Brain Sciences
March 16, 2018
Giovanni Martinotti, Rita Santacroce, Mauro Pettorruso et al.
171 citations
Hallucinogen Persisting Perception Disorder (HPPD) is a rare condition linked to hallucinogenic drug use, often diagnosed in individuals with prior psychological issues or substance misuse, but it can occur after a single exposure. This review of 45 original studies examines proposed etiologies, the hallucinogens involved, clinical features of HPPD types I and II, psychiatric comorbidities, and available or potential treatments. The findings suggest that HPPD remains poorly understood, with limited therapeutic options, highlighting the need for further research.
Brain Sciences
October 27, 2022
Gemma Perry, Vince Polito, Narayan Sankaran et al.
32 citations
Chanting, the rhythmic vocalization or mental repetition of a sound or phrase, is associated with altered states of consciousness and cognitive benefits, which in turn relate to quality of life. A global survey of 456 English-speaking regular chanters from 32 countries found that stronger intentionality (devotion, intention, sound) and higher engagement (experience, practice duration, regularity) predicted more mystical experiences, flow states, and mindfulness, and less mind wandering. Call-and-response chanters reported more mystical experiences, while repetitive prayer was linked to less mind wandering. The effects on quality of life were indirect, through altered states and cognitive benefits.
Brain Sciences
March 20, 2024
Muhammet Celik, Mark S. Gold, Brian Fuehrlein
22 citations
Alcohol use disorder contributes to over 140,000 annual deaths in the United States, over 200 related diseases globally, and 5.1% of the global disease burden, yet remains undertreated with few approved medications. This narrative review describes the current treatment landscape and novel strategies for alcohol withdrawal syndrome and AUD, including psychedelics combined with psychotherapy, noninvasive neural-circuit-based interventions, phosphodiesterase-4 inhibitors, and GLP-1 receptor agonists. Recent studies show promising results for these approaches, but further research is needed to fully understand their effectiveness. The shortage of approved medications and other treatment modalities highlights the urgent need for continued investigation.
Brain Sciences
December 22, 2023
Nicolas A. Nunez, Boney Joseph, Rakesh Kumar et al.
20 citations
Ketamine can rapidly reduce depression and suicidal thoughts in treatment-resistant depression, but its effectiveness for bipolar depression is less certain. An updated systematic review and meta-analysis of 11 studies, including 7 in the meta-analysis, found that a single ketamine infusion significantly improved depression symptoms measured by the MADRS scale at 1 and 2 days. Non-randomized studies showed a 53% response rate at study endpoint. Response and remission rates were similar for single versus serial infusions. The rate of switching to mania was about 2.4%. Evidence for esketamine in bipolar depression remains limited and based on small, non-randomized studies.
Brain Sciences
January 13, 2023
Maria Gałuszko‐węgielnik, Zuzanna Chmielewska, Katarzyna Jakuszkowiak‐wojten et al.
20 citations
Psychotic treatment-resistant depression is a severe form of major depressive disorder involving hallucinations or delusions, often underdiagnosed and undertreated. Ketamine has shown rapid antidepressant effects, and its enantiomer esketamine was approved for treatment-resistant depression in 2019. This report describes four inpatients with treatment-resistant depression and psychotic features, including one in severe suicidal crisis, who received a single 0.5 mg/kg intravenous infusion of ketamine as an add-on to standard care. Monitoring showed no worsening of psychotic symptoms in short or long term, and all patients achieved stable remission with an immediate antisuicidal effect. Ketamine may benefit individuals with this condition.
Brain Sciences
August 18, 2024
Gianmarco Salvetti, Daniele Saccenti, Andrea Stefano Moro et al.
16 citations
Psilocybin, a psychedelic compound, shows high effectiveness in reducing depressive symptoms in people with major depressive disorder (MDD) or treatment-resistant depression (TRD). A systematic review and meta-analysis of 12 studies found that both single-dose and two-dose psilocybin treatments significantly lowered depression severity. Two-dose administration sometimes produced more pronounced and lasting effects, but it remains unclear whether this is due to dosage or other factors. The findings suggest psilocybin is a promising emerging treatment for these conditions, though standardized trials comparing dosing strategies are needed.
Brain Sciences
February 6, 2025
Michael J Lucido, Boadie W Dunlop
15 citations
Non-response to initial depression treatments is common and harmful. A systematic search of US and EU clinical trial registries identified 50 trials for treatment-resistant depression, 20 for anhedonia, and 25 for suicide. Glutamate system modulation is the mechanism with the most compounds in development, including NMDA and AMPA receptor modulators. Psychedelics, especially psilocybin, have seen the greatest surge in recent years. Other mechanisms include GABA, monoamine, anti-inflammatory, and orexin modulators. Challenges for detecting efficacy include population heterogeneity, comorbid disorders, psychosocial stressors, and prior medication effects.
