The Experimental Use ofPsychedelic (LSD) PsychotherapyWalter N. Pahnke, MD, PhD; Albert A. Kurland, MD;Sanford Unger, PhD; Charles Savage, MD; and Stanislav Grof, MD

The history of research withpsychedelic drugs has pro-duced a variety of methods

for their use and conflicting claimsabout results. First came the waveof excitement among experimental-ists in the 1950s when it was claimedthat lysergic acid diethylamide(LSD) could produce a model psy-chosis which might be useful inunderstanding schizophrenia. Whilethis promise was fading, enthusi-astic reports about the possibility ofLSD as an aid to psychotherapy inthe treatment of alcoholism andother psychiatric disorders ap-peared. All these approaches wererepresented in 1959 at the first in-ternational conference devoted en-tirely to LSD. 1 Since then, therehave been at least five more pub-lished proceedings of such confer-ences on various aspects of psyche-delic drugs.v" The most recentconference on various means of pro-ducing states of consciousness wassponsored by the Menninger Foun-dation and the American Associa-tion of Humanistic Psychology onApril 7 to 11, 1969, in CouncilGrove, Kan, and was called "Vol-untary Control Of Internal States."

In the 1960s we have seen re-search attempts to test scientificallythe efficacy and safety of psyche-delic drugs for the treatment of var-ious forms of mental illness, chieflyalcoholism. At the same time, there

has been a rapidly growing interestconcerning these drugs by laymenfor pleasure, excitement, mental ex-ploration, and religious experience.The use of psychedelic drugs for allthese purposes has produced con-flicting claims both in the scientificand popular literature, intense pub-lic attention stimulated by the massmedia, and legislative attempts atcontrol of both research and theblack market.

Effects in Man Facilitated byPsychedelic Drugs

Before we turn to the use of psy-chedelic drugs as a therapeutic tool,let us review briefly some basicfacts. At the outset, it is importantto remember that psychedelic drugsare a special class of psychophar-macological agents, not to be con-fused with sedatives like barbitu-rates or alcohol, stimulants likeamphetamines or methylphenidatehydrochloride (Ritalin), tranquil-izers like chlordiazepoxide hydro-chloride (Librium) or meprobamate(Miltown) , antipsychotic agentslike the phenothiazines, or narcoticdrugs like the opiates (whether syn-thetic or natural) . Psychedelic drugsin contrast to true narcotics are notphysically addicting and produce-quite different psychological experi-ences from all these other groupsof drugs.

From the Maryland State PsychiatricResearch Center, the Johns Hopkins Uni-versity School of Medicine (Drs, Pahnke,Unger, Savage, and Grof), and the Depart-ment of Mental Hygiene, State of Mary-land (Dr. Kurland), Baltimore.

Read before the Symposium on Psyche-delic Drugs at the 118th annual conventionof the American Medical Association, New

York, July 17, 1969. Based partially on apresentation by Albert Kurland, MD, atthe American College of Neuropsycho-pharmacology, San Juan, Puerto Rico,Dec 20, 1968.

Reprint requests to Maryland Psychi-atric Research Center, Box 3235, Baltimore21228 (Dr. Pahnke).

1856 JAMA, June 15, 1970 • Vol 212, No 11

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What makes psychedelic drugsunique as a class are the psycho-logical phenomena which they facil-itate. Five major kinds of potentialpsychedelic drug experiences havebeen described in detail with ex-amples elsewhere':" and will onlybriefly be summarized here.

First is the psychotic psychedelicexperience characterized by the in-tense, negative experience of fear tothe point of panic, paranoid de-lusions of suspicion or grandeur,toxic confusion, impairment of ab-stract reasoning, remorse, depres-sion, and isolation or somatic dis-comfort or both; all of these can beof very powerful magnitude.

Second is the cognitive psyche-'delic experience, characterized byastonishingly lucid thought. Prob-lems can be seen from a novel per-spective, and the inner relationshipsof many levels or dimensions can beseen all at once. The creative ex-perience may have something incommon with this kind of psyche-delic experience, but such a possi-bility must await the results offuture investigation.

Third is the aesthetic psychedelicexperience, characterized by achange and intensification of all sen-sory modalities. Fascinating changesin sensations and perception canoccur: synesthesia in which soundscan be "seen," apparent pulsationsor lifelike movements in objectssuch as flowers or stones, the ap-pearance of great beauty in ordi-nary things, release of powerfulemotions· through music, and eyes-closed visions of beautiful scenes,intricate geometric patterns, archi-tectural forms, historical events,and almost anything imaginable.

