Tieteelliset julkaisut

Tulokset kategoriasta menetelmat hakusanalla Seuranta. 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:<span style="background-color:yellow;">Seurantatutkimus</span> 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/


Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy. (Wagner MT, Mithoefer MC, Mithoefer AT, MacAulay RK, Jerome L.., 2017)
Julkaisu:Journal of Psychopharmacology
Tiivistelmä: A growing body of research suggests that traumatic events lead to persisting personality change characterized by increased neuroticism. Relevantly, enduring improvements in Post-Traumatic Stress Disorder (PTSD) symptoms have been found in response to 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy.

There is evidence that lasting changes in the personality feature of "openness" occur in response to hallucinogens, and that this may potentially act as a therapeutic mechanism of change. The present study investigated whether heightened Openness and decreased Neuroticism served as a mechanism of change within a randomized trial of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD. The Clinician-Administered PTSD Scale (CAPS) Global Scores and NEO PI-R Personality Inventory (NEO) Openness and Neuroticism Scales served as outcome measures.

Results indicated that changes in Openness but not Neuroticism played a moderating role in the relationship between reduced PTSD symptoms and MDMA treatment. Following MDMA-assisted psychotherapy, increased Openness and decreased Neuroticism when comparing baseline personality traits with long-term follow-up traits also were found.

These preliminary findings suggest that the effect of MDMA-assisted psychotherapy extends beyond specific PTSD symptomatology and fundamentally alters personality structure, resulting in long-term persisting personality change. Results are discussed in terms of possible mechanisms of psychotherapeutic change.
Yhdiste:MDMA
Aihe:Yleiset vaikutukset, stressihäiriö
Menetelmät:Kaksoissokkoutettu, lumekontrolloitu, satunnaistettu, haastattelu, seuranta
Otoskoko:20
Muuta:Tutkimus on jatkoa artikkelille Mithoefer ym. (2011).
Tagit:
DOI:10.1177/0269881117711712
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544120/


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:<span style="background-color:yellow;">Seurantatutkimus</span> tutkimuksesta Johnson ym. 2014
Tagit:
DOI:10.3109/00952990.2016.1170135
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641975/


Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. (Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards .., 2016)
Julkaisu:Journal of Psychopharmacology
Tiivistelmä: Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety.

This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study.

High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.
Yhdiste:psilosybiini
Aihe:kuolemaan liittyvä ahdistus, masennus
Menetelmät:vaihtovuoroinen, kaksoissokkoutettu, lumekontrolloitu, seuranta
Otoskoko:56
Muuta:
Tagit: kuolemaan liittyvä ahdistus, masennus, psilosybiini
DOI:10.1177/0269881116675513
URL: http://journals.sagepub.com/doi/pdf/10.1177/0269881116675513


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...


The paradoxical psychological effects of lysergic acid diethylamide (LSD) (Carhart-Harris RL, Kaelen M, Bolstridge M, Williams TM, Will.., 2016)
Julkaisu:Psychological Medicine
Tiivistelmä: BACKGROUND:
Lysergic acid diethylamide (LSD) is a potent serotonergic hallucinogen or psychedelic that modulates consciousness in a marked and novel way. This study sought to examine the acute and mid-term psychological effects of LSD in a controlled study.

METHOD:
A total of 20 healthy volunteers participated in this within-subjects study. Participants received LSD (75 µg, intravenously) on one occasion and placebo (saline, intravenously) on another, in a balanced order, with at least 2 weeks separating sessions. Acute subjective effects were measured using the Altered States of Consciousness questionnaire and the Psychotomimetic States Inventory (PSI). A measure of optimism (the Revised Life Orientation Test), the Revised NEO Personality Inventory, and the Peter's Delusions Inventory were issued at baseline and 2 weeks after each session.

RESULTS:
LSD produced robust psychological effects; including heightened mood but also high scores on the PSI, an index of psychosis-like symptoms. Increased optimism and trait openness were observed 2 weeks after LSD (and not placebo) and there were no changes in delusional thinking.

CONCLUSIONS:
The present findings reinforce the view that psychedelics elicit psychosis-like symptoms acutely yet improve psychological wellbeing in the mid to long term. It is proposed that acute alterations in mood are secondary to a more fundamental modulation in the quality of cognition, and that increased cognitive flexibility subsequent to serotonin 2A receptor (5-HT2AR) stimulation promotes emotional lability during intoxication and leaves a residue of 'loosened cognition' in the mid to long term that is conducive to improved psychological wellbeing.
Yhdiste:LSD
Aihe:Yleiset vaikutukset
Menetelmät:Lumekontrolloitu, seuranta
Otoskoko:20
Muuta:
Tagit:
DOI:10.1017/S0033291715002901
URL: https://www.cambridge.org/core/journals/psychological-medicine/ar...


