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Introducon to Objecves Herbal Medicine ● Discuss history and role of psychedelic herbs Part II: Psychedelics, in medicine and illness. Legal Highs, and ● List herbs used as emerging legal and illicit Herbal Poisons drugs of abuse. ● Associate main plant and fungal families with Jason Schoneman RN, MS, AGCNS-BC representave poisonous compounds. The University of Texas at Ausn ● Discuss clinical management of main toxic Schultes et al., 1992 compounds.

Psychedelics

Sacraments: spiritual tools or sacred medicine by non-Western cultures vs. Dangerous drugs of abuse vs. Research and clinical tools for mental and physical

http://waynesword.palomar.edu/ww0703.htm disorders

History History ● Shamanic divinaon ○ Smulus for spirituality/religion

http://orderofthesacredspiral.blogspot.com/2012/06/t- mckenna-on-psilocybin.html http://www.cosmicelk.net/Chukchidirections.htm

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History History

http://www.10zenmonkeys.com/2007/01/10/hallucinogenic- weapons-the-other-chemical-warfare/ http://rebloggy.com/post/love-music-hippie-psychedelic- woodstock

http://fineartamerica.com/featured/misterio-profundo-pablo- amaringo.html

History

● Psychotherapy ○ 20th century: unl 1971 ● Recreaonal ○ Smulus of U.S. cultural revoluon

http://qsciences.digi-info-broker.com

http://www.uspharmacist.com/content/d/feature/c/38031/ http://en.wikipedia.org/nervous_system

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Main Groups Main Groups Tryptamines LSD, Psilocybin, DMT, Ibogaine Other Ayahuasca, Fly agaric

Phenethylamines MDMA, Mescaline, Myristicin Pseudo-hallucinogen Cannabis

Dissociative Ketamine, Phencyclidine Anticholinergics Tropanes hallucinogens (PCP), Ibogaine, Salvia

Lysergic Acid Diethylamide (LSD) Lysergic Acid Diethylamide (LSD)

● Ergot fungus (Claviceps purpurea ) ● Avoid in pre-exisng mental illness, ● Potent 5HT2A agonist parcularly schizophrenia ● Colorless, odorless, tasteless and the most ● Psychotherapy for anxiety based disorders potent drug known on the planet (mainly end of life (cancer)) and addicons ○ 20 mcg can alter consciousness for 12 hours ● Cluster headaches

Psilocybin ● Converted to Psilocin in body ● Found in many species of mushrooms

● 5HT2A agonist Ergot fungus ● Psychotherapy Claviceps purpurea ○ OCD ○ End of life anxiety (cancer) ○ MDD ○ Nicone addicon

http://en.wikipedia.org/wiki/Claviceps_purpurea ● Cluster headaches

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Psilocybe cubensis N, N Dimethyltryptamine (DMT) ● Endogenous compound in humans ○ In near death experiences, DMT secreted from pineal gland ● Virola (Epena), Anadenanthera (Yopo), Psychotria, Bufo alvarius

● 5HT2A agonist ● Broken down by monoamine oxidases, so needs

http://divawhispers.com/onthescene/ MAOI adjunct or bypass MAOIs

http://www.amazon-indians.org/yanomami.html Schultes et al., 1992

Ibogaine ● Tabernanthe iboga (Apocynaceae)

● 5HT2A agonist, NMDA receptor antagonist, kappa opioid receptor agonist ● Psychotherapy ○ An-addicon: ETOH, cocaine, opiates/opioids

Schultes et al., 1992

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Mescaline ● From various species of cac ● 5HT2A agonist, adrenergic, dopaminergic Peyote ● Psychotherapy Lophophora ○ Addicons williamsii

http://fineartamerica.com/featured/close-view-of-peyote-cacti-lophophorus-ira-block.html

MDMA (Ecstasy) Ayahuasca ● Synthesized from various plant precursors ● Mixture of two known hallucinogenic plants and ● 5HT1A, 5HT1B, 5HT2A agonist, adrenergic, many other admixture plants dopaminergic ● Bansteriopsis caapi: Beta carboline harmala ● Psychotherapy alkaloids and MAOIs ○ PTSD ● Psychotria viridis (Rubiaceae): DMT but needing ○ MDD (ECT replacement) MAOI to be acvated orally ○ Borderline personality disorder ● Ayahuasca churches

http://en.wikipedia.org/wiki/Ayahuasca http://www.telegraph.co.uk/news/picturegalleries

