The ethics of conducting psychosis-inducing experiments

Accountability in Research

Volumn 7, Issue 2-4, 1999, Pages 137-167

  Sharav, Vera Hassner ^a  

^a Citizens Responsible Care P   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PSYCHOTROPIC AGENT;

ADVISORY COMMITTEE; ARTICLE; BIOMEDICAL AND BEHAVIORAL RESEARCH; CASE REPORT; FOOD AND DRUG ADMINISTRATION; GOVERNMENT; GOVERNMENT REGULATION; HUMAN; HUMAN EXPERIMENT; HUMAN RELATION; INFORMED CONSENT; MENTAL HEALTH SERVICE; MENTAL HEALTH THERAPIES; MENTAL PATIENT; METHODOLOGY; NATIONAL BIOETHICS ADVISORY COMMISSION; NATIONAL INSTITUTE OF MENTAL HEALTH; PERSONNEL; PHYSICIAN; POLICY; RECUMBENCY; SCHIZOPHRENIA; SCIENTIFIC MISCONDUCT; SOCIAL CONTROL; STANDARD; TREATMENT WITHDRAWAL; UNITED STATES;

BIOMEDICAL AND BEHAVIORAL RESEARCH; MENTAL HEALTH THERAPIES; NATIONAL BIOETHICS ADVISORY COMMISSION; NATIONAL INSTITUTE OF MENTAL HEALTH;

ADVISORY COMMITTEES; DECEPTION; FEDERAL GOVERNMENT; GOVERNMENT; GOVERNMENT REGULATION; HUMAN EXPERIMENTATION; HUMANS; INFORMED CONSENT; MENTALLY ILL PERSONS; NATIONAL INSTITUTE OF MENTAL HEALTH (U.S.); NONTHERAPEUTIC HUMAN EXPERIMENTATION; PHYSICIANS; PSYCHOTROPIC DRUGS; PUBLIC POLICY; REFERENCE STANDARDS; RESEARCH DESIGN; RESEARCH PERSONNEL; RESEARCHER-SUBJECT RELATIONS; SCHIZOPHRENIA; SCIENTIFIC MISCONDUCT; SOCIAL CONTROL, FORMAL; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION; WITHHOLDING TREATMENT;

EID: 0033286558     PISSN: 08989621     EISSN: 15455815     Source Type: Journal    
DOI: 10.1080/08989629908573948     Document Type: Article

References (141)

1. Justice Edward Greenfield, opening statement of his decision, TD v NYS OMH, 626 N.Y.S. 2d 1015 (Sup. Ct. NY County 1995).
2. Katz, J. "Human experimentation and human rights, " Health Law Symposium, St. Louis University Law Journal, 1993, 38: 7-54.
3. Abelson, J.L. and Nesse, R.M. (1994). "Pentagastrin infusions in patients with panic disorder: I. Symptoms and cardiovascular responses, " Biological Psychiatry 36: 73-83.
4. Abi-Dargham, A., Gil, R., Krystal, J., Baldwin, R.M., Seibyl, J.P., Bowers, M., van Dyck, C.H., Charney, D.S., Innis, R.B. and Laruelle, M. (1998). "Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort, " American Journal of Psychiatry 155: 761-767.
5. Angrist, B.M. and Gershon, S. (1970). "The phenomenology of experimentally induced amphetamine psychosis: preliminary observations, Biological Psychiatry 2: 95-107.
6. Angrist, B.M., Peslow, E., Rubinstein, M., Wolkin, A. and Rotrosen, J. (1985). "Amphetamine response and relapse risk after depot neuroleptic discontinuation, " Psychopharmacology, (Berl) 85: 277-283.
7. Breier, A., Malhotra, A.K., Pinals, D.A., Weisenfeld, N.I. and Pickar, D. (1997a). "Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers, " American Journal of Psychiatry 154: 805-811.
8. Breier, A., Su, Daunders, Carson, Kolachana, de Bartolomeis, Weinberger, D., Weisenfeld, N.I., Malhotra, Eckleman, A.K. and Pickar, D. (1997b). "Schizophrenia is associated with elevated amphetamine-induced synaptic dopamnie concentrations: evidence from a novel positron emission tomography method, " Proceedings National Academy of Science 94: 2569-2574.
9. Bremner, J.D., Innis, R.B., Ng, C.K., Staib, L.H., Salomon, R.M., Bronen, R.A., Duncan, J., Soutwick, S.M., Krystal, J.H., Rich, D., Zubal, G., Dey, H., Soufer, R. and Chamey, D.S. (1997). "Positron emission tomography measurement of cerebral metabolic correlates of Yohimbine administration in combat-related posttraumatic stress disorder, " Archives of General Psychiatry 54: 246-254.
