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)ANATOMYNUCLEI 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 PONSCALLED = RAPHE NUCLEI. ACCOUNTS FOR 80% OF FOREBRAIN 5HT. 

Active

Quiet

SWS

REM

RAPHE NEURONS HAVE REGULAR SLOW SPONTANEOUS FIRING RATE (0.5 TO 2.5 SPIKES/SEC) FUNCTION: NO INFORMATION TRANSFER, ONLY MODULATION5HT APPLIED TO RAPHE NEURONS DECREASES FIRING. SPONTANEOUS ACTIVITY IS ELIMINATED DURING REM SLEEP.

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 UPTAKECATABOLISM 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 Receptors

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

Serotonin contains an indole ring with a carbon chain attached

TH

LSDPsilocybin

….So do these hallucinogens

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.

“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.”

Increased structural connectivity in grapheme-color synesthesiaRomke Rouw & H Steven Scholte

Nature Neuroscience - 10, 792 - 797 (2007)

 

                                                                                                                                  

                                   

Increased brain activation and increased anisotropy in the inferior temporal cortex in grapheme-color synesthetes.

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.

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.

HALLUCINOGENS

The term hallucination comes from the Latin lucinatio meaning "to dream or wander in the mind." One definition of hallucination is a perception in the absence of an actual external sensory stimuli. This differs from an illusion as an illusion is sensory perception arising from an external stimulus.The interdisciplinary study of psychopharmacology, has given rise to very specialized research disciplines called archeopsychopharmacology and ethnopsychopharmacology (Lukoff, Zanger, & Lu, 1990). The research methodologies of archeopsychopharmacology rely on the study of ancient artifacts, including iconographs (pyramids, carvings, cave walls drawings, and clay tablets) as well as texts (Vendenta, 5000 year old Hindu books). This approach began in 1968 when petroglyphs found in North Africa were believed to indicate the existence of a 12,000 year-old mushroom cult. Results of studying these artifacts suggested that Amanita muscaria mushrooms were the psychoactive ingredient in the potion known as Soma. Clearly, hallucinogenic substances have played a large role in ancient shamanistic healing and ceremonial practices. However, this study of understanding the role of psychoactive substances in early religious and tribal life is the domain of ethnopsychopharmacology.

Drugs that produce hallucinations (often referred to as phantasicants) included in this "functional bibliography" essentially fall into seven major chemical classes (Hoffman, 1959): 1) Indole derivatives of tryptamine (an amino acid), including the lysergic acid alkaloids, psilocybin and the harmala alkaloids 2) Phenylethylamines (e.g., mescaline) 3) Phenylpropenes (e.g., myristicin) 4) Isoxazoles (e.g., muscimol and ibotenic acid) 5) Tropanes (e.g., scopolamine) 6) Quinolizidines (e.g., cryogenine) 7) Dibenzopyrans (cannabinoids).

One yields a surprisingly similar consensus of seeing geometric images accompanied by altered feelings. For example, participants reported "I feel like I am flying". There were four consistent geometric images reported: 1) a lattice or grating; 2) a cobweb structure; 3) a tunnel or funnel alley; and, lastly, 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).

The most commonly reported experiences included eight types of forms (lines, curves, webs, lattices, tunnels, spirals, kaleidoscopes, and random images), eight colors (violet, blue, green, yellow, orange, red, white, and black), and eight movements (vertical, horizontal, oblique, explosive, concentric, rotational, pulsating, and aimless).Siegel (1977) reports that 62-72% of 500 participants tested with LSD reported similar simple forms at low doses. Also, 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.

TIMOTHY LEARY'S GOOD FRIDAY TEST (1962)20 SEMINARIANS, DRUG/NO DRUG (30 mg PSILOCYBIN) ATTENDED RELIGIOUS SERVICE. ASKED WHETHER THE DRUG EXPERIENCE CORRELATED WITH ENHANCED MYSTICAL EXPERIENCE. 

VERY MIXED RESULTS.

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.

HALLUCINOGENS AND RELIGION

The Codex Vienna Mixtec manuscript (13th century) depicted the ritual use of the

mushrooms by the Mixtec Gods.

Neural correlates of a mystical experience in Carmelite nunsM. Beauregard, V. Paquette, Univ of Montreal,Neuroscience Letters, September, 2006

Religious/mystical experiences can be generated internally…

“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…”

Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance.

R. R. Griffiths &W. A. Richards & U. McCann & R. Jesse, Johns Hopkins University School of Medicine, Psychopharmacology (August, 2006) 187:268–283

MEXICO'S MAGIC MUSHROOMS. PSILOCYBE MEXICANA.

ACTIVE INGREDIENT - PSILOCYBIN. 

(PSILOCIN IS SIMILAR IN ACTION, MORE LIPID SOLUBLE; PSILOCYBIN MAY BE FIRST CONVERTED TO PSILOCIN)

PSILOCIN IS SLIGHTLY MORE POTENT.ACTUALLY IS PHOSPHORYLATED 4-OH-BUFOTENIN.

