Cellular and molecular life sciences : CMLS
September 10, 2024
Klemens Egger, Helena D Aicher, Paul Cumming et al.
30 citations
The potent hallucinogen N,N-dimethyltryptamine (DMT) alters perception, mood, and cognition, presumably through agonism at serotonin 5-HT1A/2A/2C receptors in the brain. DMT is nearly inactive orally due to rapid first-pass metabolism, but co-administration with β-carbolines or synthetic MAO-A inhibitors—as in the Amazonian brew ayahuasca—greatly increases its bioavailability and duration of action. The synergistic effects of DMT and MAOIs may promote neuroplasticity, which presumably underlies their promising therapeutic efficacy in clinical trials for depression, addiction, and post-traumatic stress disorder. Neuroimaging reveals alterations in brain activity, functional connectivity, and network dynamics during DMT-induced altered states.
Cellular and molecular life sciences : CMLS
February 27, 2024
Radhika Rawat, Elif Tunc-Ozcan, Sara Dunlop et al.
17 citations
Ketamine's rapid and sustained antidepressant effects rely on separate biological mechanisms. A single dose rapidly improves mood by increasing activity of immature neurons in the hippocampal dentate gyrus without generating new neurons. Six doses over two weeks doubled the duration of behavioral improvement, which correlated with increased numbers of immature neurons (neurogenesis) and reduced bone morphogenetic protein (BMP) signaling, a known inhibitor of neurogenesis. Experimentally maintaining BMP signaling with a lentivirus blocked the sustained but not the rapid effects, showing that decreased BMP signaling and increased neurogenesis are necessary for ketamine's long-lasting benefits. Understanding these dual mechanisms may aid development of safer, sustained antidepressant therapies.
Cellular and molecular life sciences : CMLS
January 21, 2025
Alejandra Pulido-Saavedra, Henrique Nunes Pereira Oliva, Tiago Paiva Prudente et al.
5 citations
The opioid crisis has driven a search for new treatments for opioid use disorder (OUD). A systematic review of 40 preclinical animal studies found that the psychedelic compounds 18-methoxycoronaridine (18-MC), ibogaine, noribogaine, and ketamine generally reduced opioid self-administration, eased withdrawal symptoms, and altered conditioned place preference. However, seven studies showed no improvement over controls. Most research has focused on iboga derivatives, which appear effective but carry higher cardiovascular risk than other psychedelics. The review calls for more translational and clinical studies that test a broader range of psychedelic agents and explore mechanisms, safety, dosing, and treatment frequency.