Retrospectacle: A Neuroscience Blog

[This is part of a series I'm doing here on Retrospectacle called 'Science Vault.' Pretty much I'm just going to dig back into the forgotten and moldering annuls of scientific publications to find weird and interesting studies that very likely would never be published or done today (and perhaps never should have.) I'll probably try to do it once a week (and if you have suggestions, please do email me with them.)]

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Its been a few weeks since anything truly old and shocking as come across my plate as fodder for my ‘Science Vault’ series, but when I saw this paper, I knew I had to blog it. Basically, it is a 2007 paper by Sigafoos et al, published in Developmental Neurorehabilitation, which describes efforts in the 1960s and 1970s to treat autistic children with d-lysergic acid diethylamide (LSD). A series of studies took place from 1959-1974, which involved administering LSD to children at school and cataloging their behavior. Beyond illustrating that the therapy didn’t work, it reminds us what a different place science was then.

(Continued under the fold….)

Autism was first described by Kanner in 1943 as a constellation of symptoms and behavioral traits which varies somewhat from person to person, making it inherantly difficult to diagnose and treat.The prevailing theory in the middle of the last century was that autism represeted “a childlike version of adult psychosis or schizophrenia.” Accordingly, children diagnosed with autism were subject to a bevy of biologic treatments (electroconvulsive therapy, sub-shock insulin, amphetamines, antidepressants, etc) which were also used in adult mental health treatment regimes. One of those types of treatments was the administration of LSD.

LSD was discovered, by accident, in 1943 by the Swiss chemist Albert Hoffman. [Authors note: I can only imagine how he "accidently" discovered it, but this serendipity might have started the trend towards wearing gloves during science. Anyway.] It was soon found that this “new drug,” which produced “fantastic pictures, extrodinary shapes, with intense kaleidoscopic play of colors” was pleasant at low doses and intensely disturbing at large doses.

Hoffman, with LSD molecule.

Hoffman’s employer, Sandoz, was intrigued by LSD and approved trials for its use in normal vs. schitzophrenic adults, which produced results promising enough for clinical potential. LSD soon found itself marketed as an experimental drug for the study of psychosis and a fascilitator of psychotherapy, available to researchers. Several autism researchers became interested in LSD, as a result.

The first report of LSD being used in the treatment of children was in 1959 at a conference in Princeton, which included references to a trial on autistic/schitzophrenic children. The following year there were five more such studies. Interestingly, these initial reports claimed that the results of LSD therapy were considered promising by academia. A formal study on 12 autistic children by Freedman, Ebin, and Wilson a few years later typified the methods: 10 boys and 2 girls were given varying doses of LSD (either 50,100,or 200 ug) on one or two occasions. The drug was given orally, at school in the morning, and subsequent behavior was observed carefully. Here’s what happened:

“The researchers noted that the signs of LSD inebriation became apparent within 15-30 minutes with effects lasting 4-5 hours…Some of the children became flush and their pupils dilated, but neither pulse nor blood pressure showed much change. Behaviorally, the effects varied. Three children were said to show evidence of catatonia (strange, fixed position of hands, bizarre postures, wavy flexibility of arms). None of the children ate their lunch until the drug wore off…Psychic effects were also noted, including rapid mood swings from extreme elation to extreme depression, increased anxiety, and signs of both visual and auditory hallucinations.”

Furthermore, the children were not induced to speak in response to the drug, and remained mute. Freedman concluded that there was little hope for the use of LSD therapeutically in children. Not that this discouraged other autism researchers–in fact, the research accelerated until concerns over recreational use caused Sandoz to stop supplying LSD for experimental purposes. That put an end to the studies pretty decisively.

The logic behind using LSD in the first place is rather interesting. Sigafoos et al described it thus:

The primary justification offered for the autism/LSD studies was based on the logic of default. Simply put, nothing much seemed to work very well, so why not try LSD?

It is shocking to also realize that ethical issues regarding LSD use in children received barely a mention. Even statements concerning the procurement of parental consent were glaringly brief, or even absent, leaving the question open as to whether the parents of the children who received LSD were even informed as to its effects. But in fairness, ‘subjects rights’ were still a relatively new notion in the 1960s and it was not unusual to have informal procedures for informed consent.

Sigafoos et al. 2007.Flashback to the 1960s: LSD in the treatment of autism. Developmental Neurorehabilitation. 10 (1), 75 – 81.

Hat tip Aaron Rowe for the story. If you liked this article, please vote for me so I can get a scholarship!

Comments

#1 darkman
October 9, 2007

Serendipity played less role in the discovery of LSD-25 than one might think (actually it was just good science and a willingness to put novel chemicals synthesized in lab in one’s mouth that people don’t have as much these days).

