1 . The term "hallucinogen" is derived from the Latin alucinari, meaning
| A) | | to see the unseen. |
| B) | | spiritual awakening. |
| C) | | to wander in mind or talk idly. |
| D) | | an understanding of time and space. |
The term "hallucinogen" is derived from the Latin alucinari, meaning to wander in mind or talk idly[1]. Hallucinogens are agents that alter
perceptions without major autonomic or metabolic changes or agents that cause alterations in
perception, cognition, and mood as their primary psychobiologic action in the presence of an
otherwise clear sensorium [2]. A typical
hallucination induced by a classical hallucinogen (i.e., mescaline, peyote) is more accurately
described as a modification of regular perception, with the user usually aware of the illusory
and personal nature of their perceptions [1].
In 1956, the psychiatrist Humphrey Osmond coined the term "psychedelic," meaning
"mind-manifesting," to describe drugs such as lysergic acid diethylamide (LSD) and mescaline.
The term is a reference to the drugs' ability to illuminate normally hidden aspects of the
mind or psyche [3]. This term became
popularized in the 1960s and is often used interchangeably with the term hallucinogen to
describe both the classical hallucinogens and their effects.
2 . Lysergic acid diethylamide (LSD) was originally synthesized in 1938 by
| A) | | Salvador Dali. |
| B) | | Timothy Leary. |
| C) | | Albert Hofmann. |
| D) | | Humphrey Osmond. |
Intense interest in hallucinogens in Western society began with
the discovery of LSD. In 1938, in search of a new migraine medicine, Swiss biochemist Albert
Hofmann synthesized LSD at the Sandoz Pharmaceutical laboratories. It was not until 1943, when
some of the liquid chemical substance spilled onto his hand, that Hofmann experienced the
first recorded LSD "trip." He recounted that 45 minutes after absorbing some of the chemical
into his skin, he became increasingly dizzy, developed visual disturbances, and had a marked
desire to laugh. An hour into the experience, he asked his assistant to call a doctor and
accompany him home. In Hofmann's mind, he was not on the familiar street that led him home but
instead on a street painted by Salvador Dali, a funhouse roller coaster where the buildings
yawned and rippled [3].
3 . Perhaps one of the most promising areas of investigation involving LSD was in the treatment of
| A) | | alcoholism. |
| B) | | schizophrenia. |
| C) | | amnesia or memory loss. |
| D) | | narcissistic personality disorder. |
THERAPEUTIC USE OF HALLUCINOGENS
Perhaps one of the most promising areas of investigation
involving LSD was in the treatment of alcoholism. The initial rationale for LSD use in this
context was the perceived similarity between the LSD effect and the experience of delirium
tremens (DT) as described by patients with alcohol use disorder. It was hypothesized that
LSD could safely replicate the DT experience, inducing fear and possibly benefiting patients
with alcohol use disorder. Researchers revised their theoretical basis for using LSD for
patients with alcohol use disorder when they realized that LSD had the potential to cause a
surge of previously repressed material [50].
4 . How many Americans tried a hallucinogen for the first time in 2023?
| A) | | 250,000 |
| B) | | 1,510,000 |
| C) | | 8,200,000 |
| D) | | 10,000,000 |
In 2023, an estimated 1,510,000 Americans older than 12 years
of age tried a hallucinogen for the first time [54]. An annual national survey of drug use among high school students in the
United States found that 7.1% of 12th graders reported lifetime hallucinogen use in 2022 and
4.4% reported hallucinogen use in the past year [8]. When specifically asked about LSD use, 4.4% reported lifetime use and
2.5% reported use in the past year. The percentages among 12th graders represent decreases
compared to a peak in the late 1990s/early 2000s.