LSD Psychotherapy-Pahnke et al

Fourth is the psychodynamic psy-chedelic experience, characterizedby a dramatic emergence into con-sciousness of material that was pre-viously unconscious or preconscious.Abreaction and catharis are elementsof what may subjectively be experi-enced as an actual reliving of inci-dents from the past or a symbolicportrayal of important conflicts.

The fifth and last type of psyche-delic experience has been called byvarious names: psychedelic peak,cosmic, transcendental, or mystical,and can be summarized under thefollowing six major psychologicalcharacteristics (described in moredetail elsewhere7

): (1) sense ofunity or oneness (positive ego trans-cendence, loss of usual sense of selfwithout loss of consciousness), (2)transcendence of time and space,(3) deeply felt positive mood (joy,peace, and love), (4) sense of awe-someness, reverence, and wonder,(5) meaningfulness of psychologi-calor philosophical insight or both;and (6) ineffability (sense of diffi-culty in communicating the experi-ence by verbal description).

The Varieties of PsychedelicDrug Therapies

In the course of experimentaltherapeutic work with psychedelicdrugs (especially LSD), three majorapproaches have evolved: (1) psy-cholytic therapy, (2) psychedelic-chemotherapy, and (3) psychedelic-peak therapy. Each of these methodshas been described and discussed indetail at the international confer-ence on LSD therapy held in 1965.s.In any evaluation of therapeuticeffects, it is essential to keep inmind the differences in procedureamong the various methods, notonly because different kinds of ex-periences are facilitated, but becauseconflicting results can be correlatedwith the method used. Reactions toLSD invariably involve a complexinteraction between drug dosage, set,and setting.

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In psycholytic therapy, which ispracticed mainly in Europe, theaim is usually the uncovering of un-conscious material which can bepsychodynamically analyzed bothat the time and in subsequent psy-chotherapy sessions. There is con-siderable time spent on psycho-therapy before, during, and afterthe actual drug sessions. This typeof therapy is relatively long-termwith multiple sessions over time andusually with small doses of the drug(25/Lg to 150/Lg).

In psychedelic-chemotherapy, themajor emphasis is on administra-tion of the drug itself, during whichlimited psychotherapy mayor maynot be carried out. There is minimalpreparation and follow-up therapy.A single session with a relativelyhigh dose of the drug (200 /Lg ormore) has been the usual practice,although there have been experi-ments which consisted of weeklysessions with little or no attempt athelp with interpretation or integra-tion. This method is called hypno-delic when hypnotic induction isemployed during the preparationfor the session or before the onsetof drug effects or both with the aimof providing better control. Themajor differences between psyche-delic-chemotherapy and psycholytictherapy are the number of drugsessions, amount of therapy outsidethe drug sessions, and drug dosage.

In psychedelic-peak therapy, oneof the distinctive characteristics andimmediate goals in the drug sessionitself is the achievement of a peakor transcendental experience, butjust as important is the intensivepsychotherapy which occurs in theweeks prior to the psychedelic drugsession and the follow-up therapyin the weeks after to help with thework of integration. The LSD ses-sion can add meaningful emotionalinsight and dramatic validation ofan individual's basic self-worth, butusually only after the achievementof psychodynamic resolution and

self-understanding during the pre-paratory psychotherapy. This prep-aration, which averages about 20hours per patient, enables the ther-apist to establish close rapport withthe patient and to gain intimateknowledge of the patient's develop-mental history, dynamics, defenses,and difficulties. In specific prepara-tion for the session itself the patientis encouraged to trust the therapist,himself, and the situation, to letgo voluntarily of his usual ego con-trols and be carried by the experi-ence, and to be completely open towhatever experiences he encounters.

The experimental drug sessionsthemselves are carried out in aspecial treatment suite furnishedlike a comfortable living room, withsofa, easy chairs, rugs, drapes, pic-tures, flowers, and high-fidelitymusic equipment. The patient'stherapist and a psychiatric nurseare in constant attendance through-out the period of drug action (10 to12 hours). For most of the session,the patient reclines on the sofa witheyeshades and stereophonic ear-phones, alternately listening to care-fully selected classical music or in-teracting with his therapist. Thefunction of the music is to help thepatient let go more easily, to entermore fully into his unfolding innerworld of experience, and to facili-tate the release of intense emotion-ality.