Hoffman first synthesized LSD-25 for Sandoz in the 1930′s when assaying various chemical modifications of the core molecule lysergic acid. He noted that it had no particularly useful medical properties but also noted in his journals that that “the experimental animals became restless during the narcosis”.

In his book, Hoffman claims: “A peculiar presentiment – the feeling that this substance could possess properties other than those established in the first investigations – induced me, five years after the first synthesis, to produce LSD-25 once again so that a sample could be given to the pharmacological department for further tests.”

In spring of 1943 he re-synthesized LSD-25 for further testing. Hoffman then discovered the physiological effects of LSD-25 through self-experimentation, here’s an excerpt from his lab notebook on April 19, 1943:

Self-Experiments

17:00: Beginning dizziness, feeling of anxiety, visual distortions, symptoms of paralysis, desire to laugh.

His diary, written later, continues the story:

“Here the notes in my laboratory journal cease. I was able to write the last words only with great effort. By now it was already clear to me that LSD had been the cause of the remarkable experience of the previous Friday, for the altered perceptions were of the same type as before, only much more intense. I had to struggle to speak intelligibly. I asked my laboratory assistant, who was informed of the self-experiment, to escort me home. We went by bicycle, no automobile being available because of wartime restrictions on their use. On the way home, my condition began to assume threatening forms. Everything in my field of vision wavered and was distorted as if seen in a curved mirror. I also had the sensation of being unable to move from the spot. Nevertheless, my assistant later told me that we had traveled very rapidly. Finally, we arrived at home safe and sound, and I was just barely capable of asking my companion to summon our family doctor and request milk from the neighbors.

The dizziness and sensation of fainting became so strong at times that I could no longer hold myself erect, and had to lie down on a sofa. My surroundings had now transformed themselves in more terrifying ways. Everything in the room spun around, and the familiar objects and pieces of furniture assumed grotesque, threatening forms. They were in continuous motion, animated, as if driven by an inner restlessness. The lady next door, whom I scarcely recognized, brought me milk – in the course of the evening I drank more than two liters. She was no longer Mrs. R., but rather a malevolent, insidious witch with a colored mask.”

The journal excerpts are often published in magazine articles every year in April (might be only on anniversaries like the 60th in 2003).
#2 Zachary Tong
October 9, 2007

It should be noted that the initial discovery of LSD’s psychedelic properties was on the 16th. Hoffman accidently ingested LSD that had gotten on his fingertips while working in the lab. Seeing as doses are as low as 250ug, its not hard to believe he had a bit under his fingernail.

The first intentional dose was done on the 19th after Hoffman realized the effects felt three days prior were probably the result of LSD. Hoffman famously rode his bicycle home that day (hence the date is known as bicycling day)

In summary, always wear lab gloves kids!
#3 Orac
October 9, 2007

You might want to check out Kathleen Seidel’s website, specifically her library section. There are links to several of the original studies of LSD in autism there.
#4 Alex
October 9, 2007

I can’t get over this bit: None of the children ate their lunch until the drug wore off

I guess not…
#5 baryogenesis
October 9, 2007

From my 60′s street knowledge (as they say, what memories?)I seem to recall something like as small as 125-200 micrograms (not mg!)of good Sandoz, Owsley, or similarly responsibly-made (ha) acid would be enough to experience another world. 125-250mg dose was needed for mescaline. If children were in fact being dosed with those large amounts, I can’t even imagine what they experienced.
#6 Bob Weaver
October 9, 2007

Your premise has so many holes it’s hard for me to plug them all with facts.

I’ll try an analogy instead. Think of cancer patients for a moment. We inject them with very toxic and poisonous chemicals to cure them. Who was to say in the 60s that LSD could not be a cure for autism? It had been observed to have little to no long term health risks. It had also showed promise in many psychological applications. It is not a stretch then to assume that it might have been beneficial to autistic children.
#7 Shelley Batts
October 9, 2007

I never explicitly stated that it didn’t make any sense to try LSD, well, if there had been empirical data to that effect (there wasn’t, and not for children especially). The stretch lies in the differences between how science was perceived and practiced, as well as the concern shown for the human participants. If you want to see another experimental use for LSD around the same time, well why don’t you search my site for ‘elephant’ and ‘lsd’ to see what people could get away with, on the grounds that ‘it may help.’

I’m all for trying new and innovative, even controversial, techniques to treat disease. I just want to see some positive results, with the proper controls, before being tested on people. That *certainly* existed in the 1960s.

The “premise” was a discussion of one argued in the paper cited. If you have further problems with it, take it up with the authors.
#8 Blake Stacey
October 9, 2007

Copies of Hofmann’s book LSD — My Problem Child exist on a few different websites; one such is here.

