Drugs & Behavior Exam 3

Since energy drinks are marketed as "Supplements" they are not required to disclose amount of caffeine in one can.

True

Size of the hippocampus can predict PTSD

True

Legal Status of Marijuana

In 1970, marijuana and THC became Schedule I illegal drugs

Industrial Hemp

2014 Farm Bill Allowed to cultivate industrial hemp for research purposes 2018 Farm Bill Made industrial hemp legal CBD (cannabidiol) oil production

Atypical Antipsychotics

"Atypical" or "second-generation" drugs reduce positive symptoms of schizophrenia as well as classical drugs, but without significant motor and hormonal side effects. They are more effective for patients who do not respond to typical antipsychotics. Some new drugs do not produce TD or increase prolactin secretion. Many of them are defined as "broad-spectrum antipsychotics", because they block not only dopamine D2 receptors, but also serotonin, histamine, muscarinic cholinergic receptors, etc. Clozapine Broad-spectrum antipsychotic. Approved by the FDA in 2004. Clozapine has weak affinities for D1 and D2 and strong affinities for serotonergic, muscarinic, histaminergic, and D4 receptors. In the US, the use of clozapine is restricted to those people with schizophrenia who have failed first-line treatments. The reason for this restriction is its risk of severe side effects. It has many side effects because of its action on multiple receptors. Weight gain, agranulocytosis, sedation, cardiac toxicity, etc. Clozapine has fewer motor side effects. Clozapine Clinical trials in the UK found that clozapine was superior to the other antipsychotics in the treatment of negative symptoms. Clozapine can improve cognitive symptoms! Only clozapine is truly "atypical". Aripiprazole (Abilify) Partial dopamine agonists compete with dopamine for receptors and reduce dopamine effect. Has few side effects. Little evidence of motor side effects, weight gain. Adverse effects such as headache, agitation, insomnia, and nervousness are minor. 2002: FDA approval in for the treatment of schizophrenia. 2006: treatment of bipolar disorder (mania), as adjunctive treatment for major depressive disorder (2006). Lurasidone (Latuda) Broad-spectrum antipsychotic Blockade of D2 dopamine and 5-HT2A serotonin receptors→atypical antipsychotic effect Antagonism at the 5-HT7 receptor and partial agonism at the 5-HT1A contributes to the antidepressant properties of lurasidone. Lurasidone has low activity on muscarinic, histamine, adrenergic receptors→low risk of sedation, weight gain, hormonal effects, etc. Was FDA approved in 2010. In 2018 expanded to pediatric patients (10-17 years old)

Therapeutic Uses of Cannabis Cannabinoids

"Medical marijuana" Many states now permit legal use, but clinical studies of its efficacy have shown mixed results.

Chronic Cocaine Exposure

- Most individuals who try cocaine do not progress to a pattern of abuse or dependence. - About 10% to 15% of initial users become abusers. - People usually start cocaine by snorting. Some people have a strong anxiety response and do not try it again. - Other factors that discourage habitual use include cost and availability, social and legal consequences, fear of addiction. - The stimulating, euphoric, and confidence-enhancing effects are a powerful reinforcers in the early stages. - Crack smoking, or IV injection have greater abuse potential. - Some individuals develop a pattern of cocaine binges, episodic bouts of repeated use lasting hours to days with little or no sleep. Afterwards, an abstinence syndrome occurs. - Chronic exposure to psychostimulants can lead to tolerance (pharmacodynamics and behavioral). - In humans, cocaine's euphoric effects tend to show tolerance, which would contribute to increased drug-taking in an attempt to recapture the level of pleasure experienced during earlier episodes of use. - The reverse effect, sensitization, is also seen. Just a few exposures to cocaine or amphetamine can produce an increased responsiveness that lasts for weeks, months, or even up to year. o Continuous cocaine infusion into rats→tolerance to the locomotor-stimulating effect o Once-daily injections→behavioral sensitization, shown by enhanced stereotyped behaviors. - Although cocaine withdrawal is rarely serious it produces a number of very unpleasant side effects. Symptoms generally only last for about a week or two and may include the following: o Depression o Fatigue o Exhaustion o Increased appetite o Unpleasant dreams o Challenges in concentration o Intense craving for cocaine

Treatment of Cocaine Use Disorder

- Presently, there are no FDA-approved medications to treat cocaine addiction. - Consequently, National Institute for Drug Abuse (NIDA) is working aggressively to identify and test new medications to treat cocaine addiction safely and effectively. - While many have shown effectiveness in animal models, none are currently licensed for medical use due to unacceptable side effects and/or lack of therapeutic efficacy.

Drugs Interactions

-Alcohol or other depressants are sometimes taken along with cocaine to "take the edge off" the extreme arousal produced by cocaine. -Cocaine when mixed with alcohol produces a unique metabolite called cocaethylene, which has activity similar to cocaine, but has a longer half- life. -"Speedball" - mixture of cocaine and heroin o Aim is to increase "rush" and reduce negative effects: anxiety, hypertension, sedation, etc. o Danger of delayed opioid overdose Danger of stroke and heart attack

Mechanisms of Amphetamine Action: Dopamine and Norepinephrine

-Amphetamine and methamphetamine are agonists of the dopamine and norepinephrine systems. -They have two actions: o The drug molecules enter dopamine/norepinephrine nerve terminals via uptake by dopamine/norepinephrine transporter and cause vesicles to release dopamine/norepinephrine. o They can also block transporters or make them work in reverse: moving dopamine/norepinephrine into the synaptic cleft o →Very high dopamine/norepinephrine concentration in the synaptic cleft. -Norepinephrine-releasing effects of amphetamines occur in the brain and in the sympathetic nervous system. -Consequently, these compounds have potent sympathomimetic actions, similar to those seen with cocaine.

Pharmacokinetics of Amphetamine: Metabolism

-Amphetamine and methamphetamine are metabolized by the liver at a slow rate. -The elimination half-life of amphetamine ranges from 7 to more than 30 hours depending on the pH of the urine. Methamphetamine has a similar half-life of approximately 10 hours. -Because of long half-lives, users obtain a longer-lasting "high" from a single dose than from a dose of cocaine.

Pharmacodynamics: Behavioral Effects of Amphetamine

-Amphetamine causes heightened alertness, increased confidence, feelings of exhilaration, reduced fatigue, a generalized sense of well- being, delay in sleep onset, sustained physical effort without rest. -It can enhance athletic performance and is banned in athletic competitions. -Often used as cognitive enhancer, although benefits and long-term effects are not well studied -Appetite suppressant -Can produce insomnia -It is highly reinforcing.

Pharmacokinetics of Amphetamine: Routes of Administration

-Amphetamine is taken orally or by IV or subcutaneous injection ("skin popping"). -Methamphetamine has very strong effects on the CNS. Can be taken orally, snorted, injected IV, or smoked. o Smoking is done with a glass pipe or by heating the drug on a piece of aluminum foil ("chasing the dragon").

The Amphetamines

-Amphetamine is the parent compound of a family of synthetic psychostimulants that are structurally related to dopamine (DA), e.g. methamphetamine, MDMA. -Stimulants of natural origin, ephedrine and cathinone are also structurally similar -Amphetamine, methamphetamine are Schedule II drugs -Cathinone, MDMA - Schedule I -Ephedrine is not controlled by the Schedules

Drugs Interactions

-Barbiturates or other depressants are sometimes used to "take the edge off" during repeated injections or to aid sleep afterward -IV amphetamine or methamphetamine is sometimes combined with heroin to yield a "speedball".

Cocaine Abuse and the Effects of Chronic Cocaine Exposure

-Behavioral and psychosocial therapies: o Most are conducted as outpatient programs. o Psychosocial treatment programs involve individual, group, or family counseling designed to educate the user, promote behavioral change, and alleviate problems caused by cocaine abuse. o Twelve-step programs such as Narcotics Anonymous or Cocaine Anonymous are also available.

Amphetamines and Psychosis

-Chronic, high-dose abuse can result in psychotic reactions, including visual and/or auditory hallucinations, behavioral disorganization, and development of a paranoid state with delusions of persecution. -Some users who had an earlier psychotic reaction may undergo spontaneous recurrences ("flashbacks") even while abstinent. -Dopamine hypothesis of schizophreni

Psychomotor Stimulants :Cocaine and the Amphetamines

-Cocaine and amphetamine belong to aclass of drugs called psychomotorstimulants. -Increase motor behavior and elevate aperson's mood, level of alertness, arousaland cause behavioral excitement.2

Cocaine: Background and History

-Cocaine is an alkaloid foundin the leaves of the coca plant(Erythroxylon coca). -It is native to South Americaand is cultivated in thenorthern and central AndesMountains. -The practice of chewing cocaleaves began as early as 5000 years ago.Map of principal coca-growingregions of South America Coca chewing is still practiced by some Bolivian miners -Cocaine was first isolated (extracted from coca leaves) in 1859 by German chemist Albert Niemann. -Cocaine use became popular as many doctors and scientists lauded its properties. -Sigmund Freud, who used the drug himself, was the first to broadly promote cocaine as a tonic to cure depression and sexual impotence. He declared that it was non-addictive. -Cocaine also became popular in the U.S. and was used in many medications. -In 1886, Coca Cola was introduced, containing caffeine and cocaine. It was marketed as an alternative to alcohol as the temperance movement gained strength. -Public pressure forced the Coca-Cola company to remove the cocaine from the soft drink in 1903. -Cocaine abuse became widespread. President Taft declared it to be "public enemy number one" in 1910. -The 1914 Harrison Narcotic Act prohibited inclusion of cocaine (and opium) in over-the-counter medicines and specified other restrictions on import and sale. -Today cocaine is a Schedule II drug. -In the 1970s, cocaine use by snorting or IV injection increased. It emerged as the fashionable new drug for entertainers and businesspeople. -Recently, smoking "crack" cocaine has driven a new epidemic of cocaine use. -After cannabis, cocaine is the most frequently used illegal drug globally.

