The Report of the National Commission on Marihuana and Drug Abuse

Effects of Long-Term Cannabis Use

Patterns of marihuana use in Western countries, particularly the United States are primarily long term (two t o 10 years). Additionally, Western investigators have been able to observe those who use marihuana at most, daily and more often, moderately or intermittently. Consequently, observed effects are rare. Knowledge is incomplete but certain trends appear to be emerging in regard to American usage patterns.

The relevance of Eastern reports of heavy hashish use is uncertain. Nutrition, disease prevalence and quality of medical care impose limits on transferring Eastern observations to Western conditions of use.

DEPENDENCE AND TOLERANCE

Neither severe physical dependence, nor prominent withdrawal symptoms after abrupt termination of very heavy usage is suggested by some overseas experience (Charen and Perelman, 1946; Fraser, 1949; Ludlow, 1857, Marcovitz and Myers, 1944; Siler et al., 1933; Walton, 1938). Other studies, however, suggest marked psychological dependence from heavy use producing compulsive drug taking in very heavy users (Indian Hemp, 1893; Chopra and Chopra, 1957; Bouquet, 1944; Lambo, 1965).

Psychosomatic abstinence syndromes often reported were physical weakness, intellectual apathy, loss of appetite, flatulence, constipation, insomnia, fatigue, abdominal cramps and nervousness, restlessness, and headache. For most heavy users the syndrome of anxiety and restlessness seem to be comparable to that observed when a, heavy tobacco smoking American attempts to quit smoking.

However, the psychological dependence appears to be severe as evidenced by the f act that one group of subjects were unable to cease their habitual use although the frequency of use, was only eight to 12 times per month (Soueif, 1967). This psychological dependence may have made some users claim physical dependence so that the government did not terminate dispensing them their drug. Studies in the United States using must lower doses for shorter periods of time have revealed little if any evidence of psychological dependence (Bromberg, 1934 Mayors Committee, 1944; Williams et al., 1946).

Tolerance to the subjective and depressant effects of the drug (discussed in an earlier section) does probably occur in man, with heavy use. Thus, increasingly larger and more frequent doses become necessary to experience the desired effects.

Several investigators have recently studied the question of physiological and psychological dependence to Delta 9 THC in monkeys using intravenous self-injection techniques.

Deneau and Kaymakcalan (1971) demonstrated that no monkey initiated self-administration over a three-week period when given the opportunity to self-inject a behaviorly effective dose of 100 micrograms per kilogram of Delta 9 THC in a Tween solution. The researchers subsequently administered to these monkeys this dose every six hours. Tolerance developed to the behavioral effects within a few days. Dose administered was progressively increased up to 400 micrograms per kilogram over the course of a month. When the injections were abruptly discontinued, all six monkeys showed after twelve hours, behavioral and physiological changes described by the researchers as mild abstinence signs. Two of the six monkeys then initiated and maintained for several weeks the self-administration of THC.

The investigators believe these findings are evidence for mild psychological and physiological dependence on THC. However, vehicle controls were not included in the research design. Thus, the abstinence signs and subsequent behavior may possibly be accounted for by the biological effects in of the Tween vehicle.

Harris et al. (1972) utilized several procedures to maximize the possible conditions necessary for developing self-injection in monkeys. These procedures included: spontaneous Delta 9 THC self administration with no previous training to the technique; self-administration of A' THC after training, with cocaine alone and a mixture of cocaine and Delta 9 THC. Doses utilized ranged from 20 to 500 micrograms per kilogram suspended in polyvinylpyrrolidone. In all cases, monkeys failed to self -administer Delta 9 THC.

The researchers conclude that A' THC lacks the reinforcing effects of psychomotor stimulants and depressants which monkeys readily self infuse with no auxiliary incentives. Also Delta 9 THC lacks a reinforcing function even for monkeys that are well-trained with cocaine and have experienced several days of rather large quantities of Delta 9 THC during the early pleases of extinction of the cocaine reinforced response.

Finally, the results demonstrate that a two week period of exposure to Al THC (in a mixed solution with cocaine) does not result in the degree of homeostatic imbalance which occurs with morphine, ethanol, barbiturates and sometimes the amphetamines which accounts for the continued self-administration of these drugs.

PHYSIOLOGICAL EFFECTS

Permanent congestion of the transverse ciliary vessels of the eye and accompanying yellow discoloration is the only physical effect firmly linked to long-term marihuana use (Ames, 1958; Chopra, and Chopra, 1957; Dhunjibhoy, 1928). Although there are several suspected or reported effects, none has been conclusively demonstrated in a valid study. Some (Chopra and Chopra, 1939; Indian Hemp, 1893) claim that bronchitis, asthma and other respiratory problems may be produced by chronic and excessive use of potent compounds in India. Eastern smoking, preparations are often a mixture of tobacco and hashish.

Indian users reportedly exhibit digestive tract abnormalities, weight loss and disturbed sleep (Chopra and Chopra, 1939; Soueif, 1967). However, the contributing factors of poor living conditions, malnutrition and prevalence of communicable disease could not easily be separated.

A high percentage of heavy Moroccan users have developed obliterative arteritis of the lower extremities (Sterne, 1960) possibly related to the occurrence of tropic foot ulcers (Ganja -foot) (Miras, 1965). The progression of this abnormality is claimed to parallel prolonged use of the drugs.

