Archives of General Psychiatry
February 1, 2008
J.f.w. Deakin, Jane Lees, Shane Mckie et al.
315 citations
Ketamine, which blocks NMDA glutamate receptors and secondarily increases glutamate release, produces psychosis-like symptoms. Using fMRI, a double-blind crossover study with 33 healthy men found that ketamine caused a rapid decrease in ventromedial frontal cortex activity that predicted dissociative effects, and increased activity in posterior cingulate, thalamus, and temporal regions that correlated with psychosis scores. Pretreatment with lamotrigine, a glutamate release inhibitor, prevented many brain changes and symptoms. The findings suggest ketamine's effects involve increased glutamate release and may model two core psychosis processes: abnormal perceptions and impaired cognitive-emotional evaluation.
Current Neuropharmacology
March 2, 2018
Jonathan Hamill, Jaime E. C. Hallak, Serdar Dursun et al.
179 citations
Ayahuasca is a traditional Amazonian brew made from Banisteriopsis caapi vine and Psychotria viridis leaves, containing beta-carboline alkaloids and the hallucinogen DMT. Originally used by indigenous shamans for spiritual and healing purposes, it has been incorporated into folk medicine and religious ceremonies in Brazil and is now also used recreationally in Europe and North America. This review summarizes ayahuasca's behavioral and physiological effects, safety profile, proposed mechanisms, and potential clinical uses for psychiatric disorders and addictions. The side effect profile appears relatively mild, but more detailed studies are needed. Some researchers advocate relaxing government regulations to allow comprehensive clinical trials.
Journal of Psychopharmacology
March 19, 2021
Rafael G. Dos Santos, Jaime Ec Hallak, Glen B. Baker et al.
51 citations
Major depressive disorder affects many people worldwide and current antidepressants often work slowly, have side effects, and fail about a third of patients. Psychedelics such as LSD, psilocybin, and ayahuasca are among the few compounds with recent human evidence of fast-acting antidepressant effects. Studies from the 1950s to 1970s reported antidepressive and anxiolytic effects, which modern trials are confirming (LSD, one trial; psilocybin, five trials; ayahuasca, two trials). These drugs appear to work primarily by activating serotonin receptors, especially the 5-HT2A receptor. The promising but limited evidence of safety and efficacy has encouraged further research into psychedelics for depression.
Biomolecules
November 2, 2022
Giordano Novak Rossi, Lorena T. L. Guerra, Glen B. Baker et al.
29 citations
Ayahuasca, a psychoactive brew used in South American rituals, contains DMT from Psychotria viridis and MAO-inhibiting β-carbolines from Banisteriopsis caapi. Preclinical and clinical evidence suggests its antidepressant effects involve complex modulation of serotoninergic, glutamatergic, dopaminergic, and endocannabinoid systems, along with interactions with VMAT, TAAR1, and sigma-1 receptors. The brew also appears to beneficially modulate inflammatory and neurotrophic factors, leading to neuroprotective and neuroplastic effects. This review summarizes current knowledge of these molecular interactions and their relation to ayahuasca's potential antidepressant properties.
Expert Opinion on Drug Safety
March 18, 2022
Giordano Novak Rossi, Isabella Caroline Da Silva Dias, Glen B. Baker et al.
17 citations
In controlled settings, ayahuasca administration appears relatively safe, with no serious adverse events reported. Common side effects include nausea, vomiting, headaches, and temporary increases in heart rate and blood pressure. Research on ayahuasca's antidepressant effects is still early, lacking large, robust clinical trials. Major obstacles to its therapeutic use include dose standardization, legal prohibition of its alkaloids, and questions about compensating traditional communities if ayahuasca becomes an approved medicine.