Download Slide 1

Location of Serotonin Neurons
in the Raphe Nuclei
IN HUMANS: 90% OF TOTAL BODY SEROTONIN IS
FOUND IN GUT.
8% OF TOTAL FOUND IN PLATELETS AND MAST
CELLS.
1-2% OF TOTAL FOUND IN CNS
(PRIMARILY IN PINEAL GLAND/ WHICH IS NOT
REALLY PART OF CNS)
ANATOMY
NUCLEI OF RAPHE (MIDLINE) IN RETICULAR REGION
OF BRAIN STEM.
CAUDAL GROUP: INNERVATES SPINAL CORD
(SYMPATHETIC REGION)
EXPLAINS THE SIDE-EFFECTS OF 5HT AGENTS
ASCENDING PATHWAYS: FOUND IN PONS
CALLED = RAPHE NUCLEI.
ACCOUNTS FOR 80% OF FOREBRAIN 5HT.
RAPHE NEURONS HAVE REGULAR SLOW SPONTANEOUS
FIRING RATE
(0.5 TO 2.5 SPIKES/SEC)
FUNCTION: NO INFORMATION TRANSFER, ONLY
MODULATION
5HT APPLIED TO RAPHE NEURONS DECREASES FIRING.
SPONTANEOUS ACTIVITY IS ELIMINATED DURING REM
SLEEP.
Active
Quiet
SWS
REM
NEUROCHEMISTRY
REQUIRES TRYPTOPHAN AS PRECURSOR FROM DIET.
UPTAKE DEPENDS UPON LEVEL OF OTHER AMINO ACIDS
IN BLOOD/DIET.
HIGH CARBOHYDRATE DIET ENHANCES TRYPTOPHAN
UPTAKE.
LOW INTAKE OF TRYP. LEADS TO LOW LEVELS OF 5HT IN
CNS.
1% OF INGESTED TRYPTOPHAN IS CONVERTED TO
SEROTONIN IN THE BRAIN.
UPTAKE INTO CNS: ACTIVE, HIGH-AFFINITY TRANSPORT.
METABOLISM: CONVERTED TO 5HTP BY
TRYPTOPHAN HYDROXYLASE. (TH)
SYNTHESIS OCCURS IN TERMINALS, SO ENZYME
IS MADE AND SHIPPED TO TERMINALS.
THIS ENZYME IS USUALLY NOT SATURATED WITH
SUBSTRATE.
5HTP CONVERTED TO SEROTONIN BY
DECARBOXYLASE.
Rapid tryptophan depletion leads to symptom
relapse in recovered depressed patients
TERMINATION OF ACTION
PRIMARILY BY UPTAKE
CATABOLISM BY MAO-A IS MINOR COMPONENT.
5HT1-A ARE AUTORECEPTORS ON RAPHE NEURONS
MORE SENSITIVE TO LSD THAN TO 5HT!
DYSFUNCTION OF THESE RECEPTORS UNDERLIE ANXIETY
5-HT1-A receptors control the release of serotonin and
activity of 5HT neurons via two signaling mechanisms
Hallucinogens, e.g. LSD, Turn Off Serotonergic
Neurons in the Raphe Nuclei by Stimulating
5HT-1A and 5HT2A Receptors
Neuronal circuits implicated in the responses induced by psychoactive chemicals.
5-HT2A–Glutamate receptor complex expressed by cortical pyramidal neurons
represents the target of LSD-like psychoactive drugs that will dysregulate the
signaling properties of cortical pyramidal neurons and affect cognition and
perception processes in the brain cortex. TINS, 2009.
Genetic deletion of the 5-HT1A receptor increases
anxiety-like behavior in mice
Ratings of religiosity & spirituality inversely correlated with the number of
Serotonin 5-HT1A receptors in humans
American Journal Psychiatry 160:1965-1969,
November 2003
Stimulating 5HT-1A receptors, e.g. with BuSpar,
relieves anxiety
TH
Serotonin contains an indole ring with a carbon chain
attached
….So do these hallucinogens
Psilocybin
LSD
Hallucinogens produce synesthesia.
Synesthesia: a remarkable, rare
condition where an individual has
multimodal perceptual experiences
from a unimodal sensory event.
The ability of hallucinogens to induce
synesthesia may be related to their
ability to influence serotonergic
control over the frontal lobes.
Increased structural connectivity in grapheme-color synesthesia
Romke Rouw & H Steven Scholte
Nature Neuroscience - 10, 792 - 797 (2007)
Increased brain
activation and
increased
anisotropy in the
inferior temporal
cortex in graphemecolor synesthetes.
“Using diffusion tensor imaging, we have shown
for the first time that the extraordinary sensory
experiences in synesthesia are associated with
abnormalities in white matter structure.”
HALLUCINOGENS
"IT IS REMARKABLE THAT ONE CHARACTERISTIC WHICH SEEMS TO
SEPARATE MAN FROM THE ALLEGEDLY LOWER ANIMALS IS A RECURRING
DESIRE TO ESCAPE FROM REALITY" C.H.W. HORNE, 1963.
IN 1990, A NIDA SURVEY REVEALED THAT BETWEEN 17 AND 21 MILLION
PEOPLE IN THE US HAD USED A HALLUCINOGEN AT LEAST ONCE THAT
YEAR.
"A PSYCHEDELIC EXPERIENCE IS A JOURNEY
TO NEW REALMS OF CONSCIOUSNESS. THE
SCOPE AND CONTENT OF THE EXPERIENCE IS
LIMITLESS, BUT ITS CHARACTERISTIC
FEATURES ARE THE TRANSCENDENCE OF
VERBAL CONCEPTS, OF SPACE-TIME
DIMENSIONS, AND OF THE EGO AND
IDENTITY." TIMOTHY LEARY, 1964.
