Psychopharmacology exam 3

What are the two main phytocannabinoids in cannabis and their primary effects?

THC (tetrahydrocannabinol) - psychoactive component
CBD (cannabidiol) - anti-oxidant, anti-convulsant, anti-inflammatory, anti-anxiety, anti-psychotic, and neuro-protective properties

What is the legal status of cannabis in the United States?

Paradoxical: Medical marijuana is legal in many states and recreational use is legal in some states, but federal law classifies marijuana as Schedule I (no accepted medical use, high potential for abuse)

What are the two main types of cannabinoid receptors and where are they located?

CB1 and CB2 receptors. Located in basal ganglia, cerebellum, hippocampus, cortex, amygdala, eye, pancreas, testes, uterus, and other areas. Often found on axon terminals.

What is the mechanism of action of THC at cannabinoid receptors?

THC is a partial CB1/CB2 agonist. It binds to these metabotropic receptors causing: inhibition of cAMP formation, inhibition of voltage-gated Ca2+ channels, opening of K+ channels, and can impact gene expression via the MAPK system

How does CBD interact with THC's effects?

CBD acts as a negative allosteric modulator at cannabinoid receptors, blocking some of THC's effects

What are the two main endogenous cannabinoid neurotransmitters?

Anandamide and 2-AG (2-arachidonoylglycerol)

What is unique about endocannabinoid signaling?

Endocannabinoids use retrograde signaling - they are released from the postsynaptic neuron and travel backward to bind CB1 receptors on the presynaptic terminal, helping regulate the release of other neurotransmitters

What is the pharmacokinetic difference between smoking and ingesting cannabis?

Ingested cannabis has slower onset of effect, less predictability of action, and less user control. It undergoes first-pass metabolism, converting THC to 11-hydroxy-THC, which is more potent than THC

Why can THC metabolites be detected in the body for days to weeks?

THC is very fat-soluble and easily crosses the blood-brain barrier. It is metabolized by the cytochrome P450 system, and metabolites are stored in fat tissue, allowing detection for extended periods

What is the therapeutic index of cannabis and what does this mean?

Cannabis has a very high therapeutic index, meaning the ratio of the lethal dose to the effective dose is very large - it's extremely difficult to overdose on cannabis

What are the well-documented medical benefits of cannabis?

Treatment of chronic pain, reducing nausea and vomiting, stimulating hunger, and alleviating stiffness and muscle spasms in MS patients

What factors influence the acute effects of cannabis?

Dose, potency of the strain, ratio of THC to CBD, user's previous experience, expectations and mood, and the environment in which it is used

Is cannabis addictive? Describe tolerance and withdrawal.

Less addictive than other drugs of abuse, but can be addictive in some individuals. Regular use causes tolerance. Withdrawal symptoms can occur but are usually not severe. Treatment typically involves psychological approaches

What is hemp and how does it differ from marijuana?

Hemp is a source of fiber, fuel, and food. It contains only trace amounts of THC and is not psychoactive. Cultivation was prohibited in the U.S. until 2018

What is the entourage/ensemble effect?

The combined effect of cannabinoids with other components of the cannabis plant (terpenes and flavonoids), which may produce different effects than isolated compounds

What cannabinoid receptors does cannabinoids also bind to besides CB1 and CB2?

GABA, Serotonin, Glutamate, and other receptors

What is the source of nicotine and how toxic is it?

Nicotine is found naturally only in the tobacco plant (Nicotiana tabacum). It is one of the most toxic of all drugs and more deadly than arsenic

What are the two main components of tobacco smoke?

Gaseous components (ammonia, hydrogen cyanide, CO2, carbon monoxide) and particulate matter (nicotine and tar). Tobacco smoke contains over 4,000 substances total

What is tar in tobacco smoke?

Sticky brown particulate matter generated by burning tobacco that contains dozens of carcinogens

What is the biphasic effect of nicotine on acetylcholine receptors?

First, nicotine binds to nicotinic cholinergic receptors and excites them. Then it stays bound, which prevents neural transmission (acts as an antagonist)

Besides acetylcholine, what other neurotransmitters does nicotine affect?

Dopamine, GABA, and glutamate

How much nicotine does a smoker typically inhale per cigarette?

About 1 mg of nicotine per cigarette

What is the therapeutic index of nicotine?

21 - meaning overdose is rare but possible

How does nicotine absorption differ between cigarettes and other tobacco products?

