Biological Psychology Test 3

Distribution and Elimination of Drugs From the Body

In some cases, drugs can diffuse across cell membranes; in other cases, a drug must cross the blood-brain barrier in order to produce an effect. The speed with which the body metabolizes a drug is a factor in how long the effect of the drug will last.

Injection

Intramuscular (IM) injection—Injection of a drug into a muscle, usually the shoulder, upper arm, thigh, or buttocks. Intraperitoneal (IP) injection—Injection of a drug through the abdominal wall into the peritoneal cavity (space surrounding major organs).

Mechanisms of Psychedelic Action

Lysergic acid diethylamide is structurally similar to serotonin and is a potent serotonin agonist that binds to some serotonin receptors, especially 5-HT2A receptors, in the brainstem, medial prefrontal areas, the anterior cingulate cortex, and the somatosensory cortex. Activation of the pathways from the brainstem to the medial prefrontal cortex and the somatosensory cortex can be sufficient to initiate hallucinations independent of sensory input. Phencyclidine (PCP) is a antagonist of NMDA glutamate receptors. Blocking of glutamate activity in the medial prefrontal cortex significantly increases dopamine and serotonin activity in the medial prefrontal cortex. The psychedelic experience produced by PCP is thought to be due to this increased activity in the medial prefrontal cortex. Methylenedioxyamphetamine (MDMA) is a potent dopamine agonist. The hallucinogenic effect of MDMA is believed to be due to the increased dopamine activity in the medial prefrontal cortex. The euphoric and reinforcing effect of the amphetamines is due to increased dopaminergic activity in the mesolimbic pathway that projects from the ventral tegmental area to the nucleus accumbens.

Dangers of Marijuana Use

Marijuana use has been found to have a deleterious effect on working memory. Decreased GABA inhibition of glutamate activity in the prefrontal cortex impairs the storage and recall of an experience. Further, THC in marijuana attaches to cannabinoid receptors in the hippocampus and suppresses glutamate activity, which also contributes to the impairment of memory storage and retrieval. Marijuana also has been found to disrupt motor control and performance. THC attaches to cannabinoid receptors in the basal ganglia and inhibits the release of glutamate into the synaptic cleft, which causes impaired movement and performance. Tolerance can develop with repeated use of marijuana, but is generally only observed with high doses. Physical dependence can lead to withdrawal that includes depressed mood, aggressiveness, and irritability, but not in all marijuana users.. Psychological dependence can occur in environments associated with drug use, but only in some marijuana users. While repeated marijuana use can lead to addiction, its potential for abuse and dependency appears less than other psychoactive drugs. The use of marijuana leads to a vulnerability to the same types of cancers and respiratory problems as cigarette smokers

Treatment of opiate addiction:

Methadone Naltroxone Buprenex Suboxone

Opiates classified by origin

Natural Origin Semi-synthetic Synthetic.

Mechanisms of nicotine action

Nicotine has an agonist effect on cholinergic neurons. Nicotine binds to ionotrophic cholinergic (nicotinic) postsynaptic receptors and open Na + ion channels and to metabotropic presynaptic receptors and open Ca + + ion channels, thereby increasing the release of acetylcholine into the synaptic cleft. Nicotinic cholinergic receptors are widely distributed in the peripheral and central nervous systems. In the peripheral nervous system, nicotine increases cholinergic activity at the neuromuscular junction, which can produce muscle tremors. Increased cholinergic activity in the central nervous system produced by nicotine increases cortical arousal and improves cognitive functioning, including improved attention and memory. Nicotine also has an agonist effect on dopaminergic neurons by increasing the release of dopamine into the synaptic cleft. Further, nicotine decreases monoamine oxidase synthesis, which serves to prolong activity in dopaminergic neurons. Nicotine has a euphoric and reinforcing effects, which are due to increased dopaminergic activity in the mesolimbic pathway that projects from the ventral tegmental area to the nucleus accumbens. The motor-stimulating effects of cocaine is due to increased dopaminergic activity in the pathway from the substantia nigra to the basal ganglia

Long term effects of opiate use

Opiate use can be highly addictive, with tolerance developing very quickly with frequent use. Side effects include constipation, insomnia, irritability, and muscle spasms. Severe side effects include respiratory depression, confusion, and cardiac arrest. The withdrawal symptoms include chills, diarrhea, nausea, and sweating, with tremors and intense cramps occurring during extremely intense withdrawal that can last for several days. Physical dependence results from the suppression of endorphin production that occurs with repeated opiate use. Psychological dependence occurs as a result of conditioning of withdrawal to the environment associated with drug use.

