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Dose-Response Study of N,N-Dimethyltryptamine in Humans: I. Neuroendocrine, Autonomic, and Cardiovascular Effects

Dose-Response Study of N,N-Dimethyltryptamine in Humans: I. Neuroendocrine, Autonomic, and... Abstract Background: To begin applying basic neuropharmacological hypotheses of hallucinogenic drug actions to humans, we generated dose-response data for intravenously administered dimethyltryptamine fumarate's (DMT) neuroendocrine, cardiovascular, autonomic, and subjective effects in a group of experienced hallucinogen users. Methods: Dimethyltryptamine, an endogenous mammalian hallucinogen and drug of abuse, was administered intravenously at 0.05,0.1,0.2, and 0.4 mg/kg to 11 experienced hallucinogen users, in a double-blind, saline placebo—controlled, randomized design. Treatments were separated by at least 1 week. Results: Peak DMT blood levels and subjective effects were seen within 2 minutes after drug administration, and were negligible at 30 minutes. Dimethyltryptamine dose dependently elevated blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of β-endorphin, corticotropin, cortisol, and prolactin. Growth hormone blood levels rose equally in response to all doses of DMT, and melatonin levels were unaffected. Threshold doses for significant effects relative to placebo were also hallucinogenic (0.2 mg/kg and higher). Subjects with five or more exposures to 3,4-methylenedioxymethamphetamine demonstrated less robust pupil diameter effects than those with two or fewer exposures. Conclusions: Dimethyltryptamine can be administered safely to experienced hallucinogen users and dose-response data generated for several measures hypothesized under serotonergic modulatory control. Additional studies characterizing the specific mechanisms mediating DMT's biological effects may prove useful in psychopharmacological investigations of drug-induced and endogenous alterations in brain function. References 1. Freedman DX. On the use and abuse of LSD . Arch Gen Psychiatry . 1968;18:330-347.Crossref 2. Nichols D, Oberlender R, McKenna D. Stereochemical aspects of hallucinogenesis . In: Watson R, ed. Biochemistry and Physiology of Substance Abuse, III . Boca Raton, Fla: CRC Press Inc; 1991:1-39. 3. Cohen S. Lysergic acid diethylamide: side effects and complications . J Nerv Ment Dis . 1960;130:30-40.Crossref 4. Strassman R. Adverse reactions to psychedelic drugs: a review of the literature . J Nerv Ment Dis . 1984;172:577-595.Crossref 5. Pope H Jr, lonescu-Pioggia M, Aizley H, Varma D. Drug use and life style among college undergraduates in 1989: a comparison with 1969 and 1978 . Am J Psychiatry . 1990;147:998-1001. 6. Peroutka S, Snyder S. Multiple serotonin receptors: differential binding of [3H]5-hydroxytryptamine, [3H]lysergic acid diethylamide and [3H]spiroperidol . Mol Pharmacol . 1979;16:687-690. 7. Glennon R, Titeler M, McKenney J. Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents . Life Sci . 1985;35:2505-2511.Crossref 8. Spencer D Jr, Glaser T, Traber J. Serotonin receptor subtype mediation of the interoceptive discriminative stimuli induced by 5-methoxy-N, Ndimethyltryptamine . Psychopharmacology . 1987;93:158-166.Crossref 9. Yagaloff K, Hartig P. 125I-Iysergic acid diethylamide binds to a novel serotonergic site on rat choroid plexus epithelial cells . J Neurosci . 1985;5:3178-3183. 10. Buckholtz N, Zhou D, Freedman DX, Potter W. Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain . Neuropsychopharmacology . 1990;3:137-148. 11. Ahn H, Makman M. Interaction of LSD and other hallucinogens with dopaminesensitive adenylate cyclase in primate brain: regional differences . Brain Res . 1979;162:77-88.Crossref 12. Horita A, Hamilton A. Lysergic acid diethylamide: dissociation of its behavioral and hyperthermic effects by DL-alpha-methyl-p-tyrosine . Science . 1969;164:78-79.Crossref 13. Van de Kar L. Neuroendocrine pharmacology of serotonergic (5-HT) neurons . Ann Rev Pharmacol Toxicol . 