Psychedelic drugs 18/12/2022

Summary
-categories of psychedelic drugs
-Anticholinergies scopolamine
-

-Catecholaminergies mescaline,
-
MDMA

-Synthetic amphetamines
Hallucinogens(Serotoninergiasi-LCC,DMT, psilocybinOpsilocormethoprite
-

Categories of psychedelic drugs

I-
I I
TYPE Funcion(s) Examples
block acetylcholine, inhibiting scopolamine
Anticholinergic impulses responsible for
involuntary muscle mumts
& other bodily functions

modulate catecholamine
systems mescaline
Catecholaminergic eg. dopamine, epiphrine, MDMA
norepinephrine
stimulate/block serotonin LSD
serotoninergic systems psilocybin

Glutaminergic
bind to NMDA receptors & ketamine
NMDA receptor preventbindingofglutamate, theymemantine
are
dextromethorphan

newe cells

Anticholinergics
·

Prototype Anticholinergic (ACh)

Psychedelic
-Competitive antagonist of muscarinic type of ACh receptor
-Deliriant & intoxicants; causes amnestic, drowsiness, mild euphoria, fatigue, confusion,
loss of atta, dreamless sleep
L
Medically found in some travel-sickness products
·
common anticholinergies
scopolamine, atrophine & I-hyoscyamine
Scopolamine
· Historicalbackground
-Found widely in nature, used & misused for centuries
1 Associated with
sorcery, magic, witchcraft & aphrodisiacs
sensation of flying
-
Reports w.

Origins
·

-Potato, tomato, eggplant, pepper (without hallucinogens

-Mandrake root, deadly
nightshade,
herbane, datura
·
Effects
-Increased constipation, blurred
heart rate,
dry mouth, vision, drowsiness, amnesia
delirium, mental confusion, increased temperature, naused & vomiting,
Toxicity
-
->

fixed dilated pupils, hallucinations

-Most deaths due to accidents, homicide, suicide

Catecholaminergies
·
Structure
to be related to
Norepinephrine
&
Thought norepinephrine
-

-exert their
of nerve impulses
in the brain
psychedelic
at
actions by altering the transmission
norepinephine & serotonin synapse HuN-cHz-aH-*
atamine aline -
~ OCH 3 OCH3
HeN-CH-CHe-TET HeN-CHe-CHe-EF-OCHs
HaN-CHCHITECT
AER
CHE &OCH3

HaNeoM-RXSetE
-MDA
~OC2H3

HaN-aH-ctz XOECHz HIN-cH-CHe-ECH

-

OCHs

(?) Elemicin

HzNMAORERROR
# - -

~OC2H3 ~ OCH3

HeN=CH-cHe-FEFtOCHz HeN=CH-CHz-YOCHs
OCHs Oct3

Mescaline
Origin
·

&
Peyote cactus (legalised as part of sacrament of Nature American church)
·
Effects. Pnarmacological
-

-chewed; onset in 30-90 min, duration loh, excreted unchanged

MDMA
·
Pharmacokinetics
with less extreme visual distortions & disembodiment
but less
<metabolised to MDA,
hallucinogenic
-peak plasma concentration: 2n for MDMA, both for active metabolite
MDA

- elimination
half-life: an for MDMA, 25h for MBA

Lafter repeated
doses: MDMA causes 12th metabolic inhibition;
additional doses can cause
toxicity
Effects
· -

Neurotoxicity
& On 5-HT (serotonin) & Nt (horepinephrine) receptors
-Potent & selective serotonin neurotoxin, damaging serotonin transporter
&striatal serotonin depleted in chronic MDMA users
5 HT &S-HIAA. are severely depleted by 50-50% & occipital cortex;
DA levels unaffected
depression, anxiety, mental confusion
2
symptoms: teeth -

grinding, muscle tension, nausea,

covertime, more tolerance to the than -we effects)

L behaviorial effects could be caused
by massive release/depletion of brain serotonin
·Effects cognitive deficits
-

toxicity: penods of intense activity, eg rare parties: hyperthermia, tachycardia, disorientation,

dehydration, dilated pupils, convulsions, rigidity, kidney failure
-combined use MDMA+LSD
"candyflipping" -

produces synergistic effects in rodents

·
aka "ecstasy" "molly"
-toxicity death, hyperthermia, tachycardia, renal failure, disorientation, convulsions,
muscle breakdown
-

LCNS side effects: depersonalization, paranoia, anxiety, panic, suicidal ideation, disruption of
& reduced thirst
homeostasis inc.
hyperthermia satisfy
-but intense euphoria encourages use
heart rate loobpin
"tachy cardia: -

