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Misrepresented sometimes as a natural and safe hypnotic, the low therapeutic

index and the unknown purity of illicit supplies, particularly when sold in solution,

make GHB a potentially dangerous drug. Physical dependency is a possibility as

well. GHB, along with the benzodiazepine flunitrazepam, are considered “date rape”

drugs because they cause profound hypnosis and amnesia. This is intensified when

mixed with alcohol which is often how the sexual predator gives it to his victim.

CENTRAL NERVOUS SYSTEM STIMULANTS

Cocaine

Cocaine is a naturally occurring alkaloid derived from the Erythroxylon coca plant,

found mainly in the Andes Mountains of South America. Cocaine was first isolated in

the 1800s and was a common ingredient in tonics and elixirs of the 1900s. The

Harrison Narcotic Act of 1914 prohibited nonmedical use, and in 1970 it became a

schedule II controlled substance. According to the 2014 National Survey on Drug

Use and Health, nearly 1 million people in the continental United States have a

diagnosed cocaine use disorder within the last year which is similar to the rate in

2009.

4 Cocaine is a CNS stimulant and has vasoconstrictive and local anesthetic

properties. Cocaine’s stimulant effects are primarily caused by blockade of the

reuptake of dopamine, norepinephrine, with a small effect on serotonin. It also

facilitates the release of dopamine and norepinephrine. This results in an overall

increase in availability of neurotransmitters. Cocaine also has other indirect effects

on neurophysiology, including effects on the endogenous opioid systems.

54,55 Cocaine

is associated with compulsive use. The powerful reinforcing effects of cocaine have

been identified as occurring in brain regions rich in dopaminergic nerve terminals.

DOSAGE FORMS AND ROUTES OF ADMINISTRATION

In the manufacture of cocaine, organic solvents are used to solubilize the alkaloidal

bases from the leaves, which are then precipitated to form a sticky material, called

“pasta” or “cocaine paste.” The benzoylmethylecgonine (cocaine) in this “pasta” is

separated from most of the other plant alkaloids, converted to the hydrochloride or

other salts, precipitated, and dried. This product is the white cocaine hydrochloride

powder usually seen in the illicit market. The final product is usually “stepped on” or

“cut” (diluted) with various adulterants to increase profits for the dealers. According

to the DEA, in 2009 the average purity of cocaine was down from 68.1% in 2006 to

46.2%.

56 Powdered cocaine is generally snorted. Usually 10 to 25 mg of powdered

cocaine is placed on a mirror or flat surface, formed into a line, and then insufflated

through a straw or rolled dollar bill. A typical low to moderate user may consume 1

to 3 g/week. Cocaine powder can also be used for IV injection. The highly watersoluble powder is usually mixed with water and injected. When cocaine is injected

simultaneously with heroin, this is known as a “speedball.”

Cocaine hydrochloride melts at a high temperature, destroying much of its

psychoactivity in the process. Therefore, it is inefficient to smoke cocaine

hydrochloride in this form. The use of “freebase” cocaine became popular during the

late 1970s, because this form of cocaine has a lower melting point and can therefore

p. 1882

p. 1883

be smoked, producing an intense rush. For freebase, the cocaine hydrochloride is

dissolved into ethyl ether. The synthesis of freebase is dangerous, and the resultant

product may contain residual organic solvents, thus making it highly volatile and

putting the user at risk of burns.

In the mid-1980s a safer, easier method for extracting the cocaine base supplanted

the traditional freebase process. In the manufacture of “crack,” cocaine

hydrochloride is dissolved in water. When alkali (bleach or sodium bicarbonate) is

added to this aqueous solution, the free alkaloidal base (“crack”) precipitates out

whereas the salts and some adulterants stay in aqueous solution. The precipitate is

commonly referred to as a “rock.” The size of the rock varies but generally ranges

from one-tenth of a gram to a half a gram.

PHARMACOKINETICS AND EFFECTS

Cocaine generally produces a euphoriant action with a rapid onset and short duration.

Snorting cocaine generally produces euphoria and stimulation within 2 minutes;

smoking produces these effects within 6 to 8 seconds. Cocaine has a short

elimination half-life of approximately 30 minutes owing to its rapid metabolism by

esterases in the plasma, liver, brain, and other tissues.

54 When alcohol and cocaine

are consumed together, a metabolite, cocaethylene, is formed. Cocaethylene

intensifies the euphoric as well as the toxic effects of cocaine. The risk of death from

cocaethylene is 18 to 25 times greater than with cocaine alone.

