​In the weeds: the therapeutic benefits and risks of marijuana legalization in the us

​Nicole Rychagov
Since 1996, when the state of California first legalized cannabis usage, the United States’ public perception of cannabis has transformed from a “gateway drug” to a “harmless” mainstream (Medicinal Cannabis Guidelines; Villines, 2022). Such a narrative has been furthered by the greater legalization of cannabis within the broader United States; to date, 38 states have permitted some form of medical marijuana usage while 24 states have legalized recreational usage for adults over the age of 21 (NCSL, 2023). In fact, about 18% of Americans used cannabis at least once in 2019 (CDC, 2021). But these increasing rates of cannabis usage have been coupled with striking findings linking cannabis to the nation’s mental health crisis in young adults (Scherma et al., 2020); rates of cannabis-induced mental and behavioral health disorders have risen nearly 50% between 2019 and 2020 and have continued to increase through 2023 (Truveta Research, 2024). A 2022 study indicates individuals aged 18 to 25 account for the highest rates of cannabis-related emergency department visits (Moody-Porter, 2023). Rates of cannabis use disorder have also increased to about 16 million people in 2021, accounting for people ages 12 or older (Cannabis Research Report, 2022). Even though studies suggest cannabis has some great therapeutic potential, the impact of cannabis on mental health is complex and requires greater research, medical oversight, and federal regulation.

Historical evidence for cannabis usage in mental health applications reveals an ancient history in alleviating psychiatric symptoms; dating back to 1500 BCE, sections of the Atharva Veda, the oldest historical text of Indian medicine, suggest cannabis has anti-anxiety effects (Russo, 2016). With respect to modern usage of cannabis, meta-analyses reveal the mean prevalence of cannabis usage for mental health purposes was to address pain (67%), anxiety (52%), and depression (35%) (Kosiba et al., 2019). Studies also reveal that heavy cannabis usage is associated with an increased risk of developing psychosis or mood disorders (Hall & Degenhardt, 2008). Recreational cannabis usage is reported to induce a feeling of euphoria, decrease anxiety, and increase sociability. However, cannabis has also been reported to induce feelings of anxiety, paranoia, and psychosis. Studies of the impact of cannabis usage on anxiety point to the two predominant compounds of cannabis, cannabidiol (CBD) and tetrahydrocannabinol (THC), having opposing effects (Sharpe et al., 2020). 

CBD is a compound in cannabis that has been found to have a dose-dependent anti-anxiety effect in both animal model and human studies. Cannabis usage was associated with a reduction in intake of anti-anxiety medications or simply using cannabis as an alternative to pharmaceutical prescriptions (Sharpe et al., 2020). Furthermore, CBD usage have been noted in various clinical trials to alleviate psychotic symptoms; animal model studies further reinforce these findings, as in vivo studies of CBD function reveal a biphasic mechanism that acts similarly to the antipsychotic medication aripiprazole, suggesting that CBD may act in a way analogous to a typical antipsychotic medication and might have therapeutic potential (Patel et al., 2020). Critically, CBD has also been found to have a good safety profile and limited abuse liability, strengthening support for its therapeutic potential (Chye et al., 2019).
THC is the psychoactive compound in cannabis that is responsible for the “high” people experience when smoking marijuana and causes addiction (Stuyt, 2018).

Despite it being desirable to humans, there is an extensive body of literature linking THC to adverse mental health effects, such as psychosis and anxiety. As an active metabolite, THC downregulates CB1 receptors on neurons and upregulates CB2 receptors on microglia, resulting in microglial dysfunction that has been implicated in altered prefrontal cortex pruning (Patel et al., 2021). Cannabis usage, especially during adolescence, has been proposed to interact with pre-existing genetic and environmental factors to increase the risk of developing psychosis while also altering the neurobiological changes that occur over the course of the disorder (Rychagov et al., 2023). Moreover, research shows that higher THC potency in cannabis tends to have more pernicious effects, including a dose-dependent relationship between THC and positive psychotic symptoms in humans (Stuyt, 2018; Murray et al., 2017). In a review of studies on anxiety and cannabis usage, a consistent anxiety-inducing effect was noted in response to THC in human clinical studies, especially at higher doses of THC (Sharpe et al., 2020). 

It is undeniable that the legalization of marijuana has had a transformative impact on United States society. Marijuana was the leading drug offense for Americans in the early 2010s, with minorities and communities of color often disproportionately over-policed and targeted for marijuana possession-related arrests. Over the last decade, due to the push for cannabis legalization, arrests made for possession of marijuana have dropped by 58% (National Center for Drug Abuse Statistics, 2020). This move towards legalization may have been beneficial from a social and public health standpoint, as the first step towards better regulating cannabis was taking it out of the illegal market and into the hands of legitimate businesses, to allow those who choose to consume marijuana to do it at lesser risk (Rogers, 2023).

Since the onset of cannabis legalization, the cannabis industry has created new, potent formulations; cannabis now on the market has been tailored towards improving the “high” the consumer experiences, with THC content significantly higher than the illegal alternatives on the market decades ago (Backman, 2023). In fact, there has been a 212% increase in THC content in the marijuana flower between 1995 and 2015, with popular strains currently on the market containing a THC content from 17 to 28%. Other cannabis-derived products, such as oil and edibles, can have a THC concentration of up to 95% (Stuyt, 2018). There is no research indicating that such a high level of THC offers any medical benefits; rather, this heightened potency makes it even more dangerous and increases the likelihood of addiction.

President Biden’s administration is attempting to rehaul the United States’ position on the issue of marijuana by pushing the FDA to reclassify cannabis from a Schedule 1 drug, or a drug that has no accepted medical use and high potential for abuse, to a schedule 3 drug with moderate potential for dependence (Russel, 2024; DEA, n.d.). However, it is insufficient to simply loosen federal restrictions on the possession of marijuana; the federal government should take the next step in regulating cannabis by instituting a THC potency cap. States such as Connecticut and Vermont have already instituted upper limits on THC content within cannabis products as well as other countries that have legalized cannabis (Pacula et al., 2022). Although the legalization of cannabis has helped consumers ensure that “legal” consumption can come at a lesser risk, it is crucial to have uniform standards for all cannabis products in order to mitigate the current mental health crisis. 

About the Author
Nicole Rychagov is a senior at Harvard College, studying Neuroscience on the Mind, Brain, Behavior track.
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