Psychopharmacology 49, 307-309 (1976)

Psychopharmacology
9 by Springer-Verlag 1976

Short Reports
Increase in the Power of Human Memory in Normal Man through the Use of Drugs
S T U A R T J. D I M O N D * a n d E. Y. M. B R O U W E R S * * Department of Psychology, University College, P.O. Box 78, Cardiff CF 1 IXB, Wales, Great Britain

A b s t r a c t . N o o t r o p y l ( P i r a c e t a m ) a d r u g r e p o r t e d to

facilitate l e a r n i n g in a n i m a l s was tested for its e l e c t o n m a n b y a d m i n i s t e r i n g it to n o r m a l volunteers. T h e subjects were given 3 x 4 capsules at 400 m g p e r d a y , in a d o u b l e b l i n d study. E a c h subject l e a r n e d series o f w o r d s p r e s e n t e d as stimuli u p o n a m e m o r y d r u m . N o effects were o b s e r v e d after 7 d a y s b u t after 14 d a y s v e r b a l l e a r n i n g h a d significantly increased.
K e y words: L e a r n i n g - M e m o r y - N o r m a l h u m a n Nootropyl - Piracetam.

in the t r e a t m e n t o f senile d e m e n t i a a n d o t h e r d e g e n e r a tive d i s o r d e r s (Stegnick, 1972) suggests t h a t l e a r n i n g a n d m e m o r y i m p r o v e . The q u e s t i o n arises as to whether it is p o s s i b l e to i m p r o v e different p a r t s o f the m e n t a l m a k e u p o f n o r m a l m a n b y the use o f drugs, o f this k i n d w h e r e the e x p l a n a t i o n c a n n o t be given t h a t the effect o f the d r u g is m e r e l y to h o l d p a t h o l o g y at bay, b u t is to b e sought in the a c t i o n o f the s u b s t a n c e in a direct w a y u p o n the brain. W e b e g a n an investigation therefore to s t u d y the effects o f this d r u g on l e a r n i n g a n d m e m o r y in n o r m a l m a n .

PROCEDURE INTRODUCTION G u i r g e a (1971, 1973) d e v e l o p e d the i d e a t h a t changes c a n be i n d u c e d in the higher m e c h a n i s m s o f the b r a i n by chemical substances and that something other than c h a n g e at the m o l e c u l a r level m a y be involved. H e p r o p o s e s a new class o f drugs, the Iklootropic drugs ( N o o s = m i n d ; t r o p e i n = t o w a r d s ) , c o m p o u n d s pres u m e d to have their a c t i o n u p o n t e l e n c e p h a l i c plasticity a n d u p o n the integrative a c t i o n o f the brain. H e c a m e to these ideas o f n o o t r o p i c a c t i o n t h r o u g h the s t u d y o f P i r a c e t a m U C B 6215 ( 2 - p y r r o l i d o n e aceta m i d e ) a s u b s t a n c e w h i c h a p p e a r s to w o r k u p o n the c e r e b r a l c o r t e x a n d r e l a t e d t e l e n c e p h a l i c structures. This d r u g has been used in the study o f learning in m a n . I n a n i n v e s t i g a t i o n o n a p o p u l a t i o n o f c h r o n i c a l c o h o l i c s ( W e c k r o t h a n d M i k k o n e n , 1972) it was c o n c l u d e d t h a t an i m p r o v e m e n t takes place in the c o o r d i n a t i o n o f the i n d i v i d u a l ' s b e h a v i o u r . R e s e a r c h
* Send offprint requests to." Stuart J. Dimond, B.Sc., M.A., .Ph.D., Senior Lecturer in Psychology. ** Visiting fellow from Rijksuniversiteir te Leiden supported by the European programme for training in brain and behaviour research.