Synthetic amphetamines
derivatives
synthetic amphetamines
·

-Structurally related to mescaline & amphetamine, produce similar effects

e.g. DOM, MDA, DMA, MDE, TMA, MDMA (ecstasy)
-Behavioral stimulants with
increasing (SD-effects as dose increase
-Alteration of mescaline rule produces family of drugs similar to amphetamine,
more potent & toxic
usually
·
Types
↓ DOM
-1-6mg ->
euphoria & 6-sh of hallucination
-100x more potent than mescaline, less potent than USD
-
high dose-> tremors, convulsions, prostration, death
L MDA, DMA, MDECEve), TMA

MOMAIN-demethylag eTXNHe
MDA
-
"Designer psychedelics
of MDMA
to
>
LMDA: metabolite
CYP2B6
Hallucinogens
Predominanttypesareserotonin
· in
Serotonin
-

Ho-EITH
CHe-CHc-N
2 Actions serotonin unclear:
receptors
on are

I
structurally similar to serotonin

psilocin

EISnotenNcM
DNT - -

DMT)
(4-hydroxy
ETH GcHc-NTs
OH
-

ERH CHn-cHc-NTc
H <isocybin
y1.0 MT
e(?)
#

-NTCIk-CH
BER

Ho-PETHCHe-cHc-NTc CHso-EILTE #N-cH

**
LSD

· Pharmacokinetics
↳Rapidly absorbed orally
2 1% gets to brain, distributed easily through body & placente
Only
Lusual dose 25-300mg; low dosage diff to detect in wine; lethal dose
14g
-
Long half-life
2
Metabolized in liver

·
Effects -

psychological
-
perceptual phase
-colored lights, distorted, vivid images
-unpleasant, panic experiences due to overwhelming visual/emotional effects
2 Adverse effects
2 flashbacks
(hallucinogen persisting perception disorders
<major long-term effect
-Rapid onset & loss of tolerance; cross-tolerance
-No physical withdrawal syndrome

DNT
·
Details
I
short-acting, binds to serotonin-2 receptors
I must be smoked/ sniffed, often in marijuana cigarettes
<metabolised by MAO of action
enzymes; may be bound to
signal receptors as possible mode
Lonset 2 min, effect for 30 min
-1 of the 2 main
ingredients of ayahuasca
 Psilocybin & psilocin
·
Details
I well absorbed orally
many species of
-2 psychedelic agents found in mushrooms
L exert at serotonin 5-HTCA
agonist effect & 5-HTIA receptors
-1/200 as potent as ISD; lasts for 6-10 hours
hallucinations & sensory distortions like LSD's
I causes

NMDA
Glutminergic receptors antagonists
·
Details
i unrelated to other drugs
structurally
- First developed as surgical anesthetics
I canproduce bizarre &srs psychotic reactions, e.g. agitation, excitement, delirium,
disorientan,
hallucinagus, out-of body experiences
-e.g. PCP, Ketamine, dextromethrophan

Phencyclidine (PCP)

History
·

L
Briefly used as anesthetic
Labandoned due to psychiatric reactions
·
Mechanism
-Binds & blocks NMDA receptors on
glutamate neurons

Dosage & effects

·

I taken orally/sniffed/ smoked/injected/moist tissues of eyes, rectum, vagina

25-10mg -> relaxation, warmth,
tingling, numbness, "high"; 4-6 hours; mild depression
higher dosage ->
analgesia, stupor & coma, mania/catatonia, sudden mood changes,
disoretagn, confusion, delusional thought, drooling, repetitive actions, nystagmus
"analgesia: inability to feel pain
rnystagmus: involuntary rhythmetic/up-down/circular eye motion

Ketamine "Special K
"

Historyev,
·

in 1950s 160
2 used as veterinary
Primarily tranquilizer & anesthetic
Mainbenefit-safety; did not depress heart, breathing, by
-
Representative of "dissociative anesthetic" subject feels separated from sensory experience
-

-May represent new class of antidepressants current evidence shows anabolite

-

of Ketamine produces such effects

-Increased use as club drug
I still used
medically
 ·Pharmacokinetics
I sold to vets, dissolved in liquid
primarysourceof illicituseisdiverted/stolenreternal
suppliedoral
in
-25-50% is absorbed &
rapidly distributed
-mean plasma elimination half life: 2.3h

Dextromethorphan CDXM)

·
Detailes
&Common
ingredient in -140 varieties of over-the-counter
cough suppressants
-Roboing, dexing, robo-tipping, robo-cobbing
-I heart rate &
b.p.
produces psychological/behaviorial activation, & other somatic effects

References
-
iT video: "Psychedelic Digs", by Paul Meniff