2004 IRISH SCIENTIST YEAR BOOK

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Trinity College Dublin
Eric Downer & Veronica Campbell
Cannabis kills immature brain cells

The active ingredient of the cannabis plant, THC, activates cell death molecules in the brain of neonatal rats. The degree of fluorescence indicates the activation of cell death molecules

Cannabis has been used for recreational and medicinal purposes for many centuries. The recreational appeal of the drug is based on its ability to induce euphoric effects, while anecdotal evidence suggests that the drug may be beneficial in the treatment of chronic pain and multiple sclerosis. However, chronic use of cannabis is also associated with deleterious effects, such as memory impairment, hallucinations, and an increased risk of developing schizophrenia in susceptible individuals.

The mind-altering effects of the cannabis plant depend on the activities of a substance called Tetrahydrocannabinol (THC), an ingredient distributed throughout the cannabis plant (see figure). THC activates a cannabinoid receptor on the surface of the brain cell, which in turn triggers a biochemical cascade within the cell. Our research has identified a deleterious biochemical pathway that becomes activated by THC in the neonatal brain. The damaging effects depend on the induction of a linear cascade of cell death molecules (see figure) within the cell following the interaction of THC with the cannabinoid receptor. The pathway culminates in the fragmentation of the DNA within the brain cell nucleus, the terminal event in cell death.

Studies have shown that in utero exposure to cannabis can affect neuronal development, resulting in learning deficits in offspring. In support of this, we have also found that the damaging effects of THC on the rat brain are reliant on age, with the neonatal rat brain being particularly susceptible to the damaging effects of THC. Interestingly, this neurotoxic pathway is absent in the adult rat brain, suggesting that the maturity of the brain may determine the ability of cannabis to damage the neuronal tissue.

Overall our findings suggest that damaging effects of cannabis exist and may be operative during development by disrupting the orderly sequence of neuronal maturation. Thus, while cannabis may have therapeutic value, our results lend a cautionary note to the field, suggesting that prenatal exposure to cannabis may interfere with normal brain development and may account for some of the neuronal deficits that are found in children exposed to cannabis during pregnancy.

Contact: Eric Downer and Dr Veronica Campbell, Trinity College Institute of Neuroscience,
Department of Physiology, Trinity College, Dublin 2;
E-mail: [email protected] , [email protected]