Mixing Tobacco and Cannabis Rewires Brain’s ‘Bliss Molecule’ System, Study Finds

Dual Use of Tobacco and Cannabis Linked to Disrupted Brain Chemistry

A groundbreaking neuroscience study from the Yale School of Medicine has provided a crucial biological explanation for why individuals who use both tobacco and cannabis—a practice known as co-use—often face greater challenges with addiction, anxiety, and depression compared to those who use only one substance.

The research reveals that combining these two substances significantly alters the brain’s natural reward and mood regulation system, specifically by increasing the activity of an enzyme responsible for breaking down the brain’s own natural pleasure chemicals.

This finding offers a molecular target for developing more effective treatments for co-occurring addiction and mental health issues, which are notoriously difficult to manage in clinical settings.

The Key Finding: Elevated FAAH Enzyme Activity

The central discovery revolves around the enzyme Fatty Acid Amide Hydrolase (FAAH). FAAH is the primary enzyme responsible for degrading endocannabinoids—natural compounds produced by the body that are chemically similar to those found in cannabis.

Researchers found that individuals who regularly co-used tobacco and cannabis exhibited significantly higher levels of FAAH activity in their brains compared to control groups, single-substance users, or those who abstained entirely.

What FAAH Does to the Brain’s Reward System

FAAH’s primary target is anandamide, one of the most well-known endocannabinoids, often nicknamed the “bliss molecule” due to its role in regulating mood, pleasure, and motivation. Anandamide naturally binds to the same receptors (CB1) that THC from cannabis targets.

When FAAH levels are elevated, anandamide is broken down much faster. This rapid degradation has a profound effect:

• Reduced Natural Reward: Lower baseline levels of anandamide mean the brain has less natural capacity for pleasure and stress resilience.
• Increased Vulnerability: This deficit may contribute to the higher rates of anxiety and depression observed in co-users.
• Addiction Severity: The brain may seek external substances (like nicotine and THC) more aggressively to compensate for the internal chemical imbalance, making quitting exponentially harder.

This study suggests that co-use doesn’t just combine the effects of two drugs; it creates a unique, detrimental biological state that reinforces dependency on both substances simultaneously.

Methodology: Mapping Brain Enzymes with PET Scans

To achieve this precise measurement, the Yale research team utilized advanced medical imaging technology. They employed Positron Emission Tomography (PET) scans, a technique that allows scientists to visualize and quantify biochemical processes in the living brain.

Specifically, they used a radioactive tracer designed to bind exclusively to the FAAH enzyme. By measuring the tracer’s uptake in various brain regions, the researchers could accurately map the concentration and activity of FAAH in the study participants.

Study Participants Included:

1. Individuals who used both tobacco and cannabis (Co-users).
2. Individuals who used only cannabis.
3. Individuals who used only tobacco.
4. Healthy control subjects who used neither substance.

The PET scan results clearly demonstrated that the co-use group was the outlier, showing a distinct and significant upregulation of the FAAH enzyme that was not observed to the same extent in the single-use groups.

Implications for Mental Health and Cessation Efforts

This neurobiological finding provides a critical link between the behavioral practice of co-use and the associated clinical outcomes. Clinicians have long noted that individuals who use both substances often report more severe symptoms and struggle more intensely with cessation.

The Vicious Cycle of Co-Use

Researchers hypothesize that the elevated FAAH creates a vicious cycle. The rapid breakdown of anandamide leads to chronic low mood and increased stress sensitivity. Users may then turn to both nicotine (a stimulant and mood modulator) and cannabis (often used for relaxation or anxiety reduction) to manage these negative emotional states.

“The combination of tobacco and cannabis appears to create a unique neurochemical profile that locks users into a cycle of dependency,” explained a researcher involved in the study. “The brain is actively working against its own natural reward system, necessitating external chemical input just to maintain equilibrium.”

This cycle explains why co-users frequently exhibit higher rates of:

• Generalized Anxiety Disorder (GAD): The constant depletion of natural mood regulators increases baseline stress.
• Clinical Depression: Lack of anandamide contributes to anhedonia (inability to feel pleasure).
• Treatment Resistance: Traditional cessation programs often fail because they don’t address the underlying, combined neurochemical dysregulation caused by the dual exposure.

The Role of Nicotine

While cannabis introduces external cannabinoids (like THC), the study suggests that the nicotine component of tobacco may be the primary driver behind the FAAH upregulation. Nicotine is known to interact broadly with various neurotransmitter systems, and its influence here appears to be a crucial catalyst in disrupting the endocannabinoid balance.

Future Directions for Treatment

Understanding the role of FAAH opens up promising new avenues for pharmacological intervention. If the goal is to stabilize mood and reduce dependency, targeting the enzyme responsible for the breakdown of the “bliss molecule” could be highly effective.

One potential strategy involves the use of FAAH inhibitors. These drugs are designed to block the FAAH enzyme, preventing it from breaking down anandamide. By preserving the brain’s natural supply of anandamide, these inhibitors could potentially:

1. Elevate Mood: Restore natural pleasure and reward signaling.
2. Reduce Anxiety: Increase the brain’s natural resilience to stress.
3. Ease Withdrawal: Mitigate the severe mood disturbances often experienced during cessation attempts.

While FAAH inhibitors are still under investigation for various conditions, this study provides strong evidence that they could be particularly beneficial for treating co-use addiction, offering a way to rebalance the endocannabinoid system that has been chemically hijacked by the simultaneous use of tobacco and cannabis.

Key Takeaways for Readers

This research underscores the unique risks associated with combining tobacco and cannabis, moving beyond simple additive effects to demonstrate a distinct biological alteration.

• Biological Mechanism: Co-use significantly increases the enzyme FAAH in the brain.
• Chemical Consequence: High FAAH rapidly destroys anandamide (the “bliss molecule”), leading to lower natural mood regulation.
• Clinical Impact: This chemical imbalance correlates strongly with higher rates of anxiety, depression, and significantly greater difficulty in quitting both substances.
• Treatment Future: The findings suggest that treatments targeting FAAH inhibitors may be crucial for helping co-users achieve successful long-term abstinence and improve mental health outcomes.

If you or someone you know is struggling with the use of tobacco and cannabis, seeking help from a healthcare professional specializing in dual diagnosis or addiction medicine is recommended to address the complex neurochemical factors involved.