1991;31:289-320.Crossref 14. Meltzer H, Wiita B, Tricou B, Simonovic M, Fang V. Effects of serotonin precursors and serotonin agonists on plasma hormone levels . In: Ho B, Schoolar J, Usdin E, eds. Serotonin in Biological Psychiatry . New York, NY: Raven Press; 1980:117-139. 15. Halaris A, Freedman DX, Fang V. Plasma corticoids and brain tryptophan after acute and tolerance dosage of LSD . Life Sci . 1976;17:1467-1472.Crossref 16. Sai-Halasz A, Brunecker G, Szara S. Dimethyltryptamine: ein neues Psychoticum . Psychiatr Neurol . 1958;135:285-301.Crossref 17. Horita A, Dille J. The pyretogenic effect of lysergic acid diethylamide . Science . 1954;120:1110-1111.Crossref 18. Greiner T, Burch N, Edelberg R. Psychopathology and psychophysiology of minimal LSD-25 dosage: a preliminary dosage-response spectrum . Arch Neurol Psychiatry . 1958;79:208-210.Crossref 19. Isbell H. Comparison of the reactions induced by psilocybin and LSD-25 in man . Psychopharmacologia . 1959;1:29-38.Crossref 20. Fish M, Johnson N, Horning E. Piptadenia alkaloids: indole bases of P. peregrina (L.) Benth. and related species . J Am Chem Soc . 1955;77:5892-5895.Crossref 21. Barker S, Monti J, Christian S. N,N-dimethyltryptamine: an endogenous hallucinogen . Int Rev Neurobiol . 1981;22:83-110. 22. Gillin J, Kaplan J, Stillman R, Wyatt R. The psychedelic model of schizophrenia: the case of N,N-dimethyltryptamine . Am J Psychiatry . 1976;133:203-208. 23. Strassman R. Human hallucinogenic drug research in the United States: a presentday case history and review of the process . J Psychoactive Drug . 1991;23:29-38.Crossref 24. Spitzer R, Williams J, Gibbon M. Structured Clinical Interview of DSM-III-R: Outpatient Version . New York, NY: Biometric Research Dept, New York State Psychiatric Institute; 1987. 25. McKenna D, Peroutka S. Neurochemistry and neurotoxicity of 3,4methylenedioxymethamphetamine (MDMA, 'Ecstasy') . J Neurochem . 1990;54:14-22.Crossref 26. Price L, Ricaurte G, Krystal J, Heninger G. Neuroendocrine and mood responses to intravenous L-tryptophan in 3,4-methylenedioxymethamphetamine (MDMA) users . Arch Gen Psychiatry . 1989;46:20-22.Crossref 27. Stafford P. Psychedelics Encyclopedia . Rev ed. Boston, Mass: Houghton Mifflin Co; 1982:308-331. 28. Walker R, Mandel L, Kleinman J, Gillin J, Wyatt R, VandenHeuvel W. Improved selective ion monitoring mass-spectrometric assay for the determination of N,N-dimethyltryptamine in human blood utilizing capillary column gas chromatography . J Chromatogr . 1979;162:539-546.Crossref 29. Webley G, Mehl H, Willey K. Validation of a sensitive direct assay for melatonin for investigation of circadian rhythms in different species . J Endocrinol . 1985;106:387-394.Crossref 30. Angrist B, Gershon S, Sathananthan, Walker R, Lopez-Ramos B, Mandel L, VandenHeuvel W. Dimethyltryptamine levels in blood of schizophrenic patients and control subjects . Psychopharmacology . 1976;47:29-32.Crossref 31. Kaplan J, Mandel L, Stillman R, Walker R, VandenHeuvel W, Gillin J, Wyatt R. Blood and urine levels of N,N-dimethyltryptamine following administration of psychoactive doses to human subjects . Psychopharmacologia . 1974;38:239-245.Crossref 32. Strassman RJ, Qualls CR, Uhlenhuth EH, Kellner R. Dose-response study of N,N-dimethyltryptamine in humans, II: subjective effects and preliminary results of a new rating scale . Arch Gen Psychiatry . 1994;51:98-108.Crossref 33. Aghajanian G, Foote W, Sheard M. Action of psychotogenic drugs on single midbrain raphe neurons . J Pharmacol Exp Ther . 1970;171:178-187. 34. Deliganis A, Pierce P, Peroutka S. Differential interactions of dimrthyltryptamine (DMT) with 5-HT1A and 5-HT2 receptors . Biochem Pharmacol . 1991;41:1739-1744.Crossref 35. Jenner P, Marsden C, Thanki C. Behavioral changes induced by N,Ndimethyltryptamine in rodents . Br J Pharmacol . 1980;69:69-80.Crossref 36. Pierce P, Peroutka S. Hallucinogenic drug interactions with neurotransmitter receptor binding sites in human cortex . Psychopharmacology . 