Stimulants: Cocaine, Methamphetamine & Prescription Drugs

By the end of this module, you will be able to:

• Explain the dopaminergic mechanisms of stimulant drugs
• Differentiate between cocaine and methamphetamine effects
• Recognize the binge/crash cycle characteristic of stimulant use
• Identify cardiovascular and psychiatric complications
• Discuss the ethics and risks of prescription stimulant use

Mechanism of Action

All stimulants increase catecholamine activity (dopamine, norepinephrine) in the brain:

| Drug | Primary Mechanism | Duration | |------|-------------------|----------| | Cocaine | Blocks DAT, NET, SERT (reuptake inhibition) | 15-30 min (smoked/IV) | | Methamphetamine | Blocks reuptake + reverses transporters | 8-12 hours | | Amphetamine | Blocks reuptake + releases stored catecholamines | 4-6 hours | | MDMA | Primarily serotonin release + some dopamine | 3-6 hours |

Cocaine vs. Methamphetamine

| Feature | Cocaine | Methamphetamine | |---------|---------|-----------------| | Source | Coca plant (natural) | Synthetic | | Mechanism | Reuptake blockade only | Reuptake block + transporter reversal | | Duration | Short (15-30 min smoked) | Long (8-12 hours) | | Metabolism | Rapid hepatic | Slow, partially excreted unchanged | | Neurotoxicity | Lower | Higher (damages dopamine neurons) | | Half-life | ~1 hour | ~12 hours |

Key Difference: Methamphetamine not only blocks dopamine reuptake but also reverses the transporter, actively pumping dopamine out of neurons. This creates a much larger and longer-lasting dopamine flood.

Pattern of Use

Stimulant users often engage in "binge" patterns:

Binge Phase (hours to days):

• Repeated dosing to maintain high
• Decreased need for sleep/food
• Escalating doses as acute tolerance develops
• Hyperactivity, euphoria, grandiosity
• May continue until drug supply exhausted or physical collapse

Crash Phase (1-3 days):

• Profound exhaustion, hypersomnia
• Increased appetite
• Depression, anhedonia
• Irritability
• Strong craving

Withdrawal Phase (1-2 weeks):

• Dysphoria, anhedonia
• Fatigue
• Psychomotor retardation
• Vivid, unpleasant dreams
• Craving (may persist months)

Why This Pattern?

• Rapid tolerance develops within a single session
• Short duration (cocaine) drives frequent redosing
• Dopamine depletion causes crash
• No acute physical danger from withdrawal (unlike alcohol/opioids)
• But psychological distress drives continued use

Routes of Administration

| Route | Onset | Duration | Form | |-------|-------|----------|------| | Intranasal | 3-5 min | 15-30 min | Powder (hydrochloride) | | Smoked | 8-10 sec | 5-10 min | Crack (freebase) | | Intravenous | 10-15 sec | 15-20 min | Dissolved powder | | Oral | 10-30 min | 45-90 min | Chewed coca leaves |

Clinical Note: Faster onset = more addictive. Crack cocaine's rapid onset makes it highly reinforcing.

Acute Effects

Desired:

• Euphoria, confidence
• Increased energy, alertness
• Decreased appetite
• Enhanced sexual arousal (initially)

Adverse:

• Tachycardia, hypertension
• Hyperthermia
• Anxiety, paranoia
• Chest pain
• Seizures (high doses)

Medical Complications

Cardiovascular (leading cause of cocaine-related death):

• Myocardial infarction (even in young, healthy users)
• Arrhythmias
• Aortic dissection
• Stroke
• Sudden cardiac death

Neurological:

• Seizures
• Hemorrhagic stroke
• Movement disorders (chronic use)

Nasal (intranasal users):

• Septal perforation
• Chronic rhinitis
• Loss of smell

Psychiatric:

• Cocaine-induced psychosis (paranoia, hallucinations)
• Panic attacks
• Depression (crash/withdrawal)

Cocaethylene

When cocaine and alcohol are used together:

• Liver produces cocaethylene
• Longer-acting than cocaine
• More cardiotoxic than either drug alone
• Increases risk of sudden death
• Common combination—must screen for both

The Meth Epidemic

Methamphetamine has become a major public health crisis:

• Inexpensive to produce (precursor chemicals)
• Long duration of action (cost-effective high)
• Highly neurotoxic
• Associated with severe dental disease ("meth mouth")
• Strong association with psychosis

Acute Effects

Desired:

• Intense euphoria ("rush")
• Extreme energy, decreased need for sleep
• Increased libido
• Weight loss
• Heightened focus (initially)

Adverse:

• Severe tachycardia, hypertension
• Hyperthermia
• Bruxism (teeth grinding)
• Repetitive behaviors ("tweaking")
• Paranoia, aggression

Neurotoxicity

Methamphetamine causes direct damage to dopamine neurons:

• Oxidative stress from excess dopamine
• Mitochondrial damage
• Neuroinflammation
• Reduced dopamine transporter density
• May contribute to Parkinson's-like symptoms

Recovery: Some neurological recovery occurs with sustained abstinence (months to years), but deficits may persist.