Although the LSD session itselfis only one part of psychedelic-peaktherapy, it plays a unique andnecessary role without which thetotal therapeutic impact would notbe the same. In a dosage of 200 f.Lgor more, LSD produces a 10- to 12-hour period of striking, varied, andanomalous mental functioning; therange of possible effects or episodesof reaction or both is multiform.Certain dimensions of possible re-activity are therapeutically irrele-vant (eg, sensory changes) othershave distinctly anti therapeutic con-sequences (eg, panic, terror, or

LSD Psychotherapy-Pahnk2 et al 1857

psychotic reactions) . The majordimension of drug-altered reactivitywith therapeutic relevance is theaffective or emotional sphere; in-tense, labile, personally meaningfulemotionality is uniformly produced,with periodic episodes of over-whelming feeling. In terms of se-cuence of events, the first severalhours of a psychedelic session arenonspecific and pervasive; persist-ent preoccupations and emotionaldistress patterns are "broken" orfragmented, and subsequent recallfor this period is nearly alwayspoor. During the third to fifthhours, psychedelic reactivity usual-ly appears at peak intensity. Withskillful handling, the remainder ofthe session may be stabilized inan elevated mood state in whichpsychotic and other turbulent phe-nomena are no longer problems.Follow-up therapy begins during thereentry period of the session dayand continues the next day as thepatient and therapist review theevents of the session and attemptto integrate them. The patient isencouraged to write a detaileddescription of his experience.

If a psychedelic-peak experiencehas been achieved and stabilizedduring the session, a clinical picturewhich we have termed the psyche-delic afterglow can be observed inthe days after the session. Mood iselevated and energetic; there is arelative freedom from concerns ofthe past and from guilt and anxiety,and the disposition and capacity toenter into close interpersonal re-lationships is enhanced. These psy-chedelic feelings generally persistfor from two weeks to a month andthen gradually fade into vivid mem-ories that hopefully will still influ-ence attitude and behavior. Duringthis immediate postdrug period,there is a unique opportunity foreffective psychotherapeutic work onstrained family or other interper-sonal relationships.

It should be emphasized, how-

ever, that even with optimal pro-gramming, sueh peak experiencesare neither universally achieved norstabilized, and certainly they do notautomatically occur merely by ad-ministration of a psychedelic drug.In our research setting,profound ormarked psychedelic-peak reactionswere judged to have occurred in68% (56) of 82 consecutive alco-holic patients who received a totalof 450l-lgof LSD given in two equaldoses 45 to 60 minutes apart.

Research Projects WithPsychedelic-Peak Psychotherapy

Since 1963, at the Spring GroveState Hospital, Baltimore, and nowcontinuing at the Maryland Psy-chiatric Research Center, researchhas been in progress to investigatethe usefulness of psychedelic-peakpsychotherapy with alcoholic, neu-rotic, and narcotic addict patientsand patients who are dying of can-cer."?" The project which involvedalcoholic and neurotic patients, bothoriginally funded by research grantsfrom the National Institute ofMental Health (NIMH) were de-signed as double-blind, controlledstudies. In each project the experi-mental group received a relativelyhigh dose of LSD (350flg to 450flg)in contrast to only 50fLg for the con-trol group; both groups receivedexactly the same therapeutic prep-aration. In the study of neuroticpatients there was an additionalcontrol group of randomly assignedpatients who received an equivalentnumber of hours of group psycho-therapy without any LSD. Evalua-tion of each patient's status wasperformed by an independent ratingteam before treatment and at 6, 12,and 18 months following the treat-ment phase. Full and final analysisand evaluation of these data arestill in progress.

Results are now completed at thesix-month checkpoint for the studyof a total of 135 alcoholic patientswho were treated with psychedelic

1858 JAMA.June 15. 1970 • Vol 212. No 11

psychotherapy. While the study de-sign made it possible for the pa-tients to have up to three sessions,the vast majority in both experi-mental and control group (total of117 patients) received only onetreatment with LSD. The 18 pa-tients who had more than one LSDsession were not found to be differ-ent from the other 117 in psycho-logical and social measures basedon pretreatment testing, but as agroup they received more averagehours of treatment. Therefore, inthe interests of uniformity concern-ing amount of treatment, resultswere analyzed separately for the117 patients who had only one LSDsession (either a high or low dose) .Out of these 117 pateints, 104 werepersonally located for follow-up in-terview after six months. It shouldbe noted that the 13 patients notreached for follow-up were properlyproportioned according to the orig-inal random assignment in whichtwo thirds of the patients were al-lotted to the high-dose procedure.

