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Marijuana and Health (1982)

Chapter: BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE

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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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Suggested Citation:"BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE." Institute of Medicine. 1982. Marijuana and Health. Washington, DC: The National Academies Press. doi: 10.17226/18942.
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6 BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE The mind-altering effects of marijuana underlie its widespread and increasing popularity. Marijuana users who experience effects on mood, perception, and motivation report that they seek the "high" and the "mellowing-out." However, under some circumstances many of these same effects can be considered adverse. Perceptual distortions that are sought by users pose risks for driving cars or using other machines. There is reason to be concerned about effects on learning by students using marijuana in school. Older adults receiving A-9-THC as therapy may be highly intolerant of altered consciousness and perceived loss of control. Thus, it has become a matter of practical as well as scientific interest to learn more about the effects of marijuana on the brain and behavior. Many psychological and neuropsychological studies have been conducted to investigate specific effects of marijuana on behavior. These include studies of intellectual functions, such as memory, attention, sequential information processing, and decision-making, as well as perceptual and psychomotor functions. There is a methodolog- ical challenge in trying to design experiments that will discriminate reliably among these functions and determine precisely which is being affected when a drug produces a particular behavioral outcome. For example, one's ability to process and respond to environmental stimuli represents a chain of events. The sequence begins with a sensation or perception. Drugs can influence the manner, speed, and accuracy with which this input is received. The information must then be stored in memory, even if only very briefly, and then retrieved from memory to be integrated with recalled prior experiences and other sensory inputs. The response from the subject is the result of the integration of new and old information. A drug acting at any point in this chain of events can alter behavioral performance. Studies of the effects of marijuana on complex behavior must be carefully interpreted, because there are numerous variables that can influence the results. First, there is the drug itself. The dose, type of preparation, route of administration, and speed of administra- tion must be specified. Next, the user—his personality, level of innate ability, motivation to perform, and especially his previous experience with marijuana, are powerful influences on test results. Finally, there is the type of behavioral test and the setting in ll2

ll3 which it is performed. Simpler and well-practiced skills are less susceptible to disruption by drug effects than are novel or complex tasks. The studies in the literature vary in their attention to these factors. Most of these studies have been carried out on male college students who volunteer for marijuana research. Although this age-group (l9-25) represents a period of peak use of marijuana, it cannot be assumed that findings from a college population will generalize to other sectors of the youth population. The differing motives of student volunteers seriously confound the interpretation of results in intellectual areas, where it has been established that motivation plays a significant role in determining performance. Some dedicated users want to do well and demonstrate that marijuana has no harmful effect. Others are simply interested in obtaining the drug and enjoying its effects with little interest in the experiment. Additional methodological issues that recur in this body of research include: (a) reliance on self-reports by subjects regarding persor.al history of frequency and intensity of drug use, (b) occasional reliance on self-reports of drug dose and level of intoxication at the time of the experiment, (c) lack of standardized dosages and methods of administration of A-9-THC even when the drug is administered by the investigator, and (d) lack of attention to motives and beliefs of users and nonusers with whom they interact. A representative sample of studies will be reviewed here, and a summary table of 88 reports of the relationship between marijuana use and behavioral and psychosocial functioning is available from the Institute of Medicine by request. PERCEPTUAL AND PSYCHOMOTOR FUNCTIONS Acute Effects The studies reported here cover the range of commonly used doses* from very low up to 0.250 mg/kg of A-9-THC in marijuana cigarettes at a single sitting. These are acute effects—changes that can be seen after a single dose. The effects begin to be seen at about the same dose level at which a "high" is perceived (0.050-0.l50 mg/kg A-9-THC). Generally the effects are dose-related. In other words, low doses have small effects; higher doses tend to have greater effects. *Doses are reported in milligrams per kilogram (mg/kg) where provided by the authors or as total doses in milligrams with the route of administration.

1l4 Coordination Marijuana has been found to impair motor coordination at doses commonly used in social settings by both naive and chronic users. The functions studied include: hand steadiness (Mayor's Committee on Marihuana, l944; Clark et al., l970; Milstein et al., l975), body sway (Mayor's Committee on Marihuana, l944; Kiplinger et al., l97l; Evans et al., l973), and accuracy of execution movements (Rafaelsen et al., l973; Milstein et al., l975; Kvalseth, l977). Studies have also showed a dose-related increase in impairment of postural stability as measured by increased body sway (Kiplinger et al., l97l). Reaction Time Reaction time is defined as the time lag between a signal and the response a subject makes to that signal. Most studies examine the time that it takes a subject to respond to a visual or auditory signal. The effects of marijuana on either speed of initial detection of the signal or speed of response have been inconsistent at doses commonly used in social settings ("low to moderate"). The same subjects are impaired at some times, but not at other times (Mayor's Committee on Marihuana, l944; Clark et al., l970; Dornbush et al., l97l; Moskowitz et al., l972, l974; Borg et al., l975; Schaefer et al., l977; Peeke et al., l976; Stillman et al., l977). The meaning of this inconsistency is uncertain, but it probably involves an effect on attention mechanisms. When a subject is intoxicated with marijuana, he is probably less likely to attend to the reaction time task. Perhaps it is when he does pay attention to the task that function on this test is not impaired. Tracking Tracking is the term used to describe the act of following a moving stimulus. It is an important component of driving and flying skills. Tracking behavior is highly sensitive to the effects of marijuana. Impairment of tracking occurs even at very low doses (4.5 mg by smoking) in naive subjects (Weil et al., l968). Studies of experienced users have also demonstrated consistent impairment. The tracking impairment has been found to persist for 4 to 8 hours, well beyond the feeling of intoxication ("high") by one laboratory (Moskowitz and Sharma, l979; Moskowitz et al., l98l). No other studies have measured the effects of marijuana beyond 2 hours. This finding on the long-lasting effects has very important implications, as will be discussed later when the effects of marijuana on driving are reviewed, and, therefore, such studies should be repeated by other investigators. While reaction time studies (as noted above) showed inconsistent results, tracking behavior is regularly and significantly diminished by marijuana at doses usually used in social settings. Tracking

