Ayahuasca, an Amazonian plant medicine containing DMT and harmine, shows promise for mental health disorders but its oral use causes gastrointestinal side effects and unpredictable drug levels. This study tested new ayahuasca-analogue formulations in 10 healthy men: an oral capsule of purified DMT and harmine versus a combined oromucosal harmine tablet with intranasal DMT spray. The combined buccal/intranasal route significantly reduced variations in systemic exposure and attenuated common side effects like nausea, vomiting, and diarrhea compared to traditional oral ayahuasca. All preparations were well tolerated. This approach may enable safer, patient-friendly DMT/harmine administration for affective disorders.
Three psychoactive stimulants—MDMA, amphetamine, and the new psychoactive substance mephedrone—alter blood metabolites in overlapping but distinct ways. Using plasma samples from controlled human administration studies and liquid chromatography-high resolution mass spectrometry, researchers identified changes in metabolites linked to energy metabolism, steroid biosynthesis, and amino acid pathways. Linoleic acid and pregnenolone-sulfate shifted similarly after intake of all three drugs. Mephedrone produced a metabolic profile more like amphetamine than MDMA, particularly in energy metabolism. These findings could guide future targeted studies on pharmacological actions and help identify biomarkers of drug use.
A single 125 mg dose of MDMA alters dozens of endogenous metabolites in human plasma, including increases in cortisol, pregnenolone sulfate, and several inflammation mediators, alongside a decrease in calcitriol. These changes suggest heightened stress and serotonergic activity, activation of inflammatory pathways, and potential reduction in neuroprotective factors for brain dopamine neurons.
A single dose of MDMA (ecstasy) alters the plasma metabolome in healthy adults. In a double-blind, placebo-controlled crossover trial with 15 participants, nine metabolites showed significant concentration changes after MDMA compared with placebo. The main changes involved glycerophospholipids, which may indicate increased energy production, and the ratio of methionine-sulfoxide to methionine, a potential marker of oxidative stress. Baseline samples were essential to avoid overestimating effects due to high interday variability among individuals.