1989;97:118-122.Crossref 37. Sanders-Bush E, Breeding M. Choroid plexus epithelial cells in primary culture: a model of 5HT1C receptor activation by hallucinogenic drugs . Psychopharmacology . 1991;105:340-346.Crossref 38. Charig E, Anderson I, Robinson J, Nutt D, Cowen P. L-tryptophan and prolactin release: evidence for interaction between 5-HT1, and 5-HT2 receptors . Hum Psychopharmacol . 1986;1:93-97.Crossref 39. Vale W, Spiess J, Rivier C, Rivier J. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and β-endorphin . Science . 1981;213:1394-1396.Crossref 40. Lewis D, Sherman B. Serotonergic regulation of adrenocorticotropin secretion in man . J Clin Endocrinol Metab . 1984;58:458-462.Crossref 41. Petraglia F, Facchinetti F, Martignoni E, Nappi G, Volpe A, Genazzani A. Serotonergic agonists increase plasma levels of β-endorphin and β-lipotropin in humans . J Clin Endocrinol Metab . 1984;59:1138-1142.Crossref 42. Anderson I, Cowen P, Grahame-Smith D. The effects of gepirone on neuroendocrine function and temperature in humans . Psychopharmacology . 1990;100:498-503.Crossref 43. Calogero A, Bernardini R, Margioris A, Bagdy G, Gallucci W, Munson P, Tamarkin L, Tomai T, Brady L, Gold P, Chrousos G. Effects of serotonergic agonists and antagonists on corticotropin-releasing hormone secretion by explanted rat hypothalami . Peptides . 1989;10:189-200.Crossref 44. Kato Y, Nakai Y, lmura H, Chichara K, Ohgo S. Effect of 5-hydroxytryptophan (5-HTP) on plasma prolactin levels in man . J Clin Endocrinol Metab . 1974;38:695-697.Crossref 45. Asnis G, Eisenberg J, van Praag H, Lemus C, Friedman J, Miller A. The neuroendocrine response to fenfluramine in depressives and normal controls . Biol Psychiatry . 1988;24:117-120.Crossref 46. Demisch L, Neubauer M. Stimulation of human prolactin secretion by mescaline . Psychopharmacology . 1979;64:361-363.Crossref 47. Aloi J, Insel T, Mueller E, Murphy D. Neuroendocrine and behavioral effects of mCPP in rhesus monkeys . Life Sci . 1984;34:1325-1331.Crossref 48. Smith C, Ware C, Cowen P. Pindolol decreases prolactin and growth hormone responses to intravenous L-tryptophan . Psychopharmacology . 1991;103:140-142.Crossref 49. Van de Kar L, Lorens S, Urban J, Bethea C. Effect of selective serotonin (5-HT) agonists and 5-HT2 antagonists on prolactin secretion . Neuropharmacology . 1989;28:299-305.Crossref 50. Calogero A, Bagdy G, Szemeredi K, Tartaglia M, Gold P, Chrousos G. Mechanisms of serotonin receptor agonist-induced activation of the hypothalamicpituitary-adrenal axis in the rat . Endocrinology . 1990;126:1888-1894.Crossref 51. Snyder SH, Faillace L, Hollister L. 2,5-Dimethoxy-4-methyl-amphetamine (STP): a new hallucinogenic drug . Science . 1967;158:669-670.Crossref 52. Won S, Lin M. 5-Hydroxytryptamine receptors in the hypothalamus mediate thermoregulatory responses in rabbits . Naunyn Schmiedebergs Arch Pharmacol . 1988;338:256-261.Crossref 53. Cohen M, Fuller T, Wiley S. Evidence for 5-HT2 receptors mediating contraction in vascular smooth muscle . J Pharmacol Exp Ther . 1981;21:421-425. 54. Denber H, Merlis S. Studies on mescaline, VI:therapeutic aspects of the mescalinechlorpromazine combination . J Nerv Ment Dis . 1955;122:463-469.Crossref 55. Turner W, Merlis S. Effect of some indolealkylamines on man . Arch Neurol Psychiatry . 1959;81:121-129.Crossref 56. Dabire H, Chaouche-Teyara K, Cherqui C, Fournier B, Laubie M, Schmitt H. Characterization of DOI, a putative 5-HT2 receptor agonist in the rat . Eur J Pharmacol . 1989;168:369-374.Crossref 57. Rittenhouse P, Bakkum E, Van de Kar L. Evidence that the serotonin agonist, DOI, increases renin secretion and blood pressure through both central and peripheral 5-HT2 receptors . J Pharmacol Exp Ther . 1991;259:58-65. 58. Dreteler G, Wouters W, Saxena P. Systemic and regional hemodynamic effects of the putative 5-HT1A receptor agonist flesinoxan in the cat . J Cardiovasc Pharmacol . 