j. t, Dis.nerv.Syst. 30, Suppl. No. 2, 23-27 (1969). LSD 1797

,l.'agoo:g Mescaline and Lysergic Acid Diethylamide: Therapeutic Implications of the Drug-Induced State :oxic- P.E. HERMAN C.B. DENBER, M.D., Ph.D. )Zog/c :ago: *'I voas persuaded that by using such drugs one thylamide s_3, and mescaline _'ls. It is generally ¢ei_tl penetrate into the cavernous darkness of agreed that the effects of these two drugs are f po- _a$ illness and come to the ultimate hidde_t similar, with perhaps some minor variations of and ca_ue of these many stra_ge and different i//- a pharmacological and clinical nature _7. Their Drug _ which _j custom have come to be desig- relationship to the schizophrenic psychosis is _ork: hated as "madness". ' disputed _s, although KeeleV 9 maintains a re- So wrote Joseph Moreau de Tours in 1845 _,2 semblance does exist between them. Our studies ating _ in regard to his experimental studies with are in agreement with the latter. tal to ', hashish. He emphasized that experiencing the t-380, , dr_-induced psychotic-like syndrome could Clinical ' lead to insight regarding the patient's illness. While there is a similarity between reac- dif- Some inferences of his work, described in a tions of normal, neurotic or psychotic subjects .-ugs::250- pilpar submitted to the Academic des Sciences to both drugs, the psychotic patients tend to , of Paris for the Prix Montyon in 1845, were show a greater disorganization of thought.

,logic _ criticized by the committee who said, "unfor- Schizophrenic patients in remission will have , 26_ .tunately, the facts related to the therapeutic a recrudescence of their psychosis under use of hashish are insufficient to allow one to mescaline or lysergic acid diethylamide which draw any conclusions whose practical applica- is difficult to distinguish from the endogenous tions would be incontestable". One hundred and disorder. Artists, writers and others occasion- twenty-three years later, the situation has ally have a vivid reaction, sometimes described changed little in regard to the therapeutic ad- as leading to a profound "transcendental ex- ministration of drugs capable of producing perience". The drug accentuates the basic per- states resembling naturally occurring mental sonality pattern and has been used in some in- dimrders, stances as a diagnostic tooF °. At the present time, the use of pharmaco- The following refers to the effects of an in- l_gic compounds which can experimentally in- travenous i_jection of 500 mg. of mescaline d_ce a condition of disordered feeling or think- in hospitalized psychiatric patients, based on a hag is considered to be fraught with much dan- comprehensive study of 350 patients. Within ger s'e. GrinkeV gives the ultimate view that ten minutes (although when given orally it is "[he drugs are indeed dangerous even when much slower), a series of symptoms appeared: t used under the best of precautions and condi- Tachycardia, hypertension (hypotension also i tiqms". Restrictive regulations in many coun- may occur), mydriasis, marked anxiety, ten- i t_ concerning the experimental use of so- sion, sensations of hot and cold (frequently calk_ "hallucinogenic" drugs threatens to re- in the genital area), retching, vomiting, pep- talM and finally inhibit further research in permint taste in the mouth, choking, constric- hh_ areas. Science requires a more sober ap- tion of the chest and hyperpnea. The skin may Inrush to the problem and such is the purpose show color changes, occasionally becoming cold efthis brief review, and blanched. A desire to defecate or urinate i J Much interest has been centered on reports was expressed, although rarely necessary.

economy was met by a riddance mechanism -- ii of therapeutic activity for lysergic acid die- An external threat to the organism's inner " _f lB_ea_'ch Division, iVfanhattan State Hospital, the desire to urinate, defecate or expectorate. i_ Wlut_s Island, New York, N.Y. 10035. This took place almost immediately after the t; 23 t

I-IERI_IANC.B.DENBER

injection began, before it was terminated, and and space are described. Some patients ap- t before any- real psychologic response had taken peared to be living through a dreamy ecstatic occu place. This reaction would seem to indicate that state, undergoing an extraordinary inner ex- prok "flight" occurs before "fight", is unconscious perience with very little external display. It in c_ and might even be instinctive. Flight would would be as if they had retreated "within" ' whir appear to be more primitive of the two reac- where they and the world were the same. pro}. tions, with fight being only a later possible cot- Symbolic acting-out with gesturing is very '- leas1 tieal addition. This would suggest perhaps an common; recognition of these displays is most cone instinctual response which is present even in helpful in understanding similar phenomena horn the most primitive forms who attempt to rid from a psychodynamic point of view. Women itial themselves of noxious or poisonous agents-_k may fantasy parturition even though never any Some patients screamed, "I'm going crazy, previously pregnant. Transference feelings '-

