Stimulants, Sedatives, and Inhalants

Stimulants

Stimulants are substances that can

keep a person going, both mentally

and physically, when they are tired.

Restricted stimulants.

• Examples: Cocaine and

amphetamines.

Readily available stimulants.

• Examples: Caffeine and nicotine.

Cocaine History 1

Coca.

• A bush that grows in the Andes and produces cocaine.

• Actively cultivated for over 800 years.

The coca leaf was an important part of Inca culture.

• Used in religious ceremonies and as currency.

Some natives of the Andes still chew coca leaves to reduce fatigue.

Cocaine History 2

Cocaine wasn’t in use in Europe until the last half of the 19th century.

Angelo Mariani.

• Developed coca wine.

• Used coca leaf extract in many products, including lozenge and tea.

Cocaine was isolated before 1860.

• Simple and inexpensive processing of 500 kilograms of coca leaves

yields 1 kilogram of cocaine.

Medical use.

• Availability of pure cocaine and the newly developed hypodermic

syringe improved the drug delivery system.

• Dr. W. S. Halsted experimented with the ability of cocaine to produce

local anesthesia.

• Referred to as “the father of modern surgery.”

Cocaine History 3

Early psychiatric uses.

• Sigmund Freud studied and recommended the use of cocaine as a

treatment for depression and morphine dependence.

• Later opposed the use of drugs in the treatment of psychological problems

after nursing a friend through cocaine-induced psychosis.

Cocaine was an ingredient in many patent medicines and elixirs.

• Openly advertised as having beneficial effects.

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Early Legal Controls on Cocaine

Press and medical journals made claims connecting heinous crimes to

black men under the influence of cocaine.

• 46 states passed laws to regulate the use and distribution of cocaine

between 1887 and 1914.

• Negative, racially charged publicity about cocaine helped shape

American drug policy.

Coca paste

Crude extract created during the manufacture of cocaine.

• Often mixed with tobacco and smoked in South America

Cocaine hydrochloride.

Stable water-soluble salt.

• Snorted or injected intravenously.

Freebase

Extraction of cocaine into a volatile solvent, such as ether.

• Resulting “freed” cocaine “base” can be heated and the vapors

inhaled

Crack Cocaine

Smokable cocaine prepared by mixing cocaine with water and baking

soda, and then drying it

Cocaine: Modern Legal Controls 1

Cocaine use increased in the late 1960s.

• Cocaine was relatively expensive.

• Throughout the 1970s and early 1980s it was viewed as a drug for the

glamorous and the powerful.

By the mid- to late-1980s, crack cocaine became available.

• Relatively inexpensive and available at 5 dollars per dose.

Cocaine: Modern Legal Controls 2

Media vilified the use of cocaine and the users.

Anti-Drug Abuse Act of 1986.

• Penalties for the sale of crack cocaine were significantly more severe

than the penalties for the sale of powder cocaine.

• Two years later, the law was modified so that it applied to individuals

convicted of simple possession of five grams of crack cocaine, even

first-time offenders.

Cocaine: Mechanism of Action

Cocaine’s mechanism of action is complex.

• Cocaine blocks the reuptake of dopamine, serotonin, and

norepinephrine.

• Cocaine’s behavioral effects depend on an interaction of multiple

neurotransmitters, including monoamines, acetylcholine, GABA,

glutamate, among others.

Cocaine: Absorption and Onset of Effects

Chewing and sucking coca leaves.

• Slow absorption and onset of effects.

Snorting.

• Absorbed through nasal passages.

• Rapid absorption and onset of effects.

Intravenous injection.

• Delivers a very high concentration to brain.

• Rapid and brief effects.

Cocaine Elimination

Cocaine is metabolized by enzymes in the blood and liver.

Cocaine has a half-life of about one hour.

Major metabolites have a longer half-life of eight hours.

• Detected by urine screening tests.

