Tieteelliset julkaisut

Tulokset kategoriasta yhdiste hakusanalla MDMA. Takaisin


Safety pharmacology of acute MDMA administration in healthy subjects (Vizeli P & Liechti ME, 2017)
Julkaisu:Journal of Psychopharmacology
Tiivistelmä: 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is being investigated in MDMA-assisted psychotherapy. The present study characterized the safety pharmacology of single-dose administrations of MDMA (75 or 125 mg) using data from nine double-blind, placebo-controlled, crossover studies performed in the same laboratory in a total of 166 healthy subjects.

The duration of the subjective effects was 4.2 ± 1.3 h (range: 1.4–8.2 h). The 125 mg dose of MDMA produced greater ‘good drug effect’ ratings than 75 mg. MDMA produced moderate and transient ‘bad drug effect’ ratings, which were greater in women than in men. MDMA increased systolic blood pressure to >160 mmHg, heart rate >100 beats/min, and body temperature >38°C in 33%, 29% and 19% of the subjects, respectively. These proportions of subjects with hypertension (>160 mmHg), tachycardia, and body temperature >38°C were all significantly greater after 125 mg MDMA compared with the 75 mg dose.

Acute and subacute adverse effects of MDMA as assessed by the List of Complaints were dose-dependent and more frequent in females. MDMA did not affect liver or kidney function at EOS 29 ± 22 days after use. No serious adverse events occurred.

In conclusion, MDMA produced predominantly acute positive subjective drug effects. Bad subjective drug effects and other adverse effects were significantly more common in women. MDMA administration was overall safe in physically and psychiatrically healthy subjects and in a medical setting. However, the risks of MDMA are likely higher in patients with cardiovascular disease and remain to be investigated in patients with psychiatric disorders.
Yhdiste:MDMA
Aihe:haitta-arvio
Menetelmät:yhdistetty analyysi
Otoskoko:166
Muuta:
Tagit: faasi I, käyttöturvallisuus, MDMA, yhdistetty analyysi
DOI:10.1177/0269881117691569
URL: http://journals.sagepub.com/doi/abs/10.1177/0269881117691569


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/


MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults. (Danforth AL, Struble CM, Yazar-Klosinski B, Grob CS, 2016)
Julkaisu:Progress in Neuro-Psychopharmacology and Biological Psychiatry
Tiivistelmä: The first study of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of social anxiety in autistic adults commenced in the spring of 2014. The search for psychotherapeutic options for autistic individuals is imperative considering the lack of effective conventional treatments for mental health diagnoses that are common in this population.

Serious Adverse Events (SAEs) involving the administration of MDMA in clinical trials have been rare and non-life threatening. To date, MDMA has been administered to over 1133 individuals for research purposes without the occurrence of unexpected drug-related SAEs that require expedited reporting per FDA regulations.

Now that safety parameters for limited use of MDMA in clinical settings have been established, a case can be made to further develop MDMA-assisted therapeutic interventions that could support autistic adults in increasing social adaptability among the typically developing population.

As in the case with classic hallucinogens and other psychedelic drugs, MDMA catalyzes shifts toward openness and introspection that do not require ongoing administration to achieve lasting benefits. This infrequent dosing mitigates adverse event frequency and improves the risk/benefit ratio of MDMA, which may provide a significant advantage over medications that require daily dosing. Consequently, clinicians could employ new treatment models for social anxiety or similar types of distress administering MDMA on one to several occasions within the context of a supportive and integrative psychotherapy protocol.
Yhdiste:MDMA
Aihe:Yleiset vaikutukset, farmakologia, haitta-arvio, autismi
Menetelmät:Kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit:
DOI:10.1016/j.pnpbp.2015.03.011
URL: https://www.sciencedirect.com/science/article/pii/S02785846150006...


Treating posttraumatic stress disorder with MDMA-assisted psychotherapy: A preliminary meta-analysis and comparison to prolonged exposure therapy. (Amoroso T, Workman M, 2016)
Julkaisu:Journal of Psychopharmacology
Tiivistelmä: Since the wars in Iraq and Afghanistan, posttraumatic stress disorder (PTSD) has become a major area of research and development. The most widely accepted treatment for PTSD is prolonged exposure (PE) therapy, but for many patients it is intolerable or ineffective. ±3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy (MDMA-AP) has recently re-emerged as a new treatment option, with two clinical trials having been published and both producing promising results. However, these results have yet to be compared to existing treatments.

The present paper seeks to bridge this gap in the literature. Often the statistical significance of clinical trials is overemphasized, while the magnitude of the treatment effects is overlooked. The current meta-analysis aims to provide a comparison of the cumulative effect size of the MDMA-AP studies with those of PE. Effect sizes were calculated for primary and secondary outcome measures in the MDMA-AP clinical trials and compared to those of a meta-analysis including several PE clinical trials.