56

An initial relaxed, euphoric, gregarious, talkative, hyperactive state characterizes

the “high” of cocaine. Additionally, the person may report increased interest in

sexual matters, diminished short-term memory, periods of intense concentration on

one limited subject, diminished hunger, hypervigilance, and a peculiar, slightly outof-body sense of one’s actions. Without additional doses of cocaine, these feelings

usually resolve into a state of mild depression, fatigue, hunger, and sleepiness by 1 to

3 hours. Physiologic manifestations include mydriasis, sinus tachycardia,

vasoconstriction with hypertension, bruxism, repetitive behavior, hyperthermia, and

talkativeness. After a few hours, continuous self-administration of cocaine will begin

to progress from euphoria to dysphoria and hallucinosis and then to psychosis. Some

users engage in nonstop binges of self-administration until psychological toxicity

develops.

57

ADVERSE EFFECTS

In 2007, 553,530 cocaine-related visits to an emergency department were reported in

the United States.

58 The potential adverse effects associated with both acute and

chronic use of cocaine are numerous and involve most organ systems in the body.

The cardiac complications associated with cocaine use include hypertension,

arrhythmias, myocardial ischemia and infarction, dilated and hypertrophic

cardiomyopathy, myocarditis, aortic dissection, and acceleration of atherosclerosis.

These cardiac effects have occurred in individuals with and without underlying heart

disease who have taken large or small doses by all routes of administration and may

be associated with acute or chronic use. The cardiac events can occur before, during,

or after other toxicities, such as seizures, and can be fatal. The mechanism of

cocaine-induced myocardial infarction is most likely multifactorial, involving one or

more of the following processes: coronary artery vasoconstriction, increased

myocardial oxygen demand related to increased blood pressure and increased heart

rate, increased platelet aggregation and thrombus formation, coronary vasospasm,

and arrhythmia. The risk is greatest within the first hour after use.

59 Studies have

shown 6% of patients presenting to emergency departments with chest pain after

cocaine use have myocardial infarctions.

56,57,59

The medical management of acute coronary syndromes differs when cocaine is the

cause. Specifically, nonselective β-blocker therapy (i.e., propranolol) is

contraindicated due to unopposed alpha affects, thrombolysis should be used with

caution, and nitroglycerine and benzodiazepines are part of first-line therapy.

56,57,59

In

patients with cocaine-associated chest pain, a 12-hour observation period to rule out

myocardial infarction or ischemia is probably sufficient before discharge from a

medical facility.

57

Cocaine has also been associated with cerebrovascular catastrophes. Stroke can

occur as a result of increased blood pressure, vasoconstriction, or thrombosis.

Seizures are another CNS complication. Seizures can occur with first use and are

most often single, generalized tonic–clonic seizures. Most occur within 90 minutes of

drug use, when drug plasma concentrations are highest.

54

The route of cocaine administration also affects the nature of the adverse effects.

For example, pulmonary complications, including pneumomediastinum,

pneumothorax, pneumopericardium, acute exacerbation of asthma, diffuse alveolar

hemorrhage, pulmonary edema, and “crack lung,” are associated with smoking crack

cocaine. Crack lung is a syndrome of acute pulmonary infiltrates associated with a

spectrum of clinical and histologic findings.

56 Snorting cocaine can lead to

perforation of the nasal septum because of the drug’s local anesthetic and

vasoconstrictive effects. IV use of cocaine has been associated with renal infarction,

wound botulism, viral hepatitis, HIV infection, bacterial endocarditis, sepsis, and

other infectious complications.

COCAINE USE DISORDER

A person who uses cocaine despite adverse consequences (emergency department

visit), uses it compulsively, suffers withdrawal symptoms, and alleviates symptoms

with further use is diagnosed with cocaine use disorder per the DSM-5. Prolonged or

heavy use of cocaine has been associated with the development of tolerance to some

of its central effects. Tolerance is caused by adaptive changes in the brain.

54 A

withdrawal syndrome may follow long-term or binge use. The initial, acute

symptoms, referred to as the “crash,” consist of depression, fatigue, craving,

hypersomnolence, and anxiety. Anhedonia and hyperphagia soon follow. Although

most symptoms are mild and resolve within 1 to 2 weeks, the dysphoria and

anhedonia can persist for weeks. These symptoms do not produce profound

physiologic changes and are generally not life-threatening.