Mendelson et al. (1972) were unable to demonstrate clinically significant abnormalities in the extensive battery of tests performed which could be attributed purely to the subjects long-term use of marihuana. No histories were obtained of neurological, hepatic, renal, pulmonary, cardiac, gastrointestinal, (renitourinary, or nutritional disorders. No history of psychotic illness was given.

All subjects were Judged to be in normal mental, health by psychiatric interview and psychological tests (MMPI and Edwards Personality Preference Inventory). Three subjects were felt to be neurotic.

Pre-drug complete physical exams, chest X-ray, electrocardiogram, urinalysis, complete blood count and blood chemistry profile did not demonstrate, any clinically significant abnormalities. No subject showed evidence of poor nutrition.

Pulmonary vital capacity and one second forced expiratory volume were reduced in 12 of the 20 subjects initially. These changes were not correlated with either current cigarette smoking or f requency or duration of marihuana smoking. Histories of past cigarette use, past patterns of marihuana use and past or present contact with environmental air pollutants were inadequate to attempt to account for these pulmonary findings.

Many of the subjects were in fair to poor physical condition as judged by a cardiac exercise tolerance test.

Four of the 20 subjects' initial performance on a battery of cognitive functions tests was poorer than would have been predicted by high average to superior I.Q. scores and educational backgrounds. One of the casual subjects demonstrated improvement with retesting consistent with good brain function. Thus, behavioral impairment was present in three subjects.

Whether the impairment is related to prior drug histories, particularly the excessive use of LSD by the two heavy users, cannot be ascertained. For the casual users, nothing in the case histories possibly elucidated the reason for relatively poor performance based on the exceptionally high I.Q., 139 and 128.

Many Western investigators have suggested that smoking hashish or marihuana may possibly cause bronchitis, asthma or rhinopharyngitis (Bloomquist, 1967; Waldman, 1970; Tylden and Wild, 1967; Schwartz, 1969).

Tenant et al. (1971) described bronchitis, sinusitis, asthma and rhinopharyngitis in 22 American soldiers in Germany who smoked daily enormous quantities (100 grams or more) of hashish for six to 15 months. These conditions, believed to be caused by irritation of the respiratory tract by hashish smoke, seemed to improve, with diminished hashish use.

Twenty-one of the subjects were tobacco cigarette, smokers and occasionally smoked hashish rolled in a tobacco cigarette. Nine patients had symptomatic bronchitis. Five of these subjects underwent pulmonary function tests while consuming their usual daily amount of hashish and again three days after discontinuing use. A mild obstructive pulmonary deficit was demonstrated which was at least partially corrected with diminished hashish intake. Hashish contributed to rbinopharyngitis in 12 of the patients and this effect was not allergic in origin. Urticaria, acne, diarrhea and gastrointestinal cramps were less frequent complaints. Extensive hemotological and hentochemical studies including liver function tests were performed and were within normal limits.

Mann et a]. (1970, 1971) and Finley (1971) studied the effect of marihuana smoking on the pulmonary function of eight non-cigarette smoking marihuana smokers (20-27 years old). Marihuana smoking history was defined in marihuana cigarette-years, that is, one marihuana cigarette daily for one year or the equivalent over a longer or shorter period. The mean marihuana cigarette years for the group was 11 and the range from 2.5 to 26. Three of the marihuana users also used hashish. Chest X-ray, comprehensive spironietry deterinitiations, lung volumes and carbon monoxide diffusion studies were observed and retested with prednisone. Pulmonary functions were essentially normal for all of the non-cigarette smoking marihuana smokers and non-smoking controls.

These investigators were able to distinguish differences in quantity and structure and function in pulmonary macrophages and minor material between marihuana smokers and nonsmokers. In tobacco smokers more marked changes were noted. These changes do not indicate a diminution in defensive capacity of these cells.

Kew et al. (1969) has suggested a possible hepatotoxic effect of marihuana. right persons who smoked marihuana for two to eight years, at least six times a week, evidenced mild liver dysfunction by liver function tests and liver biopsy. Several of the patients admitted to the use of alcohol and oral amphetamines but denied use of intravenous drugs. The authors concluded that the findings were not unequivocally due to marihuana.

Hochman and Brill (1971) noted abnormal liver function tests in 10 of 50 frequent marihuana users. However, all admitted to long-term, regular and heavy use of alcohol. When these subjects abstained from alcohol for one month but continued their usual marihuana usage, evidence of disturbed liver function cleared in nine out of 10 subjects.

Recently, Liskow et al. (1971) reported the appearance of an anaphylactoid reaction in a 29year-old woman after smoking marihuana for the first time. Skin tests were positive for an allergy to marihuana, constituents. Allergy to marihuana, especially in areas of the country where it grows wild, may be more common than generally believed.

Campbell et al. (1971) presented evidence of ventricular dilatation consistent with cerebral atrophy by air encephalography in 10 young males (average age 22) with histories of consistent marihuana use for three to 11 years as well as less frequent use of LSD and amphetamines. The first four of the patients had been referred originally for neurological investigation of behavioral change, memory loss or headache. The remaining six subjects were selected from patients tinder treatment for drug abuse because of their long history of marihuana use and concomitant neurological and behavioral symptoms.

