OPEN Foundation

Day: 29 May 2014

Autisme en LSD-25 – Het Bevrijden van de Meest Gevangen Geesten?

In het begin van de jaren zestig zijn er een aantal controversiële klinische studies gepubliceerd waarin jonge kinderen met een autisme en/of ‘childhood-onset schizophrenia’ (COS) [1] diagnose LSD-25 (Lysergeenzuurdi-ethylamide) kregen toegediend. De reden dat deze studies werden uitgevoerd bij jonge kinderen was de veronderstelde gelijkenis van autisme en COS. Eerdere resultaten van onderzoek met LSD bij volwassen catatonische patiënten, gepubliceerd in Journal of Nervous and Mental Disease door Cholden, Kurland en Savage (1955), dienden als inspiratie voor dit onderzoek. “The goal in these therapeutic efforts”, schreef Bender in een artikel gepubliceerd in Recent Advances in Biological Psychiatry (1962), “has been to modify the secondary symptomatology associated with retarded, regressed, and disturbed behavior of the children”. Het grootste gedeelte van de kinderen in deze studies was tussen de zes en tien jaar oud en reageerde niet op andere vormen van therapie. Dat de kinderen niet behandeld konden worden rechtvaardigde volgens de onderzoekers het gebruik van sterke psychoactieve stoffen. Dergelijk onderzoek zou tegenwoordig uiteraard niet zomaar door de ethische commissie worden geaccepteerd.

Een farmacologische interventie door middel van LSD zou de vertraagde ontwikkeling veranderen naar een (enigszins) normaal ontwikkelingspatroon (Bender, 1962). Hoe het toedienen van LSD zou kunnen resulteren in “het bevrijden van de meest gevangen geesten” was echter nog onbekend (Mogar & Aldrich, 1969). LSD zou succesvol kunnen worden ingezet bij de behandeling van autisme vanwege het vermogen “door de autistische verdediging heen te breken” (Bender, 1963), en daarom bijzonder nuttig kunnen zijn in gebieden “closely related to the process of psychotherapy” (Simmons et al., 1966). Sommigen geloofden dat LSD bijzonder bruikbaar was om patiënten te helpen onderdrukt subbewust materiaal te “deblokkeren” in combinatie met andere psychotherapeutische methoden (Cohen, 1959). Ook waren er therapeuten die zelf LSD namen om een diepere bewustwording van de schizofrene ervaring te krijgen. “During the ‘model psychosis’ phase of LSD research when the psychedelic state was considered a chemically-induced schizophrenia”, zegt pionier LSD onderzoeker Stanislav Grof (1980), “LSD sessions were recommended as reversible journeys into the experiential world of psychotics which had a unique didactic significance”.

Sommige onderzoekers, zoals Freedman et al. (1963), onderzochten LSD vanwege de zogenaamde psychotomimetische eigenschappen, waarmee wordt bedoeld dat het middel symptomen van een psychose na zou bootsen, inclusief wanen en delierachtige verschijnselen, in plaats van alleen hallucinaties op te wekken (Sewell et al., 2009). Een versterking van ‘typische’ symptomen betekende de mogelijkheid om de (kinder)schizofrene conditie te bestuderen en mogelijk een therapeutische interventie te ontwikkelen. Andere onderzoekers (Bender et al., 1963; Rolo, et al., 1965) beschouwden de neurologische mechanismen achter de effecten van LSD, die toen nog zeer obscuur waren, als belangrijker dan de rol als facilitator van het therapeutische proces. LSD wekte bijvoorbeeld theoretische interesse omdat het serotonineactiviteit zou kunnen remmen en het autonome zenuwstelsel zou stimuleren. Bender et al. (1963) concludeerden dat “het toedienen van dagelijkse orale doseringen van 100 mcg [2] LSD-25 aan prepuberale autistische schizofrene kinderen effectief lijkt te zijn als een stimulant van het autonome en centrale zenuwstelsel”, en dat deze veranderingen “chronisch lijken te zijn bij een continue toediening van het middel”. Continue toediening bestond uit het dagelijks toedienen, variërend van enkele dagen tot een paar weken. Tot de meest robuuste effecten die werden gepubliceerd behoren een verbeterde spraak, verhoogde emotionele responsiviteit, positievere stemming (veel lachen) en een vermindering van compulsief gedrag.

