When cannabis doesn’t produce expected effects, it can be puzzling. Many wonder why they don’t get high. This stems from biological mechanisms and external factors affecting how the body processes cannabis. Understanding these reasons clarifies varied experiences.
How Cannabis Interacts with Your Body
Cannabis effects are primarily mediated by its interaction with the endocannabinoid system (ECS), a complex system maintaining bodily balance. The main psychoactive compound, delta-9-tetrahydrocannabinol (THC), binds to specific cannabinoid receptors. These receptors are found throughout the body, with two main types: CB1 and CB2.
CB1 receptors are in the brain and central nervous system. THC activation of CB1 leads to psychoactive effects like altered perception and mood. THC acts as a partial agonist at these receptors, mimicking natural endocannabinoids. CB2 receptors are predominantly in immune cells and peripheral tissues, playing a role in immune responses and inflammation. This interplay determines THC’s impact.
Factors Related to the Cannabis Product
Product characteristics influence desired effects. THC concentration, or potency, is a primary determinant, with higher percentages generally leading to stronger effects. Beyond a point, higher potency may not increase intoxication due to receptor saturation.
Poor storage (light, air, heat) degrades THC into less psychoactive compounds like CBN, reducing effectiveness. Consumption method affects onset, intensity, and duration due to varying bioavailability. Smoking or vaping offers rapid absorption (10-60% bioavailability). Edibles have slower onset (30 min-2 hrs) and lower bioavailability (4-20%) but prolonged effects. An insufficient dose also prevents noticeable effects.
Your Body’s Unique Response
Individual biological factors explain why some don’t experience cannabis effects. Regular use can lead to tolerance, where CB1 receptors desensitize or reduce (downregulation). This means higher doses are needed for the same effect, or effects diminish. A “tolerance break” (abstinence) can help restore receptor sensitivity.
Genetic variations also influence how the body metabolizes THC. Liver enzymes like CYP2C9, CYP2C19, and CYP3A4 break down cannabinoids. Genetic differences lead to faster or slower THC metabolism, affecting its concentration and duration. Variations in cannabinoid receptors (e.g., CNR1 gene for CB1) also influence sensitivity and receptor density. Some naturally have fewer or less sensitive receptors, needing more THC for a response.
Other Considerations
Other factors also influence the cannabis experience. Medications can interact with cannabis, potentially altering or masking its effects. For example, THC and CBD can affect liver enzymes (CYP3A4 and CYP2D6) that metabolize many prescription and over-the-counter drugs, potentially altering drug levels. This can lead to unexpected outcomes or diminished effects.
Psychological factors, or “set and setting,” shape the perceived experience. Mindset, expectations, and environment influence how effects are interpreted, or if any are perceived. Physiological state (e.g., fatigue, stress) may also alter the body’s response. For edibles, consuming with or after a fatty meal can impact absorption and onset, potentially delaying effects but sometimes increasing overall absorption.