Regulation of human research with LSD in the United States (1949-1987)

Review

Abstract

Human research with hallucinogens such as lysergic acid diethylamide (LSD) has been ongoing in the USA since 1949. During the 1960s, LSD was investigated for a variety of psychiatric indications, including the following: as an aid in treatment of schizophrenia; as a means of creating a “model psychosis”; as a direct antidepressant; and as an adjunct to psychotherapy. Studies with all drugs, including LSD, have always been conducted under federal regulatory controls, including the 1938 Food Drug and Cosmetic Act (FDCA; which ensured the safety of drugs) and the 1962 Kefauver-Harris Amendments to the FDCA (which described appropriate scientific methodology and ensured drug efficacy). This paper details how the 1962 Amendments introduced numerous safety and efficacy requirements that must be in satisfied during clinical drug research—and how human studies conducted with LSD in the 1960s struggled with their fulfillment. Information is provided from Senate hearings, case law, and interviews with key investigators. Examples are also drawn from scientific papers and symposia published during and since that period, with a focus on information from clinical studies conducted with LSD by psychiatrist Albert Kurland at the Spring Grove State Hospital, near Baltimore, MD. While Kurland largely conformed with these new regulations, other investigators often fell short of complying with scientific standards and federal requirements. Thus, the human hallucinogen studies of the 1960s are best understood as providing pilot data on safety and efficacy, as well as testable hypotheses for current hallucinogen studies conducted under modern scientific and regulatory standards.

Keywords

Hallucinogen LSD Clinical Regulation 

Notes

Acknowledgements

The author gratefully acknowledges the valuable discussion and comments regarding this paper provided by Dr. Silvia Calderon (Controlled Substance Staff, FDA), Dr. John Swann (FDA Historian), Ms. Nancy Sager (Office of Regulatory Policy, FDA), Dr. Steven Grant (NIDA), Drs. Richard Yensen and Donna Dryer (Orenda Institute), Dr. William Richards (Johns Hopkins University), Dr. Laura Helft (Howard Hughes Medical Institute), and Mr. Jules Asher (NIMH Press Office).

Compliance with ethical standards

Disclaimer

This paper reflects the views of the author and does not necessarily represent those of FDA.