HALLUCINOGENS
ONE FUNCTION OF CONSCIOUSNESS IS TO FILTER OUT THE
OVERWHELMING AND CONFUSING MASS OF SENSORY INPUT OUR
BRAIN RECEIVES.
THE USE OF HALLUCINOGENS THEREFORE USUALLY OCCURS IN
STRUCTURED AND PROTECTED SETTINGS.
IT SHOULD COME AS NO SURPRISE WHEN I OCCASIONALLY
DESCRIBE HOW STRICT RELIGIOUS AND SOCIAL RULES HAVE BEEN
DRAWN AROUND THE USE OF AGENTS THAT ALTER PERCEPTION.
One yields a surprisingly similar consensus of seeing geometric images
accompanied by altered feelings.
There were four consistent geometric images reported:
1) a lattice or grating
2) a cobweb structure
3) a tunnel or funnel alley
4) spiral images.
Though colors varied, participants consistently reported brightness intensification.
Moreover, the apparent size, geometrical shapes, and symmetry were strikingly
similar from participant to participant (Kluver, 1928).
62-72% of 500 participants tested with LSD reported similar simple forms at low
doses.
72% reported religious symbols and images
49% reported small animals and humans.
Images tended to pulsate and move toward a center tunnel or away from a
bright center (a phenomenon similar to reported near death experiences).
Unlike psilocybin-induced hallucination, these visions could not be consciously
controlled.
HALLUCINOGENS AND RELIGION
In Central and Southern America, use of psilocybin mushrooms was a
common religious practice. The mushroom is known as a sacred
mushroom and was considered a religious path to the spirit world.
Mushroom art and sculptures exist from 1000 BC on stones that had
religious meaning.
The Codex Vienna Mixtec manuscript (13th
century) depicted the ritual use of the
mushrooms by the Mixtec Gods.
Religious/mystical experiences can be generated internally…
Neural correlates of a mystical experience in Carmelite nuns
M. Beauregard, V. Paquette, Univ of Montreal,
Neuroscience Letters, September, 2006
PSILOCYBIN
CAN BE FOUND IN MORE THAN 75 DIFFERENT SPECIES OF MUSHROOMS.
PSILOCYBE MEXICANA IS THE MOST FAMOUS
ORAL DOSE: 2 TO 4 MUSHROOMS (DEPENDS UPON WHICH MUSHROOM IS
THE SOURCE OF THE DRUG).
LATENCY: 30 MIN. PEAKS AT 90 MIN.
EFFECTIVE DOSE: 4 MG P.O.; 1/100
AS POTENT AS LSD.
DURATION: 6 HOURS.
MINOR PHYSICAL CHANGES:
DRY MOUTH, SLIGHT NAUSEA,
DILATED PUPILS.
VIOLENT NAUSEA AND VOMITING
WELL ABSORBED FROM GI TRACT.
1570'S FRANCISCO HERNANDEZ DOCUMENTED CENTRAL AM. INDIANS
USE OF THESE MUSHROOMS (THEIR CORNUCOPIA INCLUDED USE OF
1200 HERBAL REMEDIES).
TEONANACATL "GOD'S FLESH" "SACRED MUSHROOM"
ALBERT HOFMANN 1958 ISOLATED ACTIVE INGREDIENT. (ALSO OF LSD
FAME). HE INGESTED 32 DRIED MUSHROOMS TO DETERMINE THEIR
EFFECTS. HE CLAIMED THAT THE EXPERIENCE WAS SIMILAR TO HIS
LSD EXPERIENCE.
PSILOCYBIN IS CONVERTED INTO PSILOCIN WHICH IS MORE LIPID
SOLUBLE AND THE ACTUAL PSYCHOACTIVE AGENT.
MUSHROOMS ARE EATEN RAW, COOKED INTO ANY RECIPE THAT
CALLS FOR MUSHROOMS OR STEEPED INTO A TEA.
THE POWDER IS EATEN, INSUFFLATED (BREATHED THROUGH THE
NOSE) OR SWALLOWED IN GELATIN CAPSULES.
MECHANISM: AGONIST AT 5HT-1A AND 5HT-2A RECEPTORS.
EXPERIENCE: RELAXATION, EUPHORIA, INTROSPECTION, DETACHMENT.
HIGH DOSES: LSD-LIKE CHANGES. ALTERED PERCEPTION OF SENSORY
STIMULI.
AUDITORY AND VISUAL HALLUCINATIONS. ELEVATED MOOD, GREAT
HILARITY.
UNREAL HALLUCINATIONS ARE RECOGNIZED AS SUCH BY USERS.
Side Effects: PHOTOSENSITIVITY, MUSCLE WEAKNESS, VERTIGO
OVERDOSE: HYPERTHERMIA, FLUSHING, CONVULSIONS, ANXIETY, PANIC
REACTIONS, PARANOIA.
DEATH CAN OCCUR FROM INGESTING ABOUT 2000 TIMES THE NORMAL
DOSE.
25% OF DOSE IS EXCRETED UNCHANGED BY KIDNEYS INTO
URINE.
INACTIVE METABOLITES REMAIN IN BODY FOR MANY DAYS.
DEPENDENCE: NO PHYSICAL OR PSYCHOLOGICAL SEEN.
TOLERANCE: NOT LIKELY DUE TO OCCASIONAL USE
TIMOTHY LEARY'S GOOD FRIDAY TEST IN 1962
20 SEMINARIANS, DRUG/NO DRUG (30 mg PSILOCYBIN) ATTENDED
RELIGIOUS SERVICE. CLAIMED THAT THE USING THE WOULD ENHANCE
MYSTICAL EXPERIENCE.
