Nootropic Research Articles

Pre-clinical evidence that methylphenidate increases motivation and/or reward preference to search for high value rewards

Methylphenidate is a stimulant used to treat attention deficit and hyperactivity disorder (ADHD). In the last decade, illicit use of methylphenidate has increased among healthy young adults, who consume the drug under the assumption that it will improve cognitive performance. However, the studies that aimed to assess the methylphenidate effects on memory are not consistent. Here, we tested whether the effect of methylphenidate on a spatial memory task can be explained as a motivational and/or a reward effect. We tested the effects of acute and chronic i.p. administration of 0.3, 1 or 3 mg/kg of methylphenidate on motivation, learning and memory by using the 8-arm radial maze task. Adult male Wistar rats learned that 3 of the 8 arms of the maze were consistently baited with 1, 3, or 6 sucrose pellets, and the number of entries and reentries into reinforced and non-reinforced arms of the maze were scored. Neither acute nor chronic (20 days) methylphenidate treatment affected the number of entries in the non-baited arms. However, chronic, but not acute, 1–3 mg/kg methylphenidate increased the number of reentries in the higher reward arms, which suggests a motivational/rewarding effect rather than a working memory deficit. In agreement with this hypothesis, the methylphenidate treatment also decreased the approach latency to the higher reward arms, increased the approach latency to the low reward arm, and increased the time spent in the high, but not low, reward arm. These findings suggest that methylphenidate may act more as a motivational enhancer rather than a cognitive enhancer in healthy people.

Effect of statins on oxidative stress and cognitive function in patients with cerebral atherosclerosis: results of a prospective cohort study

The widespread use of statins for cardiovascular complications prevention makes it important to study their effects on the body. There is still no unambiguous opinion regarding the effect of statins on cognitive functions (CF). Objective : to evaluate the effect of a 12-week course of statins on the parameters of oxidative stress and CF in patients with cerebral atherosclerosis (CA) and moderate cognitive impairment. Patients and methods . 106 patients aged 45–75 years with CA and vascular risks were included, they received stable therapy for 12 weeks, including antihypertensive, nootropic drugs, antiplatelet agents and statins with stable dose and combination of drugs. At baseline and after 12 weeks of treatment, parameters of oxidative stress using Fe2+-induced chemiluminescence and cognitive phenotype, using the MoCA test, including MoCA indices, were assessed in two groups of patients: treated with statins (group 1; n=34) and those who did not receive statins (group 2; n=72). Results and discussion . In patients of group 1, more pronounced manifestations of oxidative stress and lower initial values of CF indicators were revealed. The therapy made it possible to achieve an improvement in cognitive performance in all patients, but an improvement in oxidative performance was only in group 1. The positive effect of statins on CF was manifested as a significant increase in attention- (by 1.5 points versus 0.1 points; p<0.05) and memory- (by 0.9 points against 0.2 points; p<0.05) indicators; and on the oxidative status – an increase of the indicator of resistance of lipoproteins to lipid peroxidation (LPO) by 25.9 sec vs. 3.5 sec (p<0.05) and a decrease in the activity of LPO processes (-13.6 mV vs. 39.1 mV; p<0.05). Conclusion . The 3 month therapeutic course of statins in patients with CA and vascular risks helps to reduce the manifestations of oxidative stress and improve attention and mnestic function.

Tacrine Derivatives in Neurological Disorders: Focus on Molecular Mechanisms and Neurotherapeutic Potential.

Tacrine is a drug used in the treatment of Alzheimer's disease as a cognitive enhancer and inhibitor of the enzyme acetylcholinesterase (AChE). However, its clinical application has been restricted due to its poor therapeutic efficacy and high prevalence of detrimental effects. An attempt was made to understand the molecular mechanisms that underlie tacrine and its analogues influence over neurotherapeutic activity by focusing on modulation of neurogenesis, neuroinflammation, endoplasmic reticulum stress, apoptosis, and regulatory role in gene and protein expression, energy metabolism, Ca2+ homeostasis modulation, and osmotic regulation. Regardless of this, analogues of tacrine are considered as a model inhibitor of cholinesterase in the therapy of Alzheimer's disease. The variety both in structural make-up and biological functions of these substances is the main appeal for researchers' interest in them. A new paradigm for treating neurological diseases is presented in this review, which includes treatment strategies for Alzheimer's disease, as well as other neurological disorders like Parkinson's disease and the synthesis and biological properties of newly identified versatile tacrine analogues and hybrids. We have also shown that these analogues may have therapeutic promise in the treatment of neurological diseases in a variety of experimental systems.

