Interaction of Cannabis Use and Aging: From Molecule to Mind
Given the aging Baby Boomer generation, changes in cannabis legislation, and the growing acknowledgment of cannabis for its therapeutic potential, it is predicted that cannabis use in the older population will escalate. It is, therefore, important to determine the interaction between the effects of cannabis and aging. The aim of this report is to describe the link between cannabis use and the aging brain. Our review of the literature found few and inconsistent empirical studies that directly address the impact of cannabis use on the aging brain.
However, research focused on long-term cannabis use points toward cumulative effects on multimodal systems in the brain that are similarly affected during aging. Specifically, the effects of cannabis and aging converge on overlapping networks in the endocannabinoid, opioid, and dopamine systems that may affect functional decline, particularly in the hippocampus and prefrontal cortex, which are critical areas for memory and executive functioning.
To conclude, despite the limited current knowledge on the potential interactive effects between cannabis and aging, evidence from the literature suggests that cannabis and aging effects are concurrently present across several neurotransmitter systems. There is a great need for future research to directly test the interactions between cannabis and aging.
Prevalence of cannabis use in older populations
Cannabis is one of the most commonly abused substances in the United States (Substance Abuse and Mental Health Services Administration, 2016), with increasing prevalence of use due to legalization and decreasing perception of harm. Between 2002 and 2014, cannabis use among adolescents remained fairly constant, while use among adults over the age of 18 years increased consistently.
The National Survey on Drug Use and Health showed that between 2003 and 2014, the rate of past-year cannabis use rose from 2.95% to 9.08% among the 50- to 64-year-old age group and from 0.15% to 2.04% among those older than 65 years (Substance Abuse and Mental Health Services Administration. This indicates a liberalization of cannabis use in the current older-adult population, referred to as the Baby Boomer generation. In this report, we define “older adults” as individuals 50 years or older. Based on the trend of decreased perceived harm from cannabis use among older adults, the prevalence of medicinal and recreational cannabis use is expected to keep increasing.
Similar to other age groups, cannabis use is also associated with vulnerability toward comorbid neuropsychiatric and substance use disorders in older adults. Wu and Blazer posit that substance use disorder has become one of the most common psychiatric conditions found in this population. The prevalence of cannabis use disorder is rising in the general population, which increased to 2 from 1.5% in 2001–2002. The number of older users affected by cannabis use disorder appears to increase with the rate of cannabis use in older adults. For example, cannabis abuse and dependence based on Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria have increased from 0.4% to 1.3% in middle-aged to older adults (45–64 years) and 0.1% to 0.3% in those older than 65 years from 2001–2002 to 2012–2013. noted that the increase in cannabis use in older adults is attributable to both medicinal and recreational uses that are difficult to distinguish, and found that older adults are currently more accepting of the use of medicinal cannabis.
Of the older cannabis using population, the peak age of first onset of use is 18–20, suggesting that potential effects in this population are predominantly from chronic or long-term use. This implies that despite the general changes in the perception of cannabis use, the cumulative effect of more than 30 years of regular cannabis use may be predominant in current older adults, compared to that of older adults who report a relatively recent onset of use. This indicates the need to determine the effects of long-term cannabis use on aging. Considering the trend of increasing cannabis use in older adults, it is essential to provide a prospective insight into the interaction between cannabis use and the aging process.
Cannabis mechanisms
The primary psychoactive ingredient in cannabis is delta-9-tetrahydrocannabinol (THC). Of the cannabinoids, THC is most widely associated with the negative effects of cannabis, such as increased anxiety, psychotic symptoms, increased impulsivity, loss of learning capability, motor control, and substance use disorder. More recently, there is growing recognition that THC also provides therapeutic benefits that include neuroprotection against oxidative stress and from the accumulation of amyloid-β peptides related to Alzheimer’s disease. THC acts as a partial agonist at two known endocannabinoid system receptors, cannabinoid receptors 1 and 2, and is a comparable affinity analog of the endogenous agonists anandamide (AEA) and 2-arachidonyl glycerol.
Although its biochemical affinity is lower, THC also acts on the opioid system as an allosteric modulator. Thus, cannabis use directly modulates both the endocannabinoid and opioid systems. THC also indirectly modulates multiple other neurotransmitter systems, such as dopamine, serotonin, acetylcholine, and norepinephrine, which may be due to CB1Rs being one of the most common G-protein-coupled receptors in the brain (Lovinger & Mathur, 2016). Endocannabinoids regulate the activity of the aforementioned neurotransmitters in the neocortex, limbic regions, basal ganglia, and cerebellum, which are disrupted by exogenous cannabinoids such as THC.
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