1989;14:770-776.Crossref 59. Klee G, Bertino J, Weintraub W, Callaway E III. The influence of varying dosage on the effects of lysergic acid diethylamide (LSD-25) in humans . J Nerv Ment Dis . 1961;132:404-409.Crossref 60. Millson D, Haworth S, Rushton A, Wilkinson D, Hobson S, Harry J. The effects of a 5-HT2 antagonist (ICI 169, 369) on changes in waking EEG, pupillary responses and state of arousal in human volunteers . Br J Clin Pharmacol . 1991;32:447-454.Crossref 61. Rosenberg D, Isbell H, Miner E. Comparison of placebo, N-dimethyltryptamine, and 6-hydroxy-N-dimethyltryptamine in man . Psychopharmacology . 1963;4:39-42.Crossref 62. Yanai K, Ido T, Ishiwata K, Hatazawa J, Takahashi T, lwata R, Matsuzawa T. In vivo kinetics and displacement study of a carbon-11-labeled hallucinogen, N,N[11C]dimethyltryptamine . Eur J Nucl Med . 1986;12:141-146.Crossref 63. Seibyl J, Krystal J, Price L, Woods W, Heninger G, Charney D. 5-HT function in the biochemical and behavioral responses to mCPP in healthy subjects and schizophrenics . Soc Neurosci Abstr . 1989;15:1236. 64. Lowy M, Meltzer H. Stimulation of serum cortisol and prolactin secretion in humans by MK-212, a centrally active serotonin agonist . Biol Psychiatry . 1988;23:818-828.Crossref 65. Murphy D, Lesch K, Aulakh C, Pigott T. Serotonin-selective arylpiperazines with neuroendocrine, behavioral, temperature and cardiovascular effects in humans . Pharmacol Rev . 1991;43:527-552. 66. Charney D, Goodman W, Price L, Woods W, Rasmussen S, Heninger G. Serotonin function in obsessive-compulsive disorder . Arch Gen Psychiatry . 1988;45:177-185.Crossref 67. Murphy D, Mueller E, Hill J, Tolliver T, Jacobsen F. Comparative anxiogenic, neuroendocrine and other physiologic effects of m-chlorophenylpiperazine given intravenously and orally to healthy volunteers . Psychopharmacology . 1989;98:275-283.Crossref 68. Lee H, Bastani B, Friedman L, Ramirez L, Meltzer H. Effect of the serotonin agonist, MK-212, on body temperature in schizophrenia . Biol Psychiatry . 1992;31:460-470.Crossref 69. Appel JB, Freedman DX. Chemically-induced alterations in the behavioral effects of LSD-25 . Biochem Pharmacol . 1964;13:861-869.Crossref 70. Nisbet AF, Marsden CA. Increased behavioural response to 5-methoxy-N,Ndimethyltryptamine but not to RU-24969 after intraventricular 5,7-dihydroxytryptamine administration . Eur J Pharmacol . 1984;104:177-180.Crossref 71. Ebadi M, Govitrapong P. Neural pathways and neurotransmitters affecting melatonin synthesis . J Neural Transm . 1986;21( (suppl) ):125-158. 72. Hartley R, Smith J. The activation of pineal hydroxy-indole-O-methyltransferase by psychotomimetic drugs . J Pharm Pharmacol . 1973;25:751-752.Crossref 73. Strassman R, Appenzeller O, Lewy A, Qualls C, Peake G. Increase in plasma melatonin, β-endorphin, and cortisol after a 28.5-mile mountain race: relationship to performance and lack of effect of naltrexone . J Clin Endocrinol Metab . 1989;69:540-545.Crossref 74. Price L, Charney D, Delgado P, Heninger G. Serotonin function and depression: neuroendocrine and mood responses to intravenous L-tryptophan in depressed patients and healthy comparison subjects . Am J Psychiatry . 1991;148:1518-1525. 75. Lee M, Meltzer H. Neuroendocrine responses to serotonergic agents in alcoholics . Biol Psychiatry . 1991;30:1017-1030.Crossref 76. Fishbein D, Lozovsky D, Jaffe J. Impulsivity, aggression, and neuroendocrine responses to serotonergic stimulation in substance abusers . Biol Psychiatry . 1989;25:1049-1066.Crossref 77. Freedman DX. Hallucinogenic drug research: if so, so what? Pharmacol Biochem Behav . 1986;24:407-415.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

Dose-Response Study of N,N-Dimethyltryptamine in Humans: I. Neuroendocrine, Autonomic, and Cardiovascular Effects

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American Medical Association
Copyright
Copyright © 1994 American Medical Association. All Rights Reserved.
