Tulokset kategoriasta aihe hakusanalla haitta-arvio. 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.
|Tagit:||faasi I, käyttöturvallisuus, MDMA, yhdistetty analyysi|
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|
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.
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.
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.
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.
Medical Research Council.
|Menetelmät:||open label, seuranta|
|Tagit:||masennus, pilotti, psilosybiini|
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.
|Aihe:||Yleiset vaikutukset, farmakologia, haitta-arvio, autismi|
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.
|Menetelmät:||Meta-analyysi, kaksoissokkoutettu, satunnaistettu, lumekontrolloitu|
European rating of drug harms. (van Amsterdam J, Nutt D, Phillips L, van den Brink W, 2015)
|Julkaisu:||Journal of Psychopharmacology|
The present paper describes the results of a rating study performed by a group of European Union (EU) drug experts using the multi-criteria decision analysis model for evaluating drug harms.
Forty drug experts from throughout the EU scored 20 drugs on 16 harm criteria. The expert group also assessed criteria weights that would apply, on average, across the EU. Weighted averages of the scores provided a single, overall weighted harm score (range: 0-100) for each drug.
Alcohol, heroin and crack emerged as the most harmful drugs (overall weighted harm score 72, 55 and 50, respectively). The remaining drugs had an overall weighted harm score of 38 or less, making them much less harmful than alcohol. The overall weighted harm scores of the EU experts correlated well with those previously given by the UK panel.
The outcome of this study shows that the previous national rankings based on the relative harms of different drugs are endorsed throughout the EU. The results indicates that EU and national drug policy measures should focus on drugs with the highest overall harm, including alcohol and tobacco, whereas drugs such as cannabis and ecstasy should be given lower priority including a lower legal classification.
|Yhdiste:||päihteet yleisesti, LSD, psilosybiini, MDMA|
|Tagit:||alkoholi, haitallisuusarvio, päihteet, tupakka|
Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects. (Schmid Y, Enzler F, Gasser P, Grouzmann E, Preller KH, Volle.., 2015)
After no research in humans for >40 years, there is renewed interest in using lysergic acid diethylamide (LSD) in clinical psychiatric research and practice. There are no modern studies on the subjective and autonomic effects of LSD, and its endocrine effects are unknown. In animals, LSD disrupts prepulse inhibition (PPI) of the acoustic startle response, and patients with schizophrenia exhibit similar impairments in PPI. However, no data are available on the effects of LSD on PPI in humans.
In a double-blind, randomized, placebo-controlled, crossover study, LSD (200 μg) and placebo were administered to 16 healthy subjects (8 women, 8 men). Outcome measures included psychometric scales; investigator ratings; PPI of the acoustic startle response; and autonomic, endocrine, and adverse effects.
Administration of LSD to healthy subjects produced pronounced alterations in waking consciousness that lasted 12 hours. The predominant effects induced by LSD included visual hallucinations, audiovisual synesthesia, and positively experienced derealization and depersonalization phenomena. Subjective well-being, happiness, closeness to others, openness, and trust were increased by LSD. Compared with placebo, LSD decreased PPI. LSD significantly increased blood pressure, heart rate, body temperature, pupil size, plasma cortisol, prolactin, oxytocin, and epinephrine. Adverse effects produced by LSD completely subsided within 72 hours. No severe acute adverse effects were observed.
In addition to marked hallucinogenic effects, LSD exerts methylenedioxymethamphetamine-like empathogenic mood effects that may be useful in psychotherapy. LSD altered sensorimotor gating in a human model of psychosis, supporting the use of LSD in translational psychiatric research. In a controlled clinical setting, LSD can be used safely, but it produces significant sympathomimetic stimulation.
|Aihe:||haitta-arvio, yleiset vaikutukset|
|Menetelmät:||kaksoissokkoutettu, satunnaistettu, lumekontrolloitu, vaihtovuoroinen|
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.|
|Aihe:||Yleiset vaikutukset, haitta-arvio|
Psychedelics and Mental Health: A Population Study (Krebs TS & Johansen PØ, 2013)
The classical serotonergic psychedelics LSD, psilocybin, mescaline are not known to cause brain damage and are regarded as non-addictive. Clinical studies do not suggest that psychedelics cause long-term mental health problems. Psychedelics have been used in the Americas for thousands of years. Over 30 million people currently living in the US have used LSD, psilocybin, or mescaline.
