Friday, November 29, 2013

THC and Painkillers: A recipe for symptom relief without memory loss

With laws being passed in Colorado recently to make the personal use of marijuana legal, it made me think about uses for symptom relief for conditions such as glaucoma, cancer, and multiple sclerosis. The active ingredient, THC, is what helps to provide this major benefit for those suffering from chronic pain, weight loss, and other symptoms. Recently, however, THC has been shown to be involved in memory disturbance that some patients report while using medical marijuana. For some patients, the symptoms of memory loss can be more difficult to manage than the symptoms of their condition (2). It was previously thought that marijuana worked to relieve symptoms through inhibiting the COX-2 pathway, which is the same way that painkillers such as aspirin and ibuprofen work to decrease pain (2). However, recent research using mice has found that this is not that case and rather addition of pain killers to use of medical marijuana may actually decrease the memory disturbance experienced by these patients.

A study published in the science journal Cell this month investigated the mechanism of THC and found that it surprisingly works to increase the activity of the COX-2 pathway (1). Repeated exposure to this increase in the products of this pathway were shown to be involved in decreases in long-term synaptic plasticity, the mechanism for formation and recall of memories. When mice being given THC were also treated with a COX-2 inhibitor, memory impairments were either significantly reduced or removed entirely (1). Although this study is preliminary and the topic definitely requires more research, the ability to relieve the disabling side-effects associated with medical marijuana may help improve quality of life for many patients. Additionally, the researchers suggest that this could provide relief for non-medical abusers of marijuana (1). With the new law going into effect, this research may help bolster support for the safe, legal, and beneficial use of marijuana.

References

1. Chen R, Zhiang J, Fan N, Teng Z, Wu Y, Yang H, Tang Y, Sun H, Song Y, Chen C. 2013 Nov. D9-THC-Caused synaptic and memory impairments are mediated through COX-2 Signaling. Cell. 155: 1154-1165.

2. Painkillers may curb memory loss from medical marijuana. Science Magazine. http://news.sciencemag.org/brain-behavior/2013/11/painkillers-may-curb-memory-loss-medical-marijuana

5 comments:

  1. Kelsey,

    The results of these studies caught my eye. I have a few questions hopefully you can answer. I'm sorry in advance, I have quite a few questions, because I find this to be very interesting!!
    When the researchers found that THC increased the COX-2 pathway products, were prostaglandins, thromboxanes, and prostacyclins all increased or did they find one in particular that was increased? Further, did they mention how these products impair memory? Since these products are involved in the inflammatory response, I would assume it has to do something with inflammation or signal transduction. Lastly, we learned that some painkillers can caused GI problems with prolonged use. I do not know anything about this, but I feel that people using medical marijuana might use the marijuana long-term, so did the article address whether the COX-2 inhibitors would have to be taken long term as well? If this were the case, I feel that GI problems as a side effect would have to be considered when using a COX-2 inhibitor. As with all medicine, one step forward may lead to one step back, and this side effect will definitely have to be weighed against the positive of improved memory impairment.

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  3. Kelsey,

    I find this interesting as I worked in a psychiatric hospital during the summers while I was attending college. While working, I witnessed cannabis used as a treatment for weight issues. The hospital had a patient that suffered from a mental illness and convinced himself it was not good to eat consequently, he lost a significant amount of weight. Physicians attempted everything to get this patient to eat and gain weight with no luck. The only treatment that seemed to increase this patients appetite was cannabis. But, more interesting, was that his mental cognition seemed to improve with cannabis. I would be curious to know if they gave him any NSAIDS with it or if he was just malnourished and that is why his cognition seemed to be better after food consumption.

    Also, I found an article that mentioned instead of THC, that cannabidiolic acid (CBDA), was suggested as a COX-2 inhibitor (1). I will have to do more research to determine if this cannabidolic acid is only in certain forms of the cannabis; if CBDA was only in certain forms of cannabis, maybe those forms of cannabis would not require a supplement of NSAID? Very great blog!

    1. Drug Metab Dispos. 2008 Sep;36(9):1917-21. doi: 10.1124/dmd.108.020909. Epub 2008 Jun 12.

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  4. Jamie,
    Great questions! I am very glad that you found the blog post interesting. According to the paper, the researchers specifically mention an increase in the level of prostaglandin E2, which is what they targeted with the COX-2 inhibitor. Since the products of the COX-2 pathway are pro-inflammatory agents, which creates a toxic environment for the neuron's synaptic structure and plasticity thus preventing the occurrence of long-term potentiation. In terms of your last question, I would agree that there is a potential for secondary health risks related to long term use of an anti-inflammatory agent. However, this research is fairly new and has not yet been studied in humans so I believe that is yet to be determined specifically in the case of marijuana use. I feel that maybe a smaller dose, like baby aspirin, may still provide some of the benefit of a COX-2 inhibitor without a significant increase in the risk for secondary complications like bleeding risks.

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  5. Emily,
    That is great to hear a practical application of this type of research! In the paper, the researchers do mention exogenous versus endogenous forms of THC. Previous research that found that THC was a COX-2 inhibitor used an endogenous form whereas this research used an exogenous form and found opposite results of upregulation. Endogenous cannabinoids have been more studied because they are involved in typical cellular processes in addition to pathological and pharmacological. I could definitely imagine that different forms of cannabis may have different effects based on molecular make-up!

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