By Vishwanath Prathikanti, Political Science, 23’

Author’s note: Marijuana today is a very controversial topic, with some arguing for a complete criminalization of it, others advocating for complete decriminalization of it, and many more in between. To understand marijuana today, and what it does to your body, we need to unravel its complex history and proven effects. Unfortunately, this is not always clear cut.

Marijuana, according to the National Institute on Drug Abuse (NIDA) is defined as “a greenish-gray mixture of the dried flowers of Cannabis sativa” and all other relatives, including Cannabis indica, Cannabis ruderalis, and hybrids [1]. The mind-altering effects of marijuana are mainly due to the chemical delta-9-tetrahydrocannabinol, commonly known as THC, and it is the active ingredient that makes marijuana so dangerous according to NIDA. 

The reason for this mind-altering effect is due to the structural similarities between THC and anandamide, a naturally occurring cannabinoid that functions as a neurotransmitter. Anandamide is an agonist, meaning it is a chemical that binds to receptors in the human endocannabinoid system and causes a response. The endocannabinoid system is a network of receptors designed to maintain bodily homeostasis, or stable conditions for the body [13]. Anandamide activates receptors which send chemical messages between nerve cells throughout the nervous system, specifically to areas in the brain “that influence pleasure, memory, thinking, concentration, movement, coordination, and sensory and time perception” [1]. Mainly, the cerebellum, basal ganglia, and hippocampus areas are being activated the most. Due to the effects of pleasure, researchers have speculated that anandamide could be released in the early phases of brain development to strengthen positive reactions towards food consumption, essentially encouraging people to eat, although they cannot confirm it [2]. Regardless, due to its similarity to anandamide, THC is able to attach cannabinoid receptors on neurons in these brain areas and activate them. These receptors are usually activated by anandamide, but when they are activated by THC, various mental and physical functions become disrupted, such as cognitive function and balance, and various mental effects start to take place as well. These effects most commonly represent themselves as “pleasant euphoria” and other times “heightened sensory perception (e.g., brighter colors), laughter, altered perception of time, and increased appetite” [1].

Repeated interference of the endocannabinoid system due to THC can lead to various problems in areas of the brain that enable complex thinking, balance, and reaction time. THC has also been shown to have more permanent effects on developing brains, such as impairing specific learning and memory tasks, discussed in one study involving rats. Gleason et al. targeted cannabis receptor 1 (CB1), an endocannabinoid receptor that is prevalent “in the cortex, hippocampus and striatum” and is activated by THC in both mice and humans [3]. Gleason et al. administered a CB1 agonist during adolescence in one group, adulthood in another, and proceeded to observe brain development. They found that the adolescents developed long-term hippocampal learning and memory deficits, specifically manifesting in hippocampal long-term depression. Hippocampal depression is the process of reducing synaptic efficacy in the hippocampus due to a patterned behavior, in this case marijuana usage, resulting in the process of learning new information to become more difficult [17]. The adult rats in this study did not show signs of these changes. When it comes to humans though, studies show conflicting results. 

Most of the consistently observed damage done to the human brain is within the prefrontal cortex area, due to the large volume of CB1 receptors. One study that observed adults who used marijuana four times per week compared to adults of a similar demographic that did not use marijuana found that the frequent use resulted in lower volumes of orbitofrontal cortex (OFC) gray matter [10]. The OFC is tied to various aspects of decision making and is widely believed to deal with emotional and sensory details linked to decisions. The study explains that the OFC “is enriched with CB1 receptors, and is highly implicated in addictive behaviors such as those related to disruptions in motivation” [10]. The consequences of losing gray matter are not only linked to suboptimal decision-making, but in order to compensate for the loss of volume, the brain builds more connections in the OFC. Due to the higher amount of connections, the brain requires more sustenance, particularly glucose, in order to function normally. 

Despite the existence of marijuana in the world for centuries, marijuana research is still in its infancy. This is because the federal Drug Enforcement Agency (DEA) lists marijuana as a Schedule I drug, meaning “it has a high potential for abuse, no currently accepted medical use in treatment in the United States, and a lack of accepted safety for use under medical supervision” [5]. To put things into perspective, heroin, ecstasy and methamphetamine are also listed as Schedule I drugs. To study the effect on THC, researchers not only need a special permit, but they need to study individuals who are already consuming THC on a regular basis. This is a practice used for all Schedule I drugs; scientists are unable to administer heroin, methamphetamine or ecstasy to individuals in any research projects.

