opioids, fentanyl, tobacco/nicotine, caffeine, some alcohol

What are the four primary types of opioid receptors?

Mu, delta, kappa, and NOP-R (nociceptin/orphanin FQ receptor).

What is the general physiological effect of opioid receptors on cell membranes?

They are inhibitory metabotropic receptors that reduce the excitability of the cell membrane.

How do opioids affect postsynaptic neurons?

They open potassium channels, leading to hyperpolarization of the neuron.

What is the mechanism of opioid action at the axoaxonic level?

They shut calcium channels, which prevents calcium from binding to synaptotagmin and inhibits vesicle release.

What is the function of presynaptic autoreceptors in the context of opioids?

Binding to these receptors decreases the amount of neurotransmitter released.

Which endogenous opioids bind to the delta receptor?

Enkephalins.

Which endogenous opioids bind to the kappa receptor?

Endorphins and dynorphins.

What is the primary pharmacological difference between an agonist and an antagonist in the opioid system?

An agonist activates the receptor, while an antagonist binds to the receptor without activating it, effectively blocking other substances from binding.

Why is Naloxone considered a competitive antagonist?

It has a high affinity for the Mu receptor and can displace other opioids (like morphine) from the receptor site.

How does lipid solubility affect the administration of opioids?

Higher lipid solubility allows for faster onset of effects via routes like smoking or snorting (e.g., heroin), whereas low lipid solubility (e.g., morphine) limits these routes.

What are the common behavioral and physical effects of opioid use?

Analgesia, euphoria, mental clouding, pupil constriction, cough suppression, sedation, constipation, and itching due to histamine release.

What is the difference between 'first pain' and 'second pain'?

First pain is mediated by myelinated Alpha-delta fibers for immediate reflex reaction; second pain is mediated by unmyelinated C fibers and relates to the emotional, unpleasant component of pain.

What is the significance of the transdermal patch route for opioids?

It has a very slow onset of action, taking up to 16 hours to take effect.

What are 'drug depots' in the context of opioid distribution?

Sites where drugs accumulate, such as the liver, lungs, spleen, muscles, and GI tract.

How does the potency of Fentanyl compare to Morphine?

Fentanyl is significantly more potent than Morphine.

What is the primary therapeutic use of opioids regarding pain?

They are generally more effective at managing chronic pain than acute pain, with inconsistent results for the latter.

What happens when Naloxone is administered to a person with no opioids in their system?

It has no observable effect because it is a competitive antagonist with no intrinsic efficacy.

What is the historical origin of the term 'morphine'?

It is named after Morpheus, the Greek God of dreams.

How did the invention of the hypodermic needle in 1853 change opioid use?

It allowed for direct injection, which increased the addictive potential compared to oral ingestion.

Which opioid receptor does morphine primarily bind to?

The Mu receptor.

What is the difference in efficacy between Morphine, Fentanyl, and Hydromorphone?

They are considered to have equal efficacy.

Why is heroin more rapidly acting than morphine when smoked or snorted?

Heroin has higher lipid solubility, allowing it to cross the blood-brain barrier rapidly before being converted back into morphine in the brain.

What is the primary function of the descending pain modulation pathway?

It originates in the brain and travels downward to suppress pain signals, preventing the constant perception of pain.

How do opioids affect the descending pain pathway?

They upregulate the descending pathway to suppress pain signals and also suppress the perception of pain within the brain.

What are the three main mechanisms by which opioids modulate pain?

Direct inhibition of projection neurons, inhibition of excitatory spinal interneurons, and modifying pain perception through higher brain regions.

How do opioids inhibit projection neurons in the ascending pain pathway?

Opioids bind to Mu receptors on projection neurons, reducing their excitability and suppressing the transmission of pain signals.

What role do spinal interneurons play in opioid-mediated pain relief?

Opioids can inhibit excitatory interneurons, effectively canceling out positive pain signals being sent from sensory neurons.

Which brain regions are involved in the cognitive perception of pain and contain opioid receptors?

The nucleus accumbens, amygdala, thalamus, and anterior cingulate.

