Pharmaceuticals
February 3, 2021
Andreia Machado Brito-Da-Costa, Áurea Madureira-Carvalho, Diana Dias Da Silva et al.
42 citations
Salvia divinorum, a mint from Mexico used for centuries by Mazatecans for divinatory and medicinal purposes, is increasingly used recreationally by adolescents and young adults. Its main psychoactive compound, salvinorin A, is a non-nitrogenous diterpenoid that acts selectively on the κ-opioid receptor. Absorption occurs through oral mucosa or respiratory tract; when swallowed, it is rapidly broken down in the gastrointestinal system to its inactive metabolite salvinorin B. The compound is quickly distributed, accumulates in the brain, and is rapidly eliminated, matching its short-lived effects. No reports of toxicity or serious adverse outcomes were found. Proposed therapeutic applications include treatment of chronic pain, gastrointestinal and mood disorders, neurological diseases, and drug dependence, but clinical acceptance is limited by psychotropic side effects and misuse.
Pharmaceuticals
November 24, 2021
Robertas Strumila, Bénédicte Nobile, Laura Korsakova et al.
35 citations
Current interventions for people at risk of suicide have limited efficacy. This review examines whether psilocybin, a psychedelic compound with a long history of human use, could modulate thoughts and behavioral patterns in individuals at risk of suicidal behaviors. The authors summarize evidence that psilocybin directly stimulates the serotonin 2A receptor (5HT2A), targeting inflammatory and oxidative stress pathways, which may lead to rapid increases in brain plasticity, cognitive flexibility, spirituality, and empathy, while suppressing inflammation. Preliminary epidemiological data are presented, and the review calls for clinical studies to test psilocybin in individuals with suicidal ideation or at risk of suicidal behaviors.
Pharmaceuticals
December 21, 2023
Katarina Savić Vujović, Ana Jotić, Branislava Medić et al.
32 citations
Ketamine is an old drug with new clinical uses beyond anesthesia and pain relief, including treatment for asthma, epilepsy, depression, bipolar disorder, and addiction to alcohol and heroin. It works mainly as a noncompetitive blocker of the NMDA receptor, though its full mechanism is complex. Low doses and short-term use are generally safe and cause few side effects. However, ketamine is also a powerful psychostimulant and has become a commonly abused drug over the past decade.
Pharmaceuticals
August 12, 2021
Gniewko Więckiewicz, Iga Stokłosa, Magdalena Piegza et al.
30 citations
Depression remains a clinical challenge despite many available treatments. Recently, formerly illicit substances such as lysergic acid diethylamide (LSD), psilocybin, and dimethyltryptamine (DMT) have drawn scientific interest. This systematic review followed PRISMA guidelines and searched PubMed and the Cochrane Library, identifying 10 relevant papers. Most selected studies showed a significant correlation between psilocybin and DMT use and reduction in depression symptom intensity. The authors conclude that psilocybin and DMT could be useful in depression treatment, but further observations are still required.
Pharmaceuticals
January 28, 2021
Esther Papaseit, Eulàlia Olesti, Clara Pérez‐mañá et al.
30 citations
Mephedrone, a synthetic cathinone and popular new psychoactive substance, produces euphoria and well-being and increases cardiovascular effects when self-administered orally or intranasally by healthy experienced drug users. In this observational study, ten participants took a single dose orally (100–200 mg, mean 150 mg) or intranasally (50–100 mg, mean 70 mg). Although the oral route sometimes produced greater subjective effects, concentrations of mephedrone in oral fluid and total amounts in urine were considerably higher after intranasal administration. Controlled clinical trials are needed to confirm these results.
Pharmaceuticals
May 23, 2022
Danish Mahmood, Sattam Khulaif Alenezi, Md Jamir Anwar et al.
29 citations
Psychedelics like LSD, psilocybin, and mescaline produce intense effects on the brain and behavior and have recently shown efficacy in treating conditions such as anxiety, depression, mood disorders, obsessive-compulsive disorders, suicidal ideation, posttraumatic stress disorder, and substance use disorders when administered in low, medically supervised doses. Their primary mode of action involves activating serotonin 5-HT2A receptors, which modulates cognition and brain connectivity through downstream signaling pathways. Atypical antipsychotic drugs also target these receptors, and both psychedelics and some antipsychotics may act via a common serotonin–glutamate receptor interaction in cortical pyramidal neurons. Emerging hypotheses propose that psychedelics work through brain resetting mechanisms, highlighting the need for deeper research into their neurobiology to benefit psychiatric disorders including schizophrenia.
Pharmaceuticals
April 1, 2023
Aleksander Kwaśny, A. Włodarczyk, Damian Ogonowski et al.
