Epidemiology of classic psychedelic substances: results from a Norwegian internet convenience sample.

Objective: In recent years, there has been a renewed interest in investigating the use of classic psychedelics such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of mental disorders and substance use disorders. However, knowledge about the epidemiology of classic psychedelics in the Nordic countries is limited. Methods: We recruited adult, Norwegian participants who have had a memorable experience after taking a classic psychedelic substance. They filled in an anonymous internet survey with 119 items covering matters related to recreational use of psychedelics using a secure, web-based application. Data are presented by using descriptive statistics (frequencies, means, and standard deviations). Results: We recruited 841 participants, 770 (72% male; 88% 45 years or younger) of which were included in the data analysis. The intentions behind taking the psychedelic substance were mainly recreational (46.1%) or therapeutic (42.3%). Most participants reported that their most memorable experience was with psilocybin. As in modern era clinical trials, most participants were well-prepared before, did processing during, and did integration work after the experience, whereas only a minority were supported by a therapist. Self-perceived symptoms of various mental disorders and substance use disorders were prevalent in the sample. Most subjects reported improvements in their condition. Although adverse reactions were usually mild and short-lived, 4.2% lasted for 1 year or more. Persisting flashbacks were present for a year or more among 2.9% of the participants. Conclusion: In this cross-sectional sample of Norwegian, self-selecting adults, we shed light on what characterizes the most memorable experience with a classic psychedelic substance, including short- and long-term risks and benefits. For the most part, the psychedelic experience led to improvements in self-perceived symptoms of mental disorders and substance use disorders. However, a small subset experienced persisting adverse reactions.

Study protocol for "MDMA-assisted therapy as a treatment for major depressive disorder: A proof of principle study".

Background: Major depressive disorder (MDD) is a world-leading cause of disability. The available treatments are not effective in all patients, and there is a significant need for more effective treatment options. Here we present the protocol for an investigator-initiated and publicly funded trial of MDMA-assisted therapy (MDMA-AT) for MDD. This single-site, open-label study investigates the proof of principle and safety of MDMA-AT in participants with MDD and provides an initial impression of treatment effectiveness. Methods: A total of 12 participants [>18 years] with DSM-5 diagnosis of MDD will receive a flexible dose of MDMA in a therapeutic setting on two dosing days over a 4 week period preceded by three preparatory sessions. Each MDMA dosing session will be followed by three integration sessions. The primary outcome is change in MDD symptom severity, as measured by the mean change in MADRS scores from Baseline to 8 weeks after the second MDMA session. The secondary outcome is change in functional impairment, as evaluated by the mean change in Sheehan Disability Scale scores from Baseline to 8 weeks after the second MDMA session. Safety measures include vital signs, the incidence of Adverse Events and suicidality as measured by the Colombia-Suicide Severity Rating Scale. Discussion: This proof of principle trial will inform the development of fully powered clinical trials, optimize the protocol for the administration of MDMA-AT in participants with MDD and explore uncertainties including barriers to recruitment, retention and acceptability of MDMA-AT as a treatment for MDD. Clinical trial identification: EudraCT number 2021-000805-26.

Ketamine for depression - evidence and proposals for practice. / Ketamin ved depresjon ­ evidens og forslag til praksis.

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.

Psychedelic drugs in the treatment of anxiety, depression and addiction. / Psykedeliske stoffer i behandling av angst, depresjon og avhengighet.

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.

Lynx body size in Norway is related to its main prey (Roe deer) density, climate, and latitude.

We studied the effect of various factors on body size variation of the Eurasian lynx in Norway, using data from 374 lynx collected between 1960 and 1976 and whose locality of capture, year of birth, sex, and age were known. Body size of lynx in Norway was mainly affected by sex and age. Female skull size (and by implication body size) was also positively affected by the availability of its main prey (roe deer) and by latitude, and negatively by the North Atlantic Oscillation (NAO). Male size was not affected by any of the environmental factors examined. We interpret the effects of NAO and latitude on body size through their effect on the local climate and particularly snow conditions. We suggest that females are more sensitive to environmental factors than males.

The Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene may influence morphine requirements in cancer pain patients.

Catechol-O-methyltransferase (COMT) inactivates dopamine, epinephrine and norepinephrine in the nervous system. A common functional polymorphism (Val158Met) leads to a three- to-four-fold variation in the COMT enzyme activity, the Met form displaying lower enzymatic activity. The Val158Met polymorphism affects pain perception, and subjects with the Met/Met genotype have the most pronounced response to experimental pain. Based on this information we analyzed the influence from the COMT Val158Met polymorphism on the efficacy of morphine in a cohort of patients suffering from cancer pain. We genotyped 207 Caucasian cancer patients on morphine treatment with respect to the Val158Met polymorphism and compared the morphine doses, serum concentrations of morphine and morphine metabolites between the genotype groups. Patients with the Val/Val genotype (n=44) needed more morphine (155+/-160 mg/24 h) when compared to the Val/Met (117+/-100 mg/24 h; n=96) and the Met/Met genotype (95+/-99 mg/24 h; n=67) groups (P=0.025). This difference was not explained by other factors such as duration of morphine treatment, performance status, time since diagnosis, perceived pain intensity, adverse symptoms, or time until death. These results suggest that genetic variation in the COMT gene may contribute to variability in the efficacy of morphine in cancer pain treatment.

Concentrations of 137Cs in lynx (Lynx lynx) in relation to prey choice.

Concentrations of (137)Cs were determined in 747 lynxes killed in Norway during the period 1986-2001. Highly variable (137)Cs concentrations and aggregated transfer coefficient values were observed, probably caused by variable (137)Cs concentrations in prey and the lynx's extensive home ranges and roaming distances. Adult lynxes had higher (137)Cs concentrations than sub-adults, and lynxes killed in regions with extensive reindeer grazing areas were more contaminated than others. A model with (137)Cs deposition density, the year lynxes were killed, age, and extent of reindeer grazing area accounted for 50% of the variability in observed (137)Cs concentrations. The analyses were equivocal regarding the influence of stomach content on (137)Cs concentrations in lynx muscle, i.e., on the lynx's specialization in prey species. Gender was not significant. Information on caesium retention in lynx and better estimates of deposition densities in lynxes' home ranges are important for further elucidation of factors influencing (137)Cs contamination in lynxes.

Genetic analysis of the murine mu opioid receptor: increased complexity of Oprm gene splicing.

Evidence exists that mu analgesics such as morphine, methadone and fentanyl may act through distinct mu opioid receptor mechanisms. It has been proposed that the functional diversity of mu opioid receptors may be related to alternative splicing of the Oprm gene. Although a number of mu 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 mu opioid receptors.