Comparison of means before treat-ment and six months after treat-ment for global adjustment anddrinking behavior are shown inTable 1. Global adjustment includedoccupational, interpersonal, and res-idential factors as well as the pa-tient's reaction to alcohol. Ratingswere made on each patient on apredetermined 0 to 10 behavior rat-ing scale. The end points of thescale measuring drinking behaviorwere 0, indicating daily alcohol con-sumption, and 10 indicating totalabstinence. Patients were also cate-gorized according to whether a pro-found, marked, or minimal psyche-delic-peak experience was achievedduring the LSD session as rated bythe patient's therapist immediatelyafter the session. In Table 1, com-parison of means before and aftertreatment between groups receivinghigh and low doses and among thepsychedelic reactivity groups maybe seen to show statistically signifi-

LSD Psychotherapy-Pahnke et al

cant differences using an analysisof covariance statistical procedure(one-tailed test).

The percentage of patients func-tioning in an "essentially rehabili-tated" fashion is shown for thevarious groups in Table 2. A scoreof 8 or more on the 0 to 10 scalewas considered a rigorous criterion,indicating for global adjustmentthat a patient was making "goodattainment or adjustment" with re-gard to drinking, occupation, inter-personal relations, etc. A score of 8on the drinking scale indicated some,but only minimal, departure fromtotal abstinence. Statistical analysisrevealed that there were significantdifferences between the high andlow-dose groups in percentage ofpatients reaching this criterion, bothin global adjustment and on thescale measuring drinking. Thegroup of patients with the most pro-found psychedelic-peak experienceshad the highest percentage of pa-tients who showed evidence of re-habilitation. This trend was statisti-cally significant among the threepsychedelic reactivity groups forglobal adjustment, but not for drink-ing, and thus must be interpretedwith caution.

In evaluating these findings inpractical terms, we can say that agiven alcoholic patient receiving asingle high dose of LSD in the con-text of psychedelic-peak psycho-therapy and experiencing a profoundpsychedelic-peak reaction has thebest likelihood for improvement sixmonths later. Within the context ofour method, dosage appears to be amore certain outcome predictor thantype of experience, although peakexperiences do occur more frequent-ly with high doses of LSD. Also theestimation of psychedelic reactivity(from the individual judgments ofdifferent therapists) is probably notas reliable as the measurement oftherapeutic outcome made by eval-uators independent from the treat-ment team.

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Table I.-Comparison of Means of Alcoholic Patients Receiving One LSDSession

Global A~justment Drinking ,Behavior

Before 6 mo After Before 6 mo AfterPatient Group Treatment Treatment Treatment Treatment

DosageHigh

(N = 64) 4.16 6.52 2.83 7.02Low

(N =40) 3.28 5.13 2.93 5.75Psychedelic reactivity

Profound(N =31) 4.43 7.13 2.65 7.52

Marked(N =31) 3.87 6.16 2.94 6.94

Minimal(N =50) 3.50 5.34 2.92 5.82

Results of Covariance AnalysesFor Above Data F p. F P'

High dose vslow dose 3.76 0.05 4.43 0.025

Psychedelic reactivitygroups 2.42 0.05 3.09 0.025

.p values are for one-tatted tests of significance.

An NIMH-sponsored project toinvestigate the effect of psychedelic-peak psychotherapy with narcoticaddicts is well underway, but it istoo early for any indication of ther-apeutic outcome. These patients ingeneral seem to have a greater de-gree of psychopathology than thealcoholics with whom we haveworked, but the skilled implementa-tion of psychedelic psychotherapyseems to be proceeding smoothly.An observation of interest is thatthe character of the drug experiencewith LSD has been reported by theaddicts to be distinctly and qualita-tively different from what they ex-perienced under heroin (ie, a con-frontation with their problemsrather than an escape from them).

During the past several years, wehave also been exploring the poten-tial of psychedelic-peak psychother-apy with patients with cancer.t"?"The purpose has been to treat thedepression, anxiety, psychologicalisolation, and intractable pain whichso many of these patients face. Thefamilies, too, must cope with psy-chological problems which relate totheir own fears and impendingsense of loss. How to relate to thepatient and what to tell him abouthis diagnosis further complicateswhat is already a grim situation.This use of LSD is similar to thatalready outlined, except that not

quite as much time is spent inpreparation, and the treatment takesplace in a private room of a gen-eral medical facility (Sinai Hospi-tal, Baltimore). Also, family ther-apy plays a larger role.

Thus far, we have treated 35 pa-tients in a pilot project. Our find-ings must remain only suggestive atthis point, but they do give somepromising indications of the poten-tial of this form of treatment. Mea-surements before and after LSDon depression, anxiety, emotionaltension, psychological isolation, fearof death, and amount of medicationrequired for pain have shown changein a positive direction in about two-thirds of the patients. In half ofthese the improvement was dra-matic, and those patients who hadthe most profound peak experiencestended to show the most benefit.Also, patients treated earlier in thecourse of their disease were able touse the experience more, reward-ingly.