Cigarettes: better absorbed in lungs, Pipes, cigars, smokeless tobacco: better absorbed in mouth

What is the half-life of nicotine and what does this mean for smokers?

2-hour half-life, which means smokers wake up in mild withdrawal each morning

What are the two models explaining nicotine addiction maintenance?

Nicotine resource model (nicotine provides cognitive benefits) vs. Deprivation reversal model (smoking only reverses withdrawal symptoms, not providing actual enhancement)

How many Americans does tobacco kill each year?

480,000 Americans each year - more than alcohol, illegal drugs, fires, motor vehicle injuries, homicide, suicide, and AIDS combined. Tobacco addiction is the single greatest cause of premature death in the world

What are the three main life-threatening conditions caused by tobacco?

Cardiovascular disease, cancer, and chronic obstructive pulmonary disease (COPD)

What prenatal and postnatal effects are associated with maternal smoking?

Higher risk of miscarriage, stillbirth, premature birth, low infant birth weight, SIDS, cleft palate, depression, and ADHD. Almost 9% of pregnant women smoke

What is secondhand smoke and what is it classified as?

Also called passive smoke or environmental tobacco smoke. It's a combination of smoke exhaled from the smoker plus smoke rising off the lit end. Classified as a Class A carcinogen and associated with higher incidence of heart disease and lung cancer

What makes nicotine so addictive?

Nicotine is considered one of the most addictive substances ever discovered. Tobacco is both biologically and psychologically addictive, with drug-related cues inducing cravings and social factors enhancing addictive properties

How does tolerance to nicotine develop?

Tolerance develops at different speeds to different effects. Can be acute vs chronic tolerance and involves metabolic, cellular, and behavioral mechanisms

What are the main types of smoking cessation aids?

Nicotine replacement therapies (gum, patch), pharmacological treatments that don't replace nicotine (bupropion, hallucinogens), and behavioral/psychosocial treatments. Vaping efficacy for cessation is not proven

What are the main safety concerns with e-cigarettes/vaping?

Highly concentrated nicotine, lack of quality control, carcinogenic substances, exploding batteries, and EVALI (inflammatory condition). E-cigarettes have not yet been evaluated by FDA for safety

Why has cigarette use among teens reached its lowest level?

More disapproval of smoking, greater awareness of dangers, adverse publicity of tobacco industry, less advertising, smoking bans, decreased availability due to prices and age controls, and increase in e-cigarette popularity

What percentage of the U.S. population has used tobacco in the past month?

21% of the U.S. population

What other health conditions is tobacco causally associated with besides the three main life-threatening conditions?

Type 2 diabetes, Crohn's disease, tuberculosis, rheumatoid arthritis, impaired reproductive function, and impaired immune function

What is the difference between sedatives and hypnotics?

Sedatives: relieve anxiety, cause relaxation, mild CNS depressants
Hypnotics: cause drowsiness and slee

What are the two main classes of sedative/hypnotic drugs?

Barbiturates and benzodiazepines (BZDs)

What is the history of barbiturates?

Adolf von Baeyer synthesized barbituric acid. First pharmacologically active barbiturate marketed in 1903. Height of popularity was mid-20th century

What is the history of benzodiazepines?

Chlordiazepoxide discovered in 1955. More popular today than barbiturates due to better safety profile

How are barbiturates and BZDs categorized?

Based on duration of action:
More lipid-soluble (typically barbiturates): shorter acting, more likely to be abused, used as pre-anesthetic sedatives and to treat insomnia
Longer-acting (typically BZDs): used as anticonvulsants, muscle relaxants, and anxiolytics

What is the mechanism of action of benzodiazepines at the GABA receptor?

BZDs bind to a specific site on the GABAA receptor, which increases the FREQUENCY of chloride channel openings when GABA binds. GABA receptors with BZD binding sites are located in limbic system, reticular activating system, and cortex

What is the mechanism of action of barbiturates at the GABA receptor?

Barbiturates have a more general effect on GABA receptors. When they bind, they enhance the receptor's affinity for GABA, which increases the DURATION of time the chloride channel is open. Can also cause chloride channel opening even when GABA is not present

Why are benzodiazepines safer than barbiturates regarding respiratory depression?

GABA receptors that control respiration don't have many BZD binding sites, so BZDs have minimal effects on the respiratory center of the brainstem. Barbiturates affect all GABA receptors more generally

What is the therapeutic index of barbiturates and what does this mean?

