Cannabis and the immune system

Weakening of the immune response

By “immune response” we mean the defensive capacity of lymphocytes (white blood cells) against infectious diseases, foreign protein substances and probably also against certain forms of cancer. The hypothesis that the use of cannabis damages the immune response is launched, with much journalistic clamor, by G. Nahas with the article in the New York Times in April 1973. Nahas’ technical procedure consists of injecting 5 mg. of THC three times a week for two and a half months to a group of 51 volunteers who were already smoking marijuana regularly.

Now, it is known that THC is the active ingredient, but not the only component of cannabis and that the results obtained by the active ingredients are not automatically transferable to the substance. We also know that the equivalence between water-soluble synthetic THC (which must be used for injections) and natural (insoluble, therefore not injectable) is not yet scientifically proven. On the other hand, it is not clear why Nahas, having habitual smokers of marijuana available, that is, subjects who become intoxicated with this substance using it as it is almost universally used (that is, inhaling it with smoke), felt the need to proceed in this way .

The fact is that he found a 40% decrease in the immune system; but it seems doubtful that this data could be transferred from the use of synthetic THC injected to the fact of smoking natural marijuana, as Nahas did. Nahas’  ease in drawing conclusions is, moreover, homogeneous with his singular personality, as appears from the interviews given to various newspapers, from which an extremely rooted, preconceived idea of ​​the social danger of marijuana shines through.

However, Nahas’ conclusions were confirmed the following year (October 1974) by a Sudir Gupta study in which it found that the immune response of lymphocytes of cannabis users had decreased, causing it to react in laboratory cultures with sheep’s red blood cells. Subsequently, numerous studies found a decrease in immune defenses in culture cells subjected to potent doses of marijuana. All these studies found wide echo in the Eastland committee.

The hypothesis was disproved in April 1975 by a S.C White research, who found no difference in immune response between 12 chronic marijuana smokers and a control group. The same result emerged from a study by J. Silverstein and P.J. Lessin of the UCLA university. The interesting fact of the Silverstein-Lessin study is that for the first time subjects who smoke marijuana (and not injecting THC) are analyzed, and at the same time the immune response is analyzed in individuals and not in laboratory cultures: the subjects are in fact directly tested on the immune response with different techniques. The weak point of both White and Silverstein-Lessin’s research lies in the fact that the use of cannabis amounted to 3-4 times a week, a level of use lower than what could be considered “heavy”, and to which it would be necessary to refer to, to have safety margins.

The hypothesis of weakening the immune defense was then implicitly contradicted by the research carried out in Jamaica, where the 30 consumers analyzed showed neither greater frequency of infections nor signs of physical weakness, compared to 30 controls; similar conclusions have been reached by the research carried out in Costa Rica and Greece.

In summary: a) no research has, so far, shown with certainty that the use of cannabis decreases the immune response; b) the only research that has come close to real conditions (the one cited by UCLA) has shown that the use of cannabis does not alter the immune response, but only for moderate use; c) there is therefore the doubt that a weakening of the immune response can be caused by the heavy use of cannabis; d) the health conditions enjoyed by the subjects examined in Jamaica and Costa Rica suggest that, if this hypothesis is correct, it still corresponds to a reduced percentage of chronic cannabis users.

Indeed, the NIDA report also admitted that the problem of decreased immune response remains unresolved. So far there is no evidence that marijuana users are more susceptible to diseases such as virus and cancer infections, which are notoriously associated with decreased T cell production.

Decreased testosterone level

One of the rumors that has been heard most recently about the consequences of cannabis use is that of the decrease in testosterone levels in humans. This is contradictory to the fact that one of the effects most frequently reported by consumers (as we have seen) is a more intense participation in the sexual act. In this context, there has been a study (reported in the USA) on the possibility that the use of cannabis determines gynecomastia (i.e. enlarged breasts in males). The groundlessness of this hypothesis is demonstrated by a very simple consideration: such a clear disturbance, in the context of hundreds of millions of consumers around the world, would not have needed scientific research to be revealed, if it had a minimally significant impact .

More seriously, a publication by R. Kolodny in the New England Journal of Medicine showed that the blood testosterone level of 20 marijuana smokers (10 or more cigarettes per week) was lower than that of 20 non-smoking controls ; in addition, six smokers had a lower sperm count and two complained of sexual impotence (one of whom had returned to normal after quitting marijuana). What was not established in this study was the testosterone level before marijuana use.