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0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1994.03950020009001
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Abstract

Abstract Background: To begin applying basic neuropharmacological hypotheses of hallucinogenic drug actions to humans, we generated dose-response data for intravenously administered dimethyltryptamine fumarate's (DMT) neuroendocrine, cardiovascular, autonomic, and subjective effects in a group of experienced hallucinogen users. Methods: Dimethyltryptamine, an endogenous mammalian hallucinogen and drug of abuse, was administered intravenously at 0.05,0.1,0.2, and 0.4 mg/kg to 11 experienced hallucinogen users, in a double-blind, saline placebo—controlled, randomized design. Treatments were separated by at least 1 week. Results: Peak DMT blood levels and subjective effects were seen within 2 minutes after drug administration, and were negligible at 30 minutes. Dimethyltryptamine dose dependently elevated blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of β-endorphin, corticotropin, cortisol, and prolactin. Growth hormone blood levels rose equally in response to all doses of DMT, and melatonin levels were unaffected. Threshold doses for significant effects relative to placebo were also hallucinogenic (0.2 mg/kg and higher). Subjects with five or more exposures to 3,4-methylenedioxymethamphetamine demonstrated less robust pupil diameter effects than those with two or fewer exposures. Conclusions: Dimethyltryptamine can be administered safely to experienced hallucinogen users and dose-response data generated for several measures hypothesized under serotonergic modulatory control. Additional studies characterizing the specific mechanisms mediating DMT's biological effects may prove useful in psychopharmacological investigations of drug-induced and endogenous alterations in brain function. References 1. Freedman DX. On the use and abuse of LSD . Arch Gen Psychiatry . 1968;18:330-347.Crossref 2. Nichols D, Oberlender R, McKenna D. Stereochemical aspects of hallucinogenesis . In: Watson R, ed. Biochemistry and Physiology of Substance Abuse, III . Boca Raton, Fla: CRC Press Inc; 1991:1-39. 3. Cohen S. Lysergic acid diethylamide: side effects and complications . J Nerv Ment Dis . 1960;130:30-40.Crossref 4. Strassman R. Adverse reactions to psychedelic drugs: a review of the literature . J Nerv Ment Dis . 1984;172:577-595.Crossref 5. Pope H Jr, lonescu-Pioggia M, Aizley H, Varma D. Drug use and life style among college undergraduates in 1989: a comparison with 1969 and 1978 . Am J Psychiatry . 1990;147:998-1001. 6. Peroutka S, Snyder S. Multiple serotonin receptors: differential binding of [3H]5-hydroxytryptamine, [3H]lysergic acid diethylamide and [3H]spiroperidol . Mol Pharmacol . 1979;16:687-690. 7. Glennon R, Titeler M, McKenney J. Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents . Life Sci . 1985;35:2505-2511.Crossref 8. Spencer D Jr, Glaser T, Traber J. Serotonin receptor subtype mediation of the interoceptive discriminative stimuli induced by 5-methoxy-N, Ndimethyltryptamine . Psychopharmacology . 1987;93:158-166.Crossref 9. Yagaloff K, Hartig P. 125I-Iysergic acid diethylamide binds to a novel serotonergic site on rat choroid plexus epithelial cells . J Neurosci . 1985;5:3178-3183. 10. Buckholtz N, Zhou D, Freedman DX, Potter W. Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain . Neuropsychopharmacology . 1990;3:137-148. 11. Ahn H, Makman M. Interaction of LSD and other hallucinogens with dopaminesensitive adenylate cyclase in primate brain: regional differences . Brain Res . 1979;162:77-88.Crossref 12. Horita A, Hamilton A. Lysergic acid diethylamide: dissociation of its behavioral and hyperthermic effects by DL-alpha-methyl-p-tyrosine . Science . 1969;164:78-79.Crossref 13. Van de Kar L. Neuroendocrine pharmacology of serotonergic (5-HT) neurons . Ann Rev Pharmacol Toxicol . 