A single intravenous dose of R,S-ketamine (0.71 mg/kg bodyweight) administered over 40 minutes to 10 healthy volunteers did not significantly increase glutamate levels in the nucleus accumbens (NAc) when measured by proton magnetic resonance spectroscopy. However, individual changes in glutamate were positively associated with anxious ego dissolution and reductions in vigilance, suggesting that ketamine-induced glutamate alterations in the NAc may underlie specific alterations in perception and consciousness.
A randomized, placebo-controlled, double-blind trial will test a single ketamine infusion, three sessions of reward-imagery real-time fMRI neurofeedback training, and their combination in 120 people with cocaine use disorder. The study expects both interventions to reduce the proportion of cocaine use days, with ketamine increasing glutamate in the reward system and lowering craving, and neurofeedback re-sensitizing participants to natural rewards. This neurobiologically informed approach aims to open new treatment avenues through individualized pharmaco-psychotherapy.