References

  1. Abramson HA (1967) Comparison of LSD with methysergide and psilocybin on test subjects. In: Abramson HA (ed) The use of LSD in psychotherapy and alcoholism. Bobbs-Merrill Company, Inc., IndianapolisGoogle Scholar
  2. Asher J (1975) Whatever happened to psychedelic research? APA Monitor on Psychology 6(10):4–5Google Scholar
  3. Axelrod J. (2003) National Institutes of Health interview conducted by Nirenberg M and Witkop B, November 25. https://history.nih.gov/archives/downloads/Axelrod%20Julius.pdf
  4. Barrigar RH (1964) Regulation of psychedelic drugs. Psychedelic Rev 1(4):394–441Google Scholar
  5. Beringer K (1927) Der Meskalinrausch: Seine Geschichte und Erscheinungsweise (Monographien aus dem Gesamtgebiete der Neurologie und Psychiatrie). Springer, BerlinGoogle Scholar
  6. Buckman J (1966) Lysergic acid diethylamide. Brit Med J 2:302CrossRefPubMedPubMedCentralGoogle Scholar
  7. Busch AK, Johnson WC (1950) LSD 25 as an aid in psychotherapy; preliminary report of a new drug. Dis Nerv Syst 11(8):241–243PubMedGoogle Scholar
  8. Campbell ND, Stark L (2015) Making up ‘vulnerable’ people: human subjects and the subjective experience of medical experiment. Soc Hist Med 28(4):825–848CrossRefGoogle Scholar
  9. Carhart-Harris RL, Goodwin GM (2017) The therapeutic potential of psychedelic drugs: past, present, and future. Neuropsychopharmacology 42(11):2105–2113CrossRefPubMedGoogle Scholar
  10. Carpenter D (2011) Reputation and power: organizational image and pharmaceutical regulation at the FDA. Princeton University Press, PrincetonGoogle Scholar
  11. Cole and Katz (1964) The psychotomimetic drugs: an overview. JAMA 187(10):758–765PubMedGoogle Scholar
  12. D’Aguanno W to Kelsey F, memo, September 19, (1963) Folder 505.51 September, Box 3570. General Subject Files 1938-1974, Division of General Services, RG 88. FDA Records, National Archives II (College Park, College Park, MD)Google Scholar
  13. Debold RC, Leaf RC (eds) (1967) LSD, man and society. Wesleyan University Press, MiddletownGoogle Scholar
  14. Dishotsky NI, Loughman WD, Mogar RE, Lipscomb WR (1971) LSD and genetic damage. Science 172(3982):431–440CrossRefPubMedGoogle Scholar
  15. Doblin R. Regulation of the medical use of psychedelics and marijuana. Harvard University dissertation, 2001. http://www.maps.org/news/332-maps-resources/research-papers/5402-dissertation-rick-doblin,-ph-d
  16. Eisner BG (2002) Remembrances of LSD therapy past. www.maps.org/images/pdf/books/remembrances.pdf
  17. Faillace LA (1966) Clinical use of psychotomimetic drugs. Compr Psychiatry 7(1):13–20CrossRefPubMedGoogle Scholar
  18. FDA aide links LSD, birth defects (1968) Morning News, Wilmington, DelawareGoogle Scholar
  19. Food and Drug Administration (2001) Guidance for Industry: E10 Choice of Control Group and Related Issues in Clinical TrialsGoogle Scholar
  20. Food and Drug Administration (2017) Regulations, guidance, and reports related to women’s healthGoogle Scholar
  21. Fortner v. Koch (1935) 272 Mich. 273, 261 N.W. 762Google Scholar
  22. Freedman DX (1970) Problems and prospects of research with the hallucinogens. In: Gamage JR, Zerkin EL (eds) Hallucinogenic drug research: impact on science and society. Stash Press, BeloitGoogle Scholar
  23. Goble FG (1970) The third force: the psychology of Abraham Maslow. Pocket Books, New YorkGoogle Scholar
  24. Goddard JL (1966) Organization and coordination of Federal Drug Research and regulatory programs: LSD: hearings before the United States Senate Committee on Government Operations, Subcommittee on Executive Reorganization, Eighty-Ninth Congress, Second SessionGoogle Scholar
  25. Green JA, Podolsky SH (2012) Reform, regulation, and pharmaceuticals: the Kefauver-Harris amendments at 50. N Engl J Med 367:1481–1483CrossRefGoogle Scholar
  26. Grob CS (1998) Psychiatric research with hallucinogens: what have we learned? Heffter Rev Psychedelic Res 1:8–20Google Scholar
  27. Hagenbach D, Werthmuller L (2011) Mystic chemist: the life of Albert Hofmann and his discovery of LSD. Synergetic Press, Santa FeGoogle Scholar