Nootropics as Cognitive Enhancers: Types, Dosage and Side Effects of Smart Drugs.

Nootropics, also known as “smart drugs” are a diverse group of medicinal substances whose action improves human thinking, learning, and memory, especially in cases where these functions are impaired. This review provides an up-to-date overview of the potential effectiveness and importance of nootropics. Based on their nature and their effects, this heterogeneous group of drugs has been divided into four subgroups: classical nootropic compounds, substances increasing brain metabolism, cholinergic, and plants and their extracts with nootropic effects. Each subgroup of nootropics contains several main representatives, and for each one, its uses, indications, experimental treatments, dosage, and possible side effects and contraindications are discussed. For the nootropic plant extracts, there is also a brief description of each plant representative, its occurrence, history, and chemical composition of the medicinal part. Lastly, specific recommendations regarding the use of nootropics by both ill and healthy individuals are summarized.

Effectiveness of Nootropics in Combination with Cholinesterase Inhibitors on Cognitive Function in Mild-to-Moderate Dementia: A Study Using Real-World Data.

The clinical benefits of nootropics in the treatment of cognitive decline has been either limited or controversial. This study aimed to observe the effectiveness of cholinesterase inhibitor (ChEI) and nootropics combination in the treatment of cognitive impairment in dementia. Data were based on electronic medical records in a university health system. Patients with mild-to-moderate dementia and no history of prior cognitive enhancer use were included (n = 583). The subjects were categorized into the ChEI only group and the ChEI and nootropics combination group. The primary outcome measure was the change in cognitive function, as assessed by the mini-mental state examination (MMSE) from baseline to 300–400 days after the first ChEI prescription. Subsequent analyses were conducted in consideration of the dementia type, medical adherence, and type of nootropics. The changes in MMSE scores from baseline to endpoint were not significantly different between the two groups. In Alzheimer’s dementia, the combination group showed significantly less deterioration in MMSE language subscale scores compared to the ChEI only group (F = 6.86, p = 0.009), and the difference was consistent in the highly adherent subjects (F = 10.16, p = 0.002). The choline alfoscerate and the ginkgo biloba extract subgroups in Alzheimer’s dementia showed more significant improvements in the MMSE language subscale scores compared to the other nootropics subgroup (F = 7.04, p = 0.001). The present study showed that the effectiveness of ChEI and nootropics combination on cognition may appear differently according to the dementia type. This emphasizes the need for well-controlled studies to generalize the effectiveness of nootropics across various clinical settings.

Clinical Efficacy of Cerebrolysin and Cerebrolysin plus Nootropics in the Treatment of Patients with Acute Ischemic Stroke in Vietnam.

To investigate the efficacy and safety of Cerebrolysin and Cerebrolysin plus nootropics in the routine treatment of patients with acute ischemic stroke (AIS). Acute ischemic stroke (AIS) is a leading cause of disability with unmet treatment needs lacking effective drug therapy. Multimodal drugs modulating stroke pathophysiology as Cerebrolysin constitute a good therapeutic option. In this study, we assessed the effects of Cerebrolysin and Cerebrolysin plus nootropics, in comparison with other nootropic drugs alone, on functional, neurological and cognitive recovery of patients with AIS in Vietnam. This non-interventional, controlled, open-label, prospective and multicenter study included 398 AIS patients (234 males) treated with Cerebrolysin (n=190; 20 i.v. infusions of 10 ml), other nootropics (comparator group; n=86), or a combination of both (n=122). The study primary endpoint was the modified Ranking Scale (mRS) score on day 90. Secondary endpoints included study-period change in NIHSS score; percentage of well-recovered (mRS 0-2) patients, the proportion of good NIHSS response (≥6 points) cases, and MoCA scores at day 90; and safety indicators. Compared with other nootropics, both Cerebrolysin and combined therapy induced significant improvements (p<0.001) in: Functional recovery (mRS scores); percentage of well-recovered patients (Cerebrolysin: 81.6%; combination: 93.4%; comparator: 43.0%); neurological recovery (study- period NIHSS change); proportion of good NIHSS responders (Cerebrolysin: 77.5%; combination: 92.5%; comparator: 47.6%); and MoCA scores (Cerebrolysin: 23.3±4.8; combination: 23.7±4.1; comparator: 15.9±7.7). Compared to Cerebrolysin, combined therapy improved (p<0.01) mRS outcomes and NIHSS change, but not MoCA scores, in moderate-severe stroke (NIHSS>11) cases only. No drug-related adverse events were reported. Cerebrolysin alone or combined with other nootropics was effective and safe in routine AIS treatment, during both acute and recovery phases, which supports its use in daily clinical practice. Others: According to the results of this multicenter study, the importance of reducing differences in the treatment regimens of AIS in Vietnam should be further emphasized.