Tpenhisdingstuffdoommakesis occasionallyme crazy". verbalized.A feeling ofTheseim- withmarked.acting-outAggressiveto theand psychiatristhostile impulareses veryare i_ ._ s._nmptoms recede within ten minutes as the released, directed outwardly in either a random, _, , of v patient becomes increasingly fearful, suspi- diffuse fashion or towards an individual -- fre- '_ resp. cious, hostile, antagonistic and apprehensive, quently the psychiatrist, who then becomes a _ The, looking about furtively in the room and walk- symbol of feelings towards the patient's signi- ' ease: ing restlessly, ficant environmental figures (usually the par- r , still One of three events can occur between 20- ents). The physician reminded one patient of a var_ 30 minutes after the onset: a) anxiety in- her father, "He used to lock me in the room motiv creases vertically and the patient is in the grips and I'd scream and bang on the door. I hate treatr of an intense panic state which dominates the you like I hated him". In this ease, the pa- action clinical picture, b) the autonomic reaction dis- tient was referring to the treatment room door .- state_. appears as the patient rests quietly and is which was locked. These potentially destrue- revie_ withdrawn for the duration of the drug-in- tive impulses were accompanied by an intense , wider duced state, or c) anxiety decreases and symp- affeetive discharge. .* addict toms appear. Childhood memories are reactivated and re- uals, combination.The symptomsAn acusuteuallypanicappearedreaction alonecan occuror in lived with intense and extraordinary clarity, , , furth, whithe lepicture., on the Whenother nausea,hand, mutismretchingmayanddominatevomit- athoughtsccompaniedand byfeelingssimilarareemotions.so strongThethatflowtheyof i havpsycte " ing took place throughout the entire session, are difficult to repress, "The thoughts come so ' .' resul fast, before one is out, the other is there". Sex- thou: thomhe osexualsexual idcentityonflict wasor completefound in theconfusioncase his-in ual material is frequently noted and oft times tacul tory. A 21 year old Puerto Rican male with a forms the main part of the treatment session, psyc! history of marked homosexual conflict became It may be expressed openly or symbolically, studi panic stricken as he looked at the syringe used Inflating a blood pressure cuff reminded one ment to inject ehlorpromazine at the end of the treat- patient "of masturbation -- I masturbate with ment. This patient has been nauseous, retched, my right hand". Visual hallucinations are in- T vomited and expectorated throughout -_°-. frequent, although they occur more often in orde., Euphoria,expansiveness,and manic-likebe- the normal,psychoneurotica,rtistand writer. chost havior may appear. Emotions become more pro- Auditory hallucinations are reported but are line ; found, and the patient has a feeling of inner not frequent, preci awareness --the unkno_-n self that becomes The symptoms may rise and fall in waves, shoul apparent. He becomes the observer and the occasionally accompanied by nausea, and finally sion-? observed at the same time. Paranoid and recede after one hour, although they can re- easio somatic delusions, illusions, visual, auditory or main heightened up to the second hour. The atten olfactory hallucinations, depersonalization, de- symptoms slowly disappear, and by 4-6 hours exert realization, disturbances in perception of time are no longer present, ever:

24 I

MESCALINE AND LSD: THERAPEUTIC IMPLICATIONS tp- Prolonged reactionscan occur23,and two psychoticbreakdown.This refersequallywell tic occurred in this present series. These were to the "fringe group" living a communal ex- ;x- probably the result of the patient's difficulty istence using excessive amounts of alcohol, It in coping with the flood of traumatic mater'al marijuana, cocaine, heroin, mescaline, lysergic n" which otherwise was repressed. It is im- acid diethylamide, amphetamine, etc., to sus- probable that they have a biochemical basis, at tain a failing ego. The drugs should not be ;ry . least if animal data can be extrapolated. The given to patients with paranoid personalities. _st concentration of mescaline in rat brain at two Cardiac disorders and hypertension may be ac- na hours is 0.004% of the amount injected in- centuated with mescaline. en itially :4. This amount is incapable of producing Technique ,er any reaction when given as a single dose. " The isolated use of mescaline and/or ly- .gs _ Indications sergic acid diethylamide cannot be considered _ry _ Mescaline or lysergic acid diethylamide are as a form of treatment. The drug session should ,trem, _5 " of value in the psvchoneuroses that are un- be conducted in a psychodynamic frame of re- re- _ responsive to psychotherapy or chemotherapy, ference by a psychiatrist experienced in the _a - They would be appropriate for use in those use of these agents, who has had a didactic at- cases where the psychoanalysis is at a stand- analysis, and who preferably has taken either _r- still andno therapeutic work seems possible for one personally. The drugs should be admin- of a variety of reasons• The patient must be well istered as an adjunct for psychoanalytic ther- )m motivated and understand the rationale for apy to a patient already in treatment and for Lte , treatment. Resistant obsessive-compulsive re- whom there is a clear-cut need. They should )a- actions, hysterias, phobias and chronic anxiety not be given to patients who are referred "for _or _ - states are interesting areas of application. A evaluation concerning possible use of LSD or _c- review of the literature :_ suggests a much mescaline." The patient should be fasting, al- gae wider range of use -- in psychopaths, drug though this is not absolutely necessary. The , addicts, alcoholics, sexual deviates, homosex- initial dose of lysergic acid diethylamide varies re- uals, depression, etc., but these still require from 25 gamma upwards, although it is best W, _ further experimental confirmation. Both drugs to start the first treatment at this dose, in- of have been used extensively in the treatment of creasing by similar increments until a pro- _ey psychoses -- particularly schizophrenia. The ductive session is achieved. Successive treat- so _ results here, however, are controversial :°,_, al- ments are carried out with the same amount. __ though there have been unquestionable "spec- Mescaline is administered in 500 mg. doses les tacular" results with complete remission of the orally or intravenously. m. psychosis in a matter of 24 hours_t Further The patient lies on a couch in a quiet room, _y. , studies indicate the value of mescaline in treat- with the therapist constantly in attendance. He me ment-resistant schizophrenics_-t is requested to verbalize all feelings and thoughts while associating freely. Interpreta- ith C_atralndicatlons tions are offered in a fashion similar to a non- in- The use of drugs capable of inducing dis- drug session. While the drug may be allowed in orders resembling the naturally occurring psy- to run its course before terminating (4-6 er. ehoses is absolutely contraindicated in border- hours), it would appear preferable to stop after Ire , line psychotics. Their use in such patients may 1_-2 hours, using 50 mg. of chlorpromazine precipitate an overt psychotic breakdown. They given either orally or intramuscularly. es, should be used with extreme care in "depres- One or two drug sessions per week are in- ]ly sion-prone"individuals, for there have been oc- dicated, and additional time may be used to re- ¢asional reports of transitory depression and review the material in a drug-free state. But %e attempted or actual suicides _. Care should be it would still seem preferable to conduct the _rs _, exercised in treating patients who have "tried drug session along the same principles as non- • everything," for often they are verging on a drug psychoanalytic treatment. 25

