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Article ; Online: Cloaked dagger: tRNA slicing by an unlikely culprit.

Schifano, Jason M / Woychik, Nancy A

RNA biology

2016 Volume 14, Issue 1, Page(s) 15–19

Abstract: ... for the MazE antitoxin and MazF toxin), comprises 10 of the >80 TA systems in the M. tuberculosis genome. Here ... MazF family members in M. tuberculosis and other bacteria; instead it is strikingly similar ...

Abstract	The unusually high number of toxin-antitoxin (TA) systems in Mycobacterium tuberculosis, the etiological agent of tuberculosis, is thought to contribute to the unique ability of this pathogen to evade killing by the immune system and persist as a latent infection. One TA family, designated mazEF (for the MazE antitoxin and MazF toxin), comprises 10 of the >80 TA systems in the M. tuberculosis genome. Here we discuss the significance of our recent Nucleic Acids Res. paper that reports a surprising enzymatic activity for the MazF-mt9 toxin-sequence- and structure-specific cleavage of tRNA to generate tRNA halves-that underlies the growth-regulating properties of this toxin. This activity is distinct from all characterized MazF family members in M. tuberculosis and other bacteria; instead it is strikingly similar to that documented for members of another toxin family, VapC, despite the absence of sequence or structural similarity.
MeSH term(s)	Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Bacterial Toxins/chemistry ; Bacterial Toxins/genetics ; Bacterial Toxins/metabolism ; Endoribonucleases/genetics ; Endoribonucleases/metabolism ; Latent Tuberculosis/microbiology ; Mycobacterium tuberculosis/genetics ; Mycobacterium tuberculosis/metabolism ; Protein Binding ; RNA Cleavage ; RNA, Bacterial/genetics ; RNA, Bacterial/metabolism ; RNA, Transfer/chemistry ; RNA, Transfer/genetics ; RNA, Transfer/metabolism ; Structure-Activity Relationship ; Tuberculosis/microbiology
Chemical Substances	Bacterial Proteins ; Bacterial Toxins ; RNA, Bacterial ; RNA, Transfer (9014-25-9) ; Endoribonucleases (EC 3.1.-) ; MazF protein, Mycobacterium tuberculosis (EC 3.1.-)
Language	English
Publishing date	2016-11-14
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1555-8584
ISSN (online)	1555-8584
DOI	10.1080/15476286.2016.1255396
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Interleukin-1 Receptor-Associated Kinase (IRAK) Signaling in Kaposi Sarcoma-Associated Herpesvirus-Induced Primary Effusion Lymphoma.

Seltzer, Jedediah / Moorad, Razia / Schifano, Jason M / Landis, Justin T / Dittmer, Dirk P

Journal of virology

2020 Volume 94, Issue 10

Abstract: Kaposi sarcoma-associated herpesvirus (KSHV) is necessary but not sufficient for primary effusion lymphoma (PEL) development. Alterations in cellular signaling pathways are also a characteristic of PEL. Other B cell lymphomas have acquired an oncogenic ... ...