57

TREATMENT OF COCAINE USE DISORDER

Most cases of simple cocaine withdrawal do not require medical treatment.

However, multiple pharmacologic therapies to facilitate abstinence from cocaine

have been, and continue to be, under investigation. Most studies have yielded

variable results, and to date no drug exists that is proven effective in treating cocaine

dependence.

15 Studies of dopamine agonists (amantadine, selegiline,

levodopa/carbidopa, pergolide), antidepressants (desipramine, fluoxetine,

bupropion), and carbamazepine have yielded inconsistent findings. Methylphenidate

has been investigated as “maintenance treatment” to satisfy the cocaine addict’s

desire for further enhancement of mood; however, methylphenidate also can stimulate

a powerful craving for the more intense euphoria of cocaine and has significant abuse

potential. Recent research shows promise for topiramate, baclofen, tiagabine, and

modafinil, but these findings require replication.

15 A cocaine vaccine is currently

under investigation. Psychosocial treatments focusing on abstinence have been

effective in the treatment of cocaine dependence.

15 Cognitive-behavioral therapies

and behavioral therapies, such as contingency management, along with 12-step–

oriented individual counseling can be useful, although the efficacy of these therapies

varies. Participation in a 12-step self-help group (AA, NA), as an adjunct to

treatment, seems to predict less cocaine use.

3,15

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p. 1884

Amphetamines

Central nervous system stimulants have been used both with and without social

acceptance for thousands of years. The Chinese prepared ephedrine-containing

products from a plant called Ma-Huang (Ephedra vulgaris).

7 People in East Africa

and the Arabian Peninsula chew the leaves of the khat bush (Catha edulis) for the

stimulating effects of the alkaloid cathinone.

54 Caffeine is consumed worldwide in a

usually socially acceptable manner in the form of coffee and energy drinks.

Amphetamine was synthesized in 1887, and methamphetamine in 1919. The legal

sanctions against widespread prescribing of amphetamines in the 1970s restricted

their supply and fostered a black market thriving on the illicit production of

methamphetamine powder (“speed,” “meth,” “crank,” “crystal meth”). During the

1990s, California and the West Coast experienced a dramatic resurgence of

methamphetamine-related hospital admissions, poison center calls, and law

enforcement actions. Methamphetamine misuse has since become a nationwide

problem, prompting government restrictions on retail sales of ephedrine and

pseudoephedrine (precursor chemicals used in the manufacture of methamphetamine).

A new marketing tool developed by savvy drug dealers aimed at younger, new users

involves bright coloring and flavoring (strawberry, cola, cherry, orange) added to

crystal methamphetamine to help mask the bitter taste. According to the National

Survey on Drug Use and Health for 2014, there were 569,000 current users of

methamphetamine in America.

4

PHYSICAL AND PSYCHOLOGICAL EFFECTS

CASE 90-7

QUESTION 1: D.C., a college student, used amphetamine this past weekend when partying with his friends.

He has a midterm examination in 2 days and is too tired to study, so one of his friends suggests snorting some

more amphetamine and then hitting the books. D.C. finds amphetamine very much to his liking and begins to

use it daily. He goes many days at a time without sleeping or showering and starts losing weight because he

seldom has an appetite. He believes his friends are working with the DEA and tapping his phone. Are these

symptoms of a stimulant use disorder?

Methamphetamine produces CNS stimulation by enhancing the effects of

norepinephrine, serotonin, and dopamine. This is accomplished by both blocking the

reuptake and stimulating release of these neurotransmitters. These effects are greater

for dopamine and norepinephrine than for serotonin.

47

The powerful stimulating effects of amphetamine and methamphetamine have made

their use popular among a wide variety of groups, including students, athletes, the

military, dieters, and long-distance truck drivers. Initially, the user may experience

alertness, euphoria, increased energy, the illusion of increased productivity,

sociability, and decreased appetite. Continuous dosing, however, produces

stereotypical grooming and other repetitive motions. Physiologic effects include

bruxism, tremor, muscle twitching, mydriasis, hypertension, diaphoresis, elevated

body temperature, nausea, dry mouth, weight loss, and malnutrition. Continued use

for several days decreases productivity and is associated with disordered thoughts,

paranoia, and psychosis. Tolerance develops very rapidly after continued use.