• Takes about three days for metabolites to be completely eliminated

after moderate use.

Beneficial Uses of Cocaine

Local anesthesia.

• Used medically since 1884.

• Early applications were in eye surgery and dentistry.

Synthesized drugs that have few central nervous system, or CNS, effects

have largely replaced cocaine.

• Cocaine remains in use for surgery in the nasal, laryngeal, and

esophageal regions.

Cocaine produces a feeling of increased energy and well-being, effects

that can be beneficial in a variety of settings.

Concerns of Cocaine: Acute Toxicity

No evidence that occasional use of small amounts is detrimental to

health.

Potential toxicity increases with larger doses.

• Acute cocaine poisoning can lead to profound central nervous system

stimulation.

• Can lead to respiratory or cardiac arrest.

Illicit cocaine is often adulterated.

• Adulterants may be more toxic than the drug.

Cocaine Concerns: Chronic Toxicity

Drug is taken repeatedly and at

increasingly high doses.

Leads to a state of increasing irritability,

restlessness, and paranoia.

Can result in paranoid psychosis.

• Most people seem to recover once the

drug leaves the system.

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Concerns of Cocaine: Addictive Potential

Cocaine addiction occurs in some users.

• Animal and human studies have shown that cocaine is a powerfully

reinforcing drug.

• Example: Animals will readily self-administer the drug.

Concerns of Cocaine: Reproductive Issues

Crack baby” phenomenon.

• Media reports overstated the expected long-term effects of cocaine

exposure on developing fetuses.

• Recent studies indicate no consistent negative associations between

prenatal cocaine exposure and several developmental measures.

Cocaine use during pregnancy.

• Can result in an increased risk for miscarriage.

Cocaine and Patterns of Use

National Survey on Drug Use and Health found that:

• 7 to 9 percent of young adults reported use of cocaine within the past

month.

• Use of cocaine had dropped significantly in the general population.

Data from the Monitoring the Future study show that cocaine use

decreased substantially among high school seniors between 1985 and

1994.

• Less than 3 percent of people now report use in the past year,

compared to 12 percent at the peak of cocaine use in the early 1980s.

Amphetamines: History 1

The Chinese made a medicinal tea from

ma huang, which is classified under the

genus Ephedra.

• Active ingredient is ephedrine.

• Used to treat asthma.

• Stimulates the sympathetic branch of

the autonomic nervous system.

• Known as sympathomimetic drug.

Amphetamines: History 2

Amphetamine.

• Similar in structure to ephedrine.

• Patented in 1932.

• Used in the treatment of:

• Asthma.

• Narcolepsy.

• Hyperactivity in children.

• Appetite suppressant.

• Used as a stimulant.

Amphetamines: History 3

Wartime: Used to increase the efficiency of soldiers.

“Speed scene” of the 1960s.

• Many I V drug users used amphetamines either alone or in

combination with heroin.

• Obtaining prescriptions for amphetamines was not difficult.

• Reports of abuses led to federal regulation within the concept of

dangerous drugs in the 1965 law.

Amphetamines became more tightly controlled, leading to the increased

illicit manufacture of methamphetamine, called crank.

The Return of Methamphetamine

Ingredients used in the illicit manufacture of methamphetamine can be

flammable and toxic.

• Harsh components and solvents are washed away in the final stages

of the synthesis process.

In 2018, approximately 1 million individuals reported current

methamphetamine use.

Less than 15 percent of those who have ever used the drug will become

addicted.

• Overwhelming majority of users use the drug without functional

impairments.

Amphetamine Pharmacology

Chemical structure of the basic amphetamine molecule is similar to

that of the catecholamine neurotransmitters, dopamine and

norepinephrine.

• Structure of methamphetamine allows it to easily cross the blood-brain

barrier, producing more peripheral and fewer central nervous system

effects.

• Amphetamines increase the activity of monoamine neurotransmitters,

dopamine, norepinephrine, and serotonin, by stimulating their release.

