Tieteelliset julkaisut

Tulokset kategoriasta menetelmat hakusanalla open label. Takaisin


Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. (Carhart-Harris RL, Bolstridge M, Day CMJ, Rucker J, Watts R,.., 2018)
Julkaisu:Psychopharmacology
Tiivistelmä: RATIONALE:
Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy.

OBJECTIVES:
Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression.

METHODS:
Twenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure.

RESULTS:
Treatment was generally well tolerated. Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen's d = 2.2 at week 1 and 2.3 at week 5, both p < 0.001); nine and four patients met the criteria for response and remission at week 5. Results remained positive at 3 and 6 months (Cohen's d = 1.5 and 1.4, respectively, both p < 0.001). No patients sought conventional antidepressant treatment within 5 weeks of psilocybin. Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience.

CONCLUSIONS:
Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort. Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomised control trials.
Yhdiste:Psilosybiini
Aihe:Masennus
Menetelmät:open label, seuranta
Otoskoko:20
Muuta:Seurantatutkimus tutkimuksesta Carhart-Harris ym. (2016).
Tagit:
DOI:10.1007/s00213-017-4771-x
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813086/


Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression. (Roseman L, Nutt DJ, Carhart-Harris RL, 2018)
Julkaisu:Frontiers in Pharmacology
Tiivistelmä: Introduction: It is a basic principle of the "psychedelic" treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would have negligible predictive value.

Materials and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10 and 25 mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25 mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-Time and DED-by-Time interactions were the primary outcomes of interest.

Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson's correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC (p < 0.05).

Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety.
Yhdiste:Psilosybiini
Aihe:Yleiset vaikutukset, masennus
Menetelmät:Open label, seuranta, haastattelu, kysely
Otoskoko:20
Muuta:
Tagit:
DOI:10.3389/fphar.2017.00974
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5776504/


Long-term follow-up of psilocybin-facilitated smoking cessation. (Johnson MW, Garcia-Romeu A, Griffiths RR, 2017)
Julkaisu:The American Journal of Drug and Alcohol Abuse
Tiivistelmä: BACKGROUND:
A recent open-label pilot study (N = 15) found that two to three moderate to high doses (20 and 30 mg/70 kg) of the serotonin 2A receptor agonist, psilocybin, in combination with cognitive behavioral therapy (CBT) for smoking cessation, resulted in substantially higher 6-month smoking abstinence rates than are typically observed with other medications or CBT alone.

OBJECTIVES:
To assess long-term effects of a psilocybin-facilitated smoking cessation program at ≥12 months after psilocybin administration.

METHODS:
The present report describes biologically verified smoking abstinence outcomes of the previous pilot study at ≥12 months, and related data on subjective effects of psilocybin.

RESULTS:
All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (≥16 months) follow-up, with a mean interval of 30 months (range = 16-57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent. At 12-month follow-up 13 participants (86.7%) rated their psilocybin experiences among the five most personally meaningful and spiritually significant experiences of their lives.

CONCLUSION:
These results suggest that in the context of a structured treatment program, psilocybin holds considerable promise in promoting long-term smoking abstinence. The present study adds to recent and historical evidence suggesting high success rates when using classic psychedelics in the treatment of addiction. Further research investigating psilocybin-facilitated treatment of substance use disorders is warranted.
Yhdiste:Psilosybiini
Aihe:Addiktio
Menetelmät:Open label, seuranta
Otoskoko:15
Muuta:Seurantatutkimus tutkimuksesta Johnson ym. 2014
Tagit:
DOI:10.3109/00952990.2016.1170135
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641975/


Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study (Carhart-Harris RL, Bolstridge M, Rucker J, Day CM, Erritzoe .., 2016)
Julkaisu:The Lancet Psychiatry
Tiivistelmä: Background

Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression.

Methods

In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797.

Findings

Psilocybin's acute psychedelic effects typically became detectable 30–60 min after dosing, peaked 2–3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0–1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference −11·8, 95% CI −9·15 to −14·35, p=0·002, Hedges' g=3·1) and 3 months (−9·2, 95% CI −5·69 to −12·71, p=0·003, Hedges' g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted.

Interpretation

This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach.

Funding

Medical Research Council.
Yhdiste:psilosybiini
Aihe:masennus, haitta-arvio
Menetelmät:open label, seuranta
Otoskoko:12
Muuta:
Tagit: masennus, pilotti, psilosybiini
DOI:10.1016/S2215-0366(16)30065-7
URL: http://www.sciencedirect.com/science/article/pii/S221503661630065...


Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study. (Sanches RF, de Lima Osório F, Dos Santos RG, Macedo LR, Mai.., 2016)
Julkaisu:Journal of Clinical Psychopharmacology
Tiivistelmä: Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow.

In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography.

Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake.

Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers.

Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials.
Yhdiste:Ayahuasca
Aihe:Masennus, yleiset vaikutukset, aivotutkimus
Menetelmät:Open label, seuranta, SPECT
Otoskoko:17
Muuta:
Tagit:
DOI:10.1097/JCP.0000000000000436
URL: https://www.ncbi.nlm.nih.gov/pubmed/26650973


Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study (Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa .., 2015)
Julkaisu:Journal of Psychopharmachology
Tiivistelmä: Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence.

We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions.

Participants’ responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5–8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5.

There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms.
Yhdiste:psilosybiini
Aihe:addiktio
Menetelmät:Open label, seuranta
Otoskoko:10
Muuta:
Tagit: alkoholi, pilotti, psilosybiini, riippuvuus
DOI:10.1177/0269881114565144
URL: https://journals.sagepub.com/doi/abs/10.1177/0269881114565144


Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report. (Osório Fde L, Sanches RF, Macedo LR, Santos RG, Maia-de-Oli.., 2015)
Julkaisu:Revista Brasileira de Psiquiatria
Tiivistelmä: OBJECTIVES:
Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode.

METHODS:
Open-label trial conducted in an inpatient psychiatric unit.

RESULTS:
Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement.

CONCLUSIONS:
These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.
Yhdiste:Ayahuasca
Aihe:Masennus
Menetelmät:Open label, seuranta
Otoskoko:6
Muuta:
Tagit:
DOI:10.1590/1516-4446-2014-1496
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-4446...


Pilot Study of the 5-HT2AR Agonist Psilocybin in the Treatment of Tobacco Addiction (Johnson MW, Garcia-Romeu A, Cosimano MP, Griffiths RR, 2014)
Julkaisu:Journal of Psychopharmachology
Tiivistelmä: Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted.

To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-week smoking cessation treatment protocol.

Participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake.

Biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up. The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies (typically <35%).

Although the open-label design does not allow for definitive conclusions regarding the efficacy of psilocybin, these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models. The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction.
Yhdiste:psilosybiini
Aihe:addiktio
Menetelmät:Open label, seuranta
Otoskoko:15
Muuta:
Tagit: pilotti, psilosybiini, riippuvuus, tupakka
DOI:10.1177/0269881114548296
URL: http://journals.sagepub.com/doi/abs/10.1177/0269881114548296


Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. (Garcia-Romeu A, Griffiths RR, Johnson MW, 2014)
Julkaisu:Current Drug Abuse Reviews
Tiivistelmä: Psilocybin-occasioned mystical experiences have been linked to persisting effects in healthy volunteers including positive changes in behavior, attitudes, and values, and increases in the personality domain of openness. In an open-label pilot-study of psilocybin-facilitated smoking addiction treatment, 15 smokers received 2 or 3 doses of psilocybin in the context of cognitive behavioral therapy (CBT) for smoking cessation.

Twelve of 15 participants (80%) demonstrated biologically verified smoking abstinence at 6-month follow-up. Participants who were abstinent at 6 months (n=12) were compared to participants still smoking at 6 months (n=3) on measures of subjective effects of psilocybin. Abstainers scored significantly higher on a measure of psilocybin-occasioned mystical experience. No significant differences in general intensity of drug effects were found between groups, suggesting that mystical-type subjective effects, rather than overall intensity of drug effects, were responsible for smoking cessation. Nine of 15 participants (60%) met criteria for "complete" mystical experience. Smoking cessation outcomes were significantly correlated with measures of mystical experience on session days, as well as retrospective ratings of personal meaning and spiritual significance of psilocybin sessions.

These results suggest a mediating role of mystical experience in psychedelic-facilitated addiction treatment.
Yhdiste:Psilosybiini
Aihe:Addiktio
Menetelmät:Open label, seuranta
Otoskoko:15
Muuta:Jatkotutkimus tutkimuksesta Johnson ym. 2014
Tagit:
DOI:-
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342293/