The psychoactive effects of cannabis or other substances often feel diminished or altered during illness. This reflects a biological phenomenon where the body’s response to sickness interferes with the substance’s normal action. Physiological changes that occur when the immune system is activated disrupt the neurological and metabolic processes required for a typical psychoactive experience. This reduction is rooted in the interplay between the inflammatory response, nervous system receptors, and the liver’s drug processing functions.
How Psychoactive Compounds Interact with the Body
Psychoactive compounds like delta-9-tetrahydrocannabinol (THC) exert their effects by interacting with specific receptor systems. The primary target for THC is the Endocannabinoid System (ECS), a complex cell-signaling network regulating functions like mood, pain, and memory. The ECS includes two main types of receptors: Cannabinoid Receptor Type 1 (CB1) and Cannabinoid Receptor Type 2 (CB2).
CB1 receptors are densely concentrated in the brain and central nervous system, and their activation by THC produces the characteristic “high.” THC acts as a partial agonist, influencing neurotransmitter release and altering perception.
The Immune System’s Response to Illness
When the body encounters a pathogen, it mounts a rapid and systemic defense known as the inflammatory response. This process involves a sophisticated, body-wide communication network. The immune system releases specialized signaling proteins called cytokines into the bloodstream.
Cytokines, such as interleukins (IL) and tumor necrosis factor-alpha (TNF-α), act as messengers that coordinate the immune effort and signal the brain. These molecules induce changes like fatigue and malaise, which are the familiar symptoms of being sick.
Inflammation and Receptor Interference
The diminished effect stems from the interaction between inflammatory cytokines and the body’s receptor systems, particularly the CB1 receptors in the brain. High levels of pro-inflammatory cytokines can interfere with cannabinoid receptor functionality. This interference may alter the receptor’s structure or availability, making it less responsive to THC.
Inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, can change the expression levels of CB1 receptors. The overall effect in the brain is often a functional desensitization of the CB1 receptors responsible for the psychoactive effect. If the CB1 receptor is less sensitive, THC cannot trigger the same neurological response, resulting in a reduced “high.”
The body’s natural endocannabinoids are involved in regulating the immune response. Systemic inflammation shifts the priority of the ECS from regulating mood and perception to managing the immune threat. This competition means that a standard dose of THC yields only a weak signal.
Changes in Drug Processing (Pharmacokinetics)
Beyond receptor interference, illness changes how the body chemically processes psychoactive compounds, a process known as pharmacokinetics. The liver metabolizes compounds like THC using cytochrome P450 enzymes (CYP enzymes). THC is converted by enzymes like CYP2C9 and CYP3A4 into the psychoactive metabolite 11-hydroxy-THC (11-OH-THC), which contributes significantly to the overall effect.
Systemic inflammation places stress on the liver and alters the activity of these CYP enzymes. High levels of circulating cytokines downregulate the expression and activity of major CYP enzymes responsible for processing THC.
This altered enzyme activity changes the rate at which THC is broken down or converted. A change in the metabolic rate can lead to faster clearance or an altered ratio between THC and 11-OH-THC, shortening the duration or altering the intensity of the perceived effect.
Safety Implications of Consumption While Sick
Attempting to consume greater quantities of a substance to overcome the reduced effect while ill carries risks. When the body is fighting an infection, its systems, particularly the liver, are already under strain. Overloading the system with higher doses can exacerbate this stress, especially given the altered state of the CYP enzymes responsible for detoxification.
Combining psychoactive compounds with over-the-counter cold and flu medications presents additional hazards. Many common cold remedies contain ingredients like antihistamines or dextromethorphan, which can cause drowsiness and dizziness. Combining these with THC can amplify sedation, confusion, and impaired motor function, increasing the risk of accidents. Furthermore, many multi-symptom products contain acetaminophen, and the combination with cannabis may strain the liver.