Lecture Notes on Amphetamines, Cocaine, and Opiates

Professor Nick, Lecture 1 Notes (11/18/25)

  • Amphetamine:

    • Parent compound of a family of synthetic psychostimulants.

    • Has two pharmaceutical forms:

    • Benzedrine

    • Dexedrine

    • Structurally related to dopamine (DA).

    • Commonly used in street drug culture; aids individuals with ADHD.

  • Natural Compounds Related to Amphetamine:

    • Ephedrine:

    • Derived from the herb Ephedra vulgaris.

    • Used as medicine in China for over 5000 years.

    • Reduces appetite and induces a feeling of heightened energy.

    • Marketed in weight loss supplements; banned by FDA in 2004 due to safety concerns.

    • Cathinone:

    • Found in khat, a shrub native to East Africa and the Arabian Peninsula.

  • Amphetamine Pharmacokinetics:

    • Administered orally, intravenously (IV), or subcutaneously (SC).

    • Slow gastrointestinal absorption; effects may take up to 30 minutes post a typical dose of 5-15 mg.

    • Methamphetamine:

    • More potent than amphetamine; available forms include oral, snorted, IV, or smoked.

    • Smoking typically involves a glass pipe or heating on aluminum foil.

    • Crystalline methamphetamine (methamphetamine hydrochloride) is particularly suitable for smoking.

    • Inexpensive to produce, with a high potential for addiction.

    • Chronic use or high doses may result in psychotic reactions or brain damage.

    • Mechanism: Excess dopamine leads to psychosis; push dopamine back into the presynaptic terminal.

    • Amphetamines influence the membrane transporter, reversing transporter flow.

    • Autonomic Compensation:

      • Reflex adaptation of the body to environmental cues, specifically parasympathetic responses.

  • Dopamine Effects:

    • Amphetamines primarily spill dopamine (the main effect).

    • Act as reuptake blockers as a secondary action.

    • Dopamine released in the nucleus accumbens, which plays a crucial role in addiction.

    • Limbic system: Associated with emotion and reward.

    • Basal ganglia: Controls smooth movement and motor control.

    • High dopamine = increased movement; low dopamine = rigidity.

    • Post-amphetamine injection leads to significant overflow and spikes in dopamine levels.

    • Amphetamines are utilized in treating ADHD; methylphenidate is another commonly used stimulant.

    • Some paradoxical effects: Psychostimulants may help ADHD individuals but seem counterintuitive compared to effects on the general population.

    • Dense presence of dopamine transporters in the basal ganglia indicates the drug's binding efficacy.

  • Neuroscientific Factors:

    • Important nuclei involved: substantia nigra.

    • Cessation of meth use allows recovery of presynaptic terminals; however, permanent damage can lead to conditions like Parkinson's disease.

    • Genetic predisposition may influence susceptibility to Parkinson’s disease.

  • MDMA:

    • Initially used by psychotherapists to enhance patient openness (circa 1970).

    • Differs from amphetamines by primarily enhancing serotonin (5-HT) rather than dopamine and norepinephrine (NE).

    • MDMA can stimulate some dopamine release but is less potent compared to serotonin.

    • Toxicity is associated with damage to serotonergic pathways in the brain.

Professor Nick, Lecture 2 Notes (11/20/25)

  • Cocaine:

    • An alkaloid derived from the leaves of the shrub Erythroxylon coca, primarily found in South America, especially in the northern and central Andes.

    • Historical usage: Inhabitants have been consuming coca leaves for over 5000 years by chewing them, often with alkaline substances (lime or ash) to enhance absorption.

    • Coca chewing persists among Bolivian miners for stamina during work hours.

  • Cocaine Composition and Extraction:

    • Coca leaves contain approximately 0.6 - 1.8% cocaine.

    • Initial extraction creates a coca paste with about 80% cocaine.

    • Cocaine can be converted to hydrochloride salt for various methods of intake:

    • Taken orally, intranasally, or via IV injection.

    • When heated with baking soda, it hardens into forms known as “crack” or “rock” cocaine, which is lipophilic and penetrates the blood-brain barrier rapidly when smoked.

    • Following administration, cocaine is swiftly metabolized and eliminated; half-life ranges from 0.5 - 1.5 hours, with effects lasting around 30 minutes for IV or smoked doses.

    • Breakdown products persist in the body longer than cocaine itself.

  • Mechanism of Action and Effects:

    • Cocaine's reinforcing, stimulating, and addictive properties stem from its impact on dopamine levels.

    • At high doses, cocaine inhibits voltage-gated sodium channels in axons, acting as a local anesthetic when applied topically.

    • Classified as a sympathomimetic drug:

    • Increases heart rate, causes vasoconstriction, hypertension, and hyperthermia.

    • While low doses may be manageable, high doses can lead to severe consequences including heart failure, stroke, or intracranial hemorrhage.

Professor Nick, Lecture 3 Notes (11/25/25)

  • Cocaine Abuse:

    • Approximately 10-15% of intranasal cocaine users may develop addiction.

    • Users may engage in binge patterns lasting up to 3 days with consumption of up to 150g of cocaine.

    • Chronic use results in tolerance and sensitization.

  • Schizophrenia:

    • Positive Symptoms:

    • Includes thought disorders, hallucinations, delusions of persecution, grandeur, and control.

    • Negative Symptoms:

    • Characterized by flattened emotional responses, lack of initiative and persistence.

