ADVERSE EFFECTS OF MARIJUANA SMOKE ON HUMAN HEALTH

EFFECTS OF MARIJUANA (CANNABIS) SMOKE ON HUMAN HEALTH

ABSTRACT

Marijuana seems firmly established as another social drug in Western countries, regardless of its current legal status. Patterns of use vary widely. As with other social drugs, the pattern of use is critical in determining adverse effects on health. Perhaps the major area of concern about marijuana is among the very young. Using any drug on a regular basis that alters reality may be detrimental to the psychosocial maturation of young persons. Chronic use of marijuana may stunt the emotional growth of youngsters. Evidence for  a motivational syndrome is largely based on clinical reports; whether marijuana use is a cause or effect is uncertain. A marijuana psychosis, long rumoured, has been difficult to prove. No one doubts that marijuana use may aggravate existing emotional disorders. Brain damage has not been proved. Physical dependence is rarely encountered in the usual patterns of social use, despite some degree of tolerance that may develop.

The endocrine effects of the drug might be expected to delay puberty in pre-pubertal boys, but actual instances have been rare. As with any material that is smoked, chronic smoking of marijuana will produce bronchitis; emphysema or lung cancer has not yet been documented. Cardiovascular effects of the drug are harmful to those with pre-existing heart disease; fortunately the number of users with such conditions is minimal. Fears that the drug might accumulate in the body to the point of toxicity have been groundless.

The potential deleterious effects of marijuana use on driving ability seem to be self-evident; proof of such impairment has been more difficult. The drug is probably harmful when taken during pregnancy, but the risk is uncertain.

                                           INTRODUCTION

The modern era of research into the effects of cannabis in man began less than 20 years ago. Many issues about its health hazards, as they are with all drugs, remain controversial and ambiguous, adverse reactions to drugs were not recognized until after much exposure had occurred. Often these are idiosyncratic or allergic reactions. On the other hand, adverse reactions due to the extensions of the pharmacological action of a drug may be recognized both early and late. A similar pattern holds for cannabis. The ambiguity currently surrounding the health hazards of cannabis may be attributed to a number of factors besides those which ordinarily prevail.  It has been difficult to either prove or disprove health hazards in man from animal studies. When such studies of cannabis reveal possible harmful effects, the doses used are often large and the treatment is generally short. Cannabis is still used mainly by young persons in the best of health, unfortunately, the pattern of use is more often one of intermittent rather than regular use, the doses of drug usually being relatively small. This factor might lead to an underestimation of the potential impact of cannabis on health. Also, cannabis is often used in combination with tobacco and alcohol, among licit drugs, as well as a variety of other illicit drugs. Thus, potential health hazards from cannabis may be difficult to distinguish from those of concomitantly used drugs.

Marijuana often called pot, grass, reefer, weed, herb, Mary Jane, is a greenish-gray mixture of the dried, shredded leaves, stems, seeds, and flowers of Cannabis sativa—the hemp plant. In

Most users smoke marijuana in hand-rolled cigarettes called join   somchemice use pipes or water pipes called bongs, blunts, users slice open cigars, remove some of the tobacco, and mix the remainder with marijuana. Marijuana also is used to brew tea and sometimes is mixed into foods.

This report will focus on three main areas:

 (a) Acute and chronic effects of cannabis in humans;

 (b) Issues regarding its possible adverse effects on human health,

 (c) The therapeutic potential of cannabis constituents or synthetic homologs of such constituents.

LITERATURE REVIEW

2.0 Acute and Chronic Effects of Cannabis in Humans

The availability of synthetic trans-delta-9-tetrahydrocannabinol (THC), the major component of cannabis, and the chemical techniques for quantifying its content in cannabis preparations and in blood have made possible for the first time pharmacological studies which provide some precision in dose. When the material is smoked, as it is most commonly used in North America, a variable fraction of THC is lost by smoke escaping into the air or exhaled from the respiratory dead space. Relatively little is lost by pyrolysis, since it is likely that the cannabinoid is volatilized in advance of the burning segment of the cigarette. The efficiency of the delivery of a dose by smoking has been estimated to be about 18%, but frequent smokers obtain 23%, while infrequent users obtain only 10%. THC and marijuana extracts are also active by mouth; the systemic bioavailability of oral administration is only about 6%, one-third that from smoking.

