Dear Chairs and Members of the Committee on Mental Health and Substance Abuse, Honorable Senate and House of Representatives of the Commonwealth of Massachusetts,

I appreciate the opportunity to add my written testimony in support of the petition for bill No. 3594, An Act relative to benzodiazepines and non-benzodiazepine hypnotics.

I am a tenured professor with a solid record of publication and funding. I am regarded as an expert in intracellular calcium signaling and the control of neurosecretory activity. My research program straddles basic and translational science and uses cell-based models, animal models and human subjects to address questions relevant to biological function in health and disease.

I am not a physician nor am I engaged in the treatment of patients. My comments will be limited to a discussion of the relevance of the scientific findings of our published work that used animal or cell line model systems to elucidate a potential mechanism of action of benzodiazepine-induced withdrawal.

Despite controversy regarding their use, their potential off target effects and appropriate cessation of treatment, benzodiazepines are established as a widely prescribed and inexpensive medication used to treat anxiety, seizure disorders, panic attacks, and insomnia and include medications such as diazepam (Valium), alprazolam (Xanax) and temazepam (Restoril). Their use is particularly wide spread in long-term care settings.

In collaboration with colleagues at the University of Toledo we published two basic science research studies that investigated the mechanisms by which benzodiazepines contribute to changes in brain function and physical dependence [1, 2]. These studies demonstrated that benzodiazepines had unexpected, complicated effects on a class of key neuronal ion channels called voltage-activated calcium channels. Depending on the mode of their administration, treatment with benzodiazepines such as diazepam or flurazepam could inhibit or potentiate the function of calcium channels. A major finding of these studies was that benzodiazepines at clinically relevant doses enhanced calcium ion entry into neurons through voltage dependent calcium channels and contributed to changes in neurotransmitter receptor content and excitability in a region of the brain that is critical for memory formation, hyperexcitability and withdrawal-anxiety. Importantly, enhanced calcium entry into neurons was implicated in the activation of diverse biochemical pathways to increase neuronal excitability during benzodiazepine withdrawal.

Because calcium is a central and ubiquitous signal that regulates neuronal excitability, plasticity and toxicity, altered calcium channel balance may also serve as a general mechanism relevant to the debilitating side effects reported by some patients following benzodiazepine treatment.

Given the implication of the potential, wide spread off target effects induced by this class of psychotropic drugs, the protocols for informed consent, educational information, establishment of use and discontinuation protocols outlined in H.3594 are reasonable and prudent. As a concerned citizen and scientist I support the passage of Bill H.3594.

David Giovannucci, Ph.D., Professor of Neurosciences,
University of Toledo College of Medicine, Toledo OH.


  1. Earl, D.E. and E.I. Tietz, Inhibition of recombinant L-type voltage-gated calcium channels by positive

    allosteric modulators of GABAA receptors. J Pharmacol Exp Ther, 2011. 337(1): p. 301-11.

  2. Xiang, K., et al., Chronic benzodiazepine administration potentiates high voltage-activated calcium currents in hippocampal CA1 neurons. J Pharmacol Exp Ther, 2008. 327(3): p. 872-83.