What is the mesolimbic dopamine pathway's role in addiction?

It regulates reward and motivation; opioids hijack this system by increasing dopamine signaling, leading to misuse and addiction.

How do opioids cause 'disinhibition' of dopamine neurons in the VTA?

Opioids bind to Mu receptors on GABAergic interneurons, inhibiting the release of GABA, which normally suppresses dopamine neurons.

Why is Fentanyl considered highly addictive?

It is 50 times more potent than heroin, highly lipid-soluble, has a rapid onset, and a short duration of action.

What are three forms of opioid tolerance?

Metabolic (faster liver processing), cellular (reduced opioid receptors), and behavioral (drug-taking environment).

What are the diagnostic criteria for Major Depressive Disorder (MDD)?

Symptoms must last at least two weeks and significantly impact life in at least two different environments.

What is the 'Monoamine Hypothesis' of depression?

The theory that depression is caused by a depletion or imbalance of monoamine neurotransmitters like serotonin, dopamine, and norepinephrine.

What are Monoamine Oxidase Inhibitors (MAOIs)?

The first class of antidepressants; they work by inhibiting the breakdown of monoamines, though they have significant side effects.

What is the 'wine and cheese effect' associated with MAOIs?

A dangerous interaction where tyramine (found in aged foods) cannot be broken down, leading to a hypertensive crisis.

How do SSRIs and SNRIs differ from TCAs?

SSRIs and SNRIs selectively block the reuptake of serotonin or norepinephrine, whereas TCAs are 'dirtier' and also block acetylcholine and histamine receptors.

What is the 'Neurogenic Theory' of antidepressants?

The theory that antidepressants work by increasing BDNF levels, which promotes neurogenesis in the hippocampus and prefrontal cortex.

What is antidepressant discontinuation syndrome?

Withdrawal effects experienced when stopping medication, including dizziness, nausea, insomnia, and rebound depression.

What are the three main categories of hallucinogens?

Psychedelics (altered perception), deliriants (mental confusion), and dissociatives (detachment/analgesia).

What is the primary mechanism of action for classic psychedelics like LSD and psilocybin?

They act as agonists at the 5-HT2a serotonin receptor.

What is the 'head twitch response' in mice?

A behavioral marker used in research to indicate that a mouse is experiencing a psychedelic-like state.

What is the role of the 5-HT2a receptor in the psychedelic experience?

Activation of these receptors in the prefrontal cortex triggers a cascade of cellular events that leads to altered states of consciousness.

What is the 'receptor lid' mechanism of LSD?

When LSD binds to the 5-HT2a receptor, an extracellular loop closes over the receptor, trapping the LSD molecule inside.

How do dissociatives like Ketamine differ from psychedelics?

Dissociatives primarily change glutamate signaling, whereas psychedelics primarily increase serotonin signaling.

What is the 'trigger population' in the context of psychedelic action?

Pyramidal neurons in layer 5 of the prefrontal cortex that are dually excited by 5-HT2a and glutamate receptors.

What is the primary risk factor for opioid addiction mentioned in the text?

High-intensity prescribing patterns, young age, history of substance abuse, and severe depression or anxiety.

Why are opioids considered less effective for chronic non-cancer pain?

They show limited efficacy for conditions like arthritis or sports injuries compared to cancer pain.

What is the function of the VMAT (Vesicular Monoamine Transporter)?

It is responsible for the storage of neurotransmitters in vesicles; its inhibition leads to neurotransmitter depletion.

What is the relationship between stress and the hippocampus in depression?

Chronic stress elevates cortisol, which is neurotoxic and leads to reduced gray matter and decreased neurogenesis in the hippocampus.

What is the 'first-pass effect' in pharmacokinetics?

The processing of a drug by the liver before it reaches systemic circulation, which reduces its bioavailability.

What is Serotonin Syndrome?

A potentially life-threatening condition caused by having too much serotonin in the body, often due to drug interactions.

What is the historical significance of Ergot in relation to hallucinogens?

Ergot is a fungus that grows on grain and contains lysergic acid; it is linked to historical events like the Salem witch trials.

