marijuana use and human cognition

7/27/2019 Marijuana Use and Human Cognition

1/10

Psychopharmacology (1993) 110: 219-228 Psychopharmacology S p r i n g e r - V e r l a g 1 9 93

Effects of chronic marijuana use on human cognitionRobert I . Block and M.M. GhoneimDepartment of Anesthesia, University of Iowa, Iowa City, IA 52242, USAReceiv ed April 23, 1991 / Final version Jun e 15, 1992

Abstract. I m p a i r m e n t s o f h u m a n c o g n i ti o n a n d l e a rn i n gf o l lo w i n g c h r o n i c m a r i j u a n a u s e a r e o f se r i ou s c o n c e r n ,b u t h a v e n o t b e e n c l e ar l y d e m o n s t r a t e d . T o d e t e r m i n ew h e t h e r s u c h i m p a i r m e n t s o c c u r r e d , t h i s s t u d y c o m p a r e dp e r f o r m a n c e o f a d u l t m a r i j u a n a u s e rs a n d n o n - u s e r s ( N= 144 and N = 72, respec t ive ly) ma tche d o n in te l lec tua l

func t ion ing before the o nse t of drug use , i .e ., on scoresf r o m s t a n d a r d i z e d t e s t s a d m i n i s t e r e d d u r i n g t h e f o u r t hg r a d e o f g r a m m a r s c h o o l ( I o w a T e s t s o f B a si c S k il ls ).Subjec t s were g iven the twe l f th grad e vers ions o f theset e st s ( I o w a T e s t s o f E d u c a t i o n a l D e v e l o p m e n t ) a n d o t h e r ,compute r i zed cogni t ive t e s t s in succes s ive t e s t s es s ions ." H e a v y " m a r i j u a n a u s e (d e f in e d b y u s e se v e n o r m o r et imes weekly) was as so c ia ted wi th de f i c i ts in mat hem at ic a lsk il l s and verba l expres s ion in the Iow a Tes t s of Edu ca-t i o n a l D e v e l o p m e n t a n d s e le c ti v e i m p a i r m e n t s i n m e m o r yre t r i eva l proces ses in Buschke ' s Tes t . The re t r i eva l im pa i r -men t s were res t r i c t ed to word s tha t were easy to v i sual i ze.I m p a i r m e n t s d e p e n d e d o n t h e fr e q u e n c y o f c h r o n i c m a r -i juana use , i .e ., " l ight " and " in te rm edia te" m ar i ju ana use(def ined by use one to four an d f ive to s ix t imes weekly ,respec t ive ly) were not a s soc ia ted wi th de f ic i ts . In te rme di -a t e u s e w a s a s s o c i a t e d w i t h s u p e r i o r p e r f o r m a n c e i n o n ec o n d i t i o n ( " f u zz y " c o n c e p t s ) o f a C o n c e p t F o r m a t i o n t es t.Key words: M a r i j u a n a - C h r o n ic d r u g u se C o g n i t i o n -I o w a T e s ts - M e m o r y - L e a rn i n g - I m a g e r y A b s t r a c ti o n

A d v e r s e e f fe c ts o f c h r o n i c m a r i j u a n a u s e o n c o g n i t i o n a r eof s e r ious concern , s ince mar i ju ana i s the mos t wide lyused i l li c it d rug . C l in ica l impres s ion s of m an y obse rverss u g g e st t h a t c h r o n i c m a r i j u a n a u s e im p a i r s c o g n i t i v e f u nc -t ion (Na t iona l Ins t i tu t e on Drug Abuse 1982) , but exper i -me nta l s tudies of th i s is sue have f requ ent ly been me th-o d o l o g i c a l l y w e a k , a m b i g u o u s i n o u t c o m e , o r b o t h . O fa b o u t a d o z e n s t u d i es c o n d u c t e d i n th e U n i t e d S t a t es a n dC a n a d a a n d a s im i l a r n u m b e r e l s e w h er e , a m i n o r i t y o fs t u d i e s h a v e r e p o r t e d s o m e c o g n i t i v e i m p a i r m e n t s f r o m

Correspondence to." R.I. Block

chr onic m ari ju an a use (Soue if 1971, 1975, 1976; Ent in andGoldzung 1973; Page et a l . 1988; Schwartz et a l . 1989),w h i l e t h e m a j o r i t y h a v e f o u n d t h a t i m p a i r m e n t s w e r eabsent or negl ig ib le (Bowman and P ih l 1973; Weckowiczand Jan ssen 1973; Rubin an d Com i tas 1975; Car l in andTrupin 1977) . Both s tudies repor t ing impa i rment s f romm a r i j u a n a u s e a n d t h o s e r e p o r t i n g n o c h a n g e s u ff e r f r o m ase r ious methodologica l shor t coming: a c ruc ia l requi re -m e n t f o r e v a l u a t in g p e r f o r m a n c e o f c h r o n i c m a r i j u a n au s e rs i s c o m p a r i s o n w i t h a g r o u p o f n o n - u s i n g s u b je c t sw h o a r e m a t c h e d o n r e l e v a n t d e m o g r a p h i c c h a r a c t er i s ti c sa n d , m o s t i m p o r t a n t l y , o n s o m e m e a s u r e o f i n t el l ec t u a lfunc t ioning obta ined before the onse t of drug use. Ye to n l y o n e p a s t s t u d y m a t c h e d t h e m a r i j u a n a u s e r s a n dnon-use rs on in te l l ec tua l func t ioning before the onse t ofd r u g u s e a n d t h i s s tu d y f o u n d n o i m p a i r m e n t s i n t h e u s er s ,poss ib ly due to the minima l inc lus ion c r i t e r ia s t ipula tedfor mar i juana use , i . e . , use a t l eas t twice a month for oneyear (Culver and King 1974) .

W e e x a m i n e d c o g n i t iv e e f fe c ts o f c h r o n i c m a r i j u a n au s e b y c o m p a r i n g t h e p e r f o r m a n c e o f m a r i j u a n a u s er s a n dn o n - u s e r s w h o w e r e m a t c h e d o n i n t e l l e c t u a l f u n c t i o n i n gbefore the on se t of drug use, i. e., on the i r s cores d ur ing thef o u r t h g r a d e o f g r a m m a r s c h o o l o n t h e I o w a T e s t s o fBasic Ski l ls (Hieronymus et a l . 1982), s tandardized tes tst h a t h a v e b e e n a d m i n i s t e r e d t o a l m o s t a ll g r a m m a r s c h o o lchi ldren in Iowa for s evera l decades . The twe l f th gradev e r s i o n s o f t h e I o w a T e s ts a n d o t h e r , c o m p u t e r i z e d c o g -ni t ive te s t s were adm ini s t e red to de te rm ine i f chron icm a r i j u a n a u s e rs w e r e i m p a i r e d a n d , i f s o, w h e t h e r i m p a i r -m e n t s d e p e n d e d o n t h e f r e q u e n c y o f t h e i r m a r i j u a n a u se .

Materials and methodsS c r e e n i n gVolunteers were recruited through advertisements. During pre-liminary screening visits, informed con sents were obtained after thenatu re an d possible consequences of the study w ere explained.Volunteers then provided a urine sample for drug screening andinformation about their medical history, demographic character-


2/10

22 0is t ics , and use of ma ri ju ana and other drugs. T hey class if ied theirave rage weekly f r equency o f u s ing mar i jua na o r o the r cann ab i sproducts as "not a t a l l" , " less than once", one to four t imes (" l ight"users), f ive to s ix t imes (" inte rme diate" users) , or seven or mor e t im es( "heavy" use r s ) and ind ica ted the du ra t ion o f the i r u se a t t h i sf r equency. In add i t ion , t hey comple ted a ques t ionna i re (de r ived wi thmod i f i ca t ions from John s ton e t a l. 1981) conce rn ing the numbe r o foccasions on which they had used var ious drugs in their l i fe t ime,du r ing the l a s t 12 mon ths , and du r ing the l a s t 30 days . Po r t ions o fthe Diagnos t i c In t e rv iew Schedu le (DIS) Vers ion I I I -A (Rob ins andHelzer 1985) , a s t ructured psychiatr ic screen ing in terview for use byresearch s taff , were adminis tered.So that thei r scores on the Iow a Tests could be re tr ieved, subjectswere res tr ic ted to adul ts (age range, 18-42 years) who had a t tendedthe fou r th g rade o f g rammar schoo l in Iowa . Mar i juana use r s werere s t r ic t ed to ind iv idua l s who ha d used mar i ju ana a t l ea s t week ly forthe las t 2 years or more. Non-users were res tr ic ted to individualswho had no t u sed mar i juana more than twice in the i r l i ve s .So that tes t perform ance w ould not be inf luenced by acute effectso f d rugs, sub jec t s had to p romise to abs ta in f rom a lcoho l on the dayof each sub seque nt sess ion and af ter 6 p .m. on the preced ing evening;and to abs ta in f rom m ar i juana and o the r d rugs fo r 24 h be fo re eachsubsequen t s e s s ion . Sub jec t s were ques t ioned abou t compl iancewith these promises before each sess ion.