R. R. Griffiths &W. A. Richards & U. McCann & R. Jesse, Johns Hopkins
University School of Medicine, Psychopharmacology (August, 2006)
Psilocybin can occasion mystical-type experiences having substantial
and sustained personal meaning and spiritual significance.
“psilocybin occasioned experiences similar to spontaneously occurring
mystical experiences … which were evaluated by volunteers as having
substantial and sustained personal meaning and spiritual significance.
The ability to [induce] mystical experiences should permit rigorous scientific
investigations about their causes and consequences, providing insights into
underlying brain mechanisms…”
D-LYSERGIC ACID DIETHYLAMIDE, LSD
LSD IS ERGOT DERIVATIVE OR INDOLE ALKYLAMINE
THE HALLUCINATIONS PRODUCED BY THIS DRUG CAN BE ATTENUATED BY
5-HT-2 RECEPTOR ANTAGONISTS.
THEIR HALLUCINOGENIC POTENCY IN HUMANS CORRELATES WITH THEIR
AFFINITY FOR 5-HT-1A & 2A SITES
HALLUCINOGENS ACT AS AGONISTS AT 5-HT-1A & 2A RECEPTORS.
INGESTED ORALLY; LSD IS RAPIDLY ABSORBED.
DOSE: 100 UG,P.O. IS HALLUCINOGENIC. 0.3 UG/KG IS SUBJECTIVELY
DETECTABLE; 50 UG, I.V. EFFECTIVE
ONLY ABOUT 1% REACHES THE BRAIN: CONCENTRATES IN VISUAL
CORTEX, LIMBIC SYSTEMS, RETICULAR FORMATION.
METABOLIZED RAPIDLY BY LIVER; EXCRETED BY KIDNEYS AS 2-OXY-LSD.
TOLERANCE AND CROSS-TOLERANCE DEVELOPS WITHIN 3-4 DAYS WITH
CONTINUAL USE. PSYCHODELIC EFFECTS SHOW TOLERANCE AS WELL.
DEPENDENCE: NO PSYCHOLOGICAL OR PHYSIOLOGICAL DUE TO
TYPICALLY INFREQUENT USE
D-LYSERGIC ACID MONOETHYLAMIDE (A LESS LIPID VERSION OF LSD)
MAY BE RESPONSIBLE FOR SALEM WITCHCRAFT CRISIS THAT BEGAN IN
DECEMBER OF 1691.
EIGHT GIRLS SUFFERED WITH ADISTEMPERS.@ = DISORDERLY SPEECH,
ODD POSTURES AND GESTURES, & CONVULSIVE FITS.
LACKING A REASONABLE EXPLANATION THE NEW ENGLAND PURITANS
SAW THIS AS THE WORK OF SATAN BROUGHT ABOUT BY THE PRACTIVE
OF WITCHCRAFT BY SOME WOMEN OF ILL REPUTE.
BY SEPTEMBER 1692 19 MEN AND WOMEN WERE HUNG, ONE MAN WAS
PRESSED TO DEATH AND TWO DIED IN PRISON.
POISONING IS CALLED
ERGOTISM AND CAUSES A
BURNING IN THE EXTREMITIES
DUE TO VASOCONSTRICTION
OF BLOOD VESSELS. CAN
LEAD TO LIMB DEATH. 40,000
DEATHS IN AD 944 EUROPE
“SAINT ANTHONY’S FIRE.”
Ergot fungus (Claviceps purpurea) growing on corn
LATENCY IS ABOUT 30 - 90 MIN.
HALF-LIFE IS ABOUT 3 HRS.
PSYCHIC EFFECTS ARE MAXIMAL AT 1 TO 3 HOURS. AT
WHICH TIME VIRTUALLY NO LSD IS LEFT IN THE BRAIN!
SETS IN MOTION A CASCADE OF EVENTS THAT MAY
INVOLVE ENTIRE CNS. SEROTONERGIC SYSTEM MAY
ACT AS TRIGGER.
DURATION: 8 TO 12 HOURS.
METABOLIZED BY THE LIVER ALMOST ENTIRELY.
METABOLITES ARE EXCRETED IN THE BILE AND FECES.
PHYSIOLOGICAL EFFECTS: SYMPATHOMIMETIC -DUE TO
RAPHE CELL PROJECTIONS TO SPINAL CORD ONTO
PRE-GANGLIONIC AUTONOMIC NERVOUS SYSTEM
CELLS.
MECHANISM OF ACTION: LSM LOOKS LIKE 5HT.
USE CORRELATES WITH DECREASED RAPHE CELL FIRING AND
INCREASED LEVELS OF 5HT AND DECREASED LEVELS OF THE
METABOLITE 5HIAA.
BUT... BEHAVIORAL EFFECTS GREATLY OUTLAST THE SLOWING
OF RAPHE FIRING.
BEHAVIORAL EFFECTS SHOW TOLERANCE - SLOWING OF RAPHE
FIRING DOES NOT.
DESTRUCTION OF 5HT NEURONS ACTUALLY ENHANCES LSD'S
EFFECTS.
USING LSD WITH MDMA (CANDY-FLIPPING).
hippy flipping - pairing psychedelic mushrooms
kitty flipping - ketamine and ecstasy
candy flipping on a string – cocaine + LSD + MDMA.
candy flips - home-made capsules containing LSD + MDMA
HALLUCINATIONS - MECHANISM?? UNKNOWN... BUT...