i HERI_N C.B.DENBER ___

Complications stare "2 have been unable _o find evidence of , 3ro:9' Psychotic breakdown, transitory psychotic chromosomal breakage in human leukocytes ex- -_, 12. D_ behavior, acute panic state, acting-out, suicide, posed to lysergic acid diethylamide. _ gi_ brief depression, delayed reaction occurring Summary *i" 13. M: several days or weeks after_vards have been The clinical effects of mescaline and lysergic _ Dedr rep°rtedS'4" acid diethylamide have been described as well _- 20 Precautions as the indications, contraindications and tech- 14. D_ All patients should be screened carefully nique. Precautions and complications have been S,: and not accepted for treatment unless well noted. Some comments have been made on the lit known to the treating psychiatrist. Patients theoretical implications of these drugs. 15. F,64 must be under constant observation during and REFERENCES liz after the drug treatment, and family or staff 1. Baruk, H.: La vie et l'oeuvre de Moreau de P-_ should be well trained to discern incipient or Tours in Ann. Moreau de Tours, Vol. I, edited 26 delayed reactions. While these are rare, they by H. Baruk and J. Launay (Presses Univ. 16. L_ may become frightening and are potentially de France, Paris, 1962), pp. 9-14. SI dangerous to the patient. Rapid treatment at 2. Collet, C.G.: Candidature de Joseph lV[oreau 17. U this moment with neuroleptic drugs is advis- (de Tours) au Prix l_ontyon de l'Academie P' able. Should the patient develop a transitory des Sciences en 1846 in Ann. Moreau de Tours, 1_ psychotic breakdown -- a rare eventuality -- Vol. I, edited by H. Baruk and J. Launay 18. R, intensive treatment with high dosages of neu- (Presses Univ. de France, Paris, 1962_,, pp. t_,. roleptics is indicated. 15-21. ct 3. Cohen, S. : Lysergic Acid Diethylamide: Side 19. K, Commenf Effects and Complications, J. Nerv. MenL -i- th Data developed over the past 15 years in- Dis., 130:30-40, 1960. _ O" dicate that mescaline and lysergic acid die- 4. Cohen, S. and Ditman_ K.S.: Complications _ 6_ thylamide are experimental and therapeutic Associated with Lysergic Acid Diethylamide _, 20. R (LSD-25), J.A.M.A., 181: 161-162, 1962. _ C: tools which can produce states analogous to 5. Ludwig, A.M. and Levine, J. : Patterns of Hal- _ si naturally occurring psychoses and thus repre- lucinogenic Drug Abuse, J.A.M.A., 191: 92- t 21. D sent effective "models" for further study of 96, 1965. ! P these disorders. 6. Ungerleider, J.T., Fisher, D.D. and Fuller, g_ cl Efforts to limit laboratory and carefully M.: The Dangers of LSIY, J.A.M.A., 197: 389- 22. D controlled clinical studies with these drugs will 392, 1966. I IV effectively inhibit research in a field where 7. Grinker, R.R.: Bootlegged Ecstasy, J.A.M.A., | IV progress has been minimalcomparedto other 187:768,1964. 1 l_ branches of medicine. Application of the tech- 8. Geert-Jorgensen, E., Hertz, ]VL,Knudsen, K. niques of molecular biology hold much promise and Kristensen, K. : LSD-Treatment; Expert- ! for psychiat_', but the tools and models must ences Gained Within a Three Year Period, be available:t Acts Psychiat. Scand., 40 (Suppl. 180):373- Based on animal data :_, most of the mesca- 382, 1964. line has been excreted at two hours, and it is 9. Ling, T.:M.and Buckman, J. : The Use of Ly- ! difficult to imagine that a "delayed reaction" sergic Acid in Individual Psychotherapy, i " Proc. Roy. Soc. Med., 53:927-929, 1960. could be due to the drug. Other factors (ex, 10. Sandison, R.A., Spencer, A.M. and Whitelaw, i psychological) would appear to be causative. JJ:).A.: The Therapeutic Value of Lysergic Judgment must be reserved concerning chro- Acid Diethylamide in Mental Illness, J. Ment. mosomal damage :s.-_9or the production of con- Sci., 100:491-507, 1954. "i" genital malformations 3°,a_in view of the pos- 11. Abates, R.: Therapeutic Application of the i s_le experimental errors inherent in the tech- Change in Consciousness Produced by Psy- ). niques used and the fact that such changes may cholytica (LSD, Psilocybin, etc.) The Psy- 'f" be non-specific. Loughman, Sargent and Israel- chedelic Experience in the Treatment of Neu- [ I ...... __ ,_ ...... •...... ? _ _ ...... 7,_ _-.7,_: __ , _!_¢____.__._._ :,_,_ _ T_ _'_ _'_11Ir f "

