Rats prefer to lever press for cocaine over food, even to the point of starvation.
Psychoactive agents are categorized a number of different ways. For example, drugs are categorized according to their chemical structure e. What follows is a description of a few of the most well-studied drugs with emphasis on the use of the drug; behavioral, cognitive, and mood-related effects of the drug; and the CNS mechanisms by which the drug produces its effects on behavior. Stimulants produce behavioral excitation, increased motor activity, and increased alertness by enhancing excitation at neuronal synapses. The most commonly used stimulants include caffeine a xanthine , nicotine, amphetamines, and cocaine.
These stimulants have medicinal purposes, but most people are more familiar with their recreational uses. Stimulants vary greatly in the degree to which they affect behavior and in their potential for dependence and abuse. Xanthines are a family of stimulants that includes caffeine, theobromine, and theophylline, the most widely used stimulants in the world.
Caffeine is in many products e. Tea contains caffeine, theophylline, and trace amounts of theobromine, and both caffeine and theobromine are in chocolate. Caffeine and theophylline are approximately equal with regard to stimulatory effects, but theobromine is only about one-tenth as strong as the other two. How much caffeine is in coffee depends on the type of coffee bean coffea robusta having twice the caffeine content of coffee Arabica and how it is brewed caffeine in a 5-ounce cup: instant about 60 mg, percolated about 85 mg, drip-brewed about mg.
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A 5-ounce cup of medium brewed black tea has about 60 mg of caffeine, and a strong brew of tea contains as much as mg of caffeine. A 1-ounce piece of milk chocolate contains 1 to 6 mg caffeine and about 40 mg of the 10 times less stimulating theobromine. There is 75 to mg of xanthines in a cup of hot cocoa, and cocoa products contain enough caffeine and theobromine to affect behavior. Orally consumed caffeine is absorbed in the stomach and mostly intestines, with peak blood levels occurring at 30 to 60 minutes. Caffeine easily crosses the blood brain and placenta barriers.
Some foods, alcohol, smoking, hormones, age, and species affect the metabolism of caffeine. Xanthines are antagonists at adenosine A1 and A2a receptors, affecting the release of several neurotransmitters. When activated by adenosine, receptors located on presynaptic terminals inhibit spontaneous and stimulated neurotransmitter release. By blocking activation of adenosine receptors, xanthines lead to increased neurotransmitter release and increased excitation.
At high concentrations, xanthines also block benzodiazepine receptors located on the GABA receptor complex, which may account for some of the increased anxiety after consumption of enormous amounts of coffee. Because outside of the CNS theophylline is particularly good at causing smooth muscles to relax, theophylline is useful therapeutically to dilate the bronchi of the lungs in the treatment of asthma. Often people consume products containing moderate levels of caffeine because of their subjective experiences of increased alertness, improved attention, reduced fatigue, and more clear cognition.
Additionally, caffeine augments brainstem reflexes, enhances some visual processing, improves reaction time and self-reported alertness, reduces the detrimental effects of sleep deprivation on psychomotor performance, increases wakefulness, and produces insomnia. Tolerance develops to some of the subjective effects of caffeine. Small and moderate, but not large, doses of caffeine appear to have reinforcing properties. Most people manage their caffeine intake, avoiding the anxiety, tremors, rapid breathing, and insomnia associated with high doses of caffeine.
Within 12 to 24 hours of cessation, caffeine withdrawal often causes mild to severe headaches, drowsiness, muscle aches, and irritability, suggesting caffeine has some potential for producing limited physiological dependence. However, after reviewing caffeine studies, Nehlig concluded that caffeine does not affect the dopaminergic CNS centers for reward and motivation, as do cocaine and amphetamines.
Nicotine is one of the most-used psychoactive drugs in the world. The primary psychoactive active ingredient in tobacco is nicotine. Only Many of the toxic chemical compounds, other than nicotine, in tobacco products are the source of serious health problems e. Nicotine is easily absorbed into the body. When inhaled, nicotine in cigarette smoke particles tar is quickly absorbed into the bloodstream via the capillaries lining the lungs. Even though cigarettes contain about 0. Smokers easily avoid nicotine toxicity by controlling the depth and rate of smoke inhalation.
The liver metabolizes about 90 percent of the nicotine in the bloodstream before excretion. Nicotine is an agonist at acetylcholinergic nicotinic receptors. Nicotine activation of CNS nicotinic receptors located on presynaptic terminal buttons facilitates release of dopamine, acetylcholine, and glutamate throughout the brain. Physiological and psychological dependence of nicotine is due to nicotinic-induced release of dopamine from neurons projecting from the ventral tegmental area to forebrain regions mesolimbic system and prefrontal cortex mesocortical system , brain areas responsible for reinforcement.
Nicotine-induced release of acetylcholine is the likely cause of improved cognition and memory, as well as increased arousal.
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Increased glutamatergic activity due to nicotinic presynaptic facilitation contributes to enhanced memory of nicotine users. Individual differences in the cognitive effects of nicotine may be due to genetic variations in dopaminergic activity. Additionally, nicotine stimulates activity in brain regions involved in attention, motivation, mood, motor activity, and arousal.