  28. Harvey JL to Stollaroff, letter. 1965 Box 3750, General Subject Files 1938-1974, Division of General Services, RG 88. FDA Records, National Archives II (College Park, College Park, MD)Google Scholar
  29. H.E.W (1975) Reported to Have Run LSD Tests on 2,500 People, New York Times, New York, NYGoogle Scholar
  30. Hilts PJ (2003) Protecting America’s health: the FDA, business, and one hundred years of regulation. Alfred A. Knopf, New YorkGoogle Scholar
  31. Hoffer A (1970) Treatment of psychosis with LSD. In: Gamage JR, Zerkin EL (eds) Hallucinogenic drug research: impact on science and society. Stash Press, BeloitGoogle Scholar
  32. Hofmann A (1983) LSD, my problem child: reflections on sacred drugs, mysticism, and science. J.P. Tarcher, Los AngelesGoogle Scholar
  33. Hollister LE (1968) Chemical psychoses: LSD and related drugs. Charles C. Thomas, Springfield, ILGoogle Scholar
  34. Junod SW (2008) FDA and clinical drug trials: a short history. In: Davies M, Kerimani F (eds) A quick guide to clinical trials. Bioplan Inc., WashingtonGoogle Scholar
  35. Kelsey FO (1966) Organization and coordination of Federal Drug Research and regulatory programs: LSD: hearings before the United States Senate Committee on Government Operations, Subcommittee on Executive Reorganization, Eighty-Ninth Congress, Second SessionGoogle Scholar
  36. Kelsey F et al. (1965) (FDA) meeting with Henze C and Bircher R (Sandoz), memo. Folder 521.6-525.091. Box 3758, General Subject Files 1938-1974, Division of General Services, RG 88. FDA Records, National Archives II (College Park, College Park, MD)Google Scholar
  37. Kurland AA, Unger S (1967) The psychedelic procedure in the treatment of the alcoholic patient. In: Abramson HA (ed) The use of LSD in psychotherapy and alcoholism. Bobbs-Merrill Company Inc., IndianapolisGoogle Scholar
  38. Kurland AA, Unger S, Shaffer JW, Savage C (1967) Psychedelic therapy utilizing LSD in the treatment of the alcoholic patient: a preliminary report. Am J Psychiatry 123(10):1202–1209CrossRefPubMedGoogle Scholar
  39. Kurland A, Savage C, Pahnke WN, Grof S, Olsson JE (1971) LSD in the treatment of alcoholics. Pharmakopsychiat 4:83–94CrossRefGoogle Scholar
  40. Kurland AA (1997) American College on Neuropsychopharmacology (ACNP) interview by Leo E. Hollister https://www.acnp.org/programs/history.aspx#
  41. Lee MA, Shlain B (1985) Acid dreams: the complete social history of LSD: the CIA, the sixties, and beyond. Grove Press, New YorkGoogle Scholar
  42. Lehmann HE (1993) Before they called it psychopharmacology. Neuropsychopharmacology 8(4):291–303CrossRefPubMedGoogle Scholar
  43. Long SY (1972) Does LSD induce chromosomal damage and malformations? A review of the literature. Teratology 6(1):75–90CrossRefPubMedGoogle Scholar
  44. Mangini M (1998) Treatment of alcoholism using psychedelic drugs: a review of the program of research. J Psychoactive Drugs 30(4):381–418CrossRefPubMedGoogle Scholar
  45. Murphy RC (1967) A psychotherapist’s debt to LSD. In: Abramson HA (ed) The use of LSD in psychotherapy and alcoholism. Bobbs-Merrill Company, Inc., IndianapolisGoogle Scholar
  46. Neill JR (1987) “More than medical significance”: LSD and American psychiatry 1953 to 1966. J Psychoactive Drugs. (1):39–45Google Scholar
  47. Novak SJ (2004) LSD before Leary: Sidney Cohen’s critique of 1950s psychedelic drug research. In: Tracy SW, Acker CJ (eds) Altering American consciousness: the history of alcohol and drug use in the United States, 1800–2000. University of Massachusetts Press, AmherstGoogle Scholar
  48. Oakley R, Ksir C (1999) Drugs, society, and human behavior. McGraw-Hill Companies, Inc., New YorkGoogle Scholar
  49. Oram M (2014) Efficacy and enlightenment: LSD psychotherapy and the Drug Amendments of 1962. J Hist Med Allied Sci 69(2):221–250CrossRefPubMedGoogle Scholar
  50. Oram M (2016) Prohibited or regulated? LSD psychotherapy and the United States Food and Drug Administration. Hist Psychiatry 27(3):290–306CrossRefPubMedGoogle Scholar
  51. Pohlman AD (1957) The use of d-amphetamine sulfate as an adjunct to psychotherapy. J Clin Exp Psychopathol 18(2):159–165PubMedGoogle Scholar
