Monday, May 10, 2010

May 2010: Cannabinoids do not cause oxidative stress as previously thought. (Universidade do Porto; Porto, Portugal)

First some background: In order for human beings to survive, they must consume oxygen. This oxygen consumption drives the most basic of metabolic processes, allowing us to efficiently utilize carbohydrates, proteins, and fats as cellular sources of energy. The final conversion of these molecules to energy occurs within a cellular organelle known as the mitochondria. Within the mitochondria, oxygen is reduced and coupled with hydrogen to produce water, and a resulting hydrogen gradient drives the formation of ATP (cellular energy). However, this process is slightly inefficient, as some of the reduced oxygen fails to couple with hydrogen and become reactive oxygen species, such as superoxide. These reactive oxygen species may cause damage to a cell’s DNA, RNA, or proteins, but are normally converted by a series of enzymes (e.g. superoxide dismutase) into non-reactive molecules. Oxidative stress occurs when the balance between reactive species formation and conversion are disrupted, causing an accumulation of reactive oxygen species and an increase in cellular damage. Reactive oxygen species may also be formed as a byproduct of several other processes such as drug metabolism by cytochrome P450 enzymes. ∆9-Tetrahydrocannabinol (THC) has been previously reported to cause oxidative stress due to an increase in reactive oxygen species formation.1

The new information: In this experiment, mice were injected with either THC, vehicle (the contents of the THC injection without the actual THC), or nothing. The mice livers were then analyzed for the activity level of enzymes that interact with reactive oxygen species: superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, and glutathione peroxidase. Additionally, the biomarkers indicating oxidative stress in the mouse liver were lipid peroxidation, protein carbonylation, and DNA oxidation. The results showed that THC caused no change in the activity levels of all 5 enzymes and no biomarkers for oxidative stress were observed. Additionally, the vehicle actually caused an increase in glutathione peroxidase activity, indicating an increase in levels of hydroperoxides, a type of reactive oxygen species. But in the THC injection, the glutathione peroxidase activity level was normal, indicating that THC actually reduced the level of oxidative stress caused by the vehicle.

What this means: This experiment shows that THC in fact does not cause oxidative stress in the liver, and disproves several theories that have been previously presented. This goes to further dispel some of the notions that cannabinoids are more harmful than beneficial for the patient. Additionally, by opposing the increase in glutathione peroxidase activity caused by the vehicle, THC may in fact be an antioxidant in the liver as it has been shown to be in the brain.2 This indicates that cannabinoids may be beneficial in treating other liver diseases besides hepatitis C.

1Sarafian, T.A., et al. “Oxidative Stress Produced by Marijuana Smoke. An Adverse Effect Enhanced by Cannabinoids.” American Journal of Respiratory Cell and Molecular Biology. 20.6(1999): 1286-93.

2Hampson, A.J., et al. “Cannabidiol and (−)Δ9-Tetrahydrocannabinol are Neuroprotective Antioxidants.” Proceedings of the National Academy of Sciences of the United States of America. 95.14(1998): 8268-73.

Pinto, C.E., et al. “Effect of (-)-Delta(9)-Tetrahydrocannabinoid on the Hepatic Redox State of Mice.” Brazilian Journal of Medical and Biological Research. 43.4(2010): 325-9.

2 comments:

  1. This was a good blog post. K2 spice incense was helpful in some cases but if misused by someone it can be harmful.

    ReplyDelete
  2. This was good reading until I got to the "What this means" section. If you know anything about research you should know nothing is black and white. Researchers do not say "this study does in fact mean..." this is purely your interpretation. Yes study's find all kinds of different interesting results, some studies are better done than others. Next time you write what this means, just remember it means this study implies, associates, had good evidence for... then placing your opinion. Using this language is a far better way to get your point across.

    ReplyDelete