Tolerance appears to develop to the subjective mood effects of nicotine, but not to nicotine-induced changes in physiology or behavioral performance for review see Perkins, However, most smokers do develop both physiological and psychological dependence on nicotine. Typically, withdrawal from cigarettes causes intense persistent cravings, irritability, apprehension, irritation, agitation, fidgeting, trouble concentrating, sleeplessness, and weight gain.
Even people deprived of smoking just overnight report higher stress, irritability, and lower pleasure e. Abstinence symptoms can last for several months, and many smokers find the cravings to be so intense that they relapse. It is common for smokers to quit smoking many times. Decreased activity in reward brain areas e. In amphetamine, a synthetic drug similar in structure to ephedrine, was patented. That amphetamine is a potent dilator of nasal and bronchial passages easily administered as an inhalant made it a viable treatment for asthma in the early s.
Subsequently, college students used amphetamines to stay awake studying for exams, and truck drivers for staying awake on crosscountry hauls. It did not take long for word to spread that amphetamines speed caused euphoria, quickly making them an abused recreational drug.
As Schedule II drugs, amphetamines have high potential for abuse and dependence, but also have accepted medicinal use with strict restrictions. Currently, treatments for narcolepsy and attention deficit hyperactivity disorder ADHD are accepted uses of amphetamines and amphetamine-like drugs methylphenidate. Amphetamines are a group of similarly structured synthetic chemicals that cause euphoria and behavioral stimulation. The d form of amphetamine is more potent than the 1 form.
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The liver metabolizes about 60 percent of methamphetamine, amphetamine being the major active metabolite, and then the kidneys excrete the metabolites and unchanged methamphetamine. Amphetamines work both in the periphery and in the CNS.
Recreational users typically prefer methamphetamine to other amphetamines because it has fewer unpleasant peripheral effects e. Amphetamines improve mood, decrease fatigue, increase vigilance, energize, impair ability to estimate time, and diminish the desire for food and drink. Most of the performanceenhancing effects of amphetamines are limited to tasks that are routine, well-rehearsed, and well-practiced activities. The euphoria and strong reinforcing properties of amphetamines are due to increased dopamine activity in the mesolimbic system. Increased repetitive movements stereotypy in laboratory rats and behaviors punding in humans to the exclusion of eating, grooming, and sleeping are probably due to amphetamine stimulation in the nigrostriatal dopamine system.
High acute doses and chronic use probably over stimulate the mesolimbic dopamine system, producing violently aggressive paranoia and amphetamine psychosis, delusions, hallucinations, and a split from reality. The sensation that insects are crawling under the skin formication may be the basis for the self-mutilation observed in laboratory animals. Long-term chronic use of methamphetamines is particular neurotoxic, leading to irreversible brain damage and psychosis.
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The positively rewarding feelings associated with intravenously injected amphetamine, especially methamphetamine, leads to overwhelming psychological dependence. Physiological dependence on amphetamines is evident from the withdrawal symptoms of ravenous hunger, fatigue, lethargy, depression, and suicidal tendencies.
Many of the characteristics of amphetamines are similar to those of cocaine. For thousands of years, the natives of the South American Andes have increased endurance and stamina as they traveled the harsh mountain terrain by chewing the leaves of the coca plant. The plant became of interest to Europeans and Americans in the mid to late s when entrepreneurs began adding the extract of the coca leaves to many products e. In the s Dr. Because cocaine is readily absorbed in mucous membranes, it is still a local anesthetic of choice in some surgeries e.
Currently, U. In an estimated 2. Users snort the powdered hydrochloride salt form of cocaine, and when they dissolve that in water, they can inject the drug. In the s users developed a smokeable free-base form of cocaine by extracting the hydrochloride with the very volatile gas ether. The safer smokeable rock crystal crack cocaine forms when producers treat cocaine with baking soda and water.
The crack user inhales the vapors as the rock heats and makes a crackling sound. When inhaled, cocaine is rapidly absorbed by capillaries in the lungs, whereas snorted cocaine hydrochloride is absorbed more slowly into mucous membranes. Cocaine readily crosses the BBB and quickly distributes throughout the brain, where it remains for as long as 8 hours. The major metabolite benzoylecgonine is inactive and, when excreted by the kidneys in urine, is detectable for 48 hours, even as long as 2 weeks in chronic cocaine users.
Cometabolism of cocaine and alcohol produces the pharmacologically active, longer-lasting, and toxic metabolite cocaethylene. Cocaine blocks presynaptic reuptake transporters for dopamine, epinephrine, norepinephrine, and serotonin. This blockade prolongs the presence of these neurotransmitters in the synapse, allowing the neurotransmitters to bind repetitively to postsynaptic receptors. Serotonin receptors also play a role in the reinforcing effects of cocaine. Cocaine is an extremely addictive psychostimulant that in low to moderate doses produces euphoria and increases alertness, mental acuity, self-consciousness, talkativeness, and motor behavior.
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Moderate to high doses cause more intense confusion, agitation, paranoia, restlessness, tremors, and seizures. Chronic use of cocaine produces impulsive and repetitive behavior. High-dose cocaine use can cause cocaine-induced psychosis characterized by extreme agitation and anxiety; exaggerated compulsive motor behaviors; delusions of paranoia and persecution; visual, auditory and tactile hallucinations; loss of touch with reality; and permanent brain damage.