Cognition and Long-Term Use of Ganja (Cannabis) - SCIENCE, Vol. 213, 24 July 1981

Abstract. Neuropsychological variables and urine cannabinoid metabolites were evaluated in ten subjects born, raised, and educated in the United States and having histories of heavy or prolonged use of cannabis. No impairment of cognitive function was found. Cannabinoid metabolites in excess of 50 nanograms per milliliter were present in the ten urine samples. The tetrahydrocannabinol content of cannabis exceeded 8.0 percent.

    Several studies have attempted to characterize the mental or cognitive functioning of persons with histories of heavy and prolonged use of ganja (cannabis). Generally, investigators have concluded that heavy and prolonged use has not led to impairment of mental and cognitive functions consistent with brain or cerebral dysfunction (1-4).
    Although several studies have shown decrements in neuropsychological performance among those with brief or sporadic patterns of cannabis use here in the United States (5-9), comparable studies of prolonged heavy use in this country have not been performed. Thus, the only available literature is based on studies conducted in foreign countries (Jamaica, Greece, Egypt, and Costa Rica).
    We had the opportunity to observe a group of long-term heavy users of ganja in both a Southern state and a Caribbean island. The ganja was used by this group for religious purposes and symbolized the sacrament of communion--"the Green Herb of the Bible." It was used, as we observed, even during the extensive neuropsychological evaluations that we completed, in a continuous and ritualistic manner throughout virtually all waking hours. Very large cigarettes (or "spliffs") and pipes, containing ganja mixed with tobacco, were regularly shared by members of the group (10).
    We examined ten subjects (seven males and three females) ranging in age from 25 to 36 years. The mean number of years of education was 13.5 (all were born, raised, and educated in the United States), and all were Caucasian. None had any history of disease that could be related to central nervous system dysfunction. By their own report, they used between 2 and 4 ounces of the ganja-tobacco mixture per day, with a reported mean duration of use of 7.4 years (the time since joining this particular church). All subjects actively engaged in daily work, largely agricultural and business, and led active and spiritually oriented lives (10). It was not possible to collect control data in this environment, as all church members continuously smoked ganja. Thus, comparisons were made with the published standards and normative data for the psychometric instruments used.
    Subjects in this study agreed to provide approximately 15 ml of fresh urine for enzyme immunoassay of cannabinoid metabolite content. Specimens were preserved with approximately 4 mg of sodium azide per 15 ml of urine that was collected. Urine samples for each of the ten individuals studied were obtained immediately before each subject began a series of selected neuropsychological tests designed to assess a broad range of cognitive functions.
    A modified version of the Michigan Neuropsychological Test Sequence was used (11-13). Each subject was administered exactly the same group of tests in exactly the same order. General intellectual functioning was assessed on the basis of a prorated version of the Wechsler Adult Intelligence Scale (Table 1) (14). Additional neuropsychological tests included the following: Benton Visual Retention Test (administration C) (15), Rey Auditory-Verbal Learning Test (16), Symbol-Digit Modalities Test (17), Hooper Visual Organization Test (18), Raven's Progressive Matrices Test (19), and Trailmaking Test (forms A and B) (20). The following cognitive functions were assessed: language areas of function, nonlanguage areas of function, memory, complex multimodal learning, and general intellectual functioning. Auditory and visual memory functions included remote (years and months), recent (weeks, days, hours, minutes), and immediate events (within seconds).
    An enzyme immunoassay method (Emit-d.a.u.) (21) was used to analyze urine samples. The assay is a semiquantitative immunochemical test designed to detect a level of at least 50 ng of 11-nor-delta-9-tetrahydrocannabinol cabboxylic acid per milliliter of urine with greater than 95 percent confidence. Each of the ten urine samples contained concentrations of cannabinoids at 50 ng/ml (one subject) or well above this level (nine subjects).
    None of the neuropsychological test data indicated impairment of cognitive functioning. Language areas of function, nonlanguage areas of function, memory, complex multimodal learning, and general level of intellectual functioning were all completely unimpaired, compared with standardized-normative information available for each test (Table 1).
    The mean IQ scores (Table 1) are all in the superior to very superior range of intellectual functioning, ranging from the upper 6.7 percent to the upper 2.2 percent of the population (14). Scores obtained on all of the other psychometric tests were also well within the normal range for age (11-20). There was nothing found in any of the ten subjects' protocols that might suggest impaired mental functioning due to brain or cerebral dysfunction resulting from heavy and prolonged use of ganja.
    While several previous studies have reported transient cognitive impairment resulting from the acute effects of cannabis, primarily with respect to attention-concentration and visuomotor (hand-eye) coordination (8, 9, 22, 23), none of the studies involving prolonged and heavy use of ganja have shown any systematic decrements in mental abilities suggestive of impairment of brain or cerebral function and cognition (14).
    We also included toxicologic verification of urinary cannabinoid metabolites, observed the inhalation of cannabis by all subjects studied, and analyzed samples of this cannabis for THC. Analysis of cannabis mixed with tobacco (by gas chromatography) yielded a delta-9-THC content of 4.14 percent (half cannabis, half tobacco); thus the THC content of the pure cannabis exceeds 8.0 percent.
    We observed no transient decrements in cognitive functioning that often accompany intermittent or sporadic use of cannabis. The development of tolerance to one or more of the constituents of cannabis may explain this phenomenon.
    Although the obtained IQ scores were high, one could speculate that perhaps cannabis had produced a priori declines in IQ scores for all ten subjects, as well as scores on other neuropsychological measures. It was possible for us to obtain early school academic achievement test data on two of our subjects. These data included equivalent IQ conversion scores virtually identical to those we measured for those subjects. We realize that these conversion or equivalent IQ scores derived from early school achievement test data are not to be equated on a one-for-one basis with current scores. However, we do believe that IQ score ranges provide a reasonable degree of equivalency. These achievement test scores were obtained some 15 to 20 years earlier, long before either subject began the use of cannabis, by their report to us.
    Finally, we stress the commitment of the ten subjects to their religious sect and way of life. They told us and others (10) that members of the church do not use substances (drugs, alcohol, or psychoactive herbs other than ganja, and we observed them to maintain a regular diet consisting primarily of vegetables, fruit, and small amounts of meat. All ten subjects (as well as other members of the church) appear to be healthy and highly functional individuals adhering to a strict religious doctrine.