However, the patients showed personality behavioral and mental disorders, as well as histories of head trauma and psychomotor or grand mal epilepsy that are commonly associated with ventriculographic changes. Also alcoholism can be associated with these findings. Additionally, the authors compared their subjects ventriculograms with those of normal young adults originally referred for loss of consciousness, syncope and headache without subsequent development of neurological illness.

Thus, the authors demonstrated dilation of the third ventricle, of the frontal or temporal horn, or of the trigone of the lateral ventricle. All of these are commonly associated with personality and mental disorders such as these patients shelved. However, whether these changes are caused by marihuana is not proven because no specific neuropathological cause for the cerebral atrophy was identified. Further carefully designed studies are required to clarify this finding.

The LaGuardia Report (Mayor's Committee, 1944) indicated no damage to the cardiovascular, digestive, respiratory and central nervous system, nor the liver, kidney or blood in individuals who had used from two to 18 cigarettes of unknown potency (average seven) for a period of two-and a-half to 10 years (average eight). However, this study was not up to modern standards as it lacked double-blind precautions and placebo controls and adequate statistical analysis of the data. Bias was present in reporting. Small numbers of prisoners were used as subjects.

Another less comprehensive American study of 310 individuals who used marihuana on the average of seven years was performed on soldiers (Freedman & Rockmore, 1946). It did not demonstrate any evidence of physical or mental deterioration.

Another team of investigators (Meyer et al., 1971; Mirin et al., 1970) examined a group of 10 male marihuana users (average age 25) who had consumed the drug about 20 to 30 times a month for all average of 4.4 years (one-half to five year range) and had smoked daily for three of the 4.4 years. Heavy use was correlated with psychological dependence, search for insight or meaningful experience, multi-drug use, poor work adjustment, diminished goal directed activity, decreased ability to master new problems, poor social adjustment and poorly established heterosexual relationship. No physical or neurological or psychiatric abnormalities were noted in their work-up.

Indeed, numerous American investigators have not reported abnormalities in baseline, examinations of their experimental subjects who have various patterns of marihuana use from very infrequent to many times a day.

GENETICS AND BIRTH DEFECTS

Much concern about possible effects on the unborn generations has arisen because of marihuana's use by persons in their reproductive years. Presently, most studies are preliminary.

There are three isolated case reports in man (Gelehrter, 1970; Carakiishansky et al., 1969; Heelit et al., 1968) of birth defects in mail in the offspring of parents who had used marihuana and LSD. However, due to their complex gestational histories and the high level of birth defects seen in a "normal" population, a causal relationship cannot be attributed to cannabis or anything else. At present, there is no substantial evidence indicating that marihuana at the dose commonly used is a teratogen in man.

Marihuana has been implicated as a teratogen in animals by several groups at high doses. One study (Miras, 1965) showed reduced fertility in rats impregnated after being fed a diet containing marihuana extract for several months. However, the offspring were normal. The reduced fertility may be related to the finding of marked decrease rate of cellular division, but without chromosomal damage, -when Delta 9 or All THC is added to white blood cell cultures (Neu et al., 1969 Martin, 1969).

Dorrance et al. (1970) and Gilmore et al. (1970) detected no significant difference in lymphocyte chromosomes in groups of users and nonusers. No significant differences were, found in lymphocyte chromosomes between heavy, long-term. Jamaican ganja users and matched nonusers. (Rubin and Comitas, 1972)

Pregnant mice injected with cannabis resin on day six of gestation caused stunted but not malformed offspring. Fetal reabsorption occurred when the dose was given on days one to six (Persand and Ellington, 1967). A second experiment using rats injected on days one to six produced a high frequency of malformed progeny. Another investigator (Geber, 1969; Geber and Schramm, 1969) demonstrated congenital malformations in fetal hamsters and rabbits after large multiple doses of cannabis extract.

Another group (Pace et al., 1971) have administered a wide range of dosages of Delta 8 and Delta 9 THC and marihuana extract by subcutaneous, intraperitoneal and intravenous routes at varying intervals pre- and post-conception to rats, hamsters and rabbits. Delta 9 THC up to 200 mg/kg in variety of dose schedules produced reduced average litter size and stunted pups at high doses but no birth defects. A low incidence of abnormalities occurred in rats and rabbits with marihuana extract, but a high incidence of neonatal deaths was observed apparently due to inadequate material lactation.

Studies with radioactive labeled THC (Idanpaaiini-Heikkila et al., 1969) indicated that it did cross the placenta in high concentrations early in gestation during the developmentally labile phase.

These studies suggest that Delta 9 THC itself is not a teratogen. Instead, perhaps some unidentified substance or substances in the plant extract may be causing the teratogenic effect noted by this group and others when injected. It is uncertain whether this theoretical substance(s) volatilizes during smoking or enters the pulmonary vasculature (Pace et al., 1971).

Consequently, the following FDA label required of many currently prescribed psychoactive drugs warning about use in Pregnant women and women of childbearing age, appeals indicated. "Safe use of the drug during pregnancy and lactation has not been established; therefore, in administering the drug to Pregnant patients, nursing mothers, or women of childbearing potential, the potential benefits must be weighed against the possible hazards. Animal reproduction studies have yielded inconclusive results. . . . There have been clinical reports of congenital malformation associated with the use of this drug, but a causal relationship has not been confirmed."

ORGANIC BRAIN DAMAGE

Deterioration of mental functioning allegedly due to long-term use of marihuana can be subdivided into four major categories: organic brain damage, mental illness-psychosis, amotivational syndrome, and recurrent-pnuenomenia. As with alcoholism, it is quite often impossible to distinguish whether the described effects result from drug use or represent personality traits or changes which would have been present without the drug use.

