Chapter 12: Psychedelic Drugs
Psychedelic drugs induce a reality-altering experience consisting of hallucinations, sensory distortions, or
delusions. Classified into three general categories: hallucinogens, mixed stimulant-psychedelics, and dissociative
Hallucinogens represent a large class of psychedelic drugs that produce hallucinations as their main
The most representative of this drug class is lysergic acid diethylamide (LSD), which goes by the street name
acid, window pane, and blotter. This is a schedule 1 drug.
Other hallucinogens include psilocybin, mescaline, and dimethlytryptamine.
Psilocybin is the main psychoactive constituent in hallucinogenic mushrooms belonging to the genus Psilocybe.
User refers to these mushrooms as magic mushrooms or shrooms. After oral administration, psilocybin rapidly
converts to its active metabolite psilocin, a hallucinogenic substance that likely account for most of
Mesacaline is found in peyote, a small, spineless cactus. Users obtain mescaline by chewing disk-shaped
buttons within the cactus crown.
Dimethyltrypatamine (DMT) s found in Mimosa hostilis, Virola calophylla and other hallucinogenic American
Origins of LSD and Other Hallucinogens
In the past, hallucinogenic plants were used as psychic medicines to treat maladies, communicate with gods,
and perform magic.
Albert Hofmann, a chemist who worked for Sandoz Laboratories discovered LSD’s hallucinogenic effects.
The U.S. Army tested LSD as an aid for inducing captured enemy prisoners to talk more freely and also used in
During psychoanalysis era, psychiatrists used LSD to gain access to supposedly unconscious thoughts in their
Many practitioners especially feared producing prolonged bad trips, lasting as long as 48 hours. Occasionally,
bad trips led to suicides.
LSD Ingestion and Effects
LSD and most other hallucinogens are normally orally administered.
LSD is potent, with effective amounts beginning at only 0.025 mg. Researchers consider 0.075-0.15 mg a
moderate dose range capable of achieving a significantly altered state of consciousness.
Due to potency, a common preparation method involves applying drops of a solution of LSD onto small
squares of blotter paper or the glue sides of postage stamps. In either case, LSD sticks to the paper, and
recreational users ingest the drug by licking the paper.
LSD reaches peak absorption after 60 minutes. The cells in the liver metabolize LSD producing 2-oxo-3-
hydroxy-LSD. LSD’s elimination half-life is 3 hours, which facilitates pharmacological effects lasting as long
as 8 hours.
LSD and the Serotonin Neurotransmitter System
The chemical structure of LSD resembles serotonin’s chemical structure, allowing LSD to act on serotonin
LSD functions as a receptor agonist with a high binding affinity for 5-HT1A, 5-HT2A, 5-HT6, and 5-HT7
receptors. In particular, LSD activates serotonin receptors located postsynaptically on other neurotransmitter
neurons, such as glutamate and GABA neurons. In the visual cortex, LSD activates both 5-HT1A and 5-HT2A receptors. Hallucinogen activation of serotonin
receptors can interfere with modal object completion, which is a perception of object boundaries inferred from
incomplete representations of the object.
o The N170 waveform is strongly associated with modal objet completion. These reduced N170
waveform amplitudes correlated with overall decreased activity in the occipital lobe.
Second, hallucinogens alter functioning in the locus coeruleus. In the locus coeruleus, LSD’s activation of post
synaptic 5-HT2A receptors increases the activity of both glutamate and GABA neurons. LSD causes normally
suppressed sensory information from the locus coeruleus to become more refined and sailent.
In the prefrontal cortex, LSD activation of 5-HT2A receptors also causes increased glutamate release.
Enhanced glutamate release, in turn, increases activity in the prefrontal cortex, the central integration area of
processed sensory information.
The LSD-like hallucinogen psilocybin produced a significant increase in the metabolism of labeled glucose, an
index of neuronal activity in the prefrontal cortex. In addition psilocybin elicited enhanced activity in the
temporomedial cortex, a region involved in complex visual processing.
LSD’s Mild Physiological Effects and Profound Hallucinogenic Effects
Although few, if any, physiological effects occur with normally used amounts, LSD and other serotonin-
like hallucinogens exhibit pronounced subjective experiences.
A true hallucination is a perception of images or sounds that are not real. Drugs such as LSD, alter the
perception of things that are real.
Normal LSD doses cause distorted, waiving, or kaleidoscopic forms of real images in a visual field, these
are called pseudo-hallucinations.
True hallucinations can occur with LSD, but they are rare.
The overall hallucinogenic experience is called a trip.
o A good trip is characterized by having highly desirable sensory distortions and pseudo-
hallucinations. During good trips, a use may experience feelings of enhanced perception or
insightfulness, as well as synethesia (experiencing sensory stimuli in an incorrect sensory
modality). For example, often consists of experiencing sounds when seeing colours and vice versa.
o A bad trip is associated wit disturbing true hallucinations, psychotic episodes, negative emotional
states, altered perception of time, and out-of-body sensations.
