Cannabis is a plant that contains a complex array of chemical compounds called phytocannabinoids. The two most prominent are Delta-9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD). THC is primarily responsible for the plant’s intoxicating properties, while CBD is known for its non-intoxicating effects. The effects experienced by users result from how these substances interact with the body’s dedicated internal signaling network. Understanding the science behind these processes requires a focused look at the body’s internal system and the specific actions of these two major cannabinoids.
The Endocannabinoid System: The Body’s Internal Regulator
The human body possesses the Endocannabinoid System (ECS), an internal network responsible for maintaining biological balance, or homeostasis. The ECS regulates functions such as mood, sleep, appetite, pain sensation, and immune response. It is composed of three main components: cannabinoid receptors, endogenous cannabinoids, and metabolic enzymes.
Cannabinoid receptors are specialized proteins embedded in cell membranes that act as landing sites for signaling molecules. The two primary receptors are Cannabinoid Receptor Type 1 (CB1) and Cannabinoid Receptor Type 2 (CB2). CB1 receptors are concentrated in the central nervous system, modulating neurotransmitter release in the brain and spinal cord. CB2 receptors are found predominantly in peripheral tissues and immune cells, playing a role in inflammation and immune function.
The body’s natural signaling molecules are called endocannabinoids, primarily anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Unlike conventional neurotransmitters, endocannabinoids are lipid-based and synthesized on demand in response to physiological changes. They function as retrograde messengers, traveling backward across a synapse to regulate the flow of information between neurons.
These signaling molecules have short lifespans, controlled by metabolic enzymes that quickly break them down. Fatty acid amide hydrolase (FAAH) is the enzyme responsible for degrading anandamide. Monoacylglycerol lipase (MAGL) breaks down 2-AG, terminating the signal. This rapid synthesis and degradation cycle allows the ECS to act as a fine-tuning mechanism for numerous physiological processes.
The Mechanism of THC: Direct Action and Psychoactivity
Delta-9-Tetrahydrocannabinol (THC) mimics the action of the body’s endocannabinoids but with a broader and more forceful effect. The psychoactive properties of cannabis are attributable to THC’s direct interaction with the CB1 receptor. THC acts as a partial agonist, binding directly to the CB1 receptor and activating a downstream signaling cascade.
Because CB1 receptors are highly expressed in brain regions controlling memory (hippocampus), coordination (cerebellum), and higher cognition (cortex), THC activation overrides the normal, localized signaling of the ECS. This widespread activation produces characteristic euphoria, altered sensory perception, and temporary impairment of motor skills and short-term memory. THC binding modulates the release of neurotransmitters, including GABA and glutamate, disrupting normal communication between neurons.
As a partial agonist, THC activates the receptor but does not produce the maximum possible biological response. However, the concentration of THC reaching the brain is significantly higher and lasts longer than the body’s rapidly degraded endocannabinoids. This potent and prolonged activation of CB1 receptors is the direct cause of intoxication, fundamentally linking the chemical structure of THC to the experience of being “high.”
The Mechanism of CBD: Indirect Modulation and Non-Intoxicating Effects
Cannabidiol (CBD) operates through a complex, indirect mechanism, explaining its non-intoxicating nature. CBD has a low binding affinity for both CB1 and CB2 receptors, meaning it does not directly activate them like THC. Instead, CBD acts as an allosteric modulator, binding to a secondary site on the CB1 receptor.
By binding to this allosteric site, CBD changes the shape of the CB1 receptor. This alters how THC or the body’s endocannabinoids interact with the primary binding site. For THC, this effect can reduce psychoactive potency, as CBD makes it more difficult for THC to fully activate the receptor. This explains why CBD often tempers the intoxicating effects of THC when consumed together.
CBD also enhances the body’s natural endocannabinoid tone by inhibiting the enzyme FAAH, which breaks down anandamide. By slowing anandamide degradation, CBD raises its concentration in the synapse, allowing it to signal for a longer duration. This sustained presence of anandamide is thought to contribute to CBD’s therapeutic effects, such as its anxiolytic properties.
Furthermore, CBD interacts with numerous other non-cannabinoid receptor systems throughout the body. For instance, CBD directly activates the serotonin 5HT1A receptor, a mechanism linked to its anti-anxiety and antidepressant-like effects. It also acts as a positive allosteric modulator of GABA-A receptors, which are crucial for inhibitory brain signaling, suggesting a role in its potential anticonvulsant and calming effects.
Processing and Elimination of Cannabinoids
Once THC and CBD enter the bloodstream, they must be metabolized and eliminated, a process that affects their potency and duration of action. The liver is the primary site of this metabolism, relying on a family of enzymes known as cytochrome P450 (CYP450). These enzymes, particularly CYP2C9 and CYP3A4, break down the highly lipid-soluble cannabinoid molecules.
For THC, this metabolic step creates a highly potent compound called 11-hydroxy-THC (11-OH-THC). This metabolite is psychoactive and is further oxidized by CYP450 enzymes into the inactive metabolite 11-nor-9-carboxy-THC (THC-COOH). CBD is metabolized by these same liver enzymes into hydroxylated forms, such as 7-OH-CBD, before being prepared for excretion.
The route of consumption dramatically alters the metabolic pathway and resulting effects. When inhaled, THC rapidly enters the bloodstream through the lungs, largely bypassing the liver’s first-pass metabolism, leading to a quick onset of effects within minutes. When orally ingested, THC is absorbed by the gut and immediately subjected to extensive first-pass metabolism in the liver.
This heavy exposure to CYP450 enzymes results in a greater production of the potent 11-OH-THC metabolite. Edible consumption thus results in a delayed onset, often taking one to four hours to reach peak concentration. The effects are typically more intense and prolonged due to the high concentration of 11-OH-THC circulating in the body. Inactive metabolites of both THC and CBD are mainly excreted, with a majority leaving through the feces and a smaller portion through the urine.