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Studies on Lysergic Acid Diethylamide (LSD-25): III. Attempts to Attenuate the LSD-Reaction in Man by Pretreatment with Neurohumoral Blocking Agents

Studies on Lysergic Acid Diethylamide (LSD-25): III. Attempts to Attenuate the LSD-Reaction in... Abstract Interest in possible chemical transmission of impulses in the central nervous system has been increasing. The neurohumors involved include acetylcholine,1,2 norepinephrine,2-4 and serotonin.4-6 These theories of central chemical synaptic transmission have led, in turn, to hypotheses which ascribe the psychosis induced by lysergic acid diethylamide (LSD-25) and other psychotomimetic drugs to derangements in central nervous system function because of competition with one or another of the neurohumors or, on the contrary, to accentuation of the effects of the neurohumors by the psychotomimetic agents. The greatest interest has centered on possible interactions of serotonin and LSD. Woolley and Shaw5 and Gaddum6 independently evolved a hypothesis which ascribes the LSD psychosis to competition between LSD and serotonin for receptor sites on or in neurons. This hypothesis, which might be termed the serotonin-deficiency theory, is based in part on the following evidence: Serotonin is found in brain,6,7 References 1. Supplied through the courtesy of Mr. Theodore Wallace, Smith, Kline & French Laboratories, Philadelphia. 2. Supplied through the courtesy of Dr. Frederick K. Heath, Merck Sharp & Dohme, Philadelphia. 3. Feldberg, W. S.: Central and Sensory Transmission , Pharmacol. Rev. 6:85-93 ( (March) ) 1954. 4. Marrazzi, A. S.: The Effects of Certain Drugs on Cerebral Synapses , Ann. New York Acad. Sc. 66:496-507 ( (March 14) ) 1957.Crossref 5. Vogt, M.: The Concentration of Sympathin in Different Parts of the Central Nervous System Under Normal Conditions and After the Administration of Drugs , J. Physiol. 123:451-481 ( (March) ) 1954. 6. Brodie, B. B., and Shore, P. A.: A Concept for a Role of Serotonin and Norepinephrine as Chemical Mediators in the Brain , Ann. New York Acad. Sc. 66:631-642 ( (March 14) ) 1957.Crossref 7. Woolley, D. W., and Shaw, E.: A Biochemical and Pharmacological Suggestion About Certain Mental Disorders , Proc. Nat. Acad. Sc. 44:228-231 ( (April) ) 1954.Crossref 8. Gaddum, J. H.: Drugs Antagonistic to 5-Hydroxytryptamine , in Hypertension: Humoral and Neurogenic Factors , edited by G. E. W. Wolstenholme, Ciba Foundation Symposium on Hypertension, London, J. & A. Churchill, Ltd., 1954, pp. 75-77. 9. Twarog, B. M., and Page, I. H.: Serotonin Content of Some Mammalian Tissues and a Method for Its Estimation , Am. J. Physiol. 175:157-161 ( (Oct.) ) 1953. 10. Pletscher, A.; Shore, P. A., and Brodie, B. B.: Serotonin Release as a Possible Mechanism of Reserpine Action , Science 122:374-375 ( (Aug. 26) ) 1955.Crossref 11. Gaddum, J. H.: Antagonism Between Lysergic Acid Diethylamide and 5-Hydroxytryptamine , J. Physiol. 121:15P ( (July 28) ) 1953. 12. Shore, P. A.; Silver, S. L., and Brodie, B. B.: Interaction of Reserpine, Serotonin, and Lysergic Acid Diethylamide in Brain , Science 122: 284-285 ( (Aug. 12) ) 1955.Crossref 13. Woolley, D. W., and Shaw, E.: Some Neurophysiological Aspects of Serotonin , Brit. M. J. 2:122-126 ( (July 17) ) 1954.Crossref 14. Rinaldi, F.; Rudy, L. H., and Himwich, H. E.: Clinical Evaluation of Azacyclonol, Chlorpromazine, and Reserpine on a Group of Chronic Psychotic Patients , Am. J. Psychiat. 