While not all patients were helpeddramatically, none, even the mostill, appeared to have been harmed.This finding in regard to the safetyof the procedure has been consistentwith our results in alcoholic andneurotic patients.

The following case summary willserve to illustrate both the methodand possible outcome.

LSD Psychotherapy=Pa+mke et al 1859

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Table 2.-Alcoholic Patients Improved Six Months After One LSD Session

No. of Patients WithDrinking Behavior

Scores of 8, 9,or 10 (%)Patient Group

No. of Patients WithGlobal Adjustment Scores

of 8, 9, or 10 (%)

bosageHigh(N= 64) 44 (28/64) 53 (34/64)Low:-~(N~=~4~0~)__~~ ~2~5~(~10~/~4~0~) ~33~(1~3~/~4~O~ _

Psychedelic reactivityProfound(N= 23) 61 (14/23) 61 (15/23)Marked

(N= 31) 39 (12/31) 48 (48/31)

Global Adiustmentx" P'

Minimal~~(N~=_5~0~)~~~~ ~2~4_(~1~2~/5~0~) ~3~6~(18/50)~ _X2 Results For Above Data

Drinking BehaviorX· . P"

High vslow dose 2.97 0.05 3.44 0.05

Psychedelicreactivity groups 7.74f.. P values are for one-tailed tests of significance.

Report of a Case

The patient, a 58-year-old Jewishmarried woman, had suffered fromcancer of the breast for 12 years. Inspite of numerous surgical and medicalprocedures which included hysterec-tomy, oophorectomy, and adrenalec-tomy, the disease had spread widelyin her spine. At the time she was re-ferred for LSD treatment, pressure onnerves in her spine had caused numb-ness and a paralysis of the lower halfof her body. When first interviewed,the patient was anxious and depressed.

After six hours of preparatory psy-chotherapy with the patient and herfamily. over the period of a week, dur-ing which the nature and purpose ofthe treatment was explained, the pa-tient was given 300 ,..g of LSD. Thefirst few hours of her psychedelic ses-sion went well and were pleasant, buta complete psychedelic-peak experi-ence was not obtained. There were afew moments of intense positive psy-chedelic reactivity; for example, at onepoint the patient exclaimed, "This isone of the happiest days of my life. Iwill always remember it." There werealso transient episodes of apprehen-sion, confusion, and paranoia whichwere easily handled by reassuranceand support.

During the latter part of the session,the patient raised the question ofwhether or not she would walk again.This issue was handled by a realisticreview of the patient's condition, andthe therapist finally stated in a directanswer to her question that it was very·unlikely that she would be able towalk again. The patient then expressedher reluctant acceptance of the idea

1860

0.025 3.07Not

significant

that her life could still go on even ifshe were confined to bed, a conditionwhich she had previously greatlyfeared. However, the patient spontane-ously expressed her determination totry her best in physiotherapy, in spiteof the odds against her. She was sup-ported in her resolve to try, but alsodiscussed was acceptance of her condi-tion, if it could not be improved. Dur-ing the evening after the patient hademerged from the effects of the drug,the patient's family visited. This wasa time of intense closeness and inter-personal sharing. The family remarkedon the change in her mental conditionfrom that of anxiety and depression toone of peace and joy.

In the days after the session the pa-tient's mood was cheerful and hopeful.Upon discharge from the hospital sixdays after her LSD treatment, the pa-tient returned home and began inten-sive work with a physiotherapist. Shemade remarkable, quite unexpectedprogress and within four months wasable to use a walker. Six months aftertreatment the patient was doing somelimited walking with a cane.

In spite of her impressive accom-plishments, the patient again becamedepressed and difficult to manage athome because of her feelings that shewould always be an invalid. She wasespecially distressed because the back-brace which she had to wear out of bed(four to six hours a day) was cumber-some and she needed assistance by an-other person in order to put it on. Be-cause of her increasing depression,both the patient and her family re-quested another LSD treatment. Shewas seen regularly for preparation. In-terpersonal relations, her self-concept,

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and some realistic expectations for thefuture were the major issues explored.