Pharmacokinetics of Cocaine: Metabolism

-Cocaine is broken down by enzymes in the blood and liver and is rapidly eliminated, with a half-life ranging from 0.5 to 1.5 hrs. -The "high" lasts only about 30 minutes. -Breakdown products persist and can be detected in the urine for several days.

Pharmacokinetics of Cocaine: Distribution

-Cocaine is sufficiently lipophilic (fat-soluble) that it passes readily through the blood-brain barrier. -Rapid entry into the brain is believed to be an important factor in the strong addictive properties of crack cocaine.

Deep brain stimulation is an FDA-approved treatment for the Parkinson's disease.

True

Cocaine Overdose

-Excessive activation of the sympathetic nervous system: o Increase in blood pressure o Increase in heart rate o Stroke Heart attack - Increased core temperature - Kidney failure - Psychosis, agitation - Convulsions, loss of consciousness Treatments -There is no specific pharmacological antidote for cocaine overdose -Drugs to reduce blood pressure, chest pain -Cooling with a fan or water misting -Benzodiazepines: to reduce agitation, to produce relaxation -Antipsychotics

Pharmacokinetics of Cocaine: Absorption

-Extremely rapid absorption occurs with IV injection and smoking (peak in seconds-minutes). -Absorption is slower with snorting and oral use (peak in 30-60 min).

Methamphetamine: Body Damage

-Heavy methamphetamine use is associated with cardiovascular problems: heart attack, elevated blood pressure, atherosclerosis, increased risk of stroke, and increased mortality rate. -There is evidence of premature aging.

Amphetamines' Abuse/ Addiction

-In the U.S, methamphetamine is currently abused more heavily than amphetamine. -Adverse effects of chronic use are similar for amphetamine and methamphetamine. -In the DSM-5, in the chapter "Stimulant Use Disorder" there is "Amphetamine-Type Substance Use Disorder" -Withdrawal symptoms o depressed mood o increased anxiety o sleep disturbances o cognitive deficits o reduced energy o increased appetite o craving for the drug

Amphetamines overdose

-Methamphetamine has a higher risk of overdose -Acute overdose of amphetamines can result in the following: o Seizures o Hypertension o Tachycardia o Heart failure o Hyperthermia o Psychosis o Hallucinations o Stroke o Death

Methamphetamine: Brain Damage

-Methamphetamine use causes damage to DA axons and terminals. -PET images of reduced striatal DAT binding associated with psychostimulant abuse

Mechanisms of Cocaine Action: Monoamine transporters

-Most of cocaine's actions can be explained by its ability to block reuptake of three transmitters: dopamine, norepinephrine, and serotonin. -These transmitters are cleared from the synaptic cleft by membrane transporters. Cocaine binds to the transporters and inhibits their function. -Inhibition of the transporters leads to increased neurotransmitter levels in the synaptic cleft and a corresponding increase in transmission at the affected synapses. -Cocaine binds most strongly (with highest affinity) to the serotonin transporter→the dopamine transporter→the norepinephrine transporter. -But blocking dopamine reuptake appears to be most important for cocaine's stimulating, reinforcing, and addictive properties.

Mechanisms of Cocaine Action: Cocaine and the Reward system

-Nucleus accumbens dopamine has been implicated in cocaine reward using paradigms that test for drug-seeking behavior as a model of relapse. o VTA→NAcc -Reinstatement of cocaine-seeking behavior in previously extinguished rats can be stimulated by microinjection of dopamine receptor agonists directly into the nucleus accumbens.

Long-term health effects of cocaine

-Snorting cocaine: o Loss of sense of smell o Nosebleeds o Chronically inflamed, runny nose o Damage the walls of the nasal cavity -Smoking crack o Lungs damages o Worsening of asthma -Less blood flow in the gastrointestinal tract→tears and ulcerations. -Many chronic cocaine users lose their appetite and experience significant weight loss and malnourishment. -Toxic effects on the heart and cardiovascular system. -Increased risk of stroke.

Preparation of Cocaine

-The cocaine alkaloid is extracted from coca leaves and then converted to a hydrochloride (HCl) salt and crystallized. -Cocaine HCl is water-soluble and thus can be taken orally, intranasally (snorting), or by IV injection. -It is not heat-stable and cannot be smoked. -Cocaine HCl can be transformed back into cocaine freebase. -Freebase cocaine is "freed" from its natural salt -Crack cocaine is a lower quality freebase, less pure. Dried, hardened chunks that make popping sounds when heated, a.k.a. "rock cocaine" -Freebase and crack can be vaporized through heating. Those vapors are inhaled. -The term freebasing refers to smoking cocaine. -Much faster effects, more addictive. -Crack can damage the lungs.

Amphetamine-Type Substance Use Disorder

-Treatment o Currently there is no effective pharmacotherapy for amphetamine addiction o Cognitive behavioral therapy is currently the most effective clinical treatment for psychostimulant addictions. o Daily aerobic exercise, especially endurance exercise (e.g., marathon running), is an effective supplemental treatment for amphetamine addiction

Amphetamines: Therapeutic uses

-Treatment of narcolepsy and ADHD. o Adderall -Because it suppresses appetite, amphetamine has also been used to treat obesity, but because of high abuse potential, is it now rarely used. -Methamphetamine hydrochloride, under the trade name Desoxyn, has been approved by the FDA for treating severe ADHD and obesity

The Amphetamines: Background and History

-Two similar plant compounds include: o Cathinone, the active ingredient in khat (or qat) (Catha edulis), an evergreen shrub native to East Africa and Middle East. o Ephedrine, from the herb Ephedra vulgaris, used in Chinese medicine for thousands of years. -In the 1920s, purified ephedrine was found to be a valuable anti-asthmatic agent -Ephedra-containing weight loss products became very popular in the 1990s. They were banned by the FDA in 2004. -Amphetamine is a synthetic compound that was discovered in an attempt to find substitute for ephedrine in 1887. -It did not have a pharmacological use until 1934, when Smith, Kline and French began selling amphetamine as an inhaler under the trade name Benzedrine as a decongestant -Methamphetamine was synthesized from ephedrine in 1893 -In 1919, methamphetamine hydrochloride, also known as crystal meth, was synthesized from ephedrine. -Amphetamine was first used to treat asthma. Later, amphetamines were used to increase mental efficiency, as study aid, diet aid, to keep pilots and troops alert during WWII, and to increase productivity in factory workers during WWII. -After WWII, usage soared, peaking around 1970, and since that time has largely been replaced by cocaine use, except for a recent surge in methamphetamine use. -After decades of reported abuse, in 1965 the US Food and Drug Administration banned Benzedrine inhalers, and limited amphetamine to prescription use, but non-medical use remained common. -Amphetamine and methamphetamine became schedule II controlled substances in the USA under the Controlled Substances Act in 1971.

Pharmacodynamics: Behavioral Effects of Cocaine

-Typical aspects of the cocaine "high" are feelings of exhilaration and euphoria, a sense of well being, enhanced alertness, heightened energy, and great self- confidence. -Increased sociability and talkativeness. -Heightened sexual interest and performance o Cocaine's legendary ability to enhance sexual prowess is highly exaggerated. -Anger o Increased aggressive behavior may contribute to the street violence associated with cocaine use. -Appetite suppression (anorexia) -Insomnia -Severe effects are most likely with high dosages, particularly in chronic users. o Hostility o Extreme violence o Incoherent speech o Paranoia o Restlessness o Tactile hallucinations: "coke bugs"

Treatment of Cocaine Use Disorder: Search for New Therapeutics

-Various dopaminergic drugs, including receptor agonists, antagonists, and uptake inhibitors are being studied -Other drugs being studied target other neurotransmitters, including serotonin. Repurposing of existing drugs o Modafinil: narcolepsy drug o Selective, and weak dopamine reuptake inhibitor -Repurposing of existing drugs o Disulfiram (Antabuse) has produced the most consistent reductions in cocaine abuse. o A popular drug to treat alcoholism, produces unpleasant symptoms like anxiety after taking cocaine. - Scientists do not yet know exactly how disulfiram reduces cocaine use, though its effects may be related to its ability to inhibit an enzyme that converts dopamine to norepinephrine.