Brain Sciences
March 3, 2024
Mario Renato Velit-Salazar, Eloise Cherian, Paulo Shiroma
13 citations
A systematic review of 43 pharmacological trials found that psychedelics such as MDMA, psilocybin, LSD, DMT/ayahuasca, and cannabis generally produce detrimental or neutral effects on cold cognition—non-emotionally charged cognitive functions like attention, memory, and executive function—during peak drug effects, though MDMA improved psychomotor function in some cases. The review included mostly healthy subjects, with only one study on MDMA in PTSD patients and none in major depressive disorder. Small sample sizes and inconsistent methods across studies prevent firm conclusions about whether psychedelics enhance, impair, or leave cognition unchanged. Future research should assess both acute and long-term cognitive effects as psychedelics become available for psychiatric treatment.
Brain Sciences
March 13, 2018
Andrew Parrott
13 citations
All psychoactive drugs, both older (cocaine, nicotine, cannabis) and newer (MDMA, mephedrone, spice), damage well-being through similar psychobiological mechanisms. They disrupt core functions such as mood regulation, causing users to feel better on-drug and worse off-drug, with the strength of these mood fluctuations linked to addiction potential. Cyclical changes also affect information processing, psychomotor speed, homeostatic balance, HPA axis, sleep, brain rhythms, and neurocognition, increasing psychiatric vulnerability.
Brain Sciences
August 25, 2020
Micaela Tirri, Luisa Ponzoni, Sabrine Bilel et al.
9 citations
Two new psychoactive substances, DOB and PMA, which are structurally similar to MDMA and sold as ecstasy, impair motor behavior and sensorimotor responses in mice and induce hallucinatory states in zebrafish. In CD-1 male mice, acute administration of DOB and PMA (0.01–30 mg/kg) reduced spontaneous locomotion and disrupted prepulse inhibition of startle responses to visual, acoustic, and tactile stimuli. In zebrafish, lower doses of DOB (0.075–2 mg/kg) and PMA (0.0005–0.5 mg/kg) decreased swimming activity and reduced a hallucinatory score, indicating pro-psychedelic effects. These findings suggest the substances alter sensorimotor gating and may produce hallucinogen-like states.
Brain Sciences
December 11, 2020
Jakub Słupski, Wiesław Jerzy Cubała, Natalia Górska et al.
7 citations
Serum copper concentration changes during ketamine treatment in patients with treatment-resistant depression, but no clear link between copper levels and treatment response was found. Patients with major depressive or bipolar disorder received weekly ketamine infusions, and copper levels were measured before, during, and after treatment. Copper concentration was significantly higher before treatment than after the fifth infusion, and also higher after the full course than after the fifth infusion. However, changes in copper levels did not correlate with scores on depression or mania rating scales, nor with somatic comorbidities. The findings provide data on copper's role in short-term ketamine therapy but do not support copper as a marker of treatment response.
Brain Sciences
May 26, 2025
Charles Palmer, Ally T Ferber, Brian D Greenwald
4 citations
A narrative review of the literature suggests that psilocybin-assisted therapy may benefit people with traumatic brain injury by reducing inflammation, promoting neuroplasticity and neuroregeneration, and alleviating associated mood disorders. The review examined 29 articles from 2000–2025, plus additional references, and notes that positive findings in related fields—such as treatment for depression and addiction—highlight the need for more extensive clinical trials on psilocybin's role in TBI recovery.
Brain Sciences
March 31, 2024
Gabriella Smedfors, Felicia Jennysdotter Olofsgård, Anna Steinberg et al.
4 citations
Cluster headache (CH) is a debilitating condition with limited effective treatments. A survey of 314 Swedish CH patients found that less than half (46%) were satisfied with their abortive treatments, and 19% stopped functioning abortive treatments due to side effects. Among chronic CH patients, 17% had never tried the first-line preventive drug verapamil. A small subset (0–8%) had used illicit substances; psilocybin was reported effective as an abortive treatment by 100% (n = 8) and as a preventive treatment by 92% (n = 12). Verapamil showed some preventive effect for 68% (n = 85). Many patients are undertreated and experience side effects, indicating a need for new strategies and revised guidelines.
Brain Sciences
February 7, 2026
Miriam Olivola, Tiziano Prodi, Giada Versaci et al.
2 citations
During intranasal esketamine treatment for treatment-resistant depression, patients describe four distinct types of dissociative experiences: sensory alteration and perceptual flow (27.8%), time suspension and chronological drift (58.3%), body and space alteration (55.6%), and psychic distance from suffering (83.3%). Most patients frame these experiences as neutral or meaningful, often linked to temporary relief from rumination and depressive distress, though a minority report transient distress or loss of control. The findings suggest dissociation functions as a transitional subjective state whose clinical relevance depends on anticipation, framing, monitoring, and integration, supporting structured psychoeducation and in-session support in esketamine programs.