Abstract	Kaposi sarcoma-associated herpesvirus (KSHV) is necessary but not sufficient for primary effusion lymphoma (PEL) development. Alterations in cellular signaling pathways are also a characteristic of PEL. Other B cell lymphomas have acquired an oncogenic mutation in the myeloid differentiation primary response 88 (MYD88) gene. The MYD88 L265P mutant results in the activation of interleukin-1 receptor associated kinase (IRAK). To probe IRAK/MYD88 signaling in PEL, we employed CRISPR/Cas9 technology to generate stable deletion clones in BCBL-1Cas9 and BC-1Cas9 cells. To look for off-target effects, we determined the complete exome of the BCBL-1Cas9 and BC-1Cas9 cells. Deletion of either MYD88, IRAK4, or IRAK1 abolished interleukin-1 beta (IL-1β) signaling; however, we were able to grow stable subclones from each population. Transcriptome sequencing (RNA-seq) analysis of IRAK4 knockout cell lines (IRAK4 KOs) showed that the IRAK pathway induced cellular signals constitutively, independent of IL-1β stimulation, which was abrogated by deletion of IRAK4. Transient complementation with IRAK1 increased NF-κB activity in MYD88 KO, IRAK1 KO, and IRAK4 KO cells even in the absence of IL-1β. IL-10, a hallmark of PEL, was dependent on the IRAK pathway, as IRAK4 KOs showed reduced IL-10 levels. We surmise that, unlike B cell receptor (BCR) signaling, MYD88/IRAK signaling is constitutively active in PEL, but that under cell culture conditions, PEL rapidly became independent of this pathway.
MeSH term(s)	B-Lymphocytes ; CRISPR-Cas Systems ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Gene Knockout Techniques ; Herpesvirus 8, Human/genetics ; Herpesvirus 8, Human/physiology ; Humans ; Interleukin-1 Receptor-Associated Kinases/genetics ; Interleukin-1 Receptor-Associated Kinases/metabolism ; Interleukin-10/metabolism ; Interleukin-1beta/metabolism ; Lymphoma, Primary Effusion/metabolism ; Lymphoma, Primary Effusion/virology ; Myeloid Differentiation Factor 88/genetics ; Myeloid Differentiation Factor 88/metabolism ; NF-kappa B/metabolism ; Sequence Analysis ; Signal Transduction/genetics ; Transcriptome
Chemical Substances	IL10 protein, human ; IL1B protein, human ; Interleukin-1beta ; MYD88 protein, human ; Myeloid Differentiation Factor 88 ; NF-kappa B ; Interleukin-10 (130068-27-8) ; IRAK1 protein, human (EC 2.7.11.1) ; IRAK4 protein, human (EC 2.7.11.1) ; Interleukin-1 Receptor-Associated Kinases (EC 2.7.11.1)
Language	English
Publishing date	2020-05-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.02123-19
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Article ; Online: 23S rRNA as an a-Maz-ing new bacterial toxin target.

Schifano, Jason M / Woychik, Nancy A

RNA biology

2014 Volume 11, Issue 2, Page(s) 101–105

Abstract: ... to survive the stressful environments it encounters in the human host. Importantly, M. tuberculosis cells ... in actively replicating bacteria. The molecular switches that enable M. tuberculosis to slow or stop ... components of chromosomal toxin-antitoxin (TA) modules. An unusually large number of TA modules in M ...

Abstract	Mycobacterium tuberculosis, the causative agent of tuberculosis in humans, is a bacterium with the unique ability to persist for years or decades as a latent infection. This latent state, during which bacteria have a markedly altered physiology and are thought to be dormant, is crucial for the bacteria to survive the stressful environments it encounters in the human host. Importantly, M. tuberculosis cells in the dormant state are generally refractory to antibiotics, most of which target cellular processes occurring in actively replicating bacteria. The molecular switches that enable M. tuberculosis to slow or stop its replication and become dormant remain unknown. However, the slow growth and dormant state that are hallmarks of latent tuberculosis infection have striking parallels to the "quasi-dormant" state of Escherichia coli cells caused by the toxin components of chromosomal toxin-antitoxin (TA) modules. An unusually large number of TA modules in M. tuberculosis, including nine in the mazEF family, may contribute to initiating this latent state or to adapting to stress conditions in the host. Toward filling the gap in our understanding of the physiological role of TA modules in M. tuberculosis, we are interested in identifying their molecular mechanisms to better understand how toxins impart growth control. Our recent publication (1) uncovered a novel function of a MazF toxin in M. tuberculosis that had not been associated with any other MazF ortholog. This toxin, MazF-mt6, can disrupt protein synthesis by cleavage of 23S rRNA at a single location in an evolutionarily conserved five-base sequence in the ribosome active center.
MeSH term(s)	Adaptation, Physiological ; Antitoxins/genetics ; Antitoxins/pharmacology ; Bacterial Toxins/metabolism ; Base Sequence ; Binding Sites ; Conserved Sequence ; Evolution, Molecular ; Genes, Bacterial ; Humans ; Models, Genetic ; Mycobacterium tuberculosis/genetics ; Mycobacterium tuberculosis/metabolism ; Operon ; RNA, Bacterial/genetics ; RNA, Ribosomal, 23S/metabolism ; Ribosomes/metabolism
Chemical Substances	Antitoxins ; Bacterial Toxins ; RNA, Bacterial ; RNA, Ribosomal, 23S
Language	English
Publishing date	2014-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1555-8584
ISSN (online)	1555-8584
DOI	10.4161/rna.27949
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Article ; Online: Expression of the Antisense-to-Latency Transcript Long Noncoding RNA in Kaposi's Sarcoma-Associated Herpesvirus.

