451. Investigating synaptic density in youth with cannabis use: preliminary findings from a [18F]SynVesT-1 PET imaging study

Abstract

Abstract Background Adolescence is a key period for neurodevelopment, marked by synaptic pruning. Preclinical studies show that repeated cannabinoid exposure can alter synaptic structure and synaptic protein markers (Oliva et al., 2024; Rubino et al., 2015). In adults, chronic cannabis use has been linked to lower synaptic density, but it remains unclear if this is seen in youth (D’Souza et al., 2020). Aims & Objectives Here, we investigate if regular cannabis exposure in youth is related to lower synaptic density in the brain compared to those with low use, leveraging Positron Emission Tomography (PET) imaging with the radiopharmaceutical [18F]SynVesT-1. We also aim to explore the relationship between cannabis use severity, use frequency, and synaptic density. Method A preliminary sample of healthy individuals aged 16-26 from the community were recruited to complete a PET scan with the radiopharmaceutical [18F]SynVesT-1. Magnetic Resonance Imaging (MRI) scans of each participant was used to delineate six corticolimbic regions of interest (ROIs). Time-activity curves were fitted using a simplified reference tissue model (SRTM-2) with the centrum semiovale (CS) as the reference region. Non-displaceable binding potential (BPnd) were compared between individuals. Timeline Followback for the last 90 days (TLFB-90) was used to delineate low (<1x/week) and regular (≥1x/week) cannabis use (Gabrys & Porath, 2019). Use severity was assessed using the Cannabis Use Disorder Identification Test (CUDIT), and use patterns were assessed with the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU). Results Twenty-five individuals (15M, 10F, 21.9 years) completed imaging scans. In total, nine reported regular use of cannabis, having used 69 ± 19.6 days out of 90 days. Sixteen individuals reported low use of cannabis, with approximately 3 ± 4.2 days of use. Regular cannabis users showed significantly earlier initiation patterns compared to those with low use, indicated by a higher DFAQ-CU age of onset composite z-score (Regular: z=-0.08 ± 1.1; low: z=-2.8 ± 1.1; p<0.001). Of the regular users, four of the nine met threshold for hazardous use, and two met criteria for potential cannabis use disorder based on CUDIT score (mean: 9.9 ± 4.8). There was no significant difference in [18F]SynVesT-1 tracer binding between low and regular cannabis users in all ROIs. There was also no difference seen in those who had CUDIT scores at or above threshold for hazardous use. Finally, there were no correlations with CUDIT score (ρ=-0.021 to ρ=-0.273) or TLFB score (ρ=-0.064 to ρ=-0.273) with synaptic density (p>0.05). Discussion & Conclusions Our pilot findings do not support a difference in synaptic density in youth that use cannabis regularly compared to those who do not. This contrasts reports of significant decreases in synaptic density in those with cannabis use disorder, suggesting that lower synaptic density may be related to more chronic, long-term use of cannabis. This may also suggest that pre-existing differences may occur in individuals with cannabis use disorder, thereby increasing vulnerability. The lack of differences observed may also be related to the small sample size; thus, future work will continue to assess differences in synaptic density in healthy youth with cannabis use.