory depression. Mechanisms involve receptor desensitization and cAMP upregulation.

·       Dependence results from neuroadaptive changes in locus coeruleus neurons.

·       Withdrawal symptoms—pain, irritability, diarrhea, yawning, and insomnia—emerge within 6–12 hours for short-acting opioids. Though rarely life-threatening, withdrawal causes significant distress and drives relapse.

adverse effects and overdose of opioids

·       Major risks include respiratory depression, miosis (excessive constriction of pupil of the eye), constipation, and sedation.

·       Overdose leads to hypoxia, coma, and death.

·       Tolerance to respiratory suppression develops slower than to analgesic effects, increasing overdose risk.

·       Combining opioids with CNS depressants (alcohol, benzodiazepines) enhances danger.

·       Naloxone (Narcan) reverses overdose by competitively blocking mu receptors.

illicit opiods and synthetic variants

Heroin: Semi-synthetic diacetylmorphine; crosses BBB rapidly, converted to morphine; high abuse liability.
**Fentanyl:** Potent synthetic agonist (50–100× morphine potency); main contributor to overdose deaths due to contamination.

treatment of opiod use disorder OUD

- Methadone: Full mu agonist; prevents withdrawal, reduces craving.
- Buprenorphine: Partial agonist with ceiling effect; safer and widely prescribed.
- Naltrexone: Long-acting antagonist; blocks euphoric effects but requires detoxification first.
- Naloxone: Short-acting antagonist used for acute overdose reversal.
Psychosocial support, CBT, and contingency management