Effectsofmescaline,LSD-25, and Adrenochromeondepthelectograms, M.N

1 LSD187

Arch.Neurol.Psychiatr., Chicago 7__5_579 , (1956). EffectsofMescaline,LSD-25, and AdrenochromeonDepthElectograms, M.n

BERT E. $¢HWARZ, M.D. psychosis and three who had chronic schizophrenia CARL W. SEM-JACOISEN, M.D. were studied by means of the techniques of depth ond electrography developed and defined in this labora- MAGNUS C. Pt'riRSiH, M.D., Rochester, Minn. tory.* One of the epileptic and two of the schizo- +++ phrenic patients also received adrenochrome. Each l__$_l1_l3_lllull$l$_Mlllllll$__u$$llu_lll__[1$l_l__ll_l1_l_l___lillllpatientuIllu_l_l_hadLllMuexten_lliil__l_lsive _controll1lll_[1ll___li_lstudies,ul1_[_lastingi__l_lias_llong as two weeks per patient, previous to the time of In a recent report concerning the re- administration of the drug. Further control obser- versibility by chlorpromazine of psychoses vations were repeated every day of the study. Elec- induced by means of mescaline and d-lysergic trocardiograms were recorded simultaneously with depth electrograms in two patients. acid diethylamide (LSD-25), careful atten- The dose of mescaline varied between 400 rag. tion was given to the clinical and electro- and 1 gm., whereas that of LSD-25 ranged from encephalographic changes? Although the 50_ to 1503'. The dose of adrenochrome# varied clinical changes of this reversal effect were between 50 and 75 mg. The mescaline and LSD- timmediate and striking, the conventional 25 were administered orally ; the adrenochrome was electroenceph.alographic changes were mini- given intravenously as a freshly prepared solution mal, and it was difficult to assess them. It in 10 cc. of sterile water. At the presumed height of the reactions to mescaline and LSD-25, each was noted in another recent study that patient received an intravenous injection of 50 rag. mescalineand LSD-25 failed to activate of chlorpromazine dissolved in 10 cc. of sterile temporal-lobe epilepsy either clinically or water. The mescaline, LSD-25, and adrenochrome electroencephalographically} were administered during the fasting state in all instances.

Because of these f_ctors, it was hoped that CLINICAL RESULTS depth electrographic studies might be fruit- ful in elucidating the effects of these drugs. The clinical results are summarized in the It was hoped also that study by means of accompanying Table. This report is based depth electrography df the effects of adreno- on 18 observations, 6 with mescaline, 6 with chrome might elucidate its reported actions LSD-25, and 6 with adrenochrome. With of inducing a psychosis without insight in the doses of drugs used, the clinical effects volunteers 3 and increasing the paroxysmal were moderate when compared with the re- discharges in the electroencephalograms of sponses of a series of vohmteers' and a epileptics. + Scalp electroencephalography and group of epileptics 2 withont psychosis, who depth electrography: were undertaken as received substantially smaller doses than specific aids to diagnosis and as preliminary were used in this stud),. measures to definitive surgical treatment in Mescaline produced autonomic changes each patient in our study, consisting of slight pupillary dilatation and facial flushing. In the psychic sphere, three METIlOD patients who were negativistic in the control After the administration of mescaline and LSD- 25. two patients who had intractable epilepsy and " * References 5 anti 6. #A. Hoffer, M.D.. Ph.D.. director of psychi- Received for publication Jan. 9, 1955. atric research, University Hospital, Saskatoon. ; From the Rochester State Hospital. Sask., Canada, supplied pure adrenochrome. J $79 _ '_ _ _, -

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Fig. 1.----Generalizedparoxysmal burst in a schizophrenic patient. Before medication, the paroxysms occurred in(requently; after administration of 100_ o( LSD-25, they occurred every 10 to 20 seconds.

q'he clinical effects of LSD-25 closely re- raised his hand. gazed at it, and said, "My sembled those of mescaline, althbugh the arm wiggles and waves--ha, ha !" The other mescaline reactions in this study appeared schizophrenic who received adrenochrome to be more intense and were associated with (Patient 2) experienced catalepsy on two a typical facies. However, inappropriate occasions, which persisted for more than 30 laughing and giggling were noted more corn- minutes• At these times, his upper e×tremi- monly after use of LSD-25 than after admin- ties were held in unnatural positions that istration of mescaline. In several instances volunteers who served as controls coukl not when the patients were returned to the ward maintain for long. This was not his usual after receiving mescaline and LSD-25. the reaction, and a similar state did not develop nurses volunteered the observation that the with either mescaline or LSD-25. 582 MESCALINE, LSD-25, AND ADRENOCHROME