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Natural and Semi- Overdose Management Synthec Legal Highs ● Supporve therapy ● Natural: not yet on radar of public and legislave ● BZDs: mainly Avan bodies ● Restraints? ● Synthec: The Controlled Substance Analogue ● Lab and diagnosc tests: Enforcement Act of 1986, tacked on to Controlled ○ CBC, CMP, Tox screen, Cardiac enzymes, ECG, Substances Act of 1971: EEG ○ chemical structure must be structurally similar to other class I or IIs or acts same physiologically

http://en.wikipedia.org/wiki/Autonomic_nervous_system http://en.wikipedia.org/wiki/Autonomic_nervous_system

Synthec Cannabinoids Synthec Cannabinoids ● ‘Spice’ and many other common names ● Can bypass drug tests: used by law, fire and ○ Compounds synthesized and sprayed on inert armed forces plant material and sold as incense to bypass ● Many mes more potent than hash oil detecon or legal scruny ● Has been associated with psychosis, seizures, ● Over 400 compounds from work of Dr. Huffman and MIs (creaon of cannabinoids for research) ● Treatment ● 2nd most abused recreaonal drug behind ○ BZDs and Trazodone Cannabis

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Salvia ● Salvia divinorum (Lamiaceae) ● Ancient Mazatec herb for shamanic divinaon ● Kappa opioid receptor agonist, dopaminergic ● Kept from schedule I status: ○ due to being promising candidate for novel andepressant and non-addicve analgesics and anesthecs

http://winnipeg.ctvnews.ca/winnipeggers

Salvia ● Used at greater rate than ecstasy in 18-24 y/o ● Smoked ● Has been associated with anxiety and psychosis ● Treatment: ○ BZDs

http://en.wikipedia.org/wiki/File:Salvia_Divinorum

Methedione/Methylone Methedione/Methylone ● Synthec derivaves of Cathinone found in Khat ● Causes: (Catha edulis) ○ Agitaon ○ nave to East Africa and Arabian peninsula and ○ Seizures chewed for millennia for amphetamine-like ○ Excessive sympathomimec smulaon: qualies ■ Tachycardia, confusion, psychosis, ● Known as “bath salts” hyponatremia ● Potent adrenergic and MAOI ● Treatment ● Snorted and injected ○ BZDs

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http://www.jewishjournal.com/world/article/widespread_khat_addiction_threatens_yemens_future http://fauxsociety.com/bath-salts-and-the-taste-for-flesh-zombie/

Ancholinergics ● Datura, Brugmansia, Belladonna, Henbane ● Causes: ○ Tachycardia, HTN, restlessness, delirium, blurred vision ○ Hallucinaons: auditory, visual ● Treatment ○ Acetylcholinesterase inhibitor: ■ Physosgmine

Cholinergics: Isoxazoles ● Occur in the genera: Clitocybe, Inocybe and in two species of Amanita ● Muscimol: GABA agonist, seratogenic, dopiminergic ● Ibotenic acid: NMDA agonist ● Fatalies rare but possible to die with ingeson of 10 or more mushrooms

● Treatment: supporve http://en.wikipedia.org/wiki/List_of_Amanita_species

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Other Legal Highs Other Legal Highs ● Kratom (Mitragyna speciosa) ● Betel nut (Areca catechu) ○ Mitragynine: adrenerigic, mu and kappa ○ Arecaidine and arecoline: adrenergic, GABA opioid agonist, NMDA antagonist, inhibitor, cholinergic agonist, highly seratonergic carcinogenic ● Morning glory (Ipomoea violacea) ● Nutmeg (Myrisca fragrans) ○ LSA (d-lysergic acid amide): potent ○ Myrisn (MAOI): adrenergic, dopiminergic, seratonergic seratonergic