ll5 tasks differ from reaction time studies, because the subject must continuously pay attention to the task. Since reaction time tests are intermittent, continuous attention is not required, and this may explain why reaction time studies fail to show consistent marijuana effects. Sensory and Perceptual Functions Tests that measure a subject's ability to detect a brief flash of light show significant impairment by low to moderate doses (2-3 mg are examples) of smoked marijuana (Sharma and Moskowitz, l972, l973, l974; Moskowitz et al., l972, l974; Casswell and Marks, l973; Jones and Stone, l970). Sustained attention is required in signal detection tasks, and the relation between this sustained attention requirement and motivation effects has not been explored. Signal detection tasks are prototypes of perceptual demands found in man-machine interactions. The large reductions in signal detection that occur under the influence of marijuana may suggest a substantial risk for users who are operating machines. Other visual functions, such as visual search, that depend on eye movements are not impaired. Intellectual and Cognitive Functions The effects of marijuana on such intellectual and cognitive functions as verbal fluency, short-term memory, learning ability, calculation skills, ability to follow complex directions, and time sense have been investigated and are reported below. However, this area of study has been hampered by the lack of standard measures of functioning in the intellectual and cognitive areas tested. Overall, the investigation of marijuana effects on intellectual and cognitive functioning has not followed a logical progression. Learning and Memory When studying the effects of drugs on learning, it is difficult to control all of the factors that might influence the results; for example, as noted above, how hard a subject tries to perform can make a big difference even in the presence of a sedating drug. Thus, it is not surprising that early studies of marijuana's effects gave inconsistent results. More recently, several studies have demonstrated that a single moderate dose of marijuana impairs short-term memory. This effect is especially noticeable in the phases of short-term memory that are heavily dependent on attention, such as information acquisition and storage (Abel, l970, l97l; Dornbush et al., l97l; Dittrich et al., l973; Melges et al., l974; Belmore and Miller, l980). Examples of the types of impaired tasks would be remembering a sequence of numbers or syllables or memorizing and following a sequence of directions. Physiological changes have been monitored in some of the same studies in which intellectual impairment has been reported. Miller

ll6 and Cornett (l978) found that increases in heart rate are produced by marijuana to about the same degree as impairment on intellectual tasks. This linking of a physiological marker with studies of behavioral effects is a useful model for research in this field. Time Sense Another intellectual function influenced by marijuana is time sense. Under the influence of moderate doses of the drug, most investigators report that subjects consistently overestimate the amount of time that has elapsed. Thus, under the influence of marijuana, a given event is reported to last longer than it actually does last (Clark et al., l970; Vachon et al., l974; Tinklenberg et al., l976a). State-Dependent Learning State-dependent learning refers to a situation in which material that is learned while under the influence of a drug is remembered best in the state of drug intoxication in which it was originally learned. A series of studies were conducted with oral doses of 20 mg (in a subsequent study this dose was calibrated to 0.3 mg/kg) of A-9-THC to investigate the extent to which learning and memory are linked to the state of intoxication (Darley et al., l973a,b, l974, l977). This modest dose of marijuana caused learning to take place more slowly than when the subject was drug-free. Once learned, recall of the learning that occurred during intoxication was best when the subject was again under the influence of marijuana. Although state-dependent learning occurs with marijuana, the quality of learning and recall is impaired because the information or problem-solving skills learned in the marijuana- intoxicated state will be reduced or impaired. These investigators believe that the major deficit is in the attention-storage phase of learning. Oral Communication Marijuana use in low to moderate doses impairs oral communication, especially clarity of sequential dialogue with other persons (Dornbush et al., l97l; Paul and Carson, l973; Zeidenberg et al., l973; Crockett et al., l976; Miller et al., l977a-d, l978a,b, l979; Pfefferbaum et al., l977; Miller and Cornett, l978; Natale et al., l979; Belmore and Miller, l980). Marijuana at moderate doses disrupts continuity of speech by impairing short-term memory (6-l8 seconds duration) (Belmore and Miller, l980). Communication while intoxicated is also impaired by the intrusion of irrelevant words and ideas into the stream of communication. When a list of words is learned and then the subjects are asked to recall those words without regard to sequence, words that were never in the original list are inserted during recall more often by subjects given A-9-THC than by those who were drug-free (Pfefferbaum et al., l977; Miller and Cornett, l978; Miller et al., l978a,b). Zeidenberg et al. (l973) administered 5 mg A-9-THC orally and found that, in a social context, phrases became shorter, speech became slower, and there was