Maar helaas, hoe interessant en aantrekkelijk deze resultaten ook leken te zijn – het bewijs was niet sterk genoeg. Tegenwoordig zijn er geen studies naar de relatie tussen LSD en autisme en de resultaten van deze eerdere studies worden als zeer controversieel of volledig achterhaald beschouwd. Dit komt gedeeltelijk, achteraf gezien, doordat de studies zeer grote tekortkomingen hadden. De onderzoekers gingen geheel voorbij aan de conceptuele controverse omtrent de definitie van autisme en/of (kinder)schizofrenie (Bender et al., 1962). Het debat over de correcte plaats van autisme binnen de DSM (Diagnostic and Statistical Manual of Mental Disorders) blijft tot op de dag van vandaag problematisch (DSM-V), maar autisme is al lang gescheiden van de psychotische stoornissen. Hoewel beide soorten stoornissen klinische eigenschappen delen beschouwen klinisch psychologen en psychiaters ze tegenwoordig als aparte diagnostische entiteiten. Omdat LSD onder andere werd gebruikt als een versterker van reeds bestaande symptomatologie van schizofrenie (Bender et al., 1962), zou een conceptuele scheiding tussen beide stoornissen de fundering van de resultaten hebben verzwakt.

Zelfs al hadden de onderzoekers gekozen om wel in te gaan op deze controverse, dan was de validiteit van de gebruikte steekproeven in de meeste onderzoeken achteraf gezien zeer problematisch geweest. De kinderen in de onderzoeken waren demografisch en wat leeftijd betreft erg gevarieerd. Niet alle onderzoekers waren het eens over de relatie tussen leeftijd en reactie op het middel, maar Bender stelde dat in tegenstelling tot preadolescenten, jongere kinderen consistent verschillende reacties vertoonden (1962). “Older children”, concludeerden Fisher en Castile daarentegen, “were better candidates for psychedelic therapy because verbal communication was possible and also because they tended to be less withdrawn, more schizophrenic than autistic, and displayed more blatant symptomology” (Mogar & Aldrich, 1969). Daarbij komt dat de symptomen van de behandelde kinderen heterogeen waren en dat er niet werd gecorrigeerd voor de ernst van de symptomen. Er was geen sprake van randomisering en in de meeste studies was er sprake van fluctuerende doseringen en frequentie van toediening. Ten slotte varieerde de set en setting van de experimenten sterk.

Hoewel de studies die in de jaren zestig verricht zijn belangrijke gebreken hadden vanuit een experimenteel oogpunt, beargumenteren Mogar en Aldrich in een artikel dat gepubliceerd is in Behavioral Neuropsychiatry (1969) dat de resultaten, als geheel bekeken, wel aanwijzingen bieden om de potentie van LSD bij de behandeling van autisme nader te onderzoeken. “The significance of seemingly contradictory results”, zeggen Mogar and Aldrich, “has often been obscured by the persistent search for static, ‘drug-specific’ reactions to LSD”. Dit is een interessant punt; ondanks dat de resultaten niet significant zijn in experimentele termen, is er wellicht wel een therapeutisch potentieel. Mogar en Aldrich rapporteren dat sterkere therapeutische effecten gerelateerd waren aan “(a) the degree of active therapist involvement with the patient; (b) an opportunity to experience meaningful objects and interpersonal activities; and (c) congenial settings that were reasonably free of artificiality, experimental or medical restrictions, and mechanically administered procedures” (1969). In de praktijk staat klinische therapie vaak ver van de theorie. Het zou kunnen zijn dat LSD, dat zelf ook een erg onvoorspelbaar middel is, in combinatie met de therapeutische dynamiek gewoonweg moeilijk is om te onderzoeken. “The administration of LSD is inextricably embedded in a larger psychosocial process”, concluderen Mogar en Aldrich, ”which should be optimized in accordance with particular treatment goals”.

