Why smoking tobacco with cannabis may drain the brain's bliss molecule

A new study using advanced brain imaging suggests that people who use both tobacco and cannabis may have lower activity of the brain's natural "bliss molecule", hinting at why quitting feels harder

People who smoke both cannabis and tobacco may be draining a key “bliss” chemical in the brain, new research suggests.

 

The research, titled A preliminary investigation of tobacco co-use on endocannabinoid activity in people with cannabis use, published in Drug and Alcohol Dependence Reports, uses advanced Positron Emission Tomography (PET) imaging to reveal this shift in brain chemistry for the first time in humans.

 

The researchers found that people who regularly use both substances have higher levels of an enzyme called fatty acid amide hydrolase (FAAH), a molecule that breaks down anandamide, the body’s own “bliss chemical”. More FAAH means less anandamide activity, which has long been linked to anxiety, low mood, and more difficult withdrawal.

 

The discovery adds a new piece to the puzzle of why people who co-use often struggle more with quitting and mental health symptoms. 

What is the ‘bliss molecule’ anandamide? 

Anandamide is a naturally occurring endocannabinoid, which means it is produced by the body and binds to the same brain receptors as tetrahydrocannabinol (THC), the psychoactive component of cannabis.

 

Its name comes from ananda, the Sanskrit word for joy. This molecule influences mood, motivation, stress, pain responses, and emotional regulation.

 

According to research, when anandamide levels dip, it leads to: 

• heightened anxiety 
• depressive symptoms 
• stronger cravings and withdrawal difficulty 

The body carefully balances anandamide levels using an enzyme called fatty acid amide hydrolase (FAAH), which breaks it down. When FAAH levels rise, anandamide activity drops.

 

The study found that people who used both cannabis and tobacco had significantly higher FAAH levels in key brain regions compared with cannabis-only users. 

How does this affect people who use both tobacco and cannabis?

 

The discovery provides a biological explanation for something clinicians have noticed for years that people who use both substances often have: 

• more depressive symptoms 
• more anxiety 
• harsher cannabis withdrawal 
• greater difficulty quitting 
• a higher risk of cannabis dependence 

These effects have largely been observed at the behavioural and psychological level. Now, researchers have uncovered a molecular mechanism that may help explain why.

 

If anandamide is consistently depleted by elevated FAAH, the brain may be left in a more vulnerable, dysregulated state, particularly during attempts to quit cannabis.

 

The researchers highlighted that currently, the only recognised treatments for cannabis use disorder are behavioural therapies such as counselling.

 

FAAH, because of its role in regulating anandamide, could become a potential drug target.

 

The authors argue that the next steps should include larger studies, and if researchers can find a way to reduce FAAH activity safely, this may help: 

• ease withdrawal 
• improve mood 
• reduce cravings 
• support recovery, especially in people who also smoke tobacco 

If these patterns hold true, researchers may finally have a biological marker that explains the heightened challenges faced by co-users, and a path to targeted treatments. 

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