The subjects were 16 students from University College, Cardiff, 12 male and 4 female: all were in their second and third year of the Psycfiology course. The subjects were medically examined prior to and after the investigation. They were all healthyl well adjusted individuals, at the top level of health. Any not at this level were excluded from the investigation. We have confidence therefore that the subjects were normal college students in excellent health and good physical and mental condition. The daily dosage was 3 x 4 capsules at 400 mg Piracetam or 3 x 4 placebo capsules of the same appearance and taste. The total duration of the administration was 14 days. The study was made up of three sessions. The first was a pre-test before the drug had been administered, used both for matching the subjects and to act as a base level for further performance. There were two other tests, the first a week after commencement of drug administration, and the second 2 weeks after this time. The procedure was to match every subject with another subject on the basis of the minimal distance in a seven-dimensional space comprised of the individual experiments which made up the totality of the study and of which we report here only a few. These were a verbal memory task, a dichotic listening task, a pursuit rotor task, an intermanual transfer task; and in addition the level of handedness performance as measured by a Handedness Questionnaire; and additional still, the subject's age and sex. One of the matched pair at random was then given the drug, and the over the placebo. The study was a double-blind and neither the subject nor the experimenter had the knowledge as to which subjects were taking drug and which placebo.

308 APPARATUS
Each subject 1earned a series of words presented as stimuli upon a memory drum. The series consisted of nine two-syllabic words of six or seven letters each. All were singular nouns and had a word frequency of hetwecn 500 and 100 as indicated by a word frequency count (Carrel et al., 1971). The words were presented for 2 s each. After the last word the subject was required to wait for 10 s after which is was required that he write his response directly or perform a counting task for 40 s which prevented rehearsal (Peterson and Peterson, 1959). This was counting backwards in steps of three starting from a given number. The subjects saw six lists of nine words during each session. Three of these were recalled directly and three after delay: Each subject received the total eighteen lists in an order varied systematically according to a latin square design.

Psychepharmacology49 (1976) Table 1. Mean number of words learned in each condition averaged over three replications Sessions I. No drug Drug (N = 8) Direct Delayed 5.04 3.92 No drug Control (N = 8) Direct Delayed 4.92 3.92 2. Drug 5.25 4.04 No drug 5.71 3,33 3. Drug 6.21 5.21 No drug 5.63 4.25

RESULTS Two scores were computed from the data. The first the 'normal score' was obtained by straight forward counting of the number of words correct. The s e c o n d - ' t h e association score' is taken as the number of successive pairs of words correctly recalled regardless of absolute serial position (Waugh, 1963). A pooled correlation between the normal score and the association score revealed a value only of r = 0.67. We ignored the association score therefore and report here the results of the 'normal score' (Table 1). These were presented in a standardized form and the scores used as data in an Analysis of Variance (split-plot design) (Kirk, 1968). The factors examined were those of drug versus control, performance over the three sessions, the delayed, direct recall condition and the replication. A comparison of the results for the drug and the control group is shown in Figure 1. When sessions are compared it was found that overall performance in memery was r~_ot significantly different in sessions and 2 (F = 0.189 and F = 0.145, df= 1,192) but in session 3 the difference was highly significant ( F = 6.541, df= 1,192, P = 0.01). With respect to the introduction of the delay we see an overall reduction in the levet of performance (Fig. 2). Furthermore in the direct recall condition there was no significant improvement over sessions for the control (F = 1.758, df = 1,192, NS) but for the drug there was (F = 5.250, df= 1,192, P = 0.02). In the delayed condition there was no significant improvement over sessions for the control (F = 3.773, df = 1,192, NS) but once again there was a significant improvement by the group taking the drug (F = 11.531, df = 1,192, P = 0.01). As a contrast to the facilitation of verbal memory which we report here, the results of a non-verbal learning task, the pursuit rotor, in which the individual is required to follow a moving target with a stylus, showed no significant difference between the drug

1.0

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sessions
1.0-

.6.6.4.20~ ~ drug o

direct

control direct

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Fig. 1.

Effects of Piracetam (UCB 6215) on versal learning

and the control groups. The interaction session x drug/ control was non-significant (F = 1.486, df = 1,192). Interactions of sessions x drug/control on a multiple affect adjective list administered to test for changes of mood, were also non-significant. Tests performed to determine whether the individual himself was aware that he was on the drug proved negative.

