Tieteelliset julkaisut

Tulokset kategoriasta aihe hakusanalla Yleiset vaikutukset. Takaisin


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/


Studies with psychedelic drugs in human volunteers. (Sellers EM, Romach MK, Leiderman DB, 2017)