54

Illicit methamphetamine is commonly insufflated or injected and, less commonly,

taken orally. In a pattern similar to that seen with smoking cocaine, users freebase

methamphetamine and smoke it. Heating the crystals and smoking the vapor of

“crystal meth,” as with crack, is a common route of administration; however, snorting

and IV administration are also used. Absorption is rapid after smoking, and the

effects can last as long as 24 hours. Methamphetamine-induced psychosis may occur

more frequently with smoking.

D.C. will probably be able to stay awake to study if he uses more

methamphetamine; however, if he is up for too many days without sleep, his

performance on the examination will suffer.

ADVERSE EFFECTS AND TOXICITIES

D.C. is exhibiting classic signs of chronic methamphetamine abuse, which will likely

progress if he continues using. A “speed freak” or “tweaker” (chronic

methamphetamine user) is generally regarded even by other drug users as mentally

unstable, aggressive, and emotionally labile, with unpredictable periods of violent,

even homicidal, behavior. Chronic users characteristically develop complex

paranoid delusional systems with hallucinations during extended periods of

intoxication that may involve several sleepless days and nights of continuous

methamphetamine administration. This “speed psychosis” may include tactile

hallucinations, such as formication (the sensation of something crawling under the

skin). The initial treatment approach for stimulant-induced adverse psychologic

effects is nonpharmacologic. The distressed patient may be calmed by reducing

environmental stimuli and using the “ART” approach developed by the HaightAshbury Free Clinic in San Francisco: Acceptance of the patient’s immediate needs;

c a lm Reassurance that the condition is caused by the drug and will resolve

eventually; and Talk-down, which involves reassuring, reality-oriented

communication.

57 An extremely agitated, anxious, psychotic user, however, will often

require administration of a benzodiazepine, such as diazepam (10 to 30 mg orally or

2 to 10 mg intramuscularly or intravenously) or lorazepam (2 to 4 mg orally,

intramuscularly, or intravenously). If psychosis persists, a high-potency neuroleptic,

such as haloperidol (5 to 10 mg orally, intramuscularly, or intravenously) or

risperidone (2 to 4 mg orally), is preferred owing to its minimal anticholinergic

activity. Low-potency neuroleptics, such as chlorpromazine, with higher

anticholinergic activity, may worsen symptoms of delirium and hyperthermia.

57

The physiologic toxicity of stimulant drugs includes hypertension, stroke, seizures,

hyperthermia, sexual dysfunction, dental caries, rhabdomyolysis, renal failure,

cardiac arrhythmias and cardiomyopathies, myocardial infarction, and malnutrition.

The development of neurotoxicities involving dopaminergic and serotonergic

neurons (possibly through interference with monoamine transport and increased

production of reactive oxygen species) has been demonstrated in animals. It also

appears to cause permanent neuronal toxicity with prolonged use.

60

WITHDRAWAL AND TREATMENT

CASE 90-7, QUESTION 2: D.C. is arrested for assault after a bar fight. He is held in the county jail and is

unable to post bail. What withdrawalsymptoms might he experience during incarceration?

D.C. will probably suffer intense cravings for methamphetamine and initial

agitation, followed by fatigue and hypersomnolence. A withdrawal state after acute

cessation of chronic stimulant use is generally the same as that previously described

for cocaine. As with cocaine, the crash is notable for marked fatigue, depression, and

anhedonia. Most symptoms are mild and will resolve within 1 to 2 weeks, although

anhedonia and depression may persist.

Clinical studies investigating treatments for methamphetamine dependence is

similar to cocaine treatments. Currently, no pharmacologic treatments have been

proved effective for methamphetamine dependence. The most effective treatment so

far appears to be psychosocial therapies, such as cognitive-behavioral therapy and

contingency management.

57

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p. 1885

DISSOCIATIVE DRUGS: PHENCYCLIDINE,

KETAMINE, AND DEXTROMETHORPHAN

Phencyclidine (phenylcyclohexylpiperidine) and ketamine are arylcycloalkylamine,

dissociative, anesthetic agents. Phencyclidine (PCP) at one time was marketed as an

IV anesthetic agent under the trade name of Sernyl.

61 Subsequent reports of

postanesthetic dysphoric reactions caused the drug to be withdrawn in 1965. It was

reintroduced in 1967 as Sernylan and marketed as a veterinary anesthetic until 1978,

when the manufacture and sale of the drug became illegal. Ketamine is currently used

clinically as an anesthetic in both animals and humans. There is some data supporting

its use in treatment refractory depression but common side effect of dissociation has

confounded the blinding of studies and is a significant side effect. More research is

necessary but it is possible that it could be used for very short-term treatment during

the efficacy lag of established antidepressants.

