Microevidence for microdosing with psilocybin mushrooms: a double-blind placebo-controlled study of subjective effects, behavior, creativity, perception, cognition, and brain activity

The use of low sub-hallucinogenic doses of psychedelics (“microdosing”) has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies limits our knowledge of microdosing and its effects. Moreover, research conducted in laboratory settings might fail to capture the motivation of individuals engaged in microdosing protocols. We recruited 34 individuals planning to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled design, we investigated the effects of 0.5 g dried mushrooms on subjective experience, behavior, creativity, perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, which could be explained by unblinding. For the other measurements, we observed either null effects or a trend towards cognitive impairment and, in the case of EEG, towards reduced theta band spectral power. Our findings support the possibility that expectation effects underlie at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.

Using Biomarkers to Predict Memantine Effects in Alzheimer’s Disease: A Proposal and Proof-Of-Concept Demonstration

Memantine’s benefits in Alzheimer’s disease (AD) are modest and heterogeneous. We tested the feasibility of using sensitivity to acute memantine challenge to predict an individual’s clinical response. Eight participants completed a double-blind challenge study of memantine (placebo versus 20 mg) effects on autonomic, subjective, cognitive, and neurophysiological measures, followed by a 24-week unblinded active-dose therapeutic trial (10 mg bid). Study participation was well tolerated. Subgroups based on memantine sensitivity on specific laboratory measures differed in their clinical response to memantine, some by large effect sizes. It appears feasible to use biomarkers to predict clinical sensitivity to memantine.

O82 A phase 1 dose escalation study of PRS-343, a HER2/4–1BB bispecific molecule, in patients with HER2-positive malignancies

BackgroundAnticalin® proteins are recombinantly engineered human proteins based on lipocalins. PRS-343 is a first-in-class bispecific antibody-Anticalin fusion protein targeting the oncogenic tumor antigen HER2 and the costimulatory immune receptor 4-1BB on T and other immune cells. Here, we report the results of a phase 1 single-agent dose escalation trial in patients with HER2+ solid tumors.MethodsPRS-343 has been evaluated in sequential dose cohorts from 0.0005 to 8 mg/kg i.v. Doses were administered Q3W and the 8 mg/kg dose was also given Q2W. An accelerated titration design was utilized for the initial dose escalation followed by a modified 3+3 design and the option to back-fill cohorts. Dose-limiting toxicities (DLTs) were reported during the first cycle of each schedule. The primary study objectives include the safety profile and RP2D of PRS-343. Secondary objectives include ORR and DCR, PD biomarker response and PK profile. PD response was assessed in tumor biopsies (CD8+ T cell IHC) pre- and post- PRS-343 treatment.Results51 patients (median age 61.2 years, 61% female, 82% caucasian, 57% with more than three lines of prior therapy) with a variety of solid tumor indications [gastric/GEJ (n=19); BC (n=12); gynecological cancer (n=6); CRC (n=5); BTC (n=4); UC (n=2); melanoma, pancreatic and salivary duct (n=1 each)] have been treated with PRS-343. Based on pharmacokinetic analyses and observed kinetics of the CD8+ T cell expansion post-treatment, the low end of the active dose range is considered 2.5 mg/kg. 19 patients treated at active dose levels before the data cut-off on 09-06-2019 were evaluable for response [DCR 58% (11% confirmed PR) as per RECIST 1.1]. At the active doses, we observed significant and pronounced post-treatment expansion of CD8+ T cells particularly in the tumor nests, consistent with the MoA of PRS-343, while there was no increase in the doses below 2.5 mg/kg. The post-treatment expansion of CD8+ T cells was more pronounced in patients with a confirmed PR or prolonged SD. PRS-343 was very well tolerated, with no SAEs reported. The most frequent TRAEs were fatigue (9%), chills (6%) and diarrhea (5%) of mild to moderate severity. None qualified as a DLT.ConclusionsPRS-343 is the first molecule of its kind to demonstrate encouraging evidence of safety and clinical benefit with a correlative PD effect in a heavily pre-treated population. These initial data suggest that PRS-343, the first 4-1BB bispecific to enter clinical development, merits further investigation in clinical trials.Trial RegistrationNCT03330561

Evidence of Natural GHB Presence in Energy Drinks: Caution in Data Interpretation in Suspected DFSA Cases

Gamma-hydroxybutyric acid (GHB), usually reported as rape drug in drug-facilitated sexual assaults (DFSA), is an endogenous substance in human body and is also found in many beverages. This may lead to data misinterpretation in forensic cases. Herein, we aimed to collect evidence about natural GHB presence in 13 energy drinks (ED). After a liquid–liquid extraction with acidic ethyl acetate, samples were derivatized with BSTFA 1% TMCS. Analyses were carried out by a GC–MS system in SIM mode (GHB, 233, 234, 143 and 147 m/z; GHB-d6, 239, 240, 120 and 206 m/z). GHB was present in all the samples at very low concentrations ranging from 98 to 197 ng/mL. Thus, GHB presence in ED is not exclusively related to exogenous addition. Since the GHB levels are far lower than the minimum active dose (i.e., 0.5 g), it is not expected to induce any effect.

Antioxidant and Anti-Inflammatory Activities of the Crude Extracts of Raw and Fermented Tomato Pomace and Their Correlations with Aglycate-Polyphenols

Two tomato pomace (TP) were studied as feedstocks to obtain extracts that are rich in polyphenols. TPs prompt degradation impairs biomass safety, thus naturally present microflora were tested to perform conservation, and own lactic bacteria became predominant after 60 days of treatment. The extracts of TPs and TPs fermented (TPF) were chemically characterized and tested for antioxidant and anti-inflammatory activities. Flavonoids and phenolic acids were classed as aglycone-polyphenols (A-PP), the most bioactive polyphenol fraction. Fermentation led to a reduction of the A-PP amount, but no significant change in composition. Antioxidant power increased, despite the A-PP reduction, for the presence of fermentation metabolites having aromatic-substituent. TP and TPF both have anti-inflammatory properties that were strictly dependent upon the A-PP content. Fermentation preserved the anti-inflammatory activity and the Partial Least Square (PLS) identified as the most active molecules naringenin chalcone, kaempferol, gallic acid, and cinnamic acid, together with the definition of the active dose.

Special features of elimination of phosphorus compounds in aeration tanks

In the sewage treatment plants, phosphorus compounds presented constantly, due to the sources of their appearance. In urban wastewater, phosphorus stays in various compounds – dissolved, insoluble, organic, mineral, simple and complex forms. Only phosphates and total phosphorus are monitored in wastewater chemicals laboratories. The data on phosphorus compounds containing in the wastewater of a number of cities is analyzed in the study. The impact of the biological wastewater treatment process on the efficiency of phosphorus removal was assessed. The research was carried out on an experimental technological installation. It is shown that in the original wastewater not only the concentration of total phosphorus and phosphates is constantly varying, but also their ratio. In the process of biological treatment, a number of complex biochemical and physical-chemical processes are parallel: assimilation, hydrolysis, and adsorption. The effectiveness of these processes is influenced by the magnitude of the initial concentration of total phosphorus and the amount of active dose of sludge. It has been recognized that the increased efficiency of the removal of total phosphorus has an effect on both the increase in the active dose of sludge and the size of the initial concentration of total phosphorus. However, the residual concentration of total phosphorus is affected by its original content, while the initial content of the total phosphorus is affected insignificantly.