Enhancing exposure therapy for posttraumatic stress disorder (PTSD): a randomized clinical trial of virtual reality and imaginal exposure with a cognitive enhancer

Posttraumatic stress disorder (PTSD) is a significant public health issue. Yet, there are limited treatment options and no data to suggest which treatment will work for whom. We tested the efficacy of virtual reality exposure (VRE) or prolonged imaginal exposure (PE), augmented with D-cycloserine (DCS) for combat-related PTSD. As an exploratory aim, we examined whether brain-derived neurotrophic factor (BDNF) and fatty acid amide hydrolase (FAAH) moderated treatment response. Military personnel with PTSD (n = 192) were recruited into a multisite double-blind randomized controlled trial to receive nine weeks of VRE or PE, with DCS or placebo. Primary outcome was the improvement in symptom severity. Randomization was stratified by comorbid depression (MDD) and site. Participants in both VRE and PE showed similar meaningful clinical improvement with no difference between the treatment groups. A significant interaction (p = 0.45) suggested VRE was more effective for depressed participants (CAPS difference M = 3.51 [95% CI 1.17–5.86], p = 0.004, ES = 0.14) while PE was more effective for nondepressed participants (M = −8.87 [95% CI −11.33 to −6.40], p < 0.001, ES = −0.44). The main effect of DCS vs. placebo was not significant. Augmentation by MDD interaction (p = 0.073) suggested that depressed participants improved more on placebo (M = −8.43 [95% CI −10.98 to −5.88], p < 0.001, ES = −0.42); DCS and placebo were equally effective for nondepressed participants. There was an apparent moderating effect of BDNF Val66Met polymorphism on DCS augmentation (ES = 0.67). Met66 allele carriers improved more on DCS (ES = −0.25). FAAH 385 A carriers improved more than non-carriers (ES = 0.33), particularly those with MDD (ES = 0.62). This study provides a step toward precision therapeutics for PTSD by demonstrating that comorbid MDD and genetic markers may help guide treatment selection.ClinicalTrials.gov Identifier: NCT01352637.

Prospects for the Cortexin application

Cortexin is a multicomponent preparation containing low-molecular-weight neuropeptides (complex of L-amino- and ribonucleic acids), vitamins and microelements. It belongs to the group of nootropic drugs and contributes to the activation of the higher brain activity, restoration of cognitive functions, reduction of neurological deficits, and the increase in brain resistance to aggressive factors. In addition to Cortexin, nootropics include: piracetam, cerebrolysin, citicoline, mexidol and many others. There are data indicating the high efficiency of Cortexin in the treatment of ischemic strokes, diseases accompanied by cognitive impairment, epilepsy, etc. [1, 2]. Due to the fact that today the number of diseases that affect brain function is steadily growing (hemorrhagic and ischemic strokes, encephalopathies, epilepsy, encephalitis, and so on), the study of the effects of Cortexin as one of the promising nootropics and the description of the features of its use are crucial.

PHARMACOLOGICAL ACTIVITIES AND GENETIC ASPECTS OF NOOTROPIC PLANT BACOPA MONNIERI”

Among the plants considered for medicinal significance, the plant Bacopa monnieri (Brahmi) belonging to the Scrophulariaceae family is very important for its therapeutic potentials and pharmacologically relevant phytochemicals. B. monnieri has traditionally been utilized as a neurological substance and cognitive enhancer. A lot of efforts are now devoted to study its neuroprotective properties traced in traditional medicines. This plant is well known for its improvement of brain function along with memory enhancement, antioxidant, antitoxic, hepatoprotactive, anti-hypertensive, anti-diarrheal, analgesic, antiulcer, antibacterial, antifungal, anticancer, antioxidant, anti-inflammatory, antidepressant, and antiepileptic activities.