Herbal Poisons ● Acute management of poisoning ○ Immediate stabilizaon, decontaminaon, exam and labs ○ Pay close aenon to toxidrome, physical and verbal evidence for source of poisoning ○ Labs: CBC, CMP, UA, Coags, ECG, Cardiac enzymes, ABGs, Tox screen, EEG

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Herbal Poisons Algae ● Gastric decontaminaon ● Pfiesteria piscicida (dinoflagellate): toxin 1000 ○ Ipecac: no longer recommended mes stronger than cyanide, AKA “fish Ebola”, ○ Gastric lavage: no longer recommended indirect toxicity via shellfish ○ Whole bowel irrigaon: not recommended in ● Signs and symptoms: fague, arthralgias, herbal poisoning paresthesias, nausea, open sores, memory loss ○ Charcoal: case by case basis, and only if can (lasng 1-2 weeks aer exposure), disorientaon be administered in first 1-2 hours of herbal ● Treatment ingeson ○Supporve

Pteridophytes ● Pteridium aquilinum: ○ Bracken fern ● Carcinogenic ptaquiloside and thiaminase: ○ neoplasms of the upper alimentary tract ●Found throughout east Texas and the mountains of west Texas ● Treatment: ○ Prevenon de.wikipedia.org/ wiki/Pfiesteria_piscicida

Gymnosperms ● Cycadaceae: primarily Cycas revoluta (“Sago palm”) in Texas. ● Palm-like pinnate leaves, but disnct cone-like reproducve structures ● Neurodegenerave azoxy glycosides and mutagenic cycasin

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Gymnosperms ●Texas ornamental ●Signs and symptoms: ○icterus, jaundice, N/V, liver failure, weakness, seizures ●Treatment: ○Supporve

Ephedra Ephedra ● Ephedra sp. (joinirs, ma huang, mormon tea) ●Distribuon is widespread in drier regions of the world, occurs in west Texas ○Thin ●Signs and symptoms: ○Oen light green to blue ○Headache, diaphoresis, hyperthermia, MI/ ○Jointed stems with small cone-like reproducve Stroke, seizures, agitaon structures ●Treatment: ● Natural source of l-ephedrine and d- pseudoephedrine ○BZDs

Angiosperms Monocots

http://commons.wikimedia.org/wiki/ File:Ephedra_fragilis_3.JPG

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Araceae Araceae ● Araceae (Anthurium, Arisaema (Jack-in-the-pulpit), ● Alocasia, Colocasia (Taro), and Xanthosoma eaten Arum (Lords and Ladies), Caladium, Colocasia, throughout Asia and South Pacific, some variees Dieffenbachia, Monstera, Alocasia, Philodendron) with significant raphides ● Raphides (cells) contain calcium oxalate crystals in ● Signs and symptoms: edema, erythema, bullae, the shape of needles and proteolyc enzymes in altered speech, laryngeal occlusion some genera ● Treatment: ● Extremely diverse leaf morphology but generally ○Removal similar reproducve structures (spathe and spadix) ○Anhistamines ○Steroids

http://forums2.gardenweb.com/forums/load/houseplt www.meemelink.com www.sarracenia.com/

Liliaceae Liliaceae ● Colchicum (Autumn crocus), Convallaria (Lily-of-the- ● Toxins include: colchicine (highest in corms and valley), Gloriosa simplex (Gloriosa lily), Narcissus seeds), lycorine, cardiac glycosides (daffodil, narcissus), Tulipa (tulip), Hymenocallis ● Signs and symptoms: fever, leukocytosis, (spider lily), Amyrillis (naked ladies, etc.) palpitaons, dysrhythmias, shortness of breath, N/ ● Grass-like parallel veined leaves and trimerous (flower V, abdominal pain, diarrhea, hematuria, dizziness, parts in threes), showy flowers; underground stems MODS (e.g. bulbs and corms) ● Treatment: ● A few uncommon nave species, mainly ornamental ○Atropine genera are problemac ○Fab fragment angen binding