In response, Kolodny rounded up a group of 13 marijuana smokers, left them for two weeks without smoking and then left them for two weeks to smoke and then isolated them in the hospital for three months; after 11 days of further abstinence (from smoking), they could finally smoke marijuana in abundance. It was thus found that the testosterone level began to drop from the fourth week, and gradually decreased over the next two months. Kolodny drew the conclusions that the testosterone level dropped with some delay compared to the use of marijuana and that Mendelson’s experiment had lasted too little (21 days) to be able to find the effect of the substance.

But Koodny’s experiment also lends itself  to a dispute: Zinberg pointed out that the testosterone level increases with sexual arousal, and that Kolodny’s subjects had been subjected to complete sexual isolation for three months; lacking a non-smoking control group, the lowering of the level can be attributed simply to insulation. Moreover, Kolodny’s research was once again contradicted by a study by W.J. Coggins performed in Costa Rica on 38 subjects and 38 controls.

The subjects had smoked an average of 9.6 cigarettes per day for an average period of almost 17 years: a frequency and duration of use vastly higher than those of Kolodny subjects. Nevertheless, there was no difference between subjects and control study, nor difference between subjects and controls, nor differences between different levels of use.

Ultimately, it seems that the correlation between cannabis use and lowering the blood testosterone level has so far not found serious confirmation. On the other hand, it should be noted, as M. Brecher has pointed out, that the level of testosterone in the blood is one of the most inconstant values ​​of human physiology, and is subject to variations, and is subject to macroscopic variations from day to day without no apparent cause and above all without any sensitive effect.

According to Coggins, “transient decreases in the level of testosterone in the plasma … are not supposed to affect sexual functions, protein anabolism, secondary sexual characteristics of the adult male. These decreases should be more worrying in the adolescent male “; however, despite “the average age at which our subjects started using marijuana was 15 years, and in a 9-year case, medical tests revealed no signs that suggested a decrease in masculine characteristics in these subjects”.

The NIDA report on the same topic concludes as follows: “The question of the biological significance of changes in testosterone levels… remains in doubt. It could be that these results have a concrete meaning for subjects who already have a decrease in fertility or dysfunctions of the endocrine system, rather than for normal subjects. On the other hand, recent research has shown that heavy alcohol users can have a drop in the level of testosterone; this makes it more difficult to distinguish the effects of marijuana from those of alcohol, since both of these drugs are often used by the same people.

Long-term effects

The assessment of long-term effects concerns the consequences of prolonged use, in the order of decades: it is not only linked to the specific topics that we have discussed in the previous paragraphs, but also to the possibility that the use of cannabis may cause other damages so far ignored. In other words, it is a question of evaluating the psychophysical picture that emerges from prolonged use of cannabis. This assessment has so far been practically impossible in western countries, where the use of cannabis (at least on a mass level, and not of second-class ethnic minorities) is relatively recent; in addition, since the use, until very recently, was severely punished, consumers were difficult to reach.

In countries where cannabis use is traditional, reliable research was lacking. The report of the Anglo-Indian Commission, although undoubtedly serious, was, however, considered outdated from the point of view of research techniques. All that was known about those countries was that very heavy consumers present a picture of psychophysical deterioration similar to that of alcoholism in western countries, albeit with less somatic damage; the problem was to determine whether this deterioration was attributable to the use of cannabis or to the socio-economic conditions of consumers.

The information vacuum in this field was filled by the conference on chronic use of cannabis by the New York Academy of Science (NYAS). Regardless of the specific findings that emerged from the numerous works presented at the NYAS conference, it seems interesting to underline the fact that the studies carried out in Greece, Jamaica and Costa Rica involved a total of 158 subjects; these subjects, chosen with rigorous criteria among the population of the respective countries, were carefully examined from the medical point of view, subjected to the most updated diagnostic investigations, and compared with as many non-consumer subjects.

As a result, from the point of view of psychophysical conditions and behaviour, there is no significant difference between cannabis users and non-users. On the other hand, no data emerged, from which it can be inferred that the prolonged use of cannabis causes other types of alterations, in addition to those already hypothesized and widely debated. The research carried out in Pakistan by M.A. came to the same conclusion as the NYAS studies. Khan, A. Abbas and K. Jensen on 70 subjects (average age 44 years, with ages from 29 to 75 years) who had used cannabis for more than 20 years.