Exploring Irish students’ attitudes towards nootropic supplements

The vast majority of research on cognitive enhancement has focused on pharmacological cognitive enhancement (PCE), with relatively little exploration of public attitudes towards non-pharmacological cognitive enhancing substances. Limited research has investigated how the lay public ethically evaluates nootropic supplements (i.e. legal and purportedly natural over-the-counter products), or how such attitudes may differ from attitudes towards other cognitive enhancers. This experimental between-subjects study used a contrastive vignette technique to explore Irish students’ attitudes towards caffeine tablets, nootropic supplements and PCE. One-hundred-and-thirteen Irish university students participated in the study (46 male, 64 female), ranging from 18 to 25 years of age (M = 21.9). Quantitative analyses examined differences in mean attitudes between cognitive enhancement conditions and genders. Results suggest that the three forms of cognitive enhancement provoked similar moderate responses in relation to safety and authenticity, however, students were more concerned about implicit coercion in relation to PCE and reported heightened fairness concerns in relation to nootropic supplements. Nootropic supplements may have distinct ethical implications which are not simply equivalent to those that accompany PCE or caffeine tablets, raising questions surrounding the effects of novel cognitive enhancing products; financial barriers to legal non-pharmacological cognitive enhancement; and the permissibility of cognitive enhancement advertising.

Pharmacological characterization of a novel putative nootropic beta-alanine derivative, MB-005, in adult zebrafish.

Cognitive deficits represent an urgent biomedical problem, and are commonly reduced by nootropic drugs. Animal models, including both rodents and zebrafish, offer a valuable tool for studying cognitive phenotypes and screening novel nootropics. Beta-alanine and its derivatives have recently been proposed to exert nootropic activity. This study aimed to characterize putative nootropic profile of a novel β-alanine analogue, 1,3-diaminopropane (MB-005), in adult zebrafish. Nootropic profile of MB-005 was assessed in adult zebrafish in the novel tank and conditioned place aversion (CPA) tests acutely, and in cued-learning plus-maze (PMT) tests chronically. MB-005 did not alter zebrafish anxiety-like behavior or monoamine neurochemistry acutely, improved short-term memory in the CPA test, but impaired cognitive performance in both CPA and PMT tests chronically. This study reveals high sensitivity of zebrafish cognitive phenotypes to MB-005, suggesting it as a potential novel cognitive enhancer acutely, but raises concerns over its cognitive (and, possibly, other) side-effects chronically.

Neuroprotective Effect of Caffeine in Alzheimer's Disease.

Alzheimer’s disease (AD) is the leading cause of dementia, predicted to be the most significant health burden of the 21st century, with an estimated 131.5 million dementia patients by the year 2050. This review aims to provide an overview of the effect of caffeine on AD and cognition by summarizing relevant research conducted on this topic. We searched the Web of Science core collection and PubMed for studies related to the effect of caffeine on AD and cognition using title search terms: caffeine; coffee; Alzheimer’s; cognition. There is suggestive evidence from clinical studies that caffeine is neuroprotective against dementia and possibly AD (20 out of 30 studies support this), but further studies, such as the “ideal” study proposed in this review, are required to prove this link. Clinical studies also indicate that caffeine is a cognitive normalizer and not a cognitive enhancer. Furthermore, clinical studies suggest the neuroprotective effect of caffeine might be confounded by gender. There is robust evidence based on in vivo and in vitro studies that caffeine has neuroprotective properties in AD animal models (21 out of 22 studies support this), but further studies are needed to identify the mechanistic pathways mediating these effects.

Combined long-term enriched environment and caffeine supplementation improve memory function in C57Bl6 mice

Regular physical activity has been associated with healthy brain aging, reflected by beneficial effects on cognition and learning and memory. Nutritional supplements such as caffeine have been shown to act as cognitive enhancers and may possess neuroprotective properties. Interestingly, caffeine also improves athletic capabilities and is widely used by athletes because of its performance-enhancing effect, while information on potential additive beneficial effects of physical activity and caffeine on cognitive performance is scarce. In the present study, the effects of caffeine supplementation in combination with prolonged physical and cognitive stimulation in the form of the enriched environment (EE) housing for a duration of 4 months were analyzed. We demonstrate that caffeine supplementation together with prolonged environmental enrichment led to enhanced memory function, resulting in improved recognition and spatial working memory in behavioral paradigms such as the novel object recognition task or the Morris water maze in C57Bl6 wild-type mice. Mice housed under EE conditions showed increased gene expression levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. The present findings underscore the potential impact of continuous physical activity in the prevention of age-related cognitive decline and may offer new options for combinatorial approaches.

Effects of Smart Drugs on Cholinergic System and Non-Neuronal Acetylcholine in the Mouse Hippocampus: Histopathological Approach.

