Brain Glutamate Levels Were Lower in Cannabis Users and Linked to Craving During Abstinence | Research

The takeaway

In a study of 20 cannabis users who completed 21 days of abstinence, glutamate levels in the dorsal anterior cingulate cortex were significantly lower than in controls, and decreasing glutamate correlated with increasing craving.

People interested in the neuroscience of cannabis withdrawal and quitting

r = -0.72 glutamate-craving link

What the researchers found

dACC glutamate was significantly lower in cannabis users compared to controls from baseline through day 21 of abstinence (F=5.90, p=0.022). Changes in glutamate between baseline and day 21 had a significant negative correlation with changes in craving (r=-0.72, p=0.005). Baseline anxiety severity correlated with urinary THC levels.

Why it matters

Glutamate is the brain's primary excitatory neurotransmitter and plays a key role in addiction and relapse. Finding that lower glutamate is linked to higher craving during cannabis abstinence suggests a potential target for medications that could ease withdrawal.

The numbers in context

20 cannabis users and 10 controls completed protocol; dACC glutamate significantly lower in users (F=5.90, p=0.022); glutamate-craving correlation r=-0.72 (p=0.005); baseline anxiety correlated with THC levels (r=0.768, p=0.000076)

How the study worked

Prospective cohort study with 26 cannabis users and 11 controls (20 users and 10 controls completed 21-day verified abstinence). Dorsal anterior cingulate cortex glutamate and GABA measured with proton MRS at baseline and abstinence days 7 and 21. Cannabis withdrawal, craving, sleep, and mood measured concurrently.

What this study cannot tell us

Small sample of 20 users and 10 controls limits generalizability. MRS measures glutamate in a single brain region. Cannot determine whether low glutamate is a cause or consequence of cannabis use. Non-treatment-seeking sample may differ from those seeking help to quit.

How to read the evidence

Small prospective study with verified abstinence and objective brain measures, but limited sample size

When this study was published

2022 study

The bigger picture

Understanding the neurochemistry of cannabis withdrawal could lead to targeted medications. If glutamate levels predict craving, glutamate-modulating drugs already used for other conditions might be repurposed to help people quit cannabis.

Questions still open

Would glutamate-modulating medications reduce cannabis craving? Do glutamate levels recover with longer abstinence? Is the glutamate-craving link specific to cannabis or shared across substances?

Common questions

Why does low glutamate matter for cannabis withdrawal?

Glutamate is the brain's main excitatory neurotransmitter and is involved in learning, memory, and reward processing. Lower levels in cannabis users correlated with higher craving, suggesting it may play a role in the difficulty of quitting.

Do glutamate levels return to normal after quitting?

In this study, glutamate remained lower than controls through 21 days of abstinence. Whether levels eventually normalize with longer abstinence was not examined.

Read the original research

Lower dACC glutamate in cannabis users during early phase abstinence.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 47(11), 1969-1975

View on PubMed ↗Publisher’s paper ↗

Citation

Zuo, Chun S; Davis, Katherine A; Lukas, Scott E. (2022). Lower dACC glutamate in cannabis users during early phase abstinence.. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 47(11), 1969-1975. https://doi.org/10.1038/s41386-022-01321-5