The sigma-1 receptor (S1R) is linked to modulating ion channels and G-protein-coupled receptors. In the central nervous system, S1R is expressed throughout but is especially enriched in mouse spinal motor neurons, where it localizes to subsurface cisternae of cholinergic postsynaptic densities called C-terminals. S1R first appears in the endoplasmic reticulum of mouse spinal motor neurons late in embryonic development and concentrates at C-terminals only during the second week after birth. The enzyme indole-N-methyl transferase (INMT), which produces the sigma-1 ligand dimethyltryptamine (DMT), is also found at postsynaptic sites of C-terminals near S1R, suggesting that DMT is synthesized locally to activate S1R in motor neurons.
Nightmares are common, but only nightmare disorders require treatment. They can stem from PTSD, other psychiatric conditions, substance abuse, or individual predisposition. A literature review of eighteen pharmacotherapies and eleven psychotherapies for nightmare disorders was conducted to identify the best evidence-based options. For PTSD-related nightmare disorders, topiramate is recommended as first-line pharmacotherapy, nabilone as second-line, and cognitive behavior therapy, imagery rehearsal therapy (IRT), or exposure, relaxation, and rescripting therapy as appropriate psychotherapies. For non-PTSD nightmare disorders, triazolam or nitrazepam are first-line pharmacotherapies, and IRT is the psychotherapy of choice. Pharmacotherapy is prioritized over psychotherapy for PTSD-related cases; either can be first-line for non-PTSD cases.