ll7 greater lag time between the cue to talk and the actual onset of talking. These subjects were also less able to recognize three- letter nonsense syllables to which they had previously been exposed. Further, when experimental subjects were all given the same dose of A-9-THC, they reported different subjective levels of intoxication. Those who reported more intoxication showed greater disruption of two-person communication (Paul and Carson, l973). Experimental subjects who were asked to tell stories about ambiguous pictures (the Thematic Apperception Test) demonstrated drug impaired organization and integration of stories. The authors reported "a timeless, nonnarrative quality, with greater discontinuity in thought sequence and more frequent inclusion of contradictory ideas" (Roth et al., l975). When asked to talk for five minutes on any topic, subjects under A-9-THC demonstrated decreased variability of language and an increase in personal references, as well as less detailing of items mentioned in the monologue and less critical evaluation of those items (Natale et al., l979). Auto Accidents Simulator Studies A driving simulator is a laboratory instrument that requires the subject to perform a sample of the behavior required in automobile driving situations. Simulators differ from most of the laboratory studies described above in that complex behavior is required. Although simulators are representative of the multitask character of driving, no one simulator is capable of presenting all aspects of driving simultaneously. The behavior sampled varies across simulators; however, in comparison to car driving situations, the simulator has the advantage of presenting a standard stimulus to all subjects. Most simulator studies reveal impairment of driving skills following moderately intoxicating doses of marijuana such as l0-l5 mg (Crancer et al., l969; Dott, l972; Ellingstad et al., l973; Rafaelsen et al., l973; Moskowitz et al., l976; Smiley et al., l98l). These impairments have been reported in simulators that test the perceptual functions as well as those that test motor skills of car control.* *Another type of simulator study examined marijuana's effect on performance in a flying simulator (Janowsky et al., l976). Subjects smoked marijuana cigarettes with 0.09 mg/kg A-9-THC, a dose of A-9-THC commonly used in social settings. Significant impairment of short-term memory was noted. Subjects were unable to recall where they were in the execution of a task. On the simulator they tended to forget where they were in a given flight sequence.

.1l8 Test Courses Experimental studies of the effects of marijuana on closed course automobile driving performance show that this skill is impaired by marijuana. Car handling skills were reduced, as shown by objective measures (Klonoff, l974; Hansteen et al., l976; Attwood, in press). It should be noted that these studies, involving subjects under the influence of marijuana, examined performance in less complex situations than are actually met in real-life driving situations. However, a closed course has the advantages of standard conditions and safety factors. In real-life driving situations, the perceptual and cognitive demands are considerably more complex. The Klonoff (l974) study of driving performance on city streets indicates that smoked marijuana (5-l0 mg A-9-THC) impairs judgment and concentration in addition to impairing car handling skills. Accident Surveys Experimental evidence of impairments caused by marijuana on psychomotor functions, judgment, and motor skills involved in driving has led to research on the relationship of the use of marijuana and automobile accidents. A strongly positive relationship between use of alcohol and increased driving risk has long been established. The techniques used to establish the relationship of alcohol to accidents might appear to offer an excellent paradigm for comparable marijuana- accident research. However, there have been practical reasons why the roadside survey model of using breath samples obtained from accident drivers and comparing those to breath samples of randomly selected drivers who are passing the accident site in the same direction, the same time of day, and same day of the week has not worked for marijuana studies. Whereas there has been 97 percent cooperation for alcohol breath analysis, marijuana determination requires a blood sample, and only a minority of drivers willingly cooperate. Further, marijuana has a quite different body distribution pattern due to its high fat solubility. Delta-9-THC is not only technically quite difficult to detect in samples of body fluid, but it may be active in the nervous system long after it is not detectable in blood. The detrimental effects on driving skills (Moskowitz and Sharma, l979; Moskowitz et al., l98l) may even persist 4 to 8 hours beyond the time when the user has had subjective feelings of euphoria or sleepiness. Several reports of accident surveys have recently been published (Teale et al., l977; Cimbura et al., l980; McBay and Owens, l98l), but all suffer from the problems discussed above and particularly from the lack of a reasonable comparison group. For example, one study reported that l6 percent of Boston drivers had A-9-THC in their blood (Sterling-Smith, l975). There was no description of the group who declined to give a blood sample but provided breath or urine samples instead. Also, there is no information as to the frequency of finding A-9-THC in the blood of those drivers who have

