Harrison, Lana D., Michael Backenheimer and James A. Inciardi (1995), Cannabis use in the United States: Implications for policy. In: Peter Cohen & Arjan Sas (Eds)(1996), Cannabisbeleid in Duitsland, Frankrijk en de Verenigde Staten. Amsterdam, Centrum voor Drugsonderzoek, Universiteit van Amsterdam. pp. 198-205.
© Copyright 1995, 1996 Centrum voor Drugsonderzoek, Universiteit van Amsterdam. All rights reserved.

2  Pharmacology and health

• Pharmacology
• Health issues
  • Smoking
  • Motor performance
  • Driving
  • Cancer
  • Tolerance and dependence
  • Effects on fetal development
  • Additional concerns
• References

Pharmacology

The isomer most experts believe responsible for the effects of marijuana[1] is Delta-9 Tetrahydrocannabinol (THC). This isomer is a viscous, noncrystalline, water-insoluble, but highly fat soluble compound. Reported behavioral effects of marijuana must be interpreted with caution due to differences in dose, route of administration, social and cultural setting, and the experience and psychological set of the user. Critically, as is true with tobacco, the amount of active substance reaching the blood stream is dependent, in very large measure, upon the smoking technique being employed and the amount of substance destroyed or decomposed by the high temperature associated with the smoking.

According to current research, it is estimated that a marijuana cigarette when smoked with maximum efficiency will deliver no more than 50 percent of the Delta-9 THC within it. Put another way, when smoked in the cited fashion, only 50 percent of the Delta-9 THC will be absorbed into the lungs. The pharmacological effects of marijuana begin almost immediately after smoking begins, often within minutes, and blood plasma levels of Delta-9 THC peak approximately 20 minutes after ingestion (Schuckit, 1995, p. 90). With oral administration (by mouth as opposed to smoking), onset of effects is delayed, usually occurring thirty to sixty minutes later. Peak effects are also delayed, often occurring in the second or third hour after administration. These effects have been shown to correlate well with plasma concentrations. When taken orally, the effects of marijuana may linger up to 5 hours.

Marijuana is rapidly metabolized. The Delta-9 THC is converted into an inactive metabolite which is excreted in urine and feces. Peak plasma levels at first drop quickly (half-time of minutes), followed by a much slower phase (half-time of days). This slower phase is the body gradually metabolizing and eliminating the Delta-9 THC from the body. Traces of the substance exist for several days in human plasma and (from animal studies) also in the fat and brain after a single administration. Methodologies now exist that can detect the urinary metabolites of marijuana several days after the smoking of only a single marijuana cigarette. Marijuana metabolites were detected in urine in one study of heavy marijuana users 27 days after cessation of marijuana use.

There is thus little question that the technology exists to detect marijuana use days after such use has ceased. The ability to attribute importance to blood or urine concentrations of THC or its metabolites and associate this with impaired functioning is a more difficult task. Setting a blood or urine concentration level in the same fashion that blood alcohol levels (BALs) are set and associating this level with impairment is difficult, the major problem being the variability among subjects. This difficulty is further exacerbated by the fact that marijuana is very often used in combination with other substances, most frequently alcohol. Thus the issue and role of drug combinations has to be considered. Even with the cited detection technology, a positive test result stands to mean only that the subject was exposed to marijuana at some point in the recent past.

Health issues

One of the major concerns surrounding marijuana use are its effects on health. The scientific evidence is weak however, and findings from various studies sometime contradict others. A large portion of the research that has been performed, often for ethical reasons, has used animal rather than human models and there is no warranty that such models transfer automatically to humans. Nevertheless, the findings from marijuana research on animal models do pose questions of health concern.

Importantly, the authors are impressed by the literature on health effects that differentiates between 'chronic use,' 'regular use,' 'occasional use' and 'low dose' and 'high dose.' We believe it critical to be clear on these distinctions. The significant dimensions of the model, in our estimation, is 'What kinds of individuals (demographics) smoke what doses of marijuana in what quantity under what circumstances for what purposes with what results (behavioral, health and psychological effects)?' This said, however, there are some generalities which can and should be stated about the physical effects of marijuana and its potential health consequences.