Classification of Psychoactive Drugs

Opiates Psychostimulants Depressants Psychedelic drugs Marijuana

Semi synthetic origin opiates

Opiates that are combinations of natural opiates and other chemicals. Heroin Vicodin (hydrocodone and acetaminophen) Oxycontin/Percocet (oxycodone and acetaminophen)

Synthetic origin opiates

Opiates that are manufactured in the laboratory. Demerol and Darvon.

Natural origin opiates

Opium Morphine Codeine Thebaine

Routes of Ingestion

Oral ingestion Injection Inhalation Absorption

The Mechanisms of Opiate Action

Painful experiences, such as intense tissue pressure, extremes in hot or cold temperature, inflammation caused by tissue injury or infection, chemical irritation, or damage to skin, activate somatosensory pain receptors in the skin. Pain messages travel along myelinated A fibers or unmyelinated C fibers to the dorsal root ganglion. Myelinated A fibers transit fast or sharp localized pain signals, whereas unmyelinated C fibers transit delayed or slow, dull pain. Sensory neurons synapse with nociceptive neurons in the dorsal root ganglion. The axons of the nociceptive neurons terminate in the dorsal horn of the spinal cord, where substance P is released onto the ascending spinothalamic pathway, which travels to the thalamus, somatosensory cortex, and the anterior cingulate cortex. Ascending messages from the spinothalamic pathway project to the periqueductal gray area (PAG) of the pons, where a descending pain pathway originates. Neurons in the PAG project to the locus coeruleus. Excitatory adrenergic neurons in the locus coeruleus synapse with opiate interneurons in the spinal cord, which results in presynaptic inhibition of substance P to the ascending spinothalamic pathway. Opiate receptors found in the cingulate cortex, thalamus, nucleus accumbens, and amygdala also act to modulate the experience of pain.

Types of psychedelic drugs:

Peyote Mescaline Psilocybin Lysergic acid diethylamide (LSD)—A powerful synthetic psychedelic drug, also known as acid. Phencyclidine (PCP)—A powerful synthetic psychedelic drug, also known as angel dust. MDMA

Oxycontin/Percocet (oxycodone and acetaminophen)

Powerful semi-synthetic opiates derived from thebaine

Medical Uses of Marijuana

The FDA considers marijuana a Schedule I narcotic or a drug without any medical uses. Yet, drug companies have created several synthetic THC drugs that can be obtained by prescription. Dronabinol (Marinol) is a synthetic THC that was orginally listed as Schedule II drug, but was recently reclassified as a Schedule III drug. Marinol has been approved by the FDA to treat nausea and vomiting associated with cancer chemotherapy and radiation therapy. However, advocates for the medical use of marijuana claim that Marinol is not as effective as marijuana because synthetic drugs do not contain about 60 cannabinoids that are present in marijuana. Nabinone is a synthetic THC approved by the FDA as a Schedule II drug to treat nausea and vomiting related to cancer therapy as well as to treat anorexia and weight loss associated with AIDS. Other medical conditions that may be helped by marijuana include a vision-threatening increase in ocular pressure associated with glaucoma, chronic and phantom limb pain, withdrawal symptoms associated with opiate and alcohol addictions, and muscle spasms in patients with multiple sclerosis, Huntington's Disease, and Parkinson's Disease

Absorption

The administration of a drug through the lungs.

Inhalation

The administration of a drug through the lungs.

Oral ingestion

The administration of a drug through the mouth. The drug dissolves in the fluids of the mouth, esophagus, or stomach and is carried to the intestines, where it is absorbed into the bloodstream.

Half-life

The amount of time required for the body to metabolize half of a drug. The longer the half-life, the longer a drug continues to have a physiological effect.

Mechanisms of amphetamines:

The amphetamines are potent dopaminergic agonists. This agonist action occurs by 1) increased dopamine release from the presynaptic membrane and 2) binding to the vesicular transporter causing dopamine to be released from the synaptic vesicles and then transported to the synaptic cleft by reversing dopamine reuptake. The euphoric and reinforcing effect of the amphetamines is due to increased dopaminergic activity in the mesolimbic pathway that projects from the ventral tegmental area to the nucleus accumbens. The motor-stimulating effects of the amphetamines is due to increased dopaminergic activity in the pathway from the substantia nigra to the basal ganglia. The amphetamines also are potent noradrenegic agonists. This agonist action occurs by 1) increased norepinephrine release from the presynaptic membrane and 2) blocking of the reuptake transporters. The arousing influence of the amphetamines is due to the increased noradrenergic activity in the mesocortical pathway from the ventral tegmental area to the prefrontal cortex. The enhanced cognitive functioning produced by the amphetamines also is due to increased norepinephrine activity in this pathway. Increased noradrenergic activity in the pathway from the locus coeruleus to the prefrontal cortex also contributes to the effects of amphetamine on arousal and cognitive functioning. The anorexic effect of the amphetamines is due to the increased expression of the appetite-suppressing peptide cocaine and amphetamine-related transcript on the ventromedial hypothalamus.