M a t c h i n g o f t he g r o u p sEarly in the s tudy, excessive numb ers of female non-u sers werete s t ed be fo re i t became c lea r tha t t he mar i juana use r s were mos t lymen . Fo r th i s r ea son , the mos t e f f i ci ent me th od to subsequen t lyob ta in ma tched g roups o f mar i ju ana use r s (N = 144) and non-use r s(N = 72) was to se lect only a f ra ct ion of the female non- users(N = 15 of 63) for analysis . Usi ng propen si ty (P) score techniqu es(Rose nbaum and Rub in 1985) , a subse t o f f ema le non -use r s waschosen wi th the goa l o f ma tch ing use r s and non-use r s on age ,educat ion, and the f ive subtest scores of the fourth grade Iowa Tests .Ra the r than a t t empt ing to ma tch on these seven cha rac te r i s t i c sindividual ly , they were t ransformed into a s ingle var iable , the Pscore , which was calcula ted from a logis t ic mult ip le regress ion inwh ich the seven cha rac ter i s t i c s were independ en t va r i ab le s and theuse r /non -use r d i cho tomy was the dependen t va r i ab le . The P sco rerep resen ted the e s t ima ted cond i t iona l p robab i l i ty th a t a sub jec t wasa mari juana user , based sole ly on these seven character is t ics . Selec-t ion of the subset of female non-use rs was based o n these P scores ,wi th the hope tha t m a tch ing use r s and non-use r s on P sco res wou ldprodu ce m atch ing on a l l seven character is t ics . Select ions were sub-j ec ted to an add i t iona l cons t r a in t t o avo id d i s rup t ing p lannedcounterbalancing, i ,e . , female non-users were chosen such that equalnumbers o f non -use r s (ma le and f ema le combined ) came f rom eachof e ight tes t condi t ions differ ing in the orders an d a l te rnate forms ofthe tes ts . Select ions were made without reference to individuals 'scores on the twelf th grade Iowa Tests and computer ized tes ts .

T e s t in gIn one sess ion, which las ted about 3 h , four tes ts f rom the Iowa Testso f Educa t iona l Deve lop men t ( l eve l I I ) were adm in i s t e red a long wi ththe Short Test of Educat ional Abil i ty ( level 5) , a tes t of generalacademic ab i l i t y s t anda rd ized w i th the Iowa Tes t s (Sc ience Resea rchAssociates 1981) . The tes ts were adminis tered according to proced-ures specified in the tes t ma nua ls (Science Research Associates 1974;Iowa Tes t ing P rog rams 1987a ) . Al l were penc i l - and -pape r t e s t s inmult ip le-choice format . In a second sess ion, which las ted about 2 .5h , cogn i t ive and p sychom oto r t e s t s were admin i s t e red by an App le I IP lus compu te r sys t em. Sub jec t s r e sponded o ra l ly o r by p re s s ingbu t tons .Tw o different orders of the tes ts within eac h sess ion were used fordifferent subjects , as were two al te rnate form s of each tes t except theShor t Tes t o f Educa t iona l Ab i l i ty and two compu te r i zed psycho-

mot o r a s se s smen t s . The a l t e rna te fo rms were each g iven to ha l f t hesub jec t s wi th in each use r g roup , excep t tha t t h i s coun te rba lanc ingwas off by one subject am ong the heavy users .Detai ls of the funct ions assessed by the tes ts g iven in the f i rs tsess ion were as fol lows:

1. Ability to do quantitative thinking. So lv ing ma thema t i ca l wordprob lems and answer ing ques t ions a s se s s ing unde r s t and ing o fbas ic ma thema t i ca l concep t s .2. C orrectness and approp;'iateness of expression. Recognizing mis-spel led words and deciding which of a l ternat ive vers ions of aspecif ied port ion of text best expressed the idea, made the s ta te-men t g rammat ica l ly co r rec t o r mos t p rec i se , o r was co r rec t lypunc tua ted o r cap i t a l i zed .3. Vocabulary. Picking which of several words was the c losestsynonym for a specif ied word.4. Ability to interpret literary materials. Answer ing ques t ionsassess ing comprehension of a text .5. Short test of educational ability. Answer ing fou r types o f ques t ionsinvo lv ing vocabu la ry , a r i thme t i c compu ta t ion , l e t t e r s e r i e s ( r e -cogn iz ing pa t t e rns in se r ie s o f l et t er s ), and symbo l man ip u la t ion( recogn izing symbo l i c quan t i t a t ive r e l at ions) .Detai ls of the tes ts g iven in the second sess ion were as fol lows:1. Buschke's test. A l is t of 16 nouns, half "high imagery" wordsthat were easy to visual ize (e .g . , "bouquet") and the remainder " lowimagery" words that were diff icul t to visual ize (e .g . , " replacement")(Paivi o e t a l. 1968) , was presente d on the mo nito r a t a ra te of 3 s per

word. The subject t r ied to recal l as many words as possible . Sevenlearning and tes t t r ia ls were given consecut ively . The subject t r ied torecal l the wh ole l is t on each tes t t r ia l , but o n learnin g t r ia ls af ter thef i rs t , he or she was reminded only of the words missed on theimmed ia te ly p reced ing t e s t t r i a l . Th i s p rocedure a l lowed sco r ingseveral aspects of me mor y in addi t i on to to ta l recal l (Buschke 1973):in essence, recal l of a word without an immediate ly precedingrem inder ( i .e ., recal l on two successive tr ia ls) indicate d th at the w ordhad en te red ( and p re sumab ly r ema ined in ) long - t e rm s to rage . Reca llo f the word be fo re th i s occu r rence was a t t r ibu ted to sho r t - t e rmretr ieval ; af ter i t , to long-term retr ieval . Long-term retr ieval wasdes igna ted "cons i s t en t " when the word was neve r subsequen t lyomi t t ed .

2. Concept formation. The s t imu l i fo r th i s t e s t o f abs t r ac t ion wereschemat i c f aces (Reed 1972 ; Mar t in and Caramazza 1980) wi thseven varying features , each having three possible values , e .g . , eyesfacing lef t , r ight , or center . The subject s tudied a card pic tur ing f iveme mbe rs of each of two "famil ies" for 1 min. Then 20 new faces , halffrom each family , were shown at a 10 s ra te on the monitor . Thesub jec t i nd ica ted to w h ich f amily each be longed . The ca rd r em a inedpresent only while the subject c lass if ied the f i rs t ten new faces . Theent i re procedure was then repeated with a different card def ining thefamil ies . One c ard port raye d a "clear" concept : each family had tw odis t ingu ishing features , e.g. , one ha d large beards a nd r oun d noses;the o the r , smi l ing f aces and no ha i r . The o the r ca rd po r t r ayed a"fuzzy" concept (Rosch and Mervis 1975) fol lowing a s imilar pat-tern , but with some except ions , e .g . , in one family , 80% had smallbea rds ; i n the o the r , 80% had f rowning f aces. Eve ry mem ber o f onefami ly bo re more r e semblance to i t s f ami ly than the o the r , bu t thefamil ies had no uniformly dis t inguishing features .3. Text learning. The sub jec t r ead a pa rag raph f rom a magaz inea r t i c l e on the mon i to r a t h i s o r he r own pace and then r eca l l ed a smuch a s poss ib le in th ree minu te s . The sub jec t t hen r e read thepa rag r aph and r eca ll ed i t aga in . Fo l lowing th is , t he en t i r e p rocedurewas repeated with a different paragraph. The subject ' s recal l wastape - reco rded fo r l a t e r s co r ing o f the p ropos i t ions r eca l led (Mi l l e rand Kintsch 1980) .4. Free and constrained associations. For each of 100 wordspresented a t a 10 s ra te on the monitor , the subject gave a s ingleword as an associa t ion. For 50 words, the subject was cued toprovi de a "free associa t ion ", i.e. , any kin d of associa t ion tha t came tomind; for 10 words each, the subject was to pr ovide o ne of f ive typesof"constra ined associa t ions" , i .e . , h is or her response was to re la te tothe s t imulus in a specif ied way, cued by the words "another" ,


3/10

"category", "example", "opposite", or "property". T he words weredrawn from those used in a pilot study (Block et al. 1989) involvingintroducto ry psychology students , so that for each response in thepresent s tudy, the number of pilot subjects giving that response("dominance") could be scored, e.g., eight pilot subjects gave "san-dal" in response to "shoe".5. Pa ired associate learnino. A list of 30 pairs of words waspresented at a 3 s rate on the m onitor. Then the initial word fromeach pair was presented at a 5 s rate and the subject tried to respon dwith the second word from each pair. These learning and test trialswere then repeated. Following this, the entire procedure was re-peated with a different list of pairs of words. The pairs representedeight types of free and constrained associations (e.g., "carpet-laughter", "horse-tail").6. Psychomo tor tests: (a) Critical flicker fusion: the subject viewedtwo ligh t-emitting diodes. One w as flickering and the other re-mained con stantly il luminated. During the 2 s perio d of flickering orthe following 3 s interstimulus interval, the subject indicated whichdiode was flickering. The computer determined the flicker fusionthreshold b y increasing or decreasing the rate of flickering depend-ing on the correctness of the subject's responses. The task wasrepeated twice, with two threshold estimates produced each time.(b) Discriminant reaction time: the subject viewed a series of digitsflashed for 100 ms each and pressed a button as fast as possiblefollowing each "4". The interstim ulus interval, initially 400 ms, wasincreased or decreased by the computer depending on the correc-tness of the subject's responses to determine the most rapid rate atwhich accuracy could be maintained (Berchou and Block 1983).Digits were presented for 50 s. The task was repeated four times.

