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International Journal of Molecular... Jun 2024Drug repurposing, rebranding an existing drug for a new therapeutic indication, is deemed a beneficial approach for a quick and cost-effective drug discovery process by... (Review)
Review
Drug repurposing, rebranding an existing drug for a new therapeutic indication, is deemed a beneficial approach for a quick and cost-effective drug discovery process by skipping preclinical, Phase 1 trials and pharmacokinetic studies. Several psychotropic drugs, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), were studied for their potential application in different diseases, especially in cancer therapy. Fluoxetine (FLX) is one of the most prescribed psychotropic agents from the SSRIs class for the treatment of several neuropsychiatric disorders with a favorable safety profile. FLX exhibited different oncolytic effects via mechanisms distinct from its main serotonergic activity. Taking advantage of its ability to rapidly penetrate the blood-brain barrier, FLX could be particularly useful in brain tumors. This was proved by different in vitro and in vivo experiments using FLX as a monotherapy or combination with temozolomide (TMZ) or radiotherapy. In this review of the literature, we summarize the potential pleiotropic oncolytic roles of FLX against different cancers, highlighting the multifaceted activities of FLX and its ability to interrupt cancer proliferation via several molecular mechanisms and even surmount multidrug resistance (MDR). We elaborated on the successful synergistic combinations such as FXR/temozolomide and FXR/raloxifene for the treatment of glioblastoma and breast cancer, respectively. We showcased beneficial pharmaceutical trials to load FLX onto carriers to enhance its safety and efficacy on cancer cells. This is the first review article extensively summarizing all previous FLX repurposing studies for the management of cancer.
Topics: Humans; Drug Repositioning; Fluoxetine; Animals; Neoplasms; Antineoplastic Agents; Psychotropic Drugs; Selective Serotonin Reuptake Inhibitors
PubMed: 38928021
DOI: 10.3390/ijms25126314 -
Pharmacological Reports : PR Dec 2023Since its emergence in the 1960s, the serotonergic theory of depression bore fruit in the discovery of a plethora of antidepressant drugs affecting the lives of millions... (Review)
Review
Since its emergence in the 1960s, the serotonergic theory of depression bore fruit in the discovery of a plethora of antidepressant drugs affecting the lives of millions of patients. While crucial in the history of drug development, recent studies undermine the effectiveness of currently used antidepressant drugs in comparison to placebo, emphasizing the long time it takes to initiate the therapeutic response and numerous adverse effects. Thus, the scope of contemporary pharmacological research shifts from drugs affecting the serotonin system to rapid-acting antidepressant drugs. The prototypical representative of the aforementioned class is ketamine, an NMDA receptor antagonist capable of alleviating the symptoms of depression shortly after the drug administration. This discovery led to a paradigm shift, focusing on amino-acidic neurotransmitters and growth factors. Alas, the drug is not perfect, as its therapeutic effect diminishes circa 2 weeks after administration. Furthermore, it is not devoid of some severe side effects. However, there seems to be another, more efficient, and safer way to target the glutamatergic system. Hallucinogenic agonists of the 5-HT receptor, commonly known as psychedelics, are nowadays being reconsidered in clinical practice, shedding their infamous 1970s stigma. More and more clinical studies prove their clinical efficacy and rapid onset after a single administration while bearing fewer side effects. This review focuses on the current state-of-the-art literature and most recent clinical studies concerning the use of psychedelic drugs in the treatment of mental disorders. Specifically, the antidepressant potential of LSD, psilocybin, DMT, and 5-MeO-DMT will be discussed, together with a brief summary of other possible applications.
Topics: Humans; Hallucinogens; Mental Disorders; Psilocybin; Ketamine; Antidepressive Agents; Serotonin
PubMed: 37934320
DOI: 10.1007/s43440-023-00550-9 -
Epilepsy & Behavior : E&B Aug 2023Patients with epilepsy are likely to suffer from psychiatric comorbidities, including depression and anxiety. They often require treatment with multiple psychotropic...
RATIONALE
Patients with epilepsy are likely to suffer from psychiatric comorbidities, including depression and anxiety. They often require treatment with multiple psychotropic drugs (PDs). While it is clear that CYP-inducing ASMs (EIASMs) can increase the oral clearance of multiple medications (thus lowering systemic exposure), it is less clear that all PK interactions are clinically meaningful (e.g. lower efficacy). As a first step in addressing this issue, this study sought to quantify the potential impact of ASM choice, whether EIASM or non-inducer (NIASM), on surrogate markers of suggestive of clinical use, including resultant antidepressant (AD) or antipsychotic (AP) dose, frequency of combination use of AD & AP, and number of multiple drug switches of PDs. Our hypothesis is that because of PK interactions, EIAED treatment would be associated with higher psychotropic drug doses, more frequent Rx adjustments and poly psychotropic comedication, all in order to optimize therapeutic response.
