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Preliminary DescrIption Of The Reaction

Definitlon. Intoxication with C-9 refers to the sum total of mental and physlcal changes induced by Ingestion of this drug and is characterized by slow onset after oral Ingestlon, prolonged persistence of symptoms, conjunctival injection, pseudoptosis, tachycardia at rest, postural tachycardia and hypotension, and subjectlve symptoms whIch occur include drowsiness mlxed with apprehension, dryness of the mouth, difflculty in thinking and concentratlng, varlable changes in mood, and a feeling of increased sensory perceptlon.

Physical Properties. C-9 is an oily resin. It is soluble In organle solvents includlng ethyl alcohol, but is Insolubie in water. Alcoholic solutlons of the drug are stable for at least 8 months.

Method of Adminlstratlon. Because of the drugs lnsolubility In water, methods of edainlstration sre Iimited. The drug is effectlve orally and may be given In food, coffee, soft drinks, or aicoholie drinks. It is also effective when dried on fobacco and smoked, although the effects are generally milder and less consistent affer smoking as compared with oral' ingestion.

Dosage. The present descrlption is based on doses (total) of O.5 to 2.5 mg. of the drug orally. Definite cardiovasculer effects can be detected in doses of O.5 mg. Definite subjective effects

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are reported with doses of 1 mg. or more. At i mg. level, the effects are usually regarded as pleasant by experienced marihuana users. With the higher doses, subjective effects become disagreeable even to experlenced addlcts. With doses of 2 mg. or more, cardlovascular effects become very prominent and fainting may occur on standlag.

Time Course. Following oral ingestion both cardiovascular and subjectlve effects appear about one and one-half to fwo hours after administration of the drug. Maximum effect is reached four or five hours after the drug ls given. The peak effects is maintained to sbout the l6th hour following administratlon of the drug. Some effects may persist as long as 24 to 48 hours after administration. In general, the larger the dose of C-9 that is given the longer symptoms perslst.

Subjective Symptoms. During the height of the C-9 reactlon (4-ló hours) the following symptoms, which are listed by orgen systems, have been reported. The list does not Include all symptoms that have been menfioned but only those that are frequently reported.

Special Senses.

Vision.

(1} Blurring of vision.
{2] Change in spatial perceptlon.
(3) Occasionallv, elementary hallucinattons Icolored lights, patterns, etc.).on closing the eyas.

Taste.

[1] Increased acuity of taste.
[2] Dry taste.

Touch.

(2) Paresthest thot r collion the skin-33)

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Smel1.

No symptoms reported in this area.

(l) Dryness of the mouth
{2) Decreased salivation.
13] Dryness of the throat
[4] Increased appetite Iconsistently reportedl.
[5) Nausea and vomitlag lonly with the larger dosesl.

Cardiovascular.

[1 Dizziness 【2) Palpitation (3) Weakness and fatIgue (4) Fainting on standing

(1) Sense of choking (2) Air hunger

Renal No symptoms. reported.

Neuromuscular [1] Dizziness (2) Blurring of vision [3] Paresthesla (4] Drowslness 151 Sweating [6) Weakness

Mental Reaction.

Ideation. Ideation is reported as. being impaired. Patlents have. difficulfy in thinking, ftnd it hard to concentrate, and are bothered by attempts to corry out set tasks.

Nood. Mood varies. Indlviduals who are not habituated to marlhuana or who disllke the effects of the drug, are depressed

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by C-9. They become fearful, and frequently refuse to take the drug again. Unpleasant effects are accentuated by neusea and vomiting, faintness, dlzziness, and weakness on standing. lo exoerienced marihuana users, effects on mood vary wlth the situation. If patlents are observed in small social groups and not Intenslvely examined there Is a strong tendency for elation to appear. The patients laugh, giggle, tell pointless iokes, play records, and generally:behave In à silly fashlon. Under conditlons of latensive examination, tendency Is for patients to withdraw, and act in a guarded fashion though they remain qulet and cooperatlve. When doses of 2-2 mg. are given, experienced marlhuana users become -fearful and somewhat withdrawn. They state that they are afraid of "going too high" and that they wlll be unable to "come down."

Affect usually'is approprlate to the situation and the stimuli being received.

Stream and Content of Thought. No gross impalrment of abstract thinking occurs. So far as one can ascertain, there Is no abnormal thought content. Paranold ideas have not been prominent in our experlence.