10. Bremner, J.D., Innis, R.B., Salomon, R.M., Staib, L.H., Ng, C.K., Miller, H.L., Bronin, R.A., Krystal, J.H., Duncan, J., Rich, D., Price, L.H., Malison, R., Dey, H, Soufer, R. and Charney, D.S. (1997). "Positron emission tomography measurement of cerebral metabolic correlates of tryptophan depletion-induced depressive relapse, " Archives of General Psychiatry 54: 364-374.
11. Chamey, D.S., Woods, S.W., Krystal, J.H., Nagy, L.M. and Heninger, G.R. (1992). "Noradrenergic neuronal dysregulation in panic disroder: the effects of intravenous yohimbine and clonidine in panic disorder patients, " Acta Psychiatry Scandinavia 86: 273-282.
12. Daniel, D.G., Weinberger, D.R., Jones, D.W., Zigun, J.R., Coppola, R., Handel, S., Bigelow, L.B., Goldberg, T.E., Berman, K.F. and Kleinman, J.E. (1991). "The effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia, " Journal of Neuroscience 148: 78-84.
13. Delgado, P.L., Price, L.H., Miller, H.L. et al. (1991). "Rapid serotonin depletion as a provocative challenge test for patients with major depression: Relevance to antidepressant action and the neurobiology of depression, " Psychopharmacology Bulletin 27: 321-330.
14. Delgado, P.L., Price, L.H., Miller, H.L., Salomon, R.M., Aghajanian, G.K., Heninger, G. R and Charney, D.S. (1994). "Serotonin and the neurobiology of depression: effects of tryptophan depletion in drug-free depressed patients, " Archives of General Psychiatry 51: 865-874.
15. Goodwin, F.K. (1971). "Psychiatric side effects of Levodopa in man, " Journal of the American Medical Association, Dec. 27, 218: 1915-1920.
16. Gorman, J.M., Fyer, M.R., Liebowitz, M. R and Klein, D.F. (1997). "Pharmacologic provocation of panic attacks, " In: Meltzer, HY, Ed., Psychopharmacology: The Third Generation of Progress, NY: Raven Press.
17. Hollander, E., DeCaria, C.M., Nitescu, A., Gully, R., Suckow, R.F., Cooper, T.B., Gorman, J.M., Klein, D.F. and Liebowitz, M. R, "Serotonergic functions in obsessive-compulsive disorder: behavioral and neuroendocrine responses to oral m-chlorophenylpiperazine and fenfluramine in patients and healthy volunteers, " Archives of General Psychiatry 49: 21-8.
18. Hollister, L.E. (1981). "Experiences with dopamine agonists in depression and schizophrenia, " in Apomorphine and Other Dopaminomimetics, Vol. 2: Clinical Pharmacology, 57-64.
19. Iqbal, N., Asnis, G.M., Wetzler, S., Kahn, R.S., Kay S.R. and van Praag, H.M. (1991). "The MCPP challenge test in schizophrenia: hormonal and behavioral responses, " Biological Psychiatry 30: 770-778.
20. Jody, D., Lieberman, J.A., Geisler, S., Szymanski, S. and Alvir, J.M. (1990). "Behavioral response to methylphenidate and treatment outcome in first episode schizophrenia, " Psychopharmacological Bull 26: 224-230.
21. Kahn, R.S., Siever, L., Davidson, M., Gabriel, S., Amin, F., Stem, R.G., DuMont, K., Apter, S. and Davidson, M. (1992). "Serotonin function in schizophrenia: effects of meta-chlorophenylpiperazine in schizophrenic patients and healthy subjects, " Psychiatry Research 43: 1-12.
22. Koreen, A.R., Lieberman, J.A., Alvir, J. and Chakos, M. (1992). "The behavioral effect of m-chlorophenylpiperazine (mCPP) and methylphenidate in first episode schizophrenia and normal controls, " Neuropsychopharmacology 16: 61-68.
23. Kirpatrick, B., Carpenter, W.T., Buchanan, R.W., Breier, A. and Tamminga, C.A. (1992). "Plasma prolactin as a predictor of relapse in drug-free schizophrenic outpatients, " Biological Psychiatry 32: 1049-1054.
24. Krystal, J.H., Seibyl, J.P., Price, L.H., Woods, S.W., Heninger, G. R, Aghajanian, G.K. and Chamey, D.S. (1993). "m-Chlorophenylpiperazine effects in neurolepticfree schizophrenic patients: Evidence implicating serotonergic systems in the positive symptoms of schizophrenia, " Archives of General Psychiatry 50: 624-635.
25. Lahti, A.C., Koffel, B., LaPorte, D. and Tamminga, C.A. (1995). "Subanesthetic doses of ketamine stimulate psychosis in schizophrenia, "Neurpsychopharmacology 13: 9-19.
