6. Cocaine & Amphetamines

What are the primary forms of cocaine?

Raw leaves, coca paste, cocaine HCl (powder), cocaine free base, and crack cocaine.

What are the major behavioral properties of psychomotor stimulants?

They stimulate alertness and arousal, as well as motor activity.

What is the historical significance of coca use?

Reports of coca use date back approximately 8000 years, with the first European report in 1499.

What are the routes of administration for raw coca leaves?

Chewed with lime powder or ash to enhance absorption.

What is the cocaine concentration in coca paste?

Approximately 80% cocaine sulfate.

How is cocaine HCl administered?

It can be taken orally, intranasally, or injected IV, but cannot be smoked.

What is crack cocaine and how is it made?

Crack cocaine is a cruder preparation of free base made from cocaine HCl, using baking soda instead of solvents.

What was the impact of the Anti-Drug Abuse Act of 1986?

It imposed harsher mandatory-minimum sentences for crack cocaine users compared to powdered cocaine users.

What are the local anesthetic effects of cocaine?

Cocaine blocks monoamine transporters and can inhibit voltage-gated Na+ channels at high doses.

What is the half-life of cocaine?

0.5 to 1.5 hours.

What are the forms of amphetamines?

Naturally-occurring amphetamines, bath salts, amphetamine, methamphetamine, and amphetamine-related synthetics.

What is ephedrine and its traditional use?

Ephedrine comes from the Ephedra plant and has been used in traditional Chinese medicine for asthma and colds.

What is the significance of pseudoephedrine?

It is a major cold treatment but has restrictions due to its potential to be reduced into methamphetamine.

What is cathinone and where is it commonly used?

Cathinone is derived from the khat shrub and is commonly chewed in East Africa and Yemen.

What are bath salts in the context of amphetamines?

Synthetic variants of cathinone that are disguised as household products and placed on DEA Schedule I.

What is the historical use of amphetamines during WWII?

Amphetamines were widely used by the military during WWII and subsequent conflicts.

What are the routes of administration for methamphetamine?

Oral, snorted, injected IV, or smoked.

What are some common brand names for amphetamines?

Vyvanse®, Dexedrine®, Adderall®, Methedrine®.

What are the effects of repeated use of stimulants?

Withdrawal, tolerance, and sensitization.

What is MDMA and its related drugs?

MDMA, MDA, and MDE are forms of ecstasy and related substances.

What is the primary mechanism of cocaine's action?

It blocks monoamine transporters, particularly dopamine transporters (DAT).

What is the effect of combining cocaine with ethanol?

It produces cocaethylene, an active metabolite with a longer half-life than cocaine.

What was Sigmund Freud's initial view of cocaine?

He praised its effects, describing it as providing exhilaration and lasting euphoria without unpleasant after-effects.

What is the significance of the Fair Sentencing Act of 2010?

It reduced the sentencing disparity between crack and powdered cocaine from 100:1 to 18:1.

What are some historical uses of amphetamines in the military?

Amphetamines were used widely by the military during WWII to increase attention and reduce fatigue.

What percentage of the population were regular users of amphetamines in 1970?

Over 10% of the population were regular users, including truckers and housewives.

What are the current medical uses for amphetamines classified as DEA schedule II?

1) Narcolepsy 2) Attention deficit disorder (ADD, ADHD)

What is the half-life of amphetamines?

The half-life of amphetamines is 7-30 hours.

What are the major behavioral effects of amphetamines?

Increased wakefulness, reduced fatigue, and enhanced attention.

What are common withdrawal symptoms from chronic stimulant use?

Anxiety, drug craving, depressed mood, fatigue, increased appetite, and lack of motivation.

What are the negative effects of chronic amphetamine use?

Psychosis, anorexia, and physical damage such as 'meth mouth' and skin sores.

What is MDMA and what are its common names?

MDMA is methylenedioxymethamphetamine, also known as ecstasy, E, X, XTC, and molly.

What are the effects of MDMA at low doses?

Increased energy, sociability, empathy, and mild euphoria.

What are the major autonomic effects of MDMA?

Increased heart rate and temperature, decreased appetite, and jaw clenching.

What are the risks associated with high doses of MDMA?

Hyperthermia, dehydration, increased heart rate and blood pressure, which can lead to stroke.

What is the primary mechanism of action for cocaine and amphetamines?

They are indirect agonists of monoamine systems, blocking reuptake of monoamines.

What is the role of tyrosine in catecholamine synthesis?

Tyrosine is the precursor for catecholamines, and its conversion is the rate-limiting step in synthesis.

