There has been a great deal of discussion about the optimal age for allowing the non-medical purchase and use of cannabis. While 21 y/o is the age cut-off utilized in all U.S. states to date, Canadian provinces require an individual to be 18 or 19 y/o to access legal cannabis. Citing concerns of continued brain maturation until 25 y/o, some have suggested this latter age has as the optimal age cut-off for allowing access to legal cannabis. 

‍Brain Development: The vast majority of macrostructural and microstructural brain development occurs during the first few years of life (Leisman et al., 2015). Approximately 25% of brain development occurs prior to birth, 75% by 2 y/o, and 90% by 5 y/o. Sensory development is nearly complete by 6 y/o and language processes by 6 y/o. There are more subtle changes, particularly in the prefrontal cortex (regulating functions such impulse control and emotional regulation), that continue throughout adolescence (until 18 y/o to 21 y/o). Based in large part on these new neuroscience findings, in 2004 the Supreme Court ruled that individuals under the age of 18 y/o at the time of their crime could not be sentenced to death. Notably, the Court did not use a cut-off of 21 y/o. A decay in many cognitive functions, such as processing speed, working memory, long-term memory, and vocabulary begins in the early 20s, suggesting a reversal in brain maturation soon after adolescence. On the other hand, some processes (e.g., general knowledge) continue to improve until 70 y/o (Leisman et al., 2015). 

Sophisticated measures of macrostructural, microstructural, synaptic, and gene expression show variable changes over the lifetime, particularly during the first 30 years of life. Prefrontal inhibitory synapses increase dramatically from 15 y/o to approximately 21 y/o, with more subtle increases persisting past 25 y/o. In contrast, prefrontal excitatory synapses begin to markedly decrease at 5 y/o and then stabilize around 18 y/o (Insel, 2010). The magnitude and timing of changes in microstructural maturation, including major white matter tracts, deep gray matter, and subcortical white matter, is quite variable depending on the brain region assessed; developmental plateaus can be observed from 5 y/o to 30+ y/o (Lebel et al., 2008). Dendritic spine density in the prefrontal cortex during childhood exceeds adult values by two to threefold and begins to decrease from 5-10 y/o (depending on the cortical layer) (Petanjek et al., 2011). Myelinated fiber length density (MFLD), which increase the speed at which electrical impulses (known as action potentials) propagate along the myelinated fiber in nerve cells, increases rapidly during the first few years of life, stays relatively stable from 10 to 20 years of age, and then again increases in the early 20s for at least another several years (28+ y/o) (Miller et al., 2012). Between the ages of 10-30 y/o, subcortical brain development (as measured by MRI) either increases, decreases, or remains generally unchanged depending on the specific region assessed (Olsen, 2019). Changes in cerebral gray and white matter volume increase dramatically during the first few years of life, with more gradual increases in white matter volume until approximately age 20-25 y/o and gradual decreases in gray matter volume (Groeschel et al., 2010). White matter connectivity, as measured by fractional anisotropy, also varies by region assessed, although peak connectivity generally occurs around 20 y/o (Khundrakpam et al., 2016). Gradual changes in both frontal, parietal, temporal, and occipital gray matter volume and EEG slow-wave power are in individuals from 10 to 30 y/o, with no clearly identifiable age of inflection (Whitford et al., 2007). Using whole genome microarrays to measure gene expression in post mortem prefrontal cortex tissue from human individuals ranging in age from 0 to 49 years showed a peak expression in from 15-25 y/o (depending on the gene) (Harris et al., 2009).

To our read of the literature and after consultation with experts in this area, we can identify no clear demarcation of 25 y/o as the age when brain maturation is complete. Rather, the age of “maturation” is highly dependent on the specific brain region, sex, and structural/physiological/genetic process being assessed. Many processes are relatively mature within a few months or years after birth; others continue until at least 30 y/o. Those who suggest 25 y/o as the age of brain maturation have not provided citations supporting this claim.

Although speculative, the source of the 25 y/o brain maturation claim may have arisen from the work of Petanjek et al. (Petanjek et al., 2011) This group demonstrated that “synaptic pruning” continues beyond adolescence and throughout the third decade of life before stabilizing at the adult level. Synapses are the small pockets of space between neurons where messages (neurotransmitters) are communicated. There is an overproduction of synapses during the early years of life. The process of pruning, whereby synapses are remodeled and eliminated, begins in earnest during puberty. Petanjek et al. found that this process continues through the third decade of life. However, according to their 2011 publication, there does not appear to be an inflection point around 25 y/o at which synaptic pruning appears to cease. 

Another possibility is that this claim may have arisen from the work of Harris et al. (Harris et al., 2009). These investigators were interested in brain changes that occur during adolescence and may increase the risk of schizophrenia. The risk of schizophrenia onset increases between the ages of 15 to 25 y/o. Thus, these investigators assessed gene expression of processes involved in synaptic changes; specifically, the pruning (removal) of synapses that normally continues throughout adolescence. Because of these authors’ interest in risk factors for schizophrenia, they considered the ages of 15-to-25 as a single group. They then reported that there were changes in gene expression that occurred during the period 15-25 y/o. This may have been interpreted by some as meaning that these changes occurred until the age of 25 y/o. In fact, if they had considered 15-20 y/o and 20-25 y/o they may have found that it was the 15-20 y/o group that was driving the increase, not the 20-25 y/o

Brain Development vs. Higher Level Cognitive Processing: Clinicians practicing evidence-based medicine must distinguish between disease-oriented evidence (DOE) and patient-oriented evidence (POE). The presence of biochemical, structural, genotypic, or physiological changes in the brain (DOE) does not necessarily imply that these changes are associated with clinically relevant differences in behavior, cognition, or emotional regulation (POE). So the question of whether biological brain maturation continues to “develop” is not the most important question to be asking – or answering.