Ten months after her first sessionthe patient was readmitted to the hos-pital for her second LSD treatment.Her initial reaction to the session wasone of anxiety, and then the issue ofher disease was encountered. She facedthe fact that throughout her illness shehad tended to deny that she was reallysick. She remembered patients she hadknown with cancer, and her fear ofdecaying flesh was symbolized by vi-sions of vultures feeding on rottenmeat. After confronting rather than re-treating from these unpleasant feelingsand experiences, the patient had theexperience of passing through a seriesof blue curtains or veils. On the otherside she felt as if she were a bird in thesky soaring through the air. Then shewas on a high mountain top in a smallcabin alone with the snow falling. Sheexperienced wonderful feelings of peaceand harmony and visions of beautifulcolors like the rainbow. After this, shestabilized the experiences and had en-joyable reliving of happy memoriesfrom her past, the best of which washer wedding day, which she relivedin great detail including a reexperienceof the way her mother sighed as shecame down the aisle. These happymemories wer.e in contrast to the earlypart of her experience when she hadrelived some unpleasant events such asthe prejudice she felt against her as achild because she was Jewish and herfailure to take advantage of the cul-tural opportunities her father had pro-vided. In the latter part of the experi-ence the patient thought deeply abouther family while looking at their pic-tures. She was able to resolve some ofthe ambivalence she had about heryounger daughter who was to be mar-ried in three months. She felt sorry forsome of the strife they had had andcame out of the experience with a re-solve to make a more constructive at-tempt to relate to this girl in the fu-ture. When the patient's family arrivedafter supper, she had a serene smile onher face, but was reluctant to talkabout her experience too much. Shesaid, "You wouldn't believe me if I didtell you."

Subsequently, the patient left thehospital in good spirits and was able toparticipate actively in her daughter'swedding. She fulfilled her desire towalk down the aisle without the aid ofeven a cane, and during the weddingreception she amazed all the guests bydancing with her husband. Her sistersaid she had been the life of the party.

LSD Psychotherapy-Pahnke et al

Table 3.-Means of Chromosomal Aberration Rates* Before andAfter LSD Among Various Experimental Groups

Group Before LSD After LSD Difference P~32~pa~t~ie~n~t~s~~~~~~~~~~~~~~4~.~2~~8~_~=_-_-_~-_-_~_~~~5.~,971~----~~+~1.~6~3~--~N~o~t-s~ig~n~if~ic-a-nt~t---5 users 2.81 3.57 +0.i6c----'N-'-'o'-'t-=.s:ignificanf:j:---8 experimental

subiect=-s ~-'-- __"2"'.7--'9 ~'__ ---'--'--'- _2 normal

subjects 2.65

'Aberration rate = percentage of aberrant celis/total metaphases analyzed (at least 200 perculture).

tWilcoxon rnatched-palrs, signed-ranks. two-tailed test.:j:Fisherexact probability test.

Within six months the patient re-quested a third LSD treatment. At thistime she had increasing pain and wasdiscouraged because she had notworked in over two years although shehad kept the hope alive that she wouldeventually return to her old job. Thesession began smoothly but the patientbecame frightened when she saw ahuge wall of flames. After support andencouragement by the therapist, thepatient was able to go through themiddle of the flames, and at this pointexperienced positive ego transcend-ence. She felt that she had left herbody, was in another world, and was inthe presence of God which seemedsymbolized by a huge diamond-shapediridescent Presence. She did not seeHim as a Person but knew He wasthere. The feeling was one of awe andreverence, and she was filled with asense of peace and freedom. Becauseshe was free from her body, she feltno pain at all. She was quiet duringmost of the day and emerged from thesession with a deep feeling of peaceand joy. When her family had arrived,she radiated a psychedelic afterglow ofpeace and beauty which all remarkedupon. During the course of the eveningthe patient had a serious talk with herdaughters about her condition andwhat might lie ahead. Shortly there-after the patient was discharged fromthe hospital in good spirits. One effectof the treatment was that when thepatient was troubled with pain, shecould push the pain out of her mindby remembering her out-of-the-bodyLSD experience.

The patient did very well for aboutone month, until she slipped on thestairs one day and injured her back,which began causing her considerablepain again. She also became sick withinfluenza and was confined to bed. Priorto this she had been considering goingback to work at her old job, part-time,but with the worsening of her physicalcondition these plans had to be post-poned. With these physical setbacksand especially the recurrence of her

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pain, the patient again became some-what depressed. Both the patient andher family requested another LSDtreatment. The patient was seen week-ly for about a month as an outpatient,and then readmitted for a treatmentwith LSD, almost six months after herthird treatment.

The evening before her session, duroing the final preparation, the patientsuddenly asked a direct question abouther diagnosis for the first time in thealmost two years she had been in theLSD-treatment program. Although sheknew that her breast had been removedfor a tumor, she had believed therewas no further growth, but the increas-ing pain in her back had made herwonder. Her questions were answeredgently, but without evasion, and themeaning and emotional impact werediscussed with her. The family mem-bers were informed of this conversa-tion immediately thereafter, and theyreacted by becoming quite upset andangry. That very evening, in a generalfamily discussion with the patient andtherapist, however, most of them wereable to resolve their feelings. Some feltembarrassed because of their previouspretense; most felt relieved when theysaw how well the patient had dealtwith the situation. The patient statedthat she was glad to know the truthand was obviously not psychologicallyshattered or further depressed as someof the family members had feared.