Schifano, Jason M / Corcoran, Kathleen / Kelkar, Hemant / Dittmer, Dirk P

Journal of virology

2017 Volume 91, Issue 4

Abstract: The regulation of latency is central to herpesvirus biology. Recent transcriptome-wide surveys have uncovered evidence for promiscuous transcription across the entirety of the Kaposi's sarcoma-associated herpesvirus (KSHV) genome and postulated the ... ...

Abstract	The regulation of latency is central to herpesvirus biology. Recent transcriptome-wide surveys have uncovered evidence for promiscuous transcription across the entirety of the Kaposi's sarcoma-associated herpesvirus (KSHV) genome and postulated the existence of multiple viral long noncoding RNAs (lncRNAs). Next-generation sequencing studies are highly dependent on the specific experimental approach and particular algorithms of analysis and therefore benefit from independent confirmation of the results. The antisense-to-latency transcript (ALT) lncRNA was discovered by genome-tiling microarray (Chandriani et al., J Virol 86:7934-7942, 2010, https://doi.org/10.1128/JVI.00645-10). To characterize ALT in detail, we physically isolated this lncRNA by a strand-specific hybrid capture assay and then employed transcriptome sequencing and novel reverse transcription-PCR (RT-PCR) assays to distinguish all RNA species in the KSHV latency region. These methods confirm that ALT initiates at positions 120739/121012 and encodes a single splice site, which is shared with the 3'-coterminal K14-vGPCR/ORF74 mRNA, terminating at 130873 (GenBank accession number GQ994935), resulting in an ∼10,000-nucleotide transcript. No shorter ALT isoforms were identified. This study also identified a novel intron within the LANA 5' untranslated region using a splice acceptor at 127888. In summary, ALT joins PAN/nut1/T1.1 as a bona fide lncRNA of KSHV with potentially important roles in viral gene regulation and pathogenesis. Importance: Increasing data support the importance of noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and lncRNAs, which have been shown to exert critical regulatory functions without coding for recognizable proteins. Defining the sequences of these ncRNAs is essential for future studies aiming to functionally characterize a specific ncRNA. Most lncRNA studies are highly dependent on high-throughput sequencing and bioinformatic analyses, few studies follow up on the initial predictions, and analyses are at times discordant. The manuscript characterizes one key viral lncRNA, ALT, by physically isolating ALT and by a sequencing-independent assay. It provides for a simple assay to monitor lncRNA expression in experimental and clinical samples. ALT is expressed antisense to the major viral latency transcripts encoding LANA as well as the viral miRNAs and thus has the potential to regulate this key part of the viral life cycle.
MeSH term(s)	Cell Line ; Gene Expression Regulation, Viral ; Herpesvirus 8, Human/genetics ; Humans ; MicroRNAs/genetics ; RNA, Antisense/genetics ; RNA, Long Noncoding/genetics ; RNA, Messenger/genetics ; RNA, Viral ; Sequence Analysis, DNA ; Transcriptome ; Untranslated Regions ; Virus Latency/genetics ; Virus Replication
Chemical Substances	MicroRNAs ; RNA, Antisense ; RNA, Long Noncoding ; RNA, Messenger ; RNA, Viral ; Untranslated Regions
Language	English
Publishing date	2017-01-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01698-16
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Article: 23S rRNA as an a-Maz-ing new bacterial toxin target