ll9 not had an accident or otherwise come to police attention. In addition, many users of marijuana also use other drugs so that data are available on only a few subjects who only used marijuana. In an effort to obtain some reference point for the association of marijuana with accidents as compared with other drugs, Warren et al. (in press) reanalyzed the Cimbura et al. (l980) data. Twelve percent of the fatally injured drivers and pedestrians in that study had been found to have A-9-THC in their blood. The presence of other drugs was also determined and a culpability index was developed. A culpability index compares the frequency that a drug is found in drivers assigned responsibility for causing a collision with the frequency in individuals from the same sample who had not caused an accident. Aspirin was found to have a culpability index of l.0. That is, it was no more frequent in individuals assigned responsibility for a collision than on those who were not. This is of some significance because it serves as an internal check on the technique, agreeing with the a priori assumption that it would be unlikely for aspirin users to be overrepresented among those responsible for accidents. In contrast, subjects with cannabinoids present in the urine were found to have a culpability index of l.7, the same culpability level found for the presence of alcohol. This indicates an excess of A-9-THC-positive drivers in the category responsible for accidents. The presence of antihistamines produced a culpability index of l.5, and tranquilizers/antidepressants, l.8. Given the difficulties in executing epidemiologic studies where it is so difficult to obtain adequate control groups, it would appear that only tentative conclusions about marijuana's role in accidents can be reached. Supportive evidence that marijuana is a contributing cause of accidents comes from surveys of marijuana users who report they receive a higher-than-average number of tickets for driving violations and are involved in a higher-than-average number of accidents (Johnston, l980) . Nevertheless, the problems described above are yet to be solved. But the culpability index model presents a methodology that may be refined and utilized in future studies. Alcohol-Marijuana Interactions Surveys show that marijuana and alcohol are frequently consumed together (Fishburne et al., l980; Johnston et al., l980). Thus, it is important to determine what interactions, if any, occur between these two drugs. As both drugs have sedative properties, an additive effect would be expected and has been found in the few systematic investigations of the effects of this combination. One study reported that 0.05 percent blood alcohol level concentration (BAG) increased the impairment produced by 5 mg of smoked A-9-THC on tracking behavior (Manno et al., l97l). In a study using two doses of alcohol and two doses of marijuana, even the low dose of alcohol (0.07 percent BAG) and the low dose of A-9-THC (l.4 mg) impaired complex tracking in an additive fashion (Hansteen et al., l976).

l20 Higher doses produced more pronounced decrements. A combination of A-9-THC (0.320 mg/kg) and ethanol (a dose that produces a peak blood level of less than 0.08 percent BAG) has also produced an additive effect on the ability to perform on a psychomotor test (Belgrave et al., l979). This additive effect would be of concern to those operating a motor vehicle. The issue of alcohol-marijuana interactions is an important one, but currently few data are available. Clearly, more studies of marijuana's interaction with alcohol and other commonly used drugs are needed. Chronic Effects Animal Studies Studies of chronic effects are necessary to determine whether a drug produces changes that persist after administration has stopped. In view of the theoretical possibility of cumulative or persistent marijuana effects, it is surprising that only a few laboratories have conducted experiments involving repeated dosing and testing for residual effects. Mice injected with l0 mg/kg A-9-THC for 20-40 days were found to be persistently impaired in new learning l00 days after the injections stopped (Radouco-Thomas et al., l976). Similarly, rats given 20 mg/kg of A-9-THC orally for l80 days had learning still impaired 2 months after the A-9-THC treatment stopped (Fehr et al., l976). This was confirmed by the same group in two subsequent studies (Fehr et al., l979; Stiglick and Kalant, in press). Another group of investigators, however, could find no residual learning effects in monkeys 20 days after stopping comparable doses of A-9-THC (Ferraro and Grilly, l974). Human Studies Clinical reports of memory impairment, lack of concentration, lethargy, etc., in nonintoxicated chronic users of marijuana have led to studies in which psychological testing was administered to users of marijuana and controls. The results of these studies are inconclusive. Several studies show impaired performance in users as compared to controls (Agarwal et al., l975; Soueif, l976; Wig and Varma, l977; Mendhiratta et al., l978); others found no significant residual effects in the marijuana users (Bowman and Pihl, l973; Rubin and Comitas, l975; Satz et al., l976; Ray et al., l978; Schaeffer et al., l98l). All of these studies can be criticized on methodological grounds, and the results have been disputed. This is not surprising, because it is technically very difficult to obtain a sample of chronic marijuana users, get them into a truly drug-free condition, test them, and similarly test an appropriate group of controls. Several groups of investigators (Dornbush et al., l972; Frank et al., l976; Harshman et al., l976; Rossi et al., l977) examined

l2l chronic marijuana users before and after 2l-94 days of chronic intoxication in a research hospital setting. None of the investigators found any psychological changes during postdrug testing. However, 2 months of use is a relatively short period of time for a change to be detected, and the subjects had already been using marijuana for at least a year prior to entering each study (Fehr et al., l976). The available studies of chronic behavioral effects lead to no clear conclusions. Although some animal studies demonstrated a learning deficit that persisted for months after daily marijuana exposure was discontinued, the human studies have such methodological weaknesses that they cannot be interpreted. A prospective concurrent cohort study and a retrospective case-control study of possible outcomes of and risk factors for use of marijuana could add useful information. (See research recommendations at the end of this chapter.) CLINICAL SYNDROMES In this section we will discuss both acute and chronic behavioral changes that have been reported in the clinical literature to be associated with the use of marijuana. An association based on case reports does not imply causality. Studies of appropriate control groups are necessary. In general, acute or immediate clinical effects of drugs can be determined scientifically much more readily than chronic or delayed effects. This is as true for marijuana as it is for alcohol and other drugs. Thus, the acute effects of marijuana are based on more solid evidence than are the reported chronic effects. Acute Effects The acute clinical effects of marijuana seem to occur on a continuum from mild dysphoria to acute brain syndrome. In the literature, three different syndromes have been described, although there is blurring of the boundaries in this classification and no general agreement as to diagnostic criteria. Anxiety/Panic Reaction A major portion of the evidence for this effect comes from reports by marijuana users themselves. Marijuana's popularity notwithstanding, a surprisingly high proportion of users report reactions that they regard as unpleasant or undesirable. For example, 33 percent of regular users reported that while intoxicated they occasionally experienced such symptoms as acute panic, paranoid reaction, hallucinations, and unpleasant distortions in body image (Tart, l970; Negrete and Kwan, l972). Another study reported that l6 percent of

