Sophie Woodruff is a researcher with a strong focus on and passion for the therapeutic potential of psychedelics in psychiatry, particularly psilocybin. They recently earned their Research Master’s in Cognitive and Clinical Neuroscience with a specialization in drug development and neurohealth from Maastricht University, which included a nine-month internship at LSU Health in New Orleans under the supervision of Dr. Charles Nichols. Following this, they completed a three-month fellowship at Aarhus University Hospital in Denmark, supported by a stipend from the university. Under the guidance of Betina Elfving, they investigated the rapid and sustained effects on mRNA levels in brain tissue from male and female rodents after a single injection of saline, LPH-5, DOI, 25CN-NBOH, or psilocybin. Sophie is currently seeking funding through grants and stipends to begin a PhD. They aim to investigate novel antidepressant treatments, structural and functional biomarkers of depression, and the molecular mechanisms underlying treatment efficacy, with a particular focus on sex differences and variations in treatment responses across the menstrual cycle.

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Pre-Administration of Lorazepam Negates the Antidepressant-like Effects of Psilocybin in Male Wistar Kyoto Rats

An estimated 300 million people worldwide suffer from major depressive disorder. However, current conventional antidepressant therapies are often inadequate, as one-third of patients do not respond to these treatments. Given this, the classic psychedelic psilocybin has been shown to produce rapid-acting antidepressant effects that can last for up to 6 months following a single administration. In clinical practice, benzodiazepines (BZDs) are commonly prescribed alongside antidepressant therapy. A preliminary study by Hibicke et al. (2024) indicated that pre-administration of lorazepam diminished both the efficacy and longevity of psilocin’s antidepressant-like effects in male Wistar Kyoto (WKY) rats. These findings raise concerns about the potential reduction in therapeutic benefits for patients receiving psilocybin-assisted therapy while also taking BZDs. The current study aimed to confirm these preliminary results and explore psilocybin’s long-term effects on neuroplasticity-related gene expression in the medial prefrontal cortex (mPFC). Thirty-two male WKY rats were randomly assigned to one of four treatment groups: saline/saline (S/S, n = 8), lorazepam/saline (L/S, n = 8), saline/psilocybin (S/P, n = 8), or lorazepam/psilocybin (L/P, n = 8). Treatments were administered via two bolus intraperitoneal injections, spaced 30 minutes apart, with each rat receiving either saline or lorazepam first and either saline or psilocybin second. Antidepressant-like efficacy was assessed using the Forced Swim Test (FST) at 3, 5-, 7-, 9-, and 11-weeks post-treatment. Three subdivisions of the mPFC—the anterior cingulate cortex (ACC), prelimbic cortex (PL), and infralimbic cortex (IL)—were extracted to perform quantitative PCR using TaqMan® Gene Expression Assays for 17 targets of interest, normalized to Ywhaz. Results showed that S/P-treated rats exhibited sustained antidepressant-like effects for up to 9 weeks but not at 11 weeks. Pre-administration of lorazepam 30 minutes before psilocybin, however, negated psilocybin’s long-term antidepressant-like effects. Psilocybin treatment was associated with increased Gria4 expression in the PL. However, this change could not be linked to psilocybin’s sustained antidepressant-like effects, as the behavioral effects of psilocybin were absent at the time of tissue extraction. Overall, these findings underscore the potential interference of BZDs with psilocybin’s therapeutic efficacy, which is crucial to consider in the development of psilocybin-assisted therapies.