The fourth session the next day wentsmoothly, except for some nauseawhich was experienced shortly beforeadmission when she had eaten somespoiled food. Much psychodynamic ma-terial emerged concerning her feelingsabout various members of her family,especially her two daughters. In theevening the patient felt very close toher family and spent some time intalking to each of them alone in a verypersonal way. She was reluctant tohave them leave at the end of the eve-ning, even though she was very tired.In the days after the session the pa-tient felt relaxed and in good spirits.

She was not pessimistic about the fu-ture, in spite of the new knowledgeabout the diagnosis of metastatic can-cer of the spine. She was able to tol-erate the pain in the back with the aidof narcotic drugs, but did not havecomplete relief from pain.

While still in the hospital, an hy-pophysectomy was attempted as a pos-sible means to stop further spread ofher metastatic process. Because ofhemorrhage the operation could not becompleted, and the patient died a fewdays later.

This patient experienced consid-erable relief from pain, depression,and anxiety over the period of al-most two years during which shereceived four LSD treatments. Herfirst session was not judged to havehad much psychedelic content, butthe second, third, and fourth ses-sions did. The third session was themost complete psychedelic-peak ex-perience and seemed to provide themost benefit. This patient's gratify-ing physical improvement can beattributed only indirectly to theLSD treatment in that her own un-derlying resolution to pursue phys-iotherapy emerged when her depres-sion and anxiety were relieved. Bya fortunate coincidence, her condi-tion responded well to these effortson her part, contrary to the mostinformed medical prognosis. All ourpatients are told that LSD is fortreatment of psychological distressand not a cure for their physicaldisease. In this case, as happens notinfrequently, sometime during thecourse of LSD treatment the issueof diagnosis was brought up by thepatient and had to be worked outwith the patient and the family.

The Question of SafetyWhen psychedelic drugs are ad-

ministered under controlled medicalconditions (as has been the case inseveral large-scale research projectsin recent years), permanent adverseeffects have been rare. Since 1963,at the Spring Grove State Hospitaland now at the Maryland Psychi-atric Research Center, Baltimore,

LSD Psychotherapy-Pahnke et al 1861

over 300 patients have been treatedwith LSD without a single case oflong-term psychological or physicalharm directly attributable to thetreatment, although there have beentwo cases in which disturbances per-sisted in the days following theactual LSD session. Both patientssubsequently responded to conven-tional psychiatric treatment.

Throughout the years of researchwith LSD many possible harmfulphysical effects have been suggested,but careful subsequent investiga-tion has failed to furnish muchconclusive scientific evidence. Mostrecently, the question of chromo-somal damage has been raised fol-lowing the positive in vitro findingsin white blood cells by Cohen.!"Retrospective studies on personshaving taken LSD (most from theblack market and only a few undermedical supervision) have producedconflicting reports. Some research-ers20

.22 found increased chromosom-

al breakage over normal rates, andothers no Increase."?"

Because we were in a position tostudy the effect of pure LSD ofknown amount on patients whowere to be treated with psychedelicpsychotherapy, we entered into col-laboration with the cytogenetics lab-oratory of Joe-Hin Tjio, PhD, atthe National Institute of Arthritisand Metabolic Diseases to carryout a rigorously controlled study.Blood samples from 32 patients be-ing treated at the Spring GroveState Hospital were drawn and cul-tured both before and after LSDadministration. The white blood cell(WBC) chromosomes were thenstudied without prior identificationof the slides, and at least 200 meta-phases were analyzed per culture.In addition, the WBC chromosomesof five chronic LSD users werestudied before, during, and after theadministration of known doses ofLSD in research on sensory, cog-nitive, and perceptual functions atthe National Institutes of Health.