l22 regular users reported anxiety, tearfulness, confusion, dependency, or aggressive urges as a "usual occurrence" (Halikas et al., l97l). Similar findings in groups of stable, well-adjusted, moderate users have been found by other investigators (Annis and Smart, l973; Marcus et al., l974). First-time users are more likely than are experienced users to report adverse reactions. The frequency of such reactions appears to be higher when the setting for use is not a favorable one; for example, when the user sees the environment as threatening. These adverse psychological reactions also have been observed in subjects of laboratory experiments with marijuana. Such controlled observations of persons whose immediate prior mental status and whose dosage were known give a basis for concluding that acute adverse psychological reactions can occur under single moderate doses of marijuana. These effects are more likely at higher doses. They usually last no longer than 2 to 4 hours. Acute paranoid reactions under these controlled conditions have been reported (Mendelson and Meyer, l972; Tassinari et al., l973; Frank et al., l976; Melges, l976). Ingestion, in which titration of dose (dose adjustment as occurs during smoking) is difficult, may be more likely to produce adverse effects than administration by smoking marijuana. However, chronic use and interaction with other psychoactive substances are not required. As frequently as these adverse reactions are observed and self-reported, medical treatment is rarely sought. For example, a college student health clinic reported only six students per year sought medical treatment for an adverse reaction to marijuana out of a student population of 20,000 (Pillard, l970). In the general population, a diagnosis of acute cannabis reaction was found in only l0 cases out of 700,000 hospital admissions in the United States (Lundberg et al., l97l). In the U.S. Army, only l8 such cases were treated over a several-year period from a military population of 33,000 (Tennant and Groesbeck, l972). There are no recent figures showing requests for medical treatment now that the use of marijuana is more intense, widespread, and reaching younger age-groups. However, a unique monitoring of drug causality behavior documenting emergency room encounters conducted by the Drug Enforcement Administration and the National Institute on Drug Abuse (U.S. Department of Health and Human Services, l979) may in the future provide additional information about the frequency of adverse reactions to use of marijuana. Dysphoric Reaction Therapeutic trials have been carried out testing A-9-THC as a possible treatment for mood disorders (see Chapter 7). Severe dysphoric reactions characterized by disorientation, catatonialike immobility, acute panic, and heavy sedation have occurred in several patients. The dysphoric symptoms appeared at moderate doses compar- able to those used in social settings. They lasted only a few hours and responded to discontinuation of the drug and reassurance of the patients (Kotin et al., l973; Ablon and Goodwin, l974).

l23 Similar dysphoric reactions have been reported in cancer patients who were on a therapeutic trial of A-9-THC to control the nausea associated with chemotherapy. The symptoms, course, and response to ceasing use of the drug were identical to those described above. Investigators have suggested that the dysphoric response is more likely to occur in older patients not accustomed to drug use for whom the mood-altering effects are unanticipated and unwelcome (Shiling and Stillman, l980). Acute Brain Syndrome Diagnostic criteria for the syndrome now called delirium and previously called acute brain syndrome appear in Diagnostic and Statistical Manual of Mental Disorders, Third Edition, l980 (DSM III). These include: (a) a clouding of consciousness as manifested by impairment of ability to sustain attention to environmental stimuli, or impairment of ability to sustain goal-directed thinking or goal-directed behavior; (b) a disorder of memory or orientation; (c) perceptual disturbances; and (d) a change in sleep pattern and/or a change in psychomotor activity. The symptoms develop over a short period of time and fluctuate rapidly. Both the symptom pattern and the course of the acute brain syndrome fit the descriptions of one type of behavior disorder associated with use of marijuana. It has been reported to develop in persons who have a history of prolonged, regular, heavy use of marijuana. It is defined as an "acute" brain syndrome because it comes on during the period of drug use and it gradually disappears after the drug is stopped. The majority of case reports have come from Eastern countries where the cannabis products customarily used have high potency (Spencer, l970; Chopra and Smith, l974; Meyer, l975) . It has also been reported in U.S. Army personnel stationed in Viet Nam (Talbott and Teague, l969) and in Europe (Tennant, l972), where soldiers had access to very high A-9-THC concentrations in cannabis substances. In contrast to the Indian public mental hospital patients who were hospitalized for many weeks, U.S. soldiers recovered in 3 to ll days and returned to duty. This difference in duration may reflect sociocultural differences in length of in-patient treatment more than a difference in the disorder. Withdrawal Syndrome Studies of animals and human subjects given moderate to high doses of marijuana orally or by inhalation several times per day have demonstrated tolerance to many of the effects of marijuana (see Chapter l) . When such use of marijuana is stopped after several days, a withdrawal syndrome occurs. In human subjects, this resembles the typical mild withdrawal symptoms seen after prolonged sedative use (Jones and Benowitz, l976). Subjects show irritability, agitation, insomnia, and EEG changes (see Chapter 4). These symptoms are self-limiting; they peak at 30 hours and disappear by 90 hours.

