LSD treatment in Scandinavia: emphasizing indications and short-term treatment outcomes of 151 patients in Denmark

Larsen frames the study against a renewed interest in psychedelics such as LSD and psilocybin for hard-to-treat conditions (for example, end-of-life anxiety, addiction and PTSD) and mentions contemporary positive, small open-label and review studies suggesting therapeutic potential under strict safeguards. At the same time, he notes historical concerns about harms following clinical LSD use and refers to his prior long-term Danish follow-up of 151 patients treated in the 1960s, which found worrying long-term sequelae including frequent flashbacks. The present paper aims to provide a retrospective account of the short-term (acute) outcomes of LSD treatment in those same 151 Danish psychiatric patients, estimating potential beneficial and damaging effects. Larsen positions this as an analysis of archival case material held under the Danish LSD Damages Law to better characterise immediate treatment effects and possible dose–response relationships in this historical clinical cohort.

This is a retrospective review of LSD case material held in the Danish State Archives relating to 151 patients who had been treated with LSD in Denmark and who subsequently applied for and received compensation under the LSD Damages Law (applications had to be submitted by 1 June 1988). The wider context is that nearly 400 patients were treated with LSD in Denmark from 1959 to 1973, primarily at Frederiksberg Hospital but also at other psychiatric departments nationwide; the archival material here consists only of those applicants whose records were preserved for the compensation process. The tribunal handling compensation posed questions about each patient's psychiatric diagnosis and mental state before and immediately after LSD treatment. Specialist certificates addressing these questions were available for a large proportion of cases (reported as 111/154, 74%, in the extracted text) and additional responses were obtained from treating departments when needed. All reports in the archive date from roughly 25 years after the treatments and were based on contemporary case notes, patient applications and other case material; original 1960s research questionnaires were largely absent or incomplete. Larsen reviewed the archive material twice in 2013 and extracted simple categorical short-term outcomes (improved, unchanged, or worsened). He also constructed an LSD dose-index for each patient by multiplying the maximal LSD dose by the number of treatment sessions and dividing by 100, to explore a possible dose–effect relationship. Subgroup analyses described in the paper focus on neurotic diagnoses (depressive, character, anxiety and unspecified neuroses), a subgroup with anancastic (obsessive–compulsive) neurosis, and a small group treated with psilocybin either alone or in combination with LSD. The author notes that no more granular response categories were pursued beyond the basic outcome counts.

The archival material shows LSD was applied across a wide spectrum of psychiatric diagnoses. Using the categorical outcome coding, 52 patients were judged to have improved acutely after LSD treatment and 48 patients were judged to have acutely worsened; the remainder were described as unchanged or were not clearly classified in the extracted text. A few patients developed transient overexcitement during treatment (examples given: one patient in depressive neurosis, one in anancastic neurosis, two in anxiety neurosis and two in character neurosis). In subgroup analyses, 82 out of 134 patients (61%) could be classified within a cluster of neurotic diagnoses (depressive, character, anxiety and unspecified neuroses). In that subgroup the LSD dose-index was significantly higher in patients who acutely deteriorated compared with those who improved (p < .01), indicating a dose–index association with acute worsening. Treatment intensity was often high: 123/151 (81%) patients received six or more LSD sessions, five patients completed more than 50 sessions, and 35/144 (24%) completed more than 20 sessions (the number of sessions was not recorded in seven patients). Initial doses were often 25–50 micrograms and commonly increased to 200–250 micrograms; 14 patients received maximal doses above 400 micrograms. Within the neurotic subgroup nine patients received doses above 400 micrograms, distributed across improved, unchanged and deteriorated outcome categories. Nineteen patients were recorded with anancastic (obsessive–compulsive) neurosis; five of the eight patients who later underwent psychosurgery came from this group, and two additional anancastic patients were recommended psychosurgery but declined. Across the whole sample, three other psychosurgery cases were classified with depression (two patients) and anxiety neurosis (one patient). Larsen provides illustrative clinical vignettes: one female patient completed 27 sessions with a maximum dose of 550 micrograms and described marked fear and distress between sessions without benefit, while another patient underwent 56 sessions with a maximum dose of 450 micrograms and subsequently had a psychotic breakthrough requiring compulsory admission; that latter patient later received maximal compensation and free treatment. The tribunal records also included 12 patients treated with psilocybin, either alone or in combination with LSD; their outcomes were recorded alongside the LSD cases. The extracted text notes that the long-term outcome for most patients was poor, but the detailed long-term analyses are reported elsewhere.

Larsen emphasises that the archival material is uneven: contemporary 1960s records were often sparse or missing, and the follow-up reports were written about 25 years after treatment, relying on remaining case notes and patient statements. He interprets the short-term findings as showing that roughly one third of patients experienced transient improvement while about another third experienced acute deterioration after LSD treatment, a contrast with some earlier reports that found fewer deteriorations but which themselves reported serious adverse events such as suicides. Selection and procedural shortcomings are highlighted as likely contributors to adverse outcomes. The author notes that many Danish patients were not carefully screened according to early international recommendations and that psychotic or pre-psychotic individuals were sometimes treated despite cautions against this. He contrasts the Danish experience with Norwegian and Swedish series where selection criteria, lower dosing and closer follow-up may have yielded fewer deteriorations; for example, Norwegian centres generally used lower maximal doses (commonly 25–100 micrograms and seldom above 300 micrograms) and reported lower rates of worsening. Larsen situates his findings within more recent population studies that did not find an association between lifetime psychedelic use and later mental illness, and a large study that suggested reduced psychological distress and suicidality among psychedelic users. He stresses that these population analyses are not directly comparable because the Danish archive represents a highly selected clinical sample of severely ill patients who underwent clinical LSD treatment. He also acknowledges substantial confounders in the archive data, including the possibility of economic motivations to apply for compensation, incomplete preservation of records, unknown denominators (why other treated patients did not apply) and missing treatment details for some patients. The author reiterates that a higher LSD dose-index was associated with acute deterioration in his material, but notes that this dose–harm relationship has not been uniformly observed in other studies. Finally, he endorses rigorous patient selection and modern safety guidelines for clinical psychedelic research (for example, excluding individuals with current or family histories of psychotic or bipolar disorders), and concludes that, based on this historical clinical cohort, the use of LSD and psilocybin in severely ill psychiatric populations may carry a high risk of serious short- and long-term harms. Further randomised, well-controlled trials in carefully selected populations are needed before the wider clinical utility in general psychiatry can be clarified.

Larsen concludes that psychedelics such as LSD and psilocybin, when used in severely ill psychiatric patients as historically practised in Denmark, may be associated with a high risk of serious short- and long-term adverse effects. He advises careful patient selection (including exclusion of those with severe psychopathology), the use of lower doses and avoidance of outpatient-only administration to reduce risk, but cautions that no approach guarantees safety. The author calls for further trials with rigorous designs in selected populations before the clinical role of psychedelics in general psychiatry can be considered clarified.