Download Drugs of Abuse: Psychedelic Agents

Drugs of Abuse:
Psychedelic Agents
By: Nima Deljavan
Medicinal Chemistry
Dr. John Buynak
March 29, 2007
Hallucinogens
 Hallucinogenic drugs are among the oldest drugs used by
humankind. They naturally occur in mushrooms, cacti,
and various other plants.
 hallucinogens can be divided into three broad categories:
 psychedelics,
 dissociatives,
 deliriants
Psychedelics
 These classes of psychoactive drugs can
cause subjective changes in perception,
thought, emotion and consciousness.
 Unlike other psychoactive drugs, such as
stimulants and opioids, psychedelics do not
merely amplify familiar states of mind, but
rather induce experiences that are different
from those of ordinary consciousness.
History and Use
 Various cultures have endorsed the use of
hallucinogens in medicine, religion, and recreation
to varying extents, and some have regulated or
outright prohibited their use
 Starting in the mid-20th century, psychedelics have
been explored as potential therapeutic agents in
treating depression,post-traumatic stress
disorder,alcoholism, cluster headaches, and other
ailments
 Today, in most countries, the possession of many
hallucinogens, even those that are common in
nature, is considered a crime and punished by fines,
imprisonment, or even death.
History continued…
 Starting in the mid-20th century, psychedelics have been
the object of extensive attention in the Western world.
They have been explored as potential therapeutic agents
in treating depression, post-traumatic stress
disorder,alcoholism, cluster headaches, and other
ailments.
 Early military research focused on their use as
incapacitating agents and or interrogation.
 The most popular, and at the same time most stigmatized,
use of psychedelics in Western culture has been
associated with the search for direct religious experience,
enhanced creativity, personal development, and "mind
expansion".
 The use of psychedelic drugs was a major element of the
1960s, where it got associated with various political
movements, rebellion, and strife between generations.
Types of Psychedelics
 Commonly applied to any drug with perception-altering
effects such as…
 LSD (derived from grain fungus that typically grows on
rye)
 Psilocybin (present in fungi)
 Dimethyltryptamine (DMT) chemically synhesized in
1931/occurs in plants naturally
 2C-B (chemically synthesized)
 Mescaline (occurs naturally in the peyote cactus,the
San Pedro cactus, and the Peruvian Torch cactus
 DOM (chemically synthesized)
 as well as an array of other tryptamines, phenethylamines
and yet more exotic chemicals, all of which appear to act
mainly on the 5-HT2A receptor
Chemical Structures
2C-B
Psilocybin
DMT
DOM
Mescaline
LSD Blotter Paper and
Structure
Source: www.DEA.gov
Mushrooms
5-HT2A Receptor
 The mammalian 5-HT2A receptor is a subtype of
the 5-HT2 receptor which belongs to the Serotonin
receptor family and is a G-protein coupled
receptor(GPCR).
 This is the main excitatory receptor subtype among
the GPRC for serotonin(5-HT), although 5-HT2A
may also have an inhibitory effect on certain areas
such as the visual cortex.
 Necessary for mechanism of the action of
hallucinogens
 Inhibition of the firing of neurons in the visual cortex,
which are normally involved in the perception of the
objects, is thought to be the cause of the visual
hallucinations produced.
How It All Works…
 As the 5-HT2A receptor is G-protein linked, the first
step in its signaling cascade (after it is stimulated by
an agonist) is activation of its associated G-protein.
 The 5-HT2A receptor has been shown to be linked
to most major G-protein systems, but classically it
linked to the G(q) G-protein.
 Activation of this receptor stimulates phospholipase
C (PLC) activity, which subsequently promotes the
release of diacylglycerolﾊ(DAG) and inositol
triphosphateﾊ(IP3), which in turn stimulate protein
kinase Cﾊ(PKC) activity and Ca(2+)release.
Signaling Cascade
Source: Hefter Review of Psychedelic Research
General Subjective
Effects
 Many of the tryptamines and phenethylamines cause
remarkably similar effects, despite their different chemical
structure. However, most users report that the two
families have subjectively different qualities in the "feel" of
the experience which are difficult to describe.
 At lower doses, sensory distortions such as the warping
of surfaces, shape shifting, and color variations. Users
often report intense colors that they have not previously
experienced, and repetitive geometric shapes are
common.
 Higher doses often cause intense distortions of sensory
perception such as synesthesia or the experience of
additional spatial or temporal dimensions.
 2C-B has extremely tight "dose curves," meaning the
difference between a non-event and an overwhelming
disconnection from reality can be very slight.
Medicinal Possibilities
and Uses
 University of Baltimore scientists are examining LSD as a
possible treatment for addiction to…




heroin
opium
alcohol
sedative hypnotics.
 University of Miami researchers are studying the
psychedelic drug ibogaine to treat cocaine addiction.
 Other scientists are focusing their psychedelic research
on learning more about the human brain, discovering
antidotes to drug overdoses, and relieving pain in cancer
patients.
 It's still too early to say whether the drugs have medicinal
uses or not.
Thank You!