5 . The risk of hallucinogen dependence is lowest for recent-onset users of
| A) | | psilocybin. |
| B) | | mescaline. |
| C) | | phencyclidine (PCP). |
| D) | | 3,4-methylenedioxymethamphetamine (MDMA). |
During 2023, approximately 3.1 million individuals 12 years of
age or older used a hallucinogen on at least one occasion [54]. Among first-time hallucinogen users, an estimated 0.1% to 3% will become
hallucinogen dependent [9,54,55]. In a study examining the characteristics of persons who become
hallucinogen dependent, first use at an early age (10 to 11 years) was associated with
increased risk, with the median elapsed time from onset of use to onset of dependence being 12
to 13 months [12]. These data validate
previous reports of a very infrequent but tangible dependence syndrome developing soon after
the onset of hallucinogen use [12]. The risk
of hallucinogen dependence is also believed to be low if the hallucinogen was the first drug
used. The risk of hallucinogen dependence is highest for recent-onset users of mescaline,
MDMA, and PCP, and lower for psilocybin.
6 . The two main categories of classical hallucinogens are
| A) | | indole and catechol. |
| B) | | dopamine and norepinephrine. |
| C) | | anticholinergic and tryptamine. |
| D) | | phenethylamine and N-methyl D-aspartate (NMDA) antagonists. |
The classical hallucinogens are divided into two main classes
based on molecular structure: indole and catechol. The indole class, also referred to as the
tryptamines, consists of alkaloids that act on serotonin. They are thus named because the
basic structure of the neurotransmitter serotonin is referred to as an indole nucleus, which
comprises the core structure of all of the drugs in this group. Indole hallucinogens include
psilocybin, LSD, lysergic acid hydroxyethylamide (LSA), DMT, and
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) [1,5,13,58].
7 . MDMA is an example of a(n)
| A) | | deliriant. |
| B) | | amphetamine analog. |
| C) | | classical hallucinogen. |
| D) | | dissociative anesthetic. |
The catechol class, or the phenethylamines, constitutes the
second group of classical hallucinogens. This group is made up of plant alkaloids, such as
mescaline and nutmeg. The amphetamine analogs that are considered designer drugs, such as DOM,
3,4-methylenedioxyamphetamine (MDA), MDMA, 2,5-dimethoxy-4-ethylamphetamine (DOET), and
3,4,5-trimethoxyamphetamine (TMA), may also be categorized in this class. The amphetamine
analogs are a large group of drugs, and due to substitution on the ring of the catechol
nucleus, their effects more closely resemble mescaline than amphetamine. The catechol nucleus
closely resembles the catecholamine neurotransmitters dopamine and norepinephrine, and
catechol hallucinogens act on catecholamine neurotransmitter systems [5].
8 . The classical hallucinogens all share what common mechanism?
| A) | | Kappa-opioid receptor agonist activity |
| B) | | 5-HT2A receptor binding as partial agonists |
| C) | | Antagonism of acetylcholine receptors of the muscarinic subtype |
| D) | | Interaction with the serotonergic, noradrenergic, and dopaminergic receptor systems |
PHARMACOLOGY AND CLINICAL EFFECTS
Hallucinogenic drugs are pharmacologically heterogeneous and
diverse, produce dissimilar effects, and likely work through distinct mechanisms. However,
the classical hallucinogens all share a common mechanism: 5-HT2A receptor binding as partial
agonists [2,15,60]. Of the hundreds of plants known to possess hallucinogenic properties,
the active agents of these botanicals fall into surprisingly few chemical classes, with the
indole nucleus of serotonin common to the majority of these compounds [1].
9 . Hallucinations associated with LSD use are most often
| A) | | visual. |
| B) | | tactile. |
| C) | | auditory. |
| D) | | olfactory. |
PHARMACOLOGY AND CLINICAL EFFECTS
At higher doses, the initial effect consists of sympathetic
arousal 20 to 30 minutes following ingestion, manifested as dizziness, anxiety, increased
pulse and blood pressure, dilated pupils, piloerection, hyperreflexia, and mild pyrexia.