It was found that MDMA-AP had larger effect sizes in both clinician-observed outcomes than PE did (Hedges' g=1.17 vs. g=1.08, respectively) and patient self-report outcomes (Hedges' g=0.87 vs. g=0.77, respectively). The dropout rates of PE and MDMA-AP were also compared, revealing that MDMA-AP had a considerably lower percentage of patients dropping out than PE did. These results suggest that MDMA-AP offers a promising treatment for PTSD.
Yhdiste:MDMA
Aihe:Stressihäiriö, haitta-arvio
Menetelmät:Meta-analyysi, kaksoissokkoutettu, satunnaistettu, lumekontrolloitu
Otoskoko:0
Muuta:
Tagit:
DOI:10.1177/0269881116642542
URL: http://journals.sagepub.com/doi/abs/10.1177/0269881116642542


The Psychopharmacology of ±3,4 Methylenedioxymethamphetamine and its Role in the Treatment of Posttraumatic Stress Disorder. (Amoroso T, 2015)
Julkaisu:Journal of Psychoactive Drugs
Tiivistelmä: Prior to 1985, ±3,4-methylenedioxymethamphetamine (MDMA) was readily used as a psychotherapeutic adjunct. As MDMA became popular in treating various psychiatric illnesses by mental health professionals, the public started to abuse the MDMA-containing recreational drug "ecstasy." This alarmed the DEA, which led to emergency scheduling of MDMA as a Schedule I drug. Due to its scheduling in 1985, human research and clinical use has been limited.

The majority of research on MDMA has been focused on the drug's potential harmful effects rather than its possible therapeutic effects. The limitations on retrospective human studies and preclinical animal models of MDMA neurotoxicity are examined in this analysis. New research has shown that MDMA, used as a catalyst in psychotherapy, is effective in treating posttraumatic stress disorder (PTSD).

This review also examines the psychopharmacological basis for the efficacy of MDMA-assisted psychotherapy. Specifically, the brain regions involved with both PTSD and those activated by MDMA (i.e., amygdala, anterior cingulate cortex, and hippocampus) are examined. Also, the possible neurochemical mechanisms involved in MDMA's efficacy in treating PTSD are reviewed.
Yhdiste:MDMA
Aihe:Yleiset vaikutukset, farmakologia, stressihäiriö
Menetelmät:Kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit:
DOI:10.1080/02791072.2015.1094156
URL: https://www.ncbi.nlm.nih.gov/pubmed/26579955


The potential dangers of using MDMA for psychotherapy. (Parrott AC, 2014)
Julkaisu:Journal of Psychoactive Drugs
Tiivistelmä: MDMA has properties that may make it attractive for psychotherapy, although many of its effects are potentially problematic. These contrasting effects will be critically reviewed in order to assess whether MDMA could be safe for clinical usage. Early studies from the 1980s noted that MDMA was an entactogen, engendering feelings of love and warmth. However, negative experiences can also occur with MDMA since it is not selective in the thoughts or emotions it releases. This unpredictability in the psychological material released is similar to another serotonergic drug, LSD. Acute MDMA has powerful neurohormonal effects, increasing cortisol, oxytocin, testosterone, and other hormone levels. The release of oxytocin may facilitate psychotherapy, whereas cortisol may increase stress and be counterproductive. MDMA administration is followed by a period of neurochemical recovery, when low serotonin levels are often accompanied by lethargy and depression. Regular usage can also lead to serotonergic neurotoxicity, memory problems, and other psychobiological problems. Proponents of MDMA-assisted therapy state that it should only be used for reactive disorders (such as PTSD) since it can exacerbate distress in those with a prior psychiatric history. Overall, many issues need to be considered when debating the relative benefits and dangers of using MDMA for psychotherapy.
Yhdiste:MDMA
Aihe:Yleiset vaikutukset, haitta-arvio
Menetelmät:Kirjallisuuskatsaus, asiantuntijalausunto
Otoskoko:0
Muuta:
Tagit:
DOI:10.1080/02791072.2014.873690
URL: https://www.ncbi.nlm.nih.gov/pubmed/24830184


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:Seurantatutkimus 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


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


Flashback to the 1960s: LSD in the treatment of autism (Sigafoos J, Green VA, Edrisinha C, Lancioni GE, 2007)
Julkaisu:Developmental Neurorehabilitation
Tiivistelmä: Between 1959 and 1974, several groups of researchers issued reports on the use of d-Lysergic Acid Diethylamide (LSD) in the treatment of children with autism. This paper reviews that literature to consider how the authors justified these studies, as well as their methods, results, and conclusions. The justification for using LSD was often based on the default logic that other treatment efforts had failed. Several positive outcomes were reported with the use of LSD, but most of these studies lacked proper experimental controls and presented largely narrative/descriptive data. Today there is renewed interest in the use of psychedelic drugs for therapeutic purposes. While this resurgence of research has not yet included children with autism, this review of the LSD studies from the 1960s and 1970s offers important lessons for future efforts to evaluate new or controversial treatments for children with autism.
Yhdiste:MDMA
Aihe:Autismi
Menetelmät:Kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit:
DOI:-
URL: https://www.ncbi.nlm.nih.gov/pubmed/17608329


A review of the acute subjective effects of MDMA/ecstasy. (Baylen CA, Rosenberg H, 2006)
Julkaisu:Addiction
Tiivistelmä: AIM:
Although several relatively recent reviews have summarized the neuropsychiatric effects associated with chronic ecstasy use, there is no published comprehensive review of studies on the acute subjective effects (ASEs) of MDMA/ecstasy.