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


Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. (Gasser P, Holstein D, Michel Y, Doblin R, Yazar-Klosinski B,.., 2014)
Julkaisu:The Journal of Nervous and Mental disease
Tiivistelmä: A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases.

Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 μg of LSD (n = 8) or 20 μg of LSD with an open-label crossover to 200 μg of LSD after the initial blinded treatment was unmasked (n = 4).

At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months.

These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted.
Yhdiste:LSD
Aihe:kuolemaan liittyvä ahdistus
Menetelmät:kaksoissokkoutettu, satunnaistettu, lumekontrolloitu, seuranta
Otoskoko:12
Muuta:
Tagit: LSD, pilotti
DOI:10.1097/NMD.0000000000000113
URL: https://journals.lww.com/jonmd/fulltext/2014/07000/Safety_and_Eff...


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/


Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after ±3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study (Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Martin SF, .., 2013)
Julkaisu:Journal of Psychopharmacology
Tiivistelmä: We report follow-up data evaluating the long-term outcomes for the first completed trial of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for chronic, treatment-resistant post-traumatic stress disorder (PTSD) (Mithoefer et al., 2011).

All of the 19 subjects who received MDMA-assisted treatment in the original trial participated in the long-term follow-up (LTFU), with 16 out of 19 completing all of the long-term outcome measures, which were administered from 17 to 74 months after the original study's final MDMA session (mean = 45.4; SD = 17.3). Our primary outcome measure used was the Clinician-Administered PTSD Scale (CAPS). Secondary outcome measures were the Impact of Events Scale-Revised (IES-R) and the Neuroticism Extroversion Oppenness Personality Inventory-Revised (NEO PI-R) Personality Inventory.

We also collected a long-term follow-up questionnaire. Results for the 16 CAPS completers showed there were no statistical differences between mean CAPS score at LTFU (mean = 23.7; SD = 22.8) (t (matched) = 0.1; df = 15, p = 0.91) and the mean CAPS score previously obtained at Study Exit (mean = 24.6, SD = 18.6).

On average, subjects maintained statistically and clinically-significant gains in symptom relief, although two of these subjects did relapse. It was promising that we found the majority of these subjects with previously severe PTSD who were unresponsive to existing treatments had symptomatic relief provided by MDMA-assisted psychotherapy that persisted over time, with no subjects reporting harm from participation in the study.
Yhdiste:MDMA
Aihe:stressihäiriö
Menetelmät:Seuranta
Otoskoko:16
Muuta:<span style="background-color:yellow;">Seurantatutkimus</span> tutkimuksesta Mithoefer ym. (2011)
Tagit: MDMA, PTSD
DOI:10.1177/0269881112456611
URL: https://www.researchgate.net/publication/233746130_Durability_of_...


A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)- assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD). (Oehen P, Traber R, Widmer V, Schnyder U, 2013)
Julkaisu:Journal of Psychopharmacology
Tiivistelmä: Psychiatrists and psychotherapists in the US (1970s to 1985) and Switzerland (1988–1993) used MDMA legally as a prescription drug, to enhance the effectiveness of psychotherapy. Early reports suggest that it is useful in treating trauma-related disorders. Recently, the first completed pilot study of MDMA-assisted psychotherapy for PTSD yielded encouraging results.

Designed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD; our randomized, double-blind, active-placebo controlled trial enrolled 12 patients for treatment with either low-dose (25 mg, plus 12.5 mg supplemental dose) or full-dose MDMA (125 mg, plus 62.5 mg supplemental dose). MDMA was administered during three experimental sessions, interspersed with weekly non-drug-based psychotherapy sessions. Outcome measures used were the Clinician-Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale (PDS). Patients were assessed at baseline, three weeks after the second and third MDMA session (end of treatment), and at the 2-month and 1-year follow-ups.

We found that MDMA-assisted psychotherapy can be safely administered in a clinical setting. No drug-related serious adverse events occurred. We did not see statistically significant reductions in CAPS scores (p = 0.066), although there was clinically and statistically significant self-reported (PDS) improvement (p = 0.014). CAPS scores improved further at the 1-year follow-up. In addition, three MDMA sessions were more effective than two (p = 0.016).
Yhdiste:MDMA
Aihe:stressihäiriö
Menetelmät:Kaksoissokkoutettu, lumekontrolloitu, satunnaistettu, seuranta
Otoskoko:12
Muuta:
Tagit: MDMA, PTSD
DOI:10.1177/0269881112464827
URL: http://journals.sagepub.com/doi/abs/10.1177/0269881112464827


The safety and efficacy of 3,4-methylenedioxymethamphetamine- assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study (Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Doblin R, 2011)
Julkaisu:Journal of Psychopharmacology
Tiivistelmä: Case reports indicate that psychiatrists administered 3,4-methylenedioxymethamphetamine (MDMA) as a catalyst to psychotherapy before recreational use of MDMA as ‘Ecstasy’ resulted in its criminalization in 1985.