Following this, there is a period of increasingly intense perceptual distortion;
hallucinations can occur in any sensory modality, the most common being visual and the least
common auditory [17]. The perception of time
passage is often distorted. Synesthesia, whereby two or more senses are blended, and
delusions are unusual.
10 . Cross-tolerance has been demonstrated in humans between LSD and
| A) | | cannabis. |
| B) | | psilocybin. |
| C) | | amphetamines. |
| D) | | All of the above |
PHARMACOLOGY AND CLINICAL EFFECTS
Mental functions are differentially affected by LSD. Memory
is unaffected, although perception, orientation, concentration, and other measures of
cognition may be impaired in a dose-dependent manner. Cross-tolerance has been demonstrated
in humans between LSD, psilocybin, and mescaline but not between LSD and amphetamines or
cannabis. There have been no documented toxic fatalities from LSD ingestion [1].
11 . Lysergic acid hydroxyethylamide (LSA) is a tryptamine found in
| A) | | a spineless cactus. |
| B) | | Central American mushrooms. |
| C) | | the Sonoran Desert toad, Bufo alvarius. |
| D) | | the seeds of Ipomoea violacea (morning glory) and Argyreia nervosa (Hawaiian baby woodrose). |
PHARMACOLOGY AND CLINICAL EFFECTS
LSA is a tryptamine found in the seeds of Ipomoea violacea (morning glory) and Argyreia nervosa (Hawaiian baby woodrose). When ingested, the drug is
psychoactive through 5-HT2A receptor agonism. Morning glory seeds were used in Aztec
rituals in ancient Mexico, and their popularity increased in the 1960s, when the seeds
were used as a substitute for LSD. Morning glory seeds are consumed orally, either
pulverized or as an extract of the psychoactive alkaloids. Threshold effects are noted
with the ingestion of 3–6 g, with dosages of 200 to 500 seeds producing intense
hallucinations as well as intense nausea, vomiting, and abdominal pain. Morning glory
seeds and plants are sold in most nurseries and botanic supply stores. However, commercial
morning glory seed producers coat the seeds with emetic agents in an attempt to discourage
recreational ingestion [14,19].
12 . A dosage of 12–20 mg of psilocybin produces an altered state of consciousness characterized by
| A) | | depression of affect. |
| B) | | enhanced perception of time. |
| C) | | altered psychologic functioning. |
| D) | | decreased ability for introspection. |
PHARMACOLOGY AND CLINICAL EFFECTS
A dosage of 12–20 mg of psilocybin produces an altered
state of consciousness characterized by stimulation of affect; enhanced ability for
introspection; altered psychologic functioning; perceptual changes, including illusions,
synesthesia, and affective activation; and alterations of thought and time sense. As with
any hallucinogen, the potential exists for a panic or severely dysphoric reaction in the
user, although less so than with LSD [20,51].
13 . When inhaled as vapor, strongest effects of 5-methoxy-N,N-dimetheyltryptamine (5-MeO-DMT) dissipate after
| A) | | 15 seconds. |
| B) | | 5 minutes. |
| C) | | 30 minutes. |
| D) | | 1 hour. |
PHARMACOLOGY AND CLINICAL EFFECTS
5-MeO-DMT, a naturally occurring hallucinogen, is closely
related to DMT. One source of 5-MeO-DMT is the Sonoran Desert toad, Bufo alvarius, which secretes large amounts of the hallucinogen
from its parotid glands. Although the venom of B.
alvarius is known to be toxic when consumed orally, it can be safely smoked.
