Altered parahippocampal functioning in cannabis users is related to the frequency of use

Converging lines of evidence suggest an association between cannabis use and impaired episodic memory as well as related associative learning. These deficits have been associated with the duration, frequency, and age of onset of cannabis use. However, it remains unclear whether these parameters of use differently impact memory-related hippocampal functioning. Forty-two cannabis users were examined by means of functional magnetic resonance imaging while they encoded and retrieved face-profession associations. Region of interest analysis was subsequently used to compare (para-)hippocampal functioning in users with (1) a longer and shorter duration of use, (2) a higher and lower frequency of use, and (3) an earlier and later onset. To further separate the effects of these parameters of use on performance and (para-)hippocampal activity, linear regression analysis was applied. Compared to low-frequency users, high-frequency users displayed stronger blood oxygenation level-dependent response during encoding in the left parahippocampal gyrus. No differences were obvious for the groups separated according to duration of use or an earlier and later onset of use. Linear regression analysis confirmed the association between a higher frequency of use and increased activity in the left parahippocampal gyrus. Our findings suggest that the frequency of use might have a particular critical impact on intact parahippocampal functioning in cannabis users. Increased activity within the encoding-related network might reflect functional compensation to maintain cognitive functioning.