Doc 0000151829

-- .. DEPARTMENT OF HEALTH, EDUCATION, AND W~L~It-'RE PUBLIC HEALTH SEA VICJ 28 October 19.58 KadaMl lutil- ol Mcacal Hcaldl A4Aictloa ll--~~~ Cot• U.S. hllllc Kcaldl S.mce H..,ltal Lcsiapoa. ~fteky I I !I 1- ' I ·I I ! .. i I I ~ ~ . ! I . I ' : ' 1 must apologize for writing to you sooner but, as you kno\v, no~ I was away for most of the summer. my return the Si~ce possib~lity has arisen that we may get a new building \vhich would provide new space for research·here. I therefore have been working under multiple pressures and haventt had a great deal of free time. Budget. To my disappointment the National Institute of Mental Healtn was not able to provide any-additional funds to pick up any of the personnel currently in our project. ! therefore continue to be dependent on yo.u. I have asked NIMH again to include an item for salaries of part or all of these employees in the budget for fiscal 1959, but there is, of course, no way of knowing if this can be done. ·I will try to keep you informed. LSD Conoeners with Sedative Effects. 1 mentioned briefly in a letter dated 26 Ivlay 19$jj the sedative effects observed '..rith compounds. of this type. Two of these (agroclavine and dihydro agroclavine} obtained from Takeda Laboratories in Japan. A we~e third compound (No. 23194, Eli tilly & Company) is very similar in structure to triseclavine. We have now concluded preliminary experiments in which men who had slept all night received one of these drugs (or place.bo) at 8 a.m. Observations were made every half hourfor eight hours and consisted merely of checking whet~er or not the men were in bed asleep, in bed awake, or up and about. This was done to avoid any stimulation which might obscure sedative or hypnotic effect. Under these conditions the men slept more after all three drugs than after placebos. Lilly 23194 was the most potent com?ound, 40 mcg./kg. causing an average increase (.5 patients) of 1.7 hours sleep in the four hours between 8 and 12 a.m. Agroclavine (.50-60 mcg./kg.) was the next most potent, causing an increase of 1.2 hours {6 patients). Dihvdro agroclavine {60-70 mcg./kg.) was least potent, causing an average { JJ r-.... -·- -,t__'-. f -- v "\ t.I ' :'\ )'. I I ' . ·, The image displays a digital representation of information related to the MKULTRA program. On the left, a stylized graphic of a vault door is visible, symbolizing a secure repository of information. To the right of the vault graphic, white text states that the document was obtained from "The Black Vault," an online database of declassified government documents related to the MKULTRA/Mind Control Collection. This text specifies the collection contains over 20,000 declassified pages from the CIA and provides a URL for online access. The overall presentation suggests a digital presentation or a title screen for accessing declassified documents. The document is a typed letter with handwritten annotations at the top and bottom right. The letterhead indicates it's from the Department of Health, Education, and Welfare, Public Health Service, dated October 28, 1958. Handwritten notes at the top read "ET JACLEEP # 138" and a symbol resembling a '#' sign. The bottom right has a handwritten annotation "B-EE" and some obscured text. The body of the letter discusses a report on "LSD Congeners with Sedative Effects." There are no images of people, locations, equipment, or experimental procedures. Some text areas are visually slightly faded but remain legible. hours between 8 and 12 a.m. Agroclavine (.50-60 mcg./kg.) was the next most potent, causing an increase of 1.2 hours {6 patients). Dihvdro agroclavine {60-70 mcg./kg.) was least potent, causing an average { JJ r-.... -·- -,t__'-. f -- v "\ t.I ' :'\ )'. I I ' . ·, Page 2 . "I " . l' ·.. ,....}- I '-. . 0.5 (4 increase of only hours patients). Onset of action was very rapid with the two active drugs, the men being unabla to remain awake an half-hour after the drug was given. After 12 o'clock the men slept fittle, but reported subjective relaxation and lasting through the afternoon. d~owsiness These results are of interest because of the reversal of the predicted effect (excitation expected,· sedation observed), the discrepancy with animal tests (drugs are LSD-like in animals), and apparent high potency as hypnotic drugs in •. You will ~an note that the total dose of 23194 was only 2-3 mg; implica t~e tions are obvious. We are now extending these observations. The most potent drug (Lilly, 23194) will at two dose levels (2 and 4 mg. be.co~ared per 70 kg.) with secobarbital (100 and 200 mg.) and the dose range of agroclavine and dihydroagroclavine will be further explored. In addition, we are also·adding studies on ~-Lysergic acid diethylamide, which in preliminary tests seemed to al~ have sedative effects in doses as low as 15-20 mcg./kg. Nine men will receive these drugs so that we will have figures which will have some statistical meaning. I then plan to attempt to attenuate the LSD reaction with Lilly 23194, and may study some combinations of these dru·gs with alcohol and other hypnotics •. C-5. C-5. l am attaching a long overdue report on As I told you, this compounq appears to be relatively inert in man. Neuroph*siological Studies on C-9. These studies are being underta en by Dr. William R. Martin as part of a larger project. . . Dr. Martin has fo.und that, in intact cats, 0.2-0.4 mg./kg. of C.