Schifano, Jason M / Woychik, Nancy A

RNA biology. 2014 Feb. 1, v. 11, no. 2

2014

Abstract	Mycobacterium tuberculosis, the causative agent of tuberculosis in humans, is a bacterium with the unique ability to persist for years or decades as a latent infection. This latent state, during which bacteria have a markedly altered physiology and are thought to be dormant, is crucial for the bacteria to survive the stressful environments it encounters in the human host. Importantly, M. tuberculosis cells in the dormant state are generally refractory to antibiotics, most of which target cellular processes occurring in actively replicating bacteria. The molecular switches that enable M. tuberculosis to slow or stop its replication and become dormant remain unknown. However, the slow growth and dormant state that are hallmarks of latent tuberculosis infection have striking parallels to the “quasi-dormant” state of Escherichia coli cells caused by the toxin components of chromosomal toxin-antitoxin (TA) modules. An unusually large number of TA modules in M. tuberculosis, including nine in the mazEF family, may contribute to initiating this latent state or to adapting to stress conditions in the host. Toward filling the gap in our understanding of the physiological role of TA modules in M. tuberculosis, we are interested in identifying their molecular mechanisms to better understand how toxins impart growth control. Our recent publication¹ uncovered a novel function of a MazF toxin in M. tuberculosis that had not been associated with any other MazF ortholog. This toxin, MazF-mt6, can disrupt protein synthesis by cleavage of 23S rRNA at a single location in an evolutionarily conserved five-base sequence in the ribosome active center.
Keywords	Escherichia coli ; Mycobacterium tuberculosis ; bacteria ; bacterial toxins ; carrier state ; etiological agents ; humans ; protein synthesis ; ribosomes ; tuberculosis
Language	English
Dates of publication	2014-0201
Size	p. 101-105.
Publishing place	Taylor & Francis
Document type	Article
ISSN	1555-8584
DOI	10.4161/rna.27949
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: tRNA is a new target for cleavage by a MazF toxin.

Schifano, Jason M / Cruz, Jonathan W / Vvedenskaya, Irina O / Edifor, Regina / Ouyang, Ming / Husson, Robert N / Nickels, Bryce E / Woychik, Nancy A

Nucleic acids research

2016 Volume 44, Issue 3, Page(s) 1256–1270

Abstract: Toxin-antitoxin (TA) systems play key roles in bacterial persistence, biofilm formation and stress responses. The MazF toxin from the Escherichia coli mazEF TA system is a sequence- and single-strand-specific endoribonuclease, and many studies have led ... ...

Abstract	Toxin-antitoxin (TA) systems play key roles in bacterial persistence, biofilm formation and stress responses. The MazF toxin from the Escherichia coli mazEF TA system is a sequence- and single-strand-specific endoribonuclease, and many studies have led to the proposal that MazF family members exclusively target mRNA. However, recent data indicate some MazF toxins can cleave specific sites within rRNA in concert with mRNA. In this report, we identified the repertoire of RNAs cleaved by Mycobacterium tuberculosis toxin MazF-mt9 using an RNA-seq-based approach. This analysis revealed that two tRNAs were the principal targets of MazF-mt9, and each was cleaved at a single site in either the tRNA(Pro14) D-loop or within the tRNA(Lys43) anticodon. This highly selective target discrimination occurs through recognition of not only sequence but also structural determinants. Thus, MazF-mt9 represents the only MazF family member known to target tRNA and to require RNA structure for recognition and cleavage. Interestingly, the tRNase activity of MazF-mt9 mirrors basic features of eukaryotic tRNases that also generate stable tRNA-derived fragments that can inhibit translation in response to stress. Our data also suggest a role for tRNA distinct from its canonical adapter function in translation, as cleavage of tRNAs by MazF-mt9 downregulates bacterial growth.
MeSH term(s)	Anticodon/genetics ; Anticodon/metabolism ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Base Sequence ; Binding Sites/genetics ; Blotting, Northern ; Endoribonucleases/genetics ; Endoribonucleases/metabolism ; Models, Molecular ; Mycobacterium tuberculosis/genetics ; Mycobacterium tuberculosis/metabolism ; Nucleic Acid Conformation ; Protein Binding ; RNA, Bacterial/chemistry ; RNA, Bacterial/genetics ; RNA, Bacterial/metabolism ; RNA, Transfer/chemistry ; RNA, Transfer/genetics ; RNA, Transfer/metabolism
Chemical Substances	Anticodon ; Bacterial Proteins ; RNA, Bacterial ; RNA, Transfer (9014-25-9) ; Endoribonucleases (EC 3.1.-) ; MazF protein, Mycobacterium tuberculosis (EC 3.1.-)
Language	English
Publishing date	2016-01-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkv1370
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Zs.A 1067: Show issues

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Article ; Online: An RNA-seq method for defining endoribonuclease cleavage specificity identifies dual rRNA substrates for toxin MazF-mt3.