Electronic cigarettes /Vaping

2003 Chinese pharmacist Hon Lik Vaping = using of e-cigarettes E-cigarettes don't contain tobacco. They do or do not contain nicotine Long-term health effects are not known They can help people to quit smoking...? 2019: A vaping-related lung injury epidemic January, 2020: FDA bans mint- and fruit-flavored vaping products but exempts menthol and tobacco

Mechanisms of Action

A cannabinoid receptor in the CNS was identified in 1988. Receptors occur in many brain areas. CB1 receptors→brain: areas involved in locomotor control, coordination, and memory, control of appetite CB2 receptors→in the body: liver, immune system, reproductive organs Endogenous neurotransmitter-like substance that acts on the receptors are the endocannabinoids. Two main endocannabinoids have been found: anandamide and 2-AG. They are retrograde messengers - carry information in the opposite direction from normal (i.e., postsynaptic to presynaptic). THC similar to endocannabinoids binds to cannabinoid receptors located presynaptically on the nerve terminal. They are metabotropic: they work via G proteins to inhibit presynaptic voltage-sensitive Ca2+ channels, and open K+ channels. As a result, cannabinoids decrease neurotransmitter release from the terminal. Retrograde signaling by endocannabinoids

Parkinson's Disease: Postmortem examination

A definitive diagnosis of PD is currently not possible until death Depletion of melanin due to the death of neurons in the substantia nigra in Parkinson's disease is typically indicated by loss of brown color in this area. Microscopic examination reveals presence of Lewy bodies.

Diagnosis: Delusions

A delusion is a belief held with strong conviction despite superior evidence to the contrary. Karl Jaspers, 1913. Three main criteria for a belief to be considered delusional certainty (held with absolute conviction) incorrigibility (not changeable by compelling counterargument or proof to the contrary) impossibility or falsity of content (implausible, bizarre or patently untrue) Examples: Delusion of persecution involving the individual's belief that others are spying on or planning to harm him. Delusions that thoughts are imposed from an outside source, such as outer space.

Parkinson's Disease: Brain Imaging

A marker or test that reliably indicates PD in live patients would be useful for determining treatment options. DaTscanTM was approved by the Food and Drug Administration in 2011 for striatal dopamine transporter visualization to assist in the evaluation of adult patients with suspected parkinsonian syndromes. But... dopamine transporter can be reduced in the other neurological diseases, it's too costly.

Nicotine:Route of Administration: Smoking

A typical cigarette contains 10 to 14 mg of nicotine, though no more than 1 to 3 mg actually reaches the smoker's bloodstream. The amount available depends on the smoker's behavior (e.g., number of puffs and length of each puff). Absorption can also depend on the chemical form of nicotine. Freebase is absorbed better than salt. From 1960s, Marlboro started to add ammonia to their cigarettes for a better absorption of nicotine. ➢Nicotine salt + ammonia→nicotine free base→higher absorption During smoking nicotine, tar and carbon monoxide are released. Tar contributes to the taste and smell of cigarette smoke

Nicotine is

Acetylcholine agonist

Caffeine: Physiological Effects

Acute caffeine intake leads to several physiological (sympathomimetic) effects increased blood pressure increased respiration rate enhanced water excretion (diuresis)

Therapeutic Uses of Cannabis

Addiction There's some evidence that it might reduce addiction and overdoses caused by other drugs Anxiety Marijuana was shown to relieve anxiety, depression in animal studies Human studies are sparce and inconclusive Pain Treatment Pain perception: transgenic mice that lack CB1 and CB2 receptors demonstrate hyperalgesia (increased pain sensitivity). Clinical evidence for cannabinoids as analgesics has not been convincing. Nabiximols (Sativex) is a cannabis extract Was approved in the UK in 2010 to treat pain and spasticity in multiple sclerosis patients (not yet approved in the U.S.). Glaucoma A number of years ago, Jamaican researchers prepared eye drops from cannabis extracts (trade name Canasol) for the purpose of reducing ocular pressure in glaucoma patients. However, Canasol was never licensed by the FDA for legal marketing in the United States. Research studies are inconclusive

A serious effect of heavy cocaine use, that might even be fatal, is

All of the above

Etiology of Schizophrenia

Although schizophrenia is an ancient disorder described as early as 1000 BC, its causes remain unknown. It is increasingly regarded as a neurodevelopmental disorder with a strong genetic component. Importance of genetics is shown by many family, twin, and adoption studies. Other factors must be involved as well Events during perinatal brain development can contribute to the occurrence of schizophrenia. These complications include brain insult during pregnancy or delivery caused by oxygen deprivation drug use infection Exposure to viral infection (e.g., measles) in the 2nd trimester. endocrine disorders severe malnutrition During adolescence, a period of significant brain development, excessive synaptic pruning can result in loss of cortical gray matter. Cannabis use?

Etiology of Parkinson's Disease

Although there are genetic and environmental risk factors, a definitive cause has not yet been discovered. Genetics 15% of PD patients reported an affected family member 5-10% of PD cases are linked to known mutations Aging Due to an aging population, researchers project the number of people with Parkinson's will double by 2040. Traumatic brain injury Researchers looked at the medical records of >300,000 veterans: mild TBI increases risk of PD 56 percent and moderate to severe TBI increases PD risk 83 percent. Environmental factors MPP+ 1976: Bad batch of synthetic heroin (containing MPTP contaminant) produced "instant" Parkinson's Disease. MPTP is oxidized to MPP+ that damages dopaminergic cells Paraquat is structurally similar to MPP+ is currently used as herbicide A known fast-acting inducer of Parkinson's disease in primate brains In 2011, a US National Institutes of Health study showed a link between paraquat use and Parkinson's disease in farm workers. Paraquat has been banned in the European Union since 2007. It can be used in US with a license. TCE Trichloroethylene: a solvent used to clean metals and remove stains Linked to Parkinson's by human and animal studies Still widely used and is detectable in high concentrations in groundwater. There were many lawsuits about TCE groundwater and drinking water contamination from industrial discharge.

Alzheimer's Disease

Alzheimer's disease (AD) is a chronic, progressive dementia disorder that is much more widespread than PD. Dementia is an acquired and persistent syndrome of intellectual impairment. Described in 1907 by Alois Alzheimer With the aging population, cases of AD are expected to increase. Alzheimer's is preceded by mild cognitive impairment (MCI). While all cases of AD are preceded by MCI, not all cases of MCI develop into AD. As MCI progresses to AD, the first symptom is general forgetfulness, leading to progressive loss of memory. Early symptoms Memory loss that disrupts daily life Misplacing things and losing the ability to retrace steps. Challenges in planning or solving problems Confusion with time or place. New problems with words in speaking or writing Decreased or poor judgment. Withdrawal from work or social activities. Changes in mood and personality Later stages Physiological problems: disrupted sleep, incontinence, and difficulty swallowing are seen. Psychiatric symptoms: delusions, hallucinations, depressed mood, and agitation (including violent outbursts). Communication skills are diminished. Advanced stagesMuch of our sense of "self" comes from our memory and cognitive function, which is lost in those with advancing AD. AD will eventually take away completely the ability to use language, interact with or even recognize family or friends, and live independently.

What area of the brain coordinates the components of anxiety and other emotions?

Amygdala

Brain imaging techniques are currently used to diagnose schizophrenia.

False

Cannabinoids: Tolerance and Dependence

Animals exposed to THC or other CB1 agonists develop tolerance to the behavioral and physiological effects of these compounds. It appears to involve a combination of desensitization and down-regulation of CB1 receptors. Desensitization of cannabinoid receptors produced by chronic THC exposure

Alzheimer's Disease: Potential Treatments

Antibodies to tau In preclinical phase = animal studies Antibodies could decrease levels of phosphorylated tau proteins in mouse brains. Coconut oil...?

Antipsychotics: Dependence

Antipsychotic drugs cause little or no tolerance, physical dependence, or abuse potential, and have high therapeutic index. Lack of abstinence syndrome may be due to long half-life. Haloperidol 20 hrs Olanzapine 30 hrs Aripiprazole 75 hrs

In schizophrenia, the most frequent hallucinations are

Auditory

Caffeine binds to the adenosine receptors and activates them (adenosine agonist)

False

Schizophrenia: Treatments

Before drug therapy, patients were confined to mental hospitals where treatment was limited to isolation or restraint, "shock" therapy using insulin- induced seizures or electrical current, and surgery such as prefrontal lobotomy. The dramatic decrease in the number of resident patients in state and municipal mental hospitals in the United States began after 1955, when psychoactive drugs were introduced into widespread therapeutic use.

