TABLE 2.
Early clinical trials (1961–1970) assessing the use of psychedelics in “autistic schizophrenic” children. The terms “autistic” and “schizophrenic” do not reflect the currently approved terminology of the DSM-V, but rather the terminology that was used at the time of these early studies.
| Year | Title | Cohort | Design | Compound | Regimen (dose, frequency, route of administration) | Main outcomes | Side effects | Ref |
|---|---|---|---|---|---|---|---|---|
| 1961 | Treatment of Autistic Schizophrenic Children with LSD-25 and UML-491 | Hospitalized “autistic-schizophrenic” children (n = 14, 11 boys, 3 girls, 6–10.5 years old) | Open label | LSD | LSD | LSD | LSD | Bender et al. (1961) |
| L-methyl-D-Iysergic acid butanolamide (UML-491) | Acute–25 μg, intramuscular | Acute–Improved behavioural patterns. Children unusually interested in the surrounding environment and seeking physical interaction. Children engaged in playful activities such as hand clapping and body swaying. Decreased appetite | No severe side effects reported. 2 prepuberal (10-year-old) children displayed disturbed anxious behaviour and were dropped from the study UML-491 | |||||
| Repeated–100 μg, per oral solution, once per week in the early morning | ||||||||
| Subsequently increased to 100 µg per oral solution 2 to 3 times per week | Repeated - When given 2–3 times per week, effects persist: decreased aggressive behaviour towards peers, increased interaction-seeking and emotional and physical closeness with peers and adults, more spontaneously playful, improvements in physical condition, “rosy” color rather than “blue” or “gray” and increased weight gain, enhanced understanding of environmental stimuli and more appropriate reactions to them, higher maturity in the Vineland Maturity Scale rating. Increased inorganic phosphate blood level. Changes appear to become chronic with continuous administration of the drug UML-491 | Motor restlessness, irritability, localized muscle tensions or spasms, mild “crawling” skin sensations | ||||||
| Finally, 100 µg per oral solution daily for 6 weeks UML-491,8 mg divided in 4 doses daily | ||||||||
| Other pharmacological treatments interrupted at the onset of treatment with LSD and UML-491 | Enhanced mood, relief of episodic headaches, relief of perceptual hypersensitivity in visual, auditory, olfactory, and skin sensations, general sense of wellbeing with improved sleep patterns | Episodes of changing muscle tensions and kinesthetic sensations with clowning, staggering gait, and twisting of the neck, back, and arms | ||||||
| 1962 | Autistic Schizophrenic Children. An Experiment in the Use of D-Lysergic Acid Diethylamide (LSD-25) | “Autistic-schizophrenic” children (n = 12, 10 boys, 2 girls, aged 5 years 11 months to 11 years 10 months) | Open label | LSD | 100 µg (1 girl 50 μg, 1 boy 200 µg), per oral solution, once or twice. Other Pharmacological treatments (unspecified tranquillizers, interrupted 24 h prior to LSD treatment) | Increased body awareness | Sharp and rapid mood swings Severe anxiety (4 children) Moderate anxiety (3 children) Panic-like state (1 child) Children seemed to be experiencing auditory and visual (the latter more predominant) hallucinations Catatonia (3 children) |
Freedman et al. (1962) |
| Desire for increased physical contact Repetitive behaviours disappeared and then reappeared as LSD wore off Two of the non-verbal children seemed to experiment with new sounds | Acute ataxia (1 children) | |||||||
| Decreased appetite | Acute mild ataxia (4 children) | |||||||
| 1963 | Interim report on Research project: An Investigation to Determine Therapeutic Effectiveness of LSD-25 and Psilocybin on Hospitalized Severely Emotionally Disturbed Children | Hospitalized Severely Emotionally Disturbed Children (n = 12, 4 y 10 m—12 y 11 m, average 9 y 10 m) | Unknown | LSD Psilocybin | LSD alone (50–400 μg, typical dosage 200–300 µg) | Increased sociability Increased face gazing Decreased anger outbursts | 2 episodes of seizures (1 girl) developed during treatment which was discontinued in this child | Fisher and Castile, (1963) |
| Psilocybin alone (10–20 mg, typical dosage 14–16 mg) LSD (100–300 μg, typical dosage 200 µg) + psilocybin (10 mg) | Increased parent relatedness | |||||||
| Librium (10 mg) and Methedrine (5 mg) were used as pre-treatment medication in some sessions | Increased relatedness to peers and adults | |||||||
| “3 grains of dilantin” administered the night before treatment to reduce the likelihood of seizures | Increased desire to communicate | |||||||
| “Boosting” dose (LSD 25–100 µg) available if the child seemed to be a) caught in a problem or area that he could not break through, b) regressing to psychotic and stereotyped behaviour, c) defending themselves from new experiences | Decreased anxiety and compulsive behaviour for about 1 day following the treatments | |||||||
| 1–11 treatments, every 14 days–1 month | 1 self-harming girl who was in continuous restraint to prevent fatal self-harm stopped self-harming, did not need restraints anymore and became toilet-trained Children who respond better | |||||||
| - Have speech | ||||||||
| - Are more “schizophrenic” than “autistic” | ||||||||
| - Are older (10–12 y/o) | ||||||||