26. Laruelle, M., Ab-Dargham, A., van Dyck, C.H., Gil, R, D'Souza, C.D., Erdos, J., McCance, E., Rosenblatt, W., Fingado, C., Zoghbi, S.S., Baldwin, R.M., Seibyl, J.P., Krystal, J.H. and Chamey, D.S. (1996). "Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects, " Proceedings National Academy of Science, August, 9235-9240.
27. Lieberman, J.A., Kane, J.M., Gadaleta, D. et al., (1984). "Methylphenidate challenge as predictor of relapse in schizophrenia, " American Journal of Psychiatry 141: 633-638.
28. Lieberman, J.A., Kane, J.M. and Alvir, J. (1987). "Provocative tests with psychostimulant drugs in schizophrenia, " Psychopharmacology 91: 415-433.
29. Lieberman, J.A. Alvir, J., Geisler, S., Ramos-Lorenzi, J., Werner, M., Novaccenko, H., Cooper, T. and Kane, J.M. (1994). "Methylphenidate response, psychopathology and tardive dyskinesia as predictors of relapse in schizophrenia, " Neuropsychopharmacology 1994, 11: 107-118.
30. Mezzacappa, E., Steingard, R., Kindlon, D., Saul, J.P. and Earls, F. (1998). "Tricyclic antidepressants and cardiac autonomic control in children and adolescents, " Journal of the American Academy of Child and Adolescent Psychiatry 37: 52-9.
31. Mathew, R.J. and Wilson, W.H. (1989). "Changes in cerebral blood flow and mental state after amphetamine challenge in schizophrenic patients, " Neuropsychobiology 21: 117-123.
32. Morello, M., Starkstein, S., Petracca, G., Cataneo, E. A., Manes, F. and Leiguarda, R. (1996). "Drug-induced parkinsonism in schizophrenic patients: motor response and psychiatric changes after acute challenge with L-Dopa and apomorphine, " Clinical Neuropharmacology 19: 439-443.
33. Perovich, R.M., Lieberman, J.A., Fleishhacker, W.W. and Alvir, J. (1989). "The behavioral toxicity of bromocriptine in patients with psychiatric illness, " Journal of Clinical Psychopharmacology 9: 417-422
34. Sanfilipo, M., Wolkin, A., Angrist, B., van Kammen, D.P., Duncan, E., Wieland, S. and Cooper, T.B. (1996). "Amphetamine and negative symptoms of schizophrenia, " Psychopharmacology 123: 211-214.
35. Sharma, R.P., Javaid, J.I., Pandey, G.N., Jainacak, P.G. and Davis, J.M. (1991). "Behavioral and biochemical effects of methylphenidate in schizophrenic and nonschizophrenic patients, " Biological Psych. 30: 459-566.
36. Southwick, S.M., Krystal, J.H., Bremner, D., Morgan III, C.A., Nicolaou, A.L., Nagy, L.M., Johnson, D.R., Heninger, G.R. and Chamey, D. (1997). "Noradrenergic and serotonergic function in posttraumatic stress disorder, " Archives of General Psychiatry 54: 749-758.
37. Strakowski, S.M., Sax, K.W., Setter, M.J., Stanton, S.P., Keck and Jr. P.E. (1997). "Lack of enhanced response to repeated d-amphetamine challenge in first-episode psychosis: implications for a sensitization model of psychosis in humans, " Biological Psychiatry 42: 749-755.
38. van Kammen, D.P., Bunney, W.E. Jr, Dochety, J.P., Marder, S. R, Ebert, M.H., Rosenblatt, J.E. and Rayner, J.N. (1982). "d-Amphetamine-induced heterogenous changes in psychotic behavior in schizophrenia, " American Journal of Psychiatry 1982, 139: 991-997.
39. van Kammen, D.P., Dochety, J.P., Marder, S.R., Rosenblatt, J.E. and Bunney, W.E. (1985). "Lithium attenuates the activation-euphoria but not the psychosis induced by d-amphetamine in schizophrenia, " Psychopharmacology (Berl) 87: 111-115.
40. Wolkin, A., Sanfilipo, M., Angrist B., Duncan, E., Wieland, S., Wolf, A.P., Rodie, J.D., Cooper, T.B., Laska, E. and Rotrosen, J.P. (1994). "Acute d-amphetamine challenge in schizophrenia: effects on cerebral glucose utilization and clinical symptomatology, " Biological Psychiatry 36: 317-325.
41. Miller, F.G. and Rosenstein, D.L. (1997). [of NIMH], "Psychiatric symptom-provoking studies: an ethical appraisal, " Biological Psychiatry 42: 403-409. Miller serves on NIMH's Institutional Review Board, Rosenstein is a research investigator at NIMH.
42. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Report and Recommendations, (Belmont Report) DHEW Publication No. (05) 78-0006. Washington D.C.: U.S. Dept. of HEW, 1979.
43. Declaration of Helsinki TV, World Medical Association, 18th World Medical Assembly, 1964; amended Hong Kong, Sept, 1989.
44. Willowbrook: hepatitis experiments on mentally retarded children, 1950s-1960s; Tuskegee:: syphilis experiment on African-American men, 1940s-1972; Massachusetts Institute of Technology: radioactive iron/calcium given to retarded children, 1950-1953; Jewish Chronic Disease Hospital experiments injected live cancer cells into elderly patients, 1960s-1970s; For a recitation and detailed description of these and other unethical human experiments in America, see: Advisory Committee on Human Radiation Experiments, Final Report, Washington, D.C., 1995, GPO #IND 072595-A.
45. Shamoo, A.E. and Irving, D. (1993). "Accountability in research using persons with mental illness, " Accountability in Research 3: 1-17.
46. Bonnie, R.J. (1997). "Research with cognitively impaired subjects: Unfinished business in the regulation of human research, " Archives of General Psychiatry, 1997,54: 105-111.
47. Documented testimonies by victims, their families and Citizens for Responsible Care in Psychiatry and Research: Robert Aller, Janice Becker, Andrew, Mel and Muriel Brownstein, Joseph Friend, Arun Guha, Arliss Nissin, Beverley Post, Shalmah Lee Prince, Judith Vukov, Vera Hassner Sharav, NBAC meeting, Sept. 18, 1997.
48. Grady, Denise (1999). "Patient or Guinea Pig? Dilemma of Clinical Trials, " NY Times, Jan 5, C-1.
49. Whitaker, R. and Kong, D. (1998). "Doing Harm: Research on the mentally ill, " Front Page series, The Boston Globe, Nov. 15-18.
50. Goldman, D. (1943). "Studies on the Use of Refrigeration Therapy in Mental Disease with Report of Sixteen Cases, " Journal of Nervous and Mental Diseases 97:152-165.
51. Adapted from Karl Kraus, as cited at Library of Congress exhibit, "Sigmund Freud: Conflict in Culture, " 1998.
52. Shamoo, A.E. and Keay (1996). "Ethical concerns about relapse studies, " Cambridge Quarterly of Health Care Ethics 5:373-386.
53. Gilbert, P.L., Harris, M.J., McAddams, L.A. et al. (1995). "Neuroleptic withdrawal in schizophrenic patients, " Archives of General Psychiatry 52:173-186.
54. Viguera, A.C., Baldessarini, J.R., Hegarty, J.D., van Kammen, D.P. and Tohen, M. (1997). "Clinical risk following abrupt and gradual withdrawal of maintenance neuroleptic treatment, " Archives of General Psychiatry 54:49-55.
55. Ricaurte, G.A. and McCann, U.D. (1992). "Neurotoxic amphetamine analogues: effects in monkeys and implications for humans, " Annals of NY Academy of Science 648:371-82.
56. Ellison, G. (1995). "The N-methyl-E-asparate antagonists phencyladine, ketamine and dizocilpine as both behavioral and anatomical models of the dementias, Brain Research 20: 250-267.
57. Javitt, D.C. and Zukin, S.R. (1991). "Recent advances in the phencyclidine model of schizophrenia, " American Journal of psychiatry 148:1301-1308.
58. McCann, U.D., Seiden, L.S., Rubin, L.J. and Ricaurte, G.A. (1997). "Brain serotonin neurotoxicity and primary pulmonary hypertension from fenfluramine and dexfenfluramine, " JAMA, Aug. 27, 278:666-672.
59. Olney, J.W. and Farber, N.B. (1995). "NMDA antagonists as neurotherapeutic drugs, psychotogens, neurotoxins, and research tools for studying schizophrenia/' Neuropsychopharmacology 13:335-345 in Ellison [Ref. 88].
60. Robinson, T.E. and Becker, J.B. (1986). "Enduring changes in brain and behavior produced by chronic amphetamine administration, " Brain Research Reviews 11: 157-198.
61. Sharp, F.R., Butman, M, Aardalen, K., Nickolenko, J., Nakki, R., Massa, S.M. and Swanson, R.A. (1994). "Neuronal injury produced by NMDA antagonists can be detected using heat shock proteins and can be blocked with antipsychotics, " Psychopharmacology Bulletin 30:555-560.
62. Ikonamidou, C, Bosch, F., Miksa, M., Bittigau, P., Vocker, J., Dikranian, K., Tenkova, T.I., Stefovska, V., Turski, L. and Olney, J.W. (1999). "Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain, " Science, Jan. 1, 283:70-74.