Psychomotor Activity. Like mood, psychomotor actIvity varles with the sltuation and with the ladividuals. In sociat situations, outgoing individuals are prone to laugh, dance, giggle and crack many jokes. Patlents usually remain detached

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from the sltuation. They tend to laugh quletly at the outgoing individuals. When the situation Is not social, tendency Is for all types of patients to withdraw to thelr rooms and take naps. Hallucinatlons and Delusions. Hallucinatlons and delusions have not yet been observed. Occaslonally elemeatary halluclnations, lights, patterns and colorings on closing the eyes, have been reported.

General Characteristlcs of C-9 Reaction. Although the mental effects Induced by C-9 seems somewhat vague, they are definitely marlhuana-tIke and are so identifled by experlenced subjects who are well acquainted with the effects of marlhuana. Such patients stafe that the chief differences are slow onset and long perslstence of the reaction. Essentlally the drug seems to induce a mental state charactertzed by a peculiar mixture of pleasant sedatlon plus apprehension and anxtety which has no deflnite basls. A sensation of being light or floating is frequently reported. Distortion of time. sense Is often mentloned; time seems to pess more slowly. Some difficulty in vislon is present. This Is usually described as consisting of slight blurring of vision plus spatial distortion. Distances ordlnarily appear to be greater; distortion in form, shape or color is unusual.. in addition, there is.a sense of heightened sensory perceptlon - all things look better, feel better and taste better. In the proper situation there is dtminution in ego controls which, though not as great as -seen with large amounts

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of alcohol, results in-somewhat sllly, uninhibited behavior. The patients state they are able to enjoy music more, to appreclate taste of food more highiy, and. to appreclate colors and so on more, than they would without the drug. Although the test sltuatlon has precluded any direct observatlons on sexual drive all patlents consistently state that sexual urges would be enhanced in a proper sltuation.

Symptoms induced by C-9 differs sharply In overall pattern from those induced by LSD-25. In the LSD reaction, nervousness, anxlety and anorexla are prominent. In the C-9 reaction, drowsiness lalthough mixed with some mlld apprehenslon) and henger\_are commonly reported. Atropine-tike effects Idryness of the mouth etc.l are promlnent with C-9 and not prominent with LSD. Characteristtc. visual-perceptual distortion, which is so promlnent In the LSD reaction, Is scarcely mentioned by Individuals under C-9. Depersonalization la feeling that oneis body or so part of it Is not one's ownl 1s common with LSD, rare under C-9.

Oblective Effects. These include:

(ll Injection of the conjunctivae (red eyes)
(2) Pseudopfosis (drocpy lids \_ s sleepy appearance)
(3) Tachycardia (fast puise)
(4) Very fast pulse and marked drop in blood pressure on'standing.

No effects of outstanding. signiflcance have been observed on body temperature, resting blood pressure, respiratory rate, or in any phase of the neurological examination. Pupils are not dilated. There is no gross motor ataxia and no gross change on sensory

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examination. No laboratory evidence of damage to the llver, kidaey or hemopoietic system has been observed after single doses.of the drug. 1

Cordtovascular Effects. The cardlovascular effects of C\_o are also Induce'd by the members of the marihuans group (marthuana Itself and parahexyi compounds}. They conslst essentlally of tachycardla and postural hypotenslon. These effects are evident In two hours and may be present 24 to 48 hours later. They may be oresent for 24 to 48 hours after the Ingestion of doses of 2 to .2.S mg. The cardlovescular effects are most evident on quiet standing. The resting puise rate and pulse rate after one and two mlnutes standing plus blood pressure after one and two minutes standing are very useful indlcators cf the drugts effects.

Variations. As is the case with all drugs, the degree of effect obtained wlth a given dose of C-9 varles from individuai to.Individual. In some patients, intense mental effects plus cardlovascular effects, resulting in fainting on standing, may occur with doses as low as l.5 mg.In ofher individuals receiving 1.5 mgm., or even 2.0 mgm., very few subjective symptoms and only mlld changes in pulse rate and blood oressure will be observed on standing.

Psychosls After C-9. So far, no toxic psychosis has occurred after ingestion of C.9. It is, however, known that other marihuanalike druas sometimes trigger a toxic psychosls, usvally af paranoid type, in susceptlble indivicuals. It Is very likely

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that when a sufficlent number of patients have had C-9, toxlc psychoses may be reported in a few.

