The Perils of Recreational Marijuana Use: Relationships With Mental Health Among Emergency Department Patients

Abstract Introduction Marijuana is a commonly used drug in the United States. Many states have legalized the recreational use of marijuana. The effects of marijuana on mental health are unknown. Methods In this prospective survey study, eligible participants included ED patients age 18 and older, who had ever used recreational marijuana. A survey instrument was developed, piloted, and revised. Data collected included reasons for marijuana use, marijuana\u27s perceived effectiveness, and history of mental health conditions, including depression, anxiety, and suicidal thoughts. Results Among 303 participants (86% response rate), the median age of first marijuana use was 16 ([IQR 14, 19], range 6–65). The most commonly cited reasons for marijuana use included recreational use (70%; n = 211), to treat anxiety (30%; n = 89), to treat pain (25%; n = 74), and to treat depression (17%; n = 51). Mental health issues were common in the study population. A majority of patients reported anxiety in the last 30 days (59%; n = 176), and a significant minority of patients reported serious depression in the last 30 days (46%; n = 137). Some patients reported suicidal thoughts in the last 30 days (9%; n = 29). Participants who used marijuana more frequently reported more days of anxiety (median 15.5, compared to 1; P = 0.001). Among participants with mental health conditions, most began using marijuana before the onset of the mental health conditions (77%, n = 167). Earlier age of starting to use marijuana was correlated with higher number of years of anxiety or tension in lifetime (r = −0.11, P = 0.05, n = 301). Perceived effects of marijuana use on mental health were variable. Most participants stated that marijuana improved their mental health (62%; n = 163), and some reported that marijuana did not improve their mental health (37%; n = 98). Conclusions Many ED patients have used marijuana, either currently or in the past. Mental health conditions are also common, including anxiety, depression, and suicidal thoughts. Most participants reported marijuana use starting at an age under 18. Marijuana use preceded the onset of mental health conditions in the majority of participants

Bioactive Components in Fish Venoms

Animal venoms are widely recognized excellent resources for the discovery of novel drug leads and physiological tools. Most are comprised of a large number of components, of which the enzymes, small peptides, and proteins are studied for their important bioactivities. However, in spite of there being over 2000 venomous fish species, piscine venoms have been relatively underrepresented in the literature thus far. Most studies have explored whole or partially fractioned venom, revealing broad pharmacology, which includes cardiovascular, neuromuscular, cytotoxic, inflammatory, and nociceptive activities. Several large proteinaceous toxins, such as stonustoxin, verrucotoxin, and Sp-CTx, have been isolated from scorpaenoid fish. These form pores in cell membranes, resulting in cell death and creating a cascade of reactions that result in many, but not all, of the physiological symptoms observed from envenomation. Additionally, Natterins, a novel family of toxins possessing kininogenase activity have been found in toadfish venom. A variety of smaller protein toxins, as well as a small number of peptides, enzymes, and non-proteinaceous molecules have also been isolated from a range of fish venoms, but most remain poorly characterized. Many other bioactive fish venom components remain to be discovered and investigated. These represent an untapped treasure of potentially useful molecules

Bioactive components in fish venoms

Animal venoms are widely recognized excellent resources for the discovery of novel drug leads and physiological tools. Most are comprised of a large number of components, of which the enzymes, small peptides, and proteins are studied for their important bioactivities. However, in spite of there being over 2000 venomous fish species, piscine venoms have been relatively underrepresented in the literature thus far. Most studies have explored whole or partially fractioned venom, revealing broad pharmacology, which includes cardiovascular, neuromuscular, cytotoxic, inflammatory, and nociceptive activities. Several large proteinaceous toxins, such as stonustoxin, verrucotoxin, and Sp-CTx, have been isolated from scorpaenoid fish. These form pores in cell membranes, resulting in cell death and creating a cascade of reactions that result in many, but not all, of the physiological symptoms observed from envenomation. Additionally, Natterins, a novel family of toxins possessing kininogenase activity have been found in toadfish venom. A variety of smaller protein toxins, as well as a small number of peptides, enzymes, and non-proteinaceous molecules have also been isolated from a range of fish venoms, but most remain poorly characterized. Many other bioactive fish venom components remain to be discovered and investigated. These represent an untapped treasure of potentially useful molecules

Protocol for purification and identification of MHC class I immunopeptidome from cancer cell lines

Major histocompatibility complexes (MHC) play a critical role in immunity by presenting peptides on the cell surface for T cell recognition. Identification of these peptides can be valuable to develop vaccines or immunotherapeutic strategies for infectious diseases and cancers. Mass spectrometry is the only tool available for unbiased identification of the immunopeptidome. Here, we describe a protocol for purification and identification of MHC class I peptides, including in-house purification of anti-MHC-antibody from hybridoma cells and the LC-MS/MS analysis of MHC-I bound peptides. Major histocompatibility complexes (MHC) play a critical role in immunity by presenting peptides on the cell surface for T cell recognition. Identification of these peptides can be valuable to develop vaccines or immunotherapeutic strategies for infectious diseases and cancers. Mass spectrometry is the only tool available for unbiased identification of the immunopeptidome. Here, we describe a protocol for purification and identification of MHC class I peptides, including in-house purification of anti-MHC-antibody from hybridoma cells and the LC-MS/MS analysis of MHC-I bound peptides.</p