63. Tamminga, C, Holcomb, H.H., Gao, X.-M. and Lahti, A.C. (1995). "Glutamate pharmacology and the treatment of schizophrenia: current status and future directions, " International Clinical Psychopharmacology, 10 Suppl. 3:29-37.
64. Hilts, P.J. (1998). "Psychiatric Research Under Fire, " "Do Consent Forms Tell Enough?" NY Times, May 19, C-1.
65. Malhotra, A.K., Pinals, D.A., Adler, C.M., Elman, I., Clifton, A., Pickar, D. and Breier, A. (1997). "Ketamine-induced exacerbation of psychotic symptoms and cognititve impariment in neuroleptic-free schizophrenics, " Neuropsychopharmacology 17:141-150.
66. Ethics in Neurobiological Research with Human Subjects, Co-edited by Hassner [Sharav], V. and Weisburd, D., The Journal of the California Alliance of the Mentally Ill, 1994
67. Ethics in Neurobiological Research with Human Subjects, Proceedings, Ed. A.E. Shamoo, Gordon & Breach Pub., 1997
68. Lehrman, N.S. and Sharav, V.H., "Ethical problems in psychiatric research, " The Journal of Mental Health Administration, 1997, 24: 227-250
69. Lehrman, N.S. "The ethics of harmful psychiatric research: a faulty effort to defend them, " Accountability in Research, 1997, 5: 283-288.
70. Oral and written testimony was provided by Shamoo and Sharav-to NBAC, and several Congressional Committee Hearings [Gov. Reform & Oversight Committee, April 22,1998; Subcommittee on Human Resources [of Reform & Oversight], June 11, 1998].
71. Under the National Animal Welfare Act, 1966, revised numerous times, a system of independent oversight and accountability protect laboratory animals. To ensure the AWA is enforced, the Animal & Plant Health Inspection Service (APHIS) of the USDA inspects the premises of regulated facilities and takes regulatory action against persons found to be in violation of the AWA regulations. In fiscal year 1997, a staff of about 73 Animal Care inspectors conducted almost 16,000 inspections to ensure compliance with the AWA regulations. No such inspections monitor the well-being of human subjects of research.
72. [See Ref 9] Among the documents presented to NBAC, is a court affidavit by the Chief of Psychiatry at the Bronx VA Medical Center, (re: Shalmah Lee Prince's lawsuit). It states: "it was the norm and practice of researchers and IRBs not to discuss any such risk [of drug washout] in consent forms. " Published evidence of current, federally funded relapse inducing experiments [See Ref 3] were provided to NBAC. As if to underscore their disregard for com-pliance with human subject regulations, only 13 out of 100 protocols were sent to NBAC following this Presidential Commission's request to review 100 protocols and consent forms. And those reviewed failed to fully comply with current federal regulations.
73. National Bioethics Advisory Commission, Transcript of meeting, Nov. 23,1997.
74. The financial incentives-$470 million annually in NIMH grants and $10,000-$35,000 per human subject in an industry sponsored drug trial-the competitive pressure to recruit as many subjects as possible, in order to get those grants, has increased the risks for vulnerable populations. [See Ref. 11, 48] Thus, the American College of Neruropsychopharmacology, whose members are the major beneficiaries of the symptom-provocation experiments, adopted "A Statement of principles of ethical conduct for neuropsychopharmacologic research in human subjects, " [by Klein, D.F., Schooler, N.] Feb, 1996, giving its members permission to conduct experiments on incapacitaed psychiatric patients, [see, Lehrman, Sharav, Ref. 20].
75. Antony, M.M. et al. (1997). Bremner, J.D. et al. (1997). Charney, D.S. et al. (1992). Southwick, S.M. et al. (1997). [See Ref. 3].
76. Evidence of neurotoxic brain damage in animal studies with fenfluramine was well known, even before its link to pulminary/heart damage was fully known. On Dec. 15, 1993, in a letter to the FDA, a group of prominent neuroscientists, led by Dr. George Ricaurte of Johns Hopkins warned about its potential danger in humans. That warning went unheeded. On Dec. 7, 1995 a group of 22 neuroscientists again implored the FDA in a letter not to approve it until its potential to cause neurological damage in humans was further examined. See, Kerr, K., series, Dec. 3, 1997-Feb. 16, 1998, "Fen-Phen Diet drug damaging the brain?/lawyers: confusion, aggression reported" Newsday; See also, McCann, Ref. 15.
77. Coccaro, E.F., Kavoussi, R.J. and Hauger, R.L. (1997). "Serotonin function and antiaggressive response to fluoxetine: a pilot study, " Biological Psychiatry, 1997, 42: 546-52.
78. Halperin, J.M. (1997). "Serotonin, aggression and parental psychopathology in children with attention deficit hyperactivity disorder, Journal of the American Academy of Child Adolescent Psychiatry 36: 1391-1398.