Barbiturates have a very low therapeutic index (this is bad), meaning the lethal dose is close to the effective dose. Risk of overdose is greatly increased when used with opioids or other depressant drugs

What has happened to benzodiazepine overdose deaths in recent decades?

The number of deaths attributable to benzodiazepine overdose has risen almost ten-fold in the past two decades

What are the medical uses of barbiturates and BZDs?

Treatment of insomnia, anxiety disorder, seizure disorder, alcohol withdrawal, and as anesthetics

Why have BZDs largely replaced barbiturates in clinical use?

More specific effects, fewer side effects, much wider margin of safety, less potential for abuse or tolerance, less effect on REM sleep, and minimal effects on respiratory center of brainstem

What are Z-drugs and what are their effects?

Ambien, Lunesta, Sonata. They bind to the BZD site on the GABA receptor and produce sleep rhythm more like natural sleep. However, they raise the risk of motor vehicle accidents, sleep-walking, sleep-eating, sleep-sex, and sleep-driving

How does tolerance develop differently for barbiturates vs BZDs?

Barbiturates: tolerance develops via cellular and metabolic mechanisms, develops faster
BZDs: tolerance is not as fast or complete
For both: tolerance develops for sedative/hypnotic effects but NOT for anticonvulsant effects or respiratory depression

What are the withdrawal symptoms from sedative/hypnotics?

Insomnia, anxiety, tremor, headache, confusion, and difficulty concentrating. Should be medically supervised due to potential severity

What are the fetal effects of sedative/hypnotic use during pregnancy?

Potential increased risk of cleft palate and floppy infant syndrome, possible withdrawal symptoms. Otherwise no significantly increased risk of major malformations. Must weigh risks to fetus against risks of mother going off the drug

What is the drug interaction concern with sedative/hypnotics?

Synergistic effects with other depressants such as alcohol and opioids. Also interact with other drugs metabolized by CYP450 system

What is Propofol and how does it work?

Fast-acting anesthetic that affects both the GABA and endocannabinoid systems. Reduces awareness and leaves the patient with no memory of the experience

What are Quaaludes?

CNS depressant that binds to GABA receptors. Popular in the 1970s and 1980s. Now classified as Schedule I

What routes of administration are used for barbiturates and BZDs?

Oral, rectal, and injection

Compare the absorption pharmacokinetics of BZDs vs barbiturates

BZDs: less lipid soluble than barbiturates, absorbed more slowly, slower onset of action (which makes them less addictive)
Barbiturates: more lipid soluble, faster absorption and onset
Both are highly bound to plasma proteins and cross the placent

What substances were historically used to relieve anxiety and help sleep before barbiturates?

Valerian root, kava, alcohol, opium, and chloral hydrate

What is GHB and what are its dual roles?

GHB (gamma-hydroxybutyrate) is both a neurotransmitter and an illegal drug. It has dose-dependent biphasic effects

How do low vs high doses of GHB differ in their effects?

Low doses: produce excitatory effect by binding to GHB receptors
High doses: activate GABA receptors and produce sedation and sleepiness

What neurotransmitter systems does GHB affect?

Dopamine, acetylcholine, serotonin, and opioids, in addition to its effects on GABA and GHB receptors

What are the dangers of high-dose GHB?

Can lead to suppressed respiration, convulsions, coma, and death

What is the legal status of GHB?

Schedule I, except for versions approved for treatment of narcolepsy, which are Schedule III

Why are inhalants particularly concerning for adolescents?

Often a young person's first introduction to drug-induced altered consciousness. One of the most commonly used drugs in middle school and high school. Readily available, inexpensive, legal to buy and possess, easy to conceal. Among the most toxic of drugs

What are the three categories of inhalants?

1. Volatile substances (adhesives, aerosols, cleaning agents, fuels, solvents)2. Anesthetics (ether, nitrous oxide)3. Nitrites (amyl nitrite, butyl nitrite)

How many household products can be inhaled to get high?

More than 1,400 household products, with little in common in their chemical structure, pharmacology, or mechanism of action

What are the acute effects of inhalants?

Similar to alcohol intoxication. Dangers include toxic effects, sudden sniffing death syndrome, and the incoordination and recklessness that often follow their use

What are the chronic effects of inhalant use?