RELEASE POST-SYNAPTIC CELLS IN CORTEX AND SUBCORTICAL
AREAS FROM INHIBITION. MANY OF THESE CELLS ARE IN VISUAL
PROCESSING SYSTEMS, E.G. LATERAL GENICULATE, AND LIMBIC
STRUCTURES.
PERCEPTUAL EFFECTS ARE LIKE WATCHING OWN PRIVATE TV.
USER IS AWARE THAT HE IS SEEING HALLUCINATIONS, THAT
THEY ARE NOT REAL, BUT IS POWERLESS TO STOP THEM.
SYNESTHESIA – SENSORY SYSTEM CROSS-OVER OF
INFORMATION PROCESSING. VIVID SWIRLING COLORS, SOUNDS
HAVE COLORS, INTENSIFICATION OF VISUAL PERCEPTION.
LOWERED PAIN SENSITIVITY.
WITHDRAWAL.
NO SERIOUS WITHDRAWAL SYMPTOMS.
ADVERSE EFFECTS.
CHROMOSOME DAMAGE. STUDIES PERFORMED
BADLY, POORLY CONTROLLED, EXPERIMENTER BIAS,
POPULATIONS OBSERVED WERE TOO SMALL.
CHROMOSOME BREAKAGE RATES MAY BE HIGHER IN
LSD USERS,
OR ELSE PEOPLE WHO HAVE ENDOGENOUSLY HIGH
BREAKAGE RATES LIKE TO TAKE LSD. MOST RECENT
STUDIES SHOW NO EFFECT OF LSD ON CHROMOSOMES.
ACUTE PANIC REACTIONS.
BAD EXPERIENCE WITH LSD; PROBLEM IS THAT IT
CANNOT BE TERMINATED BY USER... LEADS TO PANIC.
INCREASED SUICIDES ASSOCIATED: NO CAUSE AND
EFFECT BELIEVED TO EXIST.
ADVERSE REACTIONS ASSOCIATED WITH POORLY
ADJUSTED USERS.
FLASHBACKS. SUDDEN AND "UNEXPECTED" RECURRENCES OF
ASPECTS OF EARLIER DRUG EXPERIENCE. 2256 ARMY ENLISTED
MEN,
23% REPORTED FLASHBACKS, COMPARED TO 5% FOR
AMPHETAMINE AND 1% FOR MARIJUANA.
NOT DANGEROUS, ARE OFTEN SELF-INDUCED!
OCCURS DURING HIGH STRESS, E.G. DRIVING
OR JUST BEFORE GOING TO SLEEP
SUGGESTS THAT SOME PERMANENT BRAIN DAMAGE MAY EXIST
EFFECTS ON TEMPERATURE AND TIME ESTIMATION.
LSD, MESCALINE, AND PSILOCYBIN ALL ELEVATE BODY
TEMPERATURE (SYMPATHETIC SIDE EFFECT). ALL ARE
ASSOCIATED WITH OVERESTIMATION OF TIME (TIME MOVES
FASTER FOR THEM.) EXPT. COUNT TO 60, ONE COUNT EACH
SECOND.
THESE DRUGS CAUSE FASTER COUNTING. INFARED LAMPS
CAUSE FASTER COUNTING IN UNDRUGGED SUBJECTS.
HAWAIIAN WOOD-ROSE SEEDS (Argyreia Nervosa)
BIOCHEMISTRY: SAME AS MORNING GLORY
REQUIRES 4 TO 8 WOOD-ROSE SEEDS TO GET HIGH
Many experience nausea and gas. The fuzzy husk of the seed is often removed
and not ingested because it seems to worsen the nausea. Seeds contain
D-LYSERGIC ACID MONOETHYLAMIDE
MORNING GLORY
RIVEA CORYMBOSA: ALSO KNOWN AS OLOLIUQUI,
BY THE AZTECS. DRAWINGS FROM THE 16th CENTURY
SUGGESTED THE THE MORNING GLORY WAS
INDEED "OLOLIUQUI.“ BUT IT WAS NOT UNTIL IT
WAS DISCOVERED STILL GROWING IN 1939
IN A ZAPOTEC INDIAN GARDEN IN OAXACA MEXICO
WAS THIS CONFIRMED.
CONTAINS D-LYSERGIC ACID MONOETHYLAMIDE; ONE-TENTH AS POTENT
AS LSD. DISCOVERED BY ALBERT HOFMANN.
ORALLY EFFECTIVE.
REQUIRES 100-150 MORNING GLORY SEEDS TO GET HIGH.
CAUSES A DREAMY STATE WITHIN ABOUT 20 MINUTES, FOLLOWED BY
SLEEP.
DOES NOT PRODUCE THE VISUAL HALLUCINATIONS SEEN WITH LSD.
OFTEN TAKEN WHILE ALONE.
16TH CENTURY MEXICO: MORNING GLORY SEEDS HAD MOST
RELIGIOUS SIGNIFICANCE.
A.K.A. MEXICAN BINDWEED OR "FLOWER OF THE VIRGIN"
OTHER VARIATIONS ON THIS PLANT BECAME POPULAR IN US IN
1960'S:
E.G. "HEAVENLY BLUE, PEARLY GATES, WEDDING BELLS" ARE ALL
VARIETIES OF PLANTS THAT CONTAIN THE PSYCHOACTIVE AGENT.
DMT. N,N-DIMETHYLTRYPTAMINE
LSD-LIKE DRUG.
SHORTER DURATION OF ACTION. ALSO HAS MAO-I
ACTION.
DMT DETERIORATES RAPIDLY, ESPECIALLY IN THE
STOMACH
LATENCY: 10 - 15 MIN WITH I.M. DOSE.; 2 - 3 MIN WITH
INHALATION.