79. Pine, D.S., Coplan, J.D., Wasserman, G.A., Miller, L.S., Fried, J.E., Davies, M., Cooper, T.B., Greenhill, L., Shaffer, D. and Parsons, B. (1997). "Neuroendocrine response to fenfluramine challenge in boys, " Archives of General Psychiatry 54: 839-846
80. Stoff, D.M., Pasatiempo, A.P., Yeung, J.H., Bridger, W.H. and Rabinovich, H. (1992). "Test-retest reliability of the prolactin and cortisol responses to D, L-fenfluramine challenge in disruptive behavior disorders, " Psychiatry Research 42: 65-72.
81. Executive Order #12975, October 3, 1995, Federal Register 60(193): 52063-52065.
82. Alexander Capron, PhD, Eric Cassell, MD, Alta Charo, Patricia Backlar, Diane Scott-Jones, PhD: NBAC transcript, Nov. 23, 1997.
83. Lieberman, J.A., Sheitman, B.B., Kinon, B.J., "Neurochemical sensitization in the pathophysiology of schizophrenia: deficits and dysfunction in neuronoal regulation and plasticity, " Neuropsychopharmacology, 1997, 17: 205-229.
84. Lieberman, J.A., Kane, J.M. and Alvir, J. (1987). "Provocative tests with psychostimulant drugs in schizophrenia, " Psychopharmacology, 1987, 91:1-5.
85. Ellison, 1995; Javitt, 1991 [See, Ref. 15].
86. Turner, D.M., "Ketamine: the ultimate psychedelic journey, " The Essential Psychedelic Guide online, The Vaults of Erowid, http://www.erowid.org/entheo_issues/writings/psychedelic_guide/ketamine.html.
87. Kong, D. (1998). "Drug studies are questioned, " Boston Globe, Dec. 31, front page; [See also Ref. 16].
88. Jansen, K.L.R. (1997). "The Ketamine Model of the Near Death Experience: A Central Role for the NMDA Receptor, " Journal of Near-Death Studies, Vol. 16, No.1.
89. Caldwell, C.B. and Gottesman, II (1992). "Schizophrenia-a high-risk factor for suicide: clues to risk reduction, " in Suicide and Life-Threatening Behavior, 22: 479-193
90. Shamoo, A.E., Irving, D.N. and Langenberg, P. (1997). "A review of patient outcomes in pharmacological studies from the psychiatric literature, 1966-1993, " Science and Engineering Ethics 3: 395-406.
91. American Psychiatric Association, (1997). "Practice Guideline for the treatment of patients with schizophrenia, " American Journal of Psychiatry, Suppl, 154:63pp.
92. Wyatt, R.J. (1995). "Neuroleptics and the natural course of schizophrenia, " Schizophrenia Bulletin, 1991, 17: 325-351
93. Wyatt, R.J., "Risks of withdrawing antipsychotic medications, " Archives of General Psychiatry 52:205-208.
94. Janowsky, D.S., El-Yousef, D., Davis, J.M. and Sekerke, H.J. (1973). "Provocation of schizophrenic symptoms by intravenous administration of methylphenidate, " Archives of General Psychiatry 28:185-191.
95. Laruelle (1996). [See Ref. 3].
96. Strakowski et al. (1997). [See Ref. 3].
97. Beauchamp, T.L. (1996). "Looking back and judging our predecessors, " Kennedy Institute of Ethics Journal 6:251-270.
98. U.S. Office of Protection from Research Risks, Evaluation of Human Subject Protection. UCLA, May 11, 1994; Maryland Psychiatric Research Center, Letter of findings, April 16, 1998; U.S. General Accounting Office, Report to the Senate Committee on Gov Affairs, "Scientific Research: Continued Vigilance critical to protecting human subjects, " 1996, GAO/HEHS-96-72; U.S. Office of Instpector General, Report, Institutional Review Boards: A Time for Reform, June, 1998, OEI-01-97-00193.
99. Angrist and Gershon, 1970; Goodwin, 1971; Hollister, 1981; van Kammen, 1982; Lieberman, 1987 [See Ref. 3].
100. Jody, D. and Lieberman et al. (1990). [See Ref. 3].
101. Lieberman et al. (1994). [See Ref. 3].
102. Carpenter, W.T., Schooler, N.R. and Kane, J.M. (1997). "The rationale and ethics of medication-free research in schizophrenia, " Archives of General Psychiatry 54: 401-407;
103. Applebaum, P.S. (1996). "Drug-free research in schizophrenia: An overview of the controversy, " IRB: A Review of Human Subjects Research, 18:1-5.
