In this series, we will highlight the different articles published by the PsyCoMed consortium, in a more accessible version for the general public.
For this fourth edition, let’s have a look at this study published by our colleagues from Consiglio Nazionale delle Ricerche (Italy) entitled « Repeated treatment with JWH-018 progressively increases motor activity and aggressiveness in male mice: involvement of CB1 cannabinoid and D1/D2 dopaminergic receptors ». This article is available here: https://www.sciencedirect.com/science/article/pii/S0014299925003875?via%3Dihub
Why This Study?
Synthetic cannabinoids (SCs) are lab-made chemicals designed to mimic the effects of cannabis. However, their use can lead to unexpected psychiatric effects, such as:
- agitation,
- psychosis (losing touch with reality),
- or aggressive behavior.
Previous studies have shown that these substances affect the brain, particularly by stimulating mechanisms linked to dopamine (a molecule involved in motivation, pleasure, and movement) and CB1 receptors (part of the endocannabinoid system, which regulates mood, appetite, etc.).
What Does This Study Investigate?
The researchers wanted to understand how repeated exposure to a synthetic cannabinoid called JWH-018 (a compound often found in dangerous « legal highs » or « bath salts ») affects:
- motor activity (spontaneous movements),
- aggressiveness, in adult mice.
They also tested whether drugs that block:
- CB1 receptors (using AM-251),
- dopamine D1/D5 receptors (using SCH23390),
- or dopamine D2/D3 receptors (using haloperidol, an antipsychotic), could reduce or block these effects.
Finally, they analyzed how these substances impact the expression of certain proteins in the brain, such as tyrosine hydroxylase (a key enzyme for dopamine production).
What Are the Results?
- JWH-018 gradually increases agitation and aggressiveness in mice after multiple injections.
- AM-251 (which blocks CB1 receptors) prevents these effects from the first injection and continues to block them after 3 and 7 injections.
- SCH23390 (which blocks D1/D5 dopamine receptors) reduces the effects after 7 injections.
- Haloperidol (which blocks D2/D3 receptors) completely prevents the effects after 7 injections, especially when combined with SCH23390.
- Changes in the brain were observed: levels of D1, D2 receptors, and tyrosine hydroxylase were altered in several areas (cortex, hippocampus, striatum, cerebellum).
Conclusion in Simple Terms
This study shows that: ✅ JWH-018 (a synthetic cannabinoid) causes stimulant effects (such as hyperactivity and aggressiveness) by acting on both CB1 receptors and dopamine. ✅ These effects can be blocked or reduced by drugs targeting these same receptors. ✅ The brain adapts to these substances, which can lead to lasting changes in its functioning.
Why Is This Important? This helps us understand why synthetic cannabinoids are dangerous and how their negative effects might be treated (for example, with existing medications). It also shows that these substances are not harmless and can have serious consequences on behavior and the brain.