RESUMO
Post-traumatic stress disorder (PTSD) is an anxiety disorder that often presents after exposure to a traumatic, life-threatening event. Experiencing a traumatic event is not rare, with inciting incidents ranging from being burglarized to politically motivated genocide. While traditional psychopharmacology and psychotherapy are the mainstays of the treatment of PTSD currently, psychoactive drugs (otherwise known as psychedelics) are being explored for their novel role in the treatment of PTSD patients. Psychoactive drugs such as MDMA, ketamine, and psilocybin have been shown to specifically target and decrease fear and anxiety pathways in the brain. These unique properties hold the potential to be utilized in addressing symptoms of trauma in those with refractory or treatment-resistant PTSD. Historically, federal and state laws have restricted research into how psychoactive drugs can be used to treat mental illness due to the widespread belief that these drugs present more harm than benefit. However, the current shift in public opinion on psychedelics has propelled research to look into the benefits of these drugs for patients with mental illness. This article aims to discuss the mechanisms of how MDMA, ketamine, and psilocybin work in the PTSD brain, as well as their beneficial role in treatment.
RESUMO
The global decline in malaria has stalled1, emphasizing the need for vaccines that induce durable sterilizing immunity. Here we optimized regimens for chemoprophylaxis vaccination (CVac), for which aseptic, purified, cryopreserved, infectious Plasmodium falciparum sporozoites (PfSPZ) were inoculated under prophylactic cover with pyrimethamine (PYR) (Sanaria PfSPZ-CVac(PYR)) or chloroquine (CQ) (PfSPZ-CVac(CQ))-which kill liver-stage and blood-stage parasites, respectively-and we assessed vaccine efficacy against homologous (that is, the same strain as the vaccine) and heterologous (a different strain) controlled human malaria infection (CHMI) three months after immunization ( https://clinicaltrials.gov/ , NCT02511054 and NCT03083847). We report that a fourfold increase in the dose of PfSPZ-CVac(PYR) from 5.12 × 104 to 2 × 105 PfSPZs transformed a minimal vaccine efficacy (low dose, two out of nine (22.2%) participants protected against homologous CHMI), to a high-level vaccine efficacy with seven out of eight (87.5%) individuals protected against homologous and seven out of nine (77.8%) protected against heterologous CHMI. Increased protection was associated with Vδ2 γδ T cell and antibody responses. At the higher dose, PfSPZ-CVac(CQ) protected six out of six (100%) participants against heterologous CHMI three months after immunization. All homologous (four out of four) and heterologous (eight out of eight) infectivity control participants showed parasitaemia. PfSPZ-CVac(CQ) and PfSPZ-CVac(PYR) induced a durable, sterile vaccine efficacy against a heterologous South American strain of P. falciparum, which has a genome and predicted CD8 T cell immunome that differs more strongly from the African vaccine strain than other analysed African P. falciparum strains.