DESIGN:
The present study reviewed the prevalence, intensity and duration of ASEs collected from 24 studies that provided frequency data on the prevalence of self-reported ecstasy effects and/or provided data on the intensity of ecstasy effects.

FINDINGS:
Although hundreds of ASEs have been reported following MDMA consumption, we identified a subset of effects reported repeatedly by meaningful proportions and large numbers of participants across multiple investigations, most of which were either emotional (e.g. anxiety, depression, closeness, fear, euphoria, calmness) or somatic (e.g. nausea/vomiting, bruxism, muscle aches/headache, sweating, numbness, body temperature changes, fatigue, dizziness, dry mouth, increased energy). Only one sexual ASE (sexual arousal/increased sensual awareness), one cognitive ASE (confused thought), one sensory-perceptual ASE (visual effects/changes in visual perception), one sleep-related ASE (sleeplessness) and one appetite-related ASE (decreased appetite) were reported across five or more investigations. Three factors-number of hours between ingestion and assessment, dose level, and gender-have been associated with the acute subjective experience of MDMA/ecstasy.

CONCLUSIONS:
This review provides useful information for clinicians and researchers who want to understand the desirable and undesirable ASEs that may motivate and restrain ecstasy use, for public health advocates who seek to reduce biomedical harms (e.g. fainting, dehydration, shortness of breath, bruxism) associated with recreational use of MDMA/ecstasy, and for educators who wish to design credible prevention messages that neither underestimate nor exaggerate users' experiences of this drug.
Yhdiste:MDMA
Aihe:Yleiset vaikutukset, päihdekäyttö
Menetelmät:Kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit:
DOI:10.1111/j.1360-0443.2006.01423.x
URL: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1360-0443.2006....


Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition. (de la Torre R, Farré M, Roset PN, Pizarro N, Abanades S, Se.., 2004)
Julkaisu:Therapeutic Drug Monitoring
Tiivistelmä: MDMA (3,4-methylenedioxymethamphetamine, ecstasy) is a widely misused psychostimulant drug abused among large segments of the young population. Pharmacologically it displays effects related to amphetamine-type drugs and a set of distinctive effects (closeness to others, facilitation to interpersonal relationship, and empathy) that have been named by some authors "entactogen" properties. MDMA is a potent releaser and/or reuptake inhibitor of presynaptic serotonin (5-HT), dopamine (DA), and norepinephrine (NE). These actions result from the interaction of MDMA with the membrane transporters involved in neurotransmitter reuptake and vesicular storage systems.

The most frequent effects after MDMA/ecstasy administration are euphoria, well-being, happiness, stimulation, increased energy, extroversion, feeling close to others, increased empathy, increased sociability, enhanced mood, mild perceptual disturbances, changed perception of colors and sounds, somatic symptoms related to its cardiovascular and autonomic effects (blood pressure and heart rate increase, mydriasis), and moderate derealization but not hallucinations. Acute toxic effects are related to its pharmacologic actions. The serotonin syndrome (increased muscle rigidity, hyperreflexia, and hyperthermia), among others, is characteristic of acute toxicity episodes.

MDMA metabolism is rather complex and includes 2 main metabolic pathways: (1) O-demethylenation followed by catechol-O-methyltransferase (COMT)-catalyzed methylation and/or glucuronide/sulfate conjugation; and (2) N-dealkylation, deamination, and oxidation to the corresponding benzoic acid derivatives conjugated with glycine. The fact that the polymorphic enzyme CYP2D6 partially regulates the O-demethylenation pathway prompted some expectations that subjects displaying the poor metabolizer phenotype may be at higher risk of acute toxicity episodes. In this metabolic pathway a mechanism-based inhibition of the enzyme operates because the formation of an enzyme-metabolite complex that renders all subjects, independently of genotype, phenotypically poor metabolizers after the administration of 2 consecutive doses. Therefore, the impact of CYP2D6 pharmacogenetics on acute toxicity is limited. One of the interesting features of MDMA metabolism is its potential involvement in the development of mid- to long-term neurotoxic effects as a result of progressive neurodegeneration of the serotonergic neurotransmission system.
Yhdiste:MDMA
Aihe:Yleiset vaikutukset, farmakologia
Menetelmät:Kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit:
DOI:-
URL: https://insights.ovid.com/pubmed?pmid=15228154