Frontiers in Psychiatry
October 12, 2022
Robert J Sottile, Thomas Vida
30 citations
Post-traumatic stress disorder (PTSD) affects millions worldwide, with 40–70% of patients experiencing refractory disease despite available treatments. MDMA, like classic psychedelics such as psilocybin, has been used to enhance psychotherapy since its discovery, but research into its mechanisms has been limited due to its Schedule 1 classification. The pro-social effects of MDMA are thought to improve therapeutic alliance and facilitate trauma processing, but this may not fully explain its efficacy. A more nuanced explanation combines MDMA's pro-social effects with molecular mechanisms, such as increased brain-derived neurotrophic factor (BDNF) availability in fear memory learning pathways, potentially accounting for its therapeutic actions in PTSD.
Psychoactives
February 26, 2024
Frankie A. Colosimo, Philip Borsellino, Reese I. Krider et al.
8 citations
DMT, a naturally occurring psychedelic compound, promotes neuroplasticity—the brain's ability to remodel its neural connections—by stimulating neuritogenesis, the growth of new neuronal branches. It interacts with serotonergic, sigma-1, and trace amine-associated receptors and their signaling pathways. Evidence from animal models and clinical trials suggests DMT can improve mental well-being in depression, anxiety, and PTSD, and may aid learning, memory, and recovery from brain injuries. The compound's potential to enhance neurogenesis, particularly for neurodegenerative conditions, is also explored.
Cureus
May 27, 2022
Robert Sotille, Herpreet Singh, Anne Weisman et al.
2 citations
Psilocybin, a naturally occurring psychedelic compound, may relieve depression by promoting neuronal plasticity and altering brain network connectivity. Recent clinical trials suggest it effectively reduces symptoms in major depressive disorder and treatment-resistant depression. Cellular experiments in mice demonstrate psilocybin promotes neuritogenesis, potentially addressing the cellular root of depression. Human brain imaging shows psilocybin therapy enhances functional connectivity in intrinsic networks, leading to durable improvements in depressive symptoms. This review highlights psilocybin's promise as a psychotherapeutic that targets neuronal atrophy, a model supplanting the neurotransmitter deficit hypothesis.
Pharmaceuticals (Basel, Switzerland)
May 12, 2023
Philip Borsellino, Reese I. Krider, Deanna Chea et al.
Ketamine offers rapid and enduring relief for major depressive disorder and treatment-resistant depression, unlike standard antidepressants. This narrative proposes that depression stems from neuronal atrophy and synaptic disconnection rather than a monoamine imbalance. Ketamine, its enantiomers, and metabolites act through multiple pathways, including NMDAR inhibition and enhanced glutamatergic signaling. The disinhibition hypothesis suggests ketamine causes excitatory cortical disinhibition, releasing neurotrophic factors like BDNF, VEGF, and IGF-1, which repair neuro-structural abnormalities. Ketamine's efficacy is revolutionizing psychiatric treatment and understanding of mental illness.