How are catecholamines inactivated in the brain?

Through reuptake via transporters and enzymatic degradation.

What are the two types of enzymes involved in catecholamine metabolism?

1) MAO (monoamine oxidases) 2) COMT (catechol-O-methyltransferase)

What are the effects of repeated stimulant use on tolerance?

Tolerance can develop to autonomic and anorexic effects, while sensitization can occur to rewarding and psychotomimetic effects.

What is the significance of the FDA's rejection of MDMA for PTSD therapy?

It highlights the ongoing debate and research surrounding the therapeutic potential of MDMA despite its Schedule I classification.

What is the relationship between route of administration and abuse potential of methamphetamine?

A faster route of administration increases the potential for abuse.

What are stereotypies in the context of stimulant use?

Stereotypies are persistent, repetitive behaviors with no purpose that can occur with high doses of amphetamines.

What is the difference in duration of action between cocaine and amphetamines?

Cocaine has a duration of 0.5-1.5 hours, while amphetamines last 7-30 hours.

What is the impact of amphetamines on the dopamine system?

Amphetamines lead to very high dopamine levels in the synaptic cleft, contributing to their stimulating and reinforcing properties.

What are the common forms of cocaine?

Cocaine can be found as raw leaves, coca paste, cocaine HCl (powder), and crack cocaine.

What is the significance of the term 'Faces of Meth'?

It refers to the physical damage and severe dental issues associated with chronic methamphetamine use.

What is the primary neurotransmitter affected by amphetamines?

Dopamine (DA) is the primary neurotransmitter affected, influencing mood and reward pathways.

What are the effects of chronic high-dose stimulant use?

Withdrawal symptoms are mostly psychological and can last for 3-4 weeks.

What is the common treatment for ADHD?

Most ADHD medications are stimulants, such as Adderall and Ritalin.

What is the primary function of COMT (catechol-o-methyltransferase)?

COMT is an enzyme that metabolizes catecholamines, such as dopamine and norepinephrine.

What are the primary brain metabolites of dopamine in humans and rats?

In humans, dopamine is metabolized to HVA (homovanillic acid), and in rats, it is metabolized to DOPAC.

How many dopamine receptors are there, and what are their types?

There are five dopamine receptors: D1, D2, D3, D4, and D5.

What is the role of D1-like dopamine receptors?

D1-like receptors (D1, D5) are coupled to Gs, stimulating adenylate cyclase (AC) and increasing cAMP, which enhances neuron excitability.

What is the function of D2-like dopamine receptors?

D2-like receptors (D2, D3, D4) are coupled to Gi, inhibiting adenylate cyclase (AC) and decreasing cAMP, which reduces neuron excitability.

Where are dopamine receptors primarily concentrated in primates?

Cortical dopamine receptors are concentrated in prefrontal cortex areas, affecting cognitive processes like working memory.

What are the three major dopamine pathways in the brain?

The three major pathways are the nigrostriatal pathway, mesolimbic pathway, and mesocortical pathway.

What is the nigrostriatal pathway responsible for?

The nigrostriatal pathway involves dopamine neurons in the substantia nigra targeting the dorsal striatum, playing a role in movement control.

What does the mesolimbic pathway target?

The mesolimbic pathway targets the ventral striatum (nucleus accumbens) and amygdala, influencing emotions and reward processing.

What is the role of the mesocortical pathway?

The mesocortical pathway targets the prefrontal cortex, which is involved in higher cognitive functions.

What is Parkinson's disease and its primary cause?

Parkinson's disease is caused by the progressive death of midbrain dopamine neurons, leading to motor symptoms.

What are some early symptoms of Parkinson's disease?

Early symptoms may include a tremor in one hand.

What is the treatment for Parkinson's disease?

Symptoms can be relieved by administering L-DOPA, although it may lead to drug-induced dyskinesias.

What is MPTP and its significance in Parkinson's research?

MPTP is a neurotoxin that, when ingested, can induce Parkinson's symptoms and is used in research to create dopamine lesions in animal models.

What is the role of norepinephrine in the brain?

Norepinephrine is involved in arousal, cognition, and the stress response.

What are the primary adrenergic receptors and their functions?

The primary adrenergic receptors are alpha-1 (α1), alpha-2 (α2), beta-1 (β1), and beta-2 (β2), which are involved in various physiological responses.

What is the locus coeruleus and its function?

The locus coeruleus is the major source of norepinephrine in the brain, involved in arousal and attention.

What is the Dorsal Noradrenergic Bundle (DNAB)?