Long term Effects Of Barbiturate Use

The barbiturates are highly additive. Tolerance to the barbiturates develops quickly. Side effects of the barbiturates include marked sedation, cognitive impairments, retarded motor movements, and slurred speech. Physical dependence to the barbiturates makes it difficult for the individual to stop using the drug. Withdrawal symptoms include anxiety, restlessness, insomnia, dizziness, tremors, and seizures. Psychological dependence occurs a result of conditioning of withdrawal to environments associated with drug use.

Mechanisms of Barbiturate Action

The barbiturates bind to a specific GABAA receptor, which allows GABA released into the synaptic cleft to bind more effectively and for longer periods of time. GABA acts on the GABAA receptor to open up Cl- ion channels, thereby hyperpolarizing the postsynaptic membrane of a glutamate neuron. As GABA is a glutamate antagonist, hyperpolarizing the postsynaptic membrane decreases excitatory activity in the nervous system. The sedating effects of the barbiturates are mediated by GABA receptor inhibition in the locus coeruleus, the amygdala, the hypothalamus, and cingulate cortex

Mechanisms of Benzodiazepine Action

The benzodiazepines bind to a specific GABAA receptor, which allows GABA released into the synaptic cleft to bind more effectively and for longer periods of time. GABA acts on the GABAA receptor to open up Cl- ion channels, thereby hyperpolarizing the postsynaptic membrane of a glutamate neuron. As GABA is a glutamate antagonist, hyperpolarizing the postsynaptic membrane on a glutamate neuron decreases excitatory activity in the central nervous system. The calming or anxiolytic effects of the benzodiazepines are mediated by GABA receptor inhibition in the locus coeruleus, the amygdala, the hypothalamus, and cingulate cortex.

Long-tern Effects Of Benzodiazepine Use

The benzodiazines are highly additive. Tolerance to the benzodiazines develops quickly. Side effects of the benzodiazepines include marked sedation, cognitive impairments, retarded motor movements, and slurred speech. Physical dependence to the benzodiazepines makes it difficult for the individual to stop using the drug. Withdrawal symptoms include anxiety, restlessness, insomnia, dizziness, tremors, and seizures. Psychological dependence occurs a result of conditioning of withdrawal to environments associated with drug use.

Dangers of Psychedelic Drugs

The biggest danger is the unpredictability of effects. On some occasions the psychedelic experience is positive. On other occasions, it can be very unpleasant. Flashbacks, or a hallucination re-experienced long after the original "trip", can be quite unsettling. Tolerance is generally observed with frequent use, while there is no evidence of physical dependence or withdrawal. Neurological problems such as memory deficits can occur with PCP use, while toxic reactions to MDMA include accelerated heart rate, sweating, and hypothermia, which can be life-threatening.

Substance dependence

The compulsive use of a substance.

Opiate Addiction

The concordance rate for identical twins is about 13.3% and for fraternal twins is about 2.9%.

Psychostimulant Addiction

The concordance rate for identical twins is about 14.1% and for fraternal twins is about 5.3%.

Alcohol Addiction

The concordance rate for identical twins is about 47.9% and for fraternal twins is about 32.8%.

Alcohol Barbiturate/Benzodiazepine Interaction

The consumption of alcohol with a barbiturate or benzodiazepine can be extremely dangerous. When alcohol is taken in combination with either a barbiturate or benzodiazepine, they have a synergistic effect. The more alcohol and either a barbiturate or a benzodiazepine are taken together, the worse the interaction, which can cause severe sedation, resulting in mental confusion, a loss of consciousness, and death.

Incidence of addiction:

The lifetime prevalence rates for addiction is approximately 15% (not counting tobacco) and over 45% (counting tobacco). The 2004 National Survey on Drug Use and Health estimated that 22.5 million persons aged 12 or older, or 9.4 percent of the total population, met criteria for an addiction in the past year. Some drugs are more addictive than others with a higher percentage of users of cocaine (27.8%) and heroin (67.8%) meeting the criteria for addiction than did users of marijuana (17.8%).

Mescaline

The psychoactive ingredient in peyote.

Two pathways in the mesolimbic reinforcement system regulate two different aspects of reinforcement.