METHODS
Using VA pharmacy and national encounter databases, veterans with epilepsy were identified based on having a seizure diagnosis and being prescribed concomitantly an ASM and a psychotropic drug for at least 365 days between 10/1/2010 and 9/30/2014. Patients for whom psychotropic drugs were prescribed any time between beginning and end prescriptions dates of ASMs were considered. Among those, patients receiving both an EIASM + NEIASM concomitantly were categorized with the EIASM group. Patients were evaluated for AD only, AP only and both (AD & AP). To compute average drug doses per day, averages for each patient were computed and averaged again. Multiple drug switches were defined to be for patients who had been prescribed more than three psychotropic drugs during the observation period. Pearson's Chi-Square test was used to compare relative proportions of AD, AP and AD + AP in both groups.
RESULTS
In all, 16,188 patients were identified (57.0% on EIASM, 43.0% on NIASM) with a mean age of 58.7 years (91.2% male). A larger proportion of patients on EIASM received mono treatment with any psychotropic drug, as compared to NIASM (42.0% vs 36.1%). Among all, 59.6% received AD only, 6.5% received AP only, and 33.8% received both concurrently. Of EIASM, 62.5% were on AD, 5.9% on AP, and 31.7% on both AP & AD. For NIASM, 55.9% received AD, 7.4% AP, and 36.7% on AD & AP.Chi-square showed that the distribution of PD was statistically different between EIASM and NIASM groups. Z tests showed that each difference (AD, AP and both) in proportions was statistically significant (p values (4 tests, one Chi-square, 3 Z tests <0.001) between EIASM vs NIASM. Interestingly, mean doses of AD or AP did not appear to differ between ASM groups.
CONCLUSIONS
Concurrent psychotropic drug use is quite common in the VA population with epilepsy, and a large number of patients still receive enzyme-inducing ASMs that may complicate other medical therapies. Interestingly, in seeming contradiction to our hypothesis, mean daily doses of either AD or AP did not appear to differ between inducers vs non-inducers. Similarly, use of polytherapy, and/or multiple trials of various psychotropic drugs did not appear increased in the CYP-induced group. In fact, combination therapy of AD + AP was higher in NIASM than EIASM. These data suggest that perhaps these types of PK interactions may not in fact result in meaningful clinical differences. Since the present analyses did not include clinical psychiatric measures, future analyses examining direct clinical outcomes are clearly warranted.
Topics: Humans; Male; Middle Aged; Female; Veterans; Psychotropic Drugs; Antipsychotic Agents; Antidepressive Agents; Epilepsy; Drug Interactions
PubMed: 37429123
DOI: 10.1016/j.yebeh.2023.109335 -
Fitoterapia Sep 2023Natural psychedelic compounds are emerging as potential novel therapeutics in psychiatry. This review will discuss how natural psychedelics exert their neurobiological... (Review)
Review
Natural psychedelic compounds are emerging as potential novel therapeutics in psychiatry. This review will discuss how natural psychedelics exert their neurobiological therapeutic effects, and how different neurotransmission systems mediate the effects of these compounds. Further, current therapeutic strategies for depression, and novel mechanism of action of natural psychedelics in the treatment of depression will be discussed. In this review, our focus will be on N, N-dimethyltryptamine (DMT), reversible type A monoamine oxidase inhibitors, mescaline-containing cacti, psilocybin/psilocin-containing mushrooms, ibogaine, muscimol extracted from Amanita spp. mushrooms and ibotenic acid.
Topics: Hallucinogens; Depression; Molecular Structure; N,N-Dimethyltryptamine; Neurotransmitter Agents
PubMed: 37490982
DOI: 10.1016/j.fitote.2023.105620 -
Scientific Reports Jul 2023Cannabis is a multifaceted plant with numerous therapeutic properties on one hand, and controversial psychotropic activities on the other hand, which are modulated by...
Cannabis is a multifaceted plant with numerous therapeutic properties on one hand, and controversial psychotropic activities on the other hand, which are modulated by CB1 endocannabinoid receptors. Δ9-Tetrahydrocannabinol (Δ9-THC) has been identified as the main component responsible for the psychotropic effects, while its constitutional isomer cannabidiol (CBD) has shown completely different pharmacological properties. Due to its reported beneficial effects, Cannabis has gained global popularity and is openly sold in shops and online. To circumvent legal restrictions, semi-synthetic derivatives of CBD are now frequently added to cannabis products, producing "high" effects similar to those induced by Δ9-THC. The first semi-synthetic cannabinoid to appear in the EU was obtained through cyclization and hydrogenation of CBD, and is known as hexahydrocannabinol (HHC). Currently, there is limited knowledge regarding HHC, its pharmacological properties, and its prevalence, as it is not commonly investigated in routine toxicological assays. In this study, synthetic strategies were explored to obtain an excess of the active epimer of HHC. Furthermore, the two epimers were purified and individually tested for their cannabinomimetic activity. Lastly, a simple and rapid chromatographic method employing a UV detector and a high-resolution mass spectrometer was applied to identify and quantify up to ten major phytocannabinoids, as well as the HHC epimers, in commercial cannabis samples.
