Depression treatments that target monoamine neurotransmitters often fail to achieve full remission. This narrative review examines several emerging strategies that go beyond those conventional methods: glutamatergic modulation, brain stimulation techniques, anti-inflammatory agents, interventions on the gut-brain axis, GABA modulation, and psychedelic-assisted therapy. The article describes the mechanisms, clinical efficacy, and safety profiles of these innovative approaches, offering perspectives for improving depression management and addressing current therapeutic gaps.
A single dose of psilocybin, given alongside intensive psychotherapy, produces a rapid and clinically significant decline in depressive symptoms in people with treatment resistant depression, with benefits mostly retained at 12 weeks or longer. Psilocybin was well tolerated; side effects were mostly mild to moderate and transient, including elevated blood pressure, fatigue, headache, nausea, and vertigo. Hallucinogen persisting perception disorder was occasionally reported, and there were few reports of suicidal ideation and behavior. Further controlled evaluations are necessary before routine use.
Chronic neuropathic pain affects an estimated 1.5 billion people worldwide. Its mechanisms involve peripheral and central sensitization from repeated noxious stimuli, leading to physical and emotional pain. Traditional treatments like opioid and non-opioid analgesics often cause adverse effects, addiction, or suboptimal relief. Psychedelics such as psilocybin, LSD, mescaline, and MDMA are emerging as potential therapies. They alter pain perception by activating serotonin receptors, reducing inflammation, enhancing descending inhibition, and promoting neuroplasticity and synaptic remodeling. This review describes the mechanisms, pharmacology, clinical applications, and therapeutic potential of psychedelics for neuropathic pain.