7. cocaine & stimuulants Psychomotor

Psychology 335 - Psychomotor Stimulants

Sources

• Naturally Occurring Psychomotor Stimulants:
    - Ephedrine (from Ephedra, Mah Huang)
    - Cathinone (from khat)
    - Methcathinone (known as cat)
    - Cocaine (from Erythroxylum coca)

• Synthetics:
    - Amphetamines:
      - Dextroamphetamine (D)
      - Levoamphetamine (L)
      - Mixed (DL, such as Adderall or Benzedrine)
    - Methamphetamine: (known as crystal, ice, crystal meth)
    - Methylphenidate: (known as Ritalin)

History

• Cocaine:
    - Pre-Columbian use:
      - Used since 2500 B.C.
      - Included in ancient creation myths.
      - Considered sacred to Inca civilization.
    - Isolation and Popularization:
      - Isolated by Albert Neiman in 1860.
      - Usage increased in the late 1800s including works by Freud and Sherlock Holmes.
      - Served as the first local anesthetic and added to various beverages (e.g., initial formulations of Coca-Cola).
    - Legislation:
      - The Harrison Narcotic Act of 1914 regulated cocaine use.

• Amphetamines:
    - Ephedrine use:
      - Utilized in China for 5,000 years.
      - Similarity to Epinephrine motivated its use, particularly for asthma treatment.
    - Synthesis:
      - Amphetamine synthesized in 1887; sanctioned use began in 1927.
      - Gained acceptance by the American Medical Association in 1937 for various medical uses including antidepressant effects.
    - Methylphenidate Development:
      - Developed as a competitor to amphetamines (e.g., Concerta and Ritalin).
      - Currently used primarily to treat narcolepsy and hyperactivity.
      - Cathinone: mentioned as a synthetic counterpart to mephedrone (a.k.a. bath salts).

Routes of Administration and Absorption

• Amphetamines:
    - Poorly absorbed from the digestive system.
    - More potent when administered by injection or inhalation.
    - Notable for producing an initial rush followed by a consistent release.

• Cocaine:
    - Typically consumed by Chewing leaves with lime from wood ash or sea shells.
    - Can be inhaled in a salt form.
    - Smoked as freebase; crack is cocaine prepared with Sodium Bicarbonate or baking soda.

Distribution and Excretion

• Distribution Characteristics:
    - Both drugs can cross the blood-brain barrier.
    - Concentrate particularly in the spleen, kidneys, and brain.

• Excretion Dynamics:
    - Amphetamines:
      - Excreted through urine, sweat, and saliva.
      - Half-life: Approximately 16+ hours.
      - Variability of active metabolites and formulation types.
      - Short-acting formulations: 3–4 hours; extended-release: 8–12 hours.
    - Cocaine:
      - Rapidly excreted with a half-life of about 40 minutes.

Mechanism of Action

• Impact on Monoamine Synapses:
    - Both classes act primarily on vesicular monoamine transporters.
    - Amphetamines:
      - Cause leakage of neurotransmitters from vesicles into the synaptic cleft.
      - Amplify the volume of transmitter released upon action potential.
    - Cocaine:
      - Acts as a reuptake blocker.
      - Can block up to 77% of dopamine transporters and accounts for 47% of subjective effects due to dopamine in the mesolimbic pathway, particularly impacting the nucleus accumbens.
      - In the PNS, cocaine blocks ion channels in membranes, which contributes to various physiological effects.

Effects of Amphetamines

• Physiological Effects:
    - Dextroamphetamine (Adderall) and Levoamphetamine (L): increase heart rate and blood pressure, induce vasodilation, bronchodilation, and may cause side effects like headaches, dry mouth, digestive disturbances, and weight loss.
    - Methamphetamine: Shows potent effects on the CNS with less activation of the sympathetic nervous system; often associated with increased risks of abuse.