  52. Pollan M (2015) The trip treatment. New YorkerGoogle Scholar
  53. Richards W (2015) Sacred knowledge: psychedelics and religious experiences. Columbia University Press, New YorkCrossRefGoogle Scholar
  54. Rinkel M, DeShon HJ, Hyde RW, Solomon HC (1952) Experimental schizophrenia-like symptoms. Amer. J Psychiatry 108:572Google Scholar
  55. Roseman v (1966) United States, 364 F. 2d 18—Court of Appeals, 9th circuitGoogle Scholar
  56. Ruskin A meeting with Sim, VM, memo (1965) Folder 521.6-525.091. Box 3758, General Subject Files 1938-1974, Division of General Services, RG 88. FDA Records, National Archives II (College Park, College Park, MD)Google Scholar
  57. Savage C, Fadiman J, Mogar R, Allen MH (1967) Process and outcome variables in psychedelic (LSD) therapy. In: Abramson HA (ed) The use of LSD in psychotherapy and alcoholism. Bobbs-Merrill Company Inc., IndianapolisGoogle Scholar
  58. Segal J (ed) (1975) Research in the service of mental health: report of the Research Task Force of the National Institute of Mental Health. DHEW Publication Number (ADM) 75-236, RockvilleGoogle Scholar
  59. Schorr I memo to FDA. (1964) Folder 521.6-525.091. Box 3758, General Subject Files 1938-1974, Division of General Services, RG 88. FDA Records, National Archives II (College Park, College Park, MD)Google Scholar
  60. Schumach M (1966) Distributor of LSD recalls all supplies. New York Times. April 1966Google Scholar
  61. Scully T (2013) Video: “a sketch of the early history of LSD manufacturing”. https://vimeo.com/75282865
  62. Shorter E (2011) A brief history of placebos and clinical trials in psychiatry. Can J Psychiatr 56(4):193–197CrossRefGoogle Scholar
  63. Stoll W (1947) Lysergsäure-diäthyl-amid, ein Phantastikum aus der Mutterkorngruppe. Schweiz Arch Neur 60:1–2Google Scholar
  64. Temple R (2011) Design of clinical trials. Presentation to FDA’s clinical investigator course, https://www.fda.gov/downloads/Training/ClinicalInvestigatorTrainingCourse/UCM283377.pdf
  65. Tjio JH, Pahnke WN, Kurland AA (1969a) LSD and chromosomes: a controlled experiment. JAMA 210(5):849–856CrossRefPubMedGoogle Scholar
  66. Tjio JH, Pahnke WN, Kurland AA (1969b) Pre- and post-LSD chromosomal aberrations: a comparative study. Adv Biochem Psychopharmacol 1:191–204PubMedGoogle Scholar
  67. Tone A (2009) The age of anxiety: a history of America’s turbulent affair with tranquilizers. Basic Books, New YorkGoogle Scholar
  68. Unger SM (1964) LSD and psychotherapy: a bibliography of the English-language literature. Psychedelic Review 1(4):442–49Google Scholar
  69. Unger S (1969) The psychedelic use of LSD: reflections and observations. In: Hicks RE, Fink PJ (eds) Psychedelic drugs. Grune and Stratton, New YorkGoogle Scholar
  70. US bars distribution of LSD ingredients (1966) New York TimesGoogle Scholar
  71. US makes LSD more available for research (1968) Medical World News 9(5):36Google Scholar
  72. Walsh R, Grob CS (2005) Higher wisdom: eminent elders explore the continuing impact of psychedelics. State University of New York Press, AlbanyGoogle Scholar
  73. Weinberger v. Hynson (1973) Wescott & Dunning, Inc 412 US. 609Google Scholar
  74. Yensen R and Dryer D (1992) Thirty years of psychedelic research: the Spring Grove experiments and its sequels. https://associacaopsicodelica.files.wordpress.com/2015/09/30-anos-de-pesquisa-com-psicodc3a9licos-yensen.pdf
  75. Yolles SF (1966) Organization and coordination of Federal Drug Research and regulatory programs: LSD: hearings before the United States Senate Committee on Government Operations, Subcommittee on Executive Reorganization, Eighty-Ninth Congress, Second SessionGoogle Scholar

Copyright information

© This is a U.S. government work and its text is not subject to copyright protection in the United States; however, its text may be subject to foreign copyright protection 2017

Authors and Affiliations

  1. 1.Controlled Substance Staff, Center for Drug Evaluation and Research, Food and Drug AdministrationSilver SpringUSA

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