Traditionally, the legal age of majority (the threshold of legal adulthood as recognized or declared in law, at which a person is considered sufficiently able to manage these adult activities) in the U.S. has been 21 y/o – based upon British common law. The age of majority is set at a point where society believes individuals are sufficiently mature and capable of making important life decisions independently. It is designed to protect minors from entering into contracts or engaging in activities that they might not fully understand or be emotionally ready for. It is only recently that brain maturation, as determined by neuroscience, has been utilized for this determination. And, with the exception of the Supreme Court ruling noted above regarding the death penalty, it has not been taken into account when determining the age of majority for other potentially risky behaviors, whether it be engaging in sex, driving automobiles, skydiving, entering into contracts, or using dangerous substances. 

Thus, determining the age of cannabis use by brain maturation rather than legal precedent, behavior, emotional maturity, and sociocultural norms would go against available scientific evidence.

‍Potential long-term toxicity of cannabis in individuals older than 18 y/o is not supported by empirical evidence: There is some evidence that cannabis may have long-term effects when heavily used by individuals younger than 18 y/o, although there remains a significant literature that argues this point. To our knowledge, there is no evidence that points to a long-term toxic effect of cannabis in those older than 18 y/o. Thus, the rationale that cannabis may result in significant neurophysiological, behavioral, or clinical effects in individuals older than 18 y/o is not supported by empirical evidence.

The harms of cannabis prohibition are outweighed by the benefits of legalization: It is not necessary to demonstrate that cannabis has no potential risks upon any individual to allow its use. Many potentially risky behaviors/activities are legal despite carrying some risks (e.g., driving a car, the use of most medications, alcohol/tobacco use, hang gliding). The question is not whether a behavior carries any risks, but whether the benefits outweigh the risks to the individual or society. A vast majority of individuals in the U.S. (a majority of both political parties) now support the legalization of cannabis, having judged that the harms of cannabis prohibition outweigh the risks of cannabis legalization. The highest rates of cannabis use are in individuals between 18 y/o and 25 y/o, with a significant drop-off in use after age 25 y/o. To set a minimum age of 25 y/o for the legal adult use of cannabis would be meaningless from a public health perspective, as most users would remain at risk of arrest and be denied access to regulated cannabis.

‍Conclusions: Based upon practical, neurophysiological, medical, and scientific considerations, there is a convincing rationale for limiting cannabis use to those 18 y/o or older. There is no support for limiting cannabis use to only those over 25 y/o. The decision as to whether cannabis use should be legal for individuals who are 18, 19, 20, or 21 y/o is primarily one of political expediency, not a decision based upon science. As 21 y/o is the legal age for tobacco and alcohol use, is the norm for U.S. states with legal adult use cannabis, and appears to be the age at which the majority of U.S. voters are willing to approve the legal use of cannabis in adult, DFCR supports the age of 21 y/o for adult use in the U.S. 

Doctors for Cannabis Regulation, July 22, 2023

References

1. Groeschel, S., Vollmer, B., King, M. D., Connelly, A., 2010. Developmental changes in cerebral grey and white matter volume from infancy to adulthood. Int J Dev Neurosci 28, 481-489

2. Harris, L. W., Lockstone, H. E., Khaitovich, P., Weickert, C. S., Webster, M. J., Bahn, S., 2009. Gene expression in the prefrontal cortex during adolescence: implications for the onset of schizophrenia. BMC Med Genomics 2, 28

3. Insel, T. R., 2010. Rethinking schizophrenia. Nature 468, 187-193

4. Khundrakpam, B. S., Lewis, J. D., Zhao, L., Chouinard-Decorte, F., Evans, A. C., 2016. Brain connectivity in normally developing children and adolescents. Neuroimage 134, 192-203

5. Lebel, C., Walker, L., Leemans, A., Phillips, L., Beaulieu, C., 2008. Microstructural maturation of the human brain from childhood to adulthood. Neuroimage 40, 1044-1055.

6. Leisman, G., Mualem, R., Mughrabi, S. K., 2015. The neurological development of the child with the educational enrichment in mind. Science Direct 21, 79-96.

7. Miller, D. J., Duka, T., Stimpson, C. D., Schapiro, S. J., Baze, W. B., McArthur, M. J., Fobbs, A. J., Sousa, A. M., Sestan, N., Wildman, D. E., Lipovich, L., Kuzawa, C. W., Hof, P. R., Sherwood, C. C., 2012. Prolonged myelination in human neocortical evolution. Proc Natl Acad Sci U S A 109, 16480-16485.

8. Olsen, D., 2019. Marijuana bill may violate Illinois Constitution, prosecutors say. Washington Times Reporter. Petanjek, Z., Judas, M., Simic, G., Rasin, M. R., Uylings, H. B., Rakic, P., Kostovic, I., 2011. Extraordinary neoteny of synaptic spines in the human prefrontal cortex. Proc Natl Acad Sci U S A 108, 13281-13286.

9. Whitford, T. J., Rennie, C. J., Grieve, S. M., Clark, C. R., Gordon, E., Williams, L. M., 2007. Brain maturation in adolescence: concurrent changes in neuroanatomy and neurophysiology. Hum Brain Mapp 28, 228-237.