Smoking

To begin with, smoking is almost the exclusive route by which marijuana is used (administered) in the United States. This is of concern because of potential bronchopulmonary effects. This question persists and grows because, when smoked, marijuana is deeply inhaled, and the smoke is kept in the lungs longer than tobacco smoke. It should also be noted that many of the toxic elements found in tobacco are found in marijuana. Marijuana smoke also has more irritants than tobacco smoke. The research is also clear in showing that there are more cancer-causing agents in marijuana smoke than in cigarette smoke. A recent study of marijuana smokers enrolled in a Health Maintenance Organization in California reached the conclusion that smoking marijuana on a daily basis gives evidence of being associated with respiratory conditions even among those who smoke marijuana but not tobacco (Journal of the American Medical Association, 1991, p. 2796). Smoking anything is probably bad for the lungs (Polen et al. 1993, pp. 596-601; Voelker, 1994, p. 1647). The health consequences of such damage may well be significant and are worthy of closer scrutiny. Recent research supports the possibility of serious potential damage to pulmonary function particularly among marijuana users classified as 'chronic.' It has been estimated that, because of the method of smoking, one marijuana cigarette (joint) is as harmful to the lungs as four tobacco cigarettes (Kleiman, 1992). It can thus, at a minimum, be said that the smoking of marijuana is not good for the lungs and may well pose significant health hazards to them (Tashkin and Cohen, 1988).

Motor performance

There is almost universal agreement that a prominent danger of marijuana is its effect on motor performance. Preclinical, clinical and even actual driving tests under the influence of marijuana support an impairment of motor performance. Reaction time, judgment, and the use of peripheral vision are negatively influenced in the two to three hour period following acute intoxication. Some negative effects may be clinically relevant for 24 hours after the acute intoxication (Harris and Martin, 1991, p. 136). In the 'real' world these risks and dangers are often compounded by the fact that marijuana is very commonly smoked in association with the use of alcohol thus dramatically increasing the potential 'harm' that could arise from the episode. With this in mind, a brief look at marijuana and its relationship to driving may be instructive.

Driving

In 1993 there were 53,343 drivers involved in fatal crashes in the United States. Of this number only 18.9% were tested for drugs excluding alcohol (Schuckit, 1995, pp. 90-91). Typically, fatal crashes are reviewed to determine whether or not alcohol is involved, not whether marijuana is involved. The National Highway Traffic Safety Administration (NHTSA) studied 1,882 fatally injured drivers from 13 sampling sites located in three entire states and selected counties of four additional states (NHTSA, 1993). Alcohol was found in 52% of the fatalities but another drug without alcohol was determined in only 6.3% of the fatalities. Marijuana was implicated in 6.7% of all fatalities. It was implicated alone in 1.1% of the cases, in combination with alcohol in 5.1% of the cases and with some other substance in 0.5% of the cases. While the figures for marijuana are quite small, nonetheless, the most frequently used illicit drug in these fatal crashes was marijuana. Further, the data indicate the greater number of drugs a driver takes, the greater the risk thus pointing to the hazard potential of marijuana when used in combination with other substances.

The NHTSA has conducted research to determine the extent to which marijuana impairs driver performance (NHTSA, 1993). Three studies were conducted. In the first study, marijuana was found to significantly impair a driver's ability to keep a constant lateral position within a traffic lane. The higher the marijuana dose, the greater the degree of impairment. Comparisons with alcohol studies showed the marijuana impairment on performance to be that produced by BALs between .03 and .07. (The legal BAL limit for intoxication in most states is .10.) Marijuana was not found to influence the ability to maintain constant speed.

In study two, conducted under primary highway conditions in the presence of other traffic, driving performance measures included changes in lateral position in a traffic lane, average speed, and an estimate of headway maintenance ability for a car following task. Ability to maintain a steady lateral position within a driving lane was (as in study 1) impaired with the exception of low doses where no significant impairment was noted. Marijuana had minimal effect on speed maintenance and car following ability, with the exception of low dose which produced more cautious behavior (as measured by an increase in the distance being maintained between vehicles).

Study 3 was a 40 minute drive through urban traffic only under low dose conditions. A standard rating scale was used to give an overall driving performance assessment. No effect was found between the low dose marijuana condition and driving performance in urban traffic (however, low dose alcohol did impair performance as related to vehicle handling and traffic maneuvers).

Although the three studies imply that marijuana use produces impaired driving abilities that are less in some situations than in others, no implication should be made that marijuana is safe with respect to driving. No crash data were included and many of the driving situations were somewhat artificial. It should also be noted that (some) subjects may have felt the effects of the marijuana and compensated by increasing their level of attention and concentration.

A 1988 NHTSA report to the Congress noted that virtually all classes of psychoactive drugs (with the exception of amphetamines) have been found in laboratory studies and on-the-road research to impair driving ability (NHTSA, 1994, pp. 1-2). After alcohol, marijuana is the drug most frequently associated with driving impairment. In Ontario, Canada a 1985 study of 1169 fatally injured drivers tested for the presence of marijuana and/or alcohol (NHTSA, 1988). Marijuana was found alone in 1.7% of the cases and marijuana in combination with alcohol was found in 9% of the cases. Alcohol alone was present in 57% of the cases.