The tegmentostriatal pathway Structures in the nigrostriatal pathway

Dangers of Long-term Amphetamine Use

The use of amphetamines can be highly addictive. Tolerance to amphetamines develops rapidly. Physical dependence leads to withdrawal symptoms that range from a lack of alertness and feelings of lethargy to sleeping for up to 48 hours and depression lasting several days or weeks. Psychological dependence occurs due to conditioning of withdrawal to the environments associated with amphetamine use. Frequent or excessive use of amphetamines can cause severe weight loss as well producing stimulant-induced psychosis, which is associated with paranoia (feelings of persecution) as well as delusions and hallucinations. Long-term use of amphetamines can lead to brain damage and motor and cognitive impairment .

Dangers of Long-term Caffeine Use

The use of caffeine can be highly addictive. Tolerance to caffeine's sleep-disruptive and motor-stimulating effects, but not its mood and cognitive performance effects, develops in one to two weeks due to upregulation of the enzymes that maintain adenosine receptors. Physical dependence leads to withdrawal symptoms that include headache, irritability, depression, drosiness, and fatigue. Psychological dependence occurs due to conditioning of withdrawal to the environments associated with caffeine use.

Dangers of long term cocaine use:

The use of cocaine can be highly addictive. Tolerance to cocaine develops rapidly. Physical dependence leads to withdrawal symptoms that range from a lack of alertness and feelings of lethargy to sleeping for up to 48 hours and depression lasting several days or weeks. Psychological dependence occurs due to conditioning of withdrawal to the environments associated with cocaine use. Frequent or excessive use of cocaine can cause severe weight loss as well producing stimulant-induced psychosis, which is associated with paranoia (feelings of persecution) as well as delusions and hallucinations. Long-term use of cocaine can lead to brain damage and motor and cognitive impairment .

Dangers of Long-term Nicotine Use

The use of nicotine can be highly addictive. Tolerance to nicotine develops quickly due to desensitization of the nicotinic receptor to nicotine. However, additional exposure to nicotine leads to increased sensitivity to the effects of nicotine due to the upregulation of enzymes maintaining nicotinic receptors. Side effects from nicotine use include increased heart rate and blood pressure, gastrointestinal distress, headaches, dizziness, and insomnia. Severe side-effects include cardiovascular disease including increased risk of stroke. Physical dependence leads to withdrawal symptoms that include irritability, depression, drowsiness, and fatigue. Psychological dependence occurs due to conditioning of withdrawal to the environments associated with nicotine use.

Barbiturates can be classified as:

Ultrashort-acting barbiturates Short-intermediate-acting barbiturates Long-acting barbiturates

Barbiturates

a class of depressants that are a derivative of barbituric acid and have the same of sedative-hypnotic effects as does alcohol. The barbiturates are lipid-soluble and rapidly pass through the blood brain barrier. The half-life of a barbiturate is determined by its lipid- solubility and can range from several hours to several days. The short-acting, highly lipid-soluble barbiturates can induce sleep or anesthesia within 20-30 seconds when administered intravenously. The longer acting less lipid soluble barbiturates may take up to an hour to have an effect and can be used as a sedative or an anticonvulsant.

Benzodiazepines

a class of depressants that have a core chemical structure of the fusion of a benzene ring and a diazepine ring. Benzodiazepines can be classified depending on how long the drug takes to be effective (or how lipid-soluble it is) and how long the drug continues to act (or its half-life). Short- and intermediate-acting benzodiazepines are generally used for the treatment of insomnia, while the longer-acting benzodiazepines are recommended for the treatment of anxiety. The benzodiazepines are lipid-soluble and rapidly pass through the blood brain barrier. The half-life of a specific benzodiazepine is determined by its lipid-solubility and can range from several hours to several days. The short-acting, highly lipid-soluble benzodiazepines can induce sleep or anesthesia within 20-30 seconds when administered intravenously. The longer acting less lipid soluble benzodiazepines may take up to an hour to have an effect and can be used as a sedative.

psychoactive drug (psychtropic or mind altering drugs)

a drug that affects mental functioning they exert their influence through their actions on the CNS

3 types of depressants:

alcohol barbiturates benzodiazepines

drug

any substance we can take into our body that has the power to change us either functionally or structurally

The tegmentostriatal pathway

detects whether sufficient motivation is present for voluntary behavior to occur. This neural pathway begins in the lateral hypothalamus, goes through the MFB and ventral tegmental area, terminates in the nucleus accumbens

Ephedrine

extracted from the Ephedra sinica plant

Amphetamine or levoamphetamine

first marketed as an antihistamine inhalant under the trade name Benzedrine.

Dextroamphetamine

introduced under the trade name Dexedrine to treat fatigue, narcolepsy, depression, and obesity.

Structures in the nigrostriatal pathway

play a role in the storage of a memory. This neural pathway begins in the substantia nigra and projects to the basal ganglia.