112: 678-683 ( (March) ) 1956. 15. Costa, E.: Effects of Hallucinogenic and Tranquilizing Drugs on Serotonin Evoked Uterine Contractions , Proc. Soc. Exper. Biol. & Med. 91: 39-41 ( (Jan.) ) 1956. 16. Udenfriend, S.; Weissbach, H., and Bogdanski, D. F.: Biochemical Findings Relating to the Action of Serotonin , Ann. New York Acad. Sc. 66:602-608 ( (March 14) ) 1957. 17. Feldberg, W., and Sherwood, S. L.: Injections of Drugs into the Lateral Ventricle of the Cat , J. Physiol. 123:148-167 ( (Jan. 28) ) 1954. 18. Marrazzi, A. S., and Hart, E. R.: Relationship of Hallucinogens to Adrenergic Cerebral Neurohumors , Science 121:365-367 ( (March 11) ) 1955. 19. Rothlin, E.; Cerletti, A.; Konzett, H.; Schalch, W. R., and Taeschler, M.: Zentrale vegetative LSD-Effekte , Experientia 12:154-155 ( (April) ) 1956. 20. Rothlin, E.: Lysergic Acid Diethylamide and Related Substances , Ann. New York Acad. Sc. 66:668-676 ( (March 14) ) 1957. 21. Hoch, P. H.: Experimental Psychiatry, Comments , Am. J. Psychiat. 111:787-790 ( (April) ) 1955. 22. Schwarz, B. E.; Bickford, R. G., and Rowe, H. P.: Reversibility of Induced Psychoses with Chlorpromazine , Proc. Staff Meet. Mayo Clin. 30: 407-417 ( (Sept. 21) ) 1955. 23. Isbell, H., and Logan, C. R.: Studies on the Diethylamide of Lysergic Acid: II. Effects of Chlorpromazine, Azacyclonol and Reserpine on the Intensity of the LSD-Reaction , A. M. A. Arch. Neurol. & Psychiat. 77:350-358 ( (April) ) 1957. 24. Courvoisier, S.; Fournel, J.; Ducrot, R.; Kolsky, M., and Koetschet, P.: Propríetés pharmacodynamiques du chlorhydrate de chloro-3-(dimethylamino-3′-propyl)-10 phénothiazine (4.560 R. P.) Arch. internat. pharmacodyn. 92:305-361 ( (Jan. 1) ) 1953. 25. Hiebel, G.; Bonvallet, M., and Dell, P.: Action de la chlorpromazine ("largactil," 45 60 RP) au niveau du système nerveux central , Semaine hôp. Paris 30:2346-2353 ( (June 6) ) 1954. 26. Elder, J. T., Jr.; Gogerty, J. H., and Dille, J. M.: Survey of d-Lysergic Acid Diethylamide (LSD) Antagonists , Fed. Proc. 16:293-294 ( (March) ) 1957. 27. Gogerty, J. H.; Elder, J. T., and Harita, A.: Modifications of Actions of LSD-25 by Reserpine , Fed. Proc. 16:300 ( (March) ) 1957. 28. Brodie, B. B.; Olin, J. S.; Kuntzman, R. G., and Shore, P. A.: Possible Interrelationship Between Release of Brain Norepinephrine and Serotonin by Reserpine , Science 125:1293-1294 ( (June 28) ) 1957.Crossref 29. Rinaldi, F., and Himwich, H. E.: Alerting Responses and Actions of Atropine and Cholinergic Drugs , A. M. A. Arch. Neurol. & Psychiat. 73: 387-395 ( (April) ) 1955. 30. Rinaldi, F., and Himwich, H. E.: Frenquel Corrects Certain Cerebral Electrographic Changes , Science 122:198-199 ( (July 29) ) 1955. 31. Pfeiffer, C. C., and Jenney, E. H.: The Inhibition of the Conditioned Response and the Counteraction of Schizophrenia by Muscarinic Stimulation of the Brain , Ann. New York Acad. Sc. 66:753-764 ( (March 14) ) 1957. 32. Woolley, D. W., and Shaw, E. N.: Antiserotonins in Hypertension and the Antimetabolite Approach to Chemotherapy , Science 124:34 ( (July 6) ) 1956. 