Amphetamine: Absorption and Elimination

Peak effects occur:

• 1 to 1.5 hours after oral ingestion.

• 5 to 20 minutes after intranasal administration.

• 5 to 10 minutes following intravenous injection or smoking.

Half-life.

• 5 to 12 hours.

• Completely eliminated within 2 to 3 days of the last dose.

Rapid tolerance, or a tachyphylaxis, can occur with high doses.

Beneficial Uses of Amphetamine 1

Depression.

• Treatment of choice during the 1950s and early 1960s.

• Now used as an adjunctive therapy.

• Major advantage: Antidepressant effects occur relatively rapidly.

Weight control.

• In the mid-1960s, it was widely used to reduce appetite and food

intake for short periods of time.

• Methamphetamine is currently FDA approved.

• Long-term effects on obesity are unclear.

Narcolepsy.

• Uncontrolled daytime episodes of muscular weakness and falling

asleep.

• Amphetamines and other stimulants are used to keep patients awake

during the day.

Beneficial Uses of Amphetamine

Treatment of attention-deficit slash hyperactivity disorder, or ADHD.

• Characterized by problems of inattention and hyperactivity.

• Amphetamines reduce activity levels and improve concentration in

hyperactive children and adults.

• Stimulant medications can reverse catecholamine-associated deficits

that may underlie ADHD.

• Concerns about abuse and side effects have led to other treatment

options.

• Suppression of height and weight increases during drug treatment is a

drawback of stimulant therapy.

• Data suggest that stimulant therapy is protective against substance

abuse.

Beneficial Uses of Amphetamine 4

“Smart pills.”

• May improve performance that had been disrupted by fatigue or sleep

deprivation at low doses.

• May disrupt complex performances at high doses.

Athletics.

• May produce slight improvements in athletic performance at

appropriate doses under some circumstances.

Concerns about Amphetamine: Acute Toxicity

Acute behavioral toxicity can cause dangers.

User may become suspicious to the point of paranoia when higher doses

are administered for extended periods.

• When this is combined with lack of sleep and poor nutrition, there is

even greater concern about the psychological and physical well-being

of the person.

Concerns about Amphetamine: Chronic Toxicity

Paranoid psychosis may result after sustained amphetamine use.

• Paranoid psychosis may result from dopaminergic stimulation,

probably in the mesolimbic system.

No good evidence for permanent behavioral or personality disruption

exists.

Cathinones

Structurally similar to amphetamine.

• Over the past 15 years, the popularity of synthetic cathinones has

increased because they produce mood-elevating effects similar to

those produced by the classic simulants.

Depressants

A class of drugs that decrease central nervous system, or CNS, activity.

Have a widespread effect in the brain.

Also called sedatives or hypnotics.

• Sedatives treat anxiety.

• Hypnotics treat insomnia.

History: Before Barbiturates

Chloral hydrate.

• Started with “Mickey Finn” adding the substance in drinks.

• First synthesized in 1832 and used clinically until about 1870.

• One to two grams induce sleep in less than an hour.

• Repeated use leads to gastric irritation.

Paraldehyde.

• Synthesized in 1829 and introduced clinically in 1882.

• Effective and has a wide safety margin.

• Has an extremely noxious taste and an odor that permeates the

breath of the user.

Barbiturates

First introduced in 1903.

• So popular and useful that over 2,500 examples were synthesized.

• Popular barbiturates included phenobarbital, amobarbital, and

secobarbital.

Grouped based on their duration of action, which corresponds to their

time of onset.

• Short-acting and rapid onset: Used to induce sleep and are

prescribed in high doses.

• Long-acting and delayed onset: Used to reduce anxiety and are

prescribed in low doses.

Concerns about Barbiturates

Overdose deaths.

• Intentional and accidental.

• Caused by respiratory depression.

Abuse and dependence.