Short-intermediate-acting barbiturates

take effect after 15 to 40 minutes and act for up to six hours. Used as sedatives and include pentobarbital (Nembutal) and secobarbital (Seconal)

Long-acting barbiturates

take effect in about 1 hour and last for as long as 16 hours. Used as anticonvulsant and include phenobarbital (Luminal)

Ultrashort-acting barbiturates

take effect within a minute and last for up to 3 hours. Used as anesthetics and include thiopental (Pentothal) and thiamylal (Surital)

Methamphetamine (speed)

the most powerful of the amphetamines that has potent euphoric properties.

Pharmacokinetics

the study of how a drug moves throughout the body including the process of absorption metabolism distribution to tissues and elimination

Psychopharmacology

the study of the effects of drugs on behavior

Pharmacodynamics

the study of the ways in which a drug affects the living organism and the organs of the body

Mechanisms of Marijuana Action

the synthetic cannabinoid CP-55, 940 attaches to receptors located in the prefrontal cortex, basal ganglia, cerebellum, hippocampus, amygdala, and thalamus. In the prefrontal cortex and nucleus accumbens, cannabinoid metabotrophic receptors are located on the presynaptic membranes of GABA neurons. When THC or other cannabinoids attach to these cannabinoid receptors, voltage- gated Ca++ ion channels are inhibited and less GABA is released into the synaptic cleft. THC binding to cannabinoid receptors decreases GABA-mediated neural inhibition of glutamate activity in the prefrontal cortex and dopamine activity in mesolimbic reinforcement system. When THC attaches to cannabinoid receptors in the hippocampus and basal ganglia, glutamate activity is suppressed. In 1992, William Devane and his colleagues were able to isolate an endogenous cannabinoid, arachidonoyl ethanolamine. They named this substance anandamide after the Sanskrit word ananda, which means "bliss." Anadamide plays an important role in memory storage, appetite, pain signaling, motor activity, and reward. The euphoric effects of marijuana are thought to be mediated at least in part by the disinhibition of dopamine activity in the mesolimbic reinforcement system.

Psychedelic drug

A class of drugs that profoundly alters a person's state of consciousness; also called hallucinogens. Changes in sensation, perception, and emotion occur as the result of psychedelic drug use

Depressants

A class of psychoactive drugs that acts on the central nervous system to slow down mental and physical functioning. At low doses, depressants have a calming effect, while at high doses, they have a sleep-inducing effect.

Amphetamines

A collective term for a class of psychostimulant drugs that causes a person to experience greater energy, a decreased need to sleep, reduced appetite, and positive affect (mood). Amphetamines can be ingested by various means including oral administration, nasal inhalation, smoking or intravenous injection. Peak plasma levels are reached within five minutes when smoked or intravenous injection. By contrast, peak plasma levels of amphetamines takes two to three hours with oral administration. The amphetamines are lipid soluble, which allows them to rapidly pass through the blood-brain barrier. The greater lipid solubility of methamphetamine than the other amphetamines allows it to produce a greater high. The amphetamines have a half-life of 10-15 hours. Amphetamine is metabolized into the inactive metabolites p-OH-amphetamine and norephedrine. Methamphetamine is first metabolized into amphetamine.

Tolerance

A decrease in the effects of a drug resulting from repeated use

opiate

A drug derived from the opium poppy, or a drug that has an action comparable to that of drugs derived from the opium poppy. Opiates are analgesics, used for relief of pain. A drug must act on the CNS to produce stupor or sleep-inducing effects to qualify as an opiate. Some opiates are found in nature, while others are either partially or entirely synthetic. All of the opiates are potent analgesics due to their ability to activate endorphin receptors in the spinal cord and in the brain. The half-life of the opiates differs based on how rapidly it is metabolized.

Marijuana

A drug obtained from a mixture of crushed leaves, flowers, stems, and seeds of the hemp plant Cannabis sativa. The main psychoactive ingredient in marijuana is delta-9-tetrahydrocannabinol or THC. Smoking marijuna is the most effective method of administration. Upon heating, the THC in marijuana is vaporized and readily passes through the surface of the lungs into the blood. Within seconds of inhalation, THC passes through the blood-brain barrier and enters the brain. Peak plasma levels are typically reached within a few minutes. After administration, THC is metabolized by the liver into the active metabolite 11-hydroxy-THC and then the inactive metabolite 11-nor-9-carboxy-THC. The half-life of THC ranges from 24 to 72 hours. Orally ingested marijuana is absorbed more slowly and incompletely as THC can be absorbed by dietary fats in the stomach and digestive system. Orally ingested THC must first pass through the liver where much of it is metabolized by liver enzymes. Peak plasma levels are reached in 1 to 4 hours after consumption. THC can be detected in the bloodstream as much as 2 weeks after exposure and for 3 to 4 weeks in frequent users.

