Global Increases in Brain Glucose Metabolism Following Acute N,N-Dimethyltryptamine and Harmine Administration in Healthy Volunteers: An [¹⁸F]FDG-PET Study

Abstract Classical psychedelics such N,N -dimethyltryptamine (DMT), psilocybin, and lysergic acid diethylamide (LSD) modulate consciousness via serotonergic receptor agonism, and are increasingly investigated for their psychotherapeutic potential. When combined with the monoamine oxidase A (MAO-A) inhibitor harmine-mimicking the pharmacological profile of ayahuasca-oral DMT induces a psychedelic experience lasting 4-5 hours. While neuroimaging studies have examined changes in brain activity, connectivity, and cerebral perfusion under psychedelics, their effects on cerebral glucose metabolism remain largely unexplored. Here, we used positron emission tomography with [ 18 F]fluorodeoxyglucose ([¹⁸F]FDG-PET) to assess the cerebral metabolic rate for glucose consumption (CMRglc) following buccal DMT + harmine (90 mg DMT, 120 mg harmine) versus placebo in a single-blind, placebo-controlled, crossover design in (n = 14) healthy males. Scans were acquired during peak drug effects, i.e., 100-170 min post-administration. Global CMRglc increased by 12% under DMT + harmine compared to placebo ( t = 2.57, p