Cognitive Indolence Caused by THC in Rats

In a new study published in the Journal of Psychiatry and Neuroscience, researchers at University of British Columbia in Vancouver explored the connection between marijuana use and neural mechanisms involved in cognitive processing. Wider availability, increased acceptance, and a decrease in the perceived risk of marijuana, all have an important impact on public health and safety.¹

Cannabis use disorder (CUD) is currently the most widely reported illegal substance use disorder (SUD), and approximately 30% of users exhibit signs of marijuana abuse or dependence. Marijuana use is associated with development of various neuropsychiatric conditions such as schizophrenia, anxiety, and depression. It was recently reported that multiple common genetic variants, or single nucleotide polymorphisms (SNPs), explain between 13% and 20% of the risk of lifetime cannabis use.  

In the current study, investigators have examined the acute impact of Δ9-Tetrahydrocannabinol (THC) administration on cognitive function in male Long-Evans rats, mainly willingness to exert cognitive effort for greater rewards, and whether cannabidiol (CBD) administration could potentially attenuate any of the observed performance or cognitive (ie, decision-making) deficits due to THC administration. 

They used a previously validated task [rodent cognitive effort task (rCET)] to assess the impact of THC and CBD in isolation, as well as co-administration of THC and CBD, on rats’ choice behavior (ie, the choice of 2 options differing in reward magnitude), and on cognitive effort required to obtain those rewards.

Data show that THC, the main psychoactive ingredient in cannabis, does not impair the rats’ ability to perform or complete cognitively demanding tasks, but that it does affect the decision-making process when rats are presented with a choice of either low-effort/low-reward (LR) or high-effort/high-reward (HR) task. 

More specifically, following systemic administration of THC, rats showed significantly higher preference for the LR task over the HR task. In other words, the rats exhibited a choice shift toward the task that required less cognitive effort to complete. Rats did not show impairments, however, with regard to the accuracy on HR trials following THC administration.

“Strikingly, the magnitude of this effect [THC-induced decrease in the choice of HR trials] was correlated with CB1 receptor density in the mPFC [medial prefrontal cortex] area encompassing prelimbic and anterior cingulate cortices (ACC) – areas previously implicated in task performance,” researchers noted.

On the other hand, the administration of CBD did not affect any behavioral measures, including rats’ choice between the 2 options that differed in reward magnitude. When CBD and THC were co-administered, “THC-induced laziness” was only modestly attenuated in a subset of rats.

“Together, these data implicate the cannabinoid system in decision-making regarding the allocation of cognitive effort, but not necessarily in the performance of such cognitively demanding processes…. and, unlike THC, CBD does not adversely affect executive function, and as such its inclusion in medicinal cannabis is not of primary concern,” the authors concluded.

Reference

1. Silveira MM, Adams WK, Morena M, et al. Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats. J Psychiatry Neurosci. 2016;41(6):150363.

This article originally appeared on Psychiatry Advisor