Re: How are free radicals produced?

Date: Wed Apr 5 12:31:35 2000
Posted By: Lyle Burgoon, Grad student, Pharmacology and Toxicology, College of Human Medicine, Michigan State University
Area of science: Biochemistry
ID: 954460940.Bc

Message:

Thank you for your question. It's a very interesting question, and brings us into the realm of the hotly debated/contested marijuana battle. I'm going to avoid comment on the social aspects of marijuana, and the like. Instead I'm going to focus totally on the medical/scientific aspects as they relate to marijuana use, cannabinoids, and associated items.

I’ll start off by just saying that we still don’t totally understand the safety of marijuana usage. This is mainly due to the fact that when one smokes marijuana they are exposing themselves to a whole laundry list of drugs. The most famous (or infamous depending on your stance) of these is THC (delta-9-tetrahydrocannabinol) – it’s the psychoactive component of marijuana. Other compounds that the smoker is exposing themselves to includes:

· Carbon monoxide
· Carbon dioxide
· Cannabidiol
· Cannabinoidiol
· Others…

All in all, there about 61 different cannabinoids that have been identified in the smoke of burning cannabis (1). Research is ongoing on the effects of these chemicals on the human body.

As far as we know, smoking marijuana does not in and of itself increase the overall levels of free radicals. Whether or not metabolism of some of the chemicals in marijuana will cause a local increase in free radical concentrations in areas of the brain is unknown.

So what do we know? We know that there are some forms of the cannabinoids that do in fact have a “neuroprotective” effect (2). What that means in more or less layman’s terms is that some of these cannabinoid compounds have been shown to act as antioxidants – sponges for free radical oxygen species (ROS). I’m not going to go into the mechanism of this, per se, but if you are interested in this, the paper that talks about this is:

A. J. Hampson, M. Grimaldi, J. Axelrod, and D. Wink. Cannabidiol and ( ) 9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci. Vol. 95, Issue 14, 8268-8273, July 7, 1998.

Depending on your level of education this paper may be a bit much for you, but if you need help with it, you might seek help from your chemistry teacher/prof.

Now keep in mind, that little tasty-tidbit I gave you there was concerning brain. The story with lung and the respiratory system seems to be a bit different. Researchers at the UCLA School of Medicine have published work last year that states that there is in fact an increase in oxidative stress in their respiratory system model – endothelial cells – when they are exposed to marijuana smoke. This work is backed up by research indicating that glutathione levels in alveolar macrophages from marijuana smokers is lower than glutathione taken from control (non-smoking) human subjects. This decrease in glutathione can be attributed to oxidative stress. In this research the researchers are attributing the increase in the oxygen radicals to THC – I’ve not been able to read the whole paper and come up with a decision for myself, so I’ll only go so far as to say that they’ve seen this, but I’ve not seen any replicated results of this, and am a bit skeptical until I see some replication. But nonetheless, we do see an increase in reactive oxygen species, and that is a substantial find – not a surprising one, but a substantial one, nonetheless.

Is marijuana safe? Let me put it this way – given the information in the literature I’d have to say that the risk assessment for marijuana is that it by itself is probably about as bad as alcohol or cigarettes are by themselves. However, this safety margin goes down as you start adding other drugs to the mix. The more drugs you are doing, the greater the chances of an interaction. Given the information in the literature, and the information that some of my colleagues who are studying cannabis derived compounds tell me, cannabis derived chemicals are not as nice and harmless as people want you to think (of course, neither is alcohol or nicotine). But, there is some information out there on the cannabinoids that are really interesting – like cannabinoids and cannabinol interacting with proteins that regulate gene expression, pulmonary edema, decreases in immune function, and the list goes on.

When you are taking in over 61 chemicals, there’s going to be some rather interesting interactions between those and any other drugs you might be taking. Remember what drugs are, too – any chemical that changes the way the body functions. Drugs are found in food – vitamins are drugs! Various chemicals that we expose ourselves to everyday can interact with some of our drugs of choice, and make them more or less effective, more or less toxic! So, until the research is done on the cannabis products (which won’t be for a really, really, really long time), and we know the whole story of what’s going on in the bodies of people who smoke it, not only at the whole person level, but also the cellular and protein/molecular level, I’m going to suggest that people steer clear of marijuana smoking, unless of course they like to take a lot of unknown risk.

I know I didn’t answer your exact question, but I hope this at least helped to answer your question in some small way. Again, thanks for your question – it gave me an excuse to go take a walk in the gardens to see my colleagues who work on this stuff! :0)

Lyle D. Burgoon
Graduate Assistant
Department of Pharmacology and Toxicology
College of Human Medicine
National Food Safety and Toxicology Center
Michigan State University

References:

1. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics. Ninth Edition. 1996.

2. A. J. Hampson, M. Grimaldi, J. Axelrod, and D. Wink. Cannabidiol and ( ) 9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci. Vol. 95, Issue 14, 8268-8273, July 7, 1998 http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&uid=9653176Dopt= r

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