1991;31:289-320.Crossref 14. Meltzer H, Wiita B, Tricou B, Simonovic M, Fang V. Effects of serotonin precursors and serotonin agonists on plasma hormone levels . In: Ho B, Schoolar J, Usdin E, eds. Serotonin in Biological Psychiatry . New York, NY: Raven Press; 1980:117-139. 15. Halaris A, Freedman DX, Fang V. Plasma corticoids and brain tryptophan after acute and tolerance dosage of LSD . Life Sci . 1976;17:1467-1472.Crossref 16. Sai-Halasz A, Brunecker G, Szara S. Dimethyltryptamine: ein neues Psychoticum . Psychiatr Neurol . 1958;135:285-301.Crossref 17. Horita A, Dille J. The pyretogenic effect of lysergic acid diethylamide . Science . 1954;120:1110-1111.Crossref 18. Greiner T, Burch N, Edelberg R. Psychopathology and psychophysiology of minimal LSD-25 dosage: a preliminary dosage-response spectrum . Arch Neurol Psychiatry . 1958;79:208-210.Crossref 19. Isbell H. Comparison of the reactions induced by psilocybin and LSD-25 in man . Psychopharmacologia . 1959;1:29-38.Crossref 20. Fish M, Johnson N, Horning E. Piptadenia alkaloids: indole bases of P. peregrina (L.) Benth. and related species . J Am Chem Soc . 1955;77:5892-5895.Crossref 21. Barker S, Monti J, Christian S. N,N-dimethyltryptamine: an endogenous hallucinogen . Int Rev Neurobiol . 1981;22:83-110. 22. Gillin J, Kaplan J, Stillman R, Wyatt R. The psychedelic model of schizophrenia: the case of N,N-dimethyltryptamine . Am J Psychiatry . 1976;133:203-208. 23. Strassman R. Human hallucinogenic drug research in the United States: a presentday case history and review of the process . J Psychoactive Drug . 1991;23:29-38.Crossref 24. Spitzer R, Williams J, Gibbon M. Structured Clinical Interview of DSM-III-R: Outpatient Version . New York, NY: Biometric Research Dept, New York State Psychiatric Institute; 1987. 25. McKenna D, Peroutka S. Neurochemistry and neurotoxicity of 3,4methylenedioxymethamphetamine (MDMA, 'Ecstasy') . J Neurochem . 1990;54:14-22.Crossref 26. Price L, Ricaurte G, Krystal J, Heninger G. Neuroendocrine and mood responses to intravenous L-tryptophan in 3,4-methylenedioxymethamphetamine (MDMA) users . Arch Gen Psychiatry . 1989;46:20-22.Crossref 27. Stafford P. Psychedelics Encyclopedia . Rev ed. Boston, Mass: Houghton Mifflin Co; 1982:308-331. 28. Walker R, Mandel L, Kleinman J, Gillin J, Wyatt R, VandenHeuvel W. Improved selective ion monitoring mass-spectrometric assay for the determination of N,N-dimethyltryptamine in human blood utilizing capillary column gas chromatography . J Chromatogr . 1979;162:539-546.Crossref 29. Webley G, Mehl H, Willey K. Validation of a sensitive direct assay for melatonin for investigation of circadian rhythms in different species . J Endocrinol . 1985;106:387-394.Crossref 30. Angrist B, Gershon S, Sathananthan, Walker R, Lopez-Ramos B, Mandel L, VandenHeuvel W. Dimethyltryptamine levels in blood of schizophrenic patients and control subjects . Psychopharmacology . 1976;47:29-32.Crossref 31. Kaplan J, Mandel L, Stillman R, Walker R, VandenHeuvel W, Gillin J, Wyatt R. Blood and urine levels of N,N-dimethyltryptamine following administration of psychoactive doses to human subjects . Psychopharmacologia . 1974;38:239-245.Crossref 32. Strassman RJ, Qualls CR, Uhlenhuth EH, Kellner R. Dose-response study of N,N-dimethyltryptamine in humans, II: subjective effects and preliminary results of a new rating scale . Arch Gen Psychiatry . 1994;51:98-108.Crossref 33. Aghajanian G, Foote W, Sheard M. Action of psychotogenic drugs on single midbrain raphe neurons . J Pharmacol Exp Ther . 1970;171:178-187. 34. Deliganis A, Pierce P, Peroutka S. Differential interactions of dimrthyltryptamine (DMT) with 5-HT1A and 5-HT2 receptors . Biochem Pharmacol . 1991;41:1739-1744.Crossref 35. Jenner P, Marsden C, Thanki C. Behavioral changes induced by N,Ndimethyltryptamine in rodents . Br J Pharmacol . 