Gezien de recente groei van aandacht voor dit onderzoeksveld, kan het nuttig zijn om deze oudere en nogal obscure studies te herevalueren. Onderzoekers van LA BioMed (Los Angeles Biomedical Research Institute) zijn momenteel een studie aan het opzetten waarin de effectiviteit van MDMA (3,4-methylenedioxy-N-methylamphetamine) bij de behandeling van sociale angst bij volwassenen met autisme zal worden onderzocht. Dit is de meest recente ontwikkeling in een groeiend programma van onderzoek naar de therapeutische eigenschappen van MDMA, gefinancierd door de non-profit Multidisciplinary Association for Psychedelic Studies (MAPS). “This new study will give us a chance”, zegt hoofd van het onderzoeksteam Charles Grob (2014), “to determine the actual effects of differing dosages of medication that we know for certain is pure MDMA on adults on the autism spectrum. If the results of this research warrant further investigation, data from this study will be used to design additional clinical trials”. Nu de beperkingen om de psychedelische ervaring en de therapeutische potentie van deze middelen te onderzoeken beginnen weg te vallen, en ook LSD weer opnieuw wordt onderzocht, kunnen de resultaten van deze oudere publicaties dienst doen voor het genereren van nieuwe hypothesen.


 
[1] Zie (Abramson, 1960; Bender, et al., 1962; Bender, et al., 1963; Fisher & Castile, 1963; Freedman, et al., 1962; Rolo, et al., 1965; Simmons, et al., 1966).
[2] Een gebruikelijke dosering LSD varieert van 100 tot 200 mcg, en een sterke dosering van 200 tot 600 mcg.
 
Referenties
Abramson, H.A. (Ed.) (1960). The Use of LSD in Psychotherapy. New York: Josiah Macy Foundation.
Bender, L., Faretra, G., & Cobrinik, L. (1963). LSD and UM-L treatment of hospitalized disturbed children. Recent Advances in Biological Psychiatry, 5, 84-92.
Bender, L., Goldschmidt, L., & Sankar, S.D.V. (1962). Treatment of autistic schizophrenic children with LSD-25 and UML-491. Recent Advances in Biological Psychiatry, 4, 170-177.
Cholden, L., Kurland, A., & Savage, C. (1955). Clinical reactions and tolerance to LSD in chronic schizophrenia. Journal of Nervous and Mental Disease, 122, 211-216.
Cohen, S., & Eisner, B. G. (1959). Use of lysergic acid diethylamide in a psychotherapeutic setting. AMA Archives of Neurology & Psychiatry, 81(5), 615-619.
Freedman, A.M., Ebin, E.V., & Wilson, E.A. (1962). Autistic schizophrenic children: An experiment in the use of d-lysergic acid diethylamide (LSD-25). Archives of General Psychiatry, 6, 203-213.
Gettys, T. (2014). MDMA Helps Reduce Social Anxiety for Autistic Adults, and Researchers Want to Find Out How. MAPS. Retrieved at: http://www.maps.org/media/view/mdma_helps_reduce_social_anxiety_for_autistic_adults_and_researchers_w/
Grof, S. (1980). LSD Psychotherapy. California: Hunter House Publishers.
Mogar, E. R., & Aldrich, W. R. (1969). The Use of Psychedelic Agents with Autistic Schizophrenic Children. Behavioral Neuropsychiatry, 1(8), 44-50.
Rolo, A., Krinsky. L.W., Abramson, H.A., & Goldfarb, L. (1965). Preliminary method for study of LSD with children. International Journal of Neuropsychiatry, 1, 552-555.
Sewell, R. A., Ranganathan, M., & D’Souza, D. C. (2009). Cannabinoids and psychosis. International Review of Psychiatry, 21(2), 152-162.
Simmons, J.Q., Leiken, SoJ., Lovaas, Q.I., Schaffer, B., & Perloff, B. (1966). Modification of autistic behavior with LSD-25. The American Journal of Psychiatry, 122, 1201-1211.

Autism and LSD-25 – Freeing the Most Imprisoned Minds?

In the early sixties, a number of controversial clinical investigations were published involving the administration of LSD-25 (lysergic acid diethylamide) to young children said to suffer from severe forms of autism, or childhood-onset schizophrenia (COS), which were then regarded as closely related [1]. The reason for conducting the studies with young children was the supposed similarity between autism and COS. Prompted by the apparent results of studies conducted with LSD-25 and adult mute catatonic patients by Cholden, Kurland, and Savage (1955), hypotheses were constructed to research a possible therapeutic utility. “The goal in these therapeutic efforts”, said Bender in an article published in Recent Advances in Biological Psychiatry (1962), “has been to modify the secondary symptomatology associated with retarded, regressed, and disturbed behavior of the children”. The larger part of the children treated with LSD in these studies were between six and ten years old and completely unresponsive to all other forms of treatment. That the children couldn’t be treated by other means served, in part, for the justification for using a powerful psychoactive substance in child experiments. Surely this decision would have been criticized by the ethical commission today.