When marihuana consumption was irregular, mental deterioration was not evidenced (Freedman and Rockmore, 1946) in 310 users with an average history of seven years of use. Sixty-seven heavy users in New York showed no evidence of dementia attributable to drug use although they did have underlying personality disorders. Another investigation (Mayor's Committee, 1944) of individuals who used a daily average of seven marihuana cigarettes (two to 18 range) for average of eight years (two-and-a-half to 16 range) showed no evidence of brain damage or mental deterioration.

Reports from India (Chopra, 1935; Chopra, 1940; Chopra and Chopra, 1939; Chopra, Chopra, and Chopra, 1942) relate minor impairment of judgment and memory, limited self -neglect and insomnia, when potent preparations are consumed regularly in large amounts for many years. No evidence for mental deterioration or brain damage has been noted.

Miras (1967) has described a Greek population of heavy hashish smokers who appear as outcasts from the community after 15 to 20 years of heavy hashish use. They appear mentally sluggish and depressed. They are reported to exhibit laziness, psychic instability, amorality and apparent lack of drive and ambition. Their speech and behavior has been described as -peculiar. Some degree of responsibility is retained in that some do work to cover their living and drug purchasing expenses. Some of them are still quite intelligent. Memory is not deteriorated except during the intoxication. They appear overly suspicious. Samples of their electroencephalograms were believed to demonstrate abnormalities.

However, Miras believes that this effect is related to the quantity and frequency of hashish use. He describes three categories of long-term hashish users. Type A uses low doses intermittently and is socially and mentally unaffected. Type B1 uses low doses daily and no interference is caused in function. Type B 2 uses high doses daily causing dependence and performance decrements. Type C uses very high doses daily allegedly causing mental deterioration and abnormal behavior described above. Fink and Dornbush (1971) are currently intensively studying this population. The results will be described in a later section.

Non-differentiated psychosis noted in foreign populations may also be included within this diagnostic category. These will be discussed with the psychosis.

PSYCHOSIS

The alleged connection between mental illness and cannabis derives from Africa, the Middle East and India. These areas are currently developing economically and scientifically, but for many years medical care and especially psychiatric care were given low priority. Many chronic illnesses still persist in these countries which may affect mental functioning. Furthermore, well-trained psychiatrists and methodologists are very rare in mental hospitals in these countries. Consequently, the findings of earlier studies are questionable due to lack of controls, biased sampling and poor data collection and failure to account for variables like nutrition, living standard, cultural factors and socioeconomic status.

India's mental institutions were widely quoted to support the, connection between excessive cannabis consumption and insanity. The Indian Hemp Commission performed a thorough and objective investigation of this question, although methodologically it was not up to modern standards. The Commission was unconvinced of the reliability of hospital statistics, where often the diagnosis was not made by a psychiatrist but by a referring policeman.

Therefore, the Commission examined all admissions to Indian mental hospitals for one year. They found that cannabis rise could not be considered a factor in more than seven to 13% of all cases of both acute and chronic psychosis.

Chopra et al. (1942) carefully performed the same examination of admission to Indian mental hospitals from 1928 through 1939 when cannabis use was extremely high. They found 600 cases of acute and chronic psychosis which could be traced to cannabis use. Other reports from India have produced varying estimates of the incidence of cannabis psychosis (Peebles and Mann, 1914; Chopra, 1971; Dhunjibhoy, 1930 Evens, 1904). In Egypt 27% to 33% of mental hospital admissions were cannabis related (Ireland, 1893; Warnock, 1903).

Benabud (1957) reported that cannabis users comprised 68% of all mental hospital admissions in Morocco but only 25% of these admissions could be called cannabis psychosis. Watt (1936 and 1961) reported that 2% to 3% of mental hospital admissions in South Africa were due to the use of dagga (cannabis).

Boroffka (1966) and Asuni (1964) reported that 14% of psychiatric admissions in Nigeria used cannabis. Toxic psychosis accounted for half of these and cannabis was felt to aggravate underlying schizophrenia in the remainder.

Several statistical studies from other countries including Jamaica, Colombia, Algeria, Panama and Tunisia support this type of data (Prince et al., 1970; Beaubrun, 1971 Allentuck and Bowman, 1942; Bouquet, 1951; Chevers, 1870; Defer and Dielil, 1968; Fraser, 1949; Freedman and Rockmore, 1946; Porst, 1942; Siler et al., 1933; Reales-Aroyco, 1953; Medical Staff, 1938).

Very little information is available on the prevalence of psychosis in the overall population of cannabis users. Chopra and Chopra (1939) classified 2% of the ganja and charas smokers and 0.5% of the bhang drinkers in their sample of 1,200 as psychotic.

Roland and Teste (1958) estimated that no more than 0.5% of kif (cannabis) smokers in Morocco suffer from recurrent mental conditions.

Prince et al. (1970), in a study in Jamaica, noted that about 20 patients per year are admitted to mental or general hospitals with acute psychotic reactions allegedly precipitated by ganja. In one general and one mental hospital the, ganja smokers comprised 20% of the psychiatric admissions. Furthermore, the percentage of heavy ganja smokers in the community was significantly higher than 20%. Thus, a larger percentage of psychiatric admissions were, derived from non-ganja smokers in a comparable lower socioeconomic segment of the population.