Another study relates to driving skills though it deals with marijuana effects on pilot performance (Journal of the American Medical Association, 1991, p. 2796). Separately, nine active pilots each smoked a 20 mg. THC cigarette and a placebo cigarette. By use of a flight simulator, each pilot 'flew' before smoking and at five intervals from 15 minutes to 48 hours after smoking. Marijuana was found to impair performance up to 24 hours after smoking (at which time 7 of the 9 pilots showed some degree of impairment). The complexities of human-motor performance do not lend themselves to marijuana smoking.

Cancer

While no totally definitive scientific evidence exists that marijuana causes cancer, there is considerable data that gives cause for concern. Further, several research studies have shown a definite association between smoking marijuana and the development of cancer. One study investigated 110 private patients with lung cancer with 13 of the patients being under age 45 (Sridhar et al., 1994). Of the total sample 19 (17%) had smoked marijuana at some point in their life. Noteworthy is that all 13 patients under the age of 45 had smoked marijuana and 12 reported current tobacco smoking. No tobacco only patients under age 45 were noted. Dr. Paul J. Donald of the University of California Davis found that nine of eleven young people treated for advanced head and neck cancers had a background of smoking marijuana and five of these had never used tobacco in any form (Donald, no date). While the cited evidence is not conclusive and is only associational in nature, it does beg further consideration and examination of the health consequences of marijuana smoking.

Tolerance and dependence

Recent research on tolerance and dependence with respect to marijuana is quite sparse. From earlier efforts, however, it would appear that tolerance to marijuana is not an issue, particularly (as is true in the vast majority of cases), if doses are small and use nonchronic. Supporting this position is the relatively few reports of medical problems from cessation of use. In the general population, 0.7% reported needing, or feeling dependent on marijuana in the past year (data from the 1992 National Household Survey on Drug Abuse). Among those who report using marijuana in the past 30 days, 15% said they felt dependent or that they 'needed' marijuana. However, fully 27.2% of past month marijuana users reported using marijuana daily (SAMHSA, 1993).

Effects on fetal development

All systematic work in this area has obviously been conducted within the confines of animal studies and those data do not necessarily apply to humans. Nevertheless, the results including some studies involving human observation do support a position confirming the potential harmfulness of marijuana upon the fetus if used during pregnancy (Zuckerman, 1988). Other animal research has found 'pronounced effects of THC on reproductive hormones and on ovulation and spermatogenesis' (Schuckit, 1995, p. 91). While not universally confirmed in clinical research upon chronic human marijuana smokers, the data suggest caution is dictated with respect to marijuana use and fetal development (Zuckerman, 1988). Obviously, more research is needed in this area.

Additional concerns

One question often raised is the effect marijuana may have (or not have) upon the human immune system. Research to date is at the animal level. Most of the work that shows immunosuppression has been done by in vitro studies and have been compromised by the high amounts of cannabinoids used (Hollister, 1988, p.7). No evidence exists at this time to conclusively support the hypothesis that 'consumption of cannabinoids predisposed humans to immune dysfuntion. However, and in particular with respect to AIDS and those infected with HIV, the question remains of critical importance and the best advice of leading experts (see medicalization section) is to avoid the use of marijuana.

Research shows that marijuana usually produces an increase in heart rate (not an insignificant issue to those who may have preexisting heart conditions or disease). Of equal or greater concern is the research finding that marijuana produces a significant increase in carbon monoxide content 'with resulting production of an altered form of the red pigment in red blood cells necessary for transporting oxygen to the rest of the body, including the heart' (Schuckit, 1995, p. 91). However, no conclusive evidence exists that would implicate marijuana to cardiac problems.

Although marijuana use has not been found to be causally predictive of criminal involvement or violent behavior, one study found that of 268 individuals imprisoned in New York State prisons for homicide, marijuana had played a major part in their lives. Some 86% had used the drug at some point in their lives and approximately 33% said they had used it on the day they committed homicide. Of this 33%, about 70% said they were experiencing some drug effect at the time of the homicide. Eighteen respondents (7% of the total sample) said the homicide was related to their marijuana use (Spunt et al., 1994). While no claim is made that marijuana caused the homicides, the association between the two is sufficient to warrant further investigation.