Investigation of the estuarine stonefish (Synanceia horrida) venom composition

The Estuarine stonefish (Synanceia horrida) is recognised as one of the most venomous fish species in the world but the overall venom composition has yet to be investigated using in-depth transcriptomic and proteomic methods. To date, known venom components are restricted to a hyaluronidase and a large, pore-forming toxin known as Stonustoxin (SNTX). Transcriptomic sequencing of the venom gland resulted in over 170,000 contigs with only 0.4% that were homologous to putative venom proteins. Integration of the transcriptomic data with proteomic data from the S. horrida venom confirmed the hyaluronidase and SNTX to be present, together with several other protein families including major contributions from C-type lectins. Other protein families observed included peroxiredoxin and several minor protein families such as Golgi-associated plant pathogenesis related proteins, tissue pathway factor inhibitors, and Kazal-type serine protease inhibitors that, although not putative venom proteins, may contribute to the venom's adverse effects. Biological significance: Proteomic analysis of milked Synanceia horrida venom, paired with transcriptomic analysis of the venom gland tissue revealed for the first time the composition of one of the world's most dangerous fish venoms. The results demonstrate that the venom is relatively less complex compared to other well-studied venomous animals with a number of unique proteins not previously found in animal venoms

Temporal quantitative proteomics reveals proteomic and phosphoproteomic alterations associated with adaptive response to hypoxia in melanoma cells

Hypoxia is a common feature in various solid tumours, including melanoma. Cancer cells in hypoxic environments are resistant to both chemotherapy and radiation. Hypoxia is also associated with immune suppression. Identification of proteins and pathways that regulate cancer cell survival in hypoxic environments can reveal potential vulnerabilities that can be exploited to improve the efficacy of anticancer therapies. We carried out temporal proteomic and phosphoproteomic profiling in melanoma cell lines to identify hypoxia-induced protein expression and phosphorylation changes. By employing a TMT-based quantitative proteomics strategy, we report the identification and quantitation of >7000 proteins and >10,000 phosphosites in melanoma cell lines grown in hypoxia. Proteomics data show metabolic reprogramming as one of the prominent adaptive responses in hypoxia. We identify several novel hypoxia-mediated phosphorylation changes that have not been reported before. They reveal kinase signalling pathways that are potentially involved in modulating cellular response to hypoxia. In addition to known protein expression changes, we identify several novel proteomic alterations associated with adaptive response to hypoxia. We show that cancer cells require the ubiquitin–proteasome system to survive in both normoxia and hypoxia. Inhibition of proteasome activity affects cell survival and may provide a novel therapeutic avenue to target cancer cells in hypoxia. Our study can serve as a valuable resource to pursue novel candidates to target hypoxia in cancers and improve the efficacy of anticancer therapies.</p

‘Messy’ Processing of χ-conotoxin MrIA Generates Homologues with Reduced hNET Potency

Integrated venomics techniques have shown that variable processing of conotoxins from resulted in a dramatic expansion in the number of expressed conotoxins. One conotoxin from , the χ-conotoxin MrIA, is a selective inhibitor of human norepinephrine transporters (hNET) and therefore a drug candidate for attenuating chronic neuropathic pain. It has been found that "messy" processing of the MrIA transcripts results in the expression of MrIA analogs with different truncations of the pro-peptide that contains portions of the MrIA molecule. The aim of this study was to investigate if variable processing of the expressed peptides results in modulation of the existing hNET pharmacology or creates new pharmacologies. To this end, a number of MrIA analogs found in venom were synthesized and evaluated for their activity at hNET receptors. While several of the analogs exhibited norepinephrine transporter inhibitory activity comparable to that of MrIA, none significantly improved on the potency of conotoxin MrIA, and those analogs with disrupted pharmacophores produced greatly reduced NET inhibition, confirming previous structure-activity relationships seen on χ-class conopeptides. Additionally, analogs were screened for new activities on ion channels using calcium influx assays, although no major new pharmacology was revealed

The Perils of Recreational Marijuana Use: Relationships With Mental Health Among Emergency Department Patients

Abstract Introduction Marijuana is a commonly used drug in the United States. Many states have legalized the recreational use of marijuana. The effects of marijuana on mental health are unknown. Methods In this prospective survey study, eligible participants included ED patients age 18 and older, who had ever used recreational marijuana. A survey instrument was developed, piloted, and revised. Data collected included reasons for marijuana use, marijuana\u27s perceived effectiveness, and history of mental health conditions, including depression, anxiety, and suicidal thoughts. Results Among 303 participants (86% response rate), the median age of first marijuana use was 16 ([IQR 14, 19], range 6–65). The most commonly cited reasons for marijuana use included recreational use (70%; n = 211), to treat anxiety (30%; n = 89), to treat pain (25%; n = 74), and to treat depression (17%; n = 51). Mental health issues were common in the study population. A majority of patients reported anxiety in the last 30 days (59%; n = 176), and a significant minority of patients reported serious depression in the last 30 days (46%; n = 137). Some patients reported suicidal thoughts in the last 30 days (9%; n = 29). Participants who used marijuana more frequently reported more days of anxiety (median 15.5, compared to 1; P = 0.001). Among participants with mental health conditions, most began using marijuana before the onset of the mental health conditions (77%, n = 167). Earlier age of starting to use marijuana was correlated with higher number of years of anxiety or tension in lifetime (r = −0.11, P = 0.05, n = 301). Perceived effects of marijuana use on mental health were variable. Most participants stated that marijuana improved their mental health (62%; n = 163), and some reported that marijuana did not improve their mental health (37%; n = 98). Conclusions Many ED patients have used marijuana, either currently or in the past. Mental health conditions are also common, including anxiety, depression, and suicidal thoughts. Most participants reported marijuana use starting at an age under 18. Marijuana use preceded the onset of mental health conditions in the majority of participants