Effects of δ9-tetrahydrocannabinol on human working memory function

Area of Science:

• Neuroscience
• Psychopharmacology
• Cognitive Psychology

Background:

• The endocannabinoid (eCB) system is implicated in schizophrenia pathophysiology and working memory (WM) function.
• Schizophrenia patients often exhibit significant WM deficits, suggesting a potential role for the eCB system.
• This study investigates whether manipulating the eCB system can induce abnormal WM activity in healthy individuals.

Purpose of the Study:

• To examine the effects of perturbing the endocannabinoid system on working memory function in healthy volunteers.
• To determine if the eCB system plays a role in working memory deficits observed in schizophrenia.

Main Methods:

• A placebo-controlled, cross-over pharmacological functional magnetic resonance imaging (fMRI) study.
• 17 healthy volunteers received either Δ9-tetrahydrocannabinol (an eCB agonist) or a placebo.
• Participants completed a parametric Sternberg item-recognition task across five difficulty levels.

Main Results:

• Δ9-Tetrahydrocannabinol significantly reduced working memory performance accuracy.
• While placebo increased brain activity linearly with WM load, Δ9-tetrahydrocannabinol enhanced activity at low loads.
• The drug disrupted the linear relationship between WM load and brain activity in key regions, including the prefrontal cortex.

Conclusions:

• Challenging the endocannabinoid system with Δ9-tetrahydrocannabinol can lead to abnormal WM activity and performance deficits.
• These findings support the hypothesis that the eCB system is involved in the working memory deficits seen in schizophrenia.
• The study highlights the complex role of the eCB system in modulating cognitive functions like working memory.