A pharmacological intervention by means of LSD was said to “nudge the lagging maturation” (Bender, 1962) into a (somewhat) normal developmental pattern. How exactly the administration of LSD would accomplish the “freeing of the most imprisoned minds” was still unknown (Mogar & Aldrich, 1969). LSD was supposed to achieve success through “breaking through the autistic defense” (Bender, 1963), and in this way be exceptionally helpful in “areas which are closely related to the process of psychotherapy” (Simmons et al., 1966). Some believed LSD was especially useful at helping patients to “unblock” repressed subconscious material through other psychotherapeutic methods (Cohen, 1959). Therapists took LSD to establish a connection with the experience of schizophrenia. “During the ‘model psychosis’ phase of LSD research when the psychedelic state was considered a chemically-induced schizophrenia”, says pioneer LSD researcher Stanislav Grof (1980), “LSD sessions were recommended as reversible journeys into the experiential world of psychotics which had a unique didactic significance”.

Some researchers, like Freedman et al. (1963), studied LSD for its supposed psychotomimetic (psychotogenic) properties, meaning that the drug mimics the symptoms of psychosis, including delusions and/or delirium, as opposed to merely hallucinations (Sewell et al., 2009). An exacerbation of ‘typical’ symptoms meant an opportunity for studying the (child)schizophrenic condition. Other researchers (Bender et al., 1963; Rolo, et al., 1965) considered the neurological mechanism behind the effect of LSD, which in that time was still highly obscure, as more important than its role as facilitator of the therapeutic process. For instance, LSD attracted theoretical interest as a serotonin inhibitor and an autonomic nervous system stimulant. Bender et al. (1963) concluded that “LSD-25 given daily in oral doses of 100 mcg [2] to pre-puberty autistic schizophrenic children appears to be an effective autonomic and central nervous system stimulant”, and that these changes “appear to be chronic with continuous administration of the drug”. Continuous administration consisted of daily administration over prolonged periods of time, varying from days to several weeks . The most persistent effects of LSD-25 therapy that were published included improved speech behavior, increased emotional responsiveness, positive mood (laughter) and a decrease of compulsions.

But alas, however interesting and attractive these results seemed to be — the evidence didn’t stick. Today studies into the relationship of LSD and autism aren’t being conducted and the results that were produced are regarded as highly controversial, if not completely repudiated. This was in part because, in retrospect, the studies were greatly flawed. The researchers seemed to have brushed over the conceptual controversy too quickly by choosing “not to deal with the controversial issues concerning the definitions and etiological factors of either childhood schizophrenia (1) or the autistic reaction pattern (2)” (Bender et al., 1962). The debate about the correct place of (childhood) autism within the DSM (Diagnostic and Statistical Manual of Mental Disorders) remains problematic to this day (DSM-V), but autism has long been divorced from the umbrella of schizophrenia. Although both disorders share clinical features, clinical psychologists and psychiatrists regard autism to be a separate diagnostic ‘entity’ from schizophrenia. Because LSD was used as a drug for “intensifying pre-existing symptomology” of schizophrenia (Bender et al., 1962), a conceptual detachment from autism would have disturbed the foundation of the results.

Even if the researchers had chosen to ‘deal with the controversy’, in hindsight, sampling would have still ended up being very problematic. The children treated were demographically varied and covered a broad age range. Conflicting significance is given to the relationship between age and drug response, but Bender noted that “in contrast to pre- adolescents, younger children manifest consistently different reactions” (1962). In contrast, Fisher and Castile concluded that “older children were better candidates for psychedelic therapy because verbal communication was possible and also because they tended to be less withdrawn, more schizophrenic than autistic, and displayed more blatant symptomology” (Mogar & Aldrich, 1969). In addition to age, also the symptoms of treated children were heterogeneous and weren’t corrected for severity. There was no randomization, and most studies suffered from fluctuating frequency of administration and dosage. Lastly, the set and setting of the experiments varied strongly.