While THC has been shown to have various adverse effects on the brain, there is another component in marijuana that has resulted in various positive effects, cannabidiol (CBD). CBD is the second most prevalent ingredient in marijuana, and is an essential component in medical marijuana. While THC is the main psychoactive ingredient in cannabis, responsible for physical and mental disorientation, CBD is responsible for the sense of anxiety relief [4]. Until 2018, CBD was also considered a Schedule I drug, but it has since been removed due to its benignity, meaning anyone can legally buy and sell CBD in the US as long as it is derived from hemp [4]. Hemp is another plant in the cannabis family, but has different physical and chemical properties that separate it from marijuana. Hemp is typically characterized by its sturdy stalks used in textiles as well as a low concentration of THC [16]. In particular, CBD has been essential in treating “some of the cruelest childhood epilepsy syndromes, such as Dravet syndrome and Lennox-Gastaut syndrome (LGS), which typically don’t respond to antiseizure medications” [4]. There is evidence CBD helps with numerous mental disorders, including anxiety, insomnia and chronic pain, but further research investigating side effects is required.

Returning to the hippocampus region, Demirakca et al. observed hippocampal volume reductions in users who consumed cannabis that was higher in THC content than CBD content. They concluded that there was an inverse relationship between gray matter (GM) volume and THC/CBD ratio, meaning the more THC is in a product, the more likely it is that the user will have reduced GM volume [19]. However, study spanning three years conducted by Koenders et al. found that there was no relevant correlation between cannabis usage in young adults and reduced GM volumes in multiple regions of the brain, including the hippocampus [19].

CBD in particular, has been shown to have negative effects on the amygdala, whereas THC has not shown an effect. The amygdala is popularly known as being the collection of nuclei that control your sense of fear, linking it directly to a potential effect of THC usage, anxiety [18]. Surprisingly, a link between THC and the amygdala has been disproven by multiple papers. However, CBD does affect the amygdala. One study by Rocchetti et al. in 2013 and another by Pagliaccio et al. in 2015 disproved previously held beliefs linking marijuana and amygdala damage due to size. Rocchetti et al. conducted a smaller study and proved publication bias in the preceding amygdala research while Pagliaccio produced a wide study that found variation of amygdala size between marijuana users and nonusers fell within the range of normal variation [11, 14]. However, while amygdala size may not be affected, there is evidence that indicates its functionality is decreased. A study done by Fusar-Poli et al. in 2010 found that CBD actually negatively affects the amygdala due to its anti-anxiety effects. Fusar-Poli et al. found that CBD weakens signals sent from the amygdala during fear-inducing situations, meaning that CBD usage could prompt a delayed or subdued reaction compared to normal [15]. 

This begs the question, if further research is required to understand the full effects of THC and CBD, why is marijuana considered such a charged political topic today? To understand marijuana today, it is necessary to examine its history, often motivated for political reasons rather than scientific ones.

The history of regulation and fear associated with marijuana dates back to 1930 when Harry Anslinger was appointed as the first commissioner of the Federal Bureau of Narcotics (FBN). Due to the great depression, the federal government needed to cut funding for various agencies, and at the time, the FBN mainly combated heroin and cocaine, drugs used by a relatively small number of people. Anslinger needed to find a more widely used narcotic that would get him the necessary funds to continue his war on drugs [6]. 

Anslinger decided that the drug would be cannabis, and latched on to a story of a man named Victor Licata who killed his family with an Axe after consuming cannabis. While there was no evidence that he consumed marijuana before the killing, newspapers quickly sensationalized the story, and Anslinger went onto various radio shows claiming that the drug could cause insanity. The name “marijuana” was actually given by Anslinger to associate the drug with latinos, and used racial tensions to insinuate that the drug made black and latino americans “forget their place in the fabric of society” [6]. Anslinger’s actions culminated in his testifying before congress in hearings regarding the Marihuana Tax Act of 1937 which effectively banned sales. 

Before it was categorized as a Schedule I drug however, there were numerous committees that ruled against the illegalization of marijuana. After the Marihuana Tax Act of 1937, New York City mayor Fiorello LaGuardia assembled a special committee with the New York Academy of Medicine “to make a thorough sociological and scientific investigation” on the effects of marijuana. The committee completely disproved Aslinger’s claims of insanity, saying “the basic personality structure of the individual does not change,” meaning after the “high” has passed, the user is unchanged personality-wise. They also stated that marijuana “does not evoke responses which would be totally alien [in an] undrugged state,” meaning the consumption of marijuana would not cause an individual to act out of character [7]. The information provided in the LaGuardia Report is quite consistent with research found today, and helped contribute to the supreme court overturning the Marihuana Tax Act in 1969 with Leary vs United States.

However, while the act was overturned, it was replaced soon after with the Controlled Substances Act 1971 under the Nixon presidency which established Marijuana as a schedule I drug. This act was another racially motivated law, with Nixon’s domestic Policy Advisor later admitting that “the Nixon White House had two enemies: the antiwar left and black people. We knew we couldn’t make it illegal to be either against the war or black, but by getting the public to associate the hippies with marijuana and blacks with heroin, and then criminalizing both heavily, we could disrupt those communities. We could arrest their leaders, raid their homes, break up their meetings, and vilify them night after night on the evening news. Did we know we were lying about the drugs? Of course we did” [8].