27 citations
Ketamine reduces the severity of sleep insomnia in depression. Two studies reported significant improvement in sleep measured by MADRS and QIDS-SR16 scales after intravenous ketamine and intranasal esketamine. One case report showed mitigation of symptoms in PSQI and ISI during 3-month treatment with esketamine. Two studies with objective nocturnal EEG measurements showed a decrease in nocturnal wakefulness accompanied by an increase in slow wave and REM sleep. Robust data are lacking, and more research is needed.
Pharmaceuticals
September 28, 2021
René Zeiss, Maximilian Gahr, Heiko Graf
17 citations
Psilocybin shows promise as an antidepressant for major depressive disorder, with studies reporting high treatment effect sizes. However, the exact mechanism by which it alleviates depression and the role of the psychedelic experience itself remain unclear. No severe adverse events were observed in the reviewed studies, but results are considered preliminary due to limitations. Several safety and utility questions require further research.
Pharmaceuticals
December 31, 2022
Antonio Munafò, Davide Arillotta, Guido Mannaioni et al.
15 citations
Psilocybin shows promise as a transdiagnostic treatment for psychiatric disorders, with recent evidence indicating that psychedelic-assisted psychotherapy can provide significant and lasting relief from depressive symptoms. However, existing studies have limitations including small sample sizes, inadequate blinding, short follow-up periods, and highly selected treatment populations. Additional concerns involve practitioner experience, lack of standardized protocols, the legal status of psychedelics, ethical issues, and potential adverse psychological or medical effects. The authors suggest that newer evidence, more precise protocols, and policy changes may clarify psilocybin's therapeutic potential.
Pharmaceuticals
August 1, 2023
B. Joseph, N. Nuñez, S. Kung et al.
14 citations
For adults with treatment-resistant depression, taking lamotrigine alongside intravenous ketamine or intranasal esketamine does not significantly reduce the antidepressant effect of the treatments. In a historical cohort study, response and remission rates were similar whether patients were on lamotrigine or not. There was a trend toward lower dissociation scores among those taking lamotrigine, especially with IV ketamine. The study was limited by only 13 patients on lamotrigine, so the evidence is insufficient to conclude that lamotrigine attenuates the antidepressant effect, but it may reduce dissociation.
Pharmaceuticals
January 19, 2025
Marco Bonaso, Letizia Biso, Benedetta Zucchini et al.
13 citations
Psychedelics, known for their cultural and spiritual roles, are emerging as promising therapeutic agents by profoundly altering consciousness, emotional processing, mood, and neural plasticity. They modulate brain connectivity, particularly by enhancing functional connections between sensory areas while reducing connections in associative regions like the default mode network, thereby decreasing rigidity and increasing plasticity. The relaxed beliefs under psychedelics (REBUS) model and changes in cortico-striatal thalamo-cortical loops help explain these effects. Clinical trials of MDMA, psilocybin, and LSD show significant efficacy in treating treatment-resistant PTSD, depression, and anxiety with favorable safety profiles. However, linking molecular actions to clinical outcomes remains a critical gap needing further research.
Pharmaceuticals
August 15, 2023
Daniel Martins, Eva Gil-Martins, Fernando Cagide et al.
13 citations
Adding an N-2-methoxybenzyl group to mescaline and related 2C phenethylamine drugs to create NBOMe compounds significantly increases their in vitro toxicity to both brain (SH-SY5Y) and liver (HepG2) cell lines. The NBOMe drugs had lower EC50 values, indicating greater potency, and were able to cross the blood–brain barrier. The increased toxicity was linked to higher lipophilicity, disruption of mitochondrial membrane potential, and depletion of glutathione and ATP levels. Inhibition of cytochrome P450 enzymes, particularly CYP3A4 and CYP2D6, influenced the drugs' toxicity, suggesting these enzymes play a role in detoxification or bioactivation. No reactive oxygen species overproduction was detected.
Pharmaceuticals
April 9, 2025
Hossein Omidian, Alborz Omidian
11 citations
Psilocybin, a naturally occurring psychedelic compound, is being re-evaluated for its potential to treat psychiatric and neurological disorders. This review examines its pharmacokinetics, pharmacodynamics, clinical efficacy, and safety. Emerging evidence supports its effectiveness for major depressive disorder, treatment-resistant depression, anxiety, alcohol use disorders, and cancer-related distress. However, significant barriers remain, including methodological limitations, regulatory hurdles, and a lack of diversity in clinical trial populations. Advances in biosynthetic production and better psychotherapeutic integration are needed for scalability. Future research should focus on long-term safety, precise dosing, and neurobiological mechanisms to refine therapeutic applications.
