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Byline: Tor-Morten Kvam (1), Cecilie Baar (1), Trude T. Rakvag (1), Stein Kaasa (1,2), Hans E. Krokan (1), Frank Skorpen (1) Keywords: Mu opioid receptor; Alternative splicing; Splice variants Abstract: Evidence exists that u analgesics such as morphine, methadone and fentanyl may act through distinct u opioid receptor mechanisms. It has been proposed that the functional diversity of u opioid receptors may be related to alternative splicing of the Oprm gene. Although a number of u opioid receptor mRNA splice variants have been reported, their biological relevance has been controversial, due in part to their very low abundance and a general lack of validation from independent laboratories. We have identified 11 of 17 proposed exons as well as the majority of exon combinations used to make 21 differentially spliced Oprm mRNAs from mouse whole brain cDNA, using polymerase chain reaction (PCR) conditions different from those used by the single other group that has reported multiple splice forms. Alternative splicing was shown to occur at both the 5 and 3 termini. Moreover, verification of a short variant, containing exons 1 and 4 only, suggests that splicing also occurs directly between 5 and 3 exons. Notably, a novel splice variant, MOR-1T, demonstrates for the first time that exon 4 can be used in combination with further downstream exons to make the 3 -end of MOR-1 splice variants. The putative protein encoded by MOR-1T is predicted to be identical to that of MOR-1, implying that the MOR-1 protein can be generated from at least five differentially spliced mRNAs. Our results support the view that the Oprm gene undergoes extensive alternative splicing, as a likely major contributor to the diversity of u opioid receptors. Author Affiliation: (1) Institute of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway (2) Unit for Applied Clinical Research, Department of Environmental Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway Article History: Registration Date: 19/11/2003 Received Date: 12/10/2003 Accepted Date: 03/11/2003 Online Date: 09/01/2004

Current treatment for serious depression is unsatisfactory, and many patients fail to achieve the desired effect. Ketamine represents a new treatment option, and randomised trials show a rapid effect of intravenous ketamine. Although knowledge about adverse effects and the duration of the effect is somewhat deficient, we believe that the time has come to start clinical treatment in Norway.

Bakgrunn: Det er økt interesse for psykedeliske stoffer til bruk i behandling av psykiske lidelser. Stoffene regnes som trygge når de gis innenfor en klinisk ramme. Eldre studier fra før 1970 har metodologiske svakheter, men i de senere år har det kommet lovende resultater fra bruk ved unipolar depresjon, depresjon ved livstruende sykdom, angst og avhengighet. Formålet med denne litteraturgjennomgangen er å gi en oversikt over nyere resultater og disse studienes begrensninger., Kunnskapsgrunnlag: Vi søkte i databasen PubMed etter kliniske studier fra perioden 1990-2017 med søkeordene angst, depresjon, avhengighet og psykedeliske stoffer. Kvaliteten på studiene ble så vurdert ut ifra metode og styrkeberegning., Resultater: Søket ga 424 artikler, hvorav ni ble inkludert (fire om angst og depresjon ved livstruende sykdom, to om depresjon, to om avhengighetslidelse og én om tvangslidelse). To dobbeltblinde, randomiserte, kontrollerte fase II-studier med et moderat antall pasienter fant umiddelbar, markert og vedvarende effekt av én enkeltdose psilocybin mot angst og depresjon ved livstruende sykdom. De andre studiene hadde mer usikre resultater. Det var ingen alvorlige bivirkninger eller rapportering om avhengighet., Fortolkning: Psykedeliske stoffer i behandling av flere psykiske lidelser har vist lovende resultater, men studiene er små og har metodologiske utfordringer. Det er behov for systematiske kliniske studier for å skaffe solid dokumentasjon for effekt og etablere rutiner for overvåkning av mulige bivirkninger.