Over two decades later, this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct. Twenty patients with chronic posttraumatic stress disorder, refractory to both psychotherapy and psychopharmacology, were randomly assigned to psychotherapy with concomitant active drug (n = 12) or inactive placebo (n = 8) administered during two 8-h experimental psychotherapy sessions. Both groups received preparatory and follow-up non-drug psychotherapy.

The primary outcome measure was the Clinician-Administered PTSD Scale, administered at baseline, 4 days after each experimental session, and 2 months after the second session. Neurocognitive testing, blood pressure, and temperature monitoring were performed.

After 2-month follow-up, placebo subjects were offered the option to re-enroll in the experimental procedure with open-label MDMA. Decrease in Clinician-Administered PTSD Scale scores from baseline was significantly greater for the group that received MDMA than for the placebo group at all three time points after baseline.

The rate of clinical response was 10/12 (83%) in the active treatment group versus 2/8 (25%) in the placebo group. There were no drug-related serious adverse events, adverse neurocognitive effects or clinically significant blood pressure increases. MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments.
Yhdiste:MDMA
Aihe:stressihäiriö
Menetelmät:Kaksoissokkoutettu, lumekontrolloitu, satunnaistettu, seuranta
Otoskoko:20
Muuta:
Tagit: MDMA, PTSD
DOI:10.1177/0269881110378371
URL: http://journals.sagepub.com/doi/full/10.1177/0269881110378371


Harm potential of magic mushroom use: a review. (van Amsterdam J, Opperhuizen A, van den Brink W, 2011)
Julkaisu:Regulatory Toxicology and Pharmacology
Tiivistelmä: In 2007, the Minister of Health of the Netherlands requested the CAM (Coordination point Assessment and Monitoring new drugs) to assess the overall risk of magic mushrooms.

The present paper is an updated redraft of the review, written to support the assessment by CAM experts. It summarizes the literature on physical or psychological dependence, acute and chronic toxicity, risk for public health and criminal aspects related to the consumption of magic mushrooms.

In the Netherlands, the prevalence of magic mushroom use was declining since 2000 (last year prevalence of 6.3% in 2000 to 2.9% in 2005), and further declined after possession and use became illegal in December 2008. The CAM concluded that the physical and psychological dependence potential of magic mushrooms was low, that acute toxicity was moderate, chronic toxicity low and public health and criminal aspects negligible. The combined use of mushrooms and alcohol and the quality of the setting in which magic mushrooms are used deserve, however, attention.

In conclusion, the use of magic mushrooms is relatively safe as only few and relatively mild adverse effects have been reported. The low prevalent but unpredictable provocation of panic attacks and flash-backs remain, however, a point of concern.
Yhdiste:psilosybiini
Aihe:päihdekäyttö, haitta-arvio
Menetelmät:Asiantuntijalausunto, seuranta
Otoskoko:0
Muuta:
Tagit: haitallisuusarvio, psilosybiini
DOI:10.1016/j.yrtph.2011.01.006
URL: https://www.ncbi.nlm.nih.gov/pubmed/21256914


Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer (Grob CS, Danforth AL, Chopra GS, Hagerty M, McKay CR, Halber.., 2011)
Julkaisu:Archives of General Psychiatry
Tiivistelmä: Tarkoitus: Tutkimuksessa arvioidaan hallusinogeenien kliinistä soveltuvuutta ahdistuksen hoitoon, joka on syntynyt reaktiona pitkälle edenneeseen syöpään.

Koeasetelma: Psilosybiinin (0.2 mg/kg) tehoa ja turvallisuutta tutkittiin plasebokontrolloidulla kaksoissokko asetelmalla, jossa koehenkilöt toimivat omana kontrollinaan.

Koehenkilöt: 12 pitkälle edennyttä syöpää sairastavaa aikuista, joilla on myös kuolemaan liittyvää ahdistusta.