Parkinson's Disease: Treatments

Behavioral Physical therapy is often helpful Speech therapy Exercise programs are recommended in people with Parkinson's disease. Drugs used in PD treatment include: Drugs that increase dopamine response L-Dopa Dopamine receptors agonists MAO inhibitors Levodopa (L-DOPA) a metabolite of the amino acid tyrosine, is the immediate precursor of dopamine in its metabolic pathway. L-DOPA can cross the blood-brain barrier, but dopamine cannot. L-DOPA is extremely effective, compared to other dopamine agonists. Side effects Motor fluctuations and dyskinesias: unwanted movements like severe tics Other treatments are also aimed at increasing dopamine signaling in the brain: Dopamine receptor agonists bind to dopaminergic post-synaptic receptors in the brain, have similar effects to levodopa Bromocriptine, apomorphine Side effects: impulse control disorders, such as compulsive sexual activity and eating, pathological gambling and shopping Monoamine oxidase B (MAO-B) inhibitors prevent breakdown of dopamine Selegeline Surgical Lesioning of the basal ganglia Deep brain stimulation of the basal ganglia Reduces rigidity and tremor

Nicotine use disorder : Treatment

Behavioral interventions include anti-smoking appeals in the media, Surgeon General's health warning on packages, and high taxes on tobacco products. Individual or group counseling programs can be successful, particularly if they provide social support and/or training in coping skills. The most common pharmacological intervention is nicotine replacement. Nicotine relieves withdrawal symptoms and is delivered in safer ways than smoking: nicotine gum and lozenges, transdermal patch, nasal spray and inhalers. The nasal spray and inhaler require a doctor's prescription, whereas nicotine gum, patches, and lozenges can be obtained over-the- counter (OTC). Bupropion (Zyban) Initially developed as an antidepressant. Weak antagonist at nicotinic cholinergic receptors →attenuates rewarding properties of nicotine Dopamine uptake inhibitor → reduces nicotine cravings and withdrawal symptoms Varenicline (Chantix) Partial agonist at high-affinity α4β2 nicotinic receptors expressed in the VTA and other brain areas→reduces nicotine cravings and withdrawal symptoms

Caffeine at the doses found in a cup of coffee

Blocks adenosine receptors

Marijuana: Elimination

Blood THC levels decline rapidly after smoking marijuana, but complete elimination from the body is much slower because of persistence in fat tissues. Half-life varies from few hours to 3-4 days The gradual movement of THC metabolites back out of fat stores means that urine screening tests can detect them more than 2 weeks after a single marijuana use.

All these are positive symptoms of schizophrenia except for

Blunted emotions

Diagnosis: Negative symptoms

Blunted emotions Emotions may be absent or totally inappropriate to the situation. Sudden and unpredictable changes of emotion are also common. Inability to experience pleasure Social withdrawal Lack of eye contact Lack of motivation Poverty of speech

Brain Imaging and Mental Disorders

Brain imaging techniques are currently not used to diagnose mental disorders Imaging is currently used for research purposes and is helping to identify the brain regions involved in different pathologies Adult-Onset Schizophrenia. PET scans of the brains of ( left) an adult schizophrenia patient and ( right) a person who does not have schizophrenia. Note the abnormally low blood flow in the prefrontal cortex at the top of the left scan. Brain functional changes include reduced function of the prefrontal cortex (PFC), called hypofrontality. Reduced blood flow is associated with less glucose use, which indicates how active the brain cells are. Imaging studies show less blood flow to the frontal cortex when people with schizophrenia are performing cognitive tasks, such as the Wisconsin Card Sorting Test (WCST). Eye-movement dysfunctions such as inability to visually track an object. Failure to track is also common in relatives of schizophrenic patients. The defective eye-tracking gene may be inherited along with the genes for schizophrenia.

Which of the following drugs is currently being used to help smokers withdraw from nicotine?

Bupropion (Zyban)

What drug increases dopamine level in the nucleus accumbens to the least extent or not at all

Caffeine

Caffeine: Mechanisms of Action

Caffeine has several biochemical effects, but only blockade of A1 and A2A receptors for adenosine has effects that operate at doses found in a cup of coffee. Caffeine = antagonist of adenosine receptors. Adenosine in the brain has neurotransmitter-like function and has been proposed as a key modulator in inducing drowsiness and sleep. Stimulant effect Antagonism of adenosine receptor also promotes release of dopamine, norepinephrine, and acetylcholine, which is responsible for caffeine's stimulant effects Breathing and blood pressure Caffeine blocks adenosine receptors in the medulla vasomotor and respiratory centers, which leads to increase in respiratory rate and constriction of blood vessels In addition to blocking of adenosine receptors, caffeine blocks GABAA receptors, stimulates Ca2+ release All these effects require higher doses, even into the toxic range.

Caffeine: Pharmacokinetics

Caffeine is normally consumed orally in beverages. 85-175 mg per cup of coffee Because caffeine is both water- and lipid-soluble, it readily crosses the blood-brain barrier Caffeine is absorbed by the small intestine within 45 minutes of ingestion. Peak blood concentration is reached within 1-2 hours Caffeine is converted to a variety of metabolites by the CYP450 in the liver. Average plasma half-life is about four hours (3-7 hrs). People who drink coffee repeatedly over the course of a day experience gradually rising plasma caffeine concentrations. In humans, approximately 95% of caffeine metabolites are eliminated through the urine.

THC (active ingredient in marijuana) binds to

Cannabinoid receptors

Cannabis or cannabinoid medications

Cannabis The FDA has not approved the cannabis plant for any medical use. FDA-approved medications CBD-based Synthetic THC

History of Marijuana

Cannabis probably originated in China. Medical and religious use can be traced to ancient China, India, Egypt and the Middle East. At the beginning of the 19th century, Napoleon's soldiers brought cannabis to France from Egypt in the form of hashish. It became popular with French writers and artists. Le Club des Hachichins (Hashish-Eaters' Club) in Paris. Théophile Gautier, Charles Baudelaire, Victor Hugo, Honoré de Balzac, and Alexandre Dumas. Hemp was grown in colonial America, but marijuana smoking probably came to the U.S. with Mexican and Caribbean immigrants in the early 1900s. Cannabis (Hemp) plant: High THC content → Marijuana, recreational use Low THC content (less than 0.3%) = industrial hemp In 1937, the Marijuana Tax Act instituted a national registration and taxation system aimed at discouraging all use of cannabis. It was overturned in 1969. Largely destroyed hemp industry United States Department of Agriculture lifted the tax on hemp cultivation during WW II

Cannabis use disorder

Cannabis use varies based on demographics. Research shows college students and young adults most commonly use cannabis: To socially conform (~40%) To experiment (~30%) For enjoyment (~20%) To manage stress or relax (~10%) Risk of dependence is related to drug use patterns. People who progress to daily use have a 10-20% probability of become dependent. Dependence is manifested as a difficulty in stopping one's use, a craving for marijuana, and unpleasant withdrawal symptoms (in heavy users). Irritability Increased anxiety Depressed mood Sleep disturbances Heightened aggressiveness Decreased appetite. These are similar to the symptoms of nicotine withdrawal.

Marijuana can be used as a study aid since it improves learning and memory.

False

Modafinil is an FDA-approved therapeutic for Cocaine Use Disorder.

False

Reserpine produces symptoms of depression because it increases levels of dopamine, serotonin and norepinephrine.

False

Caffeine: Chronic Use

Chronic caffeine use does lead to tolerance for some of the subjective effects and ability to disrupt sleep, as well as tolerance to the cardiovascular and respiratory effects of the drug. They may exhibit no trouble sleeping after consuming coffee right before bedtime. Withdrawal can include Headache and fatigue if they miss their morning cup of coffee Impaired concentration and psychomotor performance Mild anxiety or depression. People may develop an intense craving for coffee if they try to stop drinking it. Withdrawal symptoms can occur even in individuals who consume as little as 100 mg per day. Symptoms dissipate after a few days. Despite its ability to produce physical dependence, caffeine does not meet the criteria necessary to be considered addictive.

Nicotine use disorder

Cigarette Smoking 70% to 75% of current smokers in the United States would like to quit smoking, and about 40% to 45% of daily smokers actually attempt to quit each year. However, addiction to nicotine is so powerful that the success rate is very low. Two aspects of nicotine addiction Biomedical (abstinence syndrome, reinforcing properties of nicotine) Sociocultural

Nicotine: Acute Tolerance

Cigarette smokers undergo acute tolerance during the day. Acute tolerance dissipates during the night and mild withdrawal occurs. The 1st cigarette in the morning - the strongest effect Desensitization of midbrain DA neurons to continuous nicotine exposure

Lobotomy

Consists of cutting the connections to and from the prefrontal cortex Was used to treat psychiatric (and occasionally other) conditions from 1935 till mid-1950s Controversial procedure accompanied by frequent and serious side-effects

Alzheimer's Disease: Neurobiology

Cortical Degeneration Most affected areas are the entorhinal cortex, some parts of the frontal cortex, hippocampus, inferior temporal cortex, and posterior parietal cortex The primary sensory and motor areas are spared, as well as most of the brainstem, cerebellum, and spinal cord Cortical Degeneration Cerebral atrophy may be due in large part to the loss of dendritic arborization A significant loss of synapses (up to 45%) may be the basis for the cognitive deficits. Cellular pathologies and neuronal cell loss in AD are associated with: Pathological formations in the brain Amyloid plaques Located in the extracellular space Also found in aging brain Neurofibrillary tangles Located inside neurons Amyloid plaques = fibrous deposits around neuronal cells A plaque has a core of beta-amyloid protein surrounded by abnormal processes (dendrites or axons), with microglial cells or reactive astrocytes on the periphery. Molecules of beta-amyloid protein (or A-beta [Aβ]) are pathologically misfolded and tend to aggregate. Protein misfolding is a pathology common for many diseases (e.g., Parkinson's) Neurofibrillary tangles (NFTs) Fibrous inclusions in neuron cytoplasm. Pyramidal neurons are particularly susceptible. The misfolded tau protein is the main component. Tau protein maintains the stability of axonal microtubules.

