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Psilocybin and Consciousness Andy Alexander, Zane Andre Albert Anaya, Dan Lotz COGS175 Dr. Pineda March 12, 2008 Presentation Outline Introduction and History of use (Dan) Chemical properties and physiological mechanisms (Dan and Zane) Alternate State of Consciousness (Albert) Sensory Effects and Sustained Revelations Conclusion (everyone) (Andy) History of Magic Mushrooms First documented use found in cave paintings depicting the shamanic use of mushrooms in what is now North Africa Mayan and Aztecs relics have also been found depicting the ritual use of hallucinogenic mushrooms In the Aztec culture these mushrooms were known as teonanácatl or God’s flesh Psilocybin Psilocybin is the psychoactive component of mushrooms Classified in the tryptamine family because of the indole ring Other tryptamines; DMT, Melatonin, Serotonin, tryptophan and LSD-25 Psilocybin continued… Psilocybin is converted to the psychoactive metabolite Psilocin. Psilocin is a partial agonist at the 5-HT2A serotonin receptor in the brain Psilocin is also an agonist 5-HT1A and 5HT2C receptors Psilocybin Psilocin dephosphorilization Other Psychoactive Compounds Two other psychoactive chemicals are present in many species of psilocybe-containing mushrooms: Baeocystin and Norbaeocystin. It is important to note that while these are minor compounds to Psilocin, a dosage as little as 10mg is reported to elucidate effects These chemicals have not been the subject of any major research, and consequently no detailed information is available on them. It is known, however, that they are also Baeocystin Norbaeocystin Indole Ring The indole ring is chemically known as a benzene ring fused to a nitrogen- containing pyrrole ring, and can contain be found in many aromatic compounds, such as orange blossom scent. The indole ring makes up the primary structure of serotonin and tryptophan, and is also found in LSD, DMT, Psilocybin, Psilocin, Baeocystin, Norbaeocystin and many other hallucinogenic compounds. It is theorized that the binding mechanism of these type of psychoactive compounds is based on this chemical shape fitting the ‘keyhole’ of specific serotonin receptors. Because they are not chemically identical to serotonin, they have manifest varied effects, particularly at the 5-HT2A receptor. Indole Configurations Psilocin and Altered State Corticol-thalamic pathway modulation Hyperfrontality Psilocin and Altered State (cont.) Decrease in alpha and increase in beta in the neocortex Prepulse Inhibition Psilocin and Altered State (cont.) Comparison between Dietrich and Vollenweider •Study between druginduced ASC and placebo •Same corticalsubcortical organization •Frontal-parietal, temporal, and occipital cortex, striatum, and thalamus •Frontal-parietal and striatal network General Effects Duration (orally ingested) Total duration: ~4-7hrs Onset: 15-60min Plateu: 2nd to 4th hours After effects: Headache In general, no physiological hangover/ day after effects Sensory Effects: Visual Hallucinations (VUS subscale) – Visionary restructuralization Illusions/ hallucinations synaesthetic phenomena Enhancement of percepts – Contour distortion – Increased sensitivity to light – Closed eye visuals Auditory hallucinations Alterations in perception of time and space Sensation of buzzing in the peripheral limbs Recollective/ analytical stage Attribution of salience to random objects/ events Affective States Increases in: – Oceanic Boundlessness Scale Measures derealization and depersonalization phenomena Associated with a basic positive mood state – – – – Heightened feelings to sublime happiness (euphoria) Grandiosity Alterations in sense of time and space Giggling, giddiness, increased emotional sensitivity, sleepiness Affective states… Increase in: – AIA scale (dread of ego-dissolution) – “Measures thought disorder, anxious egodisintegration, loss of control over body and thought, and derealization phenomena associated with arousal and anxiety.” Comprises: intense feelings of fear, nausea, mild to severe anxiety, confusion, can precipitate or exacerbate existing mental disorders (i.e. schizophrenia), working memory disruption – Similarities between psilocybin-induced psychosis and early stages/ mild schizophrenia… Psilocybin-induced psychosis provides clues as to the physiological mechanisms of Schizophrenia “Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action” Vollenweider et al. 1998 – Administered psilocybin to three groups who were pre-treated with 5-HT2 antagonist ketanserin, 5-HT/ D2 antagonist risperidone, or D2 antagonist haloperidol Results: – Pre-treatment with either ketanserin or risperidone dose-dependently blocked psilocybin-induced psychosis on APZ-OAV scale – Pre-treatment with haloperidol only reduced the effect of psilocybin on the OSE subscale, no influence on psilocybin-induced visual hallucinations Haloperidol uniformly increased the AIA scores in all of the subjects treated with psilocybin – Also found that Psilocybin increased the RT on memory-guided delayed response task during peak effects of drug (evidence of impairment of working memory) Analytical/ Recollective Stage, Mysticism and Sustained Revelations the Good Friday Experiment, Pahnke 1963 Theological seminary students received either 30mg psilocybin or 200 mg of nicotinic acid in a group setting during a religious service Participants who received psilocybin showed significant elevations on the Pahnke Mystical Experience Questionaire Reported positive changes in attitudes and behavior at 6-months and at a 25-year follow up Analytical/ Recollective Stage, Mysticism and Sustained Revelations “Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance” R.R. Griffiths, 2006 2006. administered psilocybin or methylphenidate in double blind study to 36 adults in a personalized, comfortable setting. Subjects told to focus on spirituality, "look-within," strive for mystical experience 67% of the volunteers rated the experience with psilocybin to be either the single most meaningful experience of his or her life or within the top 5 most meaningful experiences Sustained revelations Continued… Evidence of sustained revelations: -family and close friends reported noticeably positive behavior and attitudes on subjects up to 2 months postexperience - longer follow up is in progress Conclusion Frontal-parietal activation might be where conscious is altered. Capacity for sustained alterations of consciousness sets psilocybin experiences apart from other hallucinogens More YouTube http://youtube.com/watch?v=B4pIxnuUG1 k&feature=related References Aghajanian GK, Marek GJ (1997). Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells. Neuropharmacology 36: 589–599 Carter O.L, et al. “Modulating the Rate and Rhythmicity of Perceptual Rivalry Alternations with the Mixed 5-HT2A and 5-HT1A Agonist Psilocybin” Neuropsychopharmacology. 2005 Jun1154-62 Griffiths R.R., et al. “Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance" Psychopharmacology. 2006 Aug 268-83 Vollenweider, F.X and Geyer, M.A. “A Systems Model of Altered Consciousness: Integrating Natural and Drug-Induced Psychoses”. Brain Res. Bull., 56(1), 495-507, 2001 Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Babler A, Vogel H, Hell D (1998). “Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action” Neuroreport 3897-3902 Wallace, Benjamin and Fischer Leslie E. Consciousness and Behavior Prospect Heights:Waveland Press Inc, 2003 Torsten Passie, et al. “The Pharmacology of psilocybin.” Addition Biology. 2002 May 357-364 Franz Vollenweider, et al. “”Advances and pathphysiological models of hallucinogen drug actions in humans: A preamble to schizophrenia research.” Pharmacopsychiatry 31:92-103; 1998 Dietrich, Arne. “Functional neuroanatomy of altered states of consciousness: The transient hypofrontality hypothesis.” Consciousness and Cognition 12:231-256; 2003 J. Wackermann, et al. “Effects of Varied doses of psilocbin on time interval reproduction in hman subjects. Neurosci. Lett. (2008). Doi: 10.1016/ I.neulet.2008.02.006