Effects of Δ9-Tetrahydrocannabinol on Neural Reward Anticipation Among Young Adult Cannabis Users

Background: Problematic cannabis use is associated with alterations in neural reward processing, but the direction and nature of these changes remain unclear. Prior evidence suggests cannabis exposure may relate to heightened or blunted striatal reward responses depending on severity and chronicity of use, while acute delta-9-tetrahydrocannabinol (Δ⁹-THC) intoxication may further modulate these effects, though findings are mixed. The present study explored (1) the relationship between problematic cannabis use and neural reward anticipation, (2) the effects of acute Δ⁹-THC intoxication on reward anticipation and whether problematic use moderates this relationship, and (3) associations between self-reported cannabis use metrics and neural reward anticipation under placebo (PBO) and Δ⁹-THC conditions. Methods: Young adult cannabis users (N=31) participated in a within-subjects, randomized, double-blind, placebo-controlled study. Participants completed self-report measures of cannabis use at baseline, then completed the Monetary Incentive Delay task during functional magnetic resonance imaging approximately 120 minutes after ingesting 7.5 mg oral Δ⁹-THC (dronabinol) or PBO in a crossover design. Neural reward anticipation (Win > Null) was examined in three striatal regions of interest (ROIs): the nucleus accumbens (NAcc), caudate, and putamen. Multiple linear regressions examined the relationship between problematic cannabis use and reward anticipation under the PBO condition (Aim 1). Repeated-measures analyses of covariance (RM-ANCOVAs) tested main and interactive effects of Δ⁹-THC (vs. PBO) and problematic cannabis use on reward anticipation (Aim 2). Correlations explored relationships between cannabis use frequency and recency metrics and reward anticipation (Aim 3). Results: Regarding Aim 1, regression analyses revealed a significant quadratic relationship between problematic cannabis use and reward anticipation in the caudate (β = −0.01, p = .031) and putamen (β = −0.02, p = .021), forming an inverted U-shaped pattern where activation was elevated at moderate levels of problematic use but decreased at both lower and higher levels. This quadratic effect remained robust in the putamen across sensitivity analyses. No significant linear or quadratic associations were observed in the nucleus accumbens. Regarding Aim 2, RM-ANCOVAs revealed Δ⁹-THC did not significantly relate to reward anticipation (compared to PBO) in any region (ps > .15), nor did it interact with problematic cannabis use. The quadratic effect of problematic use persisted across both drug conditions in the caudate (F = 6.29, p = .018) and putamen (F = 5.93, p = .022). For Aim 3, cannabis use frequency, recency, and urine drug screen results were not significantly correlated with neural reward anticipation in any ROI under either condition (all p-values ≥.18). Conclusions: Acute Δ⁹-THC intoxication did not significantly alter reward anticipation across striatal ROIs, nor did it interact with problematic cannabis use. Across both PBO and Δ⁹-THC sessions, the caudate and putamen displayed a quadratic relationship between problematic use and reward anticipation, with heightened activation at moderate levels of problematic use and reduced activation at higher levels. This pattern was the most robust in the putamen. Frequency-based metrics were not significantly correlated with reward anticipation in any condition. Together, results suggest that differences in reward circuitry may be more closely linked to the severity and consequences of use rather than frequency or acute intoxication alone. Findings emphasize the need to consider both individual differences and qualitative aspects of cannabis use when evaluating its impact on reward circuitry and the neurobiological underpinnings of problematic cannabis use.

Author dc:creator

• Emily Elizabeth Jones (23291575)

• Psychology
• Clinical

Statement dc:rights

• In Copyright

DOI dc:identifier

https://doi.org/10.25417/uic.31451341.v1

OAI identifier oai:identifier

oai:figshare.com:article/31451341