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Location of Serotonin Neurons in the Raphe Nuclei

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

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Location of Serotonin Neurons in the Raphe Nuclei

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  1. Location of Serotonin Neurons in the Raphe Nuclei

  2. 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. 

  3. 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

  4. 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)

  5. 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. 

  6. Rapid tryptophan depletion leads to symptom relapse in recovered depressed patients

  7. TERMINATION OF ACTION PRIMARILY BY UPTAKE CATABOLISM BY MAO‑A IS MINOR COMPONENT.

  8. 5HT1-A ARE AUTORECEPTORS ON RAPHE NEURONS MORE SENSITIVE TO LSD THAN TO 5HT! DYSFUNCTION OF THESE RECEPTORS UNDERLIE ANXIETY

  9. 5-HT1-A receptors control the release of serotonin and activity of 5HT neurons via two signaling mechanisms

  10. Hallucinogens, e.g. LSD, Turn Off Serotonergic Neurons in the Raphe Nuclei by Stimulating 5HT-1A Receptors

  11. Genetic deletion of the 5-HT1A receptor increases anxiety-like behavior in mice

  12. Ratings of religiosity & spirituality inversely correlated with the number of Serotonin 5-HT1A receptors in humans American Journal Psychiatry 160:1965-1969, November 2003

  13. Stimulating 5HT-1A receptors, e.g. with BuSpar, relieves anxiety

  14. TH Serotonin contains an indole ring with a carbon chain attached

  15. ….So do these hallucinogens LSD Psilocybin Hallucinogens produce synesthesia.

  16. Synesthesia: a remarkable, rare condition where an individual has multimodal perceptual experiences from a unimodal sensoryevent. The ability of hallucinogens to induce synesthesia may be related to their ability to influence serotonergic control over the frontal lobes.

  17. “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.”

  18. 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.

  19. 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

  20. 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.

  21. 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).

  22. 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.

  23. 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.  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. VERY MIXED RESULTS.

  24. 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

  25. 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 “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…”

  26. MEXICO'S MAGIC MUSHROOMS. PSILOCYBEMEXICANA. 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.

  27. 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 MUSHROOM ORAL 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 VOMITING WELL ABSORBED FROM GI TRACT.

  28. 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.

  29. 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, VERTIGO OVERDOSE: 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 USE TIMOTHY LEARY'S GOOD FRIDAY TEST, 20 SEMINARIANS, DRUG/NO DRUG, ATTENDED RELIGIOUS SERVICE. DRUG CORRELATED WITH ENHANCED MYSTICAL EXPERIENCE. 

  30. 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

  31. 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.”

  32. Ergot fungus (Claviceps purpurea) growing on corn

  33. 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.

  34. 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

  35. 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.

  36. 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.

  37. 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. 

  38. 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

  39. MORNING GLORY RIVEACORYMBOSA: 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.

  40. 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.

  41. 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!

  42. 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

  43. 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.

  44. 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.

  45. 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. 

  46. 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.

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