33. Isbell, H.; Belleville, R. E.; Fraser, H. F.; Wikler, A., and Logan, C. R.: Studies on Lysergic Acid Diethylamide: I. Effects in Former Morphine Addicts and Development of Tolerance During Chronic Intoxication , A. M. A. Arch. Neurol. & Psychiat. 76:468-478 ( (Nov.) ) 1956. 34. Winter, C. A., and Flataker, L.: Studies on Heptazone (6-Morpholino-4,4-Diphenyl-3-Heptanone Hydrochloride) in Comparison with Other Analgesic Agents , J. Pharmacol. & Exper. Therap. 98:305-317 ( (March) ) 1950. 35. Abramson, H. A.; Jarvik, M. E.; Kaufman, M. R.; Kornetsky, C.; Levine, A., and Wagner, M.: Lysergic Acid Diethylamide (LSD-25): 1. Physiological and Perceptual Responses , J. Psychol. 39:3, 1955. 36. Edwards, A. L.: Statistical Analysis for Students in Psychology and Education , New York, Rinehart & Co., Inc., 1946. 37. Wilkins, R. W.: Serotonin, Antiserotonins and Hypertension , New England J. Med. 255:115-118 ( (July 19) ) 1956. 38. Cerletti, A., and Rothlin, E.: Role of 5-Hydroxytryptamine in Mental Diseases and Its Antagonism to Lysergic Acid Derivatives , Nature 176:785-786 ( (Oct. 22) ) 1955. 39. Salmoiraghi, G. C.; Sollero, L., and Page, I. H.: Blockade by Brom-Lysergic Acid-Diethylamide (BOL) of the Potentiating Action of Serotonin and Reserpine on Hexobarbital Hypnosis , J. Pharmacol. & Exper. Therap. 117:166-168 ( (June) ) 1956. 40. Ginzel, K. H., and Mayer-Gross, W.: Prevention of Psychological Effects of d-Lysergic Acid Diethylamide (LSD-25) by Its 2-Brom Derivative (BOL-148) , Nature, London 178:210 ( (July 28) ) 1956. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png A.M.A. Archives of Neurology & Psychiatry American Medical Association

Studies on Lysergic Acid Diethylamide (LSD-25): III. Attempts to Attenuate the LSD-Reaction in Man by Pretreatment with Neurohumoral Blocking Agents

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Publisher
American Medical Association
Copyright
Copyright © 1959 American Medical Association. All Rights Reserved.
ISSN
0096-6886
DOI
10.1001/archneurpsyc.1959.02340130040003
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Abstract

Abstract Interest in possible chemical transmission of impulses in the central nervous system has been increasing. The neurohumors involved include acetylcholine,1,2 norepinephrine,2-4 and serotonin.4-6 These theories of central chemical synaptic transmission have led, in turn, to hypotheses which ascribe the psychosis induced by lysergic acid diethylamide (LSD-25) and other psychotomimetic drugs to derangements in central nervous system function because of competition with one or another of the neurohumors or, on the contrary, to accentuation of the effects of the neurohumors by the psychotomimetic agents. The greatest interest has centered on possible interactions of serotonin and LSD. Woolley and Shaw5 and Gaddum6 independently evolved a hypothesis which ascribes the LSD psychosis to competition between LSD and serotonin for receptor sites on or in neurons. This hypothesis, which might be termed the serotonin-deficiency theory, is based in part on the following evidence: Serotonin is found in brain,6,7 References 1. Supplied through the courtesy of Mr. Theodore Wallace, Smith, Kline & French Laboratories, Philadelphia. 2. Supplied through the courtesy of Dr. Frederick K. Heath, Merck Sharp & Dohme, Philadelphia. 3. Feldberg, W. S.: Central and Sensory Transmission , Pharmacol. Rev. 6:85-93 ( (March) ) 1954. 