This finding contrasts with the 68% prevalence of cannabis use among psychiatric admissions reported by Roland and Teste (1958) which is considerably higher than the prevalence of cannabis use in the general population of Morocco.

Studies based on several hundred cases indicate that the large majority of individuals hospitalized in mental institutions for "cannabis psychosis" have suffered acute toxic psychoses associated with a sharp toxic overdose or massive excesses among habitual users. Occasional smokers and moderate habitual users seldom had psychotic reactions and then only when there were substantial predisposing factors.

The acute clinical picture seen in these delirium with confusion, disorientation, terror, and subsequent amnesia is that of a severe exogenous psychosis. It does not typically involve the type of thought disorder characteristic of schizophrenia. Short recovery times ranging from a few days to six weeks are uniformly reported in sharp contrast to the lengthy recovery period of functional psychoses (Chopra et al., 1942; Roland, and Teste, 1958; Defer and Diehl, 1968; Beaubrun , 1971; Stringaris, 1939).

Consequently, the psychiatric literature on cannabis-induced chronic psychosis is quite confused. In general, it appears that cannabis use probably produces a specific psychosis, but this must be quite rare, since the prevalence of psychosis in heavy cannabis users, world-wide, is only doubtfully higher than the prevalence in general populations (Murphy, 1963). However, incidence and prevalence data for these countries on psychosis of users and non-users of cannabis does not exist.

A Morroccan investigator, Christozov (1965), studied 140 chronic heavy hashish users hospitalized in a mental hospital. Their behavior was characterized by a confusional state of consciousness, an impulsivity, an irresponsible attitude, and an instability of mood and character. The patients were often psychotic with persistent hallucinations. Intellectual functions were reduced in over half the cases although this was related to a low intellect prior to drug use. Electroencephalography showed no specific changes. In addition, it was noted that half of the patients were also alcoholics.

The majority of the patients were, sedated and showed a rapid improvement, allowing them to be discharged and be employed, Although it appeared that these characteristics are reversible, the patient often returned to heavy drug use again causing return of the syndrome.

Thus, the existence of a more long lasting cannabis-related psychosis is poorly defined. Some evidence indicates the existence, of a, quite rare slow-recovery, residual cannabis-psychosis following heavy chronic use. Patients often exhibit schizophrenic-like withdrawal, mental confusion and mild residual hallucinations; but there is little tendency for the, symptoms to become organized or proliferate. The symptoms develop gradually and then subside gradually before proceeding to full-blown psychotic symptoms. These may produce gradual psychic deterioration in the habitual excessive user after prolonged periods of time. Several authors theorized that the chronic psychosis consists of recurrent acute attacks with gradual deterioration in habitual excessive users (Roland and Teste, 1958; Chopra, et al., 1942; Stringaris, 1939; Sigg , 1963).

Most investigators, therefore, find it exceedingly difficult to distinguish a psychosis due to cannabis from other acute and chronic psychoses because, few, if any symptoms, are uniquely found in it and not observed in other psychoses. Often the diagnosis of cannabis psychosis is made because of the history of heavy marihuana or hashish use. Several have suggested that a characteristic cannabis psychosis does not exist and that marihuana will not produce a psychosis in a well-integrated, stable person (Allentuck and Bowman, 1942; Reales-Aroyco, 1953).

In addition, alcohol often played a part in producing the mental derangement (Medical Staff, 1938; Porst, 1942). Most data refers to any form of psychosis in marihuana users; not specifically cannabis psychosis.

Although it is fairly well-established that cannabis use attracts the mentally unstable, the prevalence of major mental disorder among cannabis users appears to be little if any higher than that in the general population. Therefore, true cannabis psychosis must be earlier, very rare or it must substitute for other forms of psychosis. Perhaps, cannabis use alternatively is protecting some less stable individuals from a psychosis (Murphy, 1963).

Because of these many difficulties, the role of cannabis use in acute and especially chronic psychoses in these countries is impossible to determine with certainty.

Finally, the Eastern literature often mentions the existence of a characteristic psychic degeneration among older habitues after prolonged excessive use (Chopra et al., 1942; Christozov, 1965; Indian Hemp Commission, 1893; Roland and Teste, 1958; Stringaris, 1939; Warnock, 1903). They are frequently described as showing a single minded, carefree state, such as "Kif-happy vagabonds."

Soueif (1967) administered psychomotor and cognitive performance tests to imprisoned hashish users and non-hashish users in Egypt. Preliminary results indicate that, on most of the tests, the hashish sample scored 10% to 20% below the control, and differences were larger for those with higher educational levels. These results do not necessarily indicate a causal relationship. Assessment of the significance of these findings must await further description of the samples utilized.

Experience in the U.S. and Western Europe has not involved a level of marihuana use comparable to the above-mentioned countries. Consequently, the associated chronic psychotic disturbances have not been seen.

In Western countries, Bromberg (1939) and Allentuck and Bowman (1952) reported on acute psychotic episodes with clear-cut onset during the marihuana intoxication. Most symptoms cleared within a few days although several had a, prolonged illness. These rare acute psychotic episodes, discussed earlier, have been described recently by a variety of authors in scattered countries (Smith, 1968; Weil, 1970; Bialos, 1970; Keeler, 1967; Milman, 1971; Pesyko, 1970 Kaplan, 1971; Prince et al., 1970; Baker and Lucas, 1969; Grossman, 1969; Beaubrim, 1971; Spencer, 1970).