To extract the venom, the toad is held against a flat surface while the parotid gland is
massaged. The liquid venom is then collected, dried, and smoked. Based on reported
experiences, a single deep inhalation of the vaporized venom is powerfully psychoactive
within 15 seconds. Consistent with the known effects of 5-MeO-DMT, the drug effect has
been described as intense and short-lived, characterized by auditory and visual
hallucinations. The strongest effects dissipate after five minutes, but residual changes
in perception persist longer than one hour. No toxic effects have been reported. A single
B. alvarius toad yields 0.25–0.5 g of dried venom. As
concentrations of 5-MeO-DMT in the venom may be as high as 15%, one toad can yield as much
as 75 mg of the hallucinogen that, when smoked, is effective in humans at doses of 3–5 mg.
Thus, a single toad can produce more than 15 doses of one of the most potent psychoactive
drugs found in nature [21].
14 . Peyote cactus may only be legally harvested by
| A) | | licensed growers. |
| B) | | Mexican citizens. |
| C) | | the United States government. |
| D) | | licensed representatives of the Native American Church. |
PHARMACOLOGY AND CLINICAL EFFECTS
The 1- to 4-inch diameter top portion of the cactus,
referred to as the peyote button, is the section of the plant with the highest mescaline
concentration. The peyote button can be eaten fresh or dried, steeped, or ground into a
powder. A typical dose is 6 to 12 buttons, with each button containing 45 mg of mescaline.
Mescaline is well absorbed in the gastrointestinal tract and within one hour of ingestion
induces nausea, vomiting, abdominal cramps, dizziness, sweating, restlessness, and
palpitations. The second phase of the drug effect begins within one to 3 hours of
ingestion and is characterized by visual imagery, altered perceptions, and psychologic
insight. The psychoactive effects typically last 6 to 12 hours [14]. Peyote use is legal for the 300,000
members of the Native American Church for ceremonial or religious purposes or to promote
physical and mental well-being. Only licensed representatives of the Native American
Church may legally harvest peyote cactus [19].
15 . Which of the following is NOT an undesirable effect of nutmeg use?
| A) | | Drowsiness |
| B) | | Tachycardia |
| C) | | Paresthesias |
| D) | | Excessive salivation |
PHARMACOLOGY AND CLINICAL EFFECTS
Nutmeg is the kernel inside the fruit of the evergreen
tree Myristica fragrans, indigenous to the Maluku
Islands in Indonesia. Historically, nutmeg has been used medicinally for various
afflictions, including gastrointestinal disorders, musculoskeletal problems, and
psychiatric conditions, and has a long history of recreational use. Although nutmeg use
often results in unpleasant side effects, it is preferred by some users in search of a
legal and easily obtainable euphoric drug with hallucinogenic effects. The hallucinogenic
properties of nutmeg are caused by alkyl benzene derivatives (myristicin, elemicin, and
safrole) and terpenes. Although the exact psychoactive mechanism is unclear, myristicin
and elemicin are believed to be metabolized to amphetamine-like compounds similar to
3-methoxy-4,5-methylenedioxyamphetamine (MMDA) and TMA. Ground nutmeg is ingested in 5–20
g doses, or approximately 2 tablespoons of powder. Most users develop nausea and vomiting
within an hour, followed by central nervous system (CNS) intoxication and hallucinations
for three to eight hours. Undesirable effects include blurred vision, dizziness,
drowsiness, xerostomia, flushing, palpitations, paresthesias, numbness, hypotension, and
tachycardia [14,22].
16 . The peak drug effect after consumption of Amanita muscaria occurs after
| A) | | 1 to 2 minutes. |
| B) | | 1 to 2 hours. |
| C) | | 5 to 10 hours. |
| D) | | 24 hours. |
PHARMACOLOGY AND CLINICAL EFFECTS
A. muscaria is usually
dried and consumed orally. The drying/heating process decarboxylates the ibotenic acid
into muscimol, thus reducing toxicity and increasing the psychoactive effect. All parts of
the mushroom are psychoactive, although the portion just under the skin may be most
potent. An average dose is 5–10 g, and 10–30 g of dried mushroom is considered a high
dose. The drug effect peaks 1 to 2 hours after ingestion, with a duration of 5 to 10 hours
[28].