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Angiosperms Dicots

Solanaceae Solanaceae ● Atropa belladonna (deadly nightshade), Datura ●Nave Solanum and Datura, others introduced or for (jimsonweed), Hyoscamus (henbane), Lycopersicon food, smoke and ornamentals esculentum (tomato), *Nicoana (tobacco), Solanum ●Signs and symptoms: dry mucous membranes, blurred (black nightshade, horse nele, potato, etc.), vision, hyperthermia, HTN, tachycardia, ileus, urinary Brugmansia (angel trumpet) retenon, agitaon, hallucinaons, delirium, seizures ● Diverse leave and stem morphology, flowers usually ●Treatment funnel-shaped and fused and fused stamens ○Supporve ● Toxic tropane alkaloids: hyoscyamine, atropine, ○BZDs for cocaine ○Physosgmine for tropanes scopolamine, solanine, cocaine

Schultes et al., 1992

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wikipedia/commons/a/a0/Illustration_Atropa

Anacardiaceae Anacardiaceae ● Toxicodendron (radicans=poison ivy, diversilobium ●Signs and symptoms: type I hypersensivity- and quercifolium=western and eastern poison oak extreme pruris and pain, erythrema, vesicles- respecvely, vernix=poison sumac) Mangifera bullae (mango), Anacardium (cashew) ●Treatment:

● Small viny shrubs to tall trees, resinous leaves and ○Removal: soap and water ○Anhistamines bark, finely divided leaves (pinnately compound) ○Analgesics ● Toxic compound: oleoresin (urushiol) ○Zanfel, calamine, oatmeal baths ○Severe cases: systemic or topical steroids

aloneonalimb.blogspot.com

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aloneonalimb.blogspot.com http://en.wikipedia.org/wiki/Cashew

Apocynaceae ● Adenium (desert rose), Asclepias (milkweed), Nerium (oleander), Thevea (yellow oleander), Catharanthus roseus (rosy periwinkle) ● Flowers oen fused as a tube and showy; all parts of plant (flowers not always) exude white latex when torn or broken ● Cardiac glycosides ○ Digitalis (digoxin and digitoxin) ○ Liliaceae

Apocynaceae ●Asclepias represented in Texas; other genera listed above grown as ornamentals ●Signs and symptoms: anorexia, headache, photophobia, blurred vision, dysrhythmias, dizziness, palpitaons, shortness of breath, MI/ stroke, N/V, abdominal pain, seizures, delirium ●Treatment: ○Atropine

http://commons.wikimedia.org/wiki/File:Starr_070906-8657_Catharanthus_roseus.jpg ○Fab fragment angen binding

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http://www.taiwanplant.com/finishedplants_desert_rose.htm

Fabaceae Fabaceae ● Abrus precatorius (rosary pea), Acacia, Albizia, Astralagus ● Many of these genera found growing in Texas (locoweeds), Erythrina (coral bean), Lupinus (bluebonnet, either as endemics, ornamentals, or in an lupine), Physosgma (Calabar or ordeal bean), Sophora agricultural seng secundiflora (mescal bean, Texas mountain laurel), ●Signs and symptoms: fever, blurred vision, Wisteria diaphoresis, excessive salivaon, bradycardia, ● Leaves oen pinnately compound, flowers showy, fruits shortness of breath, bronchospasm, N/V, dizziness, are always legumes muscle spasm, abnormal gait, seizures ● Cyanogenic glycosides, cyssine, physosgmine, ●Treatment: quinolizidines, curare-like alkaloids, locaine, erythrane,

coralline ○Supporve

http://www.erowid.org/

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Euphorbiaceae Euphorbiaceae ● Croton, Euphorbia, Manihot esculenta (cassava, yuca), ● Signs and symptoms: Ricinis communis (castor bean) ○Ricin: resp. distress, hypotension, bloody urine and stool (36-72hrs unl death) ● Cac-like, large trees to minute prostrate herbs, flowers ○HCN: headache, blindness, deafness, dizziness, with nectar glands, white latex with cellular damage shortness of breath, N/V, diarrhea, inebriaon, ● Ricin, amygdalin and linamian=HCN, cytotoxic diterpenes seizures, loss of sensorium ● Type I and IV hypersensivity: latex angens (prohevein), ● Treatment: mostly from Rubber tree (Hevea brasiliensis) ○HCN-hydroxocobalamin to form B12 (cyanobalamin), nitrites and thiosulfates ○Ricin-Supporve

http://www.unitedfarmersassociation.com http://en.wikipedia.org/wiki/Castor_oil_plant