Diagnosis

Criterion A. Characteristic symptoms: Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated). At least one of these should include 1-3. Six Diagnostic Symptoms Delusions Hallucinations Disorganized speech Positive symptoms Disorganized or Catatonic behavior Negative symptoms (e.g., blunted emotions) Cognitive deficits Criterion B. Social/occupational dysfunction Criterion C. Duration of 6 months Criterion D. Schizoaffective and mood disorder exclusion Criterion E. Substance/general mood condition exclusion Criterion F. Relationship to Global Developmental Delay or Autism Spectrum Disorder

Alzheimer's Disease: Treatments

Current treatments only help with the symptoms of the disease. There are no available treatments that stop or reverse the progression of the disease. Mental stimulation Physical exercise Balanced diet Pharmacological treatments Acetylcholinesterase inhibitors increase amount of acetylcholine in the synaptic cleft Donepezil, tacrine, galantamine NMDA receptor inhibitor Memantine Antibodies to A-beta protein ➢ Aducanumab (Aduhelm)➢Approved by the FDA on June 7, 2021 ➢Lecanemab (Leqembi)➢Approved by the FDA on January 6, 2023 ➢ Are the first approved drug that treat a cause of the neurodegenerative disease, rather than just the symptoms!

The psychedelic with the shortest duration of action is

DMT

Current information about schizophrenia diagnostics and treatment can be found in

DSM-V

THC metabolites can be detected during more than 2 weeks after a single marijuana use due to

Depot binding in fat tissue

What FDA-approved medication for obesity and severe ADHD contains methamphetamine?

Desoxyn

Cannabinoids: Acute Behavioral Effects

Effects of cannabinoid use vary depending on dose, frequency of use, characteristics of the user, and the setting in which use occurs. Subjective and behavioral effects of marijuana use can be separated into four stages: the "buzz," the "high," the stage of being "stoned," and the "come-down." The "high" is associated with feelings of euphoria and exhilaration, and a sense of disinhibition. Relaxation is the most commonly reported effect of being "stoned." Smoking marijuana can sometimes produce transient psychotic symptoms such as depersonalization, derealization, agitation, and paranoia. Expectation also plays a role in what effects the drug will produce, as shown by placebo studies. Marijuana negatively affects cognitive functions Decreased performance for a variety of verbal, spatial, time estimation, and reaction time tasks has been noted. Cannabinoids appear to interfere with all aspects of memory processing. Marijuana can affect psychomotor functioning under demanding task conditions, such as driving. Use of cannabis with or without alcohol is a risk factor in automobile accidents.

Nicotine:Metabolism, Withdrawal and Tolerance

Elimination half-life of nicotine is around 2 hours. To avoid withdrawal symptoms, smoking must occur repeatedly throughout the day. Frequent smoking leads to ever-increasing peak levels of nicotine during the day, since each dose builds on the residual nicotine from the previous one, but tolerance also builds.

Endocannabinoids and appetite

Endocannabinoids have been shown to play a significant role in hunger and eating behavior. Endocannabinoids enhance the incentive motivational properties of food and food-mediated reward. CB1 receptor antagonists reduce food consumption in animals and human subjects. CB1 antagonist may be useful in treating obesity.

FDA-approved medications

Epilepsy control Epidiolex, which contains a purified form of CBD derived from cannabis, was approved by the FDA in 2018 for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome, two rare and severe forms of epilepsy. Appetite Stimulation Dronabinol (Marinol), a synthetic form of THC, schedule III drug Dronabinol is used to treat loss of appetite and weight loss in people with HIV/AIDS. Dronabinol is used to treat nausea and vomiting in cancer chemotherapy patients.

Caffeine: High Doses/Overdose

Greatest health risks occur with highest doses. Caffeinism (1000 mg or more/day ) is characterized by restlessness, nervousness, insomnia, tachycardia, and GI upset. It can be difficult to distinguish from a primary anxiety disorder. More than 10 g can be lethal (~75-100 cups of coffee or a tablespoon of powdered caffeine supplements)

Diagnosis: Hallucinations

Hallucinations = a pathological form of perception Auditory hallucinations are frequent and are usually voices that are insulting or commanding. Visual hallucinations are rarer (in catatonic schizophrenia). More typical for hallucinogen use or epilepsy. Gustatory, olfactory, somatic sensations

Pathophysiology of Parkinson's Disease

Except for the resting tremor, motor symptoms are explained by loss of dopaminergic cells in the substantia nigra. As a result, there is insufficient amount of dopamine in the basal ganglia Malfunction of the basal ganglia results in the motor disturbances

Antidepressants decrease excessive serotonin release in the brain.

False

Marijuana Ingredients

Hemp also contains 70 unique compounds known as cannabinoids, plus more than 400 other identified compounds. THC = Δ9-tetrahydrocannabinol CBD = cannabidiol CBN = cannabinol The psychoactive compound THC, accounts for the use of cannabis as a drug. Marijuana potency (in terms of THC content) varies widely, depending on the genetic strain of the plant and growing conditions. Potency can be increased by preventing pollination and seed production by the female plants. This marijuana is called sinsemilla ("without seeds").

Caffeine use disorder?

ICD-10 (1992) is the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD), a medical classification list by the World Health Organization (WHO). "Caffeine addiction" was added to the ICD-10 The American Psychiatric Association's DSM-5 (2013) does not include the diagnosis of a caffeine use disorder... but describes "caffeine withdrawal" But... the DSM-5 lists "caffeine use disorder" in the "emerging models" section of the manual Many neuroscientists/clinicians think there is not enough evidence to support "caffeine addiction"

Graphic Warning Labels

In June, 2011, the FDA ordered the use of nine rotating warnings to cover 50 percent of cigarette packs with such images as diseased lungs and a cadaver lying on an autopsy table. Five tobacco companies, including R.J. Reynolds Tobacco and Lorillard Tobacco - the 2nd and 3rd biggest cigarette makers - filed a lawsuit claiming the mandate violated their First Amendment rights. U.S. District Judge Richard J. Leon has ruled for cigarette companies in three lawsuits against the FDA.

Caffeine: Behavioral Effects

In laboratory animals, low doses of caffeine have stimulant effects, but at high doses animals show reduced activity. People ingest caffeine mostly for its stimulating and fatigue-reducing effects. At high doses humans experience feelings of tension and anxiety. In controlled studies of regular caffeine users, humans report positive subjective effects such as enhanced vigor and ability to concentrate. Recent research suggests this is not just due to alleviation of withdrawal symptoms. Both caffeine consumers and nonconsumers benefitted from the caffeine treatment. Research has shown some benefit of caffeine to athletic performance. Possible mechanisms include increased force of muscle contraction, enhanced arousal and alertness, and reduced pain perception.

Cannabinoids: Reinforcement

In one study, regular marijuana users could discriminate THC-containing marijuana cigarettes from placebos with no THC, and all subjects preferred the marijuana with THC when given a choice. Animal studies have also demonstrated reinforcing properties. Lever pressing by squirrel monkeys for THC stopped when placebos were used. Mechanisms for reinforcement: Activation of the mesolimbic dopamine system: VTA→NAcc. Interactions between the cannabinoid and opioid systems may play a role in cannabinoid reward and reinforcement Opioid agonists enhance cannabinoid self-administration, and opioid antagonists have the opposite effect.

Marijuana: Chronic Behavioral Effects

In young people, amount of cannabis use is inversely related to educational performance. Some research supports the hypothesis that heavy cannabis use leads to persistent cognitive deficits, impairing school performance. Alternatively, poor school performance and rejection of mainstream values such as educational achievement may increase cannabis use Chronic cannabis use can also result in aimlessness, decreased motivation, lack of planning, and decreased productivity—amotivational syndrome. Heavy cannabis use over a long period may lead to impaired executive functioning for at least 2 to 3 weeks following cessation of use. Some data suggest that heavy, long-time users may continue to show impairment in decision-making, planning, and concept formation. It might negatively affect the prefrontal cortex. Imaging studies suggest that chronic marijuana use is associated with several kinds of abnormalities in the brain. Several studies have found a significant relationship between early heavy marijuana smoking and increased risk for later development of psychotic disorders such as schizophrenia.

Which of the following is not an effect of low to moderate doses of cocaine?

Incoherent speech

Which of the following is not an effect of caffeine reported by regular users?

Increased relaxation

Which of the following about nicotine poisoning is false?

It is frequently caused by smoking, because a pack of cigarettes contains several lethal doses.

Rapid (within hours) reduction in depression symptoms can be produced

Ketamine

What drug was approved by the FDA for treatment of depression in 2019?

Ketamine (as esketamine)

Which of the following would be a first-line treatment option for the Parkinson's disease?

L-Dopa

What hallucinogen is a synthetic compound?

LSD

Which of the following is not primarily used for treating major depression?