17 . "Fry" is the term used to describe
| A) | | LSD-soaked paper. |
| B) | | a mixture of PCP and mescaline. |
| C) | | MDMA that is ingested by smoking. |
| D) | | PCP-laced cannabis cigarettes that are soaked in embalming fluid. |
PHARMACOLOGY AND CLINICAL EFFECTS
"Fry" is the term used to describe PCP-laced cannabis
cigarettes that are soaked in embalming fluid, with embalming fluid consisting of
formaldehyde, methanol, and ethanol. In some cases, tobacco cigarettes are used. The
primary effect of smoking these cigarettes is toxic psychosis, with other effects
including hallucinations, delusions, panic, paranoia, increased sexual arousal, and loss
of consciousness. Side effects associated with the inhalation of embalming fluid include
disorganized thoughts, decreased attention span, psychomotor agitation, and sympathetic
nervous system up-regulation. Patients who have smoked this drug typically manifest severe
dysphoric effects upon emergency room admission. Exposure to embalming fluid can result in
bronchitis, body tissue destruction, impaired coordination, inflammation, brain and lung
damage, and sores in the throat, nose, and esophagus [36].
18 . Hallucinogen persisting perception disorder (HPPD), or "flashbacks," are characterized by
| A) | | a resemblance to a schizoaffective disorder. |
| B) | | compromised visuospatial integrity and memory deficits. |
| C) | | persistent perceptual abnormalities that mimic the effects of acute hallucinogen intoxication. |
| D) | | a severe distortion of sense of position or kinetic sense, leading to the perception of free-falling or flying. |
EFFECTS OF HALLUCINOGEN USE
Hallucinogen persisting perception disorder (HPPD), or
"flashbacks," are characterized by persistent perceptual abnormalities that mimic the
effects of acute hallucinogen intoxication. These abnormalities are not attributable to
another medical or psychiatric condition and persist for weeks or months after the last
hallucinogen exposure [43]. In order for a
diagnosis to be established, the perceptual symptoms must cause clinically significant
distress.
19 . Acute LSD toxicity, characterized by a severely dysphoric or panic reaction ("bad trip"), is best treated with
| A) | | neuroleptics. |
| B) | | gastric lavage. |
| C) | | antidepressants. |
| D) | | benzodiazepines. |
TREATMENT OF HALLUCINOGEN TOXICITY
Although all classical hallucinogens have the potential to
induce an extremely frightening experience, LSD probably accounts for most of the "bad
trips" that come to the attention of medical providers due to the intensity of its effects
and its prevalence relative to the other hallucinogens. Acute LSD toxicity commonly presents
to the emergency department as a severely dysphoric or panic reaction superimposed on the
drug effect. Effective management begins with a careful history and an accurate description
of the ingested substance. Adulteration is surprisingly uncommon; mistaken attribution is
more common. LSD toxicity historically has been managed with neuroleptics. However, it is
now recognized that the neuroleptics may intensify the experience. Benzodiazepines (e.g.,
diazepam 20 mg orally or alprazolam 1–2 mg intramuscularly) are widely regarded as rapid and
effective treatment, with resolution of symptoms often occurring within 30 minutes [1]. Toxic reactions to the other classical
hallucinogens should be managed in the same manner [14,16].
20 . Patients with post-dissociate depression should be maintained on antidepressant therapy for at least
| A) | | 10 to 14 days. |
| B) | | 3 to 6 weeks. |
| C) | | 3 to 9 months. |
| D) | | 1 year. |
TREATMENT OF HALLUCINOGEN TOXICITY
Long-term dissociative use suppresses the production of
dopamine and norepinephrine, which can persist into abstinence, possibly leading to
depression. Antidepressants with noradrenergic and dopaminergic specificity can counteract
this suppressant effect. Patients with post-dissociate depression should be maintained on
antidepressant therapy for at least three to nine months [16].
