Comprehensive Study Notes on Stimulants, Coca Leaf, Cocaine, Amphetamines, and ADHD Treatments

Stimulants

The Coca Leaf

Description

  • The coca leaf, scientifically known as Erythroxylum coca, is a multi-purpose drug.

Brief History of the Coca Leaf

Geographic Distribution

  • Found in the Andean regions of Bolivia, Ecuador, northern Argentina, and Peru.

Historical Context

  • The Spanish supported the coca leaf unlike hallucinogens, primarily using it as a payment method for labor and taxes.

  • However, within their own culture, the Spanish did not support coca usage.

Introduction to Europe

  • In the 1800s, the coca leaf was largely unknown in Europe.

  • Naturalists in Peru had mixed opinions about it.

  • By the 1850s, European chemists isolated cocaine, the active agent in coca leaves.

Cocaine vs. Coca Leaves

  • Cocaine is a more potent form of the coca leaf. Its absorption and distribution in the body occur much faster than that of coca leaves.

  • Routes of administration affect intensity: injections lead to faster and more intense experiences.

Early Use of Cocaine

19th-Century Usage in Europe

  • In 1884, Sigmund Freud acquired a sample of cocaine and referred to it as a "miracle drug".

  • Freud published Uber Coca, discussing its potential applications for conditions like depression, indigestion, asthma, and syphilis.

Public Reception and Medical Concerns

  • Cocaine was readily available everywhere, marketed for its tonic and nerve-stimulant properties.

  • By the end of the 19th century, medical concerns regarding cocaine began to surface, particularly focusing on issues of dependency and violent crimes.

  • This led to the passing of the Harrison Narcotics Act in 1914, which aimed to regulate cocaine and opiate narcotics.

The Amphetamines

Background

  • Following the Harrison Narcotics Act, the use of cocaine declined, paving the way for amphetamines.

  • Amphetamines were first synthesized in the late 19th century, with their medical applications beginning in the 1920s for treating colds, sinus issues, obesity, and ADHD.

Abuse and Risks

  • The 1960s saw a rise in methamphetamine use, often surpassing heroin.

  • Methamphetamine abuse led to severe health consequences, including insomnia, decreased appetite, and stimulant psychosis characterized by symptoms like formication and paranoid delusions.

Cocaine Epidemic II

Resurgence in the 1970s

  • Cocaine reemerged as a popular stimulant in the 1970s, initially becoming scarce.

  • It was often referred to as the "champagne" of stimulants during its resurgence.

Factors for Recovery

  • The decline in price and the increased availability of higher doses and forms like 'crack' cocaine contributed significantly to this resurgence.

  • Crack cocaine became especially popular after its introduction in 1986.

Methods of Use

  • Street cocaine, when prepared with hydrochloric acid, can be injected or snorted.

  • Intranasal use provides intense effects, though absorption is slower compared to injecting.

  • The method of cannabis freebasing (smoking cocaine) led to rapid absorption and intense highs, leading users to prefer it over injecting.

Complications with Use

  • Crack cocaine users experienced heightened cravings within 10 to 20 minutes post-consumption, leading to cycles of repeated use.

  • Media attention for crack cocaine rose sharply in 1985 and 1986 as public health concerns escalated.

Development of Crack Cocaine Use and Problems

Rising Health Concerns

  • By the late 1980s, cocaine-related emergency room visits increased dramatically from virtually none in the early 1970s to over 80,000 by 1990.

  • The problem was compounded by multi-drug use patterns within the population.

Cocaine Drug Wars

U.S. and Colombian Government Response

  • In the 1980s, the U.S. formed partnerships with Colombian authorities to combat drug trafficking, particularly against large cartels.

  • Prominent cartels included the Medellin and Cali cartels, both notorious for violence and murder rates associated with their operations.

Cartel Decline

  • Following the death of prominent cartel leader Pablo Escobar in 1993, the Medellin cartel declined.

  • In 1999, overall arrests succeeded in crippling the Cali cartel's leadership.

  • A slight decline in overall cocaine production occurred, alongside governmental support in Andean countries for regulated coca farming.

Legislation Against Crack Cocaine

Anti-Drug Abuse Acts

  • The Anti-Drug Abuse Act of 1986 established minimum sentences for cocaine offenses, including a 5-year minimum for possessing over 500 grams of powder cocaine versus just 5 grams of crack cocaine.

  • These laws disproportionately impacted African American communities, affecting 80% of crack offenders.

Fair Sentencing Act of 2010

  • The Fair Sentencing Act aimed to address sentencing disparities between powder and crack cocaine offenses.

The Return of Meth

Resurgence and Regulation

  • Methamphetamine, known as “Ice” and “Crank,” saw a resurgence in the late 1980s and early 2000s in various regions of the U.S.

  • The drug control measures like the Comprehensive Methamphetamine Control Act of 1996 increased punishments for manufacturing meth.

  • The Combat Methamphetamine Epidemic Act of 2006 regulated substances like pseudoephedrine to combat meth manufacture.

Public Health Concerns

  • The public health risks associated with meth included toxic waste, explosions, and pollution from “kitchen labs,” emphasizing the dangers of its production.

Bath Salts: A New Wave of Synthetic Stimulants

Introduction

  • Synthetic stimulants known as “bath salts”, including mephedrone, methylone, and methylenedioxypyrovalerone, emerged in the 2000s.