To evaluate the association between the lifetime use of psychedelics and current mental health in the adult population.
Data drawn from years 2001 to 2004 of the National Survey on Drug Use and Health consisted of 130,152 respondents, randomly selected to be representative of the adult population in the United States. Standardized screening measures for past year mental health included serious psychological distress (K6 scale), mental health treatment (inpatient, outpatient, medication, needed but did not receive), symptoms of eight psychiatric disorders (panic disorder, major depressive episode, mania, social phobia, general anxiety disorder, agoraphobia, posttraumatic stress disorder, and non-affective psychosis), and seven specific symptoms of non-affective psychosis. We calculated weighted odds ratios by multivariate logistic regression controlling for a range of sociodemographic variables, use of illicit drugs, risk taking behavior, and exposure to traumatic events.
21,967 respondents (13.4% weighted) reported lifetime psychedelic use. There were no significant associations between lifetime use of any psychedelics, lifetime use of specific psychedelics (LSD, psilocybin, mescaline, peyote), or past year use of LSD and increased rate of any of the mental health outcomes. Rather, in several cases psychedelic use was associated with lower rate of mental health problems.
We did not find use of psychedelics to be an independent risk factor for mental health problems.
|Yhdiste:||psykedeelit yleisesti, LSD, psilosybiini|
|Menetelmät:||National Survey on Drug Use and Health 2001-2004|
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.
Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. Journal of Psychopharmacology (Studerus E, Kometer M, Hasler F, Vollenweider FX, 2011)
|Julkaisu:||Journal of Psychopharmacology|
|Tiivistelmä:|| Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial.|
We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects.
All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects.
The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.
Human hallucinogen research: guidelines for safety. (Johnson M, Richards W, Griffiths R, 2008)
|Julkaisu:||Journal of Psychopharmacology|
|Tiivistelmä:|| There has recently been a renewal of human research with classical hallucinogens (psychedelics). This paper first briefly discusses the unique history of human hallucinogen research, and then reviews the risks of hallucinogen administration and safeguards for minimizing these risks.|
Although hallucinogens are relatively safe physiologically and are not considered drugs of dependence, their administration involves unique psychological risks. The most likely risk is overwhelming distress during drug action ('bad trip'), which could lead to potentially dangerous behaviour such as leaving the study site. Less common are prolonged psychoses triggered by hallucinogens.
Safeguards against these risks include the exclusion of volunteers with personal or family history of psychotic disorders or other severe psychiatric disorders, establishing trust and rapport between session monitors and volunteer before the session, careful volunteer preparation, a safe physical session environment and interpersonal support from at least two study monitors during the session. Investigators should probe for the relatively rare hallucinogen persisting perception disorder in follow-up contact.
Persisting adverse reactions are rare when research is conducted along these guidelines. Incautious research may jeopardize participant safety and future research. However, carefully conducted research may inform the treatment of psychiatric disorders, and may lead to advances in basic science.
|Yhdiste:||Psykedeelit yleisesti, LSD, psilosybiini|
Toward a comparative overview of dependence potential and acute toxicity of psychoactive substances used nonmedically (Gable RS, 1993)
|Julkaisu:||The American Journal of Drug and Alcohol Abuse|
|Tiivistelmä:|| A procedure is outlined for comparing dependence potential and acute toxicity across a broad range of abused psychoactive substances. Tentative results, based on an extensive literature review of 20 substances, suggested that the margin of safety ("therapeutic index") varied dramatically between substances.|
Intravenous heroin appeared to have the greatest risk of dependence and acute lethality; oral psilocybin appeared to have the least. Hazards due to behavioral deficits, perceptual distortion, or chronic illness were not factored into the assessments.
|Tagit:||haitallisuusarvio, päihteet, psilosybiini|