When smoked, THC is rapidly absorbed, and effects appear within minutes, If marijuana is of low potency, effects may be subtle and brief. Seldom do they last longer than 2 to 3 hours after a single cigarette, although users prolong the effects by repeated smoking. Oral doses delay the onset of symptoms for 30 min to over 2 hours, as well as prolonging the span of action of the drug. These time schedules are consistent with knowledge of the pharmacokinetics of the drug. Smoking is similar to administration in producing maximum plasma concentrations early, while administration produces slower rises of maximum plasma concentrations, which are also lower than those for smoking. Although the route of administration affects the time course and the intensity of cannabis effects in man, the pattern of these effects was well established by early investigators.

Conjunctival reddening is also consistently observed. Both this symptom and the increased pulse rate correlate quite well in time with the appearance and duration of psychic effects of the drug, as well as the plasma concentrations of the drug. Muscle strength is decreased. Appetite is consistently augmented, along with an increased food intake. Observed physiological effects have not included changes in pupil size, respiratory rate, or deep tendon reflexes.

Perceptual and psychic changes are biphasic. An initial period of euphoria or "high" is followed by drowsiness. Time sense is altered, hearing is less discriminant, and vision is apparently sharper with many visual distortions. Depersonalization, difficulty in concentrating and thinking, dream-like states are prominent. Many of these symptoms are similar to those produced by psychotomimetics.

The effects that users derive from cannabis are extremely variable. Some of this variability depends on individual variation in degree of tolerance to the drug, based on prior use. Although it is customary to ascribe some variability to difference in setting, i.e., the type of conditions and surroundings which prevail during the drug use, or to set, that is, the expectations of the user, proving the effects of either has been difficult.

B. Chronic Studies

The effects of chronic use of cannabis are more to the point when considering the issues of its status as a possible social drug. Three large-scale field trials of cannabis users have been reported, but the results of these trials have done little to allay apprehensions about the possible ill effects of chronic use. Objections have been made about the small samples used, the sampling techniques, and the adequacy of the studies performed.

Possible Adverse Effects Of Cannabis On Health

A. Immunity

A number of in vitro studies, using both human and animal material, suggest that cell-mediated immunity may be impaired after exposure to cannabis.

Clinically, one might assume that sustained impairment of cell-mediated immunity might lead to an increased prevalence of malignancy, as seen in the current epidemic of acquired immune deficiency syndrome (AIDS). No such clinical evidence has been discovered despite some degree of impairment of immune responses, the remaining immune function may be adequate, especially in the young person who are the major users of cannabis.

An impairment of cellular immunity in 51 chronic users of cannabis was shown by inhibition of lymphocyte blastogenesis from mitogen, phytohemagglutinin. A decrease in T-lymphocytes was found in 9 of 23 chronic cannabis users, employing rosette formation as a way of quantifying T-lymphocytes; the number of total lymphocytes was not different from nonusers. Thus, two early studies suggested that T-lymphocytes might be decreased in number as well as in ability to respond to an immunologic challenge. immunosuppression was shown in animals by prolonged allogenic skin graft survival, inhibited primary antibody production to sheep erythrocytes, and a diminished blastogenic response.

Further studies have tended to confirm an immunosuppressant action of cannabis in animals, whether the material was given or injected. Mice treated with THC and challenged with gram-negative bacteria showed enhanced susceptibility. However, others using in vitro techniques for studying lymphocytes, have found no alteration in nucleic acid synthesis in the presence of as much as 10.6 x 10-4 M concentrations of THC.