l24 There is no clinical evidence that physical dependence plays an important role in persistent use of marijuana. Withdrawal symptoms would not be expected in intermittent users; however, daily round-the-clock users of high-dose marijuana may be expected to show some symptoms of withdrawal soon after stopping regular use. Chronic Effects Cannabis Psychosis Cannabis psychosis refers to a chronic psychotic condition (out of contact with reality) reportedly seen in heavy marijuana users, but extending beyond the period of acute intoxication. Some authors have described a schizophrenialike picture with delusions and hallucina- tions, and others have stressed the existence of organic mental confusion. Most of the reports have come from observation of hospitalized patients in Asian and African countries (Asuni, l964; Chopra and Smith, l974; Thacore and Shukla, l976). There are no reports in the North American literature. At this time, there is insufficient evidence to say that cannabis psychosis exists as a separate clinical entity (Murphy, l963; Edwards, l976). "Amotivational Syndrome" Clinicians coined the term "amotivational syndrome" to describe a characteristic set of personality changes seen in some daily users of marijuana (McGlothlin and West, l968; Smith, l968). The changes include apathy, loss of ambition, loss of effectiveness, diminished ability to carry out long-term plans, difficulty in concentrating, and a decline in school or work performance. As usually described, these changes are seen in frequent or daily users, and thus they may be considered a form of chronic intoxication. The term "amotivational syndrome" is not an official diagnosis, but there is agreement among many clinicians who treat young people that this constellation of symptoms is common. It may also be seen in nonmarijuana users, and daily use of marijuana is not always associated with loss of motivation. The evidence presented for the linking of this syndrome with marijuana consists of case reports. For example, Baker and Lucas (l969) described the case of a man whom friends described as previously conscientious, capable, and effective; but after smoking hashish daily for 3 years, he changed into a person for whom use of drugs was a way of life and in whom a serious deterioration of social function was observed. Other reports consist of groups of cases with similar histories (Thurlow, l97l). The symptoms mentioned, in addition to loss of motivation, include falling grades, difficulties in concentration, intermittent confusion, and impaired memory. Some authors report improvement when use of marijuana is stopped (Kolansky and Moore, l97l, l972).

125 A variety of other data support such a condition. In a large survey, daily marijuana users were asked about the drug's adverse effects (Johnston et al., l980). The most common response was "loss of energy" (42 percent). Nearly a third (32 percent) of the daily users thought that marijuana caused them to be less interested in other activities than they had been before, and a third (34 percent) thought that it hurt their school and/or job performance. Another type of evidence comes from comparisons of college students who use marijuana with others who do not. Several such studies (Shean and Fechtmann, l97l; Linn, l972; Simon, l974; Finnell and Jones, l975) found marijuana users had increased levels of psychological disturbance, lower academic performance, and lower performance on scales measuring attitudes toward achievement and purpose in life. But some studies in both the United States and foreign countries have failed to show significant differences between marijuana users and abstainers (Brill and Christie, l974; Rubin and Comitas, l975). Interpretation of the evidence linking marijuana to "amotivational syndrome" is difficult. Such symptoms have been known to occur in the absence of marijuana. Even if there is an association between this syndrome and use of marijuana, that does not prove that marijuana causes the syndrome. Many troubled individuals seek an "escape" into use of drugs; thus, frequent use of marijuana may become one more in a series of counterproductive behaviors for these unhappy people. The available evidence does not allow a sorting of the various possibilities in the relationship between use of marijuana and the complex of symptoms in the "amotivational syndrome." It appears likely that both self-selection and authentic drug effects contribute to the "motivational" problems seen in some chronic marijuana users (see Chapter 2). Persons who are experiencing loss of motivation, apathy, and the other aforementioned symptoms probably will worsen the situation by taking any sedating drug. They should be warned to avoid frequent use of marijuana, alcohol, and other nonprescribed drugs. "Flashbacks" In l968, Keeler et al. reported four cases of the brief spontaneous recurrence of a mental state similar to that experienced during marijuana intoxication l to 2l days after the last drug use. Three of the four subjects complained of hallucinations comparable to flashbacks usually associated with LSD (Horowitz, l969). Three separate reports of marijuana flashbacks followed (Smith, l968; Favazza and Domino, l969; Weil, l970) and all of these latter subjects had used LSD prior to marijuana. In a survey of 720 servicemen, not a single case of flashback in any subject for whom hashish was the only drug consumed was documented (Tennant and Groesbeck, l972). But in the same sample, l5 subjects were identified who had LSD flashbacks precipitated by use of marijuana. A larger sample of 2,00l army personnel (Stanton et al., l976) revealed that use of marijuana had the highest and only statistically

