Tuesday, February 9, 2010

Marijuana Protective Against Alzheimers - Null Result

The wider community is typically unaware of the positive aspects emerging from cannabinoid research. The headline that reports this science news is an example of why that occurs, a matter I will address later in this post. For now I'll focus on this piece of research and other research into the medical use of cannabinoids.

In this research they used a very potent cannabinoid analogue, HU-210, which has previously been shown to induce neurogenesis in the hippocampus of rats. That research, and a host of other literature on cannabinoids, have clearly pointed to the potential of cannabinoids to protect neurons and proffer potential in treating a wide range of neuropathic conditions. It is important to keep in mind that HU-210 is a very potent stimulator of the CB1 receptor. This receptor is mainly found in the brain and its distribution varies across the CNS and peripheral nervous system. Its mode of action can be described as a retrograde inhibitory neurotransmitter. Current understanding indicates that when a neuron fires, particularly in response to  dopamine, the post synaptic cell which receives the signal will release endogenous cannabinoids, the two principle endogenous cannabinoids our bodies produce are 2-AG and anandamide(a Hindu word meaning "bliss"). These cannabinoids then travel back across the synapse and prevent calcium release in that cell, thereby lowering its synaptic potential and probability of generating another signal. Research has indicated that in epilepsy the mode of neuron death is induced by excitotoxicity, which causes excessive calcium release that can kill neurons. This has led to considerable research into using CB1 agonists in the treatment of epilepsy.

There is a potentially serious problem with this approach and that is that long term use of cannabinoids can induce a loss of CB1 receptors, thereby largely mitigating clinical efficacy. There is even research indicating that tolerance to the psychoactive effects of cannabinoids is a direct function of loss of CB 1 receptors. This data, and other data indicating changes in seconder messenger intra-cellular molecules like cAMP and PKA, should give any chronic heavy use of marijuana cause for concern. Typically it doesn't but I advise anyone who uses marijuana on a regular basis to have wash out periods at regular intervals.Marijuana should be used for recreational purposes not as a lifestyle. Generally speaking the latter use is associated with other issues but I have encountered a number of people who use marijuana on a daily basis and are doing very well. In Intoxication: The Universal Drive for Mind Altering Substances, the author argues that intoxication is very much like a primary driver of behavior. Perhaps that is because as the philosopher John Gray argues in "Straw Dogs: Thoughts on Humans and Other Animals",


Drug use is a tacit admission of a forbidden truth. For most people happiness is beyond reach. Fulfillment is found not in daily life but in escaping from it. Since happiness is unavailable, the mass of mankind seeks pleasure."

Perhaps that is true but I doubt it. Intoxication is just plain fun. Must we really continue to psychoanalyse and demonise behaviors just because culture says so? Unfortunately many do and in that regard psychology has a lot to answer for. The big problem with too much of psychology is that the so called theories make it all too easy to proclaim psychopathology in individuals who are not behaving in "acceptable ways". For example, I have been labeled in the following ways by people who have read too much psychology and have not learned how to think:

Dissassocative Disorder(probably some truth to that)
Lacking self esteem
Too arrogant
Too lazy
Too smart for his own good
Intellectually gifted
Intellectually impaired
biologic depression

The principle difference between psychology as it is popularly perceived and astrology is that we know the latter is a fantasy. It has been my consistent experience that mental health practitioners are far more reticent in their proclamations of psychopathology than the general public. Hollywood has a lot to answer for! Anyway, I digress, which does suggest a hint of ADHD or perhaps I just hate the habit of people who have read a little psychology but not enough to realise the enormity of the task in understanding behavior.

The news item that prompted this post had this headline: Marijuana Ineffective as Alzheimer's Treatment. This is a complete misrepresentation of the research. In fact in the very same journal where this research was subject to advance publication there are many articles highlighting the potential for cannabinoid based therapies including neuropathologies. This headline is misleading because:

  • They did not use marijuana, they used a potent cannabinoid analogue created in a lab. It is much more powerful in THC and binds the CB1 receptor for longer periods.
  • The data clearly indicates that the preferred target for cannabinoid based therapies should generally be the CB2 receptor. Neither THC or HU-210 has any known effective affinity for the CB2 receptor. This receptor is found mainly in immune cells, including microglia. CB2 activation can markedly impact on the inflammatory response and over time may induce immunosuppresssion, another important reason that chronic smokers should have wash out periods.
  • The study is based on an animal model of Alzheimer's. These models have great utility but to extrapolate from an animal model to a proclamation that marijuana cannot be used in treating Alzheimer's is not only bridge too far but there isn't even any bridge to cross.
Now I will address the problem of how scientific research is reported in the media. Many years ago I created a little heuristic to address this problem:

  1. Reports by the Mainstream Media are generally parlous, simplistic, and inaccurate.
  2. "Bookworld Logic". Popular publications on science related issues vary greatly in their quality and accuracy. As a general rule, rely on writing done by those doing the relevant research but there are a few very high quality science writers(egs: George Johnson, Phillip Ball, John Gribbin) who do present accurate, warts and all, accounts of the current research and its implications. 
  3. The Textbook View. Good introduction to the topics but tend to avoid the major conceptual and data problems. Excellent starting point - obviously!
  4. Peer Reviewed Review articles. Very good way to become quickly accounted with the current state of cutting edge research. Best read when one has also been reading the relevant primary research material. 
  5. The Primary Research. Very difficult. Reading this material takes a lot of hard work and discipline. Once you've crossed that bridge though you don't have to worry about the bridge falling down.
This research does not indicate a negative result. It indicates that the researchers tried a particular compound and found it wanting. To argue that it even suggests that marijuana compounds have no efficacy in treating Alzheimer's is propaganda and I wouldn't be at all surprised is the researchers thought the headline was a misleading representation of their research. The lead researcher states at the end of the article:

"More studies should be done before we place much hope in marijuana's benefits for Alzheimer's patients."
He does not say that this research is the end of the matter, he does not dismiss the potential of cannabinoids in treating Alzheimers, what he does say is that we need to do more research before we consider cannabinoids as a therapeutic option in treating Alzheimer's. Such a qualified remark has no place in headlines. Hence this headline is an excellent example of parlous, simplistic, and inaccurate accounts of scientific research.

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