Statist ical analysesTo check that matching of users and non-users was adequate, thescores on the fourth grade Iowa Tests , age, and education weresubmitted to analyses of variance involving user group (heavy,intermediate, light, and non-users) and sex as between-subjectsfactors. Categorical demograp hic characteris tics of users and non-users such as work status were compared by chi-square tests.Fisher's exact tests were done to com pare pairs of user groups withdecreasing intensities of marijuana use (heavy versus intermediate,intermediate versus light, and light versus non-users) on lifetimeprevalence of trying the drugs other than marijuana included on thedrug questionnaire.To assess effects of chronic marijuana use while controlling forany re sidual differences in fourth grade I owa T est scores, the twelfthgrade Iowa Tests and comp uterized tests were submitted to analysesof covariance in which the log-transformed P score LOG( (1-P )/P)served as a covariate. These analyses included between-subjectsfactors representing user group, sex, the orders in which the testswere given, and the two alt ernate forms of tests. Fr om one to threeadditional within-subjects factors representing test manipulationsapprop riate for the individual computerized tests were included inthe analyses, as follows: in Buschke's Test, seven trials and twoimagery levels of the words (high versus low imagery words); inConcept Formation, two types of concepts (clear versus fuzzyconcepts) and two test conditions (example card present versusabsent); in Text Learning, two paragraphs and two trials perparagraph; in Free and Constrained A ssociations, two classes ofassociations (free versus constrained associations) and five types ofassociative relations (e.g., "example", "prop erty"); in Pai red Associ-at~ Learning, two lists, two trials per list, and eight types ofassociative relations between pairs of words (e.g., "example","property"); in the Psych omotor Tests, two trials and two thresholdestimates per trial for Critical Flicker Fusion and four trials forDiscriminant Reaction Time. Tests for within-subjects effects andinteractions involving these effects were adjusted using the Green-house-G eisser procedur e (Wirier 1971, p 523).Adjusted means were computed and Dunnett 's tests were doneto co mpare performance of the heavy, intermediate, and light mar-ijuan a users with the non- user contr ol group. Th e significance level

221was P < 0.05, adjusted for the num ber of compariso ns made. Whenan interaction of user group w ith another factor was detected in ananalysis of covariance, similar follow-up Dunnett's tests were doneseparately for each level of the factor interacting with user group.

Results

Mari juana useA m o n g t h e m a r i j u a n a u s e r s , t h e r e p o r t e d f r e q u e n c y o fu s i n g m a r i j u a n a w a s s e ve n o r m o r e t i m e s w e e k l y f o r 52us e rs , f ive to s ix t ime s we e k ly fo r 28 us e r s , a nd one to fou rt i m e s w e e k l y f o r 6 4 us e rs . T h e s e h e a v y , i n t e r m e d i a t e , a n dl i g h t u s e r s r e p o r t e d u s i n g m a r i j u a n a a t t h e i r i n d i c a t e dfreq uen cies for m ean s ( _+ S Es) of 6 .2 _+ 0 .6 , 5.8 _ 0 .7 , an d5 .5 _+ 0 .5 y e a r s , r e s pe c t ive ly . Th e y s t a r t e d in s imi l a rg ra de s : 9 .5, 10 .1, a nd 10 .5 , r e s pe c t ive ly . In the l a s t 30 da ys ,t h e m e d i a n f r e q u e n c y o f m a r i j u a n a u s e fo r t h e h e a v y u s e rsw a s 2 0 - 3 9 t i m e s a n d t h e u p p e r q u a r t i l e ( 7 5t h p e r c e n t i l e )w a s 4 0 - 9 9 t i m es . F o r e a c h o f t h e o t h e r g r o u p s , t h e m e d i a na n d u p p e r q u a r t i l e w e r e i d e n t ic a l , b e i n g 2 0 - 3 9 , 1 0 - 1 9 , a n dz e r o t i m e s f o r t h e i n t e r m e d i a t e , l i g h t , a n d n o n - u s e r s ,r e s p e c t i v e ly . T w e l v e p e r c e n t o f t h e h e a v y u s e r s r e p o r t e du s i n g m a r i j u a n a 1 0 0 o r m o r e t i m e s i n t h e l a s t 3 0 d a y s .

Lifetime use of drugs other than marijuanaA p a r t f r o m m a r i j u a n a , a l c o h o l w a s t h e o n l y d r u g i n c l u d e do n t h e d r u g q u e s t i o n n a i r e t h a t a l l h e a v y m a r i j u a n a u s e rsh a d t r i e d a t l e a s t o n c e i n t h e i r li fe . T h e h e a v y m a r i j u a n au s e r s ' l if e t i m e p r e v a l e n c e s o f h a v i n g t r i e d t h e o t h e r d r u g ss h o w e d t h e f o l l o w i n g o r d e r i n g : c o c a i n e , 9 0 % ; p s y c h e -d e l ic s o t h e r t h a n l y s er g i c a c i d d i e t h y l a m i d e ( L S D ) , 8 8 % ;L S D , 7 9 % ; a m p h e t a m i n e s , 7 9 % ; n a r c o t i c s o th e r t h a nh e r o i n , 5 4 % ; t r a n q u i l i z e r s , 5 2 % ; a m y l o r b u t y l n i t r i t e s ,4 2 % ; b a r b i t u r a t e s , 3 1 % ; m e t h a q u a l o n e ( Q u a a l u d e ) ,2 7 % ; p h e n c y c l i d i n e , 1 2 % ; a n d h e r o i n , 1 2 % . T h e h e a v ya n d i n t e r m e d i a t e u s e r s d i d n o t d i f fe r i n l i fe t i m e p r e v a l e n c eo f h a v i n g t r i e d a n y o f th e d r u g s. T h e i n t e r m e d i a t e a n dl i g h t u s er s d i f f er e d o n l y f o r n a r c o t i c s o t h e r t h a n h e r o i n ,w h i c h h a d b e e n t r i e d b y m o r e i n t e r m e d i a t e t h a n l i g h tu s e r s, P < 0 . 01 . I n c o n t r a s t , t t i e l i g h t m a r i j u a n a u s e r s h a dt r i e d e v e r y d r u g m o r e o f t e n t h a n t h e n o n - u s e r s , P s< 0 .0 5 0 . 00 1 , e x c e p t f o r a l c o h o l a n d h e r o i n , w h i c h h a d

b e e n t r i e d b y a l m o s t a l l a n d a l m o s t n o n e i n b o t h g r o u p s ,r e s p e c t i v e ly . T h e n o n - u s e r s h a d a l m o s t n o e x p e r i e n c e w i t hd r u g s o t h e r t h a n a l c o h o l .

A m o n g t h e h e a v y m a r i j u a n a u s er s, t h e o n ly d r u g so t h e r t h a n m a r i j u a n a t h a t a n y s u b j e c ts h a d u s e d 1 0 0 o rm o r e t i m e s i n t h e i r l i fe w e r e: a l c o h o l , 8 8 % o f s u bj e c t s;c o c a i n e , 1 2 % ; a m p h e t a m i n e s , 1 2 % ; p s y c h e d e l i c s o t h e rt h a n L S D , 6 % ; L S D , 6 % ; a n d t r a n q u il i z e r s, 4 % . H i s t o r i e so f d e p e n d e n c e ( R o b i n s a n d H e l z e r 1 9 85 ) o n d r u g s o t h e rt h a n m a r i j u a n a w e r e o b t a i n e d f r o m o n e h e a v y m a r i j u a n au s e r ( 2 % , a m p h e t a m i n e s ) a n d o n e i n t e r m e d i a t e m a r i j u a n au s e r ( 4 % , h e r o i n a n d o t h e r o p i a t e s ) .

Use of drugs other than marijuana in the last 30 daysI n t h e l a s t 3 0 d a y s, t h e m e d i a n f r e q u e n c y o f a l c o h o l u s e f o rt h e h e a v y m a r i j u a n a u s e rs w a s 6 - 9 t i m e s a n d t h e u p p e r


4/10

222q u a r t i l e w a s 1 0 - 1 9 t i m e s . C o r r e s p o n d i n g f r e q u e n c i e s f o rt h e o t h e r m a r i j u a n a u s e r g r o u p s w e r e l 0 1 9 a n d 2 0 - 3 9t i m e s fo r b o t h t h e i n t e r m e d i a t e a n d l i g h t u s e rs ; a n d 3 5a n d 6 - 9 t i m e s fo r t h e n o n - u s e r s. M o r e o f t h e l ig h t m a r -i juana use r s had used a lcohol a t l eas t once in the l a s t 30d a y s t h a n t h e n o n - u s e r s o f m a r i j u a n a , P < 0 .0 0 1, b u t t h el igh t and in te r media te use r s d id no t d i f f e r in th i s r e spec t ,n o r d i d t h e i n t e r m e d i a t e a n d h e a v y u s e r s . T h e s a m ep a t t e r n h e l d w h e n f r e q u e n ci e s o f a l c o h o l u s e i n th e l a s t 3 0d a y s w e r e a n a l y z e d , t h e o n l y d i ff e re n c e b e i n g t h a t b e t w e e nl igh t and non- use r s , P < 0 .001 .

E i g h t h e a v y m a r i j u a n a u s e rs ( 1 5 % ) a n d o n e i n te r -m e d i a t e u s e r ( 4 % ) r e p o r t e d u s i n g i l l i c i t d r u g s o t h e r t h a nm a r i j u a n a m o r e t h a n t w i c e i n t h e l a st 30 d a y s t w o L S D ,o n e p s y c h e d e l i c s o t h e r t h a n L S D , t h r e e a m p h e t a m i n e s ,t w o c o c a i n e , a n d o n e b o t h c o c a i n e a n d n a r c o t i c s o t h e rt h a n h e r o i n . I n t h e u r i n e s c r e e n i n g , o n e h e a v y u s e r ( 2 % )s h o w e d c o d e i n e , a n d f o u r h e a v y u s e r s ( 8 % ) a n d t h r e ei n t e r m e d i a t e u s e rs ( 1 1 % ) s h o w e d c o c a i n e . O n e o f t h el a t t er i n t e r m e d i a t e u s e rs w a s t h e i n d i v i d u a l w i t h a h i s t o r yo f d e p e n d e n c e o n h e r o i n a n d o t h e r o p i a t es m e n t i o n e da b o v e .