l26 significant association with the precipitation of LSD flashbacks among five classes of abused drugs. Clinical studies also have provided evidence that marijuana precipitates a recurrence of the LSD flashbacks experience (Holsten, l976; Abraham, l98l). The existence of flashbacks following use of either LSD or marijuana is entirely based on self-reports, because there are no distinctive physical signs or tests, such as EEG changes, to identify this condition. There is no current pharmacological explanation of the phenomenon, and data regarding dose and time parameters do not exist. Still, the reports by users are reasonably consistent. Thus, there is clinical evidence that use of marijuana by those who have previously used LSD increases the likelihood of recurrence of the LSD experience. Effects on Preexisting Mental Illness The only evidence available regarding this issue consists of case reports of patients who had recovered and apparently were doing well until they used marijuana. There is no information on the number of mentally ill patients who have used marijuana without complications. The available data, therefore, do not prove that marijuana worsens mental illness. Still, there are sufficient numbers of uncontrolled clinical reports showing a temporal association between use of marijuana and return of mental symptoms, so that patients should be warned of this possibility. Patients with a history of schizophrenia may be particularly sensitive to marijuana's effects. Four schizophrenic patients who were otherwise well controlled with medication suffered serious relapse of their schizophrenic symptoms following use of marijuana (Treffert, l978). Other cases have been reported (Smith and Mehl, l970; Weil, l970; Bernhardson and Gunne, l972). These all were cases in which marijuana was purchased on the street, so the dose and purity were unknown. Patients with mood disorders have also been reported to show worsening of mental symptoms after use of marijuana. For example, four cases are known in which marijuana apparently precipitated a relapse of psychotic (hypomanic) behavior (Harding and Knight, l973). Furthermore, depressed patients treated with A-9-THC have been observed to show a high incidence of dysphoric reactions (Ablon and Goodwin, l974) . Effects Sometimes Reported By Users Mood Changes There is a general belief that use of marijuana alters mood. This property is one of the desired effects sought by many users. Investigators have described a number of variables that enter into the mood response to marijuana (Jones, l97l). These include dosage,

l27 past experience, attitude, expectations, and setting. For example, individuals who used marijuana in isolation tended to be relaxed and slightly drowsy; in contrast, when the user was in a group situation, marijuana was associated with euphoria and lack of sedative effect (Jones, l97l). Further evidence that mood changes are not attribut- able solely to the pharmacological action of marijuana comes from a study that found that elevation in mood occurred immediately before use of marijuana and immediately after, but that mood was not correlated with other indications of the subjective level of intoxication (Rossi et al., l978). Instead, mood was correlated significantly with the moods of others, whether or not the other persons were intoxicated. It appears that preexisting mood can influence the decision to use marijuana. High school students who exhibit symptoms of depression are more likely than are others to begin using marijuana as well as other illicit drugs (Paton et al., l977). There is some evidence that students use the drug as a self-prescribed remedy for their own mood problems, often reporting that they use marijuana as a means of psychological coping (Johnston et al., l980; Kaplan, l980). A belief that marijuana can be used to alleviate clinical depression is not supported by other studies, including one in which A-9-THC was carefully tested as an antidepressant. It was given to depressed patients as an experimental treatment without success (Ablon and Goodwin, l974) (see Chapter 7). Interpersonal Behavior Adolescents and young adults often report that they use marijuana to facilitate interaction in new social situations (Mirin and McKenna, l975). In a survey of 704 midwestern undergraduate students, most reported that marijuana was a meaningful "tool of social bonding" (Linn, l97l). There seems to be a widespread belief that marijuana smoking has several facilitative effects, including enhanced social effectiveness, closer social bonding, heightened interpersonal sensitivity and empathy, and enhanced sexual pleasure. The subcultural lore on one of these measures of interpersonal behavior— sexual effects—has not been studied systematically either in surveys or in experimental studies. The effects on sex hormones are controversial (see Chapter 5). Studies in experimental situations have failed to show any enhancement of social interaction and, in fact, some decrements were noted (Galanter et al., l974; Clopton et al., l979; Janowsky et al., l979). Data from natural settings rather than experimental settings are not available. Effects on Aggression Because marijuana users have been involved in delinquent behavior, a number of investigators have questioned whether use of marijuana enhances aggressiveness in human beings. There are specific concerns

l28 about potential links of use of marijuana to aggression. Both retrospective and experimental studies in human beings have failed to yield evidence that marijuana use leads to increased aggression. Most of these studies suggest quite the contrary effect. Marijuana appears to have a sedative effect, and it may reduce somewhat the intensity of angry feelings and the probability of interpersonal aggressive behavior (McGuire and Megaree, l974; Tinklenberg, l974; Salzman et al., l976; Taylor et al., l976; Tinklenberg et al., l976b; Hemphill and Fisher, l980). SUMMARY There is experimental evidence that marijuana seriously impairs psychomotor performance. Strong evidence for impairment has been found in: * coordination as examined by hand steadiness, body sway, and accuracy of execution of movement; * tracking performance; * perceptual tasks; * vigilance; * performance on automobile driving and flying simulators; and * operating automobiles on test roadways. Less reliable evidence of impairment or reliable evidence of a small degree of impairment was found in reaction time, simple sensory functions, and control of eye movements. Although the effects that marijuana produces on psychomotor functions used in driving are clear, studies linking marijuana to auto accidents are inconclusive. The research is impaired by methodological problems related to the pharmacology of marijuana. One recent study reported that marijuana and alcohol had a similar degree of association with fatal accidents, but more investigation is needed. Studies also have shown acute effects of marijuana on short-term memory. State-dependent learning also has been shown, in that information or problem-solving skills learned in the intoxicated state will be reduced or impaired in the drug-free state. One laboratory has shown tracking impairment to persist for 4 to 8 hours beyond the feeling of intoxication. Some animal studies demonstrate a learning deficit that persists for months after marijuana exposure has been discontinued, but human studies do not permit secure conclusions. The acute clinical effects of marijuana are fairly well established, although there is no general agreement as to how to classify them. Anxiety and panic reactions have been reported by users and observed in experimental situations. They are not uncommon, but they rarely require medical attention. When marijuana is used to treat nausea and other conditions, mental effects can occur, which some patients, especially older persons, may regard as unpleasant. These mental effects may require cessation of the treatment.

