Doc 0000151911

• I ~' EFFECT OF EPINEPHRINE ON THE LSD REAC•· TION - of the effects of LSD in animals and man suggest a ~~ny state of hyperactivity of the adrenergic autonomic nervous system. Rothlin has postulated that LSD creates a central hyperactive autonomic state. Dille and his coworkers at the University of Washington found that phenoxybenzamine blocked ·LSD-induced hyperthermia and behavioral changes in animals. The same group found that administration of LSD two hours after reserpine resulted in marked augmentation of the LSD hyperthermfa, whereas administration of LSD ten hours after reserpine resulted in little hyperthermia. Since reserpine is ·knol>m to cause a discharge of serotonin and norepinephrine in the brain, the change two hours after reserpine might be correlated with a discharge of epinephrine and norepinephrine, whereas at ten hours these substances would be depleted in the tissues. In recent experiments we were unable to show any diminution in the intensity of the mental symptoms indu~ed by LSD ~f~cr p4ctr8at- ment hu..'1lan subjects with various doses of phenoxybenzamlne •. ~f. This resuft did not ·favoi-- the adrenergic hypothes.is. It \.'as, therefore, thought desirable to determine the effect of epinephrine on the LSD-reaction since an accentuation of the effect of LSD would favor the adrenergic hypothesis. \ \ \ \------- ·--- ------------- ----------------··· -------- ------------------------- -· --- ------------------ -- .... JMETli:)DS. · Subjects. Nine forme:r-addict Negro male_s who were· serving sentences for violation of the narcotic laws served as subjects • in these.experiments. Their ages varied 21 and 38 years. bet~en All had been abstinent from morphine for several months. All had experienced the effects of LSD and were familiar with the mental changes produced by that drug. Drugs. LSD was given orally·as the tartrate in solution. The drug -was administered at 8 a.m. to patients in the fasting state. Epinephrine hydrochloride was administered subcutaneously at 10 a.m. in doses of 0.4 to 0.6 mg./70 kg. Tnese amow1ts had been shown to induce typical cardiovascular effects in the experiments involving phenoxybenzamine. The following combinations were studied, using a randomized balanced Latin-square design: L.SD plus epinephrine placebo; LSD placebo plus epinephrine 0.4 mg./70 kg.; LSD placebo plus ~- 0.6 mg. epinephrine/70 kg.; 1 mcg./kg. LSD plus 0_.4 mg. epinephrine per kg.; and, 1 mcg./kg. LSD plus 0.6 mg./70 kg. of A double-placebo was not included, eplnephrin~. cow~ination since the. important comparisons those with t.SD plus we~e epinephrine placebo and LSD plus·epinephririe. The image displays a graphical presentation related to the MKULTRA program. On the left, a stylized image of a bank vault door with complex locking mechanisms is depicted in shades of gray and bright blue. To the right of the vault image, the text "THE BLACK VAULT" is prominently displayed in a stylized, rough font. Below this title, smaller white text explains that the document was obtained from The Black Vault, an online database of declassified government documents, specifically noting its housing within the MKULTRA/Mind Control Collection by the Central Intelligence Agency (CIA). A prominent yellow URL, "http://mkultra.theblackvault.com," is provided for accessing the collection. There are no photographs of people or specific locations, no handwritten notes, no official stamps, no forms with filled-in fields, no diagrams, tables, or structured data, and no visible redacting or obscured content. The visual elements primarily serve to establish the source and context of the information as declassified documents related to a historical CIA program. 0.4 mg./70 kg.; LSD placebo plus ~- 0.6 mg. epinephrine/70 kg.; 1 mcg./kg. LSD plus 0_.4 mg. epinephrine per kg.; and, 1 mcg./kg. LSD plus 0.6 mg./70 kg. of A double-placebo was not included, eplnephrin~. cow~ination since the. important comparisons those with t.SD plus we~e epinephrine placebo and LSD plus·epinephririe. • . . · , . . ., .··-:.· . Observations. Pupillary diameter, resting systolic blood ... pressure, and threshold for were measured as kne~Jerks pt"eviously described. These determinations were I!".ade every ··hour on the hour from 7 a.m. to 4 p.m. An additional measure- ment was obtained at 10:10 a.m., ten minutes after subcutaneous administration of epinephrine and epinephrine placebo.· This timing coincides with the height of the epinephrine-effect as determined in previous experiments. The modification of the Jarvik-Abramson questionnaire was administered to the patients every hour on the half-hour from 7:30a.m. to 3:30p.m., except questionnaire was administered at 10:20 a.m., after epinephrine rather thanaat 10:30 a.m. The clinical grades of the reactions were assigned by our usual system. Analysis. The critical measures \<."ere those obtained at · 10:00 (pre-epinephrine} and at 10:10 a.m. (height of a~m. epinephrine effect} plus questionnaires at 9:30 a.m. and 10:20 a.m. These values were tabufated and averaged • . Results are shown in the· accompanying table. Since the between LSD placebo and LSD plus -v:ere differ~nces_ epinephri~e quite small and obviously-nonsignificant~ statistical calculations not made •. The figures do not indicate either v~ere inhibition or accentuation of the LSD reaction by epinephrine • ..... . . •. - ..