Research Square
March 20, 2023
Ahmed N. Hassan, Sean Ferkul, Zena Agabani et al.
A virtual Mantram Repetition Program—a brief, mindfulness-based, non-trauma-focused group intervention—was feasible, safe, and acceptable for adults with both posttraumatic stress disorder (PTSD) and substance use disorder (SUD). Of 43 enrolled participants, 35 completed the 8-week program (81.4% retention). Qualitative feedback highlighted the program's acceptability through its delivery method, informative materials, and a practical mindful tool for managing symptoms. Further controlled trials are needed to compare the program with other interventions.
Research Square
March 10, 2023
Xue Chen, Jing Li, Lisa Yu et al.
An enzyme from cane toad (Rhinella marina), named RmNMT, efficiently produces N,N-dimethylated indolethylamines, including psychedelic compounds like N,N-dimethyltryptamine. Unlike similar enzymes in mammals and fungi, RmNMT is highly efficient and promiscuous, enabling the bioproduction of new-to-nature indolethylamine derivatives. N,N-Dimethylated indolethylamines showed reduced binding and activation at 5-HT1A and 5-HT2A receptors compared to primary amines, yet only these tertiary amines induced hallucinogenic behavior in mice, suggesting metabolic stability is key. This discovery establishes a platform for producing and screening novel indolethylamines for potential psychiatric medicines.
Research Square
November 15, 2022
Kennedy Robertson, Ian Gold, Samuel P. L. Veissière et al.
Delusional ideation, or false beliefs, is linked to social factors such as feeling the presence of unseen others, loneliness, social anxiety, and empathy. A survey of 2,200 healthy adults during the COVID-19 pandemic found that all measured aspects of social imagery were positively associated with delusional ideation. The strongest predictor was felt presence, followed by loneliness, social fear, and empathic concern. The findings suggest that delusions may arise from common mechanisms with social imagination, and that alterations in social cognition contribute to delusional thinking.
Research Square
September 8, 2022
Maria Helha Fernandes-Nascimento, André Brooking Negrão, Karine Viana-Ferreira et al.
A bibliometric analysis of publications on ibogaine for treating substance-related disorders from 1991 to 2020 found that research output grew steadily, with an increase of 5.1 publications per year between 1991 and 2000. The subsequent two decades showed continued but fluctuating publication volumes, with the United States being the most prominent contributor. The analysis suggests that despite variations over time, research on ibogaine persists and points toward future directions for public health interventions.
Research Square
August 3, 2022
Lin Ban, Xiaohong Lv, Dawei Cai et al.
Death ends all biological functions and is inevitable. To cope with the fear of death, early humans developed concepts of the soul and religion, which led to burial and sacrificial customs. Shamanism, practiced by nomadic groups in northern Eurasia, is one such tradition. At the Nairentoligai Cemetery M17 in Inner Mongolia, China, archaeologists found a corpse whose face was covered with all the right ribs of a sheep. Zooarchaeological analysis identified the sheep's characteristics and, through bone-surface traces, reconstructed how the animal was dismembered. The practice may have been intended to declare the body dead and protect the soul from intrusion, reflecting shamanistic beliefs. This finding aids research into the religious views of northern Mongolian Plateau nomads.
Research Square
Alice Le Berre
In adults with treatment-resistant depression, esketamine was associated with early microstructural changes in the dentate gyrus of the hippocampus: reduced fractional anisotropy and increased orientation dispersion index, consistent with greater dendritic complexity. Lower baseline left-dentate gyrus fractional anisotropy correlated with greater improvement at two weeks, and a decrease in fractional anisotropy over that period also correlated with improvement. These changes suggest esketamine may promote hippocampal plasticity, and baseline diffusion MRI metrics could serve as candidate biomarkers for treatment response. The study included 12 adults with treatment-resistant depression and 24 matched controls, but larger studies are needed.
