Cannabis, often wrapped in myth and lore, has long occupied a curious place in both culture and science. Many users report vastly different experiences: for some, a pleasant high; for others, anxiety or disorientation. As legal access to cannabis expands in many regions, understanding why the effects vary so much becomes increasingly important. In this article, we explore the biological, psychological, and environmental factors that help explain why cannabis affects people so differently.
Different chemical profiles and doses
First, it’s essential to recognize that cannabis is far from a single, uniform substance. The plant contains hundreds of chemical compounds, including major cannabinoids like THC (tetrahydrocannabinol) and CBD (cannabidiol), alongside dozens of other cannabinoids and terpenes.
These compounds can interact in complex ways. For example, while THC is the primary psychoactive agent, CBD may modulate some of its effects. Also critical is the dose and the mode of consumption. Smoking or vaping tends to deliver a rapid onset, while edibles take longer to act but may last much longer, and the metabolism differs. Thus, one person may smoke a small amount and feel little; another may eat an edible and feel a strong, delayed effect. Differences in the potency of the product also matter: modern cannabis products often contain much higher THC levels than those of decades ago.
In short, the chemical composition of the cannabis, the dose, the route of administration, and the timing all lay the groundwork for variation.
Individual biology: metabolism, age, sex, and receptors
Beyond the product itself, the individual’s biology plays a significant role in how cannabis is processed and experienced. One key factor is how the body metabolizes THC and other cannabinoids. Recent research indicates that gene variants can affect how quickly a person breaks down THC, and those who metabolize more slowly may experience stronger or more prolonged effects, including more negative ones.
Age also matters. Our brains and systems change over time. For example, the density and distribution of cannabinoid receptors (notably the CB1 receptor) vary across developmental stages. Some studies suggest adolescents may be more vulnerable to certain effects of THC than adults.
Gender and hormones likewise influence response. Women’s hormonal cycles and sex differences in endocannabinoid system sensitivity may mean that females react differently to cannabis compared to males.
This suggests that two people consuming the same product in the same way may still have very different outcomes purely because of their individual biological makeup.
Brain region activation and cognitive variation
Another critical dimension is the way cannabis acts in the brain. Research has shown that the same cannabinoid, THC, may activate different brain circuits in different users, leading to diverging experiences. For instance, brain-imaging studies show that sensitivity to the psychosis-like effects of THC correlates with activation in certain brain regions.
One study (in animals) found that THC acting in one area of the nucleus accumbens produced rewarding effects, while acting in a different region produced more adverse, schizophrenia-related effects. In human terms, this suggests that variation in which neural circuits are most affected may contribute to why one person feels relaxed and euphoric and another becomes anxious or paranoid.
Furthermore, cognitive tasks show that adolescents appear less able to switch out of a resting brain-wave state while under THC than adults, implying developmental differences in the brain’s responsiveness to cannabis.
Thus, brain-region sensitivity and neural development influence how cannabis is experienced, especially regarding cognition, perception of time, attention, and mood.
Psychological state, environment, and expectancy
While biology is critical, psychology and environment cannot be ignored. The mindset going into a cannabis experience (“set”), the environment in which it is consumed (“setting”), and the user’s previous experiences (tolerance, expectations) all influence outcomes. Some early research suggests that individuals with low self-esteem or high anxiety may be more prone to negative experiences with cannabis, possibly because the drug amplifies pre-existing psychological states.
For example, someone using cannabis in an unfamiliar, stressful setting might become anxious or paranoid, whereas someone in a comfortable environment with positive expectations may enjoy the experience more. In this sense, the psychological and situational factors act as “modulators” of the pharmacological effect.
Tolerance, prior use, and interaction with other substances
Another variable is the user’s history: regular users often develop tolerance, meaning that the same dose produces less effect over time. Meanwhile, naïve or infrequent users may experience more intense or unpredictable effects. The interaction with other substances, like alcohol, prescription medications, or other drugs, also alters how cannabis is processed and experienced. Further, the individual’s baseline health, including mental health, general physical health, and even sleep quality, will influence how cannabis affects them.
Hence, two users with different histories of use, body composition, or co-consumption can expect dissimilar outcomes even with identical products.
Why some experiences are negative, and when the risk is greater
Because of the many interacting variables, some people will have positive experiences with cannabis, and others may have unpleasant ones. Research shows that specific negative outcomes are more likely under particular circumstances: high THC doses, younger age (especially adolescents), slower metabolism, high potency cannabis, existing anxiety or mood disorder, and irregular consumption in non-familiar environments.
Moreover, for adolescents and young adults whose brains are still developing, the impact can be greater: poorer performance on cognitive tasks, more vulnerability to disordered use, and potentially long-term consequences.
Women may also experience stronger bodily responses, such as increased heart rate and reduced heart rate variability, under higher THC doses, signals of increased physiological anxiety, even if they do not report subjective anxiety.
All of these add up to the conclusion that cannabis is not “one size fits all” and that risk and benefit must be considered in a personalized way.
Making sense of it for users and policy
From a practical standpoint, what does this mean for someone considering cannabis or policymakers trying to frame safe use guidelines? Here are a few takeaways:
- Start low and go slow. Because individual response is variable, beginning with low doses (especially for edibles) and increasing cautiously helps mitigate unexpected or unpleasant reactions.
- Know your set and setting. Being in a safe, comfortable environment and in a positive mindset helps reduce the risk of anxiety or paranoia.
- Be aware of your own biology. Age, sex, health status, metabolism, and use history all matter. For example, younger users or those with high anxiety may face a greater risk.
- Recognize that product matters. The strain, potency, route of administration (smoke, vape, edible), and ratio of cannabinoids all influence the effect.
- Policy and education should reflect variability. Public health messaging might emphasize that “everyone reacts differently” rather than assuming a universal impact. For younger populations or vulnerable groups, risk-specific guidance is beneficial.
Conclusion
In sum, the question “Why does cannabis affect people differently?” has a multifactorial answer. It depends on the chemistry of the product, the route and dose of consumption, the user’s individual biology (including metabolism, age, sex, and brain development), the brain circuits engaged, the user’s psychological state and environment, their history of use, and many other interacting factors. Science is still catching up; historically, cannabis has been understudied relative to its widespread use.
As access expands and potency rises, the need for a nuanced understanding becomes more urgent. While many people enjoy cannabis without issue, others may experience adverse effects or effects very different from those of their peers. Awareness, education, and caution can go a long way in helping individuals navigate these differences with better clarity and safety.