1980;69:69-80.Crossref 36. Pierce P, Peroutka S. Hallucinogenic drug interactions with neurotransmitter receptor binding sites in human cortex . Psychopharmacology . 1989;97:118-122.Crossref 37. Sanders-Bush E, Breeding M. Choroid plexus epithelial cells in primary culture: a model of 5HT1C receptor activation by hallucinogenic drugs . Psychopharmacology . 1991;105:340-346.Crossref 38. Charig E, Anderson I, Robinson J, Nutt D, Cowen P. L-tryptophan and prolactin release: evidence for interaction between 5-HT1, and 5-HT2 receptors . Hum Psychopharmacol . 1986;1:93-97.Crossref 39. Vale W, Spiess J, Rivier C, Rivier J. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and β-endorphin . Science . 1981;213:1394-1396.Crossref 40. Lewis D, Sherman B. Serotonergic regulation of adrenocorticotropin secretion in man . J Clin Endocrinol Metab . 1984;58:458-462.Crossref 41. Petraglia F, Facchinetti F, Martignoni E, Nappi G, Volpe A, Genazzani A. Serotonergic agonists increase plasma levels of β-endorphin and β-lipotropin in humans . J Clin Endocrinol Metab . 1984;59:1138-1142.Crossref 42. Anderson I, Cowen P, Grahame-Smith D. The effects of gepirone on neuroendocrine function and temperature in humans . Psychopharmacology . 1990;100:498-503.Crossref 43. Calogero A, Bernardini R, Margioris A, Bagdy G, Gallucci W, Munson P, Tamarkin L, Tomai T, Brady L, Gold P, Chrousos G. Effects of serotonergic agonists and antagonists on corticotropin-releasing hormone secretion by explanted rat hypothalami . Peptides . 1989;10:189-200.Crossref 44. Kato Y, Nakai Y, lmura H, Chichara K, Ohgo S. Effect of 5-hydroxytryptophan (5-HTP) on plasma prolactin levels in man . J Clin Endocrinol Metab . 1974;38:695-697.Crossref 45. Asnis G, Eisenberg J, van Praag H, Lemus C, Friedman J, Miller A. The neuroendocrine response to fenfluramine in depressives and normal controls . Biol Psychiatry . 1988;24:117-120.Crossref 46. Demisch L, Neubauer M. Stimulation of human prolactin secretion by mescaline . Psychopharmacology . 1979;64:361-363.Crossref 47. Aloi J, Insel T, Mueller E, Murphy D. Neuroendocrine and behavioral effects of mCPP in rhesus monkeys . Life Sci . 1984;34:1325-1331.Crossref 48. Smith C, Ware C, Cowen P. Pindolol decreases prolactin and growth hormone responses to intravenous L-tryptophan . Psychopharmacology . 1991;103:140-142.Crossref 49. Van de Kar L, Lorens S, Urban J, Bethea C. Effect of selective serotonin (5-HT) agonists and 5-HT2 antagonists on prolactin secretion . Neuropharmacology . 1989;28:299-305.Crossref 50. Calogero A, Bagdy G, Szemeredi K, Tartaglia M, Gold P, Chrousos G. Mechanisms of serotonin receptor agonist-induced activation of the hypothalamicpituitary-adrenal axis in the rat . Endocrinology . 1990;126:1888-1894.Crossref 51. Snyder SH, Faillace L, Hollister L. 2,5-Dimethoxy-4-methyl-amphetamine (STP): a new hallucinogenic drug . Science . 1967;158:669-670.Crossref 52. Won S, Lin M. 5-Hydroxytryptamine receptors in the hypothalamus mediate thermoregulatory responses in rabbits . Naunyn Schmiedebergs Arch Pharmacol . 1988;338:256-261.Crossref 53. Cohen M, Fuller T, Wiley S. Evidence for 5-HT2 receptors mediating contraction in vascular smooth muscle . J Pharmacol Exp Ther . 1981;21:421-425. 54. Denber H, Merlis S. Studies on mescaline, VI:therapeutic aspects of the mescalinechlorpromazine combination . J Nerv Ment Dis . 1955;122:463-469.Crossref 55. Turner W, Merlis S. Effect of some indolealkylamines on man . Arch Neurol Psychiatry . 1959;81:121-129.Crossref 56. Dabire H, Chaouche-Teyara K, Cherqui C, Fournier B, Laubie M, Schmitt H. Characterization of DOI, a putative 5-HT2 receptor agonist in the rat . Eur J Pharmacol . 1989;168:369-374.Crossref 57. Rittenhouse P, Bakkum E, Van de Kar L. Evidence that the serotonin agonist, DOI, increases renin secretion and blood pressure through both central and peripheral 5-HT2 receptors . J Pharmacol Exp Ther . 