• Effects on Sleep:
    - Induce insomnia; primarily prevent sleep, leading to long-term sleep disturbances.

Behavioral and Performance Effects in Humans

• Subjective Effects:
    - Intravenous cocaine and amphetamines produce similar feelings of euphoria, well-being, and heightened energy/exhilaration.
    - Acute Tolerance: Notable for cocaine, which has a shorter action due to a 20-30 minute rush.
    - Associated with cortical activation and subsequent comedown effects.

• Stereotyped Behaviors:
    - Punding: (repetitive or compulsive behavior).
    - Amphetamine Psychosis: Manifestations may include formication, paranoid schizophrenia, and violence.

Behavioral Effects on Nonhumans

• Unconditioned Behavior:
    - In rats, low to intermediate doses increase spontaneous locomotor and exploratory activity.
    - At high doses, behaviors such as increased sniffing and automutilation may arise, coupled with decreased food and water consumption.

Tolerance and Withdrawal Dynamics

• Acute Tolerance and Withdrawal:
    - Experiences such as coke-out (acute tolerance) and non-severe withdrawal symptoms like depression and insomnia.

• Chronic Tolerance / Sensitization:
    - Repeated administration results in tolerance to heart rate and blood pressure effects, while sensitization occurs for stereotypical behaviors and psychosis.

• Withdrawal:
    - Often presents with longer-term depressive symptoms, insomnia, and potential for "guilt birds" (monoamine-related long-term depression), similar to clinical depression experiences leading to suicidal ideation.

Self-Administration of Amphetamines

• In Humans:
    - Cocaine can be administered orally, snorted, injected, and smoked as part of social drug interactions (e.g., speedball with opioids).
    - Amphetamines experience sporadic use trends leading to behaviors such as "runs" and crashes.

• In Nonhumans (monkeys):
    - Daily intake patterns with enhancements driven by experiences with stimulants, illustrating that cocaine remains the most reinforcing drug among these self-administrations.

Risks and Harmful Effects

• Direct Effects:
    - Used in the treatment of hyperactivity (e.g., methylphenidate); notable for potential reduction in growth velocity.
    - Cocaine risks include mild jaundice/liver disease, mucous membrane inflammation, and associated costs.

• Specific Risks of Chronic Use:
    - Increased likelihood of incident psychosis and mania linked to amphetamine prescriptions, especially at high doses (>30 mg dextroamphetamine equivalents).

Treatment Approaches

• Detoxification Strategies:
    - Inclusion of positive reinforcement, counseling, and contingency management.
    - Priming and sensitization noted to increase relapse risk.
    - Consideration for substitution therapies (e.g., methylphenidate), but generally unsuccessful in cocaine abusers.

Ethical Considerations About Cognitive Enhancement

• Acknowledgment of rising demand for cognitive enhancement drugs, with significant discussions around policy and responsible use on university campuses.
• Emphasis on allowing mentally competent adults to seek cognitive enhancements responsibly and the call for collaborative policies to mitigate disparities.

Caffeine and Methylxanthines

• History and Sources:
    - Coffee: Traced back to Ethiopia and disseminated to Europe (notably, Oxford Coffeehouse in 1650).
    - Tea: Originated in China around 780 A.D., spreading to Europe by the 1600s.
    - Cocoa: Cacao tree hailed from the tropical regions of Amazon rain forest (e.g., significant consumption by Cortes in 1520).

• Effects of Methylxanthines:
    - Ingestion leads to varying effects on the body, improving attention and sensory performance while also being linked to withdrawal symptoms similar to those of amphetamines.

• Withdrawal Symptoms:
    - Symptoms can manifest as headache, drowsiness, and decreased energy, typically resolved after a short period without caffeine.

• Caffeine Dependence and Self-Administration:
    - Most common among habitual coffee drinkers, resulting primarily from the avoidance of withdrawal symptoms. Most consumption overlaps with global trends, with noted higher intakes in North America.