JEFFREY SCHAEFFER
Department of Psychiatry and
Biobehavioral Sciences. University of
California School of Medicine,
Los Angeles 90024, and
Neuroscience Associates Incorporated,
Los Angeles 90048

THERESE ANDRYSIAK
J. THOMAS UNGERLEIDER
Department of Psychiatry and
Biobehavioral Sciences, University of
California School of Medicine

Table 1. Summary of neuropsychological data (means ± standard deviations).
Test	Number correct	Scaled score
Wechsler Adult Intelligence Scale
Information Arithmetic Similarities Digit symbol Block design Picture arrangement Verbal IQ* Performance IQ* Full-scale IQ*	26.2 ± 3.12 15.2 ± 2.10 20.8 ± 2.30 69.6 ± 8.73 42.7 ± 5.96 29.1 ± 5.30 129.0 ± 10.87 124.2 ± 13.07 128.4 ± 10.36	16.5 ± 2.55 14.3 ± 1.95 14.2 ± 1.97 13.8 ± 2.49 13.8 ± 2.39 13.0 ± 2.98
Other instruments
Benton Rey Symbol-digit Hooper Raven Trailmaking (in seconds) Form A Form B	8.8 ± 1.02 14.9 ± 0.32 60.4 ± 10.25 28.7 ± 1.06 35.2 ± 0.79 28.8 ± 6.88° 53.5 ± 15.28°
*Prorated. °No errors.

1.		V. Rubin and L. Comitas, Ganja in Jamaica (Mouton, The Hague, 1975).
2.		M. C. Braude and S. Szara, Eds., Pharmacology of Marijuana (Raven, New York, 1976).
3.		R. L. Dornbush and A. Kokkevi, in (2), p. 421.
4.		C. Stefanis, J. Boulougouris, A. Liakos, in (2), pp. 659-665.
5.		I. M. Frank, P. J. Lessin, E. D. Tyrrell, P. M. Hahn, Szara, in (2), pp. 673-679.
6.		S. Y. Hill and D. W. Goodwin in (7), p. 139.
7.		S. Cohen and R Stillman, Eds., The Therapeutic Potential of Marijuana (P1enium, New York, 1976).
8.		L. L. Miller, in (7), pp. 271-292.
9.		R. T. Jones and N. Benowitz, in (2), p. 627.
10.		M. C. Dreher, personal communication (March 1980).
11.		A. Smith, in Drugs, Development and Cerebral Function. W. L. Smith, Ed. (Thomas. Springfield, Ill., 1972), pp. 27-68.
12.		_____ and C. W. Burkland, paper presented at the annual meeting of the American Psychological Association, 1967.
13.		_____, Science 153, 1280 (1966).
14.		D. Wechsler, Manual for the Wechsler Adult Intelligence Scale (Psychological Corporation, New York, 1955).
15.		A. Benton, Revised Visual Retention Test: Clinical and Experimental Applications (Psychological Corporation, New York, ed. 4, 1974).
16.		M. Lezak. Neuropsychological Assessment (Oxford Univ. Press, New York, 1976).
17.		A. Smith, Symbol Digit Modalities Test Manual (Western Psychological Services, Los Angeles, 1973).
18.		E. Hooper, The Hooper Visual Organization Test (Western Psychological Services, Los Angeles, 1973).
19.		J. C. Raven, Guide to Using the Coloured Progressive Matrices (Lewis, London, 1965).
20.		R. M. Reitan, Percept. Motor Skills 8, 271 (1958).
21.		Cannabinoid Urine Assay: Emit Cannabinoid Assay (Syva, Palo Alto, 1980).
22.		R. A. Harshman, H. Crawford, E. Hecht, in (7), pp. 205-254.
23.		"Human effects," in Marihuana Research Findings (National Institute of Drug Abuse Monorgaph No. 14, Government Printing Office, Washington, D.C., 1977), p. 128.

Individual results for Carl Olsen