DURATION: 10 MINUTES. "BUSINESSMAN'S TRIP".
EFFECTIVE HALLUCINOGENIC DOSE - 1 MG INHALATION
PRODUCES EUPHORIA, BEHAVIORAL EXCITEMENT AND
HALLUCINATION WITH EYES OPEN OR CLOSED!
MACROPSIA IS COMMON (APPARENT MAGNIFICATION OF
OBJECTS).
SE- TACHYCARDIA, HYPERTENSION, MYDRIASIS, ACUTE
ANXIETY ATTACKS, PANIC REACTIONS
TOXICATION: NUMBNESS OF LIMBS, TWITCHING OF THE
FACE, LACK OF MOTOR CONTROL, NASAL DISCHARGES,
NAUSEA, VOMITING.
NO EVIDENCE FOR PHYSIOLOGICAL OR
PSYCHOLOGICAL DEPENDENCE
TOLERANCE NOT LIKELY;
NO CROSS-TOLERANCE WITH LSD
DMT FIRST SYNTHESIZED IN 1931, ABUSE BEGAN IN 1956.
DMT: WORLDWIDE, THIS IS THE MOST IMPORTANT NATURALLY
OCCURRING HALLUCINOGENIC AGENT. S. AM. INDIANS USE IT
AS COHOBA OR VIROLA SNUFF.
A BLOOD-RED RESIN IS BOILED OUT OF THE BARK OF THE
VIROLA TREE (FOUND IN JUNGLE)
THEORY
ONCE BELIEVED TO BE AN ENDOGENOUS SCHIZOPHRENIC
AGENT.
ENZYME THAT CONVERTS TRYPTAMINE TO DMT IS FOUND IN
HUMAN CNS. BUT...NO EVIDENCE THAT IT HAPPENS YET.
LOW LEVELS OF DMT HAVE BEEN FOUND IN BRAIN OF NORMALS
AND SCHIZOPHENICS.
DMT AND DET NOT ORALLY ACTIVE.
PHENCYCLIDINE PIPERIDINE HCL. (PCP, ANGEL DUST)
SYNTHESIZED: 1957, USED AS DISSOCIATIVE
ANESTHETIC, HAD LIMITED RESPIRATORY DEPRESSION.
EMERGENCE PSYCHOSIS IN PATIENTS!
ABUSE BEGAN IN 1965.
ORALLY ACTIVE.
PCP IS USUALLY SMOKED ON CIGARETTES THAT HAVE
THICK WRAPPERS TO ABSORB THE PCP LIQUID.
USE LEADS TO PSYCHOTIC STATE.
CNS DEPRESSANT- DEATH BY CARDIAC ARREST.
DOSE: 2 - 10 MG P.O. HIGH DOSE - SEDATIVE; LOW DOSE STIMULANT = IN RATS.
LATENCY 1 HR., PEAK EFFECTS IN 5 HRS.
DURATION: 12 HRS.
FOLLOWED BY DEPRESSION THAT MAY LAST UP TO 24
HOURS.
METABOLISM: ALMOST ENTIRELY BY LIVER, EXCRETED
BY KIDNEYS.
EXPERIENCE: CHANGES IN BODY IMAGE, RELAXATION,
TINGLING FEELING, FEELINGS OF ISOLATION AND
FLOATING IN SPACE, SLOWING OF MENTAL
PROCESSES. MORE INTENSE THAN LSD, BUT MUCH
SHORTER.
PHARMACOLOGY CNS DEPRESSANT, ANESTHETIC,
TRANQUILIZER, PSYCHEDELIC.
RESEARCH SUGGESTS AND ENDOGENOUS PCP
RECEPTOR AND LIGAND.
"ANGELDUSTIN"
HAS SOME AMPHETAMINE-LIKE BEHAVIORAL EFFECTS.
TOLERANCE. DEVELOPS IN CHRONIC USERS. MILD
WITHDRAWAL SYMPTOMS. INCLUDING, DIARRHEA,
SLEEPINESS, RARELY CONVULSIONS.
PCP blocks Calcium ion entry via the NMDA glutamate
receptor channel
Dysregulation of the signaling processes of cortical pyramidal
neurons impairs cognition and normal perception in the cortex.
ADVERSE EFFECTS. CONSTIPATION, DECREASED
APPETITE.
PROLONGED DAILY USE: MEMORY AND SPEECH
DIFFICULTIES UP TO 1 YEAR LATER.
ANXIETY, DEPRESSION, PARANOIA.
CLAIMS OF INCREASED VIOLENT BEHAVIOR. NO
SYSTEMATIC EVIDENCE FOR THIS HOWEVER.
DOES NOT TURN A NORMAL PERSON WITH GOOD
MENTAL HEALTH INTO A VIOLENT PERSON.
RESEMBLES SCHIZOPHRENIA.
DEATHS ARE DIRECTLY RELATED TO ITS USE, UNLIKE
OTHER HALLUCINOGENS.
DEATH ESPECIALLY BY DROWNING IN CALIF., LOST
ORIENTATION WHILE SWIMMING, COULDN'T FIND
SURFACE; 1 PERSON DROWNED IN SHOWER), MANY
DEATHS ARE RELATED TO SUICIDE
OVERDOSE: (GREATER THAN 20 MG) GRAND MAL
SEIZURES, COMA, CARDIOVASCULAR COLLAPSE.
POSITIVE EFFECTS 60% OF USES; ADVERSE EFFECTS
100% OF TIME. WHY BOTHER?
CHRONIC USE. PERMANENT ORGANIC BRAIN DAMAGE.