  • These are synthetic analogs of cathinone, often marketed misleadingly as “plant food”.

Effects and Emergency Responses

  • High doses lead to severe psychotic effects and a significant increase in emergency calls related to these substances.

  • Emergency room visit statistics for bath salts surged from none in 2009 to over 6,000 by 2011.

Notable Incidents

  • The notorious case of Rudy Eugene, who was linked to a cannibalism incident under the influence of bath salts, prompted further investigation and regulation of these substances by the DEA as Schedule I drugs in 2011.

Pharmacokinetics of Stimulants

How Stimulants Work

  • The onset of stimulant effects varies by administration route:

    • Intravenous: approximately 30 seconds

    • Oral and intranasal: 10-15 minutes

  • Cocaine and amphetamines have different durations of action:

    • Cocaine: 20-80 minutes

    • Amphetamines: 4-12 hours

    • Synthetic cathinones: 3-4 hours

  • Metabolites can be detected in urine for 48 to 72 hours after consumption.

Mechanism of Stimulant Action

Neurological Impact

  • Stimulants primarily work by affecting monoamine neurotransmitters, primarily blocking their reuptake.

  • Amphetamines and methylphenidate specifically increase dopamine and norepinephrine levels in the brain, enhancing neurotransmission.

  • Some synthetic cathinones may increase the release of monoamines, while others block reuptake, reflecting a diverse pharmacological profile.

Self-Administration Studies

  • Evidence from animal studies indicates a propensity for self-administration of stimulants, with animals frequently choosing cocaine over other rewards, showcasing its addictive potential.

Dopamine Pathways

  • The mesolimbic pathway, involving dopamine neurons, plays a crucial role in pleasure and reward systems. Depletion of dopamine from chronic stimulant use can lead to diminished capacity to experience pleasure, often described as “cocaine blues.”

Acute Effects at Low and Moderate Doses

Physiological Effects

  • Stimulants produce sympathomimetic effects:

    • Increased heart rate and blood pressure

    • Changes in blood flow – reduced to internal organs but increased to large muscle groups and the brain

  • The anorectic effect associated with stimulants like amphetamines led to their use as diet pills, but this practice is no longer acceptable long-term for weight management.

Behavioral Effects

  • Users generally experience elevated mood, enhanced alertness, and increased physical endurance.

  • Stimulants have been marketed as ‘study drugs’, though their effectiveness varies and may impair complex task learning.

Acute Effects at High Doses

Psychotic Risks

  • High doses can lead to psychotic states, often manifesting as paranoid delusions and compulsive stereotyped behaviors.

  • Symptoms may include rocking behaviors, hair pulling, hallucinations, and formication sensations.

Overdose Statistics and Risks

  • Cocaine overdoses can occur at doses as low as 15-20 milligrams.

  • While overdose cases are rare, complications can lead to convulsions, respiratory collapse, and other life-threatening scenarios.

  • Many stimulant users engage in multi-drug use, compounding risks.

Effects of Chronic Use

Tolerance

  • Tolerance can develop acutely, necessitating higher doses over time to achieve previous effects, particularly for subjective sensations of euphoria.

Dependence and Withdrawal

  • Drug dependency manifests through withdrawal symptoms such as depression, sleep disturbances, and cravings. A phenomenon termed 'crash', characterized by intense cravings lasting several days, may occur following stimulant cessation.

  • Chronic use can lead to prolonged cravings, with symptoms of anhedonia persisting for months or years.

Stimulant Drugs and ADHD

ADHD Overview

  • Attention Deficit/Hyperactivity Disorder (ADHD) presents with challenges in attention, task accomplishment, and behavioral regulation.

  • Not all individuals show hyperactivity; inattentiveness may be the primary concern.

DSM Classification

  • The categorization of ADHD has evolved through various editions of the DSM:

    • DSM-III (1980): ADD with/without hyperactivity.

    • DSM-IV (1994): Attention Deficit/Hyperactivity Disorder.

    • DSM-V (2013): Acknowledges different presentations of ADHD and the need for traits to be present in both children and adults.

Stimulant Treatment Timeline

  • Pioneering research began with Charles Bradley in 1937, showing amphetamines elicited the opposite effect in hyperactively diagnosed children.

  • Common medications like methylphenidate (Ritalin, Concerta) and amphetamines (Adderall, Vyvanse) have seen a massive increase in prescriptions since the 1990s, rising by 500%.

Controversies Surrounding ADHD Treatment

  • Some individuals argue ADHD is not a medical disorder, instead attributing behaviors to environmental factors.

  • Others argue it is a legitimate disorder defined by failures in mechanisms of self-regulation that hinder daily functioning.

Outcomes and Concerns

  • While stimulant drugs improve educational performance outcomes according to parental and teacher assessments, the long-term effects, including potential for substance use disorder in adults, remain ambiguous.

  • Recent data suggests a significant rise in ADHD diagnoses, alongside rising concerns about misuse of stimulant medications among students.

Statistical Increase

  • ADHD diagnoses increased substantially from 1994 to 2009, raising concerns about the potential for diversion and non-medical use of stimulant medications among the youth,

  • Studies indicate a notable rate of misuse, ranging from 5% to 35% among students regarding common ADHD medications like Ritalin.