Drug regulations and trafficking: Synthetic cannabinoids and cathinones in Hungary.

In principle, new psychoactive substances (NPSs) are produced to circumvent drug regulations. However, the mixed success of regulatory efforts suggests that the dynamics of marketing is incompletely understood. To address this issue, we conducted a comprehensive study on the marketing of all synthetic cannabinoids and cathinones present in Hungary over ten years. Market evaluation was based on drug seizure data and chemical analyses provided by the Hungarian Institute for Forensic Sciences. Over ten years, 18 synthetic cannabinoids and 11 cathinones were identified. Total seizure counts were 22,906 and 10,273, respectively. When new synthetic cannabinoids emerged, seizures increased exponentially, but rapidly declined after their banning. In parallel, new synthetic cannabinoids emerged on the market. The systematic monitoring of local legislation allowed large sales between market introduction and legal control. Cathinones were also marketed in successive waves, but trading intensity was not associated with local regulations. Sales remained low throughout, likely because the risks involved by the temporal mismatch between marketing and legal control. One can hypothesize that marketing was driven by general trends in EU regulations or by measures taken by large countries. Our findings imply the existence of two different strategies for NPS marketing. The choice between the two may depend on multiple factors from the availability of skills required by rapid marketing adjustments to cost/benefit evaluations for various market segments. Studying NPS market strategies in neighboring and distant EU countries may help analyzing and predicting market events.

Chronic Oral Selegiline Treatment Mitigates Age-Related Hearing Loss in BALB/c Mice.

Age-related hearing loss (ARHL), a sensorineural hearing loss of multifactorial origin, increases its prevalence in aging societies. Besides hearing aids and cochlear implants, there is no FDA approved efficient pharmacotherapy to either cure or prevent ARHL. We hypothesized that selegiline, an antiparkinsonian drug, could be a promising candidate for the treatment due to its complex neuroprotective, antioxidant, antiapoptotic, and dopaminergic neurotransmission enhancing effects. We monitored by repeated Auditory Brainstem Response (ABR) measurements the effect of chronic per os selegiline administration on the hearing function in BALB/c and DBA/2J mice, which strains exhibit moderate and rapid progressive high frequency hearing loss, respectively. The treatments were started at 1 month of age and lasted until almost a year and 5 months of age, respectively. In BALB/c mice, 4 mg/kg selegiline significantly mitigated the progression of ARHL at higher frequencies. Used in a wide dose range (0.15-45 mg/kg), selegiline had no effect in DBA/2J mice. Our results suggest that selegiline can partially preserve the hearing in certain forms of ARHL by alleviating its development. It might also be otoprotective in other mammals or humans.

Hearing impairment and associated morphological changes in pituitary adenylate cyclase activating polypeptide (PACAP)-deficient mice.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a regulatory and cytoprotective neuropeptide, its deficiency implies accelerated aging in mice. It is present in the auditory system having antiapoptotic effects. Expression of Ca2+-binding proteins and its PAC1 receptor differs in the inner ear of PACAP-deficient (KO) and wild-type (WT) mice. Our aim was to elucidate the functional role of PACAP in the auditory system. Auditory brainstem response (ABR) tests found higher hearing thresholds in KO mice at click and low frequency burst stimuli. Hearing impairment at higher frequencies showed as reduced ABR wave amplitudes and latencies in KO animals. Increase in neuronal activity, demonstrated by c-Fos immunolabeling, was lower in KO mice after noise exposure in the ventral and dorsal cochlear nuclei. Noise induced neuronal activation was similar in further relay nuclei of the auditory pathway of WT and KO mice. Based on the similar inflammatory and angiogenic protein profile data from cochlear duct lysates, neither inflammation nor disturbed angiogenesis, as potential pathological components in sensorineural hearing losses, seem to be involved in the pathomechanism of the presented functional and morphological changes in PACAP KO mice. The hearing impairment is probably concomitant with the markedly accelerated aging processes in these animals.