Comparability of the groupsF i g u r e I ( A ) s h o w s t h e s u b j e c ts ' f o u r t h g r a d e I o w a T e s tscor es . Bef ore the onse t o f d r u g use , the gr ou ps w er e w e l lmatc hed , i .e ., they show ed n o s ign i f ican t d i f f e rences on te s ts c o re s . T a b l e 1 g i v es i n f o r m a t i o n a b o u t d e m o g r a p h i cc h a r a c t e r is t i c s o f th e s u b j ec t s. T h e g r o u p s s h o w e d n os ign i f ican t d i f f e r ences w i th r espec t to age , educa t ion , w or ks t a t u s , a n n u a l i n c o m e , H o l l i n g s h e a d O c c u p a t i o n a l S c a l eScor e ( H ol l ingshead 1949) , s ex , o r r ace .

Performance in test sessionsF i g u r e I ( B ) s h o w s p e r f o r m a n c e i n th e t w e l ft h g r a d e I o w aT e s ts . T w o o f t h e s e t es ts , t h o s e d e a l i n g w i t h m a t h e m a t i c s( A b i l it y t o D o Q u a n t i t a t i v e T h i n k i n g ) a n d v e r b a l e x -p r e s s i o n (C o r r e c t n e s s a n d A p p r o p r i a t e n e s s o f E x p r e s -s i on ) , s h o w e d i m p a i r m e n t s i n h e a v y u s e r s re l a ti v e t o n o n -use r s ( s ign i f ican t D unne t t ' s t e s t s , P < 0 .05) . H eavy use r sw er e un impa i r ed on the o the r th r ee t e s t s , i . e . , V ocabula r y ,A b i l i ty t o I n t e r p r e t L i t e r a r y M a t e r i a l s , a n d S h o r t T e s t o fE d u c a t i o n a l A b i l i t y .

O n e c o m p u t e r i z e d t e s t , B u s c h k e ' s T e s t , s h o w e d i n t e r -ac t ions ind ica t ing impa i r ments in heavy use r s . I n th i s t e s t ,w h i c h c o m p a r e d m e m o r y f o r hi g h a n d l o w i m a g e r yw o r d s , h e a v y u s e r s s h o w e d i m p a i r m e n t r e l a t i v e t o n o n -u s e rs i n l o n g - t e r m r e t ri e v a l f o r h i g h b u t n o t l o w i m a g e r yw or ds ( F ig . 2 , cen te r ; s ign i f ican t use r g r ou p x imag er yinteract ion, F3,183 = 3.1, P < 0.05, and Dunnett ' s tes t) .C o n s i s t e n t l o n g - t e r m r e t r i e v a l , w h i c h m e a s u r e d t h e n u m -ber s o f w or d s r e l i ab ly r eca l led f r om t r i a l to tr i a l w i tho utomis s ion , show ed a s imi la r pa t te r n , i . e . , impa i r ment inh e a v y u s e rs r e l a ti v e t o n o n - u s e r s f o r h i g h b u t n o t l o wimager y w or ds ( F ig . 2 , l e f t ; s ign i f ican t use r g r oup x imag-e r y in te r ac t ion , F3 ,183 = 3 .4 , P < 0 .05 , and D u nn e t t ' st e s t ) . The da ta f or shor t - t e r m r e t r i eva l sugges ted a s l igh t ,o p p o s i t e , c o m p e n s a t o r y t e n d e n c y , b u t w e r e e q u i v o c a l

A 6 -0 i ig 2

o. ;Vocab Read Lang Math Work-St CornpTest

130 B30

120 20 / -Vocab Lit ExpTest

Quart Educ

Fig. 1. A, B Scores on the Iowa Tests and the Sho rt Test ofEducational Ability. The bars indicate standard errors. A Per-formance of subjects on the Iow a Tests o f Basic Skills during thefourth grade of grammar school. The scores are grade equivalents,i.e., 4 = fourt h grade, 5 = fifth grade, et c. Vocab= Vocabulary,Read = Reading Comprehension, Lan9 = Language Skills, Math= Mathematics Ski lls, Work-St= Work-Study Skills, Comp= Com posite Score. B Performance of subjects o n the twelfth gradeversions of the Iowa Tests o f Educational Development (rightordinate ax is, standard scores) and the Short Test of EducationalAbility (left ordin ate axis, quot ient scores). Vocab = Vocabulary, Lit= Ability to Interpret Literary Materials, Exp = Correctness andAppropriateness of Expression, Quan = Ability to Do QuantitativeThinking, Educ = Short Test of Educational Ability. The fourthgrade tests most comparable to Vocab, Lit, Exp, and Quan areVocabulary, Reading Comprehension, Language Skills, and Math-ematics Skills, respectively. Significance is indicated as follows:* heavy marijuana users differ from non-users by D unn en's test,P < 0.05. (E ) Hea vy users, n = 52; (~ ) intermediate users, n = 28;(Z') light users, n = 64, except th at n = 63 for fourth gra de L an-guage Skills, Work-Study Skills, and Composite Score; (9) non-users, n = 72

( F ig . 2, r igh t ); a l th ou gh the use r g r ou p x imag er y in te r -ac t ion w as s ign i f ican t , F 3 , 1 8 3 = 3.2, P < 0.05, non-usersd i d n o t d i f f e r f r o m h e a v y u s e r s ( o r f r o m i n t e r m e d i a t e o rl ight users) .S u b j e c t s w e n t t h r o u g h s e v e n s u c c es s i ve t r ia l s, a n d t h ei m p a i r m e n t o f h e a v y u s e r s r e la t i v e t o n o n - u s e r s i n c o n -s i s ten t long- te r m r e t r i eva l t ended to be gr ea te r on in i t i a lt r i al s tha n subs eque nt t r i al s ; th is use r g r o up x t r i a l in te r -ac t ion w as s ign i f ican t by the usua l F t e s t , F 1 8 , 1 o 9 8 = 1.7,P < 0 .0 5 , b u t o n l y m a r g i n a l a f t er a d j u s t m e n t u s i n g t h eG r e e n h o u s e - G e i s s e r p r o c e d u r e , P < 0 . 1 0 . T a b l e 2 s h o w st h e a d j u s t e d m e a n s c o r e s i n B u s c h k e ' s T e s t b y u s e r g r o u p .

O n e o t h e r c o m p u t e r i z e d t e s t , t h e o n e t h a t a s s e s s e da b s t r a c t i o n ( C o n c e p t F o r m a t i o n ) , s h o w e d a n i n t e r a c t i o n


5/10

Table 1 . Demographic charac ter i s t icsof user groups

223

Use r g r oupHeavy Intermedia te Light Non(n = 52) a (n = 28) a (n = 64) a (n = 72) "M e a n S E M e a n _ + S E Mea n -t- SE Mea n SE

Ag e (ye ars ) 23.4 0.7 23.4 _+ 0.7 23.2 -t- 0.6 23.3 0.7Ed uc at io n (year s) 14.0 0.2 14.6 _+ 0.2 14.2 -t- 0.2 14.3 0.2Frequency dis t r ibut ions (%)Work statusEmp loyed (non-students) 29 14 22 18Em ploye d (students) 37 6t 41 50Un emp loye d b 35 25 38 32Annual incomeUn de r $15, 000 87 89 88 76$15, 000 to $35, 000 13 11 13 24Hollingshead OccupationalScale Score c1, 2, or 3 41 52 29 334 or 5 35 33 34 416, 7, 8, or 9 24 14 37 26

Se xMe n 81 79 75 79Wo me n 19 21 25 21RaceWh ite 100 100 97 97Non-w hi te 0 0 3 3

Note : Percentages may not add to 100 wi th in each user group due to rounding er roraOne l ight mar i juana user d id not provide informat ion on educat ion. For the Hol l ingsheadOccupat ional Scale Score , the unemployed and e ight employed s tudents who did not indica tethe i r occupat ions were excludedbAll the unemployed subjects were students except for four heavy users, two light users, and onenon-usercOccupations were scored on a nine-point scale where lower scores indicated less status(Hollingshead 1949)

6to-o 5

4

E

C L T RHigh

FL T R L T R L T R

Low High LowScore and Imagery

ST R ST RHigh Low

Fig. 2. Significant interactions of user group and imagery for con-sistent long-term retrieval (CLTR), long- term re t r ieval (LTR), an dshor t - te rm re t r ieval (STR) scores in Buschke's Test. The scores,which are averaged over trials, are based on eight high imagerywords (High) and e ight low imagery words (Low). The bars indica testanda rd errors. The performa nce of the heavy users is primarilyresponsible for the interactions for the consistent long-term retrievalscore and the long-term retrieval score. Significance is indicated asfollows: * heavy marij uana users differ from non-use rs by Du nnett 'stest, P < 0.05. ( ) Hea vy users, n = 52; ([]) interm ediate users, n= 28; ([]) light users, n = 64; (f~) non-users, n = 72

o f a w i t h i n - t e s t m a n i p u l a t i o n w i t h m a r i j u a n a u s e. I n t e r -m e d i a t e u s e r s a c h i e v e d a h i g h e r p e r c e n t a g e o f c o r r e c tr e s p o n s e s t h a n n o n - u s e r s o n f u z z y c o n c e p t s , f o r w h i c h t h ef a m i l i es o f f a c e s h a d n o u n i f o r m l y d i s t i n g u i s h i n g f e a t u r es ,w h e r e a s n o n - u s e r s d i d n o t d i ff e r f r o m h e a v y , i n t e r m e d i a t e ,o r l i g h t u s er s o n c l e a r c o n c e p t s , f o r w h i c h t h e r e w e r eu n i f o r m l y d i s t i n g u i s h i n g f e a t u r e s ( s i g n i f i c a n t u s e r g r o u px c o n c e p t i n t e r a c t i o n , F 3 . 1 8 3 = 2 .9 , P < 0 . 05 , a n d