Effects of cannabis on T-cells may be transitory. Smoking of cannabis temporarily decreased T-cell function in 13 chronic users as compared with 9 matched non-smokers, but the effects varied from subject to subject and were closely related to the time the blood samples were drawn. Although early T-cell rosette formation was impaired in ten chronic cannabis smokers, despite a normal total of circulating T-cells, the absence of clinical evidence of greater disease susceptibility among such subjects makes this observation of dubious clinical importance. Other studies cast doubt on some of the earlier positive observations of impaired cellular immunity. Dinitrochlorobenzene is used as a skin test for intact delayed hypersensitivity, mediated by cellular immunity. No differences were observed in 34 chronic marijuana smokers as compared with 279 non-smokers. The response of cultured lymphocytes from 12 long-term smokers of cannabis to two mitogens was not impaired as contrasted with lymphocytes from non-smokers. Even the ingestion of cannabis in amounts of 210 mg daily of THC failed to alter the response of the subjects lymphocytes to mitogen stimulation.

Furthermore, the degree may not be clinically significant as the reserve capacity of the body to respond to immune challenge may not be exceeded.

Clinical experience has not yet indicated an increased vulnerability of cannabis users, but further observations of the possible contribution of marijuana use to the susceptibility to develop AIDS must be awaited.

B. Chromosomal Damage

Adverse effects on chromosomes of somatic cells have been especially controversial. The techniques of human cytogenetic studies still leave much to be desired. Assessing damage to chromosomes is more of an art than a science. Interpretations are highly subjective, and it is often difficult to get agreement between any two readers of the same slide. Further, processing of cells to make chromosomal preparations may differ from one laboratory to another, so that it is possible to get conflicting results from the same specimen even when read by the same reader. One needs only recall the controversy about chromosomal damage from lysergic acid diethylamide (LSD) a few years ago to interpret any reports of chromosomal damage with great caution, as similar types and degrees of chromosomal alteration have been reported in association with other drugs commonly used in medical practice, without any clinical evidence of harm, the significance of such changes remains unclear. Early reports were positive, but more recent reports were negative. A significant increase (3.4 versus 1.2%) of chromosomal abnormalities was reported in marijuana users as compared to nonusers. Changes were largely breaks or translocations of chromosomes. More of the latter were found in chronic cannabis users than in nonusers, but when breaks were included in the counts, the differences vanished. No increase in chromosomal breaks was found in cells from subjects taking hashish extract (which contains THC as well as cannabinol), marijuana extract (containing only THC) or synthetic THC.

C. Pregnancy and Foetal Development

Virtually every drug that has been studied for dysmorphogenic effects has been found to have them if the doses were high enough, if enough species are tested, or if the treatment is prolonged. The placenta is not a barrier to the passage of most drugs, so the assumption should be made that they will reach the foetus if taken during pregnancy.

This assumption is well validated for THC, based on auto radiographic studies. A high incidence of stunting of foetuses was seen in mice treated on day 6 of pregnancy with a single dose of 16 mg of cannabis resin per kg. No reduction in litter size or apparent malformations was seen. When the same dose was given repeatedly from days 1 to 6 of pregnancy, foetal resorption was complete. Treatment of mice from days 6 to 15 of gestation with THC doses of 5, 15, 50, and 150 mg/kg had no effect on foetal weight, prenatal mortality rate, and frequency of gross external, internal, or skeletal abnormalities. Exposure of pregnant rats to either cannabis smoke or smoke from extracted marijuana throughout the gestation produced less fertile offspring with smaller reproductive organs in cannabis treated animals.

Pregnant rabbits treated with daily doses of THC at 15 mg/kg on days 6 to 18 of gestation delivered infants without visible abnormalities.

It is still good practice in areas of ignorance, such as the effects of drugs on foetal development, to be prudent. While no definite clinical association has yet been made between cannabis use during pregnancy and foetal abnormalities, such events are likely to be rare at best and could be easily missed. The belated recognition of the harmful effects on the foetus of smoking tobacco and drinking alcoholic beverages indicates that some caution with cannabis is wise.