Prohibited or regulated? LSD psychotherapy and the United States Food and Drug Administration

Oram situates the paper in the context of vigorous clinical investigation of LSD in the 1950s and early 1960s, when many psychiatrists explored the drug as an adjunct to psychotherapy and some studies reported promising outcomes (for example, a 1950s Canadian study reported a 50% improvement rate in treatment‑resistant alcoholics). Growing public recreational use of LSD in the mid‑1960s generated political alarm and a sequence of increasingly strict laws culminating in LSD's placement in Schedule I in 1970. Many historians have therefore attributed the near‑cessation of LSD psychotherapy research by the mid‑1970s to punitive federal regulation that effectively shut down legitimate research. This article challenges that standard narrative. Oram examines how the Food and Drug Administration (FDA) implemented the investigational drug (IND) regulations created by the Drug Amendments of 1962 and traces how those administrative rules, together with actions by the drug manufacturer Sandoz and changing norms for pharmaceutical research, altered the landscape for LSD psychotherapy. The paper aims to show that LSD research was not simply prohibited by the federal government; rather, the combination of formalised IND requirements, manufacturer control over proprietary data, and later methodological and funding difficulties better explains the decline in research.

Oram conducts an archival and documentary historical analysis focused on FDA regulatory files, congressional hearing transcripts, and corporate correspondence from the period 1963–1966, supplemented by contemporaneous publications and investigators' accounts. The study follows specific IND submissions and reviews—notably Sandoz's IND for LSD and psilocybin, Harold Abramson's independent IND, and the International Foundation for Advanced Study's IND—to interrogate how the new IND regime was applied in practice. The paper traces administrative decisions by examining FDA internal reviews and correspondence, the content and timing of regulatory rules (for example the IND form Form FD 1571 and the deadlines set in 1963), and exchanges between Sandoz, independent investigators, and federal agencies. Oram also uses congressional hearing records (including sessions chaired by Senator Robert F. Kennedy and other 1966 hearings) to reconstruct public controversies and the interactions among the FDA, the National Institute of Mental Health (NIMH), the Veterans Administration, and Sandoz. Where appropriate, the study integrates published scientific reports and testimony to contextualise the investigators' qualifications, research methods (psycholytic vs psychedelic therapy), and institutional settings.

Oram reports that the IND regulations introduced in 1963 required sponsors to submit detailed preclinical, manufacturing and investigator information before clinical research could proceed; research could begin on submission but the FDA retained authority to terminate an IND if the documentation was inadequate. Sandoz submitted broad, hospital‑restricted INDs for LSD and psilocybin and initially supported a limited cohort of investigators: Sandoz listed about 17 investigators early on and the number rose to approximately 70 by 1966. However, Sandoz restricted sponsorship to hospital‑based projects supported by NIMH, state agencies or the Veterans Administration, effectively cutting off many private and non‑institutional researchers. Two notable independent IND efforts failed. Harold Abramson’s IND was assessed as deficient in preclinical toxicity data and in information on manufacturing controls; because much of the required chemical and manufacturing data were held confidentially by Sandoz, Abramson could not supply them or rely on FDA access to those files without Sandoz’s written consent. The FDA concluded Abramson’s IND did not contain sufficient data to show it was reasonably safe to begin clinical work and terminated the IND (notice sent 23 July 1965). The International Foundation for Advanced Study, led by Myron Stolaroff with medical director Charles Savage, likewise struggled to supply animal and manufacturing data and was criticised for gaps in investigator qualifications and study controls. Its IND was recommended for termination multiple times and was formally terminated on 2 February 1965; Savage’s departure from the project was a decisive factor cited by the FDA. Sandoz’s voluntary withdrawal of its INDs and its decision to recall most investigator supplies occurred in April 1966, a step the company attributed to growing illicit use and public controversy. This produced an abrupt reduction in the number of active Sandoz‑sponsored studies (Senator Kennedy noted a drop from about 70 to nine in April 1966). Oram documents that federal agencies did not simply allow research to collapse: the FDA, NIMH, and the Veterans Administration met in late 1965 and agreed arrangements so that a limited number of investigators (12) could continue while they prepared INDs, and Sandoz transferred remaining stocks to the NIMH for distribution to legitimate grantees. Later statutory changes increased administrative burden: the Controlled Substances Act of 1970 placed LSD in Schedule I, which meant that research required additional registration through the Attorney General (with a review by the Secretary of Health, Education, and Welfare). Oram notes that the NIMH continued funding psychedelic research until 1974 and that research in the USA did not finally cease until the mid‑1970s, but also reports a clear decline through the 1970s. The paper highlights that other factors beyond regulatory prohibition contributed to the waning of LSD psychotherapy, notably difficulties in demonstrating efficacy in the randomized controlled trial frameworks required after the 1962 amendments, and waning scientific and funding support when trials returned mixed or underwhelming results. The extracted text also records ancillary findings such as the Foundation administering LSD to roughly 350 subjects over its active period.

Oram interprets these findings as showing that the decline of LSD psychotherapy research in the 1960s and early 1970s reflected a transformation of the research system rather than a simple, deliberate governmental prohibition. The IND regulations formalised pre‑market research, privileging sponsors who could provide detailed preclinical and manufacturing data and thereby shifting practical control toward drug manufacturers. Because Sandoz elected to restrict sponsorship and maintain the confidentiality of its data, many independent and non‑institutional investigators found it difficult or impossible to satisfy IND requirements; this corporate choice, rather than direct FDA hostility, was a key bottleneck. The paper challenges prior historical claims that the government deliberately shut down LSD research, showing instead that the FDA assessed applications according to the new statutory criteria and that the FDA, NIMH and Veterans Administration took active steps to preserve legitimate research after Sandoz’s withdrawal. Oram acknowledges, however, that subsequent legal steps—the Drug Abuse Control Amendments of 1965 and the Controlled Substances Act of 1970—tightened controls and added burdens that could discourage investigators. He also emphasises methodological and epistemological factors: the 1962 requirement for demonstration of efficacy through controlled trials was ill suited to many proponents’ claims about psychotherapeutic, context‑dependent benefits of LSD, and trial results in the late 1960s and early 1970s often failed to produce clear positive evidence. These scientific and funding developments, combined with administrative hurdles, help explain why research dwindled by the mid‑1970s. Oram notes limits in attributing causation: the archival record shows multiple interacting influences—regulatory formalisation, manufacturer policy, changing standards of evidence, public controversy and later criminal‑law scheduling—and disentangling their relative weight is complex. The author positions this case within broader histories of drug regulation, arguing that the IND regime reshaped clinical research practices and that the fate of LSD psychotherapy illustrates how novel, practice‑dependent treatments can be disadvantaged by shifting regulatory and evidentiary norms.

Oram concludes that LSD psychotherapy was transformed, not simply prohibited, during the 1960s. The Drug Amendments of 1962 and their IND regulations moved drug research toward formal, sponsor‑driven, institutionally anchored trials. Sandoz’s decision to restrict its sponsorship and to withdraw its IND in 1966 constrained many independent investigators, but federal agencies subsequently acted to preserve core research by transferring stocks and allowing interim continuance for some projects. Ultimately, the combination of regulatory formalisation, manufacturer control over proprietary data, and difficulties in demonstrating psychotherapeutic efficacy within the new clinical trial paradigms—rather than an outright governmental ban on medical research with LSD—best accounts for the discipline’s decline by the mid‑1970s.