D u n n e t t ' s t es t) . T h e p r e s e n c e v e r s u s a b s e n c e o f t h e o r i -g i n a l c a r d p i c t u r i n g f a c es o f f i ve m e m b e r s o f e a c h f a m i l y ,w h i c h w a s r e m o v e d a f t e r h a l f t h e t e s ti n g o n n e w f a c e s h a db e e n c o m p l e t e d , d i d n o t i n f l u e n c e t h e e ff e c t o f m a r i j u a n au s e . T a b l e 2 s h o w s t h e a d j u s t e d m e a n p e r c e n t a g e s o fc o r r e c t r e s p o n s e s b y u s e r g r o u p f o r f u zz y a n d c l e a r c o n -c e p ts . A p a r t f r o m t h i s o n e i n t e r a c t i o n a t t r i b u t a b l e m a i n l yt o i n t e r m e d i a t e u s e rs , i n t e r m e d i a t e a n d l i g h t u se r s n e v e rd i f f e r e d f r o m n o n - u s e r s o n a n y t e s t .

N o e f fe c ts o f m a r i j u a n a u s e w e r e s h o w n b y t h e o t h e rc o m p u t e r i z e d t e s t s , i .e ., t h e t e s t s a s s e s s i n g l e a r n i n g o fp a r a g r a p h s o f t e xt ( T ex t L e a r n i n g ) a n d a s s o c i a ti o n s b e -t w e e n p a i r s o f w o r d s ( P a i r e d A s s o c i a t e L e a r n i n g ) , t h e te s ti n w h i c h t h e s u b j e c t g a v e v a r i o u s t y p e s o f a s s o c i a t i o n s t ow o r d s ( F r e e a n d C o n s t r a i n e d A s s o c i at i o n s) , a n d t h ep s y c h o m o t o r t es ts (C r i t ic a l F l i c k e r F u s i o n a n d D i s c r i m -


6/10

224Table 2. Adjusted scores on com-puterized tests by u ser group(mean + SE)

Test anddependent variable User groupHe av y Intermediate Light NonBuschke's TestNumber of words aTotal recall 5.8 _+Long-term retrieval 5.0 _+Long-term storage 5.5 _+

Short-term retrieval 0.8 __Consistent long-term retrieval 3.7 -t-Concept formatio nPercentage correctFuzzy concepts 64.5 +_Clear concepts 83.6 Text LearningNumber of propositions recalled t2.4 +_Paired Associate LearningPercentage correct 74.7 +Free and Constrained AssociationsDominance of responses 43.3 _+Psychomotor TestsCritical flicker fusionthreshold (Hz) 37.0 _+Discriminant reaction time (s/100) 37.9 +_

0.2 6.1 _+ 0.2 6.0 + 0.1 6.2 _+ 0.10.2 5.4 +_ 0.3 5.4 _+ 0.2 5.5 _+ 0.20.2 5.8 _-/-0.3 5.8 _+ 0.2 5.8 _+ 0.20.1 0.7 + 0.1 0.7 _+ 0.1 0.7 _+ 0.10.3 4.2 +_ 0.3 4.3 +_ 0.2 4.4 +_ 0.2

2.6 77.0 !-_3.0 72.4 _+ 1.8 68.5_+ 1.82.4 85.3_+ 2.8 84.0 + 1.6 86.4_+ 1.70.8 11.9 _+ 0.9 13.4 _+ 0.5 t3.4 +_ 0.52.1 76.7+ 2.5 79.3 _+ 1.5 76.6_+ 1.51.2 44.9_+ 1.4 46.5 _+ 0.8 46.7_. 0.8

0.6 35.8_+ 0.8 36.7 + 0.4 35.9+ 0.40.4 37.4_+ 0.5 37.8 + 0.3 38 .2_+ 0.3"The scores, which are averaged over trials and types of imagery, are based on eight words

lnant Reaction Time). The adjusted mean scores by usergroup are given in Table 2.Controlling for use of other drugsLifetime use of other drugs. Between-subjects comparison sindicated overall impairments of the heavy users relativeto the non-users in two tests, the twelfth grade Iowa Testsdealing with mathematics and verbal expression. Attribut-ing these impairments to marijuana might not be justified,however, as the heavy users also had mor e experience withother drugs. This possibility was examined by re-peating the analyses of these tests with 12 additional co-variates representing lifetime frequencies of use of alcohol,cocaine, amphetamines, LSD, psychedelics other thanLSD, heroin, narcotics other than heroin, tranquilizers,amyl or butyl nitrites, barbiturates, methaqualone, andphencyclidine. The possible values for each cova riate werethe frequencies of use (0, 1-2, 3-39, 40-99, and 100 ormore times). Four intermediate frequency categories onthe drug questionnaire (3 5, 6-9, 10-19, and 20-39 times)were pooled into a single category for these analyses,because adjusted means were otherwise non-estimable(Freund and Little 1985, pp 176-180). The impairments ofthe heavy users relative to the non-users in these testsremained significant while controlling for lifetime use ofother drugs (significant Dunnett's tests, Ps < 0.05).Use of other illicit drugs in the last 30 days. Some of themarijuana users had used illicit drugs other than mari-juana in the last 30 days. This might have affected theirperformance, making it unjustifiable to attribute the im-pairments of the heavy users in the tests dealing withmathematics and verbal expression to marijuana. Thispossibility was examined by repeating the analyses de-scribed in the previous section after excluding all subjects

who had used any illicit drug other than marijuana morethan twice in the last 30 days or who showed any in theirurine. The imp airmen ts of the heavy users relative to thenon-users in these tests remained significant while simul-taneously controlling for use of other illicit drugs in thepast 30 days and lifetime drug use (significant Dunnett'stests, Ps < 0.05).History of alcohol dependence. Attributing the impair-ments of the heavy users in the tests dealing with math-ematics and verbal expression to marijuana might not bejustified, as 88% of the heavy users, compared to only49% of the non-users, had used alcohol 100 or more timesin their lifetime, raising concerns abou t the possible influ-ence of alcoho l on perfo rmance in these tests. No quantit -ative measure of heavy, long-term alcohol use was avail-able, since frequencies of lifetime alco hol use greater than100 times were not quantified in further detail. However,the influence of alcohol could be examined by comp aringperformance of the heavy marijuana users in the study,none of whom had a history of alcohol dependence, withperformance of nine additional heavy marijuana usershaving a history of alcohol dependence who were tested.These analyses indicated that performance in the testsdealing with mathematics and verbal expression did notdiffer for heavy marijuana users with and without ahistory of alcohol dependence, Ps > 0.05.

Discussion

Overall impairments associated with heavy marijuana useOn the twelfth grade Iowa Tests assessing mathematicsand verbal expression, heavy users showed overall impair-ments relative to non-users who were matched on in-


7/10

225te l lec tual funct ion ing before the onset o f d rug use . Noovera l l impai rments were detec ted in o ther capabi l i t i esinclud ing read ing comprehens ion , vocabulary , psycho-motor performance, concept fo rmat ion , associa t ive pro-cesses , and memory . The impai rments in performanceobserved in the heavy users cou ld ind ica te tha t use ofmar i juana seven or more t imes weekly for ex tendedper iods produces impai rments in CNS funct ion that ou t -last the drug's acute effects . However, possible cri t icismsof our methodology and a l t ernat ive explanat ions of thef ind ings mus t be cons idered .Reliability, validity, and intercorrelations of tests. Par ro t t(1991a, b, c) has recent ly cri t icized much human psycho-phar mac ology research for l imi ted use of complex t es t s o fh igher cogni t ive funct ion and re l i ance on performancetes t s wi th l i t t l e o r no ev idence of val id i ty and undocu-men ted re l iab i li ty , mak ing the in terpre ta t ion of find ingsd i f fi cu lt and ambiguous . In terpre ta t ion of the impai r -ments o f the heavy users in mathem at ics and verbalexpression is not suscept ible to these cri t icisms. Thetwel f th g rade Iowa Tes t s, as wel l as the four th g rade IowaTes t s and the S hor t Tes t o f Educat ion al A bi li ty, assessh igher cogni t ive funct ions and thei r developers have accu-mulated extensive evidence of val idi ty and rel iabi l i ty(Science Research Associates 1972, 1981; Hie ron ym uset al . 1982; Iow a Test in g Pro gra ms 1987b ) .The value of match in g groups o f mar i jua na users andnon-users on fou r th grade Iow a Tes t scores might a l so bequest ioned. Would these scores real ly predict intel lectualcapabi l it i es many years l a ter? This ques t ion was exa minedus ing data o f the non-users , and an af f i rmat ive answer wasind icated by subs tan t i a l Pearson product -moment corre l -a t ions of the twel f th g rade Iowa Tes t s wi th correspondingfourth grade Iowa Tests , Ps < 0.001 for al l : Vocabularywi th Vocabulary , r = 0 .59; Correctness and Appropr ia te-ness of Expressio n w ith Lan gua ge Ski l ls, r = 0.56; Abil i tyto In terpre t L i t erary Mater ia l s wi th Reading Comprehen-sion, r = 0.52; Abil i ty to Do Quant i tat ive Thinking withMathematics Ski l ls , r = 0.44.Long-lastin9 acute effects of marijuana. Sb that acu teeffec ts o f mar i ju ana smoking would no t in f luence tes tperformance, subjects had to abstain for 24 h before test -ing. We considere d this period of abstent ion sufficient toavoid acu te ef fec t s o f mar i ju ana smoking on performanceand d id no t ask sub ject s to abs ta in longer because wethought tha t do ing so would decrease recru i tment , com-pl iance , and t ru thfu lness among the heavy users . How-ever, the possibi l i ty that the impairments observed in theheavy users were due to long-last ing acute effects must becons idered .There have been a few reports of such effects . In apre l iminary , open s tudy of s imula ted f ly ing wi tho utplacebo controls , Yesavage et al . (1985) found that pi lotsperformed p oorer 24 h af t er smoking mar i ju ana thanbefore smoking. In the fi rs t of two sub seque nt s tudies withplacebo controls , they fai led to repl icate these resul ts(Leirer et al . 1989). In the second, they r eporte d a s ignific-an t im pai rme nt 24 h af t er smoking m ar i juan a based onanalyses ut i l izing mult iple, one-tai led t tes ts (Leirer et al .1991). With more convent ional , two-tai led analyses, the