Lithium therapy

Pharmacodynamics Physiological effects of cocaine

Local anesthesia -At high concentrations, cocaine also inhibits voltage-gated Na+ channels in axons, blocking nerve conduction. -When applied locally, it acts as a local anesthetic by preventing transmission of signals along sensory nerves. -Medicinal use of cocaine: cocaine is used by health care professionals to temporarily numb the lining of the mouth, nose, and throat (mucous membranes) before minor surgeries, biopsies, etc. -Other, non-addictive, local anesthetics, procaine (Novocain) and lidocaine (Xylocaine), were developed from cocaine. Sympathomimetic effects -Cocaine is sympathomimetic—it produces symptoms of sympathetic nervous system activation: o Increased heart rate, vasoconstriction, hypertension, hyperthermia. -At low doses, these changes are usually not harmful to the individual. High doses, however, can be toxic or even fatal.

Nicotine: Chronic Tolerance

Long-term exposure to nicotine causes chronic tolerance, superimposed on the acute within-a-day tolerance. In one study, a high dose of nicotine elicited an aversive reaction with some symptoms of mild nicotine toxicity in nonsmokers but no such reaction in smokers.

The monoamine hypothesis of depression states that

Low levels of the monoamine neurotransmitters cause depression

Spread of Parkinson's Disease in the Brain

Olfactory structures Loss of sense of smell. Brainstem nuclei The raphe (serotonergic neurons) and locus coeruleus (norepinephrine neurons). Substantia nigra, amygdala. Motor symptoms begin at this stage. Temporal cortex, premotor cortex Other sensory cortices, motor cortex

Marijuana: Preparation

Marijuana is produced from flowering hemp Cannabis sativa Cannabis indica Cannabis ruderalis Marijuana is a mixture of dried and crumbled leaves, small stems, and flowering tops. Hemp seeds have been used for oil and bird food. It can be consumed orally, as in cookies or brownies, but is usually smoked in rolled cigarettes known as "joints," various kinds of pipes, or in hollowed-out cigars called "blunts." Hashish is a cannabis derivative that can be smoked or eaten. It can refer to a relatively pure resin preparation with very high cannabinoid content, or a solvent extract of leaves or resin. Hash oil is an alcohol extract. A drop is placed on a tobacco or marijuana cigarette.

DSM-5: Cannabis use disorder

Marijuana use typically begins in adolescence and peaks during young adulthood. If an individual has not yet tried marijuana by his or her mid-twenties, he or she is unlikely to begin at a later age. Probability of initiating marijuana use as a function of age

Mixing alcohol and energy drinks

Mixing alcohol and energy drinks is another concern. Though subjects may feel less intoxicated, alcohol-related impairment of psychomotor performance is still present ("wide-awake drunk").

Cannabis use disorder: Treatment

Most cannabis users do not seek treatment. Treatment in outpatient programs involves cognitive-behavioral therapy, relapse prevention training, and/or motivational enhancement therapy, but patients are very vulnerable to relapse. Some research on medications to relieve withdrawal symptoms has been done.

Nicotine: Metabolism/Excretion

Most nicotine is metabolized to cotinine by the liver enzyme cytochrome P450 2A6 (CYP2A6). Cotinine and other nicotine metabolites are excreted mainly in the urine.

Marijuana Ingredients: THC

THC was identified as the major active ingredient in 1964. Burning marijuana causes the THC to vaporize and enter the smoker's lungs in small particles. Effective dose and latency to onset of effects are influenced by the amount and potency of the plant used, and patterns of smoking (e.g., breathhold duration).

In non-smokers, nicotine improves cognitive functioning.

True

Parkinson's Disease: Symptoms

Motor Symptoms Tremor The most visible outward sign of PD is a that occur when limbs are relaxed and disappears with intentional movement. Rigidity Rigidity in the joints leads to a shuffling gait. Slowness of movement Postural instability Disorders of posture and impaired balance may cause patients to lean forward or backward when upright and have stooped posture. Motor Symptoms Akinesia Difficulty in initiating movement Involuntary movements Less movement of facial muscles reduces the range of facial expression possible. Many patients with PD are described as "stone-faced" Speech disturbances Decreased speaking volume, and monotonous speech or an uncontrollable acceleration of speech. Cognitive/emotional symptoms Impoverishment of feeling, motive, and attention Sometimes anxiety Cognitive slowing Parkinson's patients may also develop dementia - Parkinson's disease dementia (PDD). It is difficult to differentiate from comorbid Alzheimer's disease (AD).

Diagnosis: Disorganized or Catatonic behavior

Motor activity is reduced and characterized by inappropriate and bizarre postures, rigidity, or purposeless and stereotyped movements (e.g., rocking or pacing). At times, people with schizophrenia, particularly the paranoid type, can be agitated and violent. Catatonia = motor immobility and behavioral abnormality manifested by stupor Stupor = lack of critical cognitive function and a level of consciousness wherein a sufferer is almost entirely unresponsive and only responds to base stimuli such as pain

Schizophrenia: Search For A New Drug

Neither 1st nor 2nd generation antipsychotic drugs improve the cognitive impairments of schizophrenia. Some new approaches: 1. Enhancing acetylcholine. Clozapine is the only drug currently in use that enhances cognition; it increases acetylcholine release in the hippocampus. 2. Selectively enhance D1 receptor signaling in PFC with D1 agonists. Hypofrontality is associated with reduced DA function in PFC, especially at D1 receptors. 3. Enhancing glutamate activity at NMDA receptors might reverse negative and cognitive symptoms. Blocking NMDA receptors by ketamine can induce psychosis, cognitive deficit➔stimulating NMDA receptors can be beneficial

Neurodegenerative Diseases

Neurodegenerative diseases are incurable and debilitating conditions that result in progressive degeneration and/or death of nerve cells. Parkinson's Disease (PD) Alzheimer's Disease (AD) Huntington's Disease (HD) Amyotrophic Lateral Sclerosis (ALS) Stephen Hawking lost control of his skeletal muscles due to the ALS

Schizophrenia: Antipsychotic drugs

Neuroleptics is an older term for antipsychotic drugs. Typical antipsychotics: Motor side effects Chlorpromazine, Haloperidol Atypical antipsychotics/2nd generation Less side effects...? Clozapine, risperidone Effectiveness of these drugs has been demonstrated hundreds of times, especially for positive symptoms. Negative and cognitive symptoms are more resistant to treatment. The law of thirds—one third of patients respond well, one third shows significant improvements, but may relapse, and one third fails to respond. After initial recovery, antipsychotic drugs are prescribed as maintenance therapy to prevent relapse. Unpleasant side effects cause many patients to stop treatment. Psychotherapy and group therapy are important additions to drug therapy. Antipsychotic drugs block D2 receptors. A strong correlation exists between ability of a drug to displace a radio-labeled ligand on DA receptors and average clinical daily dose required. D2 receptors are located in the basal ganglia, nucleus accumbens, amygdala, hippocampus, and less in the cerebral cortex. PET images show replacement of radio-labels on striatal D2 receptors by different antipsychotic drugs. D2 receptor occupancy by antipsychotic drugs The drugs also bind to other receptors, but there is no clear relationship between clinical effectiveness and binding to serotonin, α- adrenergic, histamine, or D1 receptors.

Alzheimer's Disease: Diagnosis

Neurological symptoms Post-mortem examination of the brain Imaging tests AD cannot be definitively diagnosed until after death. A histopathologic confirmation including a microscopic examination of brain tissue is required for a definitive diagnosis. PET scan with PiB compound Imaging of pathological A-beta protein with the help of Pittsburgh compound B can potentially help with diagnosis

Parkinson's Disease: Diagnosis

Neurological symptoms Reaction to the anti-Parkinson's drug L-DOPA Improvement with L-DOPA = PD Post-mortem examination of the brain Imaging tests

Government Regulation of Tobacco/Nicotine Products

On May 5, 2016, the FDA announced that nationwide tobacco regulations now extend to all tobacco products, including e-cigarettes and their liquid solutions cigars hookah tobacco pipe tobacco In December 2019, the federal government raised the legal minimum age of sale of tobacco products from 18 to 21 years December 17, 2019: The U.S. FDA authorized the marketing of two new tobacco products manufactured by 22nd Century Group Inc. - Moonlight and Moonlight Menthol, which are cigarettes that contain a reduced amount of nicotine compared to typical commercial cigarettes. On average, conventional cigarettes have nicotine content of 10 to 14 mg per cigarette. Moonlight cigarettes have nicotine content between 0.2 to 0.7 mg per cigarette. They are less addictive, but still harmful! January 2020, the FDA issued a policy on the sale of flavored vaping cartridges. Only tobacco and menthol flavors are allowed.

