Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males

Abstract

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.

Heavy cannabis use, dependence and the brain: a clinical perspective

“…Craving is stronger in more severe users and has been found to predict CUD problem severity , treatment outcome and withdrawal severity in heavy users. Craving generally decreases during intoxication , but adolescents may be less prone to these satiation‐induced decreases in craving .…”

Commentary on Meier et al. (2018): Smoke and mirrors—are adolescent cannabis users vulnerable to cognitive impairment?

“…Placebo‐controlled studies can also complement observational methods, allowing assessment of causal effects of cannabis exposure in different age groups. Indeed, we recently showed contrasting patterns of acute cannabis effects in adolescent and adult cannabis users . Specifically, adolescents experienced blunted intoxication and memory effects of cannabis, offering preliminary evidence that adolescents may be resilient to some acute effects of cannabis.…”

Time to acknowledge the mixed effects of cannabis on health: a summary and critical review of the NASEM 2017 report on the health effects of cannabis and cannabinoids

“…For example, even though human research is still in its infancy, experimental studies indicate preliminary evidence that cannabidiol may protect against the negative effects of delta‐9‐tetrahydrocannabinol (∆9‐THC) on cognition , psychotic symptoms and anxiety . Interestingly, a recent within‐subject placebo‐controlled study in human adolescents and adults showed preliminary evidence for both adolescent resilience (blunted subjective, memory, physiological and psychotomimetic effects) and vulnerability (lack of satiety and impaired inhibition) to the direct effect of cannabis (12% THC, < 1% cannabidiol) . Moreover, a study investigating psychophysical effects in frequent and occasional cannabis users following placebo, smoked, vaporized and oral THC administration showed preliminary evidence for an interaction between use history and route of administration, such that impairments were more prolonged following an oral dose, specifically in occasional cannabis users .…”