impai rm ent would n o t have been s ign if i can t fo r more tha n4 h af t er smoking . Thi s du ra t ion of effect would be some-what m ore cons i s ten t wi th anoth er g rou p 's f ind ings regar-d ing mar i juana 's ef fec t on s imula ted f ly ing (Janowskyet al. 1976).Three o ther repor t s o f long- las t ing acu te ef fec ts o fmar i ju ana have been even more equivocal. In two s tudies ,Ch ai t an d col leagues (Cha i t et al . 1985; Ch ai t 1990) fou ndonly weak ev idence that t es t per formance or sub ject ivestate in the morni~ng was affected by mari juana smokingon the preced ing day , and there were d i screpancies be-tween studies in the effects that were observed. Heishmanet al . (1990) found small residual effects on the day aftermar i juana smoking on cer ta in t es t s in some of the th reeind iv idual s they s tud ied , bu t p rov ided no s ta t is t ica l ana-lyses of the results.Othe r s tud ies have looked for long- las ting acu te ef fec tsof ma ri ju ana (B arnet t et al . 1985) or cann abis resin(L. Rafa elsen et al. 1973; O.J. R afae lsen et al. 1973), bu tfound none. These negat ive f ind ings , combined wi th theequivocal f indings in s tudies report ing long-last ing acuteeffec t s o f mar i juana, make i t seem unl ikely tha t sucheffec ts cou ld ac count fo r the imp ai rments tha t we ob-served in the presen t s tudy among the heavy users .Use of other drugs. Were the overa l l impai rments o f theheavy users re la t ive to the non-users in mathemat ics andverbal expression art i facts resul t ing from differences be-tween groups in use of o ther d rugs? The fac t tha t theheavy and intermediate users did not differ in l i fet imeprevalence of t ry ing any drugs o ther than mar i juana,together wi th the fac t tha t the he avy users showed impai r -ments and the in termedia te users d id no t , a rgue agains tth i s in terpre ta t ion . Addi t ional ev idence that the impai r -ments associa ted wi th heavy mar i juana use were no tart i facts derives from the findings that : (1) They re main edsignificant while contro l l ing for use of other i l lici t drugs inthe past 30 days and l i fet ime frequencies of use of otherdrugs . (2 ) Heavy m ar i juana users wi th a h i s to ry of a lcoholdependence were no t impai red on these t es t s re la t ive toheavy mar i juana users wi thout such a h i s to ry . Thus ,heavy ma r i juana use seems to be associa ted wi th impai r -ments even whi le con t ro l l ing for use of o ther d rugs . (Theresu lt s do no t ind ica te i f mar i ju ana use is associa ted wi thlarger o r smal ler impai rme nts th an use of o ther i l li c itdrugs, as we sought subjects who had l imited experiencewith such drugs.)Did heavy marijuana use impair C N S functio n? I f heavymari jua na use was associa ted wi th cogni tive impai rmentseven after contro l l ing for use of othe r drugs, a nd i f theseimpai rme nts were n o t due to long- las t ing acu te effect s o fmar i juana, can we conclude that heavy use producesimpai rments in CNS funct ion that ou t l as t mar i juana 'sacu te ef fect s? We ca nnot conf iden t ly d raw th i s conclus ion ;our f indings are suscept ible to other, plausible interpreta-t ions . Since our s tudy was no t a con t ro l l ed exper iment inwhich ind iv idual s were ass igned randomly to g roups ofusers and non-users , the l inkage between heavy use andimpai rments was corre la t ional ra ther than causal .Tho ugh the groups of users and non-users were balancedon intel lectual funct ion ing before onset of drug use, educa-


8/10

226t ion, income, occupa t iona l s ta tus , and other demographiccharacter ist ics, they may sti l l have differed in character-i s t ics of the i r educa t iona l , soc ioeconomic , medica l , oro the r h i s to r y - - p r e d ic to r s o r c onc om i ta n t s o f m a r i jua nause or non-use- - tha t we did not assess . Such hypothe t ica ld i f fe rences , ra ther t han heavy mar i juana use, ma y havep r oduc e d the obse r ve d im pa i rm e n t s .For example , we did not ask subjec ts how of ten theya t tende d scho ol whi le under the inf luence of mar i juana ' sacute effects. I t is possible that the heavy users did sof requent ly and, consequent ly , lea rned less than the non-users , which could he lp expla in the i r imp a irments re la t iveto the non-users on the tes ts of mathe mat ics and v erba lexpress ion. Overa l l impa irm ents of the heavy users wereclearer in these tests, which assessed uti l ization of pre-exper imenta l ly acquired informat ion, than in tes ts invol-v ing lea rning o f new inform at ion. S ince these two types oftes ts were not m atched in content , th is d i f ference cann otbe in te rpre ted wi th ce r ta in ty ; but one in t r iguing in te r -pre ta t io n is tha t e f fec ts of chron ic mar i juan a use may bemost observable in measures re f lec t ing an individua l ' scumula t ive lea rning h is tory over a per io d of years .

Qualitative changes in performance associatedwith chronic mari/uana useIn two tes ts , chronic mar i juana use was assoc ia ted wi thchanges in per formance in ce r ta in tes t ing condi t ions , butnot wi th overa l l impa irments .Effects on memory. Heavy use was assoc ia ted wi th se lec -t ive impairments in memory re t r ieva l processes inBuschke ' s Tes t , which were res t r ic ted to h igh imagerywords . Consis tent long- te rm re t r ieva l , which was par t i -cular ly sensit ive to marijuana 's effects, is presumed tore f lec t deve lopment of organized, e labora ted semant icrepresenta t ions media t ing consis tent reca l l . Heavy mar i -juan a use was assoc ia ted wi th a decrease in the s ize of thenormal imagery effect in retr ieval, i .e . , the superiority inper formance for h igh imagery re la t ive to low imagerywords . Th e decreased imagery e f fec t could a lso re f lec tdecreased or s lowed deve lopm ent of e labora te d repres-enta t ions amo ng the he avy users. This e f fec t i s s imi la r tothe acute e f fects we observed wi th the benzodiazepines(Block and Ber cho u 1984). I t is interestin g in view of thesubjec t ive ly repor ted increase in imagery fo l lowing mar i -juana smoking (Tar t 1971) , toge ther wi th our inabi l i ty inpas t work to de tec t any cor responding objec t ive changesin pe r f o r m a nc e f o llowing m a r i jua na sm ok ing ( B loc k a ndW itte nb orn 1984). The absence o f specif ic measu res ofre t r ieva l in the o ther memory tes ts may have renderedthem less sens i t ive than Buschke ' s Tes t to mar i juana ' se ffec ts. The m ore s t ruc tured mate r ia ls used in these o thertests, i .e . , text and pairs of words, may also have contr ib-uted to their lesser sensit ivity.Concept formation. In the Concept Format ion tes t , in te r -media te use rs show ed a se lec t ive impro vem ent re la t ive tonon-users in the percentage of cor rec t responses for fuzzyconcepts . Research wi th fuzzy ca tegor ies has sugges tedtha t pe op le m a y o f t e n de ve lop " p r o to type s" f o r e a c h

ca tegory represent ing the most typica l examples and thenclassify new instances by evalu ating their similar ity tothese prototype s (Reed 1972). Perhap s in te rm edia te use rsre l ied more on such a g loba l , "ges ta l t" , pe rceptua l ly medi-a ted approach than on a focussed, logica l , sys temat icsearch for distinguishing features of categories. This seemscompat ib le wi th subjec t ive ly repor ted shi f t s in thoughtprocesses fo l lowing mar i ju ana smok ing (Tar t 1971) . Ho w-ever , heavy users d id not show the same pa t te rn asin te rmedia te use rs , tending ins tead to have the lowestpe r c e n ta ge c o r r e c t o f a ny g r oup . The non- m ono to n icre la t ion be tween f requency of chronic ma r i juana use andpercentage cor rec t for fuzzy concepts ma nda te s ca ut ion inin te rpre t ing th is re la t ion , which should be consideredtenta t ive unt i l fu ture ver i f ica t ion .