Psychostimulant

A drug that produces alertness by enhancing the functioning of the sympathetic nervous system and mesocortical pathway. The euphoria and reinforcing effects of psychostimulant drugs are due to their influence on the functioning of the mesolimbic pathway.

opium

A natural opiate obtained directly from the opium poppy.

Substance Abuse

A pattern of drug use that results in negative effects.

Withdrawal symptoms

A physical or psychological problem that results from stopping the use of a drug

Vicodin (hydrocodone and acetaminophen)

A powerful semi-synthetic opiate derived from codeine.

Heroin

A powerful semi-synthetic opiate made by reacting acetic anhydride with morphine.

Lysergic acid diethylamide (LSD)

A powerful synthetic psychedelic drug, also known as acid. LSD is the most potent of all the psychoactive drugs. An effective dose begins at 25 milligrams, which is about 1,000 more potent than amphetamine or cocaine. LSD typically is ingested orally when applied to paper stamps. LSD is rapidly absorbed after oral administration and peak plasma levels are reached in about two hours. While the half-life of LSD ranges between 2 to 5 hours, its effects may last as long as 12 hours.

Phencyclidine (PCP)

A powerful synthetic psychedelic drug, also known as angel dust. Phencyclidine (PCP), also known as angel dust, was introduced in the 1950s as an anesthetic for humans and as a tranquilizer in veterinary medicine. However, clinical studies revealed that humans experienced delusions, severe anxiety, and agitation when the anesthetic effects were ending and in the mid-1960s its use as an anesthetic was stopped. As a recreational drug, PCP may be ingested, smoked, or inhaled. PCP is slowly metabolized by liver enzymes. Peak plasma levels of PCP occur 1 to 4 hours after use and its half-life ranges from 1 to 4 days.

Psilocybin

A psychedelic drug obtained from fungi (mushrooms).

Peyote

A psychedelic drug obtained from the peyote cactus plant.

Cocaine

A psychostimulant extracted from the leaves of the coca plant that increases alertness, decreases fatigue, and produces a pleasurable emotional state. Cocaine is used as a local anesthetic in eye and ear surgery and with morphine in terminally-ill patients to counteract the sleepiness produced by morphine. Crack cocaine is potent form of cocaine made by mixing cocaine hydrochloride with ammonia or baking soda and water; the resulting crystals are smoked in a pipe. Cocaine hydrochloride can be ingested by various means including oral administration, nasal inhalation, snorted or intravenous injection. Cocaine enters the brain more slowly with oral ingestion or snorting than with intravenous administration or inhalation of vaporized cocaine. Peak plasma levels are reached within five minutes with intravenous injection. By contrast, peak plasma levels of cocaine takes about an hour with intranasal administration. The inhalation of the vapors of crack cocaine also readily enter the brain, reaching a peak plasma level within five minutes. Cocaine is metabolized quickly by both blood and liver enzymes. The half-life of cocaine varies between one and one-half hours.

Nicotine

A psychostimulant found in the leaves of the tobacco plant that increases alertness and decreases fatigue. Most commonly ingested by smoking cigarettes, cigars, or pipes. Also ingested orally as chewing tobacco. Nicotine is highly lipid-soluble and readily enters the circulatory system through the linings of the mouth and lungs as well as all skin and mucous surfaces. Once in the blood, nicotine readily crosses the blood-brain barrier. The highest plasma concentrations of nicotine are produced by inhalation of smoked tobacco products. Peak plasma concentrations by inhalation are reached within 5-10 seconds. Other routes of administration, including intravenous injections, produce substantially lower peak plasma levels. However, the peak plasma concentrations are the same for all methods of administration within 30-45 minutes.

Caffeine

A psychostimulant found in various plants that increases alertness and decreases fatigue. Caffeine consumption leads to clearer thought processing, reduced drowsiness, more rapid reaction times, enhanced intellectual functioning, and an overall positive feeling. Caffeine is an alkaloid found in a variety of plants including coffee, tea, and cocoa plants. While caffeine is normally consume in caffeinated beverages, it also can be found in over the counter analegic and alertness promoting drugs. Caffeine is readily absorbed by the stomach and small intestine within 30-60 minutes of ingestion. Peak plasma concentrations are reached within two hours. Caffeine is metabolized quickly by liver enzymes. The half-life of caffeine is about three to four hours.

MDMA

A synthetic psychoactive drug that induces a state of consciousness that facilitates communication; also known as ecstasy. Methylenedioxyamphetamine (MDMA), also known as ecstasy MDMA is ingested in pill form and is slowly metabolized by liver enzymes. Peak plasma levels of PCP occur 1 to 3 hours after use and its half-life ranges from 8 to 10 hours.