Some of these reported cases are quite transient and clear rapidly with support of others and may be more like acute panic reaction than psychosis. Still others appear to fit the picture of transient toxic psychosis.

A few cases of marihuana psychosis reported by Kaplan (1971) recovered very slowly after extensive psychotherapy. However, the high incidence of schizophrenia and borderline states described in these patients and their families may indicate that marihuana use merely aggravated or precipitated an underlying psychosis in these individuals.

George (1970) reported a case in Britain in which an acute episode of confusion, disorientation, hallucination, anxiety, paranoia, agitation and memory loss related to cannabis use was followed by a more chronic schizophrenic-like syndrome with thought disorder, incongruous affect and hallucinations. This individual was experiencing considerable financial and marital stress prior to these two separate acute episodes. The chronic condition eventually responded to psychotherapy.

Bernhardson. (1969) reported aggravation by cannabis of schizophrenic conditions in several Scandinavian patients. Perna (1969) reported a case in which marihuana appeared to aggravate an extended psychosis for which the patient had required psychiatric treatment prior to the use of marihuana.

Keup (1970) reported 14 cases of prolonged psychotic symptoms requiring hospitalization associated with the use of marihuana. He noted evidence for the existence of a, high level of psychopathology in many of them which predated their marihuana use.

Kolansky and Moore (1971) in a widely publicized report of cases of individuals ages 13-to-24 has claimed profound adverse psychological effects from smoking marihuana two or more times a week.

Of 38 individuals reported, all had decompensated personalities, eight had psychoses (four attempted suicide) and 13, according to the authors became sexually promiscuous due to marihuana. These clinical impressions were, all based on, at most, a few interviews with the, individuals who were referred to these psychiatrists for consultation for problems (including one-third by legal authorities after arrest for possession of marihuana).

Unfortunately, the authors made sweeping generalizations to all young adolescent marihuana users from this biased and non-representative sample. No attempt was made to interview other young marihuana users who have not been referred for psychiatric help, and the high prevalence of promiscuity and psychopathology in comparable adolescent populations was totally disregarded. In addition, case histories of previous mental health were obtained introspectively from the patient, their families or the referral source.

Thus, it is impossible, to state unequivocally, as the authors do, that since marihuana use and psychiatric problems occurred at the same time the former is causative of the latter.

Several authors have reported acute toxic psychosis following marihuana use by soldiers in Vietnam (Talbott and Teague, 1969; Colbach and Crowe, 1970, Bey and Zecchinelli, 1971).

All these cases represented transient reactions and cleared rapidly with treatment. In many cases, personality disorders or borderline personality states appeared to be predisposing factors in the development of the psychotic state. Often revealed were problems of identify diffusion, ego weakness, low self-esteem and inability to form close interpersonal relationships. Also the stressful conditions of the setting in which the drug was used deserves emphasis.

Halikas et. al. (1971, 1972) performed intensive psychiatric interviews on a population of 100 regular marihuana users and a control group of 50 of their non-using or casually using friends. Half of each group met the criteria for some psychiatric diagnosis. Psychiatric illness and antisocial behavior most often preceded marihuana use.

Some attempts have been made to estimate the incidence, of psychosis and other adverse reactions to marihuana in Western countries. Obviously, such estimates depend on how these reactions are defined-one questionnaire study of 2,700 psychiatrists, psychologists, internists and general practitioners in the Los Angeles area reported 1,887 "adverse reactions" to marihuana in an 18-month period (Ungerleider et al., 1968). Adverse reactions were not defined by the authors in the survey. Those reported ranged from mildly unpleasant parental objections to use to severe anxiety or acute psychosis.

Keeler (1967) reported on "adverse reactions" to marihuana (paranoid feelings, etc.) which are limited to the immediate period of intoxication. These phenomena occasionally occur in such a light proportion of regular users that they are of little interest in the present discussion, e.g., 80% of users report they sometimes have paranoid reactions during the marihuana intoxication (Tart, 1970).

Other estimates have been based on hospital admissions in which marihuana use was the recognized precipitating cause. Lundberg et al. (1971) reviewed the admission records for the Los Angeles County General Hospital for the period 1961-1969 and found marihuana use was listed as the reason for admission in only nine out of 700,000 cases, and five of these were for intravenous injections.

Keup (1970) reports that 0.9 per 1,000 of the 1968 admissions to a Brooklyn psychiatric hospital were directly related to cannabis use, and in another 1.9 per 1,000 it was found to be a contributory factor.

In 1966, psychiatric hospitals in England listed 82 admissions for which cannabis use was considered a factor (Baker and Lucas, 1969) in 1967, the number was 140 (George, 1970). For the 1966 data, further analysis revealed that eight of the 82 cases were acute psychotic reactions to cannabis, 20 were related to "cannabis addiction as a way of life," and cannabis could not be established as a definite factor in the remainder (Baker and Lucas, 1969).

Colbach and Crowe (1971) estimate that among a population of 45,000 U.S. soldiers in Vietnam in 1969, some 40 to 50 per month were hospitalized for psychiatric reasons and about five of these were associated with (usually heavy) marihuana use.