Relation to other studies of chronic cannabis useThe m ost imp or ta nt f indings of our s tudy, the overa l limpairm ents in mathemat ic s and verba l express ion associ -a ted wi th heavy use , cannot be compared to pas t s tudiesof chronic use of mar i ju ana (or , mor e broadly , cannabis) ,s ince none have inc luded achievement tes ts among the i rassessments. Th ere have been repor ts of impairments oninte l l igence tes ts or subtes ts among chronic cannabisusers in Greece and India (Stefanis et a l 1976; Wig andVarma 1977) , but many other s tudies have found noimpairments on in te l l igence tes ts (e .g . , Cuber and King1974; Carl in an d Tr upin 1977 ). The impa irments tha t weobserved in mathemat ics and verba l express ion shouldnot be in te rpre ted as evidence of impaired in tel l igence.Our f inding tha t heavy mar i juana use was assoc ia tedwith se lec tive impairme nts in mem ory re t r ieva l processesin Buschke ' s Tes t accords wi th a previou s repor t of re -t r ieva l impa irment in Buschke ' s Tes t among chronic can-nabis users in Costa Rica (Page et a l . 1988). Retr ievalimpairment in Buschke ' s Tes t has a lso been observed asan ac ute effect of mar ijua na smo king (Miller e t a l. 1978;Block e t a l. 1992). Impairm ents amo ng ch ronic mar i juan ausers in the Uni t ed S ta tes and C anad a hav e been de tec tedpr imar i ly by memory tes ts . Three groups have repor tedmemory impairment in d i f fe rent te s ts (Ent in andGoldzung 1973; Gianutsos and Li twack 1976; Schwar tzet a l . 1989), whereas onl y single, isolated re ports havesuggested impairment of o ther cogni t ive func t ions (Grantet a l . 1973; Weckowicz et a l . 1977). Outside the UnitedS tat e s a nd C a na da , m e m o r y im pa i r m e n ts a m ong c h r on iccannabis use rs have a lso been rep or ted in severa l s tudies ,a s ha ve im pa i r m e n t s o f p syc hom oto r pe r f o r m a nc e a ndtime perception (Soueif 1971, 1975, 1976; Wig and Varma1977; Mendhiratta et a l . 1978; Page et a l . 1988; Varma etal . 1988). The relativ e sensitivit ies of me mo ry an d oth ercapabi l i t ie s to impairments assoc ia ted wi th chronic can-nabis use are not yet c lear .No ne o f these studies repor t ing impairmen ts assoc i -a ted wi th chronic cannabis use matched users and non-users on measures o f in te l lec tua l func t ion obta ined beforethe onse t of drug use , as we did. Thus , no ne co ntro l led forthe poss ib i l i ty tha t individua ls who became chronic can-nabis use rs might have been p oo rer in in tel lec tua l func t ioninit ial ly . To keep these num erous repor ts of cogni t ive


9/10

227i m p a i r m e n t s i n p e r s p e c t iv e , m o r e o v e r , i t s h o u l d b e n o t e dtha t : ( 1 ) they a r e a mino r i ty , s ince mos t s tud ies of e f fec t s o fc h r o n i c c a n n a b i s u s e o n c o g n i t i o n , m e m o r y , o r p s y c h o -m o t o r p e r f o r m a n c e h a v e n o t f o u n d i m p a i r m e n t s , e . g . ,B o w m a n a n d P i h l ( 19 7 3 ); (2 ) e v e n i n s tu d i e s r e p o r t i n gs o m e i m p a i r m e n t , c u m u l a t i v e l y , m a n y m o r e t e s t s h a v eb e e n f o u n d u n i m p a i r e d t h a n i m p a i re d ; ( 3) so m e t i m e s,s p e c i f i c t e s t s s h o w i n g i m p a i r m e n t i n o n e s t u d y h a v e n o ts h o w n i m p a i r m e n t i n o t h e rs ; (4 ) s t u d i es h a v e v a r i e d w i d e -l y i n m e t h o d o l o g i c a l s o u n d n e s s ; ( 5 ) t h e l i m i te d e d u c a t i o na n d f r e q u e n t i l l i t e ra c y o f s u b j e c t s i n m a n y s t u d i e s o u t s i d et h e U n i t e d S t a t es a n d C a n a d a - - a n d t h e s p e ci a l p o p u l a -t ions involved in some s tud ies , i . e . , p r i soner s ( Soue i f 1971 ,1 9 7 5, 1 9 7 6) - - r a i s e q u e s t i o n s a b o u t g e n e r a l i z a b i l i ty o f t h er esu l t s to typ ica l , edu ca te d ind iv idu a l s in indus t r i a l soc ie -t ie s a n d a p p r o p r i a t e n e s s o f t h e s t a n d a r d i z e d p s y c h o -l o g i c a l te s t s u s ed , m a n y o f w h i c h w e r e d e v e l o p e d f o r s u c hindiv idua l s .

Suggestions for further researchM o r e w o r k i s n e e d e d t o e v a l u a t e a l t e r n a t i v e i n t e r p r e t a -t i o n s o f t h e c o g n i t i v e i m p a i r m e n t s a s s o c i a t e d w i t h h e a v ym a r i j u a n a u s e: d o e s s u c h u se p r o d u c e i m p a i r m e n t s i nC N S f u n c t i o n t h a t o u t l a s t m a r i j u a n a ' s a c u t e e f fe c ts ? O r i sthe as soc ia t ion mor e ind i r ec t , e . g . , do heavy use r s l ea r nl e ss i n s c h o o l , o r f o r g e t m o r e o f w h a t t h e y l e a r n, s o t h a tm e a s u r e s r e f l e c t i n g a n i n d i v i d u a l ' s c u m u l a t i v e l e a r n i n gh i s t o r y o v e r y e a r s a r e p a r t i c u l a r l y s e n s i t i v e ? T h e l a t t e re x p l a n a t i o n a c c o r d s w e l l w i t h t h e o v e r a l l i m p a i r m e n t s i nm a t h e m a t i c s a n d v e r b a l e x p r e s s i o n t h a t w e o b s e r v e d , b u tl es s so w i t h t h e s e le c t iv e i m p a i r m e n t s i n m e m o r y r e t ri e v a lp r o c e s s e s . C o n c e i v a b l y , t h e r e t r i e v a l i m p a i r m e n t s c o u l db e a s s o c i a t e d w i t h c h a n g e s i n C N S f u n c t i o n t h a t o u t l a s tm a r i j u a n a ' s a c u t e e f f e c t s a n d c o u l d c o n t r i b u t e t o t h ei m p a i r m e n t s i n m a t h e m a t i c s a n d v e r b a l ex p r e s s i o n .

F u t u r e r e s e ar c h s h o u l d a t t e m p t t o c o r re l a t e c h a n g e s i nc o g n i t i v e f u n c t i o n a s s o c i a t e d w i t h h e a v y m a r i j u a n a u s ew i t h p o s s i b l e c h a n g e s i n b r a i n f u n c t i o n . S i nc e m o s t o f o u rs u b j e c t s w e r e y o u n g a d u l t s , m o r e w o r k i s a l s o n e e d e d t od e t e r m i n e w h e t h e r h e a v y u s e i s a s s o c i a t e d w i t h l o w e re d u c a t i o n a l a t t a i n m e n t a n d o c c u p a t i o n a l p e r f o r m a n c el a t e r i n l i f e . A n o t h e r h i g h p r i o r i t y s h o u l d b e c o n t r a s t i n gc o g n i t i v e i m p a i r m e n t s a s s o c i a t e d w i t h h e a v y u s e o f m a r i -j u a n a a n d o t h e r d r u g s , i n di v i d u al l y a n d i n c o m b i n a t i o n ,b y s t u d y i n g s u b j e c t s w h o d i f f e r i n t h e d r u g s t h a t t h e y u s em o s t f r e q u e n t l y . I n a l l t h e s e e n d e a v o r s , s e l e c t in g g r o u p s o fs u b j e c t s w h o a r e m a t c h e d o n i n t e l l e c t u a l f u n c t i o n i n g b e -f o r e t h e o n s e t o f d r u g u s e w i ll a l l o w m o r e c o n f i d e n c e i n t h ec o n c l u s i o n s .Acknowledgements.Than ks are due to K. Braverman, S. Farnha m, S.Siegel, W. Walters, an d R. Farinp our for assisting with the c ondu ctof the research; D. A. Frisbie for providing fourth grade scores on theIowa Tests and advice about these tests; G. Woodworth for statist-ical advice; and J. V. Hinrichs, R. Noyes, Jr., R. A. Forsyth , A. N.Hieronym us, J. J. Boren, and J. W. Spencer fo r advice conc erning theresearch. This research was supported in part by grant 5 R01DA03988 from the Nationa l Institute on Dru g Abuse to R. I. Blockand grant RR59 from the General Clinical Research Centers Pro-gram , Division of Research Resources, Natio nal Institutes of Heal thto the Clinical Research Center, University o f Iowa.