l29 Marijuana also has been found to produce an acute brain syndrome. This is a more severe mental problem consisting of confusion and loss of contact with reality. It lasts from several hours to several days and appears to be more likely to occur with higher doses. Chronic effects of any drug are more difficult to assess than are immediate effects. The evidence that marijuana produces a chronic psychosis is not convincing. The possible role of marijuana in causing an amotivational syndrome is a matter of great concern. Apathy, poor school work or work performance, and lack of goals characterize a number of long-term marijuana users. But it has not been possible to determine how much is caused by use of marijuana and how much was antecedent; it seems likely that both factors (drug effect and self-selection) contribute to the motivational problems seen in chronic users of marijuana. Existing studies have produced conflicting results. None of the investigators has looked at effects on the very young daily marijuana user, who is regarded as potentially at high risk for damaging effects because of physiological and psychological immaturity. There is clinical evidence that marijuana use by former LSD users may precipitate a recurrence of LSD-type hallucinations known as a "flashback." Other clinical evidence raises the possibility that marijuana use can worsen preexisting mental illness. RECOMMENDATIONS FOR RESEARCH The committee recommends the following types of studies. * Systematic research on acute behavioral and psychosocial effects of marijuana should be extended to other age groups. There are virtually no data on prepubertal children, young adolescents, older adults, and aging persons. * Studies of effects of daily use of marijuana on school children are greatly needed. These effects should include the learning of new material, physical, psychological, and social development, acquisition of coping skills, and tools of daily living. * Systematic studies of long-term effects of marijuana are increasingly possible now that longitudinal studies have identified representative panels of persons known to be chronic heavy users. These studies should cover interactive effects of marijuana and other drugs on behavioral and psychosocial responses, especially interactions of alcohol and marijuana because of their frequency of associated use. * Dosage effects should be restudied, taking into account the higher potency cannabis that is in current use. Further study is needed of the timing and depth of inhalation of cigarettes with standard doses of marijuana. More animal studies at varying doses are needed. In view of the long-term retention of marijuana in body tissues, further study is needed to see whether or not chronic users may have impairments of function even in the absence of an acute dose

l30 of marijuana. The factors that influence the persistence of effects following an acute dose are not understood. " The correlation of changes in a physiological marker, such as increased heart rate, with observations of behavioral effects should be encouraged. * Many of these recommendations, along with those of other chapters, could be consolidated and carried out as part of a study that is both a prospective cohort study and a retrospective case-control study of possible outcomes and risk factors with marijuana use. * A cohort of drug-naive junior high school students could be assembled and followed over time to see which students become marijuana users and which remain nonusers. Students would be subjected to physical and psychosocial testing at predetermined time intervals. The two groups would be evaluated in terms of the incidence of specific outcomes and the relative risks associated with these outcomes after appropriate follow-up periods. In order to identify risk factors for marijuana use, individuals who become marijuana users would be compared to individuals who remain nonusers using a case-control methodology. By combining these two epidemiologic research strategies, the etiology and effects of marijuana use may be studied. REFERENCES Abel, E.L. Marijuana and memory. Nature 227:ll5l-ll52, l970. Abel, E.L. Effects of marihuana on the solution of anagrams, memory, and appetite. Nature 23l:260-26l, l97l. Ablon, S.L. and Goodwin, F.K. High frequency of dysphoric reactions to tetrahydrocannabinol among depressed patients. Am. J. Psychiatry l3l:448-453, l974. Abraham, H.D. Visual disturbances in population of LSD users. Paper presented at the l34th Annual Meeting of the American Psychiatric Association, New Orleans, May l4, l98l. Agarwal, A.K., Sethi, B.B., and Gupta, S.C. Physical and cognitive effects of chronic bhang (cannabis) intake. Indian J. Psychiatry l7:l-7, l975. Annis, H.M. and Smart, R.G. Adverse reactions and recurrences for marijuana use. Br. J. Addict. 68:3l5-3l9, l973. Asuni, T. Socio-psychiatric problems of cannabis in Nigeria. Bull. Narcotics l6:l7-28, l964. Attwood, D.A. Cannabis, alcohol and driving: Effects on selected closed-course tasks. In Proceedings of the 8th International Conference on Alcohol, Drugs and Traffic Safety, June l5-l9, l980, Stockholm, Sweden (in press). Baker, A.A. and Lucas, E.G. Some hospital admissions associated with cannabis. Lancet l:l48, l969. Belgrave, B.E., Bird, K.D., Chesher, G.B., et al. The effects of (-)trans-A-9-tetrahydrocannabinol, alone and in combination

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