Addiction

Addiction is characterized by powerful and long-lasting behavioral changes, including cravings and reward seeking, that can reinstated after long periods of abstinence. Addiction occurs to a wide range of situations, which have no common structural features other than contributing to increased dopamine activity in the nucleus accumbens and other structures in the mesolimbic reinforcement system.

Drug experience leads to changes in the structure and function of dopaminergic neurons in the mesolimbic pathway.

After repeated drug use, the structure of the dopaminergic neurons in the mesolimbic reinforcement pathway are altered by the upregulation of the proteins CREB and c-FOS. The CREB and c-FOS proteins act to increase dendritic branching, to increase the numbers of D2 receptors, and increase the sensitivity to dopamine. Changes in the structure and sensitivity of the mesolimbic pathway allow drug-associated stimuli to elicit drug-seeking behaviors.

Long term effects of alcohol use:

Alcoholism occurs in approximately 10% of adult drinkers and where consumption of alcohol produces physical, mental, and/or social impairment. Repeated use of alcohol quickly leads to tolerance. Side effects of alcohol use include marked sedation, cognitive impairments, retarded motor movements, and slurred speech. Physical dependence leads to withdrawal symptoms that range from restlessness to tremors, insomnia, anxiety, mental confusion, and hallucinations. Psychological dependence occurs as a result of conditioning of withdrawal to environments associated with alcohol use.

Thebaine

An alkaloid found in opium that is less potent than morphine.

codeine

An alkaloid found in opium that is less potent than morphine.

morphine

An extremely potent natural opiate that is the main alkaloid compound found in opium.

Mechanism of alcohol action:

Because of its ability to pass through the lipid cell membrane, alcohol disrupts several cellular processes, including the movement of ions through ion channels, the conductance of membrane potentials, and the release and storage of neurotransmitter molecules. This disruption of cellular processes accounts for alcohol's general depressant and analgesic effects at higher doses of alcohol consumed. Alcohol is a potent GABA agonist. Alcohol appears to bind to specific GABAA receptors, including delta receptors, and acts to enable GABA to bind more tightly to its receptors. Alcohol has a calming or anxiolytic effect because the enhanced inhibitory control of GABA neurons from the prefrontal cortex to the locus coreuleus and the amygdala. Alcohol has an agonist action on opiate receptors. Activation of opiate receptors by alcohol suppresses GABAergic inhibition of dopaminergic activity in the mesolimbic reinforcement system and contributes to the euphoric and reinforcing effects of alcohol. This agonist effect of alcohol on dopaminergic neurons is opposed by the enhanced GABA-mediated inhibition of dopaminergic activity also produced by alcohol. The effects of alcohol on dopamine activity are limited because of its influence on GABA, which may explain why a significant proportion of the population can consume alcohol in moderation.

Mechanisms of Caffeine Action

Caffeine has an agonist effect on glutaminergic neurons neurons. Caffeine indirectly increases glutamate release by blocking the inhibitory effect of adenosine on the presynaptic membrane of glutaminergic neurons. The arousing influence of caffeine is due to the increased glutaminergic activity in the cortical pathway from the locus coreuleus to the prefrontal cortex. The enhanced cognitive functioning produced by caffeine also is due to increased glutaminergic activity in this pathway. Caffeine has an agonist effect on dopaminergic neurons. Caffeine indirectly increases dopamine release by blocking the inhibitory effect of adenosine on the presynaptic membrane of dopaminergic neurons. The euphoric and reinforcing effects of caffeine are due to increased dopaminergic activity in the mesolimbic pathways that projects from the ventral tegmental area to the nucleus accumbens. The motor-stimulating effects of cocaine is due to increased dopaminergic activity in the pathway from the substantia nigra to the basal ganglia. Caffeine also has an agonist effect on serotonin and noradrenergic activity by blocking the inhibitory effect of adenosine on the presynaptic membrane of serotonergic and noradrenergic neurons.

Physical dependence

Changes in the body that produce intense physical symptoms when the drug taking is stopped.

Mechanisms of cocaine action

Cocaine has an agonist effect on dopaminergic neurons. This agonist action occurs by cocaine binding to the dopamine transporter on the presynaptic membrane and blocking the normal reuptake of dopamine. The euphoric and reinforcing effects of cocaine are due to increased dopaminergic activity in the mesolimbic pathway that projects from the ventral tegmental area to the nucleus accumbens. The motor-stimulating effects of cocaine is due to increased dopaminergic activity in the pathway from the substantia nigra to the basal ganglia. Cocaine also acts to block serotonin reuptake. Increased serotonergic activity in the pathway from the ventral tegmental area to the nucleus accumbens acts to enhance dopaminergic activity in the nucleus accumbens, thereby enhancing the euphoric and reinforcing effects of cocaine. The arousing influence of cocaine is due to the increased noradrenergic activity in the mesocortical pathway from the ventral tegmental area to the prefrontal cortex. The enhanced cognitive functioning produced by cocaine also is due to increased norepinephrine activity in this pathway. Increased noradrenergic activity in the pathway from the locus coeruleus to the prefrontal cortex also contributes to the effects of cocaine on arousal and cognitive functioning.

