Molecules (Basel, Switzerland)
June 24, 2023
Daniela-Mădălina Ciucă Anghel, Gabriela Viorela Nițescu, Andreea-Taisia Tiron et al.
69 citations
Drug abuse and addiction affect millions worldwide. This review examines mechanisms and effects of opioids, stimulants, depressants, hallucinogens, and cannabis, covering acute and chronic effects, withdrawal symptoms, and cardiovascular impacts including electrocardiogram changes. It also discusses genetic susceptibility in addictions. The review draws on PubMed, grey literature, and reference lists without time limits. It provides a comprehensive overview to inform evidence-based prevention and intervention strategies.
Molecules (Basel, Switzerland)
October 11, 2018
Bronwyn M Kivell, Kelly F Paton, Nitin Kumar et al.
45 citations
A potent and selective kappa opioid receptor (KOPr) analogue of Salvinorin A, Mesyl Sal B, reduces cocaine-induced hyperactivity and behavioral sensitization to cocaine in male rats without causing aversion, sedation, anxiety, or learning and memory deficits. It does not alter sucrose self-administration. However, it increases immobility in the forced swim test, indicating pro-depressive effects. In male mice, Mesyl Sal B is less potent than Salvinorin A at reducing pain in antinociceptive assays. The compound has fewer side effects and longer in vivo action than Salvinorin A, but its pain-relieving effects are limited.
Molecules (Basel, Switzerland)
March 5, 2021
Joana Gonçalves, Ângelo Luís, Eugenia Gallardo et al.
39 citations
Consumption of new psychoactive substances of natural origin, including plants and fungi containing alkaloids with relaxing, stimulating, or hallucinogenic effects, is increasing worldwide. Use is often driven by religious or cultural reasons, leading to variable legislation. Abusive consumption poses health risks because metabolism and effects are not fully understood. These substances spread rapidly via the internet, requiring sophisticated analytical methods for detection. This review covers toxicological aspects, traditional use and therapeutic potential, and analytical methods in biological matrices for twelve plant specimens: Areca catechu, Argyreia nervosa, Ayahuasca, Catha edulis, Datura stramonium, Lophophora williamsii, Mandragora officinarum, Mitragyna speciosa, Piper methysticum Forst, Psilocybe, Salvia divinorum, and Tabernanthe iboga.
Molecules (Basel, Switzerland)
June 30, 2025
Ewa Gibuła-Tarłowska, Anna Wiszniewska, Magdalena Turyk et al.
10 citations
Ketamine, originally developed as an anesthetic, also provides potent pain relief by blocking NMDA receptors, which helps reduce chronic and neuropathic pain. It shows promise for treating substance use disorder by disrupting maladaptive reward memories and promoting neuroplasticity. Additionally, S-ketamine produces rapid antidepressant effects in treatment-resistant depression, likely through increased glutamatergic signaling and synaptic plasticity. This broad therapeutic profile makes ketamine a unique agent spanning anesthesia, pain management, addiction medicine, and psychiatry, though further research into its mechanisms and long-term effectiveness is needed.
Molecules (Basel, Switzerland)
February 22, 2024
Hanbo Yao, Xiaodong Wang, Jiaxin Chi et al.
9 citations
Major Depressive Disorder involves changes in signal transmission and brain structure. Progress in developing effective antidepressants has been slow due to the dominance of the monoamine hypothesis, and traditional drugs often have delayed effects, limited efficacy, and severe side effects. Recently, fast-acting compounds like S-ketamine and psychedelics such as LSD have emerged, prompting structural research on their target receptors. Cryo-electron microscopy has enabled high-resolution structures of the N-methyl-D-aspartate receptor and the 5-hydroxytryptamine 2A receptor, which can be used for virtual drug screening. The 5-HT1A receptor shows unique antidepressant effects in different brain regions, while AMPAR and TrkB receptors regulate synaptic plasticity. Using this structural information, highly selective antidepressants with rapid onset and fewer side effects have been designed.
Molecules (Basel, Switzerland)
August 3, 2023
Lulu Zhang, Jia Xu, Jiejie Guo et al.
9 citations
Alzheimer's disease is a brain disease with an insidious onset and multiple factors. An in silico study of the traditional Chinese herb Evodia rutaecarpa (Wuzhuyu) found that its active compounds primarily target Alzheimer's disease rather than migraines, for which the herb is traditionally used. Behavioral experiments showed that E. rutaecarpa extract improved learning and memory impairments in AD model mice. Using pharmacology networking and molecular docking, the authors found that alkaloids in the herb bind to key nodes of AD, affecting pathways including serotonergic synapse signaling (SLC6A4), hormones (PTGS2, ESR1, AR), anti-neuroinflammation (SRC, TNF, NOS3), transcription regulation (NR3C1), and molecular chaperones (HSP90AA1). Specific compounds—graveoline, 5-methoxy-N,N-dimethyltryptamine, dehydroevodiamine, and goshuyuamide II—showed stronger binding affinities to key proteins than known preclinical and clinical drugs.
Molecules (Basel, Switzerland)
August 31, 2023
Wolfgang Sadee
8 citations
G-protein-coupled receptors (GPCRs) can signal even without a ligand bound, a phenomenon called ligand-free or basal signaling. Agonists trigger signaling that can remodel the receptor, causing rapid ligand dissociation while the receptor continues to signal. This acutely activated, ligand-free signaling may enhance agonist potency at low occupancy. Sustained elevated ligand-free signaling is proposed to play a role in opioid dependence. The review focuses on opioid, serotonin, and growth hormone secretagogue receptors, and hypothesizes that ligand-free signaling of 5-HT2A receptors mediates therapeutic effects of psychedelic drugs. Research avenues are suggested to fill knowledge gaps.
