Use or Dependence? What Genetics Teaches Us About Cannabis and Mental Health

One of the largest genetic studies ever published on Cannabis and mental disorders has just been released by the journal Nature Mental Health in June 2025 (1). The question guiding the research is simple but provocative: does Cannabis cause depression, schizophrenia, or anxiety disorders? Or do people with a genetic predisposition to these conditions end up resorting to Cannabis as an attempt at emotional regulation? The answer, as always, is not binary. But science is beginning to clarify important pathways for those involved in prescription.

Occasional Use versus Dependence

The study analyzed genetic data from hundreds of thousands of individuals from large international biobanks such as UK Biobank, FinnGen, and iPSYCH. The goal was to compare two traits: lifetime Cannabis use—even if occasional—and Cannabis use disorder (CanUD), a clinical condition characterized by compulsive, persistent use with functional impairment. Based on DSM diagnostic criteria, individuals with signs such as intense craving, withdrawal, tolerance, failed attempts to quit, and impacts on health or relationships were considered (2,3).

Risk of Dependence: Context and Comparison

The data shows that about 9% to 10% of people who have ever used Cannabis in their lifetime may develop dependence (4). This number rises to 17% among those who start using in adolescence and can exceed 25% to 30% among daily users, especially without clinical supervision (5). To contextualize: the risk of alcohol dependence is around 15%, while benzodiazepines—such as clonazepam—present a dependence risk of up to 30% with prolonged use (6,7). In other words, the potential for Cannabis dependence is far from negligible, but it is not the highest among commonly used substances.

Genetic Contributions of the Study

The major contribution of the 2025 study is showing that Cannabis use disorder has a genetic profile quite distinct from occasional use. Through techniques such as global and local genetic correlation, variant colocalization, and Mendelian randomization, researchers demonstrated that CanUD shares genetic variants with various mental disorders—especially ADHD, major depression, PTSD, and schizophrenia (1). The association was statistically robust and bidirectional: both Cannabis dependence can increase the risk of these disorders, and these disorders can predispose to problematic use of the plant.

Different Genetic Patterns Between Use and Dependence

On the other hand, Cannabis use without dependence showed a very different pattern. In general, it was associated with personality traits such as openness to experience—which includes curiosity, creativity, and novelty-seeking—but without indicating a direct risk for mental illnesses (1,8). The only partial exception was ADHD, whose association with use was moderate, but still more present among people with a previous diagnosis.

Why This Differentiation is Essential

This differentiation is crucial from a clinical perspective. One cannot categorize the individual who experiments or occasionally uses Cannabis in the same way as someone who develops a pattern of dysregulated, frequent use with functional impairment. These are distinct profiles, with different determinants and risks. Generalization—whether in the direction of criminalization or romanticization—fails to recognize the nuances of human use of the plant.

Genetics as a Warning, Not a Sentence

From a genetic perspective, the main message of the study is that Cannabis dependence shares biological pathways with severe mental disorders. Therefore, Cannabis is not a sole cause but can be a trigger in predisposed individuals. Genetic vulnerability, associated with factors such as early onset, unaccompanied psychological distress, uncontrolled dose or potency use, can indeed favor negative outcomes. This does not invalidate its therapeutic use—but reinforces the importance of structured, monitored, and contextualized use.

CBD in the Treatment of Dependence Itself

An interesting example comes from a review published in 2022, which evaluated the use of cannabinoids in the treatment of Cannabis dependence itself (9). While synthetic THC use proved risky, especially in adolescents, cannabidiol (CBD) showed positive effects in reducing withdrawal symptoms, craving, anxiety, and cognitive impairments, with high tolerability. The authors argue that CBD interventions—combined with psychosocial strategies—can be safe and promising alternatives for young individuals with problematic use, especially when the goal is harm reduction rather than immediate abstinence.

Structured and Monitored Prescription

Genetics does not determine destiny but reveals points of attention. As the literature shows, therapeutic use of Cannabis can be beneficial in cases of chronic pain, sleep disorders, anxiety, and post-traumatic stress, as long as it is well-indicated and monitored (10–12). The risk lies, as always, in the absence of care. It is not the plant that causes illness—it is the lack of listening, risk screening, clinical supervision, and longitudinal follow-up.

THC: Risk and Benefit Coexist

It is important to highlight that among the plant's phytocannabinoids, Δ9THC is the only one with recognized dependence potential. Its agonist action on CB1 receptors increases dopamine in the reward system, favoring the development of craving and tolerance, especially with high-potency products (≥ 10–20 % Δ9THC), frequent use, and onset in adolescence. However, it is precisely Δ9THC that provides unique therapeutic properties: it is effective as an antiemetic in chemotherapy, appetite stimulant in HIV/AIDS cachexia, muscle relaxant, and analgesic in multiple sclerosis, as well as aiding in spasticity. This reinforces the need for balance and clarity in prescription: knowing that the risk exists but also recognizing that when well-indicated, Δ9THC can be the key element of the therapeutic effect (13).

Clinical Listening: The Role of the Prescribing Professional

Therefore, the role of the prescribing professional is, above all, a careful analysis of the context. Who is this individual? What is their family history? Are there active psychiatric symptoms? Have there been attempts at self-medication? Is Cannabis use part of a therapeutic plan or an attempt at spontaneous relief? Care for the endocannabinoid system requires this comprehensive view, which goes beyond the symptom and seeks to understand the organism in its complexity.

The Right Question: For Whom, How, and With What Support?

More than discussing whether Cannabis is good or bad, we need to ask: for whom, in what dose, with what support, and with what therapeutic objective. The answer is not in the isolated substance but in how it integrates into each individual's life. And, most importantly, in the type of clinical bond established between prescription, listening, and follow-up.

Commitment to Conscious Prescription

Science advances, and with it, our commitment to conscious prescription must also evolve. Because Cannabis can be medicine, but it can also be an escape. It is up to us to help each person navigate a safe, respectful, and evidence-based therapeutic path.

References

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