A person’s expectations and previous experiences affect LSD’s subjective effects. Factors that can affect a
person’s trip can include physical surroundings, current emotional state, comments made by friends and
many other factors.
It has been suggested that scepticism about LSD’s effects largely suppress the LSD experience.
LSD also causes hypersuggestibility, a state that can jeopardize reality testing. During some trips, users
have jumped off buildings in belief they could fly or stepped infront of traveling cars in the belief they
lacked material substance.
Hallucinogens and Flashbacks
Occasionally, users may randomly experience a striking memory of the previous trip. Such an experience is
referred to as a flashback or as symptom of hallucinogen persisting perception disorder.
o Flashback usually refers to a short, nondistressing recurrence of a previous trip. On the other hand,
hallucinogen persisting perception disorder is characterized by recurring, longer-term and
unpleasant experiences that are difficult to reverse.
Mixed Stimulant Psychedelic Drugs
Mixed stimulant psychedelic drugs refers to substances that exhibit both psychostimulant and
hallucinations as their primary pharmacological effects.
One of these drugs is 3,4 methylenedioxyethamphetamine (MDMA, or Ecstasy). o Ecstasy can refer to any number of stimulant or psychedelic preparations that may contain only
small amounts or even no amount of MDMA.
Although MDMA is best known for its psychedelic and psychostimulant effects it is also known as
entactogen meaning “touching within,” or as an empathogen, referring to enhanced empathy.
MDMA shares a similar chemical structure with amphetamine and possesses many of amphetamine’s
psychostimulant effects. Yet MDMA also produces LSD-like hallucinations, so it fits into the mixed
psychedelic-stimulant class of drugs.
This drug class also includes AMT and 5-MeO-DIPT.
MDMA is frequently used in raves, large organized parties held in dance clubs or warehouses where
electronic dance music is played with accompanying light shows. MDMA and other psychedelic drugs
enhance this club experience.
MDMA Therapeutic and Recreational Use
Beginning in the late 1970s, MDMA emerged as a recreational drug. People sought it for spiritual
enlightenment, improving sensuality in relationships, and pure enjoyment.
MDMA-assisted improvements in patients with post-traumatic stress disorder.
MDMA Metabolism and the Length of Psychedelic Drug Effects
MDMA users prefer to administer MDMA orally, usually through swallowing an MDMA-containing tablet.
After swallowing the tablet, MDMA readily absorbs through the gastrointestinal tract, reaching peak blood
plasma levels after approximately 2 hours. MDMA’s elimination half-life is approximately 9 hours.
MDMA is metabolized in the liver primarily by CYP2D6 enzymes and to a lesser extent by other enzymes
such as CYP1A2.
CYP1A2 converts MDMA to MDA. Like MDMA, MDA exhibits psychedelic drug effects. Its users thus
experience specific MDMA effects and then, after metabolic transformation, effects elicited by MDA as
Deficiencies in the CYP2D6 enzyme leads to accumulation of MDMA in the body leading to prolonged
drug effects and an increased probability of adverse effects occurring at low to moderate doses.
Inhibition of MDMA metabolism can occur in people with fully functional CYPD26 enzymes as well.
MDMA and Serotonin and Dopamine Neurotransmission
Acute administration of MDMA alters serotonin neurotransmission at axon terminals through two
First, MDMA inhibits serotonin transportation into synaptic storage vesicles. In doing so, MDMA prevents
serotonin storage and permits serotonin to escape into the synaptic cleft.
Second, MDMA causes the reversal of serotonin reuptake transporters. By reversing serotonin membrane
transporters, MDMA expels any unstored serotonin out into the synaptic cleft.
These increased serotonin levels lead to increased activation of serotonin receptors.
Like amphetamine, MDMA produces similar actions at dopamine axon terminals, leading to enhanced
extracellular levels of dopamine in the brain.
However, MDMA’s effects on dopamine axonal terminals are weaker than its effects on serotonin axonal
terminals. As a result, higher MDMA doses may be necessary to enhance dopamine levels.
Chronic administration of MDMA can produce severe damage to serotonin neurons.
Heavy MDMA users have less 5-HIAA in cerebrospinal fluid, suggesting less serotonin in their nervous
systems. Also, PET reveals lower levels of serotonin membrane transporters in routine MDMA users.
MDMA’s Psychedelic and Psychostimulant Effects
MDMA’s physiological effects resemble those of psychostimulant drugs such as amphetamine at higher
o Produces increased heart rate and blood pressure. Low MDMA elicit few physiological effects. Howev