Among college populations, Pillard (1970) estimates five to seven marihuana-associated anxiety reactions are, seen per year by the Boston University Health Service which cares for a student population of 20,000; and Bialos (1970) reported 11 cases during a one-year period (1968-1969) for a student population of 8,500.

If it is assumed that about one-third of the Vietnam and college populations are using marihuana to some degree, the annual incidence of hospitalized cases in Vietnam would be about four per 1,000 users; the rate for student-health cases, 0.3 to 1.3 per 1,000 users.

The 1972 Secretary of Health, Education and Welfare's report on Marihuana and Health prepared by the National Institute of Mental Health noted in summary that marihuana can clearly precipitate certain less serious adverse psychiatric reactions, such as simple depression and panic, particularly in inexperienced users.

In these reactions, non-drug factors may be the most important determinants. Psychotic episodes may also be precipitated in persons with a preexisting borderline personality or psychotic disorder or those persons under excessively stressful conditions. These acute psychoses appear to share considerable clinical similarities with the acute toxic psychoses noted in the Eastern literature. Both these psychoses resemble an acute brain syndrome in that they occur primarily after heavier than usual usage and are self-limited and short-lived after the drug is removed from the body.

Some reports describing a prolonged psychotic course after an initial acute episode cannot rule out the role of pre-existing psychopathology. At the present time evidence that marihuana is a suf ficient or contributory cause of chronic psychosis is weak and rests primarily on temporal association. This issue may be clarified by extensive epidemiological and controlled clinical studies. (Secretary, HEW, 1972)

AMOTIVATIONAL SYNDROME

Another type of possible mental deterioration or subtle personality and behavioral changes associated with heavy long-term cannabis use is the amotivational syndrome.

This syndrome has been described world-wide in its extreme form when the most potent preparations are, used (Miras, 1967; Chopra. and Chopra, 1957; Chopra et aL, 1942; Christozov, 1965; Indian Hemp, 1893; Benabud, 1957; Warnock, 1903). Its most extreme form depicts a loss of interest in virtually all activities other than cannabis use. The resultant lethargy social and personal deterioration and drug preoccupation may be comparable to the skid row alcoholics' state.

Benabud (1957) describes the occurrence of this syndrome in individuals chronically intoxicated with hashish. These individuals are unlikely to show conventional levels of motivation. Also the time required to obtain and consume enough drug to maintain this state is not likely to leave much time for other pursuits. The passive user tends to lose interest in work and other long-term goals.

The question of whether there exists a significant causal as opposed to an associative or correlational relationship, only attracted attention when the traditionally achievement-oriented Western youth adopted cannabis use. The traits of passivity or amotivation are commonly described among heavy cannabis user throughout the world.

A number of Eastern authors have expressed the opinion that this is a result of organicity from chronic cannabis use in large amounts, without objective studies being performed.

Recently the term has been used to describe the behavior of numbers of young Americans who are for a variety of reasons dropping out of school, refusing to prepare themselves for traditional adult roles and smoking marihuana.

This type of social maladjustment is not comparable in magnitude to that described in other cultures. However, the individual may lose the desire to work, to compete, to face challenges. Old interests and concerns are lost and the individual's life, becomes centered around his compulsive drug use. In addition, the individual may ignore personal hygiene, experience loss of sex drive and avoid social interaction (Mirin et al., 1970; Smith, 1968).

West (1970) and McGlothlin and West (1968) have described a clinical syndrome as a result of observations of regular marihuana users for four years. Their clinical impressions are that these individuals show subtle changes in personality over time which might represent an organic syndrome. These include diminished drive, lessened ambitious decreased motivation, apathy, shortened attention span, loss of effectiveness, introversion, magical thinking, derealization and depersonalization, decreased capacity to carry out complex plans or prepare realistically for the future, a peculiar fragmentation in flow of thought, and a progressive loss of insight.

Another psychiatrist, Powelson (1971), has also concluded on the basis of over five years clinical experience with drug users at the University of California, Berkeley, that the effects of marihuana are cumulative. He, feels that after a period of prolonged use a disorder of thinking characterized by a lack of coherence and a pathological thinking process results.

These disturbing findings are being reported more frequently, especially in adolescent and young-adult groups. Recently, tentative and preliminary data (Francois et al., 1970; White et al., 1970) has been presented on a group of 19 hospitalized 14-to-20-year-old patients with behavioral disorders who had used marihuana and other drugs heavily.

In addition to "amotivation," they showed primitive and magical modes of thought and low frustration tolerance. Subtle EEG patterns were detected although this finding is not uncommon in adolescents with behavior problems.

The researchers are presently carrying out a study in non-hospitalized adolescents without behavioral disorders who have similar patterns of drug use in order to clarify their findings.

Kornhaber (1971) believes that at least twice daily marihuana use for a year, in a 13-to-18-yearold population, has a deleterious effect upon the developing adolescent. The intoxicated state facilitates a regression from logical-mathematical thought processes to a more primitive conceptual mode of fantasy and magical thinking and impairs learning ability and judgment by decreasing attention and concentration. Thus, the developing youth turns away from reality toward fantasy and from structure and activity to passive dependency.

Kornhaber suggests that marihuana facilitates the development of normal adolescent turmoil into a pathological state. However, he feels that the existence of the syndrome depends partially on the individual's vulnerability to the drug influence.