Brain Sciences
August 21, 2025
Dean Bilenker, Nicole M. Avena
2 citations
Serotonergic psychedelics, especially 5-HT2A receptor agonists like psilocybin, show potential for treating eating disorders such as anorexia nervosa, bulimia nervosa, and binge eating disorder. The review connects these interventions to the serotonin hypothesis of eating disorders, highlighting serotonergic dysregulation and impaired cognitive flexibility as core features. Psychedelics may promote neuroplasticity and psychological insight through 5-HT2A signaling modulation, based on animal models, human neuroimaging, and early clinical trials. Preliminary open-label studies suggest psilocybin can improve eating disorder symptoms and quality of life, though evidence remains early and methodologically limited. The authors conclude that further controlled trials are needed, but psychedelics represent a novel mechanistic approach to entrenched eating disorder psychopathology.
Brain Sciences
June 11, 2026
Sharon Vaisvaser
Selfhood arises from embodied and relational processes, with Peripersonal Space (PPS) serving as a key interface for bodily self-consciousness, self-other relations, affect regulation, and temporal continuity. This narrative review synthesizes neuroscience, embodiment research, predictive processing, developmental science, phenomenology, and psychodynamic theory into a multidimensional neuropsychodynamic framework. Subjective time emerges from bodily rhythms, interpersonal synchronization, and predictive engagement with the environment, extending toward autobiographical continuity and mentalizing. Psychodynamic concepts like holding and containment are reinterpreted through contemporary neuroscience. Psychotherapeutic change involves reorganizing embodied, affective, and reflective dimensions via co-regulation and relational engagement.
Brain Sciences
April 30, 2026
Nathan R Luzum, Marcia H. Mccall, Charlotte Talley Boyd et al.
A single sub-anesthetic dose of ketamine, compared to midazolam, produced a non-significant reduction in the number of cigarettes smoked during a requested abstinence period among 18 adults with tobacco use disorder who were not trying to quit. No significant differences appeared in ad-lib smoking, craving, or withdrawal symptoms afterward. Participants reported more intense psychological experiences with ketamine, and about half felt it was easier to abstain. The findings suggest ketamine has little to no direct effect on quantitative smoking measures, though qualitative reports indicate improved mood and reduced craving in some individuals for several days.
Brain Sciences
February 4, 2026
Katarina Savić Vujović, Sonja Vučković, Lara Samardžić et al.
Ketamine and a ketamine-magnesium sulfate combination lower body temperature in rats through serotonergic and adrenergic mechanisms, but not through GABAA receptors. Giving yohimbine, an α2-adrenergic blocker, deepened ketamine-induced hypothermia at doses of 0.5 and 1 mg/kg, while only the highest dose (3 mg/kg) enhanced the combination's effect. Methysergide, a serotonin blocker, had opposite effects depending on dose: 1 mg/kg worsened ketamine hypothermia, whereas 0.5 mg/kg reduced the combination's cooling effect. Bicuculline, a GABAA antagonist, did not change hypothermia from either treatment. These findings clarify neurotransmitter pathways involved in NMDA antagonist-related thermoregulation.
Brain Sciences
January 7, 2026
Aleš Oblak, Sara Rigler, Liam Korošec Hudnik et al.
Patients with affective disorders experience emotional stimuli in laboratory tasks not as isolated events but as part of a complex, temporally unfolding process that can persist and blend across trials, a phenomenon termed impressionability. Two distinct alterations in affectivity were identified: affective enchantment, where intense emotions combine with superstitious thinking, and disintwinement, a sense of detachment and emotional blunting. Standardized image-based tasks often fail to elicit authentic spontaneous emotional responses in clinical populations, limiting their ecological validity. The findings underscore the need for experimental designs that capture the subtle, dynamic nature of altered affectivity, including vital feelings, to better understand emotion dysregulation.
Brain Sciences
January 24, 2025
Marco Barbaresi, Davide Nardo, Sabrina Fagioli
The human sensorimotor system naturally synchronizes with environmental rhythms like light pulses or sound beats, a phenomenon called the 'entrainment effect.' This review examines how entrainment impacts physiological rhythms, including brain activity, heart rate, and motor coordination, and its role in cognitive, motor, and affective functioning. Evidence shows measurable effects on neural oscillations, heart rate variability, and motor synchronization, which can influence cognitive processing, emotional states, and motor coordination. The authors propose defining 'physiological entrainment' as a fundamental mechanism underlying the mind–body connection, suggesting entrainment-based interventions could enhance well-being and offer rehabilitative approaches for mental health.