62 Ketamine is shorter acting and

somewhat less potent than PCP.

Abuse of arylcycloalkylamines occurs primarily in large metropolitan areas. PCP

is relatively easy to synthesize and is inexpensive; therefore, it is often

misrepresented as other street drugs, such as lysergic acid diethylamide (LSD),

amphetamine, mescaline, or Δ-9-tetrahydrocannabinol (THC). Ketamine (“K,”

“Special K,” “Super K,” “cat valium”) is commonly used as a “club drug” and is

sometimes misrepresented as 3,4-methylenedioxymethamphetamine (MDMA;

ecstasy). Ketamine is often diverted from veterinarian supplies. PCP (“angel dust,”

“dust”) in powdered form is often applied to parsley, marijuana (“dusted joint,”

“superweed”), or tobacco cigarettes and smoked. Oral, intranasal and parenteral

routes of administration are used by some. The combination of cocaine and PCP in a

freebase smoking mixture is called “SpaceBase.” Although ketamine is manufactured

as an injectable liquid, it is frequently evaporated to a powder. The powder can be

snorted or compressed into tablets.

Dextromethorphan is an antitussive agent found in some over-the-counter cough

remedies. Its appeal as a drug of abuse may be because it is inexpensive, licit, lacks

social disapproval associated with other drugs, and available over-the-counter, and

abusers believe it to be safe because it is produced by a pharmaceutical company.

Street names include “Skittles,” “DXM,” “Dex,” “Robo,” “C-C-C,” and “Red

Devils.” Use is referred to as “dexing,” “robotripping,” and “robodosing.”

Dextromethorphan is the D-isomer of the codeine analog of levorphanol. The

metabolic byproduct of dextromethorphan, dextrorphan, has weak N-methyl-Daspartate (NMDA) antagonist properties.

61 When dextromethorphan is ingested in

large doses, it produces effects similar to PCP or ketamine. When abused, doses

range from 300 to 1,800 mg. The most commonly abused form is Coricidin HBP

Cough and Cold (called “C-C-C” on the street) because it contains the highest

concentration of dextromethorphan per dosage unit on the market (30 mg).

Dextromethorphan is also available for sale on the internet in powdered form, which

can be ingested orally or snorted. The dextromethorphan “high” can last 3 to 6 hours

and can consist of euphoria, dissociation, hallucinosis, increased perceptual

awareness, altered time perception, hyperexcitability, pressure of thought, and

disorientation; increased blood pressure, heart rate, and body temperature; and blurry

vision.

61 Other ingredients found in the over-the-counter preparations, such as

acetaminophen, chlorpheniramine, guaifenesin, and alcohol, may be problematic

when ingested in large doses. PCP is considered the typical dissociative drug, and

review of its effects largely applies to ketamine and dextromethorphan as well.

Phencyclidine

PHENCYCLIDINE INTOXICATION

Persons who use PCP may appear agitated, diaphoretic, and disoriented. There is an

increase in blood pressure, pulse, and temperature, and the person may experience

vertical and horizontal nystagmus. These symptoms are consistent with PCP

intoxication. PCP and ketamine are noncompetitive antagonists of the NMDA

receptor subtype of the major excitatory neurotransmitter, glutamate. The dose, route

of administration, and serum concentration of phencyclidine all influence the

pharmacologic effects of this drug and, thus, the symptoms of intoxication.

61 PCP in

low doses causes inebriation, ataxia, changes in body image, numbness, and a mind–

body dissociative feeling. Horizontal or vertical nystagmus or both are often present,

and the anesthetic effect of the drug raises the pain threshold. Amnesia can occur

after intoxication.

As the dose of PCP increases, the patient may manifest agitation, combativeness,

catatonia (ketamine users refer to this as a “k-hole”), and psychosis. The action of

PCP on the autonomic nervous system becomes more prominent and is characterized

by a confusing combination of adrenergic, cholinergic, and dopaminergic effects. A

hypertensive response is typically encountered. Tachycardia, tachypnea, and

hyperthermia may also be noted in the moderately intoxicated patient. The agitated,

combative patient often has feelings of great strength. This, combined with the

anesthetic effect of PCP, can result in serious injury because there is no pain

sensation to stop the physical activity.

