Are Brain Chemical Levels Different in People with Tourette Syndrome?

What you need to know

• Researchers found higher levels of certain brain chemicals called endocannabinoids in people with Tourette syndrome compared to those without the disorder.
• This suggests the endocannabinoid system, which helps regulate various brain functions, may play a role in Tourette syndrome.
• The findings could help explain why cannabis-based treatments are sometimes effective for Tourette syndrome and may lead to new treatment approaches.

Understanding Tourette syndrome and the endocannabinoid system

Tourette syndrome is a neurological disorder characterized by repetitive, involuntary movements and vocalizations called tics. It often begins in childhood and can be accompanied by conditions like attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, and depression. While the exact cause is unknown, Tourette syndrome is thought to involve abnormalities in brain chemicals and circuits, particularly those involving dopamine.

The endocannabinoid system is a complex cell-signaling system in the body that plays a role in regulating various functions, including mood, memory, appetite, and movement. It consists of:

1. Endocannabinoids: Molecules produced naturally by the body that are similar to compounds found in cannabis.
2. Receptors: Proteins found throughout the body that endocannabinoids and cannabinoids bind to.
3. Enzymes: Proteins that break down endocannabinoids after they’ve carried out their function.

The two main endocannabinoids are:

• Anandamide (AEA)
• 2-arachidonoylglycerol (2-AG)

These molecules help keep internal functions running smoothly. They’re produced by the body as needed, act on nearby receptors, and are then broken down by enzymes.

Why study endocannabinoids in Tourette syndrome?

Several observations have led researchers to investigate the potential role of the endocannabinoid system in Tourette syndrome:

1. Some patients report that cannabis use reduces their tics and other symptoms.
2. Small clinical studies have shown that THC (the main psychoactive component of cannabis) and cannabis-based medicines can improve tics and related symptoms in some patients.
3. The endocannabinoid system is known to interact with other neurotransmitter systems in the brain, including dopamine, which is thought to be involved in Tourette syndrome.

Given these connections, researchers wanted to determine if there were differences in endocannabinoid levels in the brains of people with Tourette syndrome compared to those without the disorder.

How the study was conducted

The researchers collected cerebrospinal fluid (CSF) samples from 20 adults with Tourette syndrome and 19 control subjects without the disorder. CSF is the clear liquid that surrounds the brain and spinal cord, and it can provide valuable information about the chemical environment in the brain.

The researchers measured levels of:

• Anandamide (AEA)
• 2-arachidonoylglycerol (2-AG)
• Palmitoyl ethanolamide (PEA) - a molecule similar to endocannabinoids
• Arachidonic acid (AA) - a fatty acid involved in endocannabinoid production

They also collected detailed information about the participants’ tic severity and other symptoms using standardized questionnaires and rating scales.

Key findings

The study revealed several important differences between the Tourette syndrome group and the control group:

1. Higher endocannabinoid levels: People with Tourette syndrome had significantly higher levels of both AEA and 2-AG in their cerebrospinal fluid compared to the control group.

2. Elevated related molecules: Levels of PEA and AA were also significantly higher in the Tourette syndrome group.

3. Correlation with ADHD symptoms: Higher levels of 2-AG were associated with more severe ADHD symptoms in the Tourette syndrome group.

4. No correlation with tic severity: Interestingly, endocannabinoid levels did not correlate with the severity of tics or other symptoms like OCD or depression.

What do these findings mean?

The discovery of elevated endocannabinoid levels in people with Tourette syndrome is an important step in understanding the disorder. However, interpreting these results is complex, and several possibilities exist:

1. Compensation mechanism: The increased endocannabinoid levels could be the brain’s attempt to compensate for other imbalances, such as dopamine dysfunction. Endocannabinoids can modulate dopamine activity, so higher levels might be trying to “dampen” an overactive dopamine system.

2. Primary cause: Alternatively, abnormalities in the endocannabinoid system could be a root cause of Tourette syndrome, leading to downstream effects on other neurotransmitter systems.

3. Epiphenomenon: It’s possible that the elevated endocannabinoid levels are a side effect of other brain changes in Tourette syndrome and don’t play a direct role in causing symptoms.

4. Stress response: Since stress is known to worsen tics, the elevated endocannabinoid levels could reflect the body’s attempt to cope with chronic stress.

The correlation between 2-AG levels and ADHD symptoms is particularly interesting, as it suggests the endocannabinoid system may play a role in this common co-occurring condition.

Implications for treatment

These findings could have important implications for treating Tourette syndrome:

1. Support for cannabis-based treatments: The study provides a biological basis for why some patients benefit from cannabis or THC-based medications. These treatments may be working by further augmenting the already elevated endocannabinoid system.

2. New drug targets: Understanding the role of the endocannabinoid system could lead to the development of new medications that more specifically target this system.

3. Personalized medicine: In the future, measuring endocannabinoid levels might help predict which patients are most likely to respond to certain treatments.

Limitations and future research

While this study provides valuable insights, it’s important to note some limitations:

• Small sample size: The study included only 20 people with Tourette syndrome, so larger studies are needed to confirm the findings.
• Causation unclear: The study shows a correlation between Tourette syndrome and elevated endocannabinoid levels, but it doesn’t prove that these changes cause the disorder.
• Adult focus: The study only included adults, so it’s unknown if similar changes are present in children with Tourette syndrome.

Future research directions could include:

• Longitudinal studies to see how endocannabinoid levels change over time and relate to symptom fluctuations
• Investigation of endocannabinoid levels in other body fluids (like blood) that are easier to collect
• Studies examining the effects of medications or interventions on endocannabinoid levels and symptoms

Conclusions

• This study provides the first evidence of altered endocannabinoid levels in the brains of people with Tourette syndrome.
• The findings suggest that the endocannabinoid system may play a role in the disorder, potentially interacting with other neurotransmitter systems like dopamine.
• While more research is needed, these results could help explain why some patients benefit from cannabis-based treatments and may lead to new therapeutic approaches for Tourette syndrome.