Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals. Whether these findings translate to humans has not yet been investigated. Here we believe we conducted the first study to compare the acute effects of cannabis in human adolescent (n=20; 16–17 years old) and adult (n=20; 24–28 years old) male cannabis users, in a placebo-controlled, double-blind cross-over design. After inhaling vaporized active or placebo cannabis, participants completed tasks assessing spatial working memory, episodic memory and response inhibition, alongside measures of blood pressure and heart rate, psychotomimetic symptoms and subjective drug effects (for example, ‘stoned', ‘want to have cannabis'). Results showed that on active cannabis, adolescents felt less stoned and reported fewer psychotomimetic symptoms than adults. Further, adults but not adolescents were more anxious and less alert during the active cannabis session (both pre- and post-drug administration). Following cannabis, cognitive impairment (reaction time on spatial working memory and prose recall following a delay) was greater in adults than adolescents. By contrast, cannabis impaired response inhibition accuracy in adolescents but not in adults. Moreover, following drug administration, the adolescents did not show satiety; instead they wanted more cannabis regardless of whether they had taken active or placebo cannabis, while the opposite was seen for adults. These contrasting profiles of adolescent resilience (blunted subjective, memory, physiological and psychotomimetic effects) and vulnerability (lack of satiety, impaired inhibitory processes) show some degree of translation from preclinical findings, and may contribute to escalated cannabis use by human adolescents.

Episodic memory declines with older age, but it is unresolved whether this decline reflects reduced probability of successfully retrieving information from memory, or decreased precision of the retrieved information. Here, we used continuous measures of episodic memory retrieval in combination with computational modelling of participants' retrieval errors to distinguish between these two potential accounts of age-related memory deficits. In three experiments, young and older participants encoded stimulus displays consisting of everyday objects varying along different perceptual features (e.g., location, colour and orientation) in a circular space. At test, participants recreated the features of studied objects using a continuous response dial. Across all three experiments, we observed significant agerelated declines in the precision of episodic memory retrieval, whereas significant age differences in retrieval success were limited to the most challenging task condition. Reductions in mnemonic precision were evident across different object features retained in long-term memory, and persisted after controlling for age-related decreases in the fidelity of perception and working memory. The findings highlight impoverished precision of memory representations as one factor contributing to age-related episodic memory loss, and suggest that the cognitive and neural changes associated with older age may differentially affect distinct aspects of episodic retrieval.

Episodic memory declines with older age, but it is unresolved whether this decline reflects reduced probability of successfully retrieving information from memory, or decreased precision of the retrieved information. Here, we used continuous measures of episodic memory retrieval in combination with computational modelling of participants' retrieval errors to distinguish between these two potential accounts of age-related memory deficits. In three experiments, young and older participants encoded stimuli displays consisting of everyday objects varying along different perceptual features (e.g., location, colour and orientation) in a circular space. At test, participants recreated the features of studied objects using a continuous response dial. Across all three experiments, we observed age-related declines in the precision of episodic memory retrieval, whereas age differences in retrieval success were limited to the most challenging task condition. Reductions in mnemonic precision were evident for retrieval of both item-based and contextual information, and persisted after controlling for age-related decreases in the fidelity of perception and working memory. The findings highlight impoverished precision of memory representations as one factor contributing to age-related episodic memory loss, and suggest that the cognitive and neural changes associated with older age can differentially affect distinct aspects of episodic retrieval.

Introduction: Lifestyle interventions may prevent cognitive decline, but the sufficient dose of intervention activities and lifestyle changes is unknown. We investigated how intervention adherence affects cognition in the FINGER trial (pre-specified subgroup analyses).