The DNAB originates from the locus coeruleus and provides broad innervation to the forebrain, influencing cognition and arousal.

How does norepinephrine affect memory and cognition during stress?

Increased norepinephrine levels can enhance stress effects on memory and cognition due to its actions in the amygdala, hippocampus, and cortex.

What is the Yerkes-Dodson Law?

The Yerkes-Dodson Law states that there is an optimal level of arousal for performance, with norepinephrine levels correlating with arousal levels.

What is the pharmacodynamics of cocaine?

Cocaine blocks the reuptake of dopamine, norepinephrine, and serotonin, contributing to its stimulating and addictive properties.

How do amphetamines affect dopamine release?

Amphetamines block reuptake and also cause dopamine release by entering nerve terminals and reversing the transporter function.

What is TAAR1 and its role in amphetamines?

TAAR1 (trace amine-associated receptor 1) is an intracellular GPCR that, when activated by amphetamines, leads to increased cAMP and catecholamine release.

What are catecholamines?

Catecholamines include dopamine (DA) and norepinephrine (NE).

What is the role of dopamine in drug effects?

Dopamine is critical for reinforcing and locomotor effects of drugs like cocaine and amphetamines.

How do cocaine and amphetamines affect monoamines?

Both block the reuptake of monoamines and cause dopamine release.

What is the primary mechanism by which cocaine and amphetamines are reinforcing?

DAT blockade appears to be the core mechanism for reinforcement.

What are the pharmacological effects of cocaine?

Cocaine blocks reuptake of dopamine, norepinephrine, and serotonin, and can block voltage-gated Na+ channels at high concentrations.

How do amphetamines differ from cocaine in their action?

Amphetamines not only block reuptake but also cause dopamine release by entering nerve terminals and reversing the transporter.

What is the role of the mesolimbic pathway in drug effects?

Stimulant-induced dopamine in the mesolimbic pathway is associated with locomotion and reinforcement.

What is the significance of dopamine pathways in drug-induced behaviors?

Different dopamine pathways are involved in various drug-induced behavioral effects, such as reinforcement and stereotypies.

What evidence supports the role of dopamine in drug reinforcement?

Evidence includes pharmacological studies, lesion studies, neurochemical studies, and genetic studies.

What happens to dopamine levels during drug cue exposure?

Drug cues can drive dopamine release and craving for the drug.

What are the potential therapeutics for stimulant addiction?

Potential therapeutics include modafinil, disulfiram, and vaccines against cocaine.

What neurotoxic effects can amphetamines have?

Amphetamines can cause depletion of monoamines and degeneration of nerve terminals.

What is the relationship between dose and neurotoxicity in amphetamines?

High doses of amphetamines can lead to long-lasting neurotoxic effects.

What are the effects of repeated amphetamine treatment?

It produces sensitization of locomotor and reinforcing effects, as well as increased dopamine levels.

What is the impact of DAT knockout in mice?

DAT knockout mice are hyperactive, showing increased locomotion similar to the effects of DAT blockers.

What is the effect of cocaine-associated cues in animals?

Cocaine-associated cues trigger drug-seeking behavior even in the absence of the drug.

How does MDMA affect serotonin levels?

Chronic MDMA use can lead to long-lasting decreases in serotonin transporter availability.

What factors may contribute to the neurotoxicity of amphetamines?

Factors include hyperthermia, reactive oxygen species, and high extracellular dopamine.

What is the significance of pharmacological studies on transporter blockers?

They show that drugs blocking DAT are self-administered, indicating their reinforcing properties.

What is the effect of selective antagonists on amphetamine reinforcement?

Dopamine antagonists disrupt amphetamine reinforcement, while norepinephrine antagonists do not.

What is the role of the nigrostriatal pathway?

It is involved in stereotypies induced by stimulants.

What is the relationship between dopamine release and craving?

Dopamine release in response to drug cues correlates with craving.

How does methamphetamine neurotoxicity manifest in humans?

It can lead to long-lasting decreases in dopamine transporter availability.

What are the long-term effects of MDMA on serotonin axons in monkeys?

MDMA administration can cause loss of serotonin axons in the cortex and hippocampus.

What is the impact of genetic studies on understanding drug effects?

Genetic studies provide insights into the role of specific neurotransmitter systems in drug reinforcement.

What is the significance of PET imaging in studying cocaine effects?

PET imaging shows the distribution of cocaine binding matches the distribution of dopamine transporters.

What are the acute adverse effects of MDMA?

They primarily reflect dehydration and hyperthermia, rather than overdose.