The things we smoke:

Top of the list of things we smoke is tobacco in the form of cigarettes, cigars or pipe tobacco. I took up smoking these things more than 50 years ago and then, over a long weekend, took my wife and myself to the mountains, making sure that no smokers, from whom I could bum any of the above, accompany us.  I never smoked again and yet, 35 years later I developed  pains in my chest that I ascribed to a severe bronchitis.  The medical doctors, however, wanted to know; had I ever smoked? I replied that I stopped  smoking 35 years ago and they explained that this does not matter. If ever you smoked you are a cancer risk for the rest of your life.  They therefore ran a battery of tests and finally cleared me. I had, it seemed, made a lucky escape from the big C and could blame the chest pains on bronchitis.

When we smoke marijuana we inhale the same sorts of carcinogens that are contained in tobacco, along with a psychotomimetic substance, D9-tetrahydrocannabinol  (THC) and cannabidiol (CBD), just two of the most active compounds amongst a broader spectrum of about 60 cannabinoids  . While THC is psychotomimetic, CBD has antipsychotic effects. Psychotomimesis is the onset of psychotic symptoms following the administration of a drug and implies a loss of contact with reality, leading to hallucinations and delusional believes.  The severity of these effects  depends on the extent to which a smoker indulges. Excessive smoking  of marijuana can, however,  lead to lung cancer.  The dangers of smoking, of whatever kind, was highlighted in the very informative book by Siddhartha Mukherjee, The Emperor of All Maladies  and in its application to marijuana,  in a recent article by Callaghan et al entitled Marijuana use and risk of lung cancer: a 40-year cohort study (1).

The epidemiological literature in the past 20 years shows that the use of cannabis increases the risk of accidents and can result in dependence, and that there are consistent associations between regular cannabis use and poor psychosocial outcomes and mental health in adulthood. It is, however, difficult to present a reasonable argument why alcoholic beverages or the smoking of tobacco in its various forms should be legal when the detrimental effects of these are also widely acknowledged, but the smoking of marijuana is against the law.  Moreover, the world  learned much from the prohibition of alcoholic beverages in the United States during the early parts of the 20^th Century, which lead to the rise of crime syndicates. Is this where we want to go with marijuana?

The marijuana cloud, however, has a silver lining that tobacco, alcohol and other addictive drugs lack. In 1990 the cannabinoid receptor, a protein that binds THC and related compounds, was identified in rat brains.  This became  possible due to the availability of synthetic cannabinoid like compounds that were much more potent in their effects than  D9-tetrahydrocannabinol. By labeling one of the most active of these synthetic cannabinoids with tritium, it became possible to identify the cannabinoid receptors in animal brains (2).  The existence of at least two cannabinoid receptors, CB1 and CB2, are presently acknowledged, with a distinct possibility that more such receptors will be found. 

It followed logically that animals will not produce receptor proteins that specifically interact with exogenous ligands such as D9-tetrahydrocannabinol (THC). This lead to a search for the endogenous ligands that bind to these receptors and to the discovery of  an entirely new endogenous  endocannabinoid signaling system.  In its therapeutic application this system relies not only on the interaction of  endocannabinoids with the cannabinoid receptors, but also on the binding of  phytocannabinoids (i.e.plant derived) and synthetic cannabinoids to cannabinoid receptors and to an additional target,  the transient receptor potential vanilloid type 1 (TRPV1) (3).  Cannabinoids  are promising  anticancer agents through their selective killing of cancer cells and their inhibition of nausea and emesis, which are associated with chemo- or radiotherapy, appetite stimulation, pain relief, mood elevation and relief from insomnia in cancer patients. In their article entitled Cannabinoids as therapeutic agents in cancer: current status and future implications  Chakravarti and co-authors list 13 cannabinoids that have found application as therapeutic agents in various types of cancer (4).  The “runner’s high” and feeling of wellbeing which is experienced by long distance runners has also been ascribed to the production of endocannabinoids during long distance running (5).

It therefore seems as though we are on the verge of  gaining valuable insights in the multiple functions of the endocannabinoid signaling system which could have far reaching impacts  and application in medicine, and in our understanding of human and animal physiology.

(1)  Callaghan RC1, Allebeck P, Sidorchuk A (2013).  Marijuana use and risk of lung cancer: a 40-year cohort study.  Cancer Causes Control. 24, 1811 -1820. 

(2)  Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, Rice KC. Cannabinoid receptor localization in brain. (1990) Proc Natl Acad Sci U S A. 87,1932 -1936.

(3)  Zheng J1, Dai C, Steyger PS, Kim Y, Vass Z, Ren T, Nuttall AL. (2003) Vanilloid receptors in hearing: altered cochlear sensitivity by vanilloids and expression of TRPV1 in the organ of corti. J Neurophysiol. 90, 444-55.

(4) Bandana Chakravarti, Janani Ravi, and Ramesh K. Ganju (2014)

 Cannabinoids as therapeutic agents in cancer: current status and future implications .

Oncotarget 5, 5852 – 5872.

(5) Dietrich A and McDaniel WF (2004) Endocannabinoids and Exercise. British Journal of Sports Medicine 38, 536 -541.