In recent years, people in the United States and other countries have been using smart drugs, called nootropic or cognitive enhancers, to improve concentration and memory learning skills. However, these drugs were originally prescribed for attention-deficit hyperactivity disorder and dementia, and their efficacy in healthy people has not yet been established. We focused on acetylcholine in the hippocampus, which is responsible for memory learning, and elucidate the long-term effects of smart drugs on the neural circuits. Smart drugs were administered orally in normal young mice for seven weeks. The hippocampus was sectioned and compared histologically by hematoxylin and eosin (HE) staining, immunohistochemistry for acetylcholine, and immunoelectron microscopy. There were no significant changes in acetylcholinesterase staining. However, in HE, we found perivascular edema, and choline acetyltransferase staining showed increased staining throughout the hippocampus and new signal induction in the perivascular area in the CA3, especially in the aniracetam and α-glyceryl phosphoryl choline group. Additionally, new muscarinic acetylcholine receptor signals were observed in the CA1 due to smart drug intake, suggesting that vasodilation might cause neuronal activation by increasing the influx of nutrients and oxygen. Moreover, these results suggest a possible new mechanism of acetylcholine-mediated neural circuit activation by smart drug intake.

Cognitive enhancement: Effects of methylphenidate, modafinil, and caffeine on latent memory and resting state functional connectivity in healthy adults.

Stimulants like methylphenidate, modafinil, and caffeine have repeatedly shown to enhance cognitive processes such as attention and memory. However, brain‐functional mechanisms underlying such cognitive enhancing effects of stimulants are still poorly characterized. Here, we utilized behavioral and resting‐state fMRI data from a double‐blind randomized placebocontrolled study of methylphenidate, modafinil, and caffeine in 48 healthy male adults. The results show that performance in different memory tasks is enhanced, and functional connectivity (FC) specifically between the frontoparietal network (FPN) and default mode network (DMN) is modulated by the stimulants in comparison to placebo. Decreased negative connectivity between right prefrontal and medial parietal but also between medial temporal lobe and visual brain regions predicted stimulant‐induced latent memory enhancement. We discuss dopamine's role in attention and memory as well as its ability to modulate FC between large‐scale neural networks (e.g., FPN and DMN) as a potential cognitive enhancement mechanism.

Association of cognitive enhancers and incident seizure risk in dementia: a population-based study

BackgroundAlthough individuals with dementia have a high risk of developing seizures, whether seizures are associated with cholinesterase inhibitors, which are commonly prescribed to treat individuals with dementia, remains unknown. This study investigated the risk of incident seizure following cholinesterase inhibitor use in patients with dementia.MethodsA nationwide, nested case-control study was conducted using data from the Korean Health Insurance Review and Assessment Service (HIRA) from 2014 through 2018. A total of 13,767 participants aged 65–95 years who experienced incident seizure were propensity score-matched for medical comorbidities and drug exposure at a 1:3 ratio with a control group of 39,084 participants. The study examined the incidence of seizures in patients diagnosed with dementia within one year after receiving cognitive enhancers. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for seizure incidence according to cholinesterase inhibitor use were analyzed using a multivariable conditional logistic regression model.ResultsThere was no statistically significant association between duration of cholinesterase inhibitors use and seizure risk. Although there was slight increased seizure risk in patient after receiving donepezil for 1 year compared to memantine, subgroup analyses stratified age and sex did not reveal any significant association between cholinesterase inhibitors use and late-onset seizure.ConclusionsOur findings suggest no immediate increase in seizure risk is associated with cholinesterase inhibitor use, although the risk of seizure in patients with dementia did increase after one year of continued medication intake. Further study is required to obtain confirmatory results on the seizure-related safety of cognitive enhancers in patients with dementia.

Flavonoid Derivatives as Potential Cholinesterase Inhibitors in Scopolamine-Induced Amnesic Mice: An In Vitro, In Vivo and Integrated Computational Approach.