Dlagnosts. At the present time there Is no absolutely certain way of dlagnosing C-9 tor marlhuana Intoxlcation) in an unknown sltuation. The diagnosis should be suggested by the combinatlon of conjuntival Injection, pseudoptosls, tachycardia, postural hypotenslon, plus the' subjective effects of dryness of the mouth, blurring of vision, drowslness, change in time sense, spatlal perception, and helghtened auditory acuity. Negative points of Importance include lack of neurologlcal changes and absence of significant effects on resplratlon, temperature, and resting blood pressure. Differentiation from LSD-25 should be relatively easy lunless a-mixture of drugs Is given) since pupillary dilatation, eccentuation of tendon reflexes and marked vlsual perceptval distortlon are not present during the C-9 reactlon. Lack of pupittary dtlatation serves to differentiate C-9 from Scopolamine. Alcohol and barbiturates Induce definite neurological changes (aysfagmus, ataxia ln gait and station, but do not induce dryness of the mouth and the characteristlc mental changes. caused by C-9. The C-9 reaction is. not likely to be confused with any of the major psychoses; It might however be confused with anxiety reactlons or panic states.

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Definition. Acute intoxication wlth the-diethylamide of lysergic acid refers. to the physiologlcal and mental changes produced by the .lagesfion of that drug. Acute LSD intoxication Is characterized by dilatation of the pupils, Iacreased systolic and diastolic blood pressures, increased deep tendon reflexes,. decreased superficial skin reflexes, retention of the puplllary reactions to light and accomodatton and absence of changes in tests of motor coordination and sensory function. In addition, the drug induces a characteristic train of "mental" symptoms which include, in rough order of appearance, sensation that something is happening to the indivtdual, nervousness and anxiety, peculiar sensations on the skin lelectric shocks, hot and cold sensations, Insects crawling on the skin, changes In the texture of objects la blanker feels [ike a buffalo robel, difficulty in concentreting, rapld rush of thoughts, changes in mood which vary from great elation to severe depression, changes In visual perception Ithings and people appear to be blurred; people and objects change In size, shape and colorì, "elementary" hallucinations Iperception of lights, colors, diagrams, patterns rapidly changing form, shape and size which are most prominent on closing the eyes, or going into a darkened roomì, and in extreme cases, true halluctnations (seeing persons or things that are not really present).

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Desplte these experiences, the subjcet knows wio he is, where he Is and the date and time.

Variations. The description of LSD intoxicatlon set forth in the definition above includes symptoms observed in Indlviduals who experienced maximal effects from LSD-25. It must be borne in mind that. as is the case with all drugs, the effects of Identical doses of LSD vary widely In. different lndividuals. A dose of 75 mcg. may Induce only slight nervousness in one Individual, whtle another person wili experience marked visual distortions and true hallucinatlons. In the same individual, the effect may vary, dependtng upon environmental circumstances. At present, however, all the reasons for the varlatlons in thc degree of effect in dlfferent individuals are. not compietely understood.

Effect of dosage. As is the case with other drugs, the larger the dose of LSD, the greater the effect in the same Individual: under the same circumstances. A person who experiences only mlld effects after having received a dose of 75 mcg. of LSD would be expected to experience moderate to marked effects with a dose of l25 mcg., and marked to -severe effects with a dose of 150 to.175 mcg. The dose of LSD also affects the time course of the intoxication. The effects appear more quickly and persist longer with the larger doses. Time coursz. The first signs and symploms of L5D lnioxicatlon appeor 15 to 30 minutes aftor.ingestion of the drug;

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maxlmal effects are usually evident within two hours. The effecfs remain maximal untll the 4th hour of the Inicxication and, thereafter, gradualiy decline. Symptoms and signs greatly abate after eight hours and are usvally completely gone after ló hours. Occasionaliy, severe reactlons may perslsi until the l2th or lóth hour after ihe drug Is ingested, and, in certain indlviduals, symptoms may be reported for several days after Ingestlon of a single dose of the drug.

Typical LSD reacticas. Typical LSD reactions may be descrlbed as mild, moderate, marked or severe on the basls of the mental symptoms experienced.

Mild reaction. A mild reactton consisis of a perception on the part of the subject that sonething has happened; some chenge, which is difficult to deseribe, has occurred in the way the subject feels. This change consists chlefly of sensations of apprehension, anxiety and nervousness. Concomitantly, fhe subiect may experience feelings of trembling inside his body of uncomfortable sensations In the stomach or chest, prlcklings on thz skin, and heaviness in various muscles: particularly the neck. The subject has difficulty In concentreting. end carrying out tasks invoiving iatellectual effort. He is, however, able to periorm these tasks, fhough sonewhet more slowly than in fhe undrugged state. Mood,. in this grade cf reacticn, is most frequentiy-one of mild elation and easy laughter. Visualperceptual distortions (changes in shape,

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size, color, of persons or objectsl do not occur. "Elementary" hallucinations and "true" hallucinations are not present. Insight Is retaincd - fhe. subject realizes that the symptoms he 1s experlencing are due to the drug.