Pharmaceuticals
March 7, 2025
Taynah P Galdino, Lucas C Oliveira, Mateus A Luz et al.
11 citations
A systematic review of 25 studies on extracting and quantifying psilocybin and psilocin from Psilocybe mushrooms found that both the extraction method and mushroom species significantly affect compound yields. Ultrasonic bath extraction was the most efficient technique, especially for Psilocybe cyanescens and Psilocybe cubensis. High-performance liquid chromatography (HPLC) was the most common method for identifying and quantifying the compounds. Polar solvents were essential for effective solubilization, with temperature, solvent-to-material ratio, and extraction time being key parameters for optimizing yields. The review aims to support standardized protocols for ensuring compound quality and purity.
Pharmaceuticals
January 24, 2023
Adam Włodarczyk, Alicja Dywel, Wiesław Jerzy Cubała
10 citations
In patients with treatment-resistant depression, intravenous ketamine may elevate psychotic symptoms in those with epilepsy. Among 49 inpatients with major depressive or bipolar depression treated with ketamine, the presence of epilepsy was significantly associated with an increase in Brief Psychiatric Rating Scale scores over time. For the subgroup with epilepsy (6 patients), substantial fluctuations occurred across all administrations. Psychotic symptoms for other comorbid conditions were not significant. The findings indicate that careful consideration of comorbidities and close clinical supervision are needed during ketamine treatment.
Pharmaceuticals
November 30, 2022
Martin Paškan, Silvie Rimpelová, Vladimíra Svobodová Pavlíčková et al.
9 citations
A novel synthetic cathinone, 4-isobutylmethcathinone, was synthesized and its properties characterized. The substance showed significantly higher cytotoxicity compared to other synthetic cathinones, with IC50 values reaching 18–65 µM after 72 hours in human bladder, neuroblastoma, microglia, and liver cancer cells. Chiral separation enabled study of individual enantiomers, which exhibited different agonistic effects on dopamine and adrenergic receptors. The compound lacked binding affinity for serotonin receptors, placing it among monoamine drugs like MDMA.
Pharmaceuticals
July 5, 2011
Elena Puerta, Norberto Aguirre
6 citations
MDMA (ecstasy) causes long-lasting reductions in markers of serotonin neurons in animal brains, including decreased tryptophan hydroxylase activity, lower serotonin and its metabolite 5-HIAA, and reduced binding to serotonin transporters. Similar reductions in 5-HIAA and serotonin transporter density have been observed in human ecstasy users, suggesting loss of serotonergic fibers. However, some recent studies failed to show loss of the serotonin transporter protein or reactive astrogliosis after MDMA exposure, and MDMA also down-regulates serotonin transporter gene expression. These findings have led to debate: decreased protein levels do not necessarily indicate neurodegeneration, but neuromodulatory mechanisms do not rule out serotonin terminal degeneration.
Pharmaceuticals
July 1, 2025
Mateus Araújo Da Luz, H. Guedes, Antônio B. M. Bisneto et al.
5 citations
A review of 74 articles on Psilocybe mushrooms found that 66 reported psilocybin or psilocin, confirming psychoactivity, while 4 demonstrated antimicrobial and antioxidant activities of whole extracts. Across the genus, 37 chemical compounds were identified, 23 of which are alkaloids. Only alkaloids, terpenoids, and phenolic compounds were found, totaling just 36 compounds over 67 years of study. Most research focused on tryptamine alkaloids responsible for psychoactivity, with no studies examining isolated compounds against specific pathological factors except for whole-extract larvicidal, antimicrobial, and antioxidant potential. The authors suggest that future work should isolate new compounds and evaluate alternative biological activities.
Pharmaceuticals
March 23, 2025
Gregory Ian Robinson, Marta Gerasymchuk, Timur Zanikov et al.
4 citations
Psilocybin and eugenol, both individually and combined, reduced inflammation in a mouse model of liver injury induced by lipopolysaccharides. Post-treatment administration produced stronger anti-inflammatory effects than pre-treatment. Psilocybin alone showed the most pronounced reduction of pro-inflammatory cytokines IL-1β, IL-6, and MCP-1, while the combination with eugenol (1:50 ratio) also strongly reduced COX-2 and TNF-α. Histological analysis indicated improved nuclear circularity and less inflammatory infiltration. Eugenol alone increased MCP-1 and GM-CSF, an adverse effect that was mitigated by co-administration with psilocybin. The findings suggest psilocybin and its combination with eugenol as potential therapies for hepatic inflammation.