Another concern is that the use of marijuana by adolescents might prove harmful particularly with respect to motivation and emotional and psychosocial development. The difficulty and ethics of doing controlled research studies upon this important age group make such work most difficult and nearly impossible. Marijuana is known (often at small dose levels), however, to impair memory function, distort perception, impede judgment, and reduce motor skills. Such effects are most often likely to manifest their negative consequences upon the young. Research in clinical settings has also noted loss of motivation, difficulty in concentration, apathy and decline in school performance as being associated with the smoking of marijuana.

Notes

1. In the U.S., the vast majority of cannabis use is marijuana and not hashish. The terms marijuana and cannabis are used interchangeably in this report.
   

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References

DONALD, PAUL J. No Date. (University of California, Davis) as cited by Wayne J. Roques, U.S. Drug Enforcement Administration.

DONELSON, A.C., G. CIMBURA, R.C. BENNETT, AND D. M. LUCAS. 1985. The Ontario Monitoring Project: Cannabis and Alcohol Use Among Drivers and Pedestrians Fatally Injured in Motor Vehicle Accidents from March 1982 Through July 1984. Final Report From The Traffic Injury Research Foundation of Canada. Ottawa: The Traffic Injury Research Foundation of Canada, January, 1985.

HARRIS, LOUIS S. AND WILLIAM MARTIN. 1991. 'Marijuana and the Cannabinoids,' in Alcohol, Drug Abuse and Mental Health Administration Drug Abuse and Drug Abuse Research. Rockville, MD: U.S. Department of Health and Human Services.

HOLLISTER, LEO E. 1988. 'Marijuana and Immunity.' Journal of Psychoactive Drugs 20:1 (Jan-Mar. 1988), p. 7.

JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION. 1991. 'Marijuana Carry-Over Effects on Aircraft Pilot Performance.' Journal of the American Medical Association V265:21, June 5, 1991.

KLEIMAN, MARK. 1992. Against Excess. New York: Basic Books.

NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION. 1988. Use of Controlled Substances and Highway Safety: A Report to Congress. Washington, D.C.: U.S. Department of Transportation.

NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION. 1993. Data from the Fatal Accident Reporting System. Washington, D.C.: National Highway Traffic Safety Administration, U.S. Department of Transportation.

NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION. 1994. 'Marijuana Effects on Actual Driving Performance,' Traffic Tech. (62) Washington, D.C.: U.S. Department of Transportation, February, 1994.

POLEN, MICHAEL R., STEPHEN SIDNEY, IRENE S. TEKAWA, MARIANNE SADLER, AND GARY D. FRIEDMAN. 1993. 'Health Care Use by Frequent Marijuana Smokers Who Do Not Smoke Tobacco.' The Western Journal of Medicine 158:6, pp. 596-601.

SCHUCKIT, MARC A. 1995. 'Are There Dangers to Marijuana?' in James A. Inciardi and K. McElrath (eds), The American Drug Scene. Los Angeles: Roxbury Publishing Co.

SPUNT, BARRY, PAUL GOLDSTEIN, HENRY BROWNSTEIN AND MICHAEL FENDRICH. 1994. 'The Role of Marijuana in Homicide.' The International Journal of the Addictions 29:2, pp. 195-213.

SRIDHAR, KASI S., WILLIAM A. RAUB, JR., NORMAN L. WEATHERBY, LISA R. METSCH, HILARY L. SURRATT, JAMES A. INCIARDI, ROBERT C. DUNCAN, ROBERT S. ANWYL, AND CLYDE B. MCCOY. 1994. 'Possible Role of Marijuana Smoking as a Carcinogen in the Development of Lung Cancer at a Young Age.' Journal of Psychoactive Drugs 26:3, pp. 285-288.

SUBSTANCE ABUSE AND MENTAL HEALTH SERVICES ADMINISTRATION. 1993. National Household Survey on Drug Abuse: Main Findings 1992. Rockville, MD: U.S. Department of Health and Human Services.

TASHKIN, DONALD P. AND S. COHEN. 1988. 'Marijuana Smoking Worse for Lungs.' Journal of the American Medical Association 259:23, p. 3384 and The American Council on Marijuana and Other Psychoactive Drugs, Inc. 1981. Marijuana Smoking and Its Effects on the Lungs. Rockville, MD.

VOELKER, REBECCA. 1994. 'Medical Marijuana: A Trial of Science and Politics,' Journal of the American Medical Association 271:21.

ZUCKERMAN, BARRY. 1988. 'Marijuana and Cigarette smoking During Pregnancy: Neonatal Effects,' in Ira J. Chasnoff (ed.) Drugs, Alcohol, Pregnancy, and Parenting. Hingham, MA: Kluwer Academic Publishers.

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