A possibly milder variation of this syndrome has been clinically observed by Scher (1970) in individuals in the 20-to-30 age group who have used marihuana daily for five years while apparently functioning normally in society with good jobs, often creative ones. These individuals begin to experience a vague sense of functioning at reduced efficiency level. Thus, the disabilities experienced are personal and internal ,and constitute a vague neurotic depressive-like syndrome,.

In addition to the methodological problems of (Establishing causative as opposed to associative relationships, it is also very difficult to obtain a sample of heavy cannabis users in the West who have not had substantial experience, with other drugs, especially the strong hallucinogens.

Koridiaber (1971) has described a sample of 50 adolescent psychiatric patients who used marihuana daily and also took other drugs. He concluded that marihuana exercised a "chronic, tranquilizing, psychomotor-depressant effect" among these patients, and facilitated regression, fantasy and magical thinking. School performance, participation in sports, and personal hygiene also declined. He reported improvement in school performance, mood and the underlying depressive symptoms for many patients four to six weeks after discontinuing marihuana use.

Given there is a fairly strong tendency for heavy cannabis users to be passive and apathetic, to emphasize the present over the future, and to choose fantasy over rationality, there are several ways by which this relationship might come about (McGlothlin, 1972).

First,, persons who already exhibit these, traits may simply be attracted to the use of cannabis. Sociologists tend to favor this explanation, arguing that the relationship between cannabis use and various behavioral indicators is not causal, but simply one manifestation of a general pattern of youthful deviance or rebellion (Goode, 1970).

Utilizing a large sample, Johnson (1971) found that marihuana use is associated with impaired school performance and several forms of deviance; however, other indicators such as premarital sex and high school truancy predicted the dependent variable as well or better. Tobacco and alcohol use were nearly as good predictors as marihuana.

A second related explanation is that the illegal. context in which the drug is taken forces the adoption of a nonconforming life style. The users is thus further alienated from the dominant culture through his close ties with the cannabis-using group.

Third, cannabis use and associated activities may largely substitute for other interests. The individual may focus so much of his time and energy on cannabis that he has little time for other endeavors.

Fourth, heavy cannabis use may act pharmacologically to produce a chronic tranquilized state. Although the acute phase of intoxication is relatively short, there is some evidence of a lethargic hangover effect (Haines & Green, 1976).

Fifth, personality and behavior changes may result through the routine process of learning via exposure. If an impressionable youth spends a great deal of his time in the world of cannabis intoxication, he may learn to think in a similar manner when not intoxicated. In particular, he may learn to choose the drug fantasy as an alternative to solving personal problems and facing adult responsibility.

A related explanation is that cannabis acts as a catalyst, creating a condition which facilitates change, providing other necessary conditions are present. Cannabis, along with the strong hallucinogens, produces a kind of mind-loosening effect in which mechanisms providing structure and stability to perception of self-image, environment, time sense,, etc., are temporarily suspended.

The, more frequent users welcome this effect and report utilizing the loosening effect of the drug to achieve further personality change in the direction of less conformity and more spontaneity, that is. the "hang-loose ethic" (Suchman, 1968; Simmons and Winograd, 1966).

In addition, the cannabis intoxication produces a heightened suggestibility which likely makes the user more amenable to adopting the attitudes and values of the subculture in which the drug is taken. At a minimum, it may be concluded that the effects of cannabis can reinforce and provide a rationalization for previously existing tendencies.

Finally it is possible that chronic cannabis use can result in organicity (Soueif, 1967).

In summary, if cannabis use produces personality and behavior changes via one or more of the above mechanisms, the extent of such changes is likely to be strongly related to the amount consumed and the age of the user. According to evidence found in Western literature, frequent use may be quite disruptive during the formative years of adolescence.

On the other hand, the Eastern literature indicates that, although the very heavy user (200 mg. THC or more per day) is largely incapacitated, manual laborers often function adequately while consuming amounts containing 30 to 50 mg. THC per day (Roland and Teste, 1958; Chopra and Chopra, 1939). Similarly, many musicians and entertainers in the United States have lived productive lives while using marihuana (Winick, 1960).

RECURRENT PHENOMENON

Another poorly understood phenomenon is the spontaneous recurrence of all or part of the drug intoxicated state (somatic and visual sensations) when not under the influence of the drug. This phenomenon has been called a "flashback" when it occurs spontaneously or "a contact high" when it occurs in the presence of others who are intoxicated.

Flashbacks have been reported with marihuana use alone. However, these occurrences are apparently predominant in marihuana users, who have taken hallucinogenic drugs previously. These marihuana, users occasionally find that marihuana highs change for them after their hallucinogenic. experiences. For example, a simple hallucination experienced previously may reoccur while high on marihuana.

These flashbacks may be interpreted as pleasant, even desired experiences by some but unwelcome and disturbing to others. The recurrences are benign in most individuals and tend to disappear as the hallucinogenic experience recedes in time (Keeler, 1967; Smith, 1968; Weil, 1970; Bialos, 1970; Blumenfield, 1970).

Truly vivid experiences which recapture most of the elements of the original experience are extremely rare (Smith and Meld, 1970). More often they resemble an anxiety state occurring after an unpleasant high or the recurrence of a new perceptual awareness gained while high. It is difficult to differentiate these recurrences from the not uncommon deja vu phenomenon in which a person has the illusion that a perceived situation has occurred before. These recurrences are intermittent and usually occur within a few days to weeks following the use of marihuana.

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Marihuana, A Signal of Misunderstanding