What is the 'cortico-stratal-thalamo-cortical loop'?

A brain circuit that gates sensory and cognitive input; psychedelics disrupt this loop, leading to cognitive distortions.

Why is it difficult to treat depression with medication immediately?

Antidepressants often take 2-4 weeks to show therapeutic effects, likely because they require time to induce neurogenesis via BDNF.

What is the primary mechanism of action of MDMA?

It is highly focused on the serotonin system, increasing serotonin signaling by blocking the serotonin transporter (SERT), promoting serotonin release via VMAT, and inhibiting degradation enzymes.

What are the acute physiological effects of MDMA?

Sympathomimetic effects including elevated blood pressure and heart rate, teeth grinding, increased energy, arousal, and potential sexual dysfunction.

Why can MDMA use lead to fatal hyponatremia?

Users may retain fluid while experiencing polydipsia, which disrupts sodium levels, potentially leading to brain swelling, loss of consciousness, and death.

What is the therapeutic rationale for MDMA-assisted therapy?

It helps patients reach and maintain a peak emotional experience, facilitating an 'afterglow' that reduces guilt and anxiety and enhances the capacity for close relationships.

How does microdosing with psychedelics potentially remodel brain connections?

It acts as a psychoplastogen, increasing synaptogenesis and the growth of dendritic spines on neurons.

What is the primary mechanism of action for dissociatives like ketamine and PCP?

They act as uncompetitive, open-channel NMDA receptor antagonists, which increases glutamate signaling.

How do dissociatives affect the brain's dopamine system?

They increase the synthesis and release of dopamine, contributing to agitation, stimulation, and increased motor activity.

What is the 'schizophrenia model' regarding dissociatives?

It suggests that the imbalance between glutamate and serotonin signaling induced by these drugs mimics symptoms of schizophrenia.

How does nicotine affect the dopamine system in the nucleus accumbens?

Nicotine binds to nicotinic acetylcholine receptors on GABA, glutamate, and dopamine terminals, modulating the release of dopamine from the VTA.

What is the biphasic effect of nicotine?

At low doses, it acts as a stimulant; at higher exposures, it induces a depolarization block, leading to rapid desensitization of receptors.

Why do smokers report that the first cigarette of the day is the most satisfying?

Because tolerance has built up overnight, and the first cigarette effectively alleviates withdrawal symptoms.

What is the role of cotinine in nicotine metabolism?

Cotinine is a major active metabolite of nicotine that has been studied for potential beneficial effects on the acetylcholine system, such as in Parkinson's disease.

How does the onset of nicotine delivery compare between smoking and smokeless tobacco?

Smoking provides a rapid onset (10-15 seconds) to the brain, whereas smokeless tobacco provides a slower, continuous delivery over approximately 30 minutes.

What is the structural composition of nicotinic acetylcholine receptors (nAChRs)?

They are ionotropic receptors composed of five subunits, with specific combinations (like 2 alpha and 3 beta) determining their affinity for nicotine.

Why is it difficult to die from nicotine poisoning via ingestion?

Nicotine induces vomiting, which acts as a protective mechanism to expel the toxin before lethal levels are absorbed.

What are the long-term risks associated with chronic MDMA use?

Potential risks include erosion of tooth enamel, liver damage, depression due to serotonin system downregulation, and possible cognitive or memory deficits.

What is the function of the 5-HT2b receptor in MDMA use?

Its activation contributes to feelings of calmness and minor hallucinogenic effects.

How does nicotine affect sensorimotor gating?

Nicotine is thought to augment prepulse inhibition, which is the ability to modulate behavioral responses to external sensory stimulation, a function often deficient in schizophrenia.

What is the cellular mechanism of tolerance for nicotine?

Chronic use leads to changes in the expression of acetylcholine receptors, while acute use causes rapid desensitization of GABAergic signals.

What happens to the serotonin system after chronic LSD or psilocybin use?

There is a rapid down-regulation of 5-HT2a receptors, which provides a form of cellular tolerance that may protect against addiction.

What is Hallucinogen Persisting Perception Disorder (HPPD)?