Käytetyt mittarit: Koehenkilöiden kehon lämpötilaa ja verenapainetta mitattiin kokeen aikana ja sitä ennen. Seurantamittaukset sisälsivät BDI (Beck Depression Inventory), POMS (Profile of Mood States) ja STAI (State-Trait Anxiety Inventory) asteikot, joihin koehenkilöt vastasivat sokkoutuksen purkamisen jälkeen kuuden kuukauden ajan.

Tulokset: Fysiologisten vasteiden ja psykologisten mittausten perusteella arvioituna hoito vaikutti turvalliselta. Psilosybiini ei aiheuttanut koehenkilöille kliinisesti merkittävää haittaa. Koehenkilöiden ahdistustaipumuksessa havaittiin tilastollisesti merkitsevää laskua 1 ja 3 kuukautta hoidon jälkeen. BDI:llä mitattuna koehenkilöiden mielialassa havaittiin tilastollisesti merkitsevää kohenemista kuusi kuukautta hoidon jälkeen. Myös POMS mittauksissa havaittiin koehenkilöiden mielialan kohenemista, joka ei kuitenkaan ollut tilastollisesti merkitsevää.

Johtopäätökset: Tämä tutkimus osoitti psilosybiinin annostelun olevan turvallista ja soveltuvaa pitkälle edenneestä syövästä sairastuneilla potilailla, joilla on kuolemaan liittyvää ahdistusta. Osa aineistosta viittasi positiivisiin muutoksiin koehenkilöiden mielialassa ja ahdistuneisuudessa. Tulosten valossa lisätutkimus vaikuttaa perustellulta tällä pitkään sivuutetulla alalla.
Yhdiste:psilosybiini
Aihe:kuolemaan liittyvä ahdistus
Menetelmät:kaksoissokkoutettu, lumekontrolloitu, seuranta
Otoskoko:12
Muuta:
Tagit: kuolemaan liittyvä ahdistus, masennus, psilosybiini
DOI:10.1001/archgenpsychiatry.2010.116
URL: http://jamanetwork.com/journals/jamapsychiatry/fullarticle/210962


Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. (Griffiths RR, Johnson MW, Richards WA, Richards BD, McCann U.., 2011)
Julkaisu:Psychopharmacology
Tiivistelmä: RATIONALE:
This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior.

OBJECTIVES:
This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions.

METHODS:
Participants were 18 adults (17 hallucinogen-naïve). Five 8-h sessions were conducted individually for each participant at 1-month intervals. Participants were randomized to receive the four active doses in either ascending or descending order (nine participants each). Placebo was scheduled quasi-randomly. During sessions, volunteers used eyeshades and were instructed to direct their attention inward. Volunteers completed questionnaires assessing effects immediately after and 1 month after each session, and at 14 months follow-up.

RESULTS:
Psilocybin produced acute perceptual and subjective effects including, at 20 and/or 30 mg/70 kg, extreme anxiety/fear (39% of volunteers) and/or mystical-type experience (72% of volunteers). One month after sessions at the two highest doses, volunteers rated the psilocybin experience as having substantial personal and spiritual significance, and attributed to the experience sustained positive changes in attitudes, mood, and behavior, with the ascending dose sequence showing greater positive effects. At 14 months, ratings were undiminished and were consistent with changes rated by community observers. Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose, with the lowest dose showing significant effects.

CONCLUSIONS:
Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. Implications for therapeutic trials are discussed.
Yhdiste:Psilosybiini
Aihe:Yleiset vaikutukset
Menetelmät:Kaksoissokkoutettu, lumekontrolloitu, seuranta
Otoskoko:18
Muuta:
Tagit:
DOI:10.1007/s00213-011-2358-5
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308357/


Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness. (MacLean KA, Johnson MW, Griffiths RR, 2011)
Julkaisu:Journal of Psychopharmacology
Tiivistelmä: A large body of evidence, including longitudinal analyses of personality change, suggests that core personality traits are predominantly stable after age 30. To our knowledge, no study has demonstrated changes in personality in healthy adults after an experimentally manipulated discrete event.

Intriguingly, double-blind controlled studies have shown that the classic hallucinogen psilocybin occasions personally and spiritually significant mystical experiences that predict long-term changes in behaviors, attitudes and values. In the present report we assessed the effect of psilocybin on changes in the five broad domains of personality - Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness.

Consistent with participant claims of hallucinogen-occasioned increases in aesthetic appreciation, imagination, and creativity, we found significant increases in Openness following a high-dose psilocybin session. In participants who had mystical experiences during their psilocybin session, Openness remained significantly higher than baseline more than 1 year after the session.