Schifano, Jason M / Vvedenskaya, Irina O / Knoblauch, Jared G / Ouyang, Ming / Nickels, Bryce E / Woychik, Nancy A

Nature communications

2014 Volume 5, Page(s) 3538

Abstract: ... leaderless mRNAs in M. tuberculosis. ...

Abstract	Toxin-antitoxin (TA) systems are widespread in prokaryotes. Among these, the mazEF TA system encodes an endoribonucleolytic toxin, MazF, that inhibits growth by sequence-specific cleavage of single-stranded RNA. Defining the physiological targets of a MazF toxin first requires the identification of its cleavage specificity, yet the current toolkit is antiquated and limited. We describe a rapid genome-scale approach, MORE (mapping by overexpression of an RNase in Escherichia coli) RNA-seq, for defining the cleavage specificity of endoribonucleolytic toxins. Application of MORE RNA-seq to MazF-mt3 from Mycobacterium tuberculosis reveals two critical ribosomal targets-the essential, evolutionarily conserved helix/loop 70 of 23S rRNA and the anti-Shine-Dalgarno (aSD) sequence of 16S rRNA. Our findings support an emerging model where both ribosomal and messenger RNAs are principal targets of MazF toxins and suggest that, as in E. coli, removal of the aSD sequence by a MazF toxin modifies ribosomes to selectively translate leaderless mRNAs in M. tuberculosis.
MeSH term(s)	Bacterial Proteins/metabolism ; DNA-Binding Proteins/metabolism ; Endoribonucleases/metabolism ; Escherichia coli ; Escherichia coli Proteins/metabolism ; Mycobacterium tuberculosis ; Protein Structure, Secondary ; RNA Cleavage ; RNA, Messenger/metabolism ; RNA, Ribosomal, 16S/metabolism ; RNA, Ribosomal, 23S/metabolism ; Ribonucleases/metabolism ; Sequence Analysis, RNA ; Toxins, Biological
Chemical Substances	Bacterial Proteins ; DNA-Binding Proteins ; Escherichia coli Proteins ; MazF protein, E coli ; RNA, Messenger ; RNA, Ribosomal, 16S ; RNA, Ribosomal, 23S ; Toxins, Biological ; Endoribonucleases (EC 3.1.-) ; MazF protein, Mycobacterium tuberculosis (EC 3.1.-) ; Ribonucleases (EC 3.1.-)
Language	English
Publishing date	2014-04-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/ncomms4538
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Article ; Online: Mycobacterial toxin MazF-mt6 inhibits translation through cleavage of 23S rRNA at the ribosomal A site.

Schifano, Jason M / Edifor, Regina / Sharp, Jared D / Ouyang, Ming / Konkimalla, Arvind / Husson, Robert N / Woychik, Nancy A

Proceedings of the National Academy of Sciences of the United States of America

2013 Volume 110, Issue 21, Page(s) 8501–8506

Abstract: ... are known as "mRNA interferases." Here we demonstrate that a MazF family member from M. tuberculosis ... sequences. We then discovered that MazF-mt6 also cleaves M. tuberculosis 23S rRNA at a single UUCCU ...