DISCUSSION Although it appears that Piracetam is a substance which acts upon the higher levels of the brain an ex-

S. J. Dimond and E. Y. M. Brouwers : Increase in the Power of Human Memory through the Use of Drugs

309

tensive research effort may be necessary before the exact mode of its actions can be determined. At present the point to be emphasized is not the mode of its action but that it acts at all. The fact is that the adminstration of Piracetam promotes verbal learning and in this it would appear to be a substance which in a specific respect is capable of extending the intellectual functions of man. It therefore represents a forerunner of a class of drugs which could act to lead him to learn or to remember better, and thus the effect is in the actual enhancement of performance. The point has been stressed that the subjects of this investigation were essentially normal healthy college undergraduates, Investigations of the past illustrating enhancement of mental function in man have almost invariably done so in individuals exhibiting a pathological condition. Where normals previously have been studied, for example in the administration of Levadopa (Loranger et al., 1972) no significant effect has been reported. Increase in alertness ax~td enhanced mental ability could be attributed in such cases to the effect of the drug in counteracting the pathology, or acting against the pathology in such a way that the mental processes were enhanced. Such an explanation cannot be proposed here for our results because our subjects were not senile, suffering from generalized brain disorder, confusional states, or any other pathology of the brain. The effect therefore is essentially of enhancement of the mnemonic power of the brain by the action of the drug upon the brain processes themselves rather than its action in holding some pathology known or unspec!fied at bay. Although we-have no IQ data on our subjects, by virtue of the selection procedure through which they pass to become students they are all almost certainly individuals scoring in the upper intelligence ranges, and all almost certainly gifted with facility in verbal rnemory. It is therefore possible to extend the power which they possess to still higher levels despite the fact that the range of their achievement is already high. It is clear from these results that the effect of this is something which is not observed as a generalized phenomenon over the span of what the brain can do. Whilst on tests of verbal learning there is clear evidence

of enhancement, on the pursuit rotor non-verbal learning test, on the other tests reported here there was not. It would appear therefore that the drug can act specifically and selectively within a realm of mental action, and that its effect need not extend to all areas of the intellect. We do not as yet know the bounds of its influence upon mental action. It may improve a broad spectrum of the intellect or just verbal learning as demonstrated here, but the fact of its action shows that human brain power can be selectively increased, and if this is so within the orbit of verbal memory, then the next step is to seek out substances which selectively improve yet other facets of mental life which go to make up the constellation of human intellect.

REFERENCES
Carrol, J. B., Davies, P., Richman, B.: The american heritage. Boston: Haughton Mifflin 1971 Guirgea, C. : The pharmacology of piracetem (UCB 6215]: A nootropic drug. Report UCB-Pharm. Division. DRDM, rue Berkenduel 58, Brussels, Belgium (1971) Guirgea, C.: The nootropic approach to the pharmacology of the integrative action of the brain. Conditional Reflex 8, 108115 (1973) Kirk, R. E.: Experimental design: Procedures for the behavioral sciences. Belmont, California: Brooks Cole 1968 Loranger, A. W., Goodell, H., Lee, J. E., McDowell, F. : Levadopa treatment of Parkinson's syndrome. Improved intellectual functioning. Arch. gen. Psychiat. 26, 163-168 (1972) Peterson, L. R., Peterson, M. J. : Short-term retention of individual verbal items. J. exp. Psychol. 58, 193-198 (1959) Stegnick, A. J.: The clinical use of piracetam; a new nootropic drug. The treatment of symptoms of senile involution. Arzneimittel-Forsch. (Drug. Res.) 22, 975-977 (1972) Thiebauld, C. : Improvement of intellectual performance: Contribution of a specific cortical therapy. Paper delivered to the 38th Congress of Medicine. Bayrouth, 1971 Waugh, N. C.: Two methods for testing serial memorization. J. exp. Psychol. 65, 2J5--216 (1963) Weckroth, J., Mikkonen, H. : On the effect of UCB 6215 on certain intellectual, perceptual and psychomotor performance traits and traits of subjectively rated mental state. Communication of the 30th Int. Congress on Alcoholism and Drug Dependence, Sept. 1972, Amsterdam, The Netherlands

Received March 29, 1976