_rrECTS ON DElTa ELECTKOGi^._t at the rate of 3 per second (Fig. 2). The The effects on the depth electrogram also pulse,rate during the entire test was at no are summarized in the Table. A generalized time more than 120 beats per nlinute. At diminution in voltage of the depth rhythms the time of the persistent double spikes, the from the two epileptic patients was noted patient, as judged by the facial expression. approximately 30 minutes to 2 hours after behavioral reactions, and verbal admission. the oral administration of mescaline and was continuously disturbed, presumably with LSD-25. The three schizophrenic patients pronounced hallucinations. Continnous focal responded to these drugs with an increased high-voltage activity at this stage was re- paroxysmal activity (Fig. 1). There was no corded from the ventromedial region of the apparent correlation between the dose of frontal lobe (Fig. 2, bottom tracing). The

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Fig. 2.--Changes in the depth electrogram after administration of 1 gin. of mescaline to an epileptic patient. Note diminution in voltage of the spike discharges and appearance of a persistent new double-spike focus.

these drugs and the effects produced clini- temporal double-spike discharge very in- cally or on the depth electrograms, frequently ceased during the test for more In the two epileptic patients, foci of spike than six to eight seconds. Patient 4, the waves that existed in the control period on other epileptic, at the height of the reaction occasions tended to decrease greatly after to mescaline and while having visual hallu- the administration of mescaline and LSD-25. cinations, showed polyphasic spike dis- The tracings from Patient 5, an epileptic, charges from the depths of the occipital showed a new activity in the form of spike region t Fig. 3, upper strip). These were waves recorded from the depths of the tern- more prominent in the presence of synesthetic poral lobe. They were double spikes that visions induced b.v mescaline. In some re- were present continuously for several hours spects, these discharges resembled lambda 583 .I. M. .q. .tN( HIIF.S 01: .X'E(IgOLO(;F .I.VI) I'NIc tlI.ITRV waves, as seen front electroencephalograms control patterns present before the use of recorded from the scalp. However. in the mescaline and I.SI)-25. Itowever, tile re- depth records they consisted of a burst of versal process in Patient 5 was characterized ix)lyphasic spikes. Lamhda waves in depth by complex changes, as illnstrated in Figures are monophasic or hil)hasic, '_ as seen in the 4 and 5. In one instance (1)atient 5), the top strip of Figure 3. record changed spontaneously hefore tile use I'atient 4. who was especially cooperative of chlorpromazine, with the al)pearance of while under the influence of mescaline, also fast activity; it then went directly from this had waxing and waning of the alpha-like state to the premescaline state, with less pro- spindles from the depths of the occipital re- nounced complex changes I Figs. 4 and 5 I. gion that corresponded with the rhythms of On this occasion, the tracing resembled tile music (Fig. 3, middle and lower strips), i)remescaline recording for five minutes he- For instance, she had one pattern with a fore it reverted to the mescaline type of

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Fig. 3.--l)epth cleetrograms in another epileptic patient. Control lambda waves with the patient looking at a picture are recorded in the top strip. The middle strip illustrates the polyphasic spike discharges associated with synesthetic visions induced by administration of mescaline. The lower strip show_ synchronous waxin_ and waning of alpha-like discharges associated with music during the mescaline effect. All three strips were recorded from the same electr(_les. " relaxing harmonica waltz, another with some recording. As seen in Figures 4 and 5. the swing nmsic, and still a third pattern with double spikes from the depths of tile temporal a mournful hillbilly tune. This synchronous lobe disappeared and the epileptic foci re- alpha-like activity occnrred at the height sumed their control appearance, in Patient of her mescaline-induced state, whereas it 4, musically driven occipital bursts associ- never appeared without music or in the ated with visual hallucinations under the control period with music, influence of mescaline were not present after Within a few minutes after the intravenous use of chlorpromazine. ( )ther thanl occasional administration of 50 rag. of chlorpromazine, slight drowsiness, which was accompanied the electrographic recordings reverted to the infrequently by slower frequencies, the pa- 584 s i I

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,.M_,. x.ooou_ Fig. 4.--Fffect of chlorpromazine on the electrogram of an epileptic I)aticnt. N.te tlw appearance of fast activity one minute after the intravenous injection of 50 rag. of chh)rl)romazine.

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Fig. 5.--Further effects of chlorpromazin¢ in _ame patient who_e el_c_rogram i- .(-_n in Figure 4. Note the complex changes before the record reverte_| t¢, tbe preme_:al:n(: .ta_e. .4. M. .4. ARCHII'ES OF A'EUROLOG)" ..INI) PSI'( ItI. I'I'RV

tients clinically resembled their control con- not accompanied hv an 3" clinical changes dition. They were always readily alertable other than relaxation. and had clear sensoriums. The electrocardiograms showed no gross An increase in the existing paroxysmal changes; as recorded in two schizophrenic activity was noted in the two schizophrenics patients, between the control states and the (Patients 1 and'2) who received varying states induced by the use of mescaline, , doses of adrenochrome at different times. LSD-25, and adrenochrome. Patient 1 showed a focal sharp wave in activity recorded from the temporal region at rare cost MENT intervals during the control study. This had It would appear that administration of some resemblance to similar activity de- mescaline, LSD-25, and adrenochrome can

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_ I,qma. Fig. 6.--Effects off adrenoehrome on the electrogram M a schizophrenic. Note the f_:al sharp wave seen at rare intervals.in the control recording and its persistent appearance with higher voltage after administration of 50 rag. of adren_hrome.