Nixon appointed a commission to investigate the effects of marijuana in 1972, and the report returned recommending the decriminalization of marijuana. The report argued that “Criminal law is too harsh a tool to apply to personal possession even in the effort to discourage use…It implies an overwhelming indictment of the behavior which we believe is not appropriate. The actual and potential harm of use of the drug is not great enough to justify intrusion by the criminal law into private behavior, a step which our society takes only with the greatest reluctance” [9]. In response to the report, Nixon not only refused to decriminalize marijuana, but created the DEA the next year, which would enforce the laws regarding marijuana as a Schedule I drug.

Because of the strict regulations on it today, marijuana research is still in its infancy. However, due to the aforementioned loosening of regulations on CBD research, marijuana is being pushed into the spotlight once again. This, coupled with marijuana’s past history and present realities of it being tied to members of the African American communities have made the marijuana debate into a hotbed for political discourse. Whether or not recreational marijuana becomes legal federally in the near future, it is clear that marijuana warrants further investigation in order to clear up the various inconsistencies surrounding its effects, both long-term and short-term, on the human body.

References

1. National Institute on Drug Abuse research report series “Marijuana” https://www.drugabuse.gov/publications/research-reports/marijuana/what-marijuana
2. Stephen V. Mahler, et. al “Endocannabinoid Hedonic Hotspot for Sensory Pleasure: Anandamide in Nucleus Accumbens Shell Enhances ‘Liking’ of a Sweet Reward.” Neuropsychopharmacology. 2007. https://www.nature.com/articles/1301376
3. Kelly A. Gleason, et al. “Susceptibility of the adolescent brain to cannabinoids: long-term hippocampal effects and relevance to schizophrenia” Nature. 2012. https://www.nature.com/articles/tp2012122
4. Peter Grinspoon, “Cannabidiol (CBD) — what we know and what we don’t” Harvard Health Blog, Harvard Health Publishing. August 24, 2018. https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-we-dont-2018082414476 
5. DEA “Drugs of Abuse (2017 edition)” 2017. https://www.dea.gov/sites/default/files/drug_of_abuse.pdf
6. CBS News “The man behind the marijuana ban for all the wrong reasons” Nov. 17, 2016 https://www.cbsnews.com/news/harry-anslinger-the-man-behind-the-marijuana-ban/
7. The LaGuardia Committee Report https://daggacouple.co.za/wp-content/uploads/1944/04/La-Guardia-report-1944.pdf
8. Drug Policy Alliance “Top Adviser to Richard Nixon Admitted that ‘War on Drugs’ was Policy Tool to Go After Anti-War Protesters and Black People” http://www.drugpolicy.org/press-release/2016/03/top-adviser-richard-nixon-admitted-war-drugs-was-policy-tool-go-after-anti
9. Schafer library of drug policy, “Marihuana: A Signal of Misunderstanding” http://www.druglibrary.org/schaffer/Library/studies/nc/ncmenu.htm
10. Francesca M. Filbey, et al. “Long-term effects of marijuana use on the brain” PNAS. 2014. https://www.pnas.org/content/111/47/16913
11. David Pagliaccio et al. “Shared Predisposition in the Association Between Cannabis Use and Subcortical Brain Structure” JAMA Psychiatry. October 2015. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2429550
12. Albert Batalla et al. “Structural and Functional Imaging Studies in Chronic Cannabis Users: A Systematic Review of Adolescent and Adult Findings” PLOS One. February 2013. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0055821
13. Cannabis research initiative “Human endocannabinoid system” UCLA Health. https://www.uclahealth.org/cannabis/human-endocannabinoid-system
14. Matteo Rochetti et al. “Is cannabis neurotoxic for the healthy brain? A meta‐analytical review of structural brain alterations in non‐psychotic users” Psychiatry and Clinical Neurosciences. Sept. 2013. https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcn.12085
15. Paolo Fusar-Poli et al. “Modulation of effective connectivity during emotional processing by Δ9-tetrahydrocannabinol and cannabidiol” International Journal of Neuropsychopharmacology. May 2010. https://academic.oup.com/ijnp/article/13/4/421/712253
16. NIDA Blog. “What is Hemp?” National institute on drug abuse for teens. November 2015. https://teens.drugabuse.gov/blog/post/what-is-hemp
17. Peter Massey et al. “Long-term depression: multiple forms and implications for brain function” Cell. April 2007.  https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(07)00043-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0166223607000434%3Fshowall%3Dtrue
18.  Nicole Haloupek “What is the Amygdala?” Live Science. January 2020. https://www.livescience.com/amygdala.html
19. Traute Demirakca et al. “Diminished gray matter in the hippocampus of cannabis users: Possible protective effects of cannabidiol” April 2011. https://www.sciencedirect.com/science/article/pii/S0376871610003364?via%3Dihub
20. Laura Koenders et al. “Grey Matter Changes Associated with Heavy Cannabis Use: A Longitudinal sMRI Study” May 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880314/