The findings suggest a specific role for psilocybin and mystical-type experiences in adult personality change.
Yhdiste:Psilosybiini
Aihe:Yleiset vaikutukset
Menetelmät:Kirjallisuuskatsaus, kaksoissokkoutettu, lumekontrolloitu, seuranta
Otoskoko:0
Muuta:
Tagit:
DOI:10.1177/0269881111420188
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537171/


Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. (Griffiths R, Richards W, Johnson M, McCann U, Jesse R, 2008)
Julkaisu:Journal of Psychopharmacology
Tiivistelmä: Psilocybin has been used for centuries for religious purposes; however, little is known scientifically about its long-term effects. We previously reported the effects of a double-blind study evaluating the psychological effects of a high psilocybin dose.

This report presents the 14-month follow-up and examines the relationship of the follow-up results to data obtained at screening and on drug session days. Participants were 36 hallucinogen-naïve adults reporting regular participation in religious/ spiritual activities. Oral psilocybin (30 mg/70 kg) was administered on one of two or three sessions, with methylphenidate (40 mg/70 kg) administered on the other session(s).

During sessions, volunteers were encouraged to close their eyes and direct their attention inward. At the 14-month follow-up, 58% and 67%, respectively, of volunteers rated the psilocybin-occasioned experience as being among the five most personally meaningful and among the five most spiritually significant experiences of their lives; 64% indicated that the experience increased well-being or life satisfaction; 58% met criteria for having had a 'complete' mystical experience. Correlation and regression analyses indicated a central role of the mystical experience assessed on the session day in the high ratings of personal meaning and spiritual significance at follow-up. Of the measures of personality, affect, quality of life and spirituality assessed across the study, only a scale measuring mystical experience showed a difference from screening.

When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences that, at 14-month follow-up, were considered by volunteers to be among the most personally meaningful and spiritually significant of their lives.
Yhdiste:Psilosybiini
Aihe:Yleiset vaikutukset
Menetelmät:kaksoissokkoutettu, lumekontrolloitu, seuranta
Otoskoko:36
Muuta:<span style="background-color:yellow;">Seurantatutkimus</span> tutkimuksesta Griffiths ym. (2006).
Tagit:
DOI:10.1177/0269881108094300
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050654/


MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder. (Bouso JC, Doblin R, Farré M, Alcázar MA, Gómez-Jarabo G, 2008)
Julkaisu:Journal of Psychoactive Drugs
Tiivistelmä: The purpose of this study was to investigate the safety of different doses of MDMA-assisted psychotherapy administered in a psychotherapeutic setting to women with chronic PTSD secondary to a sexual assault, and also to obtain preliminary data regarding efficacy. Although this study was originally planned to include 29 subjects, political pressures led to the closing of the study before it could be finished, at which time only six subjects had been treated. Preliminary results from those six subjects are presented here. We found that low doses of MDMA (between 50 and 75 mg) were both psychologically and physiologically safe for all the subjects. Future studies in larger samples and using larger doses are needed in order to further clarify the safety and efficacy of MDMA in the clinical setting in subjects with PTSD.
Yhdiste:MDMA
Aihe:stressihäiriö
Menetelmät:Kaksoissokkoutettu, satunnaistettu, lumekontrolloitum seuranta
Otoskoko:6
Muuta:
Tagit:
DOI:10.1080/02791072.2008.10400637
URL: https://www.ncbi.nlm.nih.gov/pubmed/19004414


Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. (Griffiths RR, Richards WA, McCann U, Jesse R, 2006)
Julkaisu:Psychopharmacology
Tiivistelmä: RATIONALE:
Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects.

OBJECTIVES:
This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable, supportive conditions.

MATERIALS AND METHODS:
The participants were hallucinogen-naïve adults reporting regular participation in religious or spiritual activities. Two or three sessions were conducted at 2-month intervals. Thirty volunteers received orally administered psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) in counterbalanced order. To obscure the study design, six additional volunteers received methylphenidate in the first two sessions and unblinded psilocybin in a third session. The 8-h sessions were conducted individually. Volunteers were encouraged to close their eyes and direct their attention inward. Study monitors rated volunteers' behavior during sessions. Volunteers completed questionnaires assessing drug effects and mystical experience immediately after and 2 months after sessions. Community observers rated changes in the volunteer's attitudes and behavior.

RESULTS:
Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 months, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers.

CONCLUSIONS:
When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences. The ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.
Yhdiste:Psilosybiini
Aihe:Yleiset vaikutukset
Menetelmät:kaksoissokkoutettu, lumekontrolloitu, seuranta
Otoskoko:30
Muuta:
Tagit:
DOI:10.1007/s00213-006-0457-5
URL: https://link.springer.com/article/10.1007%2Fs00213-006-0457-5