104. Goodwin, F.K. and Hadley, S.W. (1994). "Enhancing the climate of trust in clinical psychiatric research, " in Shamoo pp. 253-263 [See Ref. 25] Lieberman, J.A. et al. [See Ref 3].
105. Reports in the press about harm to individuals: Kerr, K. "Drug Study Questioned: All subjects in city test were minorities, " NY Newsday, April 14, 1998, A-32
106. Hilts, P., "Experiments On Children Are Reviewed, " NY Times, April 15, 1998, B-1
107. Montero, D. "Did City Hosps Jeopardize Kids to Conduct Research?" NY Post, April 14, 1998, p. 4, on-going follow-up
108. Wadman, M., "Row erupts over child aggression study, " Nature, April, 1998, 747
109. Schoofs, M., "Did Doctors Mislead the parents of Kids the Experimented On?" Village Voice, May 5, 1998
110. Weiss, R., "Research Volunteers Unwittingly at Risk, " Washington Post, Aug. 1, 1998, A-1
111. Kerr, K., "Informed Consent? Drug researchers criticized for involving psychiatric patients without fully explaining the risks, " NY Newsday, Sept. 8,1998, C-6-7
112. Davis, R., "U.S. Human Medial Tests Lack Oversight, " USA Today, front page
113. Wadman, M., "Research Roulette" CityPaper, July 1, 1998.
114. Birnbaum, G. (1999). "Science or Abuse? State Testing Prozac on 6-Year Olds, " NY Post, Jan. 31, pp. 7-8.
115. Strassman, R.J. (1995). "Hallucinogenic drugs in psychiatric research and treatment: perspectives and prospects, " Journal of Nervous Diseases 183:127-138.
116. Center Watch, Inc., "An Investigator's Guide to Clinical Research, " monthly/weekly; "CRO Directory"; & Internet Clinical Trial Listing Service, Boston, MA.
117. Stecklow, S. and Johannes, L. (1997). 'Test Case: Drug Makers Relied on Clinical Researchers Who Now Await Trial-Two Professors Are Accused of Endangering Patients And Stealing $10 Million, " The Wall Street Journal, August 15, front page.
118. Miller, F., "Comments on the second report of the Maryland Attorney General's Research Working Group, " Journal of Health Care Law & Policy, 1:193-202.
119. Capron [See Ref. 27].
120. Davidson, M., Keefe, R.S.E., Mohs, R.C. et al. (1987). "L-Dopa challenge and relapse in schizophrenia, " American Journal of Psychiatry 144:934-938.
121. L-dopa consent form obtained under Freedom of Information is in author's file Concerns about this experiment were discussed previously: see, Hassner [Sharav], "What's ethical, what's not, where do you draw the line?" 1994; Lehrman and Sharav, 1997 [See Ref. 19]; Miller and Rosentstein, 1997, found it especially troubling ethically. [See Ref. 2].
122. The transcript was downloaded in June, 1997 from NBAC's website by an investigative reporter for the Boston Globe. When he attempted to retrieve a section that he had accidentally erased, the transcript was no longer available on NBAC's website. After public protests by Citizens for Responsible Care & Research, the transcript reappeared.
123. A Sept 2, 1998 letter from OPRR to Andrew Brownstein, a former research subject at NIMH, confirmed that: "OPRR has completed its evaluation of human subject protections, " and "NIMH has taken the following corrective actions. ": "ensuring that subjects sign only one copy of an informed consent document. " "Provision of a reminder to NIMH investigators of their responsibilities in regard to documentation of informed consent and assessment of decisional capacity of research subjects. "
124. U.S. DHHS, Office of Protection from Research Risks, Letter of Finding, Re: "Human Subject Protection Under Multiple Assurance (MPA) M-1155, Research Projects Involving Human Subjects with Schizophrenia, " January 18, 1999. Citing the Code of Federal Regulations, OPRR's letter states: "OPRR finds that informed consent documents. failed to include the following elements required by Department of Health and Human Services regulations at 45 CFR 46.116" "An explanation of the purposes of the research; a complete and accurate description of the procedures (i.e.,. the plan for a 4-week washout period prior to sinemet [L-dopa] challenge; the plan to withhold neuroleptic medication for up to one year or until relapse); An adequate description of all reasonably foreseeable risks and discomforts to the subject (i.e., the risk of schizophrenic relapse from either sinemet challenge or withdrawal of neuroleptic agents for up to one year, as well as the potential psychiatric, physical, social, and legal effects of such relapse; the psychological stress and anxiety.; all the known major side effects of haldol, sinemet (L-dopa) and selegiline, as well as possible adverse effects resulting from interactions of these medications" "A description of appropriate alternative procedures or courses of treatment that might be advantageous to the subject. " OPRR also found that "the MSSM IRB lacked sufficient information to make the determinations required for approval of research under HHS regulations" and "failed to conduct continuing review"-as required under the Code of Federal Regulations.
