Ask the experts: Cannabis chemistry in the body
Last updated on Apr 4, 2025
Created on Apr 4, 2025
Article written by
Dr. Miyabe Shields PhDCannabis expert
Dr. Riley Kirk PhDCannabis expert
Ever wonder how cannabis actually works within your brain and body? Learn from the experts as they break down marijuana chemistry and metabolism.
Riley Kirk, PhD, and Miyabe Shields, PhD, are pharmaceutical scientists specializing in cannabis biochemistry. They are co-founders of the Network of Applied Pharmacognosy, a nonprofit organization that bridges the gap between research, industry, and patients to amplify cannabis education and science.
Keep reading for their answers to commonly asked questions about how cannabis works in your body at the chemical level.
Leafwell language note: “Cannabis” vs. “marijuana”
The term “marijuana” has a complicated history and ties to racism in the early 1900s, when it was used during cannabis prohibition to fuel xenophobia against Mexican immigrants.
We prefer to use the term “cannabis,” which is the plant’s scientific name. However, we may occasionally use the term “marijuana” because it is widely recognized and used by patients.
What does marijuana do to your brain chemically?
Riley Kirk, PhD: Cannabis affects the brain primarily through the endocannabinoid system (ECS), a network of receptors, signaling molecules, and enzymes that control functions such as mood, appetite, pain, and memory.
The active compounds in cannabis, like tetrahydrocannabinol (THC) and cannabidiol (CBD), interact with cannabinoid receptors (CB1 and CB2) and other receptor systems to alter the release of brain chemicals.
THC is a partial activator of the CB1 receptor. There are many CB1 receptors in the brain, and consuming THC leads to changes in how dopamine, serotonin, and gamma-aminobutyric acid (GABA) are absorbed. This causes the euphoric, relaxing, and sometimes disorienting effects of cannabis.
CBD, on the other hand, changes receptor activity rather than directly activating receptors, influencing serotonin and GABA signaling. This is why it is studied for its anti-anxiety and brain-protecting effects.
Miyabe Shields, PhD: One underappreciated aspect of cannabis is how it changes brain plasticity over time. Long-term use can increase or decrease receptor sensitivity, depending on your pattern of use.
There’s also emerging evidence that cannabinoids affect mitochondrial function, which plays an important role in neuroprotection and energy balance.
What part of the brain does marijuana affect?
Dr. Kirk: Cannabis primarily affects the cerebral cortex, hippocampus, basal ganglia, and cerebellum — regions rich in CB1 receptors, which THC binds to.
The hippocampus is responsible for memory formation, which is why cannabis can sometimes affect short-term memory.
However, certain terpenes like linalool show promise in counteracting some memory deficits! Terpenes are compounds in cannabis that give it its unique smell and provide therapeutic effects.
Dr. Shields: Cannabis also affects the prefrontal cortex, which regulates decision-making and impulse control, especially in young adults.
Chronic cannabis use may affect cognitive development in both positive and potentially damaging ways.
The amygdala, which processes emotions and fear, is also influenced. This may explain why cannabis can both relieve anxiety and sometimes cause paranoia.
Does weed change your brain chemistry?
Dr. Kirk: Yes, chronic cannabis use can lead to changes in the ECS, including downregulation of CB1 receptors with heavy use (they become less responsive) and upregulation after stopping use (they become more responsive).
Downregulation can lead to some positive effects, like reduced anxiety or fewer post-traumatic stress disorder (PTSD) symptoms in people who have higher amounts of CB1 receptors in the brain.
Additionally, this is why people experience tolerance to THC over time and may experience withdrawal symptoms, like appetite changes, sleep disturbances, or mood shifts, when stopping cannabis use.
Dr. Shields: Cannabis affects how brain cells communicate. Long-term effects depend on factors like dose, frequency, and your individual body and brain.
Interestingly, cannabis might increase the brain’s ability to adapt and get stronger over time, which is why researchers are interested in it as a treatment for PTSD and brain disorders.
Does marijuana affect serotonin?
Dr. Kirk: Yes! CBD is known to act on a key serotonin receptor that’s involved in anxiety and mood regulation. This is why CBD is being studied for depression and anxiety disorders.
Dr. Shields: THC does not directly bind to serotonin receptors. However, it acts on CB1 receptors, which change serotonin signaling.
Cannabinoids produced by your body — called endocannabinoids — share many pathways with serotonin. This is why cannabis can affect mood, sleep, and cognition.
Does marijuana affect dopamine?
Dr. Kirk: Yes, THC triggers dopamine release, which is part of why cannabis can feel rewarding and pleasurable. This effect is similar to other substances that increase dopamine, or even non-drug stimuli like social media.
Dr. Shields: There’s evidence that CB1 receptors affect dopamine release in the prefrontal cortex and basal ganglia — two brain areas critical for motivation and motor control.
Chronic cannabis use can decrease dopamine receptor function, which is important to remember when thinking about cannabis’s role in mental health.
How is marijuana metabolized in the body?
Dr. Kirk: Cannabis is metabolized mainly by enzymes in your liver. These are the same enzymes that metabolize pretty much all drugs, including pharmaceuticals. This is why there is a potential for drug-drug interactions between cannabis and pharmaceuticals.
These enzymes convert THC into a similar compound called 11-hydroxy-THC, which is more potent and longer-lasting than THC.
This explains the stronger and longer effects of edibles compared with smoking — more THC reaches your liver when you eat or drink cannabis than when you smoke it, and therefore more 11-hydroxy-THC is made.
Dr. Shields: Metabolism varies widely between people, which is why some experience stronger effects from edibles than others. After metabolism, THC is stored in fat tissue.
Does cannabis accumulate in the body?
Dr. Kirk: Yes, THC accumulates in fat cells. This is why heavy users can test positive for cannabis weeks after they stop consuming.
Dr. Shields: Since cannabis dissolves in fat, it takes longer to clear from the body than substances that dissolve in water. This means people who consume cannabis frequently may have cannabinoids in their body systems for extended periods, even if they don’t feel high.
Dr. Kirk: Because of this, we believe cannabis shouldn’t be routinely screened for in drug tests. We don’t currently have a method to test for short-term intoxication.