"Meth Mouth"

Severe dental decay characteristic of chronic meth use:

Causes:

• Xerostomia (dry mouth) from sympathetic activation
• Bruxism (grinding)
• Poor oral hygiene during binges
• High sugar consumption (cravings)
• Acidic nature of drug

Presentation:

• Extensive caries
• Tooth fractures
• Gum disease
• Tooth loss

Methamphetamine-Associated Psychosis

Prevalence: Up to 40% of chronic users experience psychotic symptoms

Features:

• Paranoid delusions
• Auditory/visual hallucinations
• Delusions of parasitosis ("meth mites"—feeling bugs under skin)
• May persist weeks after cessation

Risk Factors:

• Higher doses
• Longer duration of use
• Sleep deprivation
• Pre-existing mental illness
• Family history of psychosis

Medications

| Drug | Brand Names | Indication | |------|-------------|------------| | Amphetamine/Dextroamphetamine | Adderall | ADHD, Narcolepsy | | Methylphenidate | Ritalin, Concerta | ADHD | | Lisdexamfetamine | Vyvanse | ADHD, Binge Eating |

The "Study Drug" Phenomenon

Non-medical use of prescription stimulants is common among students:

Motivations:

• Academic performance enhancement
• Weight loss
• Staying awake
• Recreational high

Prevalence:

• 5-35% of college students report non-medical use
• Often obtained from peers with prescriptions
• Perceived as "safe" because prescribed

Risks of Non-Medical Use

Physical:

• Cardiovascular events
• Seizures
• Hyperthermia

Psychiatric:

• Anxiety, panic
• Psychosis (high doses)
• Depression (crash)

Addiction:

• Tolerance develops
• Escalating doses
• Diversion to intranasal/IV use
• Transition to illicit stimulants

Ethical Considerations

Diagnostic Accuracy:

• Are ADHD diagnoses always appropriate?
• Pressure from patients/parents for prescriptions?
• Inadequate assessment?

Cognitive Enhancement:

• Is it "cheating" for non-ADHD students?
• Fairness concerns
• Pressure to use for competitive advantage

Prescriber Responsibility:

• Monitoring for diversion
• Prescription drug monitoring programs
• Balancing access for those who need it

Challenges

Unlike opioids, no FDA-approved medications for stimulant use disorder:

• No agonist therapy (like methadone for opioids)
• No antagonist (like naltrexone)
• Behavioral treatments are primary approach

Evidence-Based Approaches

Contingency Management (CM):

• Rewards (vouchers, prizes) for negative drug tests
• Most effective behavioral treatment for stimulants
• Strong evidence base
• Challenges: Cost, implementation

Cognitive Behavioral Therapy (CBT):

• Identify triggers and high-risk situations
• Develop coping strategies
• Address maladaptive thoughts
• Relapse prevention planning

Community Reinforcement Approach (CRA):

• Restructure environment to support recovery
• Vocational, social, recreational activities
• Family involvement

Matrix Model:

• Intensive outpatient program
• Combines CBT, family therapy, 12-step, drug testing
• Developed specifically for stimulant users

Emerging Pharmacological Approaches

Under Investigation:

• Mirtazapine (for meth)
• Bupropion + naltrexone combination
• Topiramate
• N-acetylcysteine (NAC)
• Psychostimulant agonist therapy (controversial)

• Stimulants increase catecholamine activity through reuptake blockade and/or release
• Methamphetamine is more neurotoxic and longer-acting than cocaine
• The binge/crash cycle is characteristic of stimulant use patterns
• Cardiovascular complications are the leading cause of stimulant-related death
• Cocaethylene forms when cocaine and alcohol are combined, increasing toxicity
• No FDA-approved medications exist for stimulant use disorder
• Contingency management has the strongest evidence for behavioral treatment
• Prescription stimulant misuse is common and raises ethical concerns

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