125. OPRR's findings-at UCLA, Maryland Psychiatric Research Center, Mount Sinai Medical Center-demonstrate serious ethical violations-including failure to disclose relevant risks, thereby invalidating the informed consent obtained. Despite such repeated findings, and despite widespread criticism in the press no investigator or institution has been held accountable, no actions or even a reprimand were issued. [See Katz, 1993, Ref. 2; Shamoo and Irving, 1993, Ref. 8; Hassner [Sharav], 1994, Lehrman and Sharav, 1997, Ref. 20; Victim Testimonies, 1997, Ref. 9]. [See: Hilts, P., NY Times, Ref. 17; Borr, J., "Mental patients at risk in research, " Baltimore Sun, June 7, 1998, front page; Wadman, M., "Research Roulette: Are the Maryland Psychiatric Research Center's Schizophrenia Studies Harming Patients?" CityPaper, July 1, 1998, cover story; St. Louis Post Dispatch, Editorial 1998; Whitaker and Kong, Boston Globe, series: "Doing Harm: Research on the Mentally Ill, " Nov. 15-18, 1998, front page] [See also Ref. 46].
126. Dr. William Carpenter, Director, and Dr. Carol Tamminga, Deputy Director of MPRC were honored this year by the IOM. They, and James Childress, chairman of NBAC's human subjects sub-committee, were inducted as new IOM members.
127. Bowdie, T.A., Radant, A.D., Cowley, D.S., Kharasch, E.D., Strassman, R.J. and Roy-Byrne, P.P. (1998). "Psychedelic effects of ketamine in healthy volunteers, " Anesthesiology 88: 82-88.
128. Cohen, S. (1960). "Lysergic acid diethylamide: side effects and complications, " Journal of Nervous Mental Diseases, 130:30-40.
129. Kurland, A.A., Yensen, R. and Dryer, D.A., "The relationship between peak experience and outcome in LSD assisted psychostherapy with substance abusers, " a current project at the Orenda Institute, University of Maryland, www.maps.org/ news.
130. Prospectus, Heffter Research Institute, West Lafayette, Indiana, online at: www.well.com/user/dpd/heffter.html.
131. Geyer, M.A., "Behavioral studies of hallucinogenic drugs in animals: implications for schizophrenia research, " Pharmacopsychiatry, 1998, July 31 Suppl. 2:73-79.
132. Krystal, J.H., Petrakis, I.L., Webb, E., Cooney, N.L., Karper, L.P., Namanworth, S., Stetson, P., Trevisan, L.A. and Charney, D.S. (1998). "Dose-related ethanol-like effects of the NMDA antagonist, ketamine, in recently detoxified alcoholics, " Archives of General Psychiatry 55:354-360.
133. Schwartz, R.H. and Miller, N.S. (1997). "MDMA (Ecstasy) and the Rave: A Review, " Pediatrics 100: 705-708.
134. Ricaurte, G.A. (1989). "Studies of MDMA-induced neurotoxicity in nonhuman primates: a basis for evaluating long-term effects in humans, " In: Asghar, K., DeSouza, E., eds. Pharmacology and toxicology of amphetamines and related designer drugs. NIDA Res. Monogr., 94:306-22.
135. Ricaurte, G.A. and McCann, U.D. (1992). "Neurotoxic amphetamine analogues: effects in monkeys and implications for humans, " Annals of the NY Academy of Sciences 648:371-382.
136. McCann, U.D., Szbo, Z., Scheffel, U., Dannals, R.F. and Ricaurte, G.A. (1998). "Positron emission tomographic evidence of toxic effect of MDMA ("Ecstasy") on brain serotonin neurons in human beings, " Lancet 352:1433-1437.
137. Morris and Kelly (1998). "Ecstasy users face consequences of neurotoxicity, " Lancet, Dec. 12, 352:1913.
138. Editorial, "Walking on the moon, " Lancet, 1996; 347:207. 69.
139. Grob, C.S., Poland, R.E., Chang, L. and Ernst, T. (1996). "Psychobiologic effects of 3,4-methylenedioxymsethamphetamine in humans: methodological considerations and preliminary observations, " Behavioral Brain Research, 1996, 73: 103-107. Updated information about this project is available on websites of the Hefter Institute and the Multidisciplinary Association of Psychedelic Studies, www.70. Editorial, St. Louis Post Dispatch, May, 1998; 71. Editorial, The Boston Globe, Nov. 18, 1998.
140. Marshall, Elliot (1999). "NIMH to screen studies for science and human risks, " Science, Jan. 22, pp. 464-165.
141. Hilts, P. (1999). "Federal Reviews Are Urged for Experiments on Mental Patients, " The NY Times, Feb. 4, A-22.