-.;. /. ·e Discussion. Like the experiment with phenoxybenzamine, .· . the results do not favor, but also do not disprove, the adrenergic hypothesis of the LSD reaction. In this connection, ···it ls important to remember that epinephrine is known to have ·effects on the central nervous system (changes in the activity of the reticular activating system), so that the lack of effect is probably not attributable to difficulty in penetration of the blood brain barrier by epinephrine. -------·- --- ····- -- --· --------------------- ------------------------------------ - ,. - . ..._ - - ~-· '.t·, ,) -......~- EFFECT OF EPINEPI-UUNE ON THE LSD REACTION ~ ME./\ SURE AND TIME •.. EATt~ Questions Questions Questions Grade (lr: . .Je Pulse Pulse Blood Blood . Pupils Pupils Knee- 1\nee·- . -·/, Rate Rate Pressure Pressure Jerk Jerk ~ . ·;· 10 AM 10:10 AM 10 AM 10: 10 The page is a typewritten document with a heading that reads "EFFECT OF EPINEPHRINE ON THE LSD REACTION". There are several handwritten annotations on the page. In the upper right corner, there is a circled number "118". In the lower right corner, there is a handwritten annotation "A-412". Scattered throughout the page are small, dark spots that appear to be ink splatters or imperfections in the original document. No photographs, diagrams, stamps, forms, or tables are present on this page. -......~- EFFECT OF EPINEPI-UUNE ON THE LSD REACTION ~ ME./\ SURE AND TIME •.. EATt~ Questions Questions Questions Grade (lr: . .Je Pulse Pulse Blood Blood . Pupils Pupils Knee- 1\nee·- . -·/, Rate Rate Pressure Pressure Jerk Jerk ~ . ·;· 10 AM 10:10 AM 10 AM 10: 10 AH 10 AM 10:10 AM 10 AM 10: 10 AM 9:30 Nvl 10:20 AM Tota 1 9:30 A.llil F~: - . ~, AI'1 [:~ ., . . t·i .. h . . :l . : ·;~ ,, >D o 1acebo :·!.{ :'" ~ ' '(. ... epinephrine 111 117 4· 7 4.8 1.3 1.2 1 1 2 0 '·4 mg./70 kg. 70 74 . I . \ ·: l 5 u 0 s. 1 e . p 0 i n m e c p g h . r /k in g e . . 6.6 6.7 2.3 2.6' 1'7 17 67 2.2 L . . , . .. · ? - 80. 84 122 126 ~.4 mg./70 kg. SO 1.0 mcg./kg. 1.33 1. ·)6 ·l l u ac s e b e o p i · n ephrine · 69 66 117 124 6.2 . 6.2' 1.6 1.6 11 12 ~-9 so placebo plus pincphrine 77 119 118 4-9 4· 7 1.0 1.3 1 0 1 0 'I .6 mg./70 kg. 72 ~l.J 1.0 mcg.jkg. _0 · ·l . y L .l e < p J i o n /7 e 0 p k h g ri . ne 78 85 ·.12 . 3 127 7.0 7.0 2.7 2•6 1 15 ll~ 6 -·- ---· 1 -------------------------------------------------------------------------------~ .~ ~- ( - \ - ' ·.·• I · Figures are averages on 9 subJe?ts. _._.; .. ' \I The page contains typed text detailing a research study involving former-addict Negro males, LSD, and epinephrine. There are no photographs, official stamps, forms, diagrams, or tables. Handwritten marginalia appears in the lower right corner, reading "A-411". There are no visual elements suggesting experimental procedures, equipment, or facilities. This document page contains primarily typed text, describing experimental procedures and observations, likely from a scientific study. There's a handwritten annotation in the upper right corner that appears to be "A-410." The document is a single page with no photographs, stamps, forms, diagrams, tables or structured data. There are no visible redactions or obscured content, and no direct visual evidence of experimental procedures, equipment, or facilities. This page is a typed document with a handwritten annotation in the upper right corner, "A-409". The text discusses an experiment with phenoxybenzamine and the adrenergic hypothesis of the LSD reaction, noting that the results do not definitively prove or disprove the hypothesis. The document appears to be a research report or memorandum, with a section title "Discussion" underlined and a few scattered dark marks and specks that could be ink blots or dust. There are no photographs, stamps, forms, diagrams, tables, or visible evidence of experimental procedures. The image displays a table with experimental data from what appears to be a study on the effect of epinephrine on LSD reactions. The table includes columns for patient treatments and time-stamped measurements of pulse rate, blood pressure, pupil size, knee jerk reflexes, and questions answered, along with grades. Handwritten annotations are visible in the top right corner, including "A-405." The content suggests a structured scientific experiment with quantitative data collection. The table is presented in a clear, grid-like format, common for scientific reports, and includes a note at the bottom indicating the figures are averages from nine subjects. There are no photographs, diagrams, stamps, or redacted content present in the visible portion of the image.