scribed in an earlier paper3 However, in the cause striking changes in the depth electro- control period of Patient 1, it was impossible gram. Because the observations in this study to determine whether he had hallucinations were confined to two patients who had epi- at the time of this focal sharp discharge, lepsy with psychosis and three who had After injection of adrenochrome, there was chronic schizophrenia, these definite limita- persistent appearance of this focal sharp tions preclude any general statements with wave of maximal amplitude from the tern- regard to the effects of these drugs. How- poral region (Fig. 6). In the epileptic ever, it should be noted that the activation of (Patient 5), the administration of adreno- the temporal depths by mescaline and chrome was followed immediately by the LSD-25 in one patient appeared to coincide appearance of high-voltage waves of 2 or with a period of active auditory and visual 3 cps, associated with drowsiness. This was hallucinations. It should be noted also that 586 MESC.4LINE, LSD-25. .-IA'L} .4DRE.\'OCHRO31E

the douhle spikes produced hv mescaline and deep in the temporal lobe in one epileptic I.SI)-25 appeared in the proximity of a patient. region from which a similar discharge was The clinical effects and those on tile depth found in a patient during spontaneous hal- electrogram produced by mescaline and lucinations without any previous admin- LSD-25 were reversed by tile injection of istration of drugs.; A common mechanism chlorpromazine. might be activated that accounts for the acute Intravenous administration of adreno- psychotic episode. The immediate reversing chrome to two patients who had chrouic effects of intravenous administration of schizophreniaproduced an increase in par- chlorpromazine on the clinical and electro- oxysmal activity manifested by waves of 2 graphic states induced by means of mescaline to 5 cps. An increase in paroxysnlal activity and LSD-25 are suggestive of a possible of 2 to 3 cps occurred in a IXatient who bad mode of action centered in this region, a psychosis with a convulsive disorder.

The psychic effects and those produced on REFERENCES the depth electrograms in the two schizo- 1. Schwarz, B. E. : Bickford, R. G., and Rome, phrenics by use of adrenochrome are similar H. P.: Reversibility of Induced Psychosis with to those reported by Szatmari and associ- Chlorpromazine, Proc. Staff Meet. Mayo Clin. ates/ who described an increase in bilateral _0:407-417 (Sept. 21) 1955. paroxysmal abnormalities in electroenceph- 2. Schwarz, B. E.: Bickford, R. G.: Mulder, alograms recorded from the scalps of epilep- D.W., and Rome, H. P. : Mescaline and d-l.ysergic" tics. The observation that adrenochrome Acid Diethylamide in the Activation of Temporal- failed to induce clinical and electrographic Lobe Epilepsy, Neurology, to be published. changes similar to those produced by mescal- 3. Hoffer, A.; Osmond, H., and Smythies, J.: ine and LSD-25 in our epileptic (Patient 5) YeaSchizr'osphrenReseaia:rchA, J.NewMenAt.pproSc.ach:100:II.29-4Re5 sult(Jan.of) a suggests that adrenochrome or one of its 1954. degradation products is not involved in the 4. Szatmari, A.: Hoffer, A., and Schneider, R. : mediating action of mescaline and LSD-25, iThe Effect of Adrenochrome and Niacin on the as hypothesized previously. Electroencephalogram of Epileptics, Am. J. Psy- chiat. 111:603-616 (Feb.) 1955. SUMMARY 5. Sere-Jacobsen, C. _V.; Pctcrsen, M. C.: Lazarte, J. A.; I)odge, H. W., Jr., and Holman, During depth-electrographic studies, mes- C.B.: Electroencephalographic Rhythms from the caline and d-lysergic acid diethylamide Depths of the Frontal Lobe in 60 Psychotic I'a- (LSD-25) have been administered to five tients, Electroencephalog. & Clin. Neurophysiol. '/: patients; two of them had psychosis with 193-210 (May) 1955. convulsive disorders, and three had chronic 6. Sem-Jacobsen, C. Vf.; Pctcrscn, M. C.; schizophrenia. The most striking observa- Dodge, H. W., Jr.; Lazarte, J. A., and Holman, C. B. : Electro-Encephalographic Rhythms from the tion in the epileptics was that mescaline and I)epths of the Parietal, Occipital aml Temporal LSI)-25 had a pronounced quieting effect on Lobes in Man, Electroencephalog. & Clin. Neuro- the spike and sharp-wave foci in depth physiol., to be published. recordings. An increase in paroxysmal ac- 7. Sem-Jacobsen, C. XV.: Petersen, M. C.; tivity characterized by waves of 2 to 5 cps Lazarte, J. A.; Dodge, H. Vl'., Jr., and Holman,

occurred in the patients who had chronic fromc. B. Psycho: Intracerebraltic PatientEs lectDurrogiraphng ic HallucRecordininationsgs schizophrenia. Mescaline and LSD-25 elic- and Agitation: Preliminary Report. Am. J. Ps)-- ited the appearance of a double-spike focus chiat. 112:278-288 (Octo 1955.