1991;259:58-65. 58. Dreteler G, Wouters W, Saxena P. Systemic and regional hemodynamic effects of the putative 5-HT1A receptor agonist flesinoxan in the cat . J Cardiovasc Pharmacol . 1989;14:770-776.Crossref 59. Klee G, Bertino J, Weintraub W, Callaway E III. The influence of varying dosage on the effects of lysergic acid diethylamide (LSD-25) in humans . J Nerv Ment Dis . 1961;132:404-409.Crossref 60. Millson D, Haworth S, Rushton A, Wilkinson D, Hobson S, Harry J. The effects of a 5-HT2 antagonist (ICI 169, 369) on changes in waking EEG, pupillary responses and state of arousal in human volunteers . Br J Clin Pharmacol . 1991;32:447-454.Crossref 61. Rosenberg D, Isbell H, Miner E. Comparison of placebo, N-dimethyltryptamine, and 6-hydroxy-N-dimethyltryptamine in man . Psychopharmacology . 1963;4:39-42.Crossref 62. Yanai K, Ido T, Ishiwata K, Hatazawa J, Takahashi T, lwata R, Matsuzawa T. In vivo kinetics and displacement study of a carbon-11-labeled hallucinogen, N,N[11C]dimethyltryptamine . Eur J Nucl Med . 1986;12:141-146.Crossref 63. Seibyl J, Krystal J, Price L, Woods W, Heninger G, Charney D. 5-HT function in the biochemical and behavioral responses to mCPP in healthy subjects and schizophrenics . Soc Neurosci Abstr . 1989;15:1236. 64. Lowy M, Meltzer H. Stimulation of serum cortisol and prolactin secretion in humans by MK-212, a centrally active serotonin agonist . Biol Psychiatry . 1988;23:818-828.Crossref 65. Murphy D, Lesch K, Aulakh C, Pigott T. Serotonin-selective arylpiperazines with neuroendocrine, behavioral, temperature and cardiovascular effects in humans . Pharmacol Rev . 1991;43:527-552. 66. Charney D, Goodman W, Price L, Woods W, Rasmussen S, Heninger G. Serotonin function in obsessive-compulsive disorder . Arch Gen Psychiatry . 1988;45:177-185.Crossref 67. Murphy D, Mueller E, Hill J, Tolliver T, Jacobsen F. Comparative anxiogenic, neuroendocrine and other physiologic effects of m-chlorophenylpiperazine given intravenously and orally to healthy volunteers . Psychopharmacology . 1989;98:275-283.Crossref 68. Lee H, Bastani B, Friedman L, Ramirez L, Meltzer H. Effect of the serotonin agonist, MK-212, on body temperature in schizophrenia . Biol Psychiatry . 1992;31:460-470.Crossref 69. Appel JB, Freedman DX. Chemically-induced alterations in the behavioral effects of LSD-25 . Biochem Pharmacol . 1964;13:861-869.Crossref 70. Nisbet AF, Marsden CA. Increased behavioural response to 5-methoxy-N,Ndimethyltryptamine but not to RU-24969 after intraventricular 5,7-dihydroxytryptamine administration . Eur J Pharmacol . 1984;104:177-180.Crossref 71. Ebadi M, Govitrapong P. Neural pathways and neurotransmitters affecting melatonin synthesis . J Neural Transm . 1986;21( (suppl) ):125-158. 72. Hartley R, Smith J. The activation of pineal hydroxy-indole-O-methyltransferase by psychotomimetic drugs . J Pharm Pharmacol . 1973;25:751-752.Crossref 73. Strassman R, Appenzeller O, Lewy A, Qualls C, Peake G. Increase in plasma melatonin, β-endorphin, and cortisol after a 28.5-mile mountain race: relationship to performance and lack of effect of naltrexone . J Clin Endocrinol Metab . 1989;69:540-545.Crossref 74. Price L, Charney D, Delgado P, Heninger G. Serotonin function and depression: neuroendocrine and mood responses to intravenous L-tryptophan in depressed patients and healthy comparison subjects . Am J Psychiatry . 1991;148:1518-1525. 75. Lee M, Meltzer H. Neuroendocrine responses to serotonergic agents in alcoholics . Biol Psychiatry . 1991;30:1017-1030.Crossref 76. Fishbein D, Lozovsky D, Jaffe J. Impulsivity, aggression, and neuroendocrine responses to serotonergic stimulation in substance abusers . Biol Psychiatry . 1989;25:1049-1066.Crossref 77. Freedman DX. Hallucinogenic drug research: if so, so what? Pharmacol Biochem Behav . 1986;24:407-415.Crossref

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Feb 1, 1994

References