Pharmaceuticals
June 15, 2011
Elena Escubedo, Sara Garcia-Ratés, Jordi Camarasa et al.
4 citations
Amphetamine derivatives like methamphetamine (METH) and MDMA (ecstasy) are neurotoxic in animal models and linked to cognitive impairments in heavy users. Their main targets are monoamine transporters, causing increased monoamine release. A key cause of neurotoxicity is increased production of reactive oxygen species (ROS). Blockade of α7 nicotinic acetylcholine receptors (nAChR) inhibits METH- and MDMA-induced ROS production in striatal synaptosomes, a process dependent on calcium and NO-synthase activation. α7 nAChR antagonists attenuated neurotoxicity in vivo, and memantine prevented cognitive impairment. MDMA acts as a partial agonist on α7 and an antagonist on heteromeric nAChR, with sustained calcium increases leading to calpain and caspase-3 activation.
Pharmaceuticals
May 3, 2021
Natalia Górska, Wiesław Jerzy Cubała, Jakub Słupski et al.
2 citations
Magnesium levels in the blood change over the course of ketamine treatment for depression. In patients with major depressive disorder or bipolar disorder, serum magnesium concentration was significantly higher before treatment began than after five or seven ketamine infusions. However, changes in magnesium levels were not correlated with depression scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) or with mania scores on the Young Mania Rating Scale (YMRS). The study also found no link between magnesium concentration and somatic comorbidities. While the findings support the idea that magnesium plays a role in treatment-resistant depression, especially with ketamine, there is no clear evidence of a straightforward relationship between magnesium levels and treatment response or other health conditions.
Pharmaceuticals
July 8, 2026
Rodrigo Foss da Silva, Lennon Machado Alves, Fernanda Conte et al.
NBOHs, a class of new psychoactive substances acting on serotonin receptors, show varying neurotoxicity. In human neuron-like cells, two derivatives, 25E-NBOH and 25B-NBOH, reduced cell viability, caused mitochondrial hyperpolarization, and increased oxidative species. In fruit flies, 25B-NBOH impaired climbing ability, and both 25E-NBOH and 25B-NBOH elevated catalase and acetylcholinesterase enzyme activities at 50 nM. These results suggest that 25E- and 25B-NBOH are more toxic than 25I-NBOH, with potential mechanisms involving mitochondrial signaling, oxidative stress, and cholinergic disruption.
Pharmaceuticals
February 28, 2026
Oliver Grundmann, Allison Henderson
Indole alkaloids such as ibogaine and mitragynine activate μ-opioid receptors as biased full or partial agonists that recruit β-arrestin much less than non-biased agonists. Because β-arrestin recruitment is linked to adverse effects like respiratory depression, this biased activation may limit those effects. The molecular mechanism likely involves the indole structure altering the spatial orientation of amino acid residues in transmembrane regions 2 and 3 and extracellular helix 8. These naturally occurring compounds may provide a scaffold for developing new opioid modulators with an improved risk-to-benefit ratio.
Pharmaceuticals
February 14, 2026
Petra Dolenec, Goran Pelčić, Kristina Pilipović et al.
Glaucoma is an ischemic neurodegenerative disease driven not only by high eye pressure but also by vascular, metabolic, and inflammatory damage that progressively disconnects retinal neurons from the brain. Current treatments lower eye pressure but do not address this neurodegeneration or restore lost connections. Ischemia triggers excitotoxicity, oxidative stress, and chronic inflammation involving microglia and astrocytes, which suppress the brain's natural ability to repair itself. Psychoplastogens—compounds like ketamine, psilocybin, and DMT—rapidly enhance structural and functional neuroplasticity through BDNF-TrkB-mTOR signaling and also exert anti-inflammatory effects. This review integrates insights from cerebral ischemia to propose psychoplastogens as potential neurorestorative and anti-inflammatory agents for glaucoma, while outlining translational challenges.
Pharmaceuticals
November 3, 2025
Jay Toulany, Jasmyn E. A. Cunningham, Abraham Nunes
Lithium is the standard long-term treatment for bipolar disorder, but only 30% of patients respond, and there is no way to predict who will benefit. Ketamine, a rapid antidepressant, may work better in patients whose symptoms typically predict poor lithium response. This scoping review of 19 preclinical and 23 clinical studies found that ketamine and lithium act on overlapping biological pathways (GSK-3β/mTOR and synaptic plasticity), but the clinical predictors of response diverge: ketamine response is linked to metabolic risk, anxiety, and mixed features—factors that predict poor lithium response. No study directly tested whether ketamine response predicts lithium response. The findings suggest mechanistic overlap but clinical divergence, though sampling bias may confound results.