Topics: Dronabinol; Psychotropic Drugs; Cannabinoids; Cannabis; Cannabidiol; Hallucinogens
PubMed: 37422571
DOI: 10.1038/s41598-023-38188-5 -
Palliative & Supportive Care Aug 2023People with terminal illnesses often experience psychological distress and associated disability. Recent clinical trial evidence has stimulated interest in the... (Review)
Review
OBJECTIVES
People with terminal illnesses often experience psychological distress and associated disability. Recent clinical trial evidence has stimulated interest in the therapeutic use of psychedelics at end of life. Much uncertainty remains, however, mainly due to methodological difficulties that beset existing trials. We conducted a scoping review of pipeline clinical trials of psychedelic treatment for depression, anxiety, and existential distress at end of life.
METHODS
Proposed, registered, and ongoing trials were identified from 2 electronic databases (ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform). Recent reviews and both commercial and non-profit organization websites were used to identify additional unregistered trials.
RESULTS
In total, 25 studies were eligible, including 13 randomized controlled trials and 12 open-label trials. Three trials made attempts beyond randomization to assess expectancy and blinding effectiveness. Investigational drugs included ketamine ( = 11), psilocybin ( = 10), 3,4-methylenedioxymethamphetamine ( = 2), and lysergic acid diethylamide ( = 2). Three trials involved microdosing, and fifteen trials incorporated psychotherapy.
SIGNIFICANCE OF RESULTS
A variety of onging or upcoming clinical trials are expected to usefully extend evidence regarding psychedelic-assisted group therapy and microdosing in the end-of-life setting. Still needed are head-to-head comparisons of different psychedelics to identify those best suited to specific indications and clinical populations. More extensive and rigorous studies are also necessary to better control expectancy, confirm therapeutic findings and establish safety data to guide the clinical application of these novel therapies.
Topics: Humans; Hallucinogens; Lysergic Acid Diethylamide; Psilocybin; Terminal Care; Death
PubMed: 37334486
DOI: 10.1017/S147895152300069X -
International Journal of Environmental... Sep 2023This scoping review aimed to identify predisposing, enabling, and need factors associated with the use of mental health services, including psychotropic medications,... (Review)
Review
Predisposing, Enabling, and Need Factors Associated with Psychotropic Medication and Mental Health Service Use among Children in Out-of-Home Care in the United States: A Scoping Review.
This scoping review aimed to identify predisposing, enabling, and need factors associated with the use of mental health services, including psychotropic medications, among children in out-of-home care in the United States. We searched the PsycInfo, SocINDEX, Medline, and Scopus databases, and 22 studies met inclusion criteria and were systematically analyzed. Among the included studies, 7 studies examined predictors associated with taking psychotropic medications, and 16 examined factors associated with using other mental health services. Significant predisposing, enabling, and need factors associated with greater use of mental health services, including psychotropic medications, were identified. The most frequently identified predisposing factors were child race/ethnicity, age, gender, and maltreatment. Important enabling factors were out-of-home placement type and length of care, and need factors included children's mental/behavioral problems. The results provide insight into maximizing factors facilitating children's use of mental health services to address mental health problems of children in out-of-home care. Further, the results imply the importance of the appropriate use of psychotropic medication (e.g., the type and dosage of medications) among children in out-of-home care. The identified factors can inform child welfare agencies and stakeholders on ways to improve access to mental health services and the appropriate use of psychotropic medications among children in out-of-home care in the United States.
Topics: Humans; United States; Child; Psychotropic Drugs; Child Protective Services; Databases, Factual; Home Care Services; Mental Health Services
PubMed: 37754629
DOI: 10.3390/ijerph20186769 -
Gut Microbes Dec 2023The gut microbiome is involved in the bi-directional relationship of the gut - brain axis. As most studies of this relationship are small and do not account for use of...