4. Marrazzi, A. S.: The Effects of Certain Drugs on Cerebral Synapses , Ann. New York Acad. Sc. 66:496-507 ( (March 14) ) 1957.Crossref 5. Vogt, M.: The Concentration of Sympathin in Different Parts of the Central Nervous System Under Normal Conditions and After the Administration of Drugs , J. Physiol. 123:451-481 ( (March) ) 1954. 6. Brodie, B. B., and Shore, P. A.: A Concept for a Role of Serotonin and Norepinephrine as Chemical Mediators in the Brain , Ann. New York Acad. Sc. 66:631-642 ( (March 14) ) 1957.Crossref 7. Woolley, D. W., and Shaw, E.: A Biochemical and Pharmacological Suggestion About Certain Mental Disorders , Proc. Nat. Acad. Sc. 44:228-231 ( (April) ) 1954.Crossref 8. Gaddum, J. H.: Drugs Antagonistic to 5-Hydroxytryptamine , in Hypertension: Humoral and Neurogenic Factors , edited by G. E. W. Wolstenholme, Ciba Foundation Symposium on Hypertension, London, J. & A. Churchill, Ltd., 1954, pp. 75-77. 9. Twarog, B. M., and Page, I. H.: Serotonin Content of Some Mammalian Tissues and a Method for Its Estimation , Am. J. Physiol. 175:157-161 ( (Oct.) ) 1953. 10. Pletscher, A.; Shore, P. A., and Brodie, B. B.: Serotonin Release as a Possible Mechanism of Reserpine Action , Science 122:374-375 ( (Aug. 26) ) 1955.Crossref 11. Gaddum, J. H.: Antagonism Between Lysergic Acid Diethylamide and 5-Hydroxytryptamine , J. Physiol. 121:15P ( (July 28) ) 1953. 12. Shore, P. A.; Silver, S. L., and Brodie, B. B.: Interaction of Reserpine, Serotonin, and Lysergic Acid Diethylamide in Brain , Science 122: 284-285 ( (Aug. 12) ) 1955.Crossref 13. Woolley, D. W., and Shaw, E.: Some Neurophysiological Aspects of Serotonin , Brit. M. J. 2:122-126 ( (July 17) ) 1954.Crossref 14. Rinaldi, F.; Rudy, L. H., and Himwich, H. E.: Clinical Evaluation of Azacyclonol, Chlorpromazine, and Reserpine on a Group of Chronic Psychotic Patients , Am. J. Psychiat. 112: 678-683 ( (March) ) 1956. 15. Costa, E.: Effects of Hallucinogenic and Tranquilizing Drugs on Serotonin Evoked Uterine Contractions , Proc. Soc. Exper. Biol. & Med. 91: 39-41 ( (Jan.) ) 1956. 16. Udenfriend, S.; Weissbach, H., and Bogdanski, D. F.: Biochemical Findings Relating to the Action of Serotonin , Ann. New York Acad. Sc. 66:602-608 ( (March 14) ) 1957. 17. Feldberg, W., and Sherwood, S. L.: Injections of Drugs into the Lateral Ventricle of the Cat , J. Physiol. 123:148-167 ( (Jan. 28) ) 1954. 18. Marrazzi, A. S., and Hart, E. R.: Relationship of Hallucinogens to Adrenergic Cerebral Neurohumors , Science 121:365-367 ( (March 11) ) 1955. 19. Rothlin, E.; Cerletti, A.; Konzett, H.; Schalch, W. R., and Taeschler, M.: Zentrale vegetative LSD-Effekte , Experientia 12:154-155 ( (April) ) 1956. 20. Rothlin, E.: Lysergic Acid Diethylamide and Related Substances , Ann. New York Acad. Sc. 66:668-676 ( (March 14) ) 1957. 21. Hoch, P. H.: Experimental Psychiatry, Comments , Am. J. Psychiat. 111:787-790 ( (April) ) 1955. 22. Schwarz, B. E.; Bickford, R. G., and Rowe, H. P.: Reversibility of Induced Psychoses with Chlorpromazine , Proc. Staff Meet. Mayo Clin. 30: 407-417 ( (Sept. 21) ) 1955. 23. Isbell, H., and Logan, C. R.: Studies on the Diethylamide of Lysergic Acid: II. Effects of Chlorpromazine, Azacyclonol and Reserpine on the Intensity of the LSD-Reaction , A. M. A. Arch. Neurol. & Psychiat. 