Autistic Schizophrenic Children: An Experiment in the Use of D-Lysergic Acid Diethyladmide (LSD-25)

Earlier research reviewed by Freedman noted widespread experimentation with LSD-25 since its accidental discovery, both as a psychotomimetic to model psychosis and as a possible therapeutic adjunct. Investigators disagreed about whether LSD experiences truly replicated naturally occurring psychosis; some described drug-induced anxiety and symptom magnification that could free repressed material, while others reported temporary behavioural ‘‘normalizations’’ in some schizophrenic patients. Reports also highlighted large interindividual variability, development of tolerance with repeated dosing, and generally uncertain value of LSD for treating chronic schizophrenia. Against this background, Freedman and colleagues set out to observe the acute effects of LSD in a group of autistic, largely mute, schizophrenic children attending a specialised day school. The study aimed to characterise somatic and psychic reactions after single oral doses, with particular interest in whether LSD might produce marked changes in autism-related behaviours such as muteness or social withdrawal. The investigators framed the work as an exploratory clinical experiment rather than a controlled therapeutic trial.

The investigators conducted an open, observational study at a day school for children with schizophrenia. From a total school population of 40, they selected 12 well-known pupils who met the authors' criteria of autistic schizophrenia; the sample comprised 10 boys and 2 girls aged 5 years 11 months to 11 years 10 months. Seven were essentially mute and the other five used words or phrases only occasionally. Six children were on regular tranquillisers; these medications were withheld for 24 hours prior to LSD administration. LSD was given orally in a familiar vehicle (for example Coca‑Cola or orange juice) to ease administration. Dosing was 100 µg for ten children, 50 µg for one small girl, and one boy received 100 µg initially and a further 100 µg about 2 hours later on one occasion, and 200 µg on a separate occasion; two children received the drug on two occasions. Only one child was dosed per day and a paediatric psychiatrist known to the child remained present from ingestion until the drug’s effects subsided. Physiological measures (blood pressure and pulse) were taken immediately after ingestion when feasible, and careful behavioural notes were recorded. No control group, blinding, or statistical analysis plan is reported in the extracted text; the study is descriptive and based on direct observation of acute reactions. Onset and duration of observable effects were timed and tabulated by the observers.

Onset of observable effects occurred rapidly, typically within about 20 minutes (reported onsets included 15 minutes in 4 instances, 20 minutes in 2, 25 minutes in 3, and 30 minutes in 5). Effects were apparent for a minimum of 4 hours; eight children showed effects for roughly 4–5 hours and one child for more than 5 hours. Somatic findings included facial flushing and pupillary dilatation appearing between about 5 minutes and over 2 hours after ingestion (one child had no obvious facial flush). Pulse and blood pressure showed only changes associated with anxiety; no consistent autonomic instability was described. Evidence of catatonia was observed in 3 instances, with ‘‘waxy flexibility’’ apparent in one child given 200 µg. Marked ataxia occurred in one child and milder ataxia in four others. Appetite was markedly reduced in all children during the drug effect, with virtually none accepting the usual school lunch. Changes in body awareness were common: all but 4 children repeatedly stroked or manipulated a particular area (often lips or mouth) and many sought increased physical contact, sitting on the clinician's or teacher's lap or clinging more than usual. Psychic effects were heterogeneous but notable for rapid mood swings from elation to depression or anxiety. Euphoria occurred in all but one child; that child showed predominating depression and anxiety for over 3 hours. Anxiety ranged from moderate in some instances to severe, with at least one episode described as panic (elevated pulse, shaking, guarding gestures, and clinging). Behaviour suggestive of hallucinations was observed on 7 occasions, with visual phenomena predominating but auditory features also reported. Ten experiments showed increased remoteness from the environment; alertness decreased in about half the cases while it increased in a minority. Eye contact decreased in four children; the extracted text does not clearly report the exact number in whom eye contact increased. Children who already used some words or phrases tended to vocalise more under LSD but did not produce new words; two children experimented with novel sounds. The paper provides case vignettes illustrating variability. ‘‘Nancy’’ (7 years 11 months) became euphoric and highly vocal after 50 µg, later developed prolonged depression and novel whistling but produced no speech. ‘‘Ralph’’ (8 years 4 months) showed marked improvement in affect and activity on one administration (attempting puzzles, apparent joy), later visual hallucination‑like behaviours and alternating elation and depression; on a second 100 µg dose he showed pleasant hallucination‑like signs, transient catatonic hand posturing, and later irritability. Across the group, the hoped‑for change from muteness to sustained speech did not occur.

Freedman and colleagues compared the children's responses to those previously reported in adult schizophrenic patients and found many similarities: mood lability, euphoria, anxiety, disorganisation of behaviour and thought, transient increases in affective display and social contact, and occasional hallucination‑like phenomena. The investigators emphasised that not all children showed identical responses—catatonia and ataxia occurred only in subgroups—but alterations in body awareness and increased vocalisation were common. The authors noted the well documented phenomenon of tolerance to LSD with repeated dosing in both humans and animals and argued that this would limit the potential therapeutic usefulness of repeated administrations in this population. They recognised that children’s inability to verbalise internal experiences constrained interpretation of subjective effects, but considered the observed behavioural changes comparable with adult reactions. Ultimately, the investigators expressed limited optimism about therapeutic benefit: demonstrating clinical utility would require dosing strategies that overcome tolerance, and prior adult experience suggested little reason for optimism regarding durable improvement in schizophrenia. Limitations acknowledged or evident in the report include the small, non‑random sample, the uncontrolled and unblinded design, primarily single acute administrations with minimal follow‑up reported, and reliance on observational notes rather than standardised outcome measures. The authors suggested that continued use on a schedule that could overcome tolerance would be required to test therapeutic potential, but they tempered this by referencing the modest outcomes seen in adult studies.

Twelve autistic, mostly mute, schizophrenic children received LSD on 14 occasions (ten children 100 µg, one 50 µg, one child 100 + 100 µg on one occasion and 200 µg on another). Effects began on average about 20 minutes after ingestion and lasted approximately 4 hours. Somatic effects included facial flushing, pupil dilatation, occasional catatonia and ataxia, loss of appetite, altered body awareness, and increased desire for physical contact. Psychic effects comprised rapid mood swings (elation to depression or anxiety), episodes suggestive of auditory and visual hallucinations, variable changes in alertness and eye contact, increased remoteness in many instances, and greater quantity of vocalisation but no emergence of sustained speech. The authors concluded that although acute behavioural changes were evident, the hoped‑for conversion from muteness to speech did not occur and the prospects for therapeutic success in this population appeared limited.