With large doses of PCP, marked CNS depression occurs, and nystagmus may no

longer be present. In addition to the physiologic effects noted earlier, respiratory

depression, seizures, acidosis, and rhabdomyolysis may further compromise the

patient’s condition. Rhabdomyolysis, particularly in the presence of acidemia, can

result in acute renal failure.

57 Opisthotonic posturing and muscular rigidity occur

frequently in the severely intoxicated patient.

MEDICAL MANAGEMENT OF INTOXICATION

Diagnosis of PCP intoxication should be confirmed through a blood or urine

specimen. Currently, no clinically useful antidote to PCP exists, and treatment should

be supportive. Environmental stimuli should be minimized. Even attempts to talk

down the patient may trigger a combative response, and chemical restraints may be

indicated. Physical restraints may increase risk of rhabdomyolysis and should be

reserved for patients who pose threat of great danger to themselves or others.

Benzodiazepines are useful in the management of the anxious, agitated patient with

mild to moderate PCP intoxication. If benzodiazepines are insufficient, haloperidol

(5 mg IM) is effective.

57 Low-potency neuroleptics should be avoided because a

greater possibility of precipitating a hypotensive response or a seizure exists.

Hypertension may be managed with β-blockers or calcium-channel blockers.

Diazepam (5 to 10 mg intravenously to 30 mg total) is a useful anticonvulsant for the

management of PCP-induced seizures.

57 Because extreme agitation, seizures, and

hyperthermia can initiate rhabdomyolysis and secondarily cause myocardial, renal,

or hepatic dysfunction, anxiolytics, neuroleptics, anticonvulsants, and cooling

measures should be used as needed.

The urinary excretion of PCP (a basic compound) is enhanced when the urine is

acidic; however, this approach is not recommended because it may exacerbate

myoglobinuric renal failure.

51 Activated charcoal in a dose of 50 to 150 g initially,

then 30 to 40 g every 6 to 8 hours, can prevent the intestinal reabsorption of this drug

and promote its elimination.

57

PSYCHOLOGICAL AND PROLONGED EFFECTS

Chronic PCP use can result in prolonged residual psychological symptoms, including

anxiety, depression, and psychosis.

57

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p. 1886

Pharmacotherapy for these symptoms may be necessary. Prolonged psychiatric

sequelae are almost always associated with premorbid psychopathology. Perceptual

disorders, including auditory and visual hallucinations, such as after images seen

following moving objects (“trails”), may also occur. Flashbacks (discussed in detail

in the subsequent section on LSD) have been reported after PCP use.

The DSM-5 does not recognize PCP withdrawal; however, about one-fourth of

heavy PCP users report symptoms after discontinuation of use.

57 These symptoms

include depression, anxiety, irritability, hypersomnolence, diaphoresis, and tremor.

Animal studies have described a withdrawal syndrome, but it is unclear whether a

true withdrawal syndrome occurs in humans.

57 Currently, no pharmacologic

treatments for PCP use disorder exist. Some animal data indicate neurotoxicity;

however, the long-term consequences and significance for humans are unknown and

require further study. Chronic users often complain of feeling “spaced”; they may be

irritable and antisocial and feel depersonalized and isolated from people. Memory

lapses, speech and visual disturbances, and confusion have been described in longterm users as well.

HALLUCINOGENS

Hallucinogens can be categorized as indole alkylamines (e.g., LSD, psilocybin, and

dimethyltryptamine) or phenethylamines (e.g., mescaline; MDMA). LSD is

considered the prototype hallucinogen. Although MDMA is classified as a

phenethylamine, it has structural similarities to amphetamine and mescaline. It has

been labeled an entactogen or empathogen because of its strong empathy-producing

effects and mild hallucinogenic effects. The term entactogen can be translated as “a

touching within.” Hallucinogens are commonly referred to as psychedelics.

In 2014, 1.2 million Americans were current hallucinogen users. The popularity of

MDMA (ecstasy, X) has risen dramatically in recent years, partly because of its use

as a “club drug.” In 2014, 609,000 Americans reported using MDMA sometime in

the past month.

4 The usual pattern of use for hallucinogens is occasional selfadministration for enhancement of recreational activities, such as dancing, or for

“mind expansion.” Certain individuals may develop psychological dependence and

use hallucinogens in a more chronic and compulsive manner.