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http://www.myessentia.com/blog/why-natural-hevea-rubber-is- awesome/

Apiaceae Apiaceae ● Aethusa spp. (fools parsley), Cicuta maculata (water ● Poison hemlock nave to Texas, the rest are found hemlock), Conium maculatum (poison hemlock) elsewhere in N. America ● Small to large herbs, the inflorescence of flowers ● Phytophotodermas: fucocoumarins arranged in an umbel ● Signs and symptoms: tachycardia to bradycardia, ● Poisonous alkaloids, cicutoxin, coniine, resins; hypotension, N/V, abd pain, severe seizures, especially poisonous are leaves, unripe fruits and shock, coma, death roots ● Treatment: ○ Supporve

http://www.skinps.com/blog/category/skin-conditions/

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Others Others ● Rosaceae: ● Order Ranunculales: ○Prunus spp. (apricots, plums, bier almonds, ○Includes Ranunculaceae and Papaveraceae peach, and black cherry) and Pyrus spp. (pear) ■Aconum (monkshood), Anemone, ○ Contain amygdalin which hydrolyzes into HCN Aquilegia (columbine), Argemone (prickly ■ occurs in seeds, leaves, and bark, but most poppy), Clemas, Delphinium (larkspur), highly concentrated in seeds Papaver (poppies) ○ All of which mostly have toxic alkaloids

http://images.google.com/imgres?imgurl

http://www.biology-blog.com/imag/columbine http://www.burma-all.com/new%20burma

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Mycotoxins

http://ipcblog.org/2011/09/06/mother-natures-most-toxic/

Case Study Case Study ● 38 y/o female presenng with N/V, severe abd. ● Repeatedly (-): CBC, CMP, amylase, lipase, abd. pain, conspaon alternang with diarrhea; 6 US, stool exam with O&P, tTG, Hepas A,B,C, similar episodes in last year all requiring ED visits, hCG, UA, FIT, ECG only tramadol effecve in pain management ● Only significant findings: (+) ESR, colonoscopy: ● No PMH areas of inflammaon without any ulceraon ● Lives on farm and all protein needs met from ● Subsequent invesgaon revealed highly farm animals elevated AFB1 levels in farm animals, strong evidence supporng aflatoxicosis as eology

Environmental/Food-related ● Aflatoxins ● Ochratoxin ● Citrinin ● Patulin ● Fusarium

http://en.wikipedia.org/wiki/File:Aspergillus_on_tomato.jpg

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Case Study Cyclopepdes ● 55 y/o woman and her daughters collected wild mushrooms for soup and ate it with son and ● Occur in the genus Amanita granddaughter ● Amatoxin: alpha-amanin ● Within 12 hours all experienced N/V, abd cramping, ● Inhibits protein synthesis in hepatocytes and diarrhea causes nephrotoxicity ● All were treated for diarrhea with fluid resuscitaon ● Can not be deacvated by heat

● The children all died of fulminant hepac and renal ● Cause ~90% of all fungi poisoning deaths and failure within the next few days ● The mother survived aer 4 weeks of intensive ~30% of individuals with cyclopepde poisoning supporve care die

Case Study ● 49 y/o Korean female presented to ED with GI irritability and voming, D/C aer symptomac treatment, returned with interpreter next day to inform and give example of wild mushrooms eaten, pt with intense abd. pain, voming and chills ● PE: vitals WNL, abd. tenderness, rare bowel sounds http://en.wikipedia.org/wiki/Amanita_phalloides

Case Study -Hydrazine ● Labs: LDH-243, Total bili-63 ● Occur in Gyromitra spp. (false morels) ● Symptomac treatment and IV pyridoxine ● Monomethylhydrazine administered ● Can be inacvated with heat but volalizaon ● For 4 more days: pt. with lethargy, abd. pain, during cooking process can cause poisoning anorexia, N/V; Labs on day 5: LDH-693, AST-431, ● Similar to Isoniazid toxicity, as it causes B6 ALT-472 (pyridoxine) depleon which stops GABA synthesis ● Eventual full recovery ● Fatalies occur ~10% of the me