The gut microbiome is involved in the bi-directional relationship of the gut - brain axis. As most studies of this relationship are small and do not account for use of psychotropic drugs (PTDs), we explored the relations of the gut microbiome with several internalizing disorders, while adjusting for PTDs and other relevant medications, in 7,656 Lifelines participants from the Northern Netherlands (5,522 controls and 491 participants with at least one internalizing disorder). Disorders included dysthymia, major depressive disorder (MDD), any depressive disorder (AnyDep: dysthymia or MDD), generalized anxiety disorder (GAD) and any anxiety disorder (AnyAnx: GAD, social phobia and panic disorder). Compared to controls, 17 species were associated with depressive disorders and 3 were associated with anxiety disorders. Around 90% of these associations remained significant (FDR <0.05) after adjustment for PTD use, suggesting that the disorders, not PTD use, drove these associations. Negative associations were observed for the butyrate-producing bacteria in participants with AnyDep and for in AnyAnx participants, along with many others. Tryptophan and glutamate synthesis modules and the 3,4-Dihydroxyphenylacetic acid synthesis module (related to dopamine metabolism) were negatively associated with MDD and/or dysthymia. After additional adjustment for functional gastrointestinal disorders and irritable bowel syndrome, these relations remained either statistically (FDR <0.05) or nominally ( < 0.05) significant. Overall, multiple bacterial species and functional modules were associated with internalizing disorders, including gut - brain relevant components, while associations to PTD use were moderate. These findings suggest that internalizing disorders rather than PTDs are associated with gut microbiome differences relative to controls.
Topics: Humans; Depressive Disorder, Major; Depression; Gastrointestinal Microbiome; Anxiety Disorders; Anxiety; Psychotropic Drugs
PubMed: 38017662
DOI: 10.1080/19490976.2023.2281360 -
Drug Metabolism Reviews 2024Due to legal, political, and cultural changes, the use of cannabis has rapidly increased in recent years. Research has demonstrated that the cannabinoids cannabidiol...
Due to legal, political, and cultural changes, the use of cannabis has rapidly increased in recent years. Research has demonstrated that the cannabinoids cannabidiol (CBD) and Δ-tetrahydrocannabinol (THC) inhibit and induce cytochrome P450 (CYP450) enzymes. The objective of this review is to evaluate the effect of CBD and THC on the activity of CYP450 enzymes and the implications for drug-drug interactions (DDIs) with psychotropic agents that are CYP substrates. A systematic search was conducted using PubMed, Scopus, Scientific Electronic Library Online (SciELO) and PsychINFO. Search terms included 'cannabidiol', 'tetrahydrocannabinol', and 'cytochrome P450'. A total of seven studies evaluating the interaction of THC and CBD with CYP450 enzymes and psychotropic drugs were included. Both preclinical and clinical studies were included. Results from the included studies indicate that both CBD and THC inhibit several CYP450 enzymes including, but not limited to, CYP1A2, CYP3C19, and CYP2B6. While there are a few known CYP450 enzymes that are induced by THC and CBD, the induction of CYP450 enzymes is an understudied area of research and lacks clinical data. The inhibitory effects observed by CBD and THC on CYP450 enzymes vary in magnitude and may decrease the metabolism of psychotropic agents, cause changes in plasma levels of psychotropic medications, and increase adverse effects. Our findings clearly present interactions between THC and CBD and several CYP450 enzymes, providing clinicians evidence of a high risk of DDIs for patients who consume both cannabis and psychotropic medication. However, more clinical research is necessary before results are applied to clinical settings.
Topics: Animals; Humans; Cannabidiol; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dronabinol; Drug Interactions; Psychotropic Drugs
PubMed: 38655747
DOI: 10.1080/03602532.2024.2346767 -
CNS Drugs Mar 2024Psychodermatology, the multidisciplinary field that explores the intricate interplay between the mind and the skin, has gained increasing recognition over the past... (Review)
Review
Psychodermatology, the multidisciplinary field that explores the intricate interplay between the mind and the skin, has gained increasing recognition over the past decade. However, several knowledge gaps and unmet needs persist in the field. The objective of this narrative review was to investigate the unmet needs in the field of psychodermatology as they pertain to medical training, treatment, research, and care access. PubMed was searched from inception through December 2023 to identify articles related to psychodermatology. Findings revealed several unmet needs within the field of psychodermatology. First, there is a need for further investigation into the pathophysiology that links psychological stress to cutaneous disease including the development of novel therapies targeting key neuropeptides. Second, the existing literature focuses primarily on the pharmacologic treatment of body dysmorphic disorder and body-focused repetitive behaviors, as well as delusional parasitosis, for which the first-line agents are selective serotonin reuptake inhibitors and atypical antipsychotics, respectively. However, additional research into the efficacy and safety of the remaining psychotropic medications and the treatment of other common psychocutaneous diseases is required. Finally, there exists a significant gap in knowledge amongst clinicians tasked with treating psychocutaneous diseases. Dermatologists report low rates of training in psychodermatology and discomfort with prescribing psychotropic medications. In conclusion, increasing resources for dermatologist education on psychotropic agent use, development of new drugs targeting stress-induced skin conditions, and research on the psychocutaneous applications of current medications may greatly improve the quality and access of psychodermatology care.
Topics: Humans; Skin Diseases; Psychotropic Drugs; Antipsychotic Agents; Selective Serotonin Reuptake Inhibitors
PubMed: 38386200
DOI: 10.1007/s40263-024-01068-1