Research Square
Taqwa B. Thanoon, Zeina A. Althanoon
Depression during pregnancy can harm offspring brain development and behavior. Common antidepressants like SSRIs carry risks because they cross the placenta. Ketamine is being explored as an alternative. This study in mice examined the effects of ketamine on offspring of mothers that experienced stress. Female mice were divided into groups: control, maternal stress, stress plus fluoxetine, and stress plus ketamine. Behavioral tests measured anxiety, anhedonia, and despair in the offspring. Maternal stress increased anxiety-like behaviors, and both ketamine and fluoxetine reversed some effects. However, fluoxetine was more effective at reducing despair. Ketamine moderately reduced anhedonia compared to controls. More research on dose and timing is needed to optimize ketamine treatment.
Research Square
Sean Viña
People who use psychedelics are less likely to seek formal mental health care, including medication and outpatient treatment, even when experiencing high psychological distress. Analyzing data from over 458,000 participants in a national US survey between 2010 and 2018, the study found that as distress levels increase, psychedelic users become even less inclined to use formal care compared to non-users. This suggests a heightened risk of self-medication as psychedelics become more culturally and legally accepted.
Research Square
Majid Eslami, Laleh Khorshidi, Maryam Ghasemi et al.
In rats, the recreational drug MDMA (Ecstasy) impairs spatial memory and increases oxidative stress and cell death in the hippocampus. Atorvastatin (5, 10, 20 mg/kg) and rosuvastatin (20 mg/kg), given orally for 21 days, prevented these memory deficits and reduced the MDMA-induced rise in reactive oxygen species, lipid peroxidation, and caspase-3 and -9 activities. The results suggest that these statins protect against MDMA neurotoxicity by suppressing oxidative stress and apoptosis.
Research Square
Jack Swain, Davis Carter, Leonardo Vando et al.
Among 13,963 adults with moderate-to-severe sleep disturbances who received at-home ketamine-assisted therapy for depression, 67.4% showed at least a 1-point improvement on a single sleep-related item from a depression screening tool after two sessions. By session six, 76.8% of completers met that threshold, and the average score dropped 48.8% from baseline. However, the study could not separate sleep changes from mood improvement because all participants were treated for depression and no control group was included. Side effects were reported by 3.7% to 5.0% of participants across sessions.
Research Square
Amit Kumar
A 24-year-old woman experienced possession trance attacks, a condition involving altered consciousness where a person's identity is replaced by a spirit or deity, with amnesia for the event. Her entire family developed shared delusional beliefs, and multiple members also had possession attacks over time. Such attacks can be misdiagnosed as psychotic illnesses like schizophrenia. The case highlights the cultural and familial context of possession trance, which must cause distress or impairment and not be due to psychosis or substance use.
Research Square
Katelyn Halpape, Raelle Pashovitz, Annabelle Wanson et al.
A small pilot program evaluated a hospital-to-outpatient intranasal racemic ketamine maintenance therapy for treatment-resistant depression. Five adult inpatients who had responded to intranasal ketamine in hospital continued treatment at a community centre, completing up to 14 sessions over 192 days. Depressive symptoms decreased or stabilized, and quality of life increased or stabilized. No serious adverse events occurred; mild side effects included anxiety and nausea, and slight blood pressure increases did not require intervention. The authors conclude the therapy appears feasible and well tolerated, but limited effectiveness conclusions can be drawn from this small study.
Research Square
Minna Chang
Ketamine can cause ulcerative cystitis, a bladder condition with lower urinary tract symptoms and kidney damage, in over 25% of regular recreational users. This complication had not been reported in therapeutic use for depression until now. A 28-year-old woman started on ketamine for depression developed cystitis, confirmed by urine tests. This is the first reported case of ketamine-induced cystitis from treatment-dose ketamine for antidepressant therapy.
Research Square
Norihiro Okada, Kenshiro Oshima, Akiko Maruko et al.
Non-responders to ketamine treatment for depression show elevated viral infection markers based on intron retention (IR) gene analysis of RNA-seq data. Several IR genes associated with viral infection returned to healthy levels after ketamine regardless of responder status, suggesting non-responders are not resistant to ketamine but rather have an extremely high inflammatory state that the drug's effects cannot overcome. Excluding one transcriptomic outlier with extreme viral infection did not change IR gene conclusions but did alter differentially expressed gene (DEG) results, supporting the authors' claim that IR genes may be more useful markers of depression than DEGs.