Syndrome characterized by physiological arousal symptoms related to a traumatic event is called

PTSD

Nicotine Poisoning

Nicotine is a toxic substance that can be fatal at high doses. LD50 ~40-60 mg Such dose can not be reached via inhalation. A large number of poisonings occur among children who eat tobacco. Contact with tobacco in the field ("green tobacco sickness"), or insecticides that contain nicotine. However, two protections against death quick first pass metabolism through liver activation of vomiting center

Nicotine: Behavioral Effects

Nicotine is both a stimulant and a relaxant To separate the effects of nicotine from the behavioral aspects of smoking, subjects are given pure nicotine through injection, skin patches, or gum. In smokers, nicotine produces a calm or relaxed state In nonsmokers, it tends to elicit heightened tension or arousal, along with lightheadedness, dizziness, and even nausea. Nesbitt's Paradox Nicotine appears to cause an arousal in most studies. However, most smokers report that they smoke because smoking a cigarette relaxes them. Nicotine changes from stimulant to sedative with increase of dose Cognition Because acetylcholine plays an important role in aspects of cognitive functioning, several studies have examined effects of nicotine on cognitive function. In animals and humans alike, nicotine administration temporarily improves visual attention and working memory. Abstinent smokers given nicotine show enhanced performance on many kinds of cognitive and motor tasks. Continuous nicotine administration to nonsmokers enhances performance Cognition Some benefits for Alzheimer's disease: nicotinic receptor agonists. High smoking rates in people with schizophrenia (which includes significant cognitive dysfunction) may be an attempt to self-medicate their cognitive deficits.

Nicotine: Reinforcement

Nicotine on its own is reinforcing: humans and other animals will self- administer nicotine. The mesolimbic DA pathway from the VTA to the nucleus accumbens (NAcc) plays a key role in reinforcement. Lesioning the dopaminergic innervation of NAcc significantly attenuates nicotine self-administration High-affinity nicotinic receptors in the VTA stimulate firing of DA neurons, increasing DA release in the NAcc. Research in this area usually involves injected nicotine, but one study showed the same result when rats were inhaling cigarette smoke. Activation of midbrain DA neuron by tobacco smoke in the VTA (A) and substantia nigra (B)

Nicotine: Absorption

Nicotine readily passes through the absorbent surface of the lungs to the bloodstream. The nicotine first reaches the brain in about 7 seconds, which is approximately twice as fast as when the drug is administered intravenously. It is absorbed to a lesser extent through the mouth and nostrils when tobacco is chewed or snorted as snuff.

Nicotine: Mechanisms of Action

Nicotine works by activating nicotinic cholinergic receptors (nAChRs), one of the two subtypes of acetylcholine (ACh) receptor. They are ionotropic receptors made up of five subunits. High-affinity nAChRs are found in many parts of the brain, neuro- muscular junctions and in the ganglia of the autonomic nervous system.

Nicotine: Physiological Effects

Nicotinic receptors are abundant in the autonomic nervous system. Smoking can activate both sympathetic and parasympathetic systems, causing a wide range of physiological effects, including tachycardia and elevated blood pressure. This can increase risk of cardiovascular disease. Nicotine also reduces appetite and increases metabolic rate, resulting in weight loss. Smokers in general weigh less than nonsmokers. Quitting usually results in weight gain.

In the Schedule of Controlled Substances nicotine is located in

None of the above

What drug can be used to treat loss of appetite in cancer and AIDS patients?

None of the above

Parkinson's Disease

Parkinson's disease (PD) is a chronic, progressive, neurodegenerative disorder. First described by James Parkinson, an English doctor in 1817. Risk of PD increases with age, but an early-onset variant occurs before age 40. Several processes contribute to degeneration of neurons, including mitochondrial dysfunction, oxidative stress, inflammation, excitotoxicity, protein misfolding. Protein misfolding Protein folding is a physical process of the formation a highly organized molecular structure, with a characteristic, thermodynamically stable conformation, by a polypeptide chain In many neurodegenerative diseases proteins that do not folder properly (=misfolded proteins) produce pathological changes in the brain In PD, pathology is linked to misfolded α-synuclein In healthy cells, α-synuclein mediates vesicle movement at axon terminals. Lewy bodies Misfolded α-synuclein molecules tend to aggregate and form Lewy bodies Lewy bodies = dense, circular clusters (or aggregates) of protein within cells. Lewy bodies consist of α-synuclein and other proteins. They interrupt cell function and trigger apoptotic cell death. They can be detected during postmortem examination of PD brain. Lewy bodies are formed by abnormal accumulations of proteins

Pathology = Study of Disease

Pathology addresses the following components of disease: cause/etiology mechanisms of development (pathogenesis) structural alterations of cells, tissues and organs functional alterations of cells, tissues and organs (pathophysiology) the consequences of changes (clinical symptoms)

Cannabinoids: Acute Physiological Effects

Physiological responses includeincreased blood flow to the skin and flushingincreased heart rateincreased hunger

Caffeine: Therapeutic Uses

Potentiates analgesic properties of aspirin and acetaminophen. It is included in some OTC pain medications Anacin =Aspirin +Caffeine Excedrin = Aspirin +Paracetamol +Caffeine Effective in treatment of apnea in premature newborns. Caffeine can normalize breathing.

Classification of Mental Disorders: DSM-5

Psychiatric disorders are listed in the DSM= The Diagnostic and Statistical Manual of Mental Disorders It is published by the American Psychiatric Association (APA) 1.2 Section II: diagnostic criteria and codes 1.2.1Neurodevelopmentaldisorders 1.2.2Schizophreniaspectrumandotherpsychoticdisorders

What scheduled drug is currently in clinical trials as a potential treatment for depression

Psylocybin

Bar graph on slide "Hallucinogenic Drugs: Mechanism of Action" shows that effects of psilocybin are blocked by

Serotonin receptor antagonists

Which of the following is not a typical symptom of schizophrenia?

Severe anxiety

Caffeine: Background

The major source of caffeine is coffee beans, the seeds of the plant Coffea arabica. Caffeine is also present in tea, chocolate, etc. Caffeine is one of the most widely used drugs in the world.

Characteristics of Schizophrenia

The most typical feature of schizophrenia is psychosis severe distortions of reality, disturbances in perception, intellectual functioning, affect, motivation, social relationships, and motor behavior relapsing episodes They can be so incapacitating that voluntary or involuntary hospitalization is required.

Negative symptoms of schizophrenia are the most resistant to antipsychotic drugs.

True

One of the most reliable physiological effects of cannabis use in humans is increased hunger.

True

Patients with anxiety disorders can have alterations in the volume of the amygdala.

True

Which of the following is not a symptom of opioid (including fentanyl) overdose?

Rapid heart rate

Neurobiology of Schizophrenia: Structural Changes

Recent advances in technology have revealed abnormalities of brain structure and function in individuals with schizophrenia. Many studies show cerebral atrophy and enlargement of fluid-filled ventricles following cell loss. Numerous studies show that hippocampal cells of patients with schizophrenia are more disorganized than those of healthy subjects

Neurobiology of Auditory Hallucinations

Reduced gray matter volume in the temporal lobe Hyperactivation of temporal lobe regions due to impairment of pre- frontal executive inhibitory functions.

Etiology of Alzheimer's Disease

Risk factors for AD include: Advanced age Family history of dementia or AD: genetic predisposition (1-5%) Obesity, untreated hypertension, high cholesterol, stress, and sedentary lifestyle Head trauma or hypoxic brain injury, depression, bipolar disorder, or PTSD Environmental toxins (e.g., aluminum)...? A slow-acting virus

The first choice for treating chronic anxiety disorders are

SSRIs

In the Schedule of Controlled Substances, methamphetamine is placed in

Schedule II

On the Schedule of Controlled Substances, ketamine is placed in

Schedule III

Schizophrenia: Cognitive deficits

Schizophrenia is a thought disorder, characterized by illogical thinking, lack of reasoning, and inability to recognize reality. Cognitive symptoms - impaired working memory, executive functioning, and attention. Many cognitive deficits impair the ability to function at school, jobs, etc.

Which of the following is not a hallucinogenic drug?

Serotonin

Antipsychotics: Side Effects

Side effects depend on which receptor the drug binds to. Dopamine pathways in the brain are important for understanding drug action: Nigrostriatal pathway (Substantia nigra→Striatum): Motor side effects. Hypothalamus→Pituitary gland pathway (regulates pituitary hormone secretion): Hormonal side effects. Parkinsonism: motor side effects that resemble symptoms of Parkinson's disease. tremors akinesia (slowing or loss of voluntary movement) muscle rigidity restlessness (inability to sit still) loss of facial expression. Parkinson's is caused by loss of cell bodies in the substantia nigra, which gives rise to the nigrostriatal pathway. Lack of DA function in the striatum causes the motor effects. Tardive dyskinesia (TD) is characterized by stereotyped involuntary movements, particularly of the face and jaw, quick and uncontrolled movements of the arms and legs, and other motor effects. Incidence of TD increases with duration of treatment. Neuroendocrine effects: decreased sex drive no menstruation increased prolactin release inhibition of growth hormone release Metabolic effects: weight gain Inability to regulate body temperature Neuroleptic malignant syndrome (NMS) is serious and life- threatening. Characterized by fever, rigidity, altered consciousness, and autonomic nervous system instability (including rapid heart rate and fluctuations in blood pressure). Rapid diagnosis and immediate action have significantly reduced mortality risk.

Marijuana: Administration and Absorption

Smoking Smoking marijuana is the quickest way to absorb the THC, with blood levels peaking between 9 and 10 minutes into a smoke session. THC is easily absorbed by the lungs, and blood plasma levels rise quickly. Eating marijuana in the form of "edibles" Is thought to yield peak THC blood levels within 1 to 5 hours post-ingestion. Poor absorption results in low and variable plasma levels, probably due to degradation in the stomach, first-pass metabolism.