Flavonoids are one of the most exciting types of phenolic compounds with a wide range of bioactive benefits. A series of flavone derivatives (F1–F5) were previously synthesized from substituted O-hydroxy acetophenone and substituted chloro-benzaldehydes. The titled compounds F1–F5 in the present study were evaluated for their anticholinesterase potential (against AChE and BuChE). The obtained results were then validated through a molecular docking approach. Compound F5 was found to be the most potent inhibitor of AChE (IC50 = 98.42 ± 0.97 µg/mL) followed by compound F4, whereas compound F2 was found to be the most promising inhibitor of BuChE (IC50 = 105.20 ± 1.43 µg/mL) among the tested compounds. The molecular docking analysis revealed a similar trend in the binding affinity of compounds with the targeted enzymes and found them to be capable of forming highly stable complexes with both receptors. The selected compounds were further subjected to in vivo assessment of cognitive function in a scopolamine-induced amnesic animal model, in which almost all compounds F1–F5 significantly attenuated the amnesic effects as evaluated through Y-Maze Paradigm and novel object discrimination (NOD) tasks, findings that were further supported by ex vivo experimental results. Among (F1–F5), F5 showed significant anti-amnesic effects in scopolamine-induced amnesic models and ameliorated the memory loss in behavioral model studies as compared to counterparts. In ex vivo study, noteworthy protection from oxidative stress in the brains of scopolamine-induced amnesic mice was also recorded for F5. These findings also confirmed that there were no significant differences among the in vivo and ex vivo results after administration of F1–F5 (7.5 or 15 mg/kg) or donepezil (2 mg/kg). These synthesized flavonoids could serve as potential candidates for new neuroprotective and nootropic drugs. However, further studies are needed to validate their observed potential in other animal models as well.

M6A Modification Involves in Enriched Environment-Induced Neurogenesis and Cognition Enhancement.

Although previous studies have shown that an enriched environment (EE) promotes neurogenesis and alters DNA and histone modifications, it remains largely unknown whether an EE affects epitranscriptome in the context of neuronal development. Here, we showed that EE exposure enhanced the pool of adult neural stem/progenitor cells (aNSPCs) and promoted neuronal differentiation of aNSPCs. EE exposure also improved cognitive capabilities and altered the expression of genes relating to neuronal development, neurogenesis, and memory. N 6-Methyladenosine (m6A) immunoprecipitation combined with deep sequencing (MeRIP-seq) data analysis revealed that EE exposure increased the global level of m6A and led to differential m6A mRNA modification. Differential m6A modification-associated genes are involved in neuronal development, neurogenesis, and so on. Notably, EE exposure decreased the protein level of m6A eraser Fto, but did not affect the protein level of m6A writers METTL3 and METTL14. Taken together, our results suggest that enriched environment exposure induces differential m6A mRNA modification and adds a novel layer to the interaction between the environment and epigenetics in the context of postnatal neuronal development.

As-Needed Prescribing and Administration of Psychotropic Medications in Assisted Living: A 7-State Study.

Psychotropic medications administered on an as-needed basis, often designated as pro re nata (or PRN, hereafter as-needed), can alleviate acute symptoms and facilitate deprescribing, although as-needed use is associated with negative outcomes such as polypharmacy and drug interactions. The aim of this study was to examine the extent to which PRN psychotropic medications are prescribed and administered to assisted living (AL) residents, overall and in relation to resident- and community-level characteristics. Cross-sectional study. All AL residents and select staff in 250 AL communities in 7 states. Data regarding prescribing and administration of 5 types of PRN psychotropic medications in the prior 7days (antipsychotics, mood stabilizers and antiepileptics, antidepressants, anxiolytics/hypnotics, and cognitive enhancers) were abstracted and compared across resident and community characteristics. Prescribing of PRN psychotropics in AL is low (10.3%). Of prescribed PRN medications, 2.5% of residents were administered a PRN and 8% had PRN that was not administered in the previous 7days. Anxiolytics were administered PRN more commonly compared with antipsychotics (2.0% vs 0.2%). Of all PRN psychotropic prescriptions (n= 1039), 70.5% had a written indication describing the reason for administration. Among PRN medications administered (n= 242), the proportion with an indication was lower (62.0%). PRN psychotropic medication prescribing was higher among residents with dementia and a psychiatric diagnosis, and in larger AL communities and those with a higher proportion of dementia care beds. The prescribing and administration of PRN psychotropic medications in AL is relatively rare, although more common among residents with dementia. Emerging psychotropic medication policies should be expanded to address mental health care, anxiolytic/hypnotic use for residents living with dementia, PRN prescribing in chart review, and the use of detailed indications for PRN use, especially when medications are administered by unlicensed care staff.

The “Smart Pill” High: A Case of Phenibut Intoxication and Withdrawal

Phenibut is an anxiolytic and nootropic drug, discovered in the Soviet Union used to treat several psychiatric disorders. Currently it is available online as supplement. The case report highlights the abuse potential of phenibut, with the associated clinical presentation of intoxication, withdrawal, and relapse, as well as the use of baclofen as a potential treatment of phenibut withdrawal.