ReferencesBarnett G , Licko V, Tho mps on T (1985) Behavioral p harm a-eokinetics o f marijuana. Psyc hop harm acol ogy 85 : 51 56Berehou R, Block R I (1983) Use of computerized psychomo tortesting in determining CNS effects of drugs. Percep t M ot Skills57 : 691-7 00Block RI, Berchou R (1984) Alprazolam and lorazepam effects onmem ory acquisition and retrieval processes. Pharm acol BiochemBehav 20 : 233-241Block RI, Wittenb orn JR (1984) Mariju ana effects on visual imageryin a paired-associate task. Percept M ot Skills 58: 759 -766Block RI, Farnham S, Braverman K, Hinrichs JV, Ghoneim MM(1989) Norm s for free associations and five types of constrainedassociations. Psych ol Rep 64:10 65 1066Block RI, Farin pou r R, Brave rman K (1992) Effects of marijua nasmoking on cognition and their relationship to smokin g tech-nique. Pharmacol Biochem Behav (in press)Bowm an M, Pihl RO (1973 ) Cannabis: psychological effects ofchronic hea vy use: a controlled study o f intellectual functioningin chronic users of high potency cannabis. Ps ycho pharm acolo gia29:159-170Buschke H (1973) Selective reminding for analysis o f me mo ry andlearning. J Verb Learn Verb Behav 1 2:543 550Carlin AS, Trupin EW (1977) The effect of long-term chronicmarijuan a use on neuropsycho logical functioning. Int J Addict12:617-624Chait LD (1990) Subjective and behavioral effects of marijuana themorn ing after smoking. Psy cho pharm acolo gy 100 : 328-333Chait LD, Fischm an MW, Schuster CR (1985) 'Han gov er' effects themorning after marijuana smoking. Drug Alcohol Depend15 : 229-238Culver CM, King FW (1974) Neuropsychological assessment ofundergraduate marihuana and LSD users. Arch Gen Psychiatry31 : 707-711Entin EE, Gold zun g PJ (1973) Residual effects of marih uana usageon learning and memo ry. Psycho l Rec 23 : 169-178Freun d R J, Littell RC (1985) SAS for linear models: a g uide to theANO VA and GLM procedures. SAS Institute, Cary, NorthCarolinaGianutsos R, Litwack AR (1976) Chronic marijuana smokers show

reduced coding into long-term storage. Bull Psychon Soc7:277 279Gra nt I, Roch ford J, Fleming T, Stunkard A (1973) A neuro-psychological assessment of the effects of moderate marih uanause. J Nerv Ment Dis 156:278-280Heishman SJ, Huestis MA, Henningfield JE, Cone EJ (1990) Acuteand residual effects of marijuana: profiles o f plasma TH C levels,physiological, subjective, and performance measures. Pharm acolBiochem Behav 37:561-565Hieronymus AN, Lindquist EF, Hoover HD (1982) Manual forscho ol administrators, Iow a tests of basic skills. Riverside Publi-shing, ChicagoHollingshead AB (1949) Elmto wn's yout h: the impa ct of socialclasses on adolescents. Wiley, New YorkIowa Testing Programs (1987a) ITED examiner's manual, direc-tions for testing, Iow a tests o f educationa l development, forms X-8 and Y-8. Iowa Testing P rograms, Th e University of Iowa, Iow aCity, IowaIowa Testing Progra ms (1987b) ITED m anual for teachers, adminis-trators, and counselors, Iowa tests o f educational development,forms X-8 and Y-8. Iow a Testing P rograms, T he University ofIowa, Iowa City, IowaJanowsky DS, Meacham MP, Blaine JD, Schoor M, Bozzetti LP(1976) Mariju ana effects on simulated flying ability. Am J Psych-iatry 133 : 384-388Johnston LD, Bachman JG, O'Malley PM (1981) Student drug usein America: 1975-1981. Nation al Institute on D rug Abuse, Rock -ville, Marylan dLeirer VO, Yesavage JA, Mo rrow D G (1989) Marijuana, aging, andtask difficulty effects on pilo t performance. A viat Space En viro nMed 60:1145-1152


10/10

228Leirer VO, Yesavage JA, Morrow DG (1991) Ma ri jua na carry-overeffects on aircraft pi lot performance. Aviat Space Envi ron M ed62:221-227Mart i n RC, Ca ramaz za A (1980) Classif ication in well-defined andil l -defined categories: evidence for c omm on processing strategies.J Exp Psychol [Gen] 109:320 353Mendhirat ta SS, Wig NN, Verma SK (1978) Some psychologicalcorrelates of long-term heavy c annab is users. Br J P sychiatry132:482-486Miller JR, K intsch W (1980) Readabil i ty and recall of short prose

passages: a theoret ical analysis . J Exp Psychol [ Hu m Learn]6 : 335-354Miller L, Cornet t T, M cFa rland D (1978) Mari jua na: an analysis ofstorage.and retr ieval defici ts in memory with the technique ofrestricted reminding. Pharm acol Biochem Behav 8:32 7-3 32Nat iona l Ins t i tu te on Drug Abuse (1982) Mar i juana and youth:cl inical observat ions on motivat ion and learning. National In-st i tute on Drug Abuse, Rockvil le, MarylandPage JB, Fletcher J , True WR (l 988) Psycho sociocul tural perspect-ives on chronic cannabis use: the Costa Rican fol low-up.J Psychoactive Drugs 20:57-6 5Paivio A, Yuil le JC, M adigan SA (1968) Concreteness, imagery, andmeaningfulness values for 925 nouns. J Exp Psychol 76:1 25Parrot t AC (1991a) Performance tests in human psychopharmaco-logy (1): test rel iabi l i ty and standardizat ion. Hum Psychophar-macol 6 : t - 9Parrot t AC (1991b) Performance tests in human psychopharmaco-logy (2): content validity, criterion validity, and face validity.Hum Psychopharmacol 6 :91 98Parrot t AC (1991c) Performance tests in human psychopharmaco-logy (3): construct val idi ty and test interpretat ion. Hu m Psycho-pharmacol 6 :197 207Rafaelsen L, Christrup H, Bech P, Rafaelsen OJ (1973) Effects ofcannabis and alcohol on psychological tests . Nature242:117-118Rafaelsen O J, Bech P, Ch rist iansen J , Christrup H, Nyb oe J , Rafael-sen L (1973) Cannabis and alcohol: effects on simulated cardriving. Science 179 : 920-9 23Reed SK (1972) Pat tern recognit ion and categorizat ion. CognitPsychol 3 : 382-407Robins L N, Helzer JE (1985) Diag nost ic interview schedule (DIS)version III-A. Washington Universi ty School of Medicine, StLouisRosch E, Mervis CB (1975) Family resemblances: studies in theinternal s t ructure of categories. Cognit Psychol 7 :573 605Rose nbau m PR, Rubi n DB (1985) Constru ct ing a control group

using mult ivariate matched sampling methods that incorporatethe pro pens ity score. A m S tatist 39 : 33-3 8Rubin V, Comitas L (1975) Ganja in Jamaica: a medical anthropo-logical s tudy of chronic marihuana use. Mouton, The HagueSchwartz RH , Gru enew ald P J , Kli tzner M, Fe dio P (1989) Short-t e rm m emory impai rment in cannabi s -dependent adolescents .Am J Dis C hild 143 : 1214-121 9Science Research A ssociates (1972) Interpretat ive manu al , short testof educational ability, STEA, levels 3-5. Science Research Asso-ciates, ChicagoScience Research Associates (1974) Ex aminer 's m anual , STE A, shorttest of edu catio nal ability, levels 3 5. Science Research Associ-ates, ChicagoScience Research A ssociates (1981) IT ED , Iowa tests of edu catio naldevelopmen t , forms X5 and Y5, technical report addend um: 1978standardizat ion. Science Research Associates, ChicagoSoueif MI (1971) T he use of cannabis in Egypt: a beh avioural s tudy.Bull N arc 23 : 17-28Soueif MI (1975) Chron ic can nabis users: further analysis of objec-tive test results. Bull Narc 27 : 1-26Soueif MI (1976) Some de term inan ts of psycho logical deficits associ-ated w ith chronic ca nnabis con sump tion. Bull Narc 28 : 25-42Stefanis C, Boul oug ouri s J, Liakos A (1976) Clinica l and psycho-physiological effects of cannabis in long-term users. In: BraudeMC, Szara S (eds) Pharmacology of marihuana, vol 2. Raven

Press, New York, pp 659-665Tart C T (1971) On being stoned: a psychological s tudy of mari juan aintoxicat ion. Science and Behavior Books, P alo Alto, Cal iforniaVarma VK, M alhot ra AK, Dan g R, Das K, Nehra R (1988) Canna-bis and cognit ive funct ions: a prospect ive study. Dr ug A lcoholDepen d 21:147 152Weckowicz TE, Jansse n D V (1973) Cognit ive funct ions, personal i tytrai ts , and social values in heavy mari juana smokers and non-smoker cont ro l s . J Ab norm Psychol 81:264-269Weckowicz TE, Coll ier G, Spreng L (1977) Field dependence,cognit ive funct ions, personal i ty t rai ts, and social values in heavycannabi s users and n onuser cont rol s . Psycho Rep 4 1:291-302Wig NN, Varma VK (1977) Pat terns of long-term heavy cannabisuse in north India and i ts effects on cognit ive funct ions: aprel iminary report . Drug Alcohol Depen d 2:211 219Winer BJ (1971) Statistical principles in experimental design, 2ndedn. McGraw-Hil l , New YorkYesavage JA, Leirer VO, De nari M, Holl is ter LE (1985) Carry-overeffects of mar i juana intoxicat ion o n aircraft pi lot performance: aprel iminary report . Am J Psychiatry 142:132 5-1329

marijuana use and human cognition

Documents