Nosebleeds, rashes, weight loss, depression, hostility, paranoia, increased risk of cancer, damage to liver, kidneys, lungs, bone marrow, and brain, and cognitive impairments

What was the historical use of ether and nitrous oxide?

Both were commonly inhaled as intoxicants before being used as anesthetics during dental and surgical procedures

Why is it difficult to determine the true effects of chronic inhalant use?

It's difficult to determine to what degree observed effects are due to the inhalants themselves, their pattern of use, or to pre-existing differences in the users

What is sudden sniffing death syndrome?

A dangerous acute effect of inhalant use that can cause sudden death

What Schedule classification is cannabis under federal law?

Schedule I (defined as having no accepted medical use and high potential for abuse), despite being legal for medical use in many states and recreational use in some states

What is the most commonly used illicit drug in the United States?

Cannabis

What happens to cannabis use among high schoolers as their perception of risk increases?

As perception of risk increases, cannabis use decreases

Describe the relationship between cannabis legalization and arrest disparities

Hundreds of thousands of people are arrested each year in America for cannabis possession. Blacks are arrested and incarcerated significantly more than whites

What percentage of Americans support the legalization of marijuana?

Most Americans support legalization - support has reached near-high levels of 68% according to Gallup polls

What are synthetic cannabinoids? Give examples.

Synthetic cannabinoids are lab-created compounds. Examples include Dronabinol (Marinol, used medically) and Spice (illegal street drug)

What does it mean that THC is metabolized by the cytochrome P450 system?

The CYP450 system breaks down THC in the liver. This can lead to drug interactions with other substances metabolized by the same enzyme system

Where are CB1 and CB2 receptors primarily located in the body?

CB1: primarily in the brain (basal ganglia, cerebellum, hippocampus, cortex, amygdala)
CB2: primarily in immune system and peripheral tissues (eye, pancreas, testes, uterus)

What is the function of the endocannabinoid system?

A widespread system that controls many important physiological effects and helps maintain homeostasis in the body

What are some adverse effects of cannabis that come from factors other than the drug itself?

Some adverse effects come from collateral damage due to criminal penalties, or from one's diminished reaction time and coordination (accidents)

What potential medical benefits of cannabis are currently being investigated?

Anti-inflammatory effects, treating seizure disorders, cancer, stroke, Alzheimer's disease, diabetes, irritable bowel disease, depression, and potentially reducing use of prescription opioid pain drugs, alcohol, and cocaine

Can high doses of cannabis raise the risk of schizophrenia?

Yes, high doses may raise the risk of schizophrenia in a susceptible minority of users

Can high doses of cannabis impair fertility?

Yes, high doses may impair fertilization

What legal precedent was set in Gonzales v. Raich (2005)?

Even when individuals or businesses are in compliance with state cannabis laws, they are still violating federal cannabis laws

What legal precedent was set in Coats v. Dish Network (2015)?

If you have a doctor's recommendation for medical marijuana and have acquired it according to state laws, you can still get fired for testing positive for marijuana from your employer's mandated drug test

What percentage of pregnant women smoke?

Almost 9% of pregnant women smoke

How do smoking rates differ between pregnant and non-pregnant women by age?

Smoking rates in pregnant women are lower than rates in women who are not pregnant, except in those under age 25

What is the only factor associated with concluding that passive smoking is not harmful?

Whether an author was affiliated with the tobacco industry

What increases the odds of successfully quitting tobacco?

Pharmaceutical aids and cessation programs increase the odds of successfully quitting

Do most people who smoke want to quit?

Yes, most people who smoke want to quit

What happens to the pH and nicotine levels of tobacco during the curing process?

The method of curing (drying) changes the pH and nicotine levels of tobacco

What harmful additives are added to tobacco after harvest?

Manufacturers add many harmful additives to shredded tobacco during storage, though specific additives vary by product

When were barbiturates at their height of popularity?

Mid-20th century

What was the first pharmacologically active barbiturate and when was it marketed?

The first pharmacologically active barbiturate was marketed in 1903

Who synthesized barbituric acid?

Adolf von Baeyer

When was chlordiazepoxide (the first benzodiazepine) discovered?

1955

What effects do barbiturates and BZDs both have on tolerance development?

Tolerance develops for sedative and hypnotic effects, but does NOT develop for anticonvulsant effects or respiratory depression

Why must sedative/hypnotic withdrawal be medically supervised?

Due to the potential severity of withdrawal symptoms and risk of complications