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Coprine ● Occur in Coprinus spp. (inky caps) ● Disulfirum-like reacon-hyperacetaldehydemia with ETOH ● Can not be inacvated with heat

http://en.wikipedia.org/wiki/File:Frühjahrslorchel.JPG

Orelline+Orellanine ● Occur in Cornarius spp. ● Disrupt the cytoskeleton and protein synthesis in renal tubular cells ● Can not be inacvated with heat

http://www.mushroomexpert.com/images/kuo/coprinus_micaceus_06big.jpg

Resources Psychedelics: Alper, K., Lotsof, H., Frenken, G., Luciano, D. & Basaans. (1999). Treatment of acute opioid withdrawal with Ibogaine. The American Journal on Addicons, 8(3), 234-242. Grob, C., Danforth, A., Chopra, G., Hagerty, M., McKay, C., Halberstadt, A., & Greer, G. (2011). Pilot study of Psilocybin treatment for anxiety in paents with advanced-stage cancer. Arch. Gen. Psychiatry, 68(1), 71-78. Krebs, Teri & Johansen, P. (2012). Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. Journal of Psychopharmacology, 26(7), 994-1002. Nu, D. (2007). The development of a raonal scale to assess the harm of drugs and potenal misuse. The Lancet, 369, 1047-1053. Preva-Smith, K. & Prisinzano, T. (2010). New therapeuc potenal for psychoacve natural products. Natural Product Reports, 27, 23-31. Prisinzano, T. (2009). Natural products as tools for neuroscience: Discovery and development of novel agents to treat drug abuse. Journal of Natural Products, 72, 581-587. Ross, S. (2011) Serotonergic hallucinogens and emerging targets for addicon pharmacotherapies. Psychiatr. Clin. N. Am., 35, 357-374. Schultes, R., Hoffman, A. & Ratsch, C. (1992). Plants of the Gods. Their Sacred, Healing, and Hallucinogenic Powers. Vermont: Healing Arts. Sessa, B. (2012). The Psychedelic Renaissance. London: Musmell Hill. Sewell, R., Halpern, J. & Pope, H. (2006). Response of cluster headache to psilocybin and LSD. Neurology, 27(66), http://www.mushroomexpert.com/cortinarius_iodes.html 1920-1922.

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Resources Resources Poisonous herbals and management: Legal Highs: Das, R., Parajuli, S., & Jayakumar, J. (2007). Last supper with mushroom soup: a case report of amatoxin poisoning. Evren, C. & Bozkurt, M. (2013). Synthec Cannabinoids: Crisis of McGill Journal of Medicine, 10(2), 93-95. Gresham, C., and Wilbeck, J. (2011). Toxicology in the emergency department: a review for the advanced pracce the decade. The Journal of Psychiatry and Neurological Sciences, nurse. Advanced Emergency Nursing Journal, 34(1), 43-54. Leathem, A., Dorran, T. (2007). Poisoning due to raw Gyromitra esculenta (false morels) west of the Rockies. CJEM, 26, 1-11. 9(2), 127-130. Jerry, J., Collins, G., & Streem, D. (2012). Synthec legal Lippinco’s Manual of Toxicology. (2012). Lippinco, Williams & Wilcons. intoxicang drugs: The emerging ‘incense’ and ‘bath salt’ Lewis, W., & Elvin-Lewis, M. (2003). Medical Botany: Plants Affecng Human Health. New York: John Wiley. phenomenon. Cleveland Clinic Journal of Medicine, 79(4), 258-264. Nelson, L., Lewin, N., Howland, M. Hoffman, R., Goldfrank, L. & Flomenbaun, N. (2010). Goldfrank’s Toxicologic Emergencies, 9th Ed. New York: McGraw-Hill Zawilska, J.B. (2011). “Legal highs”-New players in the old drama. Perduri, R., Gobbs, S. (2009). Unexpected aflatoxin exposure in a women in Northern Italy: a case report. Cases Current drug abuse reviews, 4, 122-130 Journal, 2, 7736.

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