77:350-358 ( (April) ) 1957. 24. Courvoisier, S.; Fournel, J.; Ducrot, R.; Kolsky, M., and Koetschet, P.: Propríetés pharmacodynamiques du chlorhydrate de chloro-3-(dimethylamino-3′-propyl)-10 phénothiazine (4.560 R. P.) Arch. internat. pharmacodyn. 92:305-361 ( (Jan. 1) ) 1953. 25. Hiebel, G.; Bonvallet, M., and Dell, P.: Action de la chlorpromazine ("largactil," 45 60 RP) au niveau du système nerveux central , Semaine hôp. Paris 30:2346-2353 ( (June 6) ) 1954. 26. Elder, J. T., Jr.; Gogerty, J. H., and Dille, J. M.: Survey of d-Lysergic Acid Diethylamide (LSD) Antagonists , Fed. Proc. 16:293-294 ( (March) ) 1957. 27. Gogerty, J. H.; Elder, J. T., and Harita, A.: Modifications of Actions of LSD-25 by Reserpine , Fed. Proc. 16:300 ( (March) ) 1957. 28. Brodie, B. B.; Olin, J. S.; Kuntzman, R. G., and Shore, P. A.: Possible Interrelationship Between Release of Brain Norepinephrine and Serotonin by Reserpine , Science 125:1293-1294 ( (June 28) ) 1957.Crossref 29. Rinaldi, F., and Himwich, H. E.: Alerting Responses and Actions of Atropine and Cholinergic Drugs , A. M. A. Arch. Neurol. & Psychiat. 73: 387-395 ( (April) ) 1955. 30. Rinaldi, F., and Himwich, H. E.: Frenquel Corrects Certain Cerebral Electrographic Changes , Science 122:198-199 ( (July 29) ) 1955. 31. Pfeiffer, C. C., and Jenney, E. H.: The Inhibition of the Conditioned Response and the Counteraction of Schizophrenia by Muscarinic Stimulation of the Brain , Ann. New York Acad. Sc. 66:753-764 ( (March 14) ) 1957. 32. Woolley, D. W., and Shaw, E. N.: Antiserotonins in Hypertension and the Antimetabolite Approach to Chemotherapy , Science 124:34 ( (July 6) ) 1956. 33. Isbell, H.; Belleville, R. E.; Fraser, H. F.; Wikler, A., and Logan, C. R.: Studies on Lysergic Acid Diethylamide: I. Effects in Former Morphine Addicts and Development of Tolerance During Chronic Intoxication , A. M. A. Arch. Neurol. & Psychiat. 76:468-478 ( (Nov.) ) 1956. 34. Winter, C. A., and Flataker, L.: Studies on Heptazone (6-Morpholino-4,4-Diphenyl-3-Heptanone Hydrochloride) in Comparison with Other Analgesic Agents , J. Pharmacol. & Exper. Therap. 98:305-317 ( (March) ) 1950. 35. Abramson, H. A.; Jarvik, M. E.; Kaufman, M. R.; Kornetsky, C.; Levine, A., and Wagner, M.: Lysergic Acid Diethylamide (LSD-25): 1. Physiological and Perceptual Responses , J. Psychol. 39:3, 1955. 36. Edwards, A. L.: Statistical Analysis for Students in Psychology and Education , New York, Rinehart & Co., Inc., 1946. 37. Wilkins, R. W.: Serotonin, Antiserotonins and Hypertension , New England J. Med. 255:115-118 ( (July 19) ) 1956. 38. Cerletti, A., and Rothlin, E.: Role of 5-Hydroxytryptamine in Mental Diseases and Its Antagonism to Lysergic Acid Derivatives , Nature 176:785-786 ( (Oct. 22) ) 1955. 39. Salmoiraghi, G. C.; Sollero, L., and Page, I. H.: Blockade by Brom-Lysergic Acid-Diethylamide (BOL) of the Potentiating Action of Serotonin and Reserpine on Hexobarbital Hypnosis , J. Pharmacol. & Exper. Therap. 117:166-168 ( (June) ) 1956. 40. Ginzel, K. H., and Mayer-Gross, W.: Prevention of Psychological Effects of d-Lysergic Acid Diethylamide (LSD-25) by Its 2-Brom Derivative (BOL-148) , Nature, London 178:210 ( (July 28) ) 1956.

Journal

A.M.A. Archives of Neurology & PsychiatryAmerican Medical Association

Published: Jan 1, 1959

References