Example' of mild LSD reaction. A negro male, age 40, recelved 138 mcg. of LSD-25 orally at 8 a.m. At 8:30, pup1ls had increased I mm. in diameter; deep tendon reflexes were unchanged. No sybjective symptoms were reported at this time. By 9 otclock, puplls had increased.2 mm. In dlameter and deep tendon reflexes had increased f.rom a barely perceptible jerk to a vigorous, rapld twitch. At 9 o'clock, patient reported sensations of unsteadiness, neryousness and Increased salivation. At l0 gtclock, puplis had increased 3 mm. as compared with the pre-drugged state; the knee jerks remained hyperactive. The patlent continued to report Increased nervousness, unsteadiness and indescribable sensations that things were different. No change in hls overt behavior was observed.At Il otclock, pupils had lncreased 4 mm. in diameter; knee jerk had become repetitive on a single light tap. The pattent continued to report nervousness; overt behavior remained. uachanged: Eight. hours after LSD wastaken. puotls were 3 mm. lerger thaa prior to ingestion of the drug. Knee Jerks were stili more active than beforc the drug, but, by this time, the patient was no longer reporting subjedtive tensatlons of any kind and he had begun to read again. The following morning he reported that he experienced no further

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tvz subiect/sensations after 2 p.m. This Is, therefore, an Illustration of a very mild reaction to a rafher large dose of LSD and despite the occurence of marked physiologlcal changes.

Moderate reaction. This degree of LSD effect Includes all the symptoms listed above under the mild reaction, In addition, the subject experiences changes in visual perception. These consist largely of alteration in the size, shape and color of the subjectts own body, or parts of his body, of other people, or of inanimate objects. Nood in this grade. of reactlon Is usually one of slight depression. Ordinarily, & distinct changes In overt behavlor occurs. The patient stops reading and does not spontaneously carry out any other activity reguiring Intellectual effort; rather sits quletly by himself. However, he can converse rationally, answer-questjons accurately, and carry out tasks involving some degree of mental effort, although:the time required to carry out these tasks is increased. Cccasionally, pafients are quite elated, laughing and gigglIng. Subject is definltely apprehensive; he may perceive a few "elementary" hallucinations llights, coiors posslbiy forming diagrams and oatterns which are most prominent on closing the eyes or golng into the. darkl. True hallucinations do not dccur.. Subject ts "oriented" (krows who and where. he is and the day of thz monthl. Inslght is retained: the subject realizes that his subjective experiences are due to the drug: He does not reporf experiencing a. sensation -that he Is ancther person or that a part of his

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body does not belong.to him.

Example of moderate reaction. A white male, age 27, received. 75 mcg. of LSD at 9:45 a.m. At 10:l5, pupils were dilated I am., and knee jerks had Increasedi At this time the patlent reported sensations that some change was occurring and that he feli nervous and was trembling inside. At l0:45, these sensafions were Increasing, pupils were now 3 mm. larger than before taking the drug and the knee-jerk had become extremely hyperactive, The potlent initially was elated, talked very volubty, but by l2:45, preferred to. sit quietly, although he answered questions readily when Interviewed. At l2:45, he reported that hls vision was blurred; that his-hands appeared to change size and shape as he watched them. At tlmes,other people appeared to be quite small and, at other fimes, extremely large.. On closing his eyes the patient saw shimmering white lights. Despite the distortioa of his hands,ather persons and inanimate objects, he identified the hands as being his own and unerringly ldentified other objects and other persons. At 4:4S pom., the pafient no longer reported visual disicriions, but stlll was experienciag apprehension and nervousness. These symptoms gradualiydeclined and had completely disappeared by l0 p.m. This, therefore, represents an exanple of roderate reaction to LSD, since it includes distorilons in visual perception as well as anxiety and apprehension. lote that thc

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dose in this partlcular individual was smaller than in the Individual with the mild reaction, even though the effect due to the drug was greater.