FLASH BACK PSYCHOSIS IN SOME PEOPLE WHEN THEN
QUIT.
POSITIVE EFFECTS. 80% OF CHRONIC USERS ENJOYED
FIRST TIME. "EXHILARATING AND EUPHORIC", "PERFECT
DREAM WORLD". VERY INTENSE EXPERIENCE!
USERS AND ANIMAL STUDIES SUGGEST THAT PCP
EFFECTS IN BRAIN ARE NOT LIKE ANY OTHER DRUG OF
ABUSE.
KETAMINE
SIMILAR TO PHENCYCLIDINE, BUT 1/10 AS POTENT, SHORTER ACTIN.
DEVELOPED AS SURGICAL ANESTHETIC.
USED EXTENSIVELY IN VIETNAM.
EMERGENCE REACTIONS INCLUDED VIVID HALLUCINATIONS 1 - 2 MG/KG
I.M. GIVES INTENSE EXPERIENCE.
DURATION: 1 - 2 HOURS.
EXPERIENCE: FLOATING, EUPHORIA, RELIGIOUS EXPERIENCES.
ADVERSE REACTIONS: ATAXIA, SLURRING OF SPEECH, DIZZINESS.
DOSE-DEPENDENTLY CAN ACT A STIMULANT, DEPRESSANT OR
HALLUCINOGEN.
METABOLISM IS EXTREMELY SLOW, SO ITS EFFECTS CAN BE CUMULATIVE.
DOES NOT DEPRESS CIRCULATORY OR RESPIRATORY SYSTEMS!
DOES APPEAR TO BE ADDICTIVE.
KNOWN AS VITAMIN K OR SPECIAL K ON STREET.
USUALLY OBTAINED AS LIQUID FROM VETS OFFICES, DRIED BY
COOKING AND GROUND INTO A POWDER.
JOHN LILLY, THE SCIENTIST WHO PIONEERED COMMUNICATION
WITH DOLPHINS, BECAME CONVINCED THAT HE HAD BROKEN
THROUGH INTO A HIGHER REALITY INHABITED BY BEINGS THAT
CONTROLLED OUR OWN VERSION OF THE UNIVERSE.
KNOWN AS VITAMIN K OR SPECIAL K ON STREET.
USUALLY OBTAINED AS LIQUID FROM VETS OFFICES, DRIED BY
COOKING AND GROUND INTO A POWDER.
JOHN LILLY, THE SCIENTIST WHO PIONEERED COMMUNICATION
WITH DOLPHINS, BECAME CONVINCED THAT HE HAD BROKEN
THROUGH INTO A HIGHER REALITY INHABITED BY BEINGS THAT
CONTROLLED OUR OWN VERSION OF THE UNIVERSE.
IN 1997, AT THE HAIGHT ASHBURY FREE CLINIC (SAN FRANCISCO)
ONE CHRONIC VIT K USER BECAME CONVINCED THAT HE WAS THE
MESSAIH AND BEGAN GATHERING APOSTLES (WHO WERE NOT
DRUG USERS- JUST VERY NAIVE!).
KNOWN AS VITAMIN K OR SPECIAL K ON STREET.
USUALLY OBTAINED AS LIQUID FROM VETS OFFICES, DRIED BY
COOKING AND GROUND INTO A POWDER.
JOHN LILLY, THE SCIENTIST WHO PIONEERED COMMUNICATION
WITH DOLPHINS, BECAME CONVINCED THAT HE HAD BROKEN
THROUGH INTO A HIGHER REALITY INHABITED BY BEINGS THAT
CONTROLLED OUR OWN VERSION OF THE UNIVERSE.
IN 1997, AT THE HAIGHT ASHBURY FREE CLINIC (SAN FRANCISCO)
ONE CHRONIC VIT K USER BECAME CONVINCED THAT HE WAS THE
MESSAIH AND BEGAN GATHERING APOSTLES (WHO WERE NOT
DRUG USERS- JUST VERY NAIVE!). A COUNSELOR AT THE CLINIC
CONVINCED HIM THAT IF HE REALLY WAS WHO HE THOUGHT HE
WAS, HIS DIVINE IDENTITY WOULD CONTINUE WITHOUT HIS USING
KETAMINE.
KNOWN AS VITAMIN K OR SPECIAL K ON STREET.
USUALLY OBTAINED AS LIQUID FROM VETS OFFICES, DRIED BY
COOKING AND GROUND INTO A POWDER.
JOHN LILLY, THE SCIENTIST WHO PIONEERED COMMUNICATION
WITH DOLPHINS, BECAME CONVINCED THAT HE HAD BROKEN
THROUGH INTO A HIGHER REALITY INHABITED BY BEINGS THAT
CONTROLLED OUR OWN VERSION OF THE UNIVERSE.
IN 1997, AT THE HAIGHT ASHBURY FREE CLINIC (SAN FRANCISCO)
ONE CHRONIC VIT K USER BECAME CONVINCED THAT HE WAS THE
MESSAIH AND BEGAN GATHERING APOSTLES (WHO WERE NOT
DRUG USERS- JUST VERY NAIVE!). A COUNSELOR AT THE CLINIC
CONVINCED HIM THAT IF HE REALLY WAS WHO HE THOUGHT HE
WAS, HIS DIVINE IDENTITY WOULD CONTINUE WITHOUT HIS USING
KETAMINE. AFTER DETOXING, THE CLIENT RECOGNIZED HIS
DELUSIONAL STATE FOR WHAT IT WAS AND DISBANDED HIS
DISCIPLES, TELLING THEM THAT HE HAD MADE “TERRIBLE MISTAKE.”
