Effects and action of tetrahydrocannabinol (THC) on human brain. Anatomical model of brain is near leaf of hemp and notepad inscribed with title tetrahydrocannabinol and drawn it chemical formula.

Highlights from Petrie-Flom Center Discussion on Neuroscience and Cannabis

By Minsoo Kwon

The legalization of cannabis has raised ethical, regulatory, and scientific questions. Panelists discussed these topics during a recent webinar hosted by the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics. This article highlights key points made during the conversation.

First, Stephanie Tabashneck, Senior Fellow in Law and Applied Neuroscience at the Center for Law, Brain & Behavior at Massachusetts General Hospital and the Petrie-Flom Center, began by providing an overview of the legal landscape of cannabis and the war on drugs.

  • Cannabis continues to be illegal on a federal level, pursuant to the Controlled Substance Act of 1970. Recent efforts, however, are pushing against this federal prohibition on Cannabis.
    • Along with drugs like heroin and cocaine, Cannabis is classified as a Schedule One drug with no currently accepted medical use and a high potential for abuse.
    • “Most recently, the Cannabis Administration Opportunity Act was introduced, which would decriminalize cannabis on a federal level,” Tabashneck said. “There’s also been other sort of chip away bills that have been filed, including the Veterans Medical Marijuana Safe Harbor Act, which would authorize VA Personnel to prescribe medical cannabis in states where it is not permitted under state law.”
  • Since 2022, more states have granted recreational use authorization under state law.
    • “In 2022, the last time that we did this presentation, there were 37 states that authorized cannabis for medical use,” Tabashneck said. “In 2023, we saw the addition of five states: Maryland, Missouri, New York, Rhode Island, and South Dakota.”
    • In Kentucky, a medical cannabis bill approving recreational cannabis use was passed by popular referendum and will go into effect later this year.
  • Despite recent expansions of authorized recreational and medical uses of cannabis, about one of ten arrests in the United States are for cannabis (the majority of which are for possession and not distribution).
  • The enforcement of drugs laws in the U.S. is racially biased.
    • Arrests are racially disproportionate: “At every intersection of the criminal justice system… when someone is stopped, searched, arrested, charged, whether they’re charged with a mandatory minimum, whether they’re found guilty or not, what sentence they receive… race influences all of these different domains.”
    • Black individuals are jailed for cannabis-related offenses at rates 13.4 times higher than whites.
    • Even in states where cannabis is legal, “Black people are more likely to be arrested for cannabis possession than white people.”
    • Higher arrest rates for Black people are dissonant with data on usage: “The lifetime use for someone who is Black or African-American is lower than a person who’s white. So we would expect that there would be parity in the arrests and incarceration of people across race, but that’s not what we’re seeing, we’re seeing very disparate enforcement of these laws.”

Then, Yasmin Hurd, professor of psychiatry and neuroscience and Director of the Addiction Institute at the Icahn School of Medicine at Mount Sinai, explored the science of cannabis, CBD, and the future of substance use disorder treatment.

  • Cannabis is complex on all fronts: Its history, legal status, and mechanisms of action within our bodies.
  • “When people say, well cannabis is just impacting on our natural endocannabinoid system, that is true. But we’re talking about magnitudes of change.”
    • For example, “even 95 days after animals were exposed to high-dose THC, they show very high levels of the stress hormone cortisol.”
  • CBD is distinct in mechanism and effects from THC.
    • “CBD is being used in everything from water, to coffee, and even for pets who have high anxiety. But THC and CBD are very different. THC definitely mediates reward. Not CBD. Intoxication, that is associated with THC, not CBD. And even though many of our patients will tell us that they use cannabis to alleviate their anxiety, actually high dose THC exacerbates anxiety, and CBD reduces that.”
  • Cannabis use can cause functional and epigenetic changes. Environmental factors, specifically stress, interact with an individual’s genetic risks.
    • Adults with a history of early life trauma/abuse will start using cannabis earlier. They also “have a shorter time to relapse for the drug, and show a greater severity of relapse.”
  • Cannabis use disorder is real.
    • “There is a clinical diagnosis for cannabis use disorder, and it’s estimated that past one year of cannabis use, about 30% of users will develop a cannabis use disorder, and in the general population [of cannabis users] about 11% of people do develop a cannabis use disorder. This number is close to other substances like cocaine or heroin, and it’s not because cannabis is as addictive as those substances, rather it is more abundantly experimented with.”
    • “We know that cannabis use disorder does come with a high psychiatric comorbidity, mood disorders, depression, anxiety type disorders, also aspects of psychosis as well. And when you look in the brain… you see morphological changes that are very similar to some of the morphological changes that you see with other substance use disorders and even on a functional level, aspects of the brain that are critical for working memory, attention, reward anticipation, emotional regulation, decision making.”
    • While large Genome-Wide Association Studies (GWAS) have attempted to identify genetic variations that make individual particularly vulnerable to SUDs, “it’s very difficult to pick up a signal that there is this specific smoking gun of this genetic risk.”
  • Cannabis use during pregnancy affects the developing fetus. When children with exposure to cannabis in utero are born, they exhibit higher cortisol levels, and “you could see that there is highly increased anxiety, aggression in these kids.”
    • However, these effects might also be related to general maternal stress. “The thing that to emphasize is that actually there’s a very strong synergistic interaction between prenatal cannabis exposure and stress, so that yes cannabis increases, for example, anxiety in their kids and stress but the combination of early life exposure to cannabis and stress produce a much greater effect.”
  • The risk of addiction and negative effects on psychiatric health, as well as the potential influence on the developing brain, are of concern in policy debates about cannabis. However, because cannabis affects people differently, this complicates the discussion.
    • “There is such a heterogeneity of the impact of cannabis … and these individual differences relate to aspects of genetics, behavioral traits (in terms of psychiatric comorbidity), environment, the developing brain, and, perhaps, cannabis content.”
    • “It’s important to emphasize that cannabis is not necessarily all equal for the brain. But one of the things that is clear is that these epigenetic changes are reversible.”

This transcript has been edited and condensed. Watch the full event video here. This event was sponsored by the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School and is part of the Project on Law and Applied Neuroscience, a collaboration between the Center for Law, Brain and Behavior at Massachusetts General Hospital and the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School, with support from the Oswald DeN. Cammann Fund at Harvard University.

Minsoo Kwon

Minsoo Kwon is a Junior at Harvard University studying Neuroscience and an intern at the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School.

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