NFL-102 contains all the components present in NFL-101 but includes additional compounds derived from tobacco leaves, resulting in a broader and enriched composition. While NFL-101 is a standardized, denicotinized aqueous tobacco extract primarily designed to modulate immune and neuroinflammatory processes, NFL-102 is a nicotine-depleted tobacco protein extract developed to extend biological activity toward molecular mechanisms involved in the persistence and chronicity of nicotine addiction.

NFL-102 is designed to act on the long-lasting neurobiological adaptations that maintain vulnerability to relapse after smoking cessation. Unlike therapies that primarily modulate nicotinic receptor signaling to reduce withdrawal symptoms, NFL-102 targets downstream intracellular pathways involved in the stabilization of addictive states.

Preclinical data indicate that NFL-102 modulates key transcriptional and stress-related signaling pathways associated with maladaptive neuroplasticity, including CREB, NF-κB, and JNK. CREB is considered a central regulator of addiction-related transcriptional programs that promote synaptic remodeling and reinforcement of addictive behaviors. NF-κB contributes to the stabilization of transcriptional adaptations and neuroimmune signaling, while JNK regulates structural remodeling of neuronal circuits and stress-related plasticity.

NFL-102 has been shown to reduce the activity of these pathways in preclinical models, particularly during post-cessation phases when neuroadaptations are already established. This modulation is associated with a reduction in astroglial reactivity, as reflected by decreased markers of astrogliosis, suggesting that NFL-102 also acts on neuro-glial interactions that contribute to the rigidification of addiction-related neural circuits.

By simultaneously modulating transcriptional facilitation, cellular stress signaling, and glial activation, NFL-102 aims to restore neuronal plasticity and functional flexibility within motivational and reward circuits. Through this multi-pathway neuro-glial mechanism, NFL-102 is intended to address the biological persistence of addiction and reduce relapse vulnerability, rather than solely alleviating acute withdrawal symptoms.