• Reinforcing effects of a drug are related to the rapidity of onset of

effects.

Concerns led to the search for safer medications.

Meprobamate

Widely prescribed after approval in 1955.

Can produce physical dependence like barbiturates.

Still available as a prescription drug.

• Largely replaced by benzodiazepine

Methaqualone 1

Other names.

• Brands such as Quaalude and Sopor.

• Slang includes “ludes” or “sopors.”

Despite problems in other countries, the drug was introduced in the

United States in 1965.

• Package insert read “Addiction potential not established.”

• Physicians overprescribed, thinking the drug was a safe alternative to

barbiturates.

• Widely misused and abused.

Scheduling history.

• Put on schedule 2 in 1973.

• Put on schedule 1 in 1985.

Benzodiazepines 1

First introduced in 1960.

• Chlordiazepoxide, or Librium, the first commercially marketed

benzodiazepine.

• Reduces anxiety and produces less drowsiness than barbiturates.

• Much larger safety margin before overdose death occurred in animals.

• Physical dependence was rare.

• Overdose occurred only when combined with other depressants or alcohol.

1972 to 1978.

• Diazepam, or Valium, became the best seller among all prescription

drugs.

Benzodiazepines 2

However, dependence and overdose can occur.

Dose level and time course are critical factors.

• Overdose deaths are more likely when large doses of sedating drugs

are taken together with other depressants.

• Physical dependence occurs when the drug leaves the system more

rapidly than the body can adapt.

Are benzodiazepines safer than barbiturates?

• More differences might exist among the barbiturates and among the

benzodiazepines.

• Fewer differences might exist between these two classes of drugs.

Benzodiazepines: Rohypnol

A 1990s version of the “Mickey Finn.”

Produces profound intoxication when mixed with alcohol.

Reportedly used as a “date-rape” drug.

• Slipped into drinks of women.

• In 1997, a change in the formulation caused it to produce a distinctive

color when dissolved in a drink.

• Rohypnol effects are not much different from the effects of other CNS

depressants.

Nonbenzodiazepine Hypnotics

Informally referred to as the “Z-drugs.”

• Similar to benzodiazepines but have a different chemical structure.

Zolpidem, or Ambien, became the most widely prescribed hypnotic

drug.

• Short duration of action.

• Rapid onset.

Initially thought to be safer than benzodiazepines.

• Withdrawal symptoms have been reported.

Listed in schedule 4.

Mechanism of Action: Sedatives and Hypnotic

Benzodiazepines bind to their receptor site and enhance the inhibitory

effects of GABA on its receptors, and barbiturates act as a separate

binding site nearby.

• GABA receptor complex includes the barbiturate binding site and the

benzodiazepine receptor.

Nonbenzodiazepine hypnotics.

• Entirely new class of drugs that may selectively bind to different sites

on the GABA receptor complex.

Beneficial Uses of Depressants

Anxiolytics.

• Sedatives often prescribed to reduce

anxiety.

• Four benzodiazepines are among the top

100 most commonly prescribed

medications in the United States.

• Xanax.

• Ativan.

• Klonopin.

• Valium. Ryan McVay/Getty Images

Concerns: Anxiolytics

Sedatives are not appropriate for all anxiety disorders.

• Example: Obsessive compulsive disorder or specific phobias.

Overprescribed?

• Most of the prescriptions for antianxiety medications are neither

written by psychiatrists, nor are they written for patients with clearly

defined anxiety disorders.

Hypnotics, or Sleeping Pills

A large enough dose of a hypnotic drug is

taken to help one get to sleep more quickly.

Almost 17 percent of women and about 9

percent of men reported insomnia in a

national health survey.

• People who visit their doctors complaining

of insomnia should probably be evaluated

for depression.

• Effective nonmedical ways of dealing with

insomnia exist.