-9 intravenously causes depression of body temperature, ataxia, relaxation of nictitating membrane, depression of the pinnal reflex, diminished muscle tone, loss of righting reflex, sorr~o­ lence, and taming. These effects appear after two hours and.r.zy persist for as long as three days (0.4 mg./kg.). Bradycardia, which has been shown to be due to the temperature fall, is also observed. In unanesthetized curarized depression of the pinnal reflex, diminished muscle tone, loss of righting reflex, sorr~o­ lence, and taming. These effects appear after two hours and.r.zy persist for as long as three days (0.4 mg./kg.). Bradycardia, which has been shown to be due to the temperature fall, is also observed. In unanesthetized curarized cats with electrodes in cortex and in the reticular formation in the mesencephalon C-9 causes marked EEG slowing; increase in 'the threshold for · activation of the £EG; decreased lengths and altered quality of the activation response; fall in blood pressure, with narro\IT pulse pressure; increased threshold for elicitation of a blood pressure rise by mesencephalic stimulation; and decrease in pressure response once it has been elicited. Page 3 During a visit to the University of Rochester I have also learned that Or. E. ·s. Boyd of the Department of Pharmacology has become interested in this group of drugs. He has the methyl- and ~sted dimethyl-heptyl-derivatives and is attempting to study the effects in cats with the view of investigating the metabolic fate of the compounds. You are doubtless aware of his work. K-302. A report on· this material, and· on the crude form, is attached. As I told you previously, both the crude material and K-302 are active. Psilocybin. Attached is a thermofax copy of letter from Or. Henze of Sandoz indicating that psilocybin will be available to me in the near future. I should be able to undertake pre 1 iminary \vork with this compound about the middle or end of November. Narcotics of High Potency. Or. P. Janssen of Eupharma Laboratories, Belgium, visited us this month. He·told us about some benzimi dazoles with analgesic properties. of extreme potency. These compounds belong to the series originally developed by Ciba. One of Janssen's compounds is said to be 3-thousand times as potent as morphine in monkeys; and anothe.r, a rather unstable fluorinated compound, is 300-thousand times as potent as morphine. I believe that Dr. Janssen talked with Dr. N. B. Eddy and with persons .from the Army Chemical Center concerning these drugs. It is quite lil<ely that members of this series will come to us via the Drug Addiction after testing in monkeys in Michigan has been Cornmitt~e completed. Inventory for Subjective Effects of Drugs. My psychological staff is attempting develop a self-administered machine-scored t~ "inventory" which will discriminate between the subjective effects of opiates, barbfturates, alcohol, chlorpromazine, amphetamines, This document page contains only text and handwritten annotations. There are no photographs, stamps, forms, diagrams, tables, or evidence of experimental procedures. The handwritten annotation in the upper left corner, "(b/5)", is accompanied by a horizontal line, and there is another handwritten annotation in the lower right corner, "B-6,". The rest of the page consists of typed text, with some potential smudges or ink blots scattering the page. this series will come to us via the Drug Addiction after testing in monkeys in Michigan has been Cornmitt~e completed. Inventory for Subjective Effects of Drugs. My psychological staff is attempting develop a self-administered machine-scored t~ "inventory" which will discriminate between the subjective effects of opiates, barbfturates, alcohol, chlorpromazine, amphetamines, LSD, and pyrahexyl. In its present form the test consists of more than 500 true or items and includes validating and fa~se lylng scales. The number of items will be sharply reduced after item analysis has been done, and it may be possible to develop sub-inventories for each of these classes of drugs. We hope that ~ the inventory will improve our methods for measuring the subjective effects of the drugs and that the inventory can eventually become a quantitative instrument. The project is however very long-range and may require as much as two more years for conpletion. I expect to be in Lexington for the next three months except for November 20 and 23, when I will meet with the Council on Mental Health, MAA, in Chicago. 1 would welcome a visit from you at any time. With kindest personal regards, Enclosures The document is a typed letter, page 3 of a larger document, as indicated by the "Page 3" annotation and a handwritten "(6)/3)" in the top left corner. There are no photographs, diagrams, forms, or tables present. The only handwritten elements are a signature and title at the bottom right, "Harris Isbell, M.D. Director," and a marginal note "B-61" on the right side. There are no official stamps visible, and no redacted or obscured content. The document discusses chemical compounds and their effects, but provides no visual evidence of experimental procedures or facilities.