Molecules (Basel, Switzerland)
December 4, 2024
Kaja Tusiewicz, Olga Wachełko, Marcin Zawadzki et al.
5 citations
Lysergic acid diethylamide (LSD) analogs, synthesized to evade drug regulations, pose challenges for forensic identification, especially their isomeric forms. Gas chromatography-mass spectrometry (GC-MS) and UV spectroscopy analyzed 13 LSD analogs. Solvents like diethyl ether, tert-butyl methyl ether, dichloromethane, and acetone provided the best sensitivity and stability, while methanol caused alcoholysis of many analogs, potentially leading to false results. Effective chromatographic separation was achieved for isomers including LSD, MiPLA, LAMPA, 1P-LSD, 1P-MiPLA, 1cP-LSD, and 1cP-MiPLA. Key mass spectrometry ions (e.g.
Molecules (Basel, Switzerland)
September 6, 2022
Joana Gonçalves, Ângelo Luís, Eugenia Gallardo et al.
5 citations
Ayahuasca, an Amazonian drink containing β-carboline alkaloids and N,N-dimethyltryptamine, was tested for wound-healing potential using decoctions of a commercial mixture, four individual plants, and four two-plant mixtures. Only one sample showed cytotoxicity; all others promoted migration of skin fibroblasts in a wound-healing assay with NHDF cells. A parallel artificial membrane permeability assay and transepithelial electrical resistance and Lucifer yellow permeability assays showed that the psychoactive compounds were not absorbed by the cell layer and generally did not affect its permeability or integrity. This is the first evaluation of ayahuasca's wound-healing potential.
Molecules (Basel, Switzerland)
May 23, 2024
Shiyun Li, Bin Wen, Wei Zhao et al.
4 citations
Sub-anesthetic doses of ketamine rapidly reduce depression and suicidal tendencies in patients with treatment-resistant depression and major depressive disorder, but its anesthetic and psychotomimetic side effects limit clinical use. A novel series of ketamine derivatives designed as NMDAR antagonists was synthesized; compounds 23 and 24 showed improved activity compared with ketamine, offering a new direction for developing rapid-acting antidepressants.
Molecules (Basel, Switzerland)
February 18, 2025
Veronica de Melo Sacramento, Vanessa de Andrade Royo, Pedro Henrique Fonseca Veloso et al.
2 citations
Diplopterys pubipetala, a liana from the Brazilian Cerrado used in Ayahuasca, has limited research on its chemical makeup and biological activities. This investigation identified 25 major volatile compounds in its leaves, including ethyl dodecanoate and nonanoic acid, which are known for antifungal, antioxidant, and antimicrobial properties. The crude extract and ethyl acetate fraction demonstrated strong antioxidant capacity, with EC50 values of 9.83 µg/mL and 6.42 µg/mL, respectively. Antifungal effects were observed against Candida species. This is the first comprehensive chemical and biological profile of D. pubipetala, highlighting its therapeutic potential.
Molecules (Basel, Switzerland)
January 8, 2026
Anna W Sobańska, Andrzej M Sobański, Elżbieta Brzezińska
1 citation
Most of 250 compounds from three chemical families (ergolines, tryptamines, and phenylethylamines), including ketamine and serotonergic psychedelics, are likely to cross the human placenta easily, primarily by passive diffusion. A multivariate model based on drug-likeness, Caco-2 membrane permeability, protein binding, volume of distribution, and heteroatom count predicted this passage. Atomic contributions from Morgan fingerprinting suggest that carbonyl, hydroxyl, nitro-, and phosphoryloxy groups promote placental transport, while rigid polycyclic structures, bulky alkyl/aryl groups, and halogens restrict it. All compounds are expected to be synthetically accessible, raising concerns about illegal drug production and the need for further in silico pharmacological study.
Molecules (Basel, Switzerland)
January 9, 2026
Anna Trynda, Katarzyna Karwowska, Weronika Karpowicz et al.
Synthetic cathinones like mephedrone and clephedrone, popular as cheaper substitutes for stimulants such as cocaine and MDMA, alter the surface charge density of red blood cell and platelet membranes. At tested concentrations of 170 ng/mL and 2700 ng/mL, these compounds change the electrical properties of blood cell membranes, as measured by microelectrophoresis. Despite their presence on the market since 2005, the precise toxicological impacts of synthetic cathinones on the human body remain unknown, underscoring the need for continued research.
Molecules (Basel, Switzerland)
November 18, 2025
Agata Kot-Wasik, Agnieszka Potęga, Justyna Aszyk-Woźniak et al.
Electrochemical oxidation of the psychoactive substance 25B-NBOMe in a flow cell produced key phase I metabolites—hydroxylated and N-desalkylated products along with dehydrogenated derivatives—and smaller amounts of O-desmethylated and bis-O,O-desmethylated forms. The O-desmethylated metabolite was also found in gastric contents, blood, and urine from severely intoxicated individuals. Phase II metabolites (glucuronide and sulfonate conjugates) appeared only in biological samples. The electrochemical method rapidly generated potential in vivo metabolites, partially matching authentic human samples, supporting its use as a screening tool for metabolism and toxicological risk assessment of novel psychoactive substances.