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 CAN BE FOUND IN MORE THAN 75 DIFFERENT SPECIES OF MUSHROOMS.PSILOCYBIN IS UNIQUE: ONLY KNOWN NATURALLY OCCURRING INDOLE TO CONTAIN PHOSPHORUS. 0.2 ‑ 0.5% OF MUSHROOMORAL DOSE: 2 TO 4 MUSHROOMS. 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, (ANTI‑CH EFFECTS).VIOLENT NAUSEA AND VOMITINGWELL ABSORBED FROM GI TRACT.

THE MYCELIUM, THE PART OF THE MUSHROOM COMPLEX THAT IS ROUGHLY ANALOGOUS TO ROOTS IN A PLANT, IS SOLD IN A GROWING MEDIUM, SUCH AS COOKED RICE, CAKED MARIJUANA OR WELL-ROTTED WOOD CELLULOSE.

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.

25% OF DOSE IS EXCRETED UNCHANGED BY KIDNEYS INTO URINE.INACTIVE METABOLITES REMAIN IN BODY FOR MANY DAYS.MECHANISM: RELATED TO ACTION OF 5HT SYSTEM. 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, VERTIGOOVERDOSE: HYPERTHERMIA, FLUSHING, CONVULSIONS, ANXIETY, PANIC REACTIONS, PARANOIA.DEATH CAN OCCUR FROM INGESTING ABOUT 2000 TIMES THE NORMAL DOSE.

DEPENDENCE: NO PHYSICAL OR PSYCHOLOGICAL SEEN.TOLERANCE: NOT LIKELY DUE TO OCCASIONAL USETIMOTHY LEARY'S GOOD FRIDAY TEST, 20 SEMINARIANS, DRUG/NO DRUG, ATTENDED RELIGIOUS SERVICE. DRUG CORRELATED WITH ENHANCED MYSTICAL EXPERIENCE. 

LSD IS ERGOT DERIVATIVE OR INDOLE ALKYLAMINETHE 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. EFFECTIVEONLY 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 DIETHYLAMIDE, LSD

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.

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.”

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.

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).

candy flips - home-made capsules containing LSD + MDMA

hippy flipping - pairing psychedelic mushrooms

kitty flipping - ketamine and ecstasy

candy flipping on a string – cocaine + 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 SLEEPSUGGESTS 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 GLORYREQUIRES 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 CENTURYSUGGESTED THE THE MORNING GLORY WASINDEED "OLOLIUQUI.“ BUT IT WAS NOT UNTIL ITWAS DISCOVERED STILL GROWING IN 1939IN A ZAPOTEC INDIAN GARDEN IN OAXACA MEXICOWAS 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 SIGNI FICANCE.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.  "BUSINESS MAN'S TRIP". 

EFFECTIVE HALLUCINOGENIC DOSE ‑ 1 MG INHALATIONPRODUCES 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 DEPENDENCETOLERANCE 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 HALLU CINOGENIC 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)

THEORYONCE 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. 

MAY ALTER DA FUNCTION, BLOCKS NE‑REUPTAKE, IS A MAO-I AND ACHE-I.

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.

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 HALLU CINOGEN.

NUTMEG AND MACE (A RED SHEET OF MATERIAL THAT SURROUNDS THE INNER NUT) COME FROM NUTMEG TREE, MYRISTICA FRAGRANS, ACTIVE AGENT (MYRISTICIN-NUTMEG OR CLEMICIN-MACE) 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 DOSESLATENCY 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-INHIBITORSORIGINATE 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, R- and S- ibogamine, desethylcoronaridine, and harmaline) reduced cocaine self-administration 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. 

SORCERORS 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.

1990:(NEUROREPORT 1:5) POPULAR AMONG STREET ADDICTS IN EUROPE FOR TREATMENT OF OPIOID 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.

BUFOTENINFOUND 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 as an entheogen by indigenous Mazatec shamans. Salvinorin A is a hallucinogenic compound with dissociative effects. It is structurally quite distinct from other naturally occurring hallucinogens such as N,N-dimethyltryptamine, psilocybin, and mescaline and from synthetic hallucinogens such as lysergic acid diethylamide (LSD), and ketamine. Salvinorin A has been reported to be 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. In that way Salvinorin A's qualitative potency may be compared with LSD, though it is otherwise dissimilar, having quite different effects and timeframes. Salvinorin A can produce psychoactive experiences in humans with a typical duration of action being several minutes to an hour or so depending on the method of ingestion.[1]Salvinorin A is found together with several other structurally related salvinorins. Salvinorin is a trans-neoclerodane diterpenoid. 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 is a trans-neoclerodane diterpenoid, chemical formula C23H28O8.[2] Unlike other known opioid-receptor ligands, salvinorin A is not an alkaloid — it does not contain a basic nitrogen atom.[3] Salvinorin A has no actions at the 5-HT2A serotonin receptor, the principal molecular target responsible for the actions of classical psychedelics.[3]Salvinorin A is the most potent naturally-occurring psychoactive compound known.[4] It is active at doses as low as 200 µg.[2][4][5] Recent research has shown that salvinorin A is a potent and selective κ (kappa) opioid receptor agonist.[2] It has been reported that the effects of salvinorin A in mice are blocked by kappa opioid receptor antagonists.[6] This makes it unlikely that another mechanism contributes independently to the compound’s effects. Salvinorin A is unique in that it is the only naturally occurring substance known to induce a visionary state via this mode of action.