ABSTRACT
Introduction: Interest in the therapeutic use of cannabidiol (CBD) has reached a fever-pitch in recent months, as CBD-containing products appear everywhere from online retailers to grocery stores and gas stations. The widespread availability of hemp-derived CBD products is confounding given that CBD is a U.S. Food and Drug Administration (FDA)-approved drug, and thus precluded from being added to food and beverages, or included in dietary supplements. The use by manufacturers of disease-related claims on marketing materials and product labels, along with the federal legalization of hemp in December 2018, has created political pressure on FDA to promulgate regulations. Conclusions: Accurate and informative labeling of hemp and hemp-derived CBD products is an important public health issue. FDA-regulated product labels are considered an essential tool for protecting consumers and enabling informed decision-making. Untruthful or unsubstantiated health-related claims, and unallowed Drug Claims, in marketing materials and on labels of CBD products may create harm by enticing consumers to forgo more evidence-based medical interventions. Furthermore, missing or inaccurate labeling of the amount of CBD, delta-9 tetrahydrocannabinol (THC), and potentially harmful contaminants such as pesticides, naturally-occurring yeast and mold or heavy metals may result in harm and/or lack of efficacy. Manufacturers of these products may reasonably be expected to understand and adhere to FDA regulations for labeling and marketing of food, dietary supplements and drugs, both over-the-counter (OTC) and prescription, even though FDA has interpreted federal law as excluding them from these categories. As manufacturers prepare for forthcoming regulations, a better understanding of the basic framework for FDA labeling and marketing regulations for food, dietary supplements and drugs is warranted.
ABSTRACT
The occurrence of intrinsic oscillations (IOs) in a unit's discharge is reflected by a prominent peak in the power spectrum (i.e., Fourier transform of the autocorrelation function) of spike trains obtained from single-unit discharge, at a frequency independent of stimulus spectral characteristics. IOs have been reported by researchers in the dorsal cochlear nucleus (DCN) of both the cat and the Mongolian gerbil. It has been hypothesized that IOs are related to inter-spike interval (ISI) regularity (e.g., [Hear. Res. 58 (1992) 153]). This hypothesis is tested in this paper. Responses to multiple presentations of 50-300 ms duration tone bursts, at and near the unit's best frequency (BF) at 20-60 dB re threshold were recorded from DCN units of barbiturate-anesthetized (30 units), as well as decerebrate (53 units) Mongolian gerbils. IOs in the recordings were then compared with the IOs in simulations of spiking-neuron models. The models were selected because: (1) their ISI regularity characteristics follow those of experimental data and (2) their IO properties are completely determined by their ISI regularity. Such comparison reveals that Ghoshal's hypothesis fails for a fraction of the units. These results suggest a re-evaluation of the purported relationship between IOs, ISI regularity, and SAM response. Alternate hypotheses are proposed here using computational models that are based on convergence of multiple neural inputs onto the unit under study. These models produce non-renewal statistics that resemble those of the experimental data, as is evident from IO-based analysis.