Abstract	The Mycobacterium tuberculosis genome contains an unusually high number of toxin-antitoxin modules, some of which have been suggested to play a role in the establishment and maintenance of latent tuberculosis. Nine of these toxin-antitoxin loci belong to the mazEF family, encoding the intracellular toxin MazF and its antitoxin inhibitor MazE. Nearly every MazF ortholog recognizes a unique three- or five-base RNA sequence and cleaves mRNA. As a result, these toxins selectively target a subset of the transcriptome for degradation and are known as "mRNA interferases." Here we demonstrate that a MazF family member from M. tuberculosis, MazF-mt6, has an additional role--inhibiting translation through targeted cleavage of 23S rRNA in the evolutionarily conserved helix/loop 70. We first determined that MazF-mt6 cleaves mRNA at (5')UU↓CCU(3') sequences. We then discovered that MazF-mt6 also cleaves M. tuberculosis 23S rRNA at a single UUCCU in the ribosomal A site that contacts tRNA and ribosome recycling factor. To gain further mechanistic insight, we demonstrated that MazF-mt6-mediated cleavage of rRNA can inhibit protein synthesis in the absence of mRNA cleavage. Finally, consistent with the position of 23S rRNA cleavage, MazF-mt6 destabilized 50S-30S ribosomal subunit association. Collectively, these results show that MazF toxins do not universally act as mRNA interferases, because MazF-mt6 inhibits protein synthesis by cleaving 23S rRNA in the ribosome active center.
MeSH term(s)	Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Mycobacterium tuberculosis/genetics ; Mycobacterium tuberculosis/metabolism ; Protein Biosynthesis/physiology ; RNA, Bacterial/genetics ; RNA, Bacterial/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; RNA, Ribosomal, 23S/genetics ; RNA, Ribosomal, 23S/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Ribosome Subunits, Large, Bacterial/genetics ; Ribosome Subunits, Large, Bacterial/metabolism ; Ribosome Subunits, Small, Bacterial/genetics ; Ribosome Subunits, Small, Bacterial/metabolism
Chemical Substances	Bacterial Proteins ; RNA, Bacterial ; RNA, Messenger ; RNA, Ribosomal, 23S ; RNA-Binding Proteins
Language	English
Publishing date	2013-05-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1222031110
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Article ; Online: "Spiceophrenia": a systematic overview of "spice"-related psychopathological issues and a case report.

Papanti, Duccio / Schifano, Fabrizio / Botteon, Giulia / Bertossi, Francesca / Mannix, Jason / Vidoni, Daniela / Impagnatiello, Matteo / Pascolo-Fabrici, Elisabetta / Bonavigo, Tommaso

Human psychopharmacology

2013 Volume 28, Issue 4, Page(s) 379–389

Abstract: Objectives: The use of synthetic cannabimimetics (SC; "spice" drugs) is increasing, especially among teenagers and young adults. In parallel with this, the number of studies describing intoxication episodes associated with psychotic symptoms in SC users ...

Abstract	Objectives: The use of synthetic cannabimimetics (SC; "spice" drugs) is increasing, especially among teenagers and young adults. In parallel with this, the number of studies describing intoxication episodes associated with psychotic symptoms in SC users is growing. We present both a systematic review of the related literature and a case report, which seems to highlight the existence of a possible association between SC use and psychosis. Methods: Some 223 relevant studies were here identified and reviewed. Out of these, 120 full text articles were assessed for eligibility, and 41 were finally included in the systematic review. Results: According to the available data from the studies here identified, SC's average age of users was 22.97 years, and the male/female ratio was 3.16:1. SC compounds most often reported in studies using biological specimen analysis were JWH-018, JWH-073, JWH-122, CP-47,497, and JWH-250. Mounting evidence seemed to suggest that psychotic symptoms such as hallucinations and delusions may occur in acute/chronic SC users. Conclusions: Although a clear causal link may not be here identified, the available evidence suggests that SC can trigger the onset of acute psychosis in vulnerable individuals and/or the exacerbation of psychotic episodes in those with a previous psychiatric history.
MeSH term(s)	Adolescent ; Adult ; Cannabinoids/adverse effects ; Cannabinoids/chemical synthesis ; Female ; Humans ; Male ; Marijuana Smoking/adverse effects ; Marijuana Smoking/psychology ; Psychoses, Substance-Induced/diagnosis ; Psychoses, Substance-Induced/psychology ; Street Drugs/adverse effects ; Street Drugs/chemical synthesis ; Young Adult
Chemical Substances	Cannabinoids ; Street Drugs
Language	English
Publishing date	2013-07
Publishing country	England
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	632931-7
ISSN	1099-1077 ; 0885-6222
ISSN (online)	1099-1077
ISSN	0885-6222
DOI	10.1002/hup.2312
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