Psychological dependence

Craving for the way the drug makes the individual feel, for the pleasure and/or relief from discomfort that come from taking the drug

Treatment of alcohol addiction:

Disulfiram (Antabuse) Naltroxone

The mesocortical reinforcement system also appears to contribute to compulsive behaviors like pathological gambling, hypersexuality, compulsive eating, and compulsive shopping as well as drug dependency and abuse.

Dopamine agonists, such as pramipexole and ropinirole, significantly increased the likelihood of compulsive behaviors. A gene variation that produces fewer dopamine receptors in the mesocortical reinforcement system has been found in individuals who engage in compulsive behaviors.

Agonists can act in several ways:

Drug binds to and activates postsynaptic receptors or increases neurotransmitter effect Drug blocks deactivation by blocking degradation or reuptake Drug increases neurotransmitter synthesis Drug increases neurotransmitter amount by destroying degrading enzymes Drug increases amount of neurotransmitter release Drug binds to autoreceptors and blocks their activity Drug is a false transmitter, preventing a neurotransmitter from binding to a receptor by attaching to the receptor itself Drug blocks neurotransmitter synthesis Drug causes neurotransmitter to leak from vesicles Drug blocks release of neurotransmitter from presynaptic neuron Drug activates autoreceptors

Mechanisms of Drug Action

Drugs can either facilitate or inhibit the transmission of neural impulses.

Antagonists

Drugs that block or inhibit the effects of a neurotransmitter.

Agonists

Drugs that mimic or enhance the activities of a neurotransmitter.

Amphetamines Encompasses four related drugs:

Ephedrine Amphetamine or levoamphetamine Dextroamphetamine Methamphetamine (speed)

Alcohol

Ethyl alcohol (ethanol) is a powerful depressant that strongly influences consciousness and the ability to respond effectively to the environment. Alcohol is both water and lipid-soluble and readily diffuses across all cell membranes. Once ingested, alcohol rapidly passes through the blood-brain barrier, allowing alcohol to reach neural tissue quickly. While blood alcohol level (BAC) is important, the behavioral effects of a specific blood alcohol level vary from person to person. A blood alcohol level that might be especially impairing to one individual may not affect another person. Almost all alcohol that is consumed is metabolized by the enzyme alcohol dehydrogenase into acetaldehyde and then into acetic acid by the enzyme aldehyhyde dehydrogenase. Metabolism begins in the stomach and continues in the liver. About 25-30 % of alcohol that is ingested is metabolized before it reaches the nervous system. Metabolism then continues at a slower rate or about the equivalent of one shot of 40 proof whiskey, one 4-ounce glass of wine or one 12-ounce bottle of beer per hour. The symptoms of hangover (nausea, vomiting, sweating, dizziness, and severe headaches) are produced by acetaldehyde when large amounts of alcohol are consumed and not metabolized quickly by the enzyme aldehyhyde dehydrogenase.

Individual differences in preference for drugs may reflect differences in the mesolimbic reinforcement pathway.

Genetic differences appear to be an important cause of the variability in response to reinforcers, which may explain why some people exhibit a greater potential for substance dependence than others. It appears that a defect in the dopaminergic system causes people to abuse certain substances in order to obtain greater stimulation of their dopaminergic reward system.

Genetic Contribution to Addiction

Genetics has a significant influence on the development of an addiction. What is inherited is only a susceptibility or genetic predisposition to develop an addiction.

Role of the Mesolimbic Reinforcement System

High levels of instrumental or operant behavior are exhibited when responding leads to activation of the mesolimbic reinforcement system. The mesolimbic reinforcement system plays a significant role in addiction. The mesolimbic reinforcement system is the part of central nervous system that mediates the influence of reinforcement on behavior. The reinforcing properties of cocaine and amphetamines results, in part, from their ability to activate the dopaminergic mesolimbic reinforcement pathway. Natural reinforcers, such as food and water, cause the release of dopamine into the nucleus accumbens. Researchers have also found increased dopamine levels in the nucleus accumbens following the administration of alcohol, marijuana, and nicotine. In animals, destruction of dopaminergic neurons in this pathway weakens the reinforcing properties of cocaine and amphetamine. Additionally, drugs that block dopamine receptors cause animals to reduce or stop behaviors they have been using to obtain cocaine or amphetamine.