| 1963 | LSD and UML treatment of hospitalized disturbed children | Hospitalized children (n = 50). Half displayed autism spectrum disorder features and half displayed psychotic features | Open label | LSD | LSD gradually increased from 50 to 150 µg daily, divided in two doses UML gradually increased from 4 to 12 mg daily, divided in two doses | Increased responsiveness to environmental stimuli | No serious adverse events | Bender et al. (1963) |
| UML | Daily administration, duration of treatment: 2–12 months | Increased alertness, awareness, and affectionate behaviour | Some of the quieter “autistic” children became mildly aggressive | |||||
| Some of the more aggressive children became remarkably quieter after LSD treatment | ||||||||
| Decrease of regressive behaviour in some “autistic” children | ||||||||
| Improved food habits and interest in new foods | ||||||||
| Improved vocabulary in some of the children | ||||||||
| After taking the children off LSD their behaviour regressed but to a lesser extent | ||||||||
| 1966 | Modification of autistic behaviour with LSD-25 | “Autistic” twin males (4 years 9 months old at study start, 5 years 2 months at study end) | Double-blind placebo-controlled | LSD | LSD 50 µg per oral solution 9 treatments, twice weekly 50 mg oral. chlorpromazine to terminate the LSD effects after 3 h | Increased eye-to-face contact during LSD sessions | None reported | Simmons et al. (1966) |
| Increased responsiveness to adults | ||||||||
| Increased movements towards the experimenter; decreased movements away from the experimenter | ||||||||
| Decreased repetitive behaviours during LSD sessions | ||||||||
| Increased smiling and laughing behaviour | ||||||||
| 1966 | The Treatment of Childhood Schizophrenia with LSD and UML | “Autistic”, regressed, verbal, psychotic and “schizophrenic” (different groups) pre-and post-puberty male and female children 6–15 years of age (total n = 54) | Open label | LSD | LSD | Prepuberty “autistic” boys | In “autistic” prepuberal boys, no regressions were observed although some children had episodic occurrences of aggressive contact with other children and feces smearing | Bender et al. (1966) |
| UML | 100–150 μg, daily in 2 doses UML | All participants show some mild (variable) degree of favorable response with slow and steady progression | One of the “autistic” prepuberal girls became too active and aggressive towards other children (reserpine was administered with LSD to counteract these effects) | |||||
| 12 mg daily, divided in 2 doses | ||||||||
| Duration of treatment: 2–18 months, with an average of 9 months | Participants were happier following the ingestion of the drug and this tended to carry over through the whole day | Some of the “autistic” postpuberal boys attempted to interact with others via biting and pinching | ||||||
| Participants became spontaneously more playful with toys, other children and adults | ||||||||
| Participants sought and responded to physical contact and affection | ||||||||
| Decreased overall aggressive behaviour | ||||||||
| Food habits and toilet-training improved in some participants | ||||||||
| Improved skin color and overall physical health | ||||||||
| Decreased rhythmic and stereotyped behaviour | ||||||||
| Increased responsiveness to environmental cues, stimuli and patterns | ||||||||
| Increased laughing behaviour | ||||||||
| Increased maturity in the Vineland Social Maturity Scale (the authors suggest that the real improvements are underestimated by this scale) | ||||||||
| Prepuberty “autistic” girls | ||||||||
| No detectable improvement in maturation or social maturity | ||||||||
| Two of the three girls seemed brighter and improved in color, weight gain, and eating and toilet habits | ||||||||
| Postpuberty “autistic” boys | ||||||||
| Similar responses to younger “autistic” children although responses are attenuated compared to prepuberty “autistic” boys | ||||||||
| Increased typical behaviours such as climbing, ball bouncing and rocking | ||||||||
| Strong improvement in verbalization and speech appropriateness in one boy | ||||||||
| For the first time, some children attempted to contact/approach adults | ||||||||
| 1970 | The Psycholytic Treatment of a Childhood Schizophrenic Girl | Case report (1 of the “autistic-schizophrenic” girls of the clinical trial by Freedman et al., 1962 | Open label | LSD Psilocybin | 16 treatments over 11 months with LSD alone (50–300 μg, n = 13 treatments), psilocybin alone (10–20 mg, n = 2 treatments), or LSD (200 µg) + psilocybin (10 mg, n = 1 treatment) | Increased motor and verbal behaviour, increased desire for physical contact, the child was delighted and excited with perceptual changes. Decreased repetitive movements. Enhanced sense of humor; she was able to feel and relate to others in a “normal” way | Mood swings including | Fisher, (1970) |
| Methedrine (5 mg) and Librium (10–25 mg) given in some instances in combination with LSD (200–300 µg) and psilocybin (10 mg) + LSD (200 µg) | At the end of the treatment she reached a state of deep acceptance and profound feelings of love and personal integration. She ceased her isolated, “autistic” behaviour, talked rationally, and helped other children. Despite scarce follow-up records, she seemed to have stabilized at 5 years follow-up | Anxious behaviour, restless behaviour, angry behaviour, stuffing objects in her mouth | ||||||
| Emergence of internal conflict and anger led to anxious, agitated, and self-harming behaviour | ||||||||
| At the end of treatment 4, she became very violent and tried to choke herself as well as others |