No difference was found in therate of chromosomal aberrations be-fore and after administration ofLSD when the data from these 37separate individuals were statisti-cally analyzed. Also, chromosomalanalysis after LSD administrationwas done on eight normal subjectswho had received LSD in researchexperiments in the past, and no in-crease over normal chromosomalbreakage rate was found. A sum-mary of these results is presentedin Table 3. The mean rates beforeLSD in the 32 patients (4.28%)and the five LSD users (2.81%)are comparable to each other andto the values obtained from sam-ples from two normal control sub-jects for eight to ten consecutivedays (2.65%). The differences be-tween the rates before and afterreceiving LSD for both the 32 pa-tients (+1.63%) and the five LSDusers (+0.76%) are not statistical-ly significant. The mean chromo-somal aberration rates for the 32patients and five LSD users (in-cluding those both before and afteradministration of LSD), eight ex-perimental LSD subjects (after LSDadministration), and two normalcontrols (no LSD) only vary from2.65% to 5.91%. Detailed reportsof this research have been presentedand published.t+'"

CommentPart of the conflicting evidence

about the efficacy of psychedelicdrugs as a therapeutic tool for thetreatment of mental illness comesfrom the differences in the methodsemployed by various groups ofresearchers. Unfortunately, ratherthan replicating each other's meth-ods, each research team seems tohave developed its own procedure.

In spite of such diversity of ap-proach, several points seem to beclear by now. Use of LSD is not asubstitute for skilled psychotherapy.Experiments where LSD was usedprimarily as a chemotherapeutic

1862 JAMA, June 15, 1970 • Vol 212, No 11

agent or with a minimum of psycho-therapy have not shown any greaterefficacy regarding therapeutic out-come, especially with alcoholics,than control groups."e-3! The evi-dence from the psycholytic use ofLSD by European researchers andpsychedelic-peak therapy as prac-ticed at the Maryland PsychiatricResearch Center indicates that LSDcan be an enhancer of skilled psy-chotherapy when integrated withan intensive psychotherapeutic pro-gram of sufficient duration (30 to50 hours).

The scientific evidence concern-ing possible genetic hazards of LSDis conflicting and inconclusive. Thedifference in results between ourcarefully controlled study beforeand after administration of LSD inpatients and the research on LSDabusers may be explained by themany uncontrolled variables suchas viral infections and the effects ofother drugs. Certainly much moreresearch needs to be done in thiscomplex area before valid conclu-sions can be drawn.

Research with psychedelic drugsneeds to be continued to learn moreabout their effective use. Questionsneed to be answered, such as whatkinds of patients will benefit mostand under what circumstances. Asour research progresses and we gainmore experience we expect to mod-ify our implementation of psyche-delic-peak psychotherapy. Newerpsychedelic drugs may have certainadvantages over more well-knownones. For example, we have beentesting dipropyltryptamine (DPT)developed by Szara'" at the NIH,which has a duration of action offrom two to four hours dependingon dosage. If this drug proves tobe as effective and safely manage-able as the much longer-acting LSD,it could result in a psychedelic pro-cedure that could be more flexiblyand easily implemented than thatwith LSD.

In spite of the potential uses

LSD Psychotherapy-Pahnke et al

for psychedelic drugs suggested byour work, the future of such re-search, unfortunately, seems uncer-tain. Contributing factors for thisdim prognosis are sensationalism ofthe effects of LSD along with a con-tinuing spread of illicit use, publicfear stimulated especially by reportsof irreversible genetic and psycho-logical damage, the decreasingamount of research being initiated,the dearth of investigators who havehad first-hand clinical or researchexperience with LSD, and the diffi-culty of obtaining such training.

Our hope is that the current pub-lic concern over abuse can give wayto a resurgence of careful and in-formed research including special-ized training and experience forthose interested in this area. Ourpast and present research continuesto intrigue us with the promise ofpsychedelic drugs, but they are ob-viously powerful tools that need tobe used and handled wisely. Hope-fully, it is not too late for them tobe harnessed for medical and re-search use in a variety of ways inthe future.

These investigations were supported inpart by Public Health Service researchsupport grants MH-13747 (PsychedelicTherapy Research Program), MH-15555(Program for Treatment of the NarcoticAddict), MH-08474 (Controlled Study ofLSD Therapy with Alcoholics), MH-1100l(A Controlled Study of LSD Therapy withNeurotics), and FR-05546 (General Re-search Support Program). These grantswere administered by Friends of Psychi-atric Research, Ine, Baltimore.

The lysergic acid diethylamide used inthis research was manufactured by theSandoz Pharmaceutical Co., Basel, Switzer-land, and distributed by the FDA-NIMHCommittee for psychomimetic drug re-search.

Lee McCabe, PhD, Sidney Wolf, MA,William Richards, STM, and Thomas Ci-monetti, MD, collaborated in these studies.James Olsson, PhD, performed the statisti-cal analyses. Harry Shock, LLB, headedthe independent evaluation follow-up team.Louis Goodman, MD, Sinai Hospital, Balti-more, Md, arranged the clinical facilitiesfor the study of patients with cancer.

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