Although the studies conducted in the sixties had major flaws from an experimental point of view and therefore didn’t hold up to scientific scrutiny, Mogar and Aldrich argue in an article published in Behavioral Neuropsychiatry (1969) that the results considered as a whole do point to a utility of administering LSD to autistic children. “The significance of seemingly contradictory results”, say Mogar and Aldrich, “has often been obscured by the persistent search for static, ‘drug-specific’ reactions to LSD”. This is an interesting point; despite that the results don’t indicate significance in an experimental sense, there may still be a therapeutic utility. Mogar and Aldrich report that the greatest therapeutic benefit was related to “(a) the degree of active therapist involvement with the patient; (b) an opportunity to experience meaningful objects and interpersonal activities; and (c) congenial settings that were reasonably free of artificiality, experimental or medical restrictions, and mechanically administered procedures” (1969). In practice clinical therapy is usually far removed from theory. It could be that testing LSD, itself being a highly unpredictable drug, in combination with the therapy dynamic is too hard to substantiate. Mogar and Aldrich conclude that “the administration of LSD is inextricably embedded in a larger psychosocial process which should be optimized in accordance with particular treatment goals”.

Considering the recent growth of interest into this area of research, these older and rather obscure studies deserve to be excavated from the psychedelic research literature. Researchers at LA BioMed (Los Angeles Biomedical Research Institute) are now constructing a study which is said to test the already established anecdotal therapeutic relationship between MDMA (3,4-methylenedioxy-N-methylamphetamine) and autism in adults. The study is the latest in an expanding program of research into the therapeutic use of MDMA funded by the nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS). “This new study will give us a chance”, says Charles Grob head researcher at LA BioMed (2014), “to determine the actual effects of differing dosages of medication that we know for certain is pure MDMA on adults on the autism spectrum. If the results of this research warrant further investigation, data from this study will be used to design additional clinical trials”. Now that the limitations for research into the psychedelic experience and its therapeutic effects are being removed and LSD is once again an object of study, these previously published results could serve for the production of new hypotheses.


 
[1] See (Abramson, 1960; Bender, et al., 1962; Bender, et al., 1963; Fisher & Castile, 1963; Freedman, et al., 1962; Rolo, et al., 1965; Simmons, et al., 1966).
[2] A common psychedelic dosage of LSD ranges from 100 to 200 mcg, a strong dose being 200 to 600 mcg.
 
References
Abramson, H.A. (Ed.) (1960). The Use of LSD in Psychotherapy. New York: Josiah Macy Foundation.
Bender, L., Faretra, G., & Cobrinik, L. (1963). LSD and UM-L treatment of hospitalized disturbed children. Recent Advances in Biological Psychiatry, 5, 84-92.
Bender, L., Goldschmidt, L., & Sankar, S.D.V. (1962). Treatment of autistic schizophrenic children with LSD-25 and UML-491. Recent Advances in Biological Psychiatry, 4, 170-177.
Cholden, L., Kurland, A., & Savage, C. (1955). Clinical reactions and tolerance to LSD in chronic schizophrenia. Journal of Nervous and Mental Disease, 122, 211-216.
Cohen, S., & Eisner, B. G. (1959). Use of lysergic acid diethylamide in a psychotherapeutic setting. AMA Archives of Neurology & Psychiatry, 81(5), 615-619.
Freedman, A.M., Ebin, E.V., & Wilson, E.A. (1962). Autistic schizophrenic children: An experiment in the use of d-lysergic acid diethylamide (LSD-25). Archives of General Psychiatry, 6, 203-213.
Gettys, T. (2014). MDMA Helps Reduce Social Anxiety for Autistic Adults, and Researchers Want to Find Out How. MAPS. Retrieved at: http://www.maps.org/media/view/mdma_helps_reduce_social_anxiety_for_autistic_adults_and_researchers_w/
Grof, S. (1980). LSD Psychotherapy. California: Hunter House Publishers.
Mogar, E. R., & Aldrich, W. R. (1969). The Use of Psychedelic Agents with Autistic Schizophrenic Children. Behavioral Neuropsychiatry, 1(8), 44-50.
Rolo, A., Krinsky. L.W., Abramson, H.A., & Goldfarb, L. (1965). Preliminary method for study of LSD with children. International Journal of Neuropsychiatry, 1, 552-555.
Sewell, R. A., Ranganathan, M., & D’Souza, D. C. (2009). Cannabinoids and psychosis. International Review of Psychiatry, 21(2), 152-162.
Simmons, J.Q., Leiken, SoJ., Lovaas, Q.I., Schaffer, B., & Perloff, B. (1966). Modification of autistic behavior with LSD-25. The American Journal of Psychiatry, 122, 1201-1211.

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