Lessons 10+11: Drugs and the Brain

Drug

A chemical substance that, when taken into the body, alters the structure or functioning of the body in some way.

Psychoactive Drug

A drug that affects the brain and nervous system.

Ligand-Receptor Interaction

Drugs either mimic neurotransmitters (agonists) or block them (antagonists).

Agonist

A ligand that activates a receptor, mimicking neurotransmitter action.

Antagonist

A ligand that blocks neurotransmitter access to a receptor.

Bioavailability

Proportion of a drug that enters circulation and can act on targets.

Binding Affinity

Degree of chemical attraction between ligand and receptor.

Efficacy

Ability of a ligand to activate a receptor.

Subcutaneous (SC) Injection

Drug injected under the skin.

Intramuscular (IM) Injection

Drug injected into large muscles.

Intravenous (IV) Injection

Drug injected into veins; reaches brain rapidly.

Oral Administration

Easy and safe but absorption is unpredictable.

Inhalation

Absorbed through lung capillaries; rapid onset.

Mucous Membrane Absorption

Drug absorbed through nose, mouth, or rectum.

Drug Metabolism

Primarily occurs in the liver via CYP450 enzymes.

Drug Excretion

Primarily through kidneys; also sweat, feces, breath, breastmilk.

Dose‑Response Curve (DRC)

Graph showing relationship between drug dose and effect.

ED50

Dose that produces 50% of maximal effect.

TD50

Dose at which 50% of subjects show toxicity.

LD50

Dose at which 50% of subjects die.

Therapeutic Index (TI)

Ratio of LD50 to ED50; indicates drug safety margin.

High Therapeutic Index

Large separation between ED50 and LD50; safer drug.

Low Therapeutic Index

Small separation between ED50 and LD50; higher risk.

Addiction

A chronic disease involving compulsive drug seeking and use despite harm.

Substance Use Disorder (SUD)

Pattern of symptoms including cravings, tolerance, withdrawal, and continued use despite negative effects.

Tolerance

Needing more of a substance to achieve the same effect.

Withdrawal

Symptoms opposite the drug's effects when use stops.

Dependence

Body adapts to drug presence and functions normally only with it.

Relapse

Return to drug use after abstinence.

Conditioned Drug Tolerance

Environmental cues trigger compensatory responses, craving, and relapse.

Mesolimbocortical Pathway

VTA → Nucleus Accumbens; central to reward and addiction.

Dopamine in Addiction

Many drugs increase dopamine in the nucleus accumbens.

Self‑Administration Studies

Animals press a lever to receive drugs, showing motivation.

Electrical Self‑Stimulation

Rats stimulate reward pathways even at the expense of eating/drinking.

Examples of Opioids

Morphine, Fentanyl, Carfentanil, Oxycodone, Heroin.

Opioid Mechanism of Action

Bind to opioid receptors → reduce pain signals → disinhibit VTA → greater dopamine.

Opioid Acute Effects

Euphoria, relaxation, pain relief, respiratory depression, nausea.

Opioid High‑Dose Effects

Coma, death.

Opioid Withdrawal Symptoms

Muscle pain, diarrhea, vomiting, sweating, anxiety, insomnia.

Opioid Addiction Potential

High; strong reinforcement via dopamine.

Opioid Therapeutic Uses

Pain management, anesthesia, cough suppression (historically).

Narcan (Naloxone)

Opioid receptor antagonist used to reverse overdose.

Medication‑Assisted Treatment (MAT)

Methadone, buprenorphine; reduce withdrawal and cravings.

Examples of Cannabinoids

THC, Dronabinol, CBD.

Cannabinoid Mechanism of Action

Agonist at CB1/CB2 receptors; increases dopamine neuron firing.

Cannabinoid Acute Effects

Relaxation, mood changes, increased appetite, impaired judgment, motor deficits.

Cannabinoid High‑Dose Effects

Paranoia, confusion, respiratory issues, pseudo‑hallucinations.

Cannabinoid Withdrawal

Irritability, insomnia, decreased appetite, anxiety (mild).

Cannabinoid Therapeutic Uses

Epilepsy, nausea relief, chronic pain, anorexia.

Examples of Stimulants

Caffeine, Nicotine, Cocaine, Amphetamine, Methamphetamine, Adderall, Ritalin, Vyvanse.

Nicotine Mechanism

Agonist at nicotinic ACh receptors → greater dopamine release.

Cocaine Mechanism

Blocks dopamine reuptake transporters → dopamine stays in synapse longer.

Amphetamine Mechanism

Reverses dopamine transporter (DAT) → pumps dopamine into synapse.

Stimulant Acute Effects

Increased alertness, energy, elevated HR/BP, decreased appetite.

Stimulant High‑Dose Effects

Psychosis, cardiovascular strain, stroke risk, insomnia, anxiety.

Stimulant Withdrawal

Headaches, fatigue, depression, irritability, cravings.

Stimulant Addiction Potential

High; ~70% of smokers become addicted.

Stimulant Therapeutic Uses

ADHD, narcolepsy, local anesthetic (rarely cocaine).

Alcohol Mechanism of Action

GABA agonist (increases inhibition) and NMDA glutamate antagonist.

Alcohol Acute Effects

Relaxation, lowered inhibition, motor impairment.

Alcohol High‑Dose Effects

Liver disease, cardiovascular problems, brain atrophy, dependence.

Alcohol Withdrawal Phase 1

Tremors, nausea, sweating, vomiting (5-6 hrs).

Alcohol Withdrawal Phase 2

Convulsions (15-30 hrs).

Alcohol Withdrawal Phase 3

Delirium tremens (24-48 hrs).

Alcohol Therapeutic Uses

None (recreational only).

Alcohol Use Disorder Treatments

Benzodiazepines, naltrexone, acamprosate, disulfiram, CBT.

Examples of Psychedelics

LSD, Mescaline, Psilocybin, MDMA.

LSD Mechanism

Agonist at serotonin 5‑HT2A receptors → greater serotonin activity.

MDMA Mechanism

Blocks serotonin & dopamine reuptake; enters neurons and increases release.

Psychedelic Acute Effects

Visual hallucinations, altered time perception, emotional intensity, disrupted logical thought.

Psychedelic Long‑Term Effects

Bad trips, dehydration, serotonin toxicity.

Psychedelic Withdrawal

Depression, mood swings.

Psychedelic Therapeutic Research

PTSD, depression, substance‑use disorders (experimental).

Schedule I Definition

Drugs with no accepted medical use and high potential for abuse.

Schedule I Examples

Heroin, LSD, Psilocybin, Mescaline, MDMA, Cannabis (THC).

Schedule II Definition

Drugs with accepted medical use but high potential for abuse and dependence.

Schedule II Examples

Morphine, Fentanyl, Carfentanil, Oxycodone, Cocaine, Amphetamine, Methamphetamine, Dronabinol (synthetic THC).

Schedule III Definition

Drugs with moderate to low physical dependence but high psychological dependence.

Schedule III Examples

Ketamine, anabolic steroids, testosterone.

Pharmacokinetics

Study of drug absorption, distribution, metabolism, and excretion

Pharmacodynamics

The study of what the drug does to the body