The main objection to the validity of the data that emerged from the NYAS Conference concerns neither the completeness nor the accuracy of the investigations (to give an idea, we will remember that the group of researchers who carried out the research in Jamaica worked full time to two years), but the low number of subjects studied: in all 158, of which only 118 have gone through all the analyzes.

in practice it means that certain consequences of cannabis use, if not particularly frequent, could have been overlooked by researchers. According to the NYAS Conference Report, “a cannabis-related disorder that occurs less than 20/1000 would not have been detected in these studies.”

This conference, however, showed that the long-term effects of cannabis have, at worst, a considerable safety margin (98%), and that Kaplan was not wrong when he already said in 1970: “even if all the doubts about the harmfulness of cannabis were resolved in the most unfavorable sense, they would still be less than the dangers known from the use of alcohol “.

Conclusions

One of the arguments that are most often put forward by those in favour of cannabis prohibition is that “we still don’t know enough”. From the documentation we have reported, it was precisely to start from an illegal condition, in which all the possible negative consequences were taken for granted, cannabis was subjected to a series of deeper and more extensive investigations of most of the substances. chemicals that come into contact with the human body. We can therefore agree with Zinberg that “we know about cannabis at least as much as any other substance”:

no intoxicant or any medicine or drug is totally safe and harmless. In a sense, no human activity is totally harmless. However, my opinion is that marijuana is totally harmless. However, my opinion is that marijuana only poses minimal risk to the user.

Having found that the use of cannabis cannot be considered harmless, it may be appropriate to make a realistic assessment of the limits of its harmlessness. From what we have explained, we seem to be able to say that two “areas of uncertainty” persist on the habitual use of cannabis, on which scientific research has not yet provided incontrovertible data: (1) effects on the immune response and (2) effects on testosterone level. To set the question with the utmost clarity, you need to ask yourself a few questions:

1) What is the meaning of these alterations in terms of functionality, that is, of actual consequences on the functioning and well-being of the individual?

2) What is the meaning of these alterations in terms of percentage impact on the mass of consumers?

3) What is the meaning of these alterations with respect to the level of consumption?

4) Having established the values for the three questions we have asked, how can they be assessed in comparison to other substances commonly consumed by humans?

As for the functional significance of certain biological alterations, we must not forget that they do not always (as seen in the case of testosterone level and chromosomal alterations) correspond to alterations in their biological functions.

As for the functional significance of certain biological alterations, we must not forget that they do not always (as seen in the case of testosterone level and chromosomal alterations) correspond to alterations in their biological functions.

In regards to the percentage incidence on the mass of consumers, it has been seen that it is certainly low: the studies carried out on relevant demoscopic samples of “heavy” consumers from countries where the use of cannabis is traditional and intense have in fact not detected any connectable effect with the decrease in the level of testosterone.

Regarding  the relationship between harmfulness and use level it is reasonable to assume that for cannabis as for any other substance the harmfulness is proportional to the use level, and that the possibility exists (as has been shown by Silverstein-Lessin’s research on the immune response) to establish within which levels of use the safety margins fall. In this respect, it seems to us that this should be the fundamental objective of the research, rather than to establish “In the abstract” if cannabis (or any other substance) does “good” or “bad”.

Regarding the relationship with the harmfulness of other substances, one wonders in which social hazard stage the two “areas of uncertainty” relating to the use of cannabis can be located in relation to the dramatic certainties of alcohol use (cirrhosis of the liver , cerebral atrophy, psychosis) and tobacco (pulmonary emphysema, heart attack, and probably lung cancer), which express themselves concretely in hundreds of thousands of deaths per year; and in relation to the harmful effects of pollution to which humanity is subjected in spite of itself, with no choice.

Finally, there is one last point to be clarified: the relationship between potential harmfulness and illegality. In other words, one wonders whether the potential harmfulness of a given behaviour should be considered a sufficient reason for illegality. From this point of view, the debate on cannabis is somewhat paradoxical. The supporters of the illegality had left with the aim of demonstrating that cannabis is just as dangerous as hard drugs: cannabis had to remain illegal because it is “a drug like any other”.

Since all the more drastic hypotheses on the possible damages of the substance fell one by one, it had to be agreed that cannabis was no more harmful than legal drugs such as alcohol and tobacco; Finally, evidence had to be accepted that the use of cannabis is less harmful than that of legal drugs. But this is no longer considered as a sufficient reason to abolish legal control: what is claimed today is a certainty of “absolute harmlessness”.

At this point, and accepting this logic, the position of those who are against legal control appears desperate: assuming that they manage (and it is already practically impossible) to prove “harmlessness”, how then will they be able to prevent “utility” or even “necessity” from being placed as essential conditions for obtaining legality?

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