LSD trips and the space flights of the astronauts are comparable in many respects. Both enterprises require very careful preparations, as far as measures for safety as well as objectives are concerned, in order to minimize dangers and to derive the most valuable results possible. The astronauts cannot remain in space nor the LSD experimenters in transcendental spheres; they have to return to earth and everyday reality, where the newly acquired experiences must be evaluated.
#9 Blake Stacey
October 9, 2007

Oh, also, there’s an annotated bibliography of LSD in psychiatry, over at Advances in the History of Psychology.
#10 DuWayne
October 10, 2007

I have done fairly copious quantities of acid in my time. I also have a few autistic friends, as does my son. This just seems to me, like a very bad idea. I can certainly see why someone might think it might do something, but having done quite a bit of it myself, I am loathe to imagine what those kids felt. Talk about a mindscrew.

Though it is rather amusing, trying to imagine one of my friends in particular, on acid…
#11 David Harmon
October 10, 2007

See also the Whos’ song “The Acid Queen”, from their classic album Tommy….

I’d say the other take-home message is that these guys were farting around with both a drug, and a condition, that they didn’t have a clue about.
#12 Evan Martin
October 10, 2007

You should do more homework!

When done in a mindful context, LSD work with autistic and schzophrenic children was miraculously successful. Many children who were psychotic, mute, agressive, intenseley anti-social, etc., after (humane) treatment with LSD and Psilocybin were fully functional, sociable and in school with peers within a year.
Look into the work of Gary Fisher.
Here are some links to get you started:

A Paper:
http://www.hofmann.org/papers/fisher/fisher_4.htm

An immensely fascinating interview from a remarkable book: (‘Treating the Untreatable’)
http://tinyurl.com/ytargu

And here is an audio file:
http://www.matrixmasters.net/blogs/?p=187
#13 Dan
October 10, 2007

Hoffman was testing LSD and other ergot derivatives in rats for signs of beneficial effects on the circulatory system in an attempt to develop heart medication, which tanked. He accidentally absorbed a little of it while going out to resume investigations into it and noticed some mind-bending effects, and then did the later well-cataloged and planned self-tests on ‘bicycle day’.

Once you learn pharmacology, it’s with you forever.

As for LSD in treating anything, I’m extremely skeptical. Much of the data on it was collected by very high researchers (seriously), back before it was illegal, which harms their credibility immensely- and this apart from the fact that there was no control group. If I’m going to be malicious, I might note that ice pick lobotomies also enjoyed a fair following at the time- that is to say, psychiatry wasn’t particularly scientific.

That’s not to say that banning the drug beyond even research use wasn’t a rather stupid knee-jerk reaction to its street use, but the studies back in the day were still pretty bad.
#14 Azkyroth
October 11, 2007

Test
#15 Brad S
October 11, 2007

LSD as a treatment for schizophrenia is a hoot. Its an agonist on the system that is likely to cause schizophrenia due to overactivity. It’d pretty much exacerbate the situation.
#16 MonoKnight
October 13, 2007

@Dan: Your assumption that researchers were “very high” while conducting their work shows the extent of your knowledge about the area. Unfortunately, it’s hype and unfounded claims like your’s which distort the hard work of individuals. I’m currently conducting a meta-analytical survey of these studies.

@Brad S: Although LSD can certainly bring about schizophrenia in those with a predisposition to it, it (along with therapy) was also shown to permanently reduce symptoms in many schizophrenics (see the work of Gary Fischer, Jaime G. Rojas-Bermudez, and others). This was actually observed during studies. To say LSD as treatment is a “hoot”, isn’t a very accurate summation of the issue.

Many people wish to paint psychedelics as either completely black or white. The truth is somewhere in between. Due to politics legitimate research was brought to a halt. As a result we do not know the full dangers or the full benefits of LSD. Sensationalism such as the posts above are largely responsible for this.
#17 Nick
October 14, 2007

Thanks Shelly and others.

NewScientist had an article on the use of LSD for treating mental illness, particularly depression. So this is of interest to me, particularly more so for the failures.
#18 Dan
October 18, 2007

I did say “much of” the data rather than “all of”. It’s possible my (entirely nonscientific) look-over of the data on the medical use of psychedelics ended up with a highly nonrepresentative sample- I was also admittedly focused more on MDMA than LSD- but such is life.
#19 jvb
September 16, 2009

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#20 Mandy
November 18, 2010

A lot of my friends have started to try acid. Some say its not worth it but, others got addicted and couldn’t stop. So, not always educating students about them can keep them from doing drugs. But, then again, we don’t really have that affective methods of drug prevention. If you tell a teen not to do something, they will immediatelly want to do it. That’s just the way they are.