i :M-ESCALINE AND LSD: THERAPEUTIC IMPLICATIONS

rosis,Acta Psychiat. Seand., &0 (Suppl. 180: 23. Stevenson, I. and Richards, T.W.: Prolonged ce Of 397-408, 1964. Reactions to Mescaline. A Report of Two ._. ex- - 12. Delay, J. and Eenda, P. : L'Experience Lyser- Cases, Psychopharmacologia, 1:241-2550, gique, L'Encephale, 3:169-209, 1958. 1960. *!" 13. Mariategui, J. and Zambrano, M.: Psicosm- 24. Denber, H.C.B.: Intracellular Localization of dr0mes Experimentales Con Lo_ DerivadoL: Psychotomimetic and Psychotropic Drugs. _rgic ' Del Acido Lisergico, Rex'. Neuro-Psiquiat., Ph.D. Thesis. Graduate School of Arts and well .t. 20:451-474, 1957. Science. :New York University, pp. 1-62, 1967. :ech- ' 14. D_nber, H.C.B. and Merlis, S.: A Note on 25. Crocket, R., Sandison, R.A. and Walk, A.: , been Sane Therapeutic Implications of the :_Iesca- Hallucinogenic Drugs and Their Psychother- n the l_e- Induced State, Psychiat. Quart., 28:6_ apeutic Use. Springfield, Charles C. Thomas, q_t0, 1954. pp. 1-185, 1963. 15. Frederking, W.: Intoxicant Drugs (i_fesca- 26. Postel, J. and Cossa, P.: La Therapeutique line and Lysergic Acid Diethylamide) in Par la Psychose Induite (Chlorpromazine et au de Psychotherapy, J. Nerv. Ment. Dis., 121:262- Mescaline), Ann. Med.-Psyeh., 14:254-282, edited _6, 1955. 1956. Univ. 16. Leuner, H.C. : Die Experimentelle Psychose, 27. Turns, D. and Denber, H.C.B. : Mescalin und /_pringer-Verlag, pp. 1-275, 1960. Psychotherapie, Arzn. Forseh., 16:251-253, 1966. _oreau 1_. Unger, S.M. : _Iescaline, LSD, PsilOcybin, and 28. Irwin, S. and Egozcue, J. : Chromosomal Ab- demie Personality Change, Psychiatry, 26:111-125, 1963. normalities in Leukocytes From LSIY-25 rours, Users, Science, 157:313-314, 1967. aunay 18. ]_ubicek, J.: Similarities and Differences Be- 29. Cohen, I_I.M. and Marinello, M.M.: Chromo- }, pp. tween Schizophrenia and Experimental Psy- somal Damage in Human Leukocytes Induced c_oses, Rev. Czech. Med., 4: 125-134, 1958. by Lysergic Acid Diethylamide, Science, 155: : Side 19. Keeler, I_I.H.: Similarity of Schizophrenia and 1417-1419, 1967. Merit. -;. the Psilocybin Syndrome as determined by 30. Geber, W. F.: Congenital Malformations In- ; Objective Methods, Int. J. Neuropsych., 1: duced by Mescaline, Lysergic Acid Eriethyla- _t/ons - _0-634, 1965. mide, and Bromolysergic Acid in the Hamster, mmide _ 20. Ropert, _I.: La l_Iescaline en Psychiatric Science, 158:265-266, 1967. ;2. , __inique et Experimentale. Thesis. Univer- 31. Alexander, G.J., Miles, B.E., Gold, G.M. and ,f Hal- _ s/ty of Paris, pp. 1-427, 1957. Alexander, R. B.: LSD: Injection Early in 1: 92- 21. Denber, H.C.B.: Studies on _,Iescaline VIII: Pregnancy Produces Abnormalities in Off- ]Psychodynamic Observations, A_mer. J. Psy- spring of Rats, Science, 157: 459-460, 1967. Fuller, _': ehiat., 115:239-244, 1958. 32. Loughman, W.D., Sargent, T.W. and Israel- ': 389- 22. Denber, H. C. B. and l_Ierlis, S.: Studies on stare, D_M.: Leukocytes of Humans Exposed _,¢escaline VI. Therapeutic Aspects of the to Lysergic Acid Diethylamide: Lack of _M_A., _ _escaline_Chlorpromazine Combination, J. Chromosomal Damage, Science, 158:508-510, ]_erv. l_lent. IYis., 122:463-469, 1955. 1967. _en, K. ,_xperi- Period, )) :373-

_Ly- _.,'apy, SO. _itelaw, _-sergic . Ment-

(_the y Psy- i i