KNOWN AS VITAMIN K OR SPECIAL K ON STREET.
USUALLY OBTAINED AS LIQUID FROM VETS OFFICES, DRIED BY
COOKING AND GROUND INTO A POWDER.
JOHN LILLY, THE SCIENTIST WHO PIONEERED COMMUNICATION
WITH DOLPHINS, BECAME CONVINCED THAT HE HAD BROKEN
THROUGH INTO A HIGHER REALITY INHABITED BY BEINGS THAT
CONTROLLED OUR OWN VERSION OF THE UNIVERSE.
IN 1997, AT THE HAIGHT ASHBURY FREE CLINIC (SAN FRANCISCO)
ONE CHRONIC VIT K USER BECAME CONVINCED THAT HE WAS THE
MESSAIH AND BEGAN GATHERING APOSTLES (WHO WERE NOT
DRUG USERS- JUST VERY NAIVE!). A COUNSELOR AT THE CLINIC
CONVINCED HIM THAT IF HE REALLY WAS WHO HE THOUGHT HE
WAS, HIS DIVINE IDENTITY WOULD CONTINUE WITHOUT HIS USING
KETAMINE. AFTER DETOXING, THE CLIENT RECOGNIZED HIS
DELUSIONAL STATE FOR WHAT IT WAS AND DISBANDED HIS
DISCIPLES, TELLING THEM THAT HE HAD MADE “TERRIBLE MISTAKE.”
MOST OF HIS DISCIPLES REFUSED TO BELIEVE THAT HE WAS NOT THE
MESSAIH AND BECAME VERY ANGRY AT THE CLINIC FOR “CORRECTING” HIS
MISTAKE. (REPORTED BY R.B. SEYMOUR, DIRECTOR OF CLINIC)
MESCALINE
CHIEF PSYCHOACTIVE INGREDIENT OF CACTUS
(LOPHOPHORA WILLIAMSII). DRINK PREPARED
FROM THIS CACTUS WAS CALLED PEYOTE.
PEYOTE.
60 DIFF ALKALOIDS CONTRIBUTE TO ITS EFFECTS. CA-RELATED
AGENT MAY BE DERIVED FROM PHENYLETHYLAMINE
MANY CACTI CONTAIN HALLUCINOGENIC ALKALOIDS. MANY CAN
BE BOUGHT IN NURSERIES.
ORALLY EFFECTIVE.
MAXIMUM BRAIN LEVELS 1 - 2 HRS AFTER INGESTION.
Effective Dose: EUPHORIA 3 MG/KG; HALLUCINATIONS 5 MG/KG.
HALF-LIFE - ABOUT 6 HRS.
DURATION: 5-12 HRS.
EFFECTS: FIRST 1 TO 2 HOURS ARE VERY UNPLEASANT.
HANGOVER BEFORE THE HIGH. NAUSEA, TREMOR,
ELEVATION OF BODY TEMPERATURE, PERSPIRATION, PUPIL
DILATION, INCREASED PULSE RATE AND BLOOD PRESSURE
(EXCITATION OF SYMPATHETIC).
DEATH BY RESPIRATORY DEPRESSION.
PRIMARY EFFECTS ARE ON VISION = BRIGHTLY COLORED LIGHTS
AND GEOMETRIC DESIGNS. "COLOR COMING FROM A WOVEN
RUG"
EUPHORIA ASSOCIATED WITH MENTAL AND PHYSICAL ENERGY.
"THESE SHOWS ARE EXPENSIVE...THE EXPERIENCE,
HOWEVER, IT WAS WORTH ONE SUCH HEADACHE AND
INDIGESTION, BUT IT WAS NOT WORTH A SECOND."
TOLERANCE PROBABLY CAN BE PRODUCED, BUT LITTLE
PSYCHOLOGICAL DEPENDENCE OR PHYSICAL
DEPENDENCE DEVELOPS WITH USE.
CROSS-TOLERANCE WITH LSD AND PSILOCYBIN.
EXCRETED UNCHANGED FROM KIDNEYS.
MECHANISM: MAY ACT UPON 5HT SYSTEMS IN BRAIN
FOR HALLUCINOGENIC EFFECTS.
SPICES: NUTMEG & MACE.
AUTOBIOGRAPHY OF MALCOLM X DESCRIBES USE OF NUTMEG IN
PRISON AS HALLUCINOGEN.
NUTMEG AND MACE (A RED SHEET OF MATERIAL THAT SURROUNDS
THE INNER NUT) COME FROM NUTMEG TREE, MYRISTICA
FRAGRANS, ACTIVE AGENT (MYRISTICIN-NUTMEG OR CLEMICINMACE) IS AN AROMATIC ETHER SIMILAR TO MESCALINE.
ALSO FOUND IN PARSLEY AND CARROTS!!
TREE FOUND IN SPICE (OR NUTMEG) ISLANDS OF SOUTH PACIFIC IN
INDONESIA.
DOSE: NUTMEG- 10 TO 30 GMS DISSOLVED IN JUICE OR WATER.
REACTIONS VARY CONSIDERABLY FROM NOTHING AT ALL...TO
EUPHORIA AT LOW DOSES, TO MARIJUANA-LIKE OR LSD-LIKE
EXPERIENCES AT HIGHER DOSES
LATENCY 10 MIN TO 4 HOURS. LASTS UP TO 2 DAYS!
CAUSES NAUSEA, DIZZINESS, HEADACHES, ANXIETY AND
DELIRIUM.
ENDS WITH SEVERE HANGOVER.
MOST PEOPLE NEVER TRY NUTMEG AGAIN!