    • Physical indicators: Enlarged ventricles may signify tissue loss in the brain—acute symptoms indicate greater brain damage.

  • Historical Treatments:

    • Prior to the mid-1950s, effective treatments for schizophrenia were scarce.

    • Insulin shock therapy was one approach.

    • Significant progress arrived with the discovery of chlorpromazine in 1950, initially utilized as an antihistamine.

    • Chlorpromazine was demonstrated to reduce hallucinations and delusions while increasing activity in previously catatonic patients.

    • Dopamine Receptor Blockers:

    • Chlorpromazine and haloperidol function by blocking postsynaptic dopamine receptors.

    • Excess dopamine is linked with psychosis and increased movements.

    • Over time, antagonists can lead to an upregulation of postsynaptic receptors, exacerbating psychotic symptoms once the medication wears off, resulting in dyskinesia.

    • The dynamics of two dopamine systems underscore the significance of D2 antagonist properties, which do not activate addiction pathways because they block the dopamine signal.

Professor Nick, Lecture 4 Notes (12/2/25)

  • Dopamine Pathways and Movement:

    • Key pathways include the substantia nigra to the basal ganglia; loss of dopamine here leads to increased rigidity.

  • Depression Diagnosis:

    • DSM criteria involve:

    1. Depressed mood

    2. Anhedonia (loss of pleasure)

    3. Reduced energy

    • Severe depression can exhibit psychotic symptoms like hallucinations and delusions.

    • High prevalence observed, with studies indicating that around 75% of women report depressive symptoms (higher frequency than men).

  • Comorbidity with Alcohol:

    • Mixing alcohol with depression is deemed dangerous; it can exacerbate symptoms.

  • Bipolar Disorder:

    • Prescription rates for antipsychotics are rising.

    • Bipolar I disorder occurs more frequently in males than females.

  • Dopamine and Behavioral Activation:

    • Consuming dopamine-stimulating media (e.g., social media) may drive dopamine circuits.

    • Increasing serotonin levels can contribute to elevated feelings of joy.

  • Neurotransmitter Interaction in Depression:

    • Involve several key neurotransmitters such as DA, NE, and 5-HT (serotonin), all penetrating the frontal cortex and anterior cingulate cortex, which act as a comprehensive emotional map.

    • Substance P: Related to pain responses, SSRIs can help mitigate perseveration symptoms.

    • Psychotherapy: The application of the Mirror Neuron Hypothesis validates therapeutic empathy.

    • The amygdala plays a critical role in threat perception and emotional responses.

  • Early Antidepressant History:

    • MAOIs (Monoamine Oxidase Inhibitors) emerged as the first antidepressants; they increase neurotransmitter levels post-release and were serendipitously developed for tuberculosis treatment.

Professor Nick, Lecture 5 Notes (12/4/25)

  • Opiates:

    • Considered the most effective painkillers available; they alleviate pain, induce relaxation, and foster sleep without inducing unconsciousness—except at high doses (risk of coma and death).

    • Opium is obtained from the opium poppy, California being a notable region for cultivation.

    • Notable side effect: Severe constipation.

  • Active Ingredients:

    • The primary compound in opium is morphine, alongside others like codeine and thebaine.

    • Heroin: A semi-synthetic opioid that converts to morphine upon reaching the brain.

  • Opioid Mechanisms:

    • Opioid receptors are G-protein coupled and function by:

    • Opening K+ channels and closing Ca++ channels, modulating vesicle release by inhibiting GABA neurons in the VTA (ventral tegmental area) and promoting dopamine (DA) release.

    • Key opioid receptor subtypes include:

    • Mu, Delta, Kappa: Each exhibiting different distributions and effects throughout the brain and spinal cord.

  • Tolerance and Dependence:

    • Long-term opiate use leads to tolerance, indicated by downregulation of dopamine receptors and upregulation of GABA receptors.

  • Endorphins and Exercise:

    • Exercise promotes the release of endogenous opiates, often described as a “runners’ high”.

    • Victims of overdose often die due to respiratory depression (insufficient oxygen intake).

  • Methadone:

    • High affinity for opioid receptors; however, low impact on dose-response effects, making it a useful maintenance therapy for opioid dependence.

  • Marijuana:

    • Contains over 60 distinct compounds collectively termed cannabinoids.

    • Enhanced tetrahydrocannabinol (THC) levels are linked with increased psychoactive effects.

    • Cannabis can be ingested in various forms; notable is THC's prolonged half-life when stored in fat tissues despite rapid plasma level decline.

    • Mechanism: Cannabinoids activate CB1 receptors, inhibiting a spectrum of neurotransmitter releases, including glutamate and GABA.

    • Anandamide: A key endogenous cannabinoid worth remembering.

    • Users of marijuana exhibit tolerance and withdrawal symptoms.

    • A strong correlation exists between marijuana use and the development of schizophrenia.

  • Hallucinogens:

    • Certain hallucinogenic plants can be consumed raw or prepared.

    • LSD: Synthesized from ergot fungus on grains.

    • Hallucinogens typically do not induce addiction or withdrawal signs.

    • Ketamine: A white powder associated with bodily sensation hallucinations, functioning as a non-competitive antagonist that blocks excitatory circuits in the brain.

    • Used surgically to induce anesthesia but with potential for hallucinations to occur post-administratively.