Halcion can produce an unusual number of

adverse psychiatric reactions in patients

Concerns: Nonbenzodiazepine Hypnotic

Concerns about nonbenzodiazepine hypnotics include sleepwalking,

eating, and driving while people are in a semi-waking state.

• As a result, all hypnotic drugs were required to carry a warning label.

Anticonvulsants

Barbiturates and benzodiazepines may be prescribed for epileptic

seizures.

Other antiepileptic drugs are prescribed in preference to

benzodiazepines or barbiturates, but they may be used in combination.

Potential concerns.

• Tolerance can make it difficult to find a dose that is effective but

doesn’t cause excessive drowsiness.

• Abrupt withdrawal is likely to cause seizures

Causes for Concern for Depressants: Abuse Liability

Psychological dependence.

• Associated with short-acting sedatives.

Physical dependence.

• Withdrawal syndrome is similar to the alcohol withdrawal syndrome

and is potentially life-threatening.

• Common side effects after chronic use of benzodiazepines include anxiety,

impaired concentration and memory, insomnia, nightmares, muscle

cramps, increased sensitivity to touch and to light, and so on.

• More severe symptoms, which may include delirium tremens, delusions,

convulsions, and severe depression, occur after abrupt withdrawal from

chronic use of larger doses.

• Cross-dependence occurs among barbiturates, benzodiazepines, and

alcohol.

Causes for Concern for Depressants: Toxicity

Behavioral toxicity.

• Depressants produce alcohol-like intoxication with impaired judgment

and incoordination.

• Additive effects result if they are combined with alcohol.

Physiological toxicity.

• Depressants:

• Produce respiratory depression.

• Are dangerous if combined with alcohol.

Inhalants

Examples of products that contain inhalable solvents that produce

effects similar to those of depressants.

• Gasoline, glue, paint, lighter fluid, spray cans, nail polish, and Liquid

Paper.

Gaseous Anesthetics

Abuse occurs among physicians and others with access to these gases.

Nitrous oxide was first used in the early 1800s.

• Acquired the name “laughing gas.”

Still used for light anesthesia by dentists.

Used as a propellant in whipping-cream containers and is sold in small

bottles for use in home whipping-cream dispensers.

Nitrites

Amyl nitrite: First introduced into medicine as a treatment for chest pain.

• Relaxes blood vessels.

• Increases blood flow and briefly lowers blood pressure.

• Used as a treatment for cyanide poisoning.

• With high doses, there might be a brief sense of lightheadedness or

faintness resulting from lower blood pressure.

• Butyl, isopropyl, and isobutyl nitrite produce effects similar to those of

amyl nitrite.

• Used in various cleaning products.

• Some users have inhaled these products to achieve the effect of

inhaling nitrites.

Volatile Solvents 1

The modern era of solvent abuse can be traced back to a 1959

investigative article in the Sunday supplement of a Denver, Colorado,

newspaper.

• News articles and education programs demonstrated how to abuse

volatile solvents.

• Use may have spread because of increased publicity.

In general, abuse tends to occur as localized fads.

Most users are very young.

• 4.7 percent of eighth-graders reported use in the past year.

• 1.9 percent of high-school senior class reported use in the past year.

Volatile Solvents 2

Volatile substances.

• Paint, paint thinners, paint removers, nail polish remover, correction

fluid, and glues.

• Some ingredients include petroleum, acetone, and toluene.

Dangers of Inhaling Solvents

Several solvents have been linked to:

• Kidney damage.

• Brain damage.

• Peripheral nerve damage.

• Irritation of the respiratory tract.

• Severe headaches.

• Death by suffocation.

Gamma Hydroxybutyric Acid, or GHB

Naturally occurring chemical found in the brain and other parts of the

body.

Structurally similar to the inhibitory neurotransmitter GABA.

Is a CNS depressant.

Behavioral effects are similar to those of alcohol.

Schedule 1 drug, except for Xyrem.

• Reduces frequency of cataplexy, which is a narcolepsy symptom.