LSD

EFFECTS

Perhaps the most famous of all hallucinogens, LSD-25 was first synthesized by

Albert Hofmann of Sandoz Laboratories in 1938. It was developed as an analeptic

agent but produced significant uterine stimulation and caused experimental animals to

become excited or cataleptic. Five years later, while resynthesizing LSD-25 for

further pharmacologic testing, Dr. Hofmann experienced a restlessness that forced

him to go home. This was followed by 2 hours of intense visual hallucinations of

kaleidoscopic images and colors. Later, he identified LSD-25 as a potent

hallucinogen. Clinical experimentation produced hundreds of papers describing LSD

as a drug that could facilitate psychotherapy, particularly in the management of

addictive behavior. Widespread public self-experimentation with LSD for recreation

and self-exploration, coupled with growing attention to adverse psychological

consequences, led Sandoz to discontinue production of LSD-25 (as well as

psilocybin, psilocin, and related congeners) in August 1965. The United States made

LSD a schedule I controlled substance in 1970 after the proliferation of illicit

suppliers to meet the huge public demand for this drug.

Although the mechanism of action of classic hallucinogens is not fully understood,

they appear to predominately act as agonists or partial agonists at serotonin (5-HT)

receptors, specifically the 5-HT2

receptor.

63 LSD, one of the most potent

hallucinogens known, is active at doses of 25 to 250 mcg. Most users take about 100

to 150 mcg of LSD for a significant effect. This dose produces mild to moderate

sympathomimetic effects, profound visual hallucinosis, and the sensation of

disordered integration of sensory input. For example, sounds and music are

perceived as visual imagery, odors are felt, and inanimate objects assume lifelike

qualities. In addition to these sensory-perceptual effects, psychic effects occur, such

as depersonalization, dreamlike feelings, and rapid alterations of affect. These are

accompanied by somatic effects, including dizziness, nausea, weakness, tremor, and

tingling skin.

63 These combined effects begin within an hour of ingestion of LSD and

usually peak in intensity during the first 2 to 4 hours. After taking LSD, most people

feel they have returned to a normal psychological state by 10 to 12 hours.

64 Within an

hour after ingestion, a person will begin to experience altered sensations of his/her

surroundings, in addition to some psychic and somatic effects.

ADVERSE EFFECTS

The most frequently encountered adverse reaction associated with the hallucinogenic

drugs is a mental state of acute anxiety and fear, typically referred to as a “bad trip.”

The hallucinogen experience is influenced by set (the user’s mental state and

expectations of drug effects) and setting (the environment in which drug use takes

place, including the social conditions). Users may be able to calm themselves

without outside intervention. The initial therapy of people undergoing a bad trip is

frequently called “reality therapy” and consists of talking down the fear and panic.

This consists of getting the person to a quiet, relaxed setting and helping him or her

focus on explanations for the uncertainties that are causing the panic. This process

also tends to reassure the person that he or she is in a safe physical environment and

that the drug effects will diminish in a few hours. Most of these bad trips are

resolved during the state of intoxication (generally, 6–12 hours), but some last as

long as 24 to 48 hours.

57

If the talk-down approach is not successful in resolving the panic, drug therapy can

be considered. Sedation with an oral benzodiazepine (i.e., diazepam 10–30 mg) or a

parenteral benzodiazepine (i.e., lorazepam 2 mg IM) will frequently alleviate the

panic.

57 Supportive talking down should be continued because the benzodiazepine

will not stop the trip; it will simply sedate the patient. Haloperidol 2 mg IM may also

be used if benzodiazepines are insufficient. Phenothiazines should not be used for

initial management of bad trips because they have been associated with poor

outcomes.

57

Regarding adverse physical effects, classic hallucinogens have a high margin of

safety, although patients should be monitored for seizures or elevations in body

temperature, which may indicate a potential hyperthermic crisis. Anticonvulsant

therapy may not be effective until body temperature has been lowered.

57

FLASHBACKS AND LONG-TERM EFFECTS

Use of hallucinogens can trigger a transient psychosis or unmask an underlying

psychiatric disorder; however, a true psychotic episode is rare. Psychiatric

conditions after hallucinogen use that persist more than a month are likely caused by

preexisting psychopathology.

57 Hallucinogen use does not seem to be associated with

any cognitive impairment.

64

Hallucinogen persisting perceptual disorder (HPPD), commonly referred to as

flashbacks, is characterized by recurrences of part

p. 1886

p. 1887

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