Diagnosis: Disorganized speech

Sometimes called "word salad" Speech can follow grammatical rules, but the content makes little sense Frequent change of conversation topics with no connection between sentences

Parkinson's Disease: Future Treatments

Stem cell treatment Introducing new dopamine cells into the brain may help replace lost cells in PD. Stem cells can be used in the lab to generate many other types of cells, including dopamine cells. October 2019 the group of Dr.Takahashi in Kyoto completed the first transplant into human brain. They used induced pluripotent stem cells (iPS cells) are derived from adult cells (usually from skin or blood) and can be manipulated to act like stem cells In US, Dr.Studer is about to move to clinical trials with dopamine cells derived from human embryonic stem cells.

Schizophrenia: Onset

Symptoms most often begin during the late teenage years and early twenties, but there are gender differences—after age 36, more women than men experience their first episode.

Nicotine: Background and History

The Maya, who lived in what is now Southern Mexico and Central America, had a great civilization which was at its height about 2,000 years ago. Tobacco smoke initially was used by Maya in religious ceremonies, rituals and in medicinal practices. They passed on the custom of smoking to almost every other Indian group in North and South America. Tobacco was first encountered by Europeans when Columbus reached the West Indies. Tobacco smoking was quickly taken up by Europeans. In the 1600s, England commercialized tobacco growing in the Virginia colony. Cigarettes began to be used in Europe in the mid nineteenth century. Their popularity in the United States exploded over the next 30 years new methods of curing tobacco leaves that improved flavor invention of the cigarette machine, which increased production dramatically. During World War II (1939-1945), cigarette sales are at an all time high. Cigarettes were included in a soldier's C-Rations (like food). Tobacco companies sent millions of cigarettes to the soldiers for free, and when these soldiers came home, the companies had a steady stream of loyal customers. In 1971, television ads for cigarettes are finally taken off the air in the U.S. AMA: tobacco = health hazard, a cause for cancer, as well as other respiratory and circulatory diseases. Nicotine was first isolated in 1828. It constitute about 5% of the weight of dry tobacco leaves Nicotine is an oily water-soluble substance, a colorless liquid which changes color to yellow and brown on contact with air or slowly with light. It's odorless and tasteless. And that's why it can be used for vaping in combination with different flavors. It is a potent neurotoxin with particular specificity to insects; therefore, nicotine was widely used as an insecticide.

Nicotine use disorder: Cigarette Smoking

The amount of cigarette smoking in the United States has varied over the past 100 years. Smoking increased dramatically up to the 1960s. Declines since then are related to the Surgeon General's reports on health consequences, antismoking ads, high cigarette taxes, and societal disapproval of smoking.

Cigarette Smoking: Health Effects

The deleterious health effects stem from carbon monoxide from burning tobacco, tar, and nicotine Nicotine enters the smoker's lungs on tiny particles called tar, a complex mixture of chemicals, some of which are known to be carcinogenic. Other chemicals that can be found in cigarette smoke include Ammonia - found in toilet cleaners. Acetone - found in nail varnish remover. Cadmium - a highly poisonous metal used in batteries. Napthtalene - used in moth balls. Cyanide - used in the gas chambers. Formaldehyde - used to preserve dead bodies. Smoking is a major cause of illness and premature death. Cigarette smoking is the major preventable cause of death among Americans. Increases the risk for many life-threatening illnesses: cancer, cardiovascular disease, and respiratory disease.

Neurochemical Models of Schizophrenia

The dopamine hypothesis: excess DA function results in positive symptoms of schizophrenia. It was suggested by the fact that amphetamine (that increases dopamine) can produce a psychotic reaction in healthy individuals that can be reversed by DA antagonists. There is a strong correlation between D2 receptor blockade and reduction of schizophrenia symptoms. DA imbalance hypothesis reduced DA function in mesocortical neurons (negative symptoms and impaired thinking) = D1 receptors excess DA function in mesolimbic neurons (positive symptoms) = D2 receptors Hypoglutamate hypothesis Blocking NMDA receptors with PCP or ketamine produces schizophrenia-like symptoms in healthy individuals and exacerbates symptoms in schizophrenic patients. PCP and ketamine produce both the positive and negative symptoms. Antipsychotic drug clozapine interacts with the glutamate receptor and increases glutamate levels in the PFC of rats

Energy Drinks

The increased popularity of energy drinks may result in more caffeinism. Overconsumption of energy drinks can have serious health effects, including agitation, tremors, seizures, damage to the liver and kidneys, GI distress, respiratory problems, cardiac arrhythmia, tachycardia, and even heart failure.

Tobacco preparation for recreational use

The leaves of the plant contain 80-85% water. Curing is the process that brings out the aroma and flavor of each variety of tobacco. After the curing cycle, there is essentially no water left. The actual nicotine content of the cured tobacco leaf may reach as much as 6.17%. Tobacco for chewing (smokeless tobacco): One to three high-quality leaves are braided and twisted into a rope while green, and then are cured in the same manner as other tobacco. Tobacco snuff is made by grinding dried tobacco leaves to a very fine powder. Tobacco for burning is made into cigars, cigarettes, or pipe tobacco. Snus was invented in in early 18th-century Sweden. Placed between the upper lip and gum for extended periods. Snus is not fermented.

Marijuana: Adverse Health Effects

There are no reports of death from overdose. Smoking marijuana can damage lungs with chronic use: smoke contains tar, other carcinogens, carbon monoxide, etc. THC vaping can damage lungs acutely Immune system suppression THC may affect reproductive functions: In women it can affect ovulation In men, regular smoking has been shown to decrease testosterone levels and sperm counts. Animal work has demonstrated pregnancy failure, abnormal embryonic development, and even fetal death with THC administration.

All of the following are antipsychotic drugs except

They are all antipsychotic drugs

Which of the following regarding people who are tolerant and/or dependent on caffeine in coffee is FALSE?

They are considered addicted to caffeine.

Which of the following about hallucinogenic mushrooms is false?

They produce mescaline.

Caffeine: Reinforcement?

Until recently, it was though that caffeine does not increase dopamine level in the nucleus accumbens 2002: in freely moving rats caffeine can preferentially increase extracellular levels of dopamine in the Nacc. These effects could be reproduced by the administration of a selective adenosine A1 receptor antagonist but not by a selective adenosine A2A receptor antagonist.

In animal studies (shown on slide #26), inhalation of tobacco smoke increased firing of

VTA neurons

Which of the following is not a symptom of the nicotine abstinence syndrome?

Weight loss

Which of the following about serotonin syndrome is false?

While frightening, the syndrome is not life-threatening.

In what country coffee trees were first cultivated on plantations

Yemen

On the Schedule of Controlled Substances, marijuana is listed as

a schedule I drug

Tardive diskynesia is

a side effect of antipsychotics

Monoamine oxidase inhibitors increase response produced by

all of the above

Nicotine

all of the above

The effects of cocaine can be mimicked by

amphetamine

Dopamine hypothesis of schizophrenia is supported by the fact that

antipsychotic drugs block dopamine receptors

All of the following were treatments used for schizophrenia prior to 1955 except

antipsychotics

Dyskinesia (impaired control of movement) is a common side effect of

antipsychotics

People do not abuse

antipsychotics

Amphetamine and related psychostimulants in the amphetamine-like family

are psychomotor stimulants

What drugs have mechanism of action similar to alcohol

barbiturates

Which of the following toxic substances is not produced or released during the smoking of tobacco?

carbon dioxide

All of the following are effects that have been correlated with chronic use of marijuana except

development of anxiety disorders.

Re-experiencing the hallucinations sometime after drug use has stopped is called

flashbacks

The most consistent functional abnormality in the brains of individuals with schizophrenia is

hypofrontality.

Observation that blocking NMDA receptors with PCP or ketamine produces schizophrenia-like symptoms supports:

hypoglutamate hypothesis of schizophrenia

Psychoses are characterized by all of the following except

increases in intelligence.

Caffeine

is rapidly and completely absorbed through the gastrointestinal tract

Why crack cocaine is more addictive that cocaine hydrochloride?

it can be smoked

Cocaine acts in the nervous system by blocking _______ and _______.

monoamine transporters; voltage-gated sodium channels

Schizophrenia is treated with

none of the above

Cannabinoids could be used therapeutically to treat all of the following except

obesity

Hallucinogenic drugs are not considered to be addictive in the "classic sense" of the word because

people who use these drugs generally do not experience craving, withdrawal symptoms or strong dependence.

Nicotine replacement therapy has employed all of the following formulations except for

pill

Caffeinism (1000 mg or more/day ) is characterized by the following except

relaxation

Amphetamine and methamphetamine affect synaptic transmission by

releasing dopamine from synaptic vesicles

Research has shown that human subjects receiving high doses of ketamine develop symptoms of

schizophrenia

Parkinsonian symptoms in schizophrenia include all of the following except

sedation

Psychedelic effects can be produced

serotonin agonists

For nicotine the fastest way to reach the brain through

smoking cigarettes

Acute tolerance to nicotine

takes place in the course of a single day.

Anti-anxiety effect of barbiturates is based on the following mechanism of action

they activate GABA receptors and increase inhibition in the brain

Green tobacco sickness occurs from the following route of nicotine administration

transdermal