Cannabis use has become increasingly common, with about one in four Americans and Canadians having used it in the past year. As laws have relaxed, daily use has climbed as well⁽¹⁾. 

This trend has renewed concern among clinicians and researchers about how frequent cannabis exposure affects mental health, particularly in adolescents and young adults⁽²⁾. 

During these years, the brain is still developing and more vulnerable to problems such as depression, anxiety, psychosis, and suicidal thoughts associated with heavy cannabis use⁽³⁾.

An often-overlooked fact is that up to 80 percent of cannabis users also use tobacco⁽⁴⁾.

Many smoke cigarettes, while others mix tobacco with cannabis in joints or vape both substances. This overlap matters because research on 'cannabis use' may actually reflect the combined effects of both drugs. Several factors help explain this pattern.

Tobacco can intensify or prolong the high from cannabis, and both are commonly smoked⁽⁵⁾.

In addition, genetic, personality, and environmental factors that increase vulnerability to one substance often apply to the other⁽⁶⁾.

The Brain’s Endocannabinoid System: The Body’s Internal Regulator

The brain contains its own 'cannabis-like' signaling network, known as the endocannabinoid system (eCB system). This system helps regulate mood, stress, and emotional balance, functioning somewhat like a thermostat that keeps internal conditions steady.

A key messenger in this system is anandamide, often called the “bliss molecule” for its role in maintaining emotional stability. The enzyme FAAH (fatty acid amide hydrolase) breaks down anandamide once it has done its job. When FAAH activity is too high, it can deplete anandamide levels, leaving the brain with less of this natural mood buffer. Low anandamide levels have been linked to higher rates of depression, anxiety, and other mood disorders⁽⁷⁾.

How Cannabis and Tobacco Affect This System

Heavy cannabis use can disrupt the endocannabinoid system. Brain imaging studies show that frequent users have fewer cannabinoid (CB1) receptors, which are the sites that both cannabis and anandamide act on, especially in regions that regulate motivation and emotion⁽⁸⁾.

These changes often reverse after periods of abstinence, suggesting the brain is attempting to adapt to constant exposure.

Tobacco affects the same network in a similar way. People who smoke regularly also show fewer CB1 receptors and lower anandamide levels, particularly in brain areas tied to memory, movement, and decision-making⁽⁹⁾. 

In essence, both substances strain the brain’s internal regulatory system, though through slightly different mechanisms.

When Both Substances Are Used Together

Because cannabis and tobacco influence overlapping brain circuits, using them together may magnify their individual effects. To investigate this, researchers used PET brain imaging with a tracer called [11C]CURB, which binds to FAAH and reveals how active it is in different brain regions.

The study compared two groups:

• Individuals who used both cannabis and tobacco
• Individuals who used cannabis only

Researchers focused on brain areas rich in both cannabinoid and nicotine receptors, the regions most likely to reflect interaction between the two systems⁽¹⁰⁾.

What the Study Found

People who used both cannabis and tobacco had higher FAAH activity in several regions, including the cerebellum and substantia nigra, which are involved in movement, emotion, and habit formation. In practical terms, this means the enzyme that breaks down anandamide was more active, essentially 'clearing out' more of this mood-stabilizing chemical.

The more tobacco participants reported using, the higher their FAAH levels tended to be. Cannabis use alone did not show this pattern. These results suggest that tobacco, either by itself or through interaction with cannabis, may drive these changes.

Earlier studies found that cannabis-only users often have lower FAAH levels than non-users, which may account for some of the differences observed here. The current findings point toward a unique biological interaction between nicotine and cannabis that may make the endocannabinoid system less stable or more reactive.

Why This Matters

Higher FAAH activity means less available anandamide, the brain’s natural emotional stabilizer. This imbalance could help explain why people who use both cannabis and tobacco often experience greater anxiety, depressive symptoms, stronger cravings, and more intense withdrawal than those who use cannabis alone⁽¹¹⁾.

In effect, the combination appears to reduce the brain’s natural resilience to stress and negative emotions, leaving people more vulnerable to psychological distress.

What Comes Next

This study offers valuable insight but also has limits. The sample size was small, and it did not include tobacco-only or non-using control groups. Measures of mental health symptoms were not included, and tobacco use was assessed primarily through cigarette smoking rather than other products such as e-cigarettes.

Future research with larger, more diverse samples could help clarify:

• Whether tobacco alone raises FAAH levels or whether the combination with cannabis is responsible
• Whether these brain changes predict mental health outcomes
• Whether treatments that target FAAH could reduce withdrawal symptoms or dependence in people who co-use

The Bottom Line

Both cannabis and tobacco alter the brain’s internal system that regulates mood and stress. When used together, their combined effects may disrupt that balance more profoundly which helps to explain why using them together is often linked to stronger dependence and greater emotional challenges.

Understanding how these substances interact at the molecular level not only deepens our knowledge of addiction but also points to a promising therapeutic target: FAAH, the enzyme that helps maintain the brain’s emotional equilibrium.

If you are experiencing cannabis-related cognitive symptoms, consider the following:

• Try a slow taper. Gradually decrease the potency (THC content) of cannabis you use or how frequently you use it over the course of several weeks, especially if you have a history of cannabis withdrawal.
• Work with your clinician. Be honest and open with your clinician about your cognitive symptoms, as other medical or psychiatric factors may be at play. Your clinician can also assist you with navigating a cannabis taper safely, and potentially more comfortably, using other supportive means.
• Give it time. It may take up to a month before you experience improvements after reducing your dose, as cannabis can remain in the body for 2-4 weeks.
• Try objective cognitive tracking. Use an objective means such as an app or a test such as the mini-mental status exam to track your brain function. This may be more accurate than self-observation, which is quite subjective. Your mental health provider may be able to assist with administering occasional cognitive assessments.
• Consider alternative strategies. Brain function is not static, like eye color or the number of toes on our feet. Aerobic exercise, strength training and engaging in mindfulness, meditation, and psychotherapy may improve long-term cognition.

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