CHRONIC USE CAN PRODUCE A PSYCHOTIC REACTION SIMILAR
TO STIMULANT PSYCHOSIS.
OTHER SPICES:
SPICES SUCH AS SAFFRON, FENNEL, DILL, CINNAMON, AND
ANISE CONTAIN SIMILAR PSYCHOACTIVE ETHERS, SUCH AS
SAFROLE, EUGENOL AND MYRISTICIN. CLOVE CIGARETTES
CONTAIN EUGENOL - PRODUCES MILDER THC LIKE EFFECTS
HARMALINE AND HARMINE: LSD-LIKE AGENTS THAT ARE
MAO-INHIBITORS
ORIGINATE FROM MANY THICK VINE PLANTS (E.G.,
PEGANUM HARMALA) FOUND IN THE AMAZON RAIN
FOREST. DRINK CALLED YAGE (MADE FROM
HAEMADICTYON AMAZONIA), CAAPI, OR AYAHUASCA,
AVINE OF THE SOULS,
(BOTH FROM BANISTEROCOPSIS CAAPI)
THEY ARE INDOLE ALKALOIDS WITH A BETA-CARBOLINE
SKELETON= DERIVED FROM TRYPTOPHAN.
SOME PLANTS ALSO CONTAIN DMT.
METHYLATED HARMAN MOLECULES CAN BE FOUND IN
HUMAN BRAIN AT AUTOPSY
LATENCY OF ONSET WITH ORAL DOSE IS 5 MIN!
DURATION: 4 - 8 HOURS
SYMPTOMS: NAUSEA, VOMITING, DIARRHEA, STOMACH
CRAMPS FOLLOW THE EXPERIENCE.
HALLUCINATIONS: REGARDLESS OF BACKGROUND,
VISIONS OF PANTHERS, JAGUARS, AND OTHER LARGE
CATS!
CALLED A PSYCHIC SEDATIVE.
IBOGAINE
DEA CONTROLLED SUBSTANCE LIST. MAJOR PSYCHOACTIVE
AGENT OF AN AFRICAN SHRUB (TABERNANTHE IBOGA).
IS ACTUALLY AN ANALOGE TO SEROTONIN, TRYPTOPHAN.
SIMILAR TO ENDOGENOUS BDZS, I.E. THE BETA-CARBOLINES.
COMPETES FOR BINDING AT GLUTAMATE NMDA RECEPTOR SITES.
1998 REVIEW: USE DEPENDENT BLOCK OF NMDA RECEPTOR-COUPLED
CATION CHANNELS, INTERACTIONS WITH DOPAMINE RE-UPTAKE
TRANSPORTERS, K-OPIOID RECEPTORS AND SEROTONIN RECEPTORS.
EXTRACTS OF PLANT USED BY AFRICAN NATIVES WHILE STALKING GAME,
TO ENABLE THEM TO REMAIN MOTIONLESS FOR AS LONG AS 2 DAYS WHILE
REMAINING ALERT.
Ibogaine and several iboga alkaloids (tabernanthine, R- and S-coronaridine, Rand S- ibogamine, desethylcoronaridine, and harmaline) reduced cocaine selfadministration in humans and rats; these effects were seen the day after
injection.
"A little over an hour after taking ibogaine, a strong desire to lie
down occurs and a feeling of dizziness. Then a television or movie
screen appears and the person pictorially reviews his or her life.
This view of events seems emotionally dissociated from the present
time, and past errors and poor decisions are recognized and
assimilated impartially. People wake up believing they have a new
understanding and control of their life."
Hallucinations are interesting: childhood imagery, frequent
explosions of rage directed at incidents that occurred in
childhood. Effects last 8 to 12 hours.
Sorcerers of the Bwiti African tribe use it to speak with
ancestors and spirits. Initiation into the tribe hinges on one’s
having a vision of the god plant Bwiti via the use of iboga
plant extracts.
Popular among street addicts in Europe for treatment of
heroin and cocaine dependence. Lab animal studies could
not confirm its effectiveness to prevent withdrawal symptoms.
Currently patented for treatment of opiate, amphetamine,
cocaine and ethanol addition.
BUFOTENIN
FOUND IN LOW QUANTITIES IN FISH (RUDDER FISH, OFF NORFOLK
ISLAND) DREAM FISH: VIVID DREAMS AFTER INGESTION OF FISH.
ALSO FOUND IN SKIN AND GLANDS OF A S. AM. TOAD.
COHOBA - CONTAINS BUFOTENIN
FOUND IN ACACIA NIOPO CENTRAL AM. MIMOSA
USE- AS SNUFF OR ENEMA,
Side Effects- PURPLE FACE, VOMITING.
VISUAL HALLUCINATIONS.
IN ORINOCO BASIN, SEEDS OF SOME PEAS (PIPTADENIA
PEREGRINA) ARE GROUND MIXED WITH LIME, AND USED AS SNUFF
CALLED "YOPO". USING A FORKED TUBE MADE FROM CHICKEN
BONES, THE BOYS BLOW IT INTO EACH OTHERS NOSTRILS.
May be found in the mushroom Amanita muscaria.
Salvinorin A is the main active psychotropic molecule in Salvia
divinorum, a Mexican plant which has a long history of use by Mazatec
shamans. Salvinorin A is a hallucinogenic compound.
It is structurally quite distinct from other naturally occurring hallucinogens.
It is the most potent naturally occurring psychoactive drug known to date,
with an effective dose in humans in the 200- to 1,000-µg range when
smoked.
It acts as a kappa opioid receptor
agonist and is the first known
compound acting on this receptor
that is not an alkaloid.
Salvinorin A has no actions at
the 5-HT2A receptor.