Marked reactlon. The marked reacfion Includes all the signs and symptoms of lhe mild and moderate reactlons and, in additton, the. degree of perceptual distortlon is greater and elementary halluclnations are very prominent. True hallucinattons do not occur.. The subject retains lnsight and realizes that the effects are due to the drug. In this degree of reactlon, the subject frequently reports confusion, even though he retains complete orlentation. The feeling of confusion is described variously as being: (l) fhings. appear to be quite unreal; or (2l the pattent is fearful of becoaing permanently insane; or 13] is fearful that the effects.of the LSD will not disappear. Example of marked reaction. A white male, age 62, recelved 75 mcg. of LSD at 9:00 a.m. At. 9:30, the pupils had: increased 2 mm. in size, and knee jerks had become quite hyperactive. At this time the patlent reported that he wes extremely nervous, was experiencing hot and cold sensations: feelings that Inserts were crawling on his skin, was trembling, felt unsteady and dizzy, and had sone difficulty in breathing. At ll otclock, pupils hed Incrzased 4 mm. in size; knee jerks had incrzased grzafly in amplitude and had becone iwiichy and repetitive. Patlent now reported that he felf ill, was nauseated, his lips and-poriions of his skin were numb. He was unsteady, had

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difflcutty in breathing, was aware of hls heart beat, hls hands felt extremely iight, hts eyesight was markedly blurred and he had difflculty In focustng hls vtstop. On looking at hīs hands, they became very large or shrank to,small slze. Other people appeared to be qulte small and of red color. At other times, only part of the person was altered. The wlndows appeared to be wide at the top and narrow at the. bottom. The patlent was extremely apprehenslve; he was afrald that he was gotng permanently Insane. Overt 'behavior was markedly changed. He jumped at the slightest sounds, stared into space and, from. time to time,held up hls hands and observed them In a puzzled way. Op closing his eyes, he deseribed many cólored lights, patterns and dlagrams. Despite this, he could answer questtons ratlonaliys attributed the effects he was experlenclng to the drugs and sald that he was afrald that he would not recover. At 12 otclock, he went lnto the bathroom, sat on the floor and refused to get up. He would give no explanation of this, but, however, readtly talked about mutual experlences, hls past life and so on. Later, he said that he could not get up from the floor because one of. his legs was gone. Symptoms began to abate about I' p.m., but marked visual dlstorttons were reported up untll 4 p.m. On the following day, he reported that he remalned nervous and tense until about l a.m., but thet he did not see colored. Ifghts or experience vlsual distortion after 4 p.m. Thls Is, therefore,

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an example of a marked reaction to LSD, since it includes nervousness, apprehenston, marked visual perceptual distortlons, elementary hallucinations and à feeling of depersonalizaflon Iloss of hts legl. Note that this effect occurred with the same dose which induced only a moderate reactlon in another subject.

Marked reactlon. The marked LSD reaction Includes all the symptoms. descrlbed under mild, moderate and marked grades and, In addition, true hallucinations occur and patient has at least partial loss of insight ldoes not realize at all times that the effects he Is experiencing are due to the drugsì.

Example of marked reacfion. A negro male, age 33, received 104 mcg. of LSD at 8 o'clock. By 8=30, puptls had increased I mm. In size;.but deep tendon reflexes were unaffected. By 9 o'clock, pupils had Increased 2 mm. in size and the knee jerk had become. greatly Increased in amplitude and was fwltchy. By l0 atclock patlent was reporting sensatlons of dizziness, unsteadiness, Insects crawling on the skin, pressure in the ears, blurring In vision, difficulty of focusing his eyes, shapes and colors were undergoing rapld alterations. Objects appeared to move in and out as he watched them and his hands felf qulte clumsy. Sy ll otclock, alt symptoms had become. very savere; pupils had Increased 4 mm. in diameter and fhe knee jerks were very great In amplitude. àt this time, patient was reporting and
great anxlety, dizziness, unsteadiness.fthat his hands and feet

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were constantly changing in size and shape. He became unsure whether he wes the subject or the inierviewer. He reported thaf he could see the interviewer's heart beating. He saw a doctor attempting to go into the next room, although at the time this was described, no other person was nearby. Volces In the walls werz holding conversatlons, some of which were addressed to. the patient. The patient was unable to carry out any .tasks requiring Intellectuel effort. He could not fill out a simple questionnarle, but, however, responded readlly to verbal questions. He was extremely apprehensive and fearful that fhe effects would not abate and that he would be permanently Insane. The effects remained Intense until 12 otclock and, thereafter, gradually declined. By 4 ciclock, the patient-was reporting only mild anxiety, lack of appetlte and a feeling that he was changed in some wey. At this time all hallucinations and. distortlons In visual perception had disappeared. The patient remalned somewhat apprehensive until l0 otclock that night. At this time he weat to sleep end on the following morning eppeared to be completely normel. This, therefore, is an exanpiz of marked reoction to LSD, since the patlent experlenced true hallucinefions and had partial loss of insight.

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