This is Your Brain on Drugs: A Call for Caution on Cannabis Use and Brain Health

In early 1987, the Partnership for a Drug-Free America (PDFA) developed several televised public service announcements (PSAs) specifically targeting teens and adolescence and the potential negative health effects of illicit drug use. “This is your brain on drugs: any questions?” became a well-known iconic meme for the eighty’s generation’s war on drugs.¹ Much of the political and social landscape has changed since 1987, particularly in terms of acceptance, decriminalization, and state-specific legalization of cannabis, medicinally and then recreationally. In parallel, our understanding of the pharmacological effects on tetrahydrocannabinol (THC) and cannabidiol (CBD) has also evolved. However, relative to the rapid expansion in cannabis use, the scientific knowledge in its health effects has been stunted, as cannabis remains a schedule 1 controlled substance. This has limited investigators’ from conducting prospective clinical studies, particularly for second generation cannabis products. Instead, signals about the safety and efficacy of cannabis has been limited to retrospective observational studies and animal models. These data provide important insights into the health effects of cannabis, and they suggest a variety of neurological effects.

In this clinical science statement from the American Heart Association (AHA), Testai et al provide a robust evaluation of the current science to date on cannabis use and brain health.² Based on their summary of the evidence, several key points emerge. First, as THC disrupts the endocannabinoid signaling pathways, animal data suggest exposure during adolescence can potentially lead to functional alternations of brain which may negatively impact cognition. Just as smoking tobacco during pregnancy can have potential fetal harms, maternal cannabis use during pregnancy was also associated with various adverse mental and neurocognitive effects in children that manifest later in youth at ages 9 to 10. From a public health standpoint, these data fully support strict state policies that cannabis—similar to nicotine, tobacco, and alcoholic products—should not be sold to minors and not be used during pregnancy.

Second, acute cannabis use is associated with impairment of working and episodic memory, impulsivity, and behavioral disinhibition, with potential long-term cognitive effects in chronic use. These findings have significant public health implications, including driving under the influence. In 2007, the National Highway Traffic Safety Administration found that 8.6% of weekend nighttime drivers tested positive for THC (based on the combined oral fluid and/or blood tests), whereas in the 2013–2014, this had increased to 12.6%, a 48% increase.³ Testing for drug impairment is problematic due to the limitations of drug-detecting technology and the lack of an agreed-upon limit to determine impairment. While the nationally recognized level of impairment for drunken driving is 0.08 g/mL blood alcohol concentration, no similar national standard for THC and CBD exists.

Finally, several studies have demonstrated an association between cannabis and stroke, particularly among young adults. This risk may potentially be increased or even confounded with concomitant cigarette smoking. In a cross-sectional analysis using the 2014–2015 nationwide Veterans Affairs Healthcare database and the Veterans with Premature AtheroscLerosis (VITAL) registry, Mahtta et al found that polysubstance use with recreational substances such as cannabis, tobacco, alcohol, cocaine, and amphetamines was strongly associated with premature atherosclerotic cardiovascular disease (ASCVD) risk.³ When used recreationally by itself, cannabis was associated with more than a 2.5 fold increased risk of ASCVD (adjusted odds ratio (OR): 2.65, 95% confidence interval (CI): 2.59 to 2.71) and more than a five-fold increased risk in women (Adjusted OR: 5.52, 95% CI: 4.13-7.37). Not surprisingly, a statistically significant graded increase in ASCVD risk occurred as the number of substances used increased from one (adjusted OR: 2.05, 95% CI: 2.02-2.08) to greater than four (adjusted OR: 8.85, 95% CI: 8.63-9.08).⁴

Several important queries do remain. First, does the dose or chronicity of cannabis use impact long-term brain plasticity and health, particularly among adolescents and young adults? Second, since many of the studies evaluated included first generation cannabis products, would the same findings still hold true with second generation high-potency THC and CBD products? Finally, does cannabis use qualify as a new risk factor for stroke and ASCVD? Meanwhile, the safety signals highlighted by this AHA statement warrant close attention by health care professionals and public health stakeholders. As highlighted by the authors, perhaps it is time to re-implement the old 1980’s PSAs directed at teens and adolescents, this time through social media and modified from “any questions” to “many questions” still exist.