A condition characterized by the recurrence of perceptual disturbances or 'flashbacks' after the drug's effects have worn off.

How do dissociatives modify pain transmission in the spinal cord?

They provide direct inhibition of projection neurons and inhibit excitatory interneurons, while also interacting with inhibitory spinal interneurons.

Why are adolescent brains more susceptible to nicotine dependence?

The adolescent brain responds to nicotine differently, making it significantly more likely to develop a pathological, lifelong dependence.

What is the effect of cytochrome P450 liver enzymes on nicotine?

They metabolize nicotine into active metabolites; individuals with slower metabolism may be less likely to become dependent but are more prone to toxic accumulation.

How does nicotine act on GABAergic interneurons?

Nicotine binds to receptors on GABA neurons, leading to acute desensitization and making these neurons more sensitive to depolarization block.

What is the primary difference between Tobacco Nicotiana rustica and Nicotiana tabacum?

Rustica is a smaller leaf indigenous to the US, while tabacum is a larger leaf indigenous to South America, often preferred for its taste.

How does nicotine affect glutamate and dopamine levels?

Binding to glutamate receptors increases both glutamate and dopamine release.

What is the difference in desensitization between Alpha 4 Beta 2 and Alpha 7 nicotine receptors?

Alpha 4 Beta 2 receptors are highly sensitive and desensitize rapidly under high nicotine levels, whereas Alpha 7 receptors are less sensitive and take much longer to desensitize.

How does nicotine affect sensorimotor gating in individuals with schizophrenia?

It may act as a form of self-medication to help normalize sensorimotor gating.

What is the 'nicotine advantage' regarding attentional processing?

Nicotine improves the detection of stimuli in low-attention environments, but this effect is lost in high-attention or 'on edge' environments.

How does adolescent nicotine exposure affect ethanol self-administration in rat models?

It impairs KCC2 function in the VTA, leading to hyperactive GABAergic neurons that require significantly higher amounts of ethanol to achieve a reward signal.

What is the primary mechanism of action for caffeine?

Caffeine acts as an antagonist to adenosine receptors.

Why does caffeine have 100% bioavailability when taken orally?

It is rapidly absorbed by the small intestine and bypasses the first-pass effect in the liver.

What are the primary metabolites of caffeine and their functions?

Paraxanthine (increases fat breakdown), Theobromine (bronchodilator and cardiac stimulant), and Theophylline (vasodilator and diuretic).

What is the role of adenosine in the sleep-wake cycle?

Adenosine builds up in the brain throughout the day to create sleep pressure; caffeine blocks this by binding to adenosine receptors.

How do A1 and A2a adenosine receptors differ in their signaling?

A1 receptors are inhibitory (G-protein coupled) and inhibit adenyl cyclase, while A2a receptors are stimulatory and activate adenyl cyclase to increase cAMP.

What is the effect of caffeine on the Tuberomammillary nucleus (TMN)?

Caffeine prevents the inhibition of histamine release, thereby promoting wakefulness and vigilance.

What was the primary goal of the Women's Christian Temperance Union?

To reduce alcohol consumption, initially focusing on moral suasion and later moving toward complete abstinence and political lobbying.

What was the purpose of the Volstead Act?

It provided the legal framework for law enforcement to enforce the 18th Amendment (Prohibition).

Why was the 18th Amendment repealed in 1933?

The Great Depression created a need for tax revenue and jobs, and Prohibition had spurred organized crime and eroded government trust.

What is the difference between ethanol and methanol metabolism?

Both are processed by alcohol dehydrogenase, but methanol produces toxic formaldehyde, while ethanol produces acetaldehyde.

What is the function of aldehyde dehydrogenase in alcohol metabolism?

It converts acetaldehyde into acetic acid, preventing the buildup of toxic acetaldehyde.

What is the physiological cause of a hangover?

It is largely attributed to the metabolism of methanol and the buildup of toxic metabolites.

How does caffeine affect heart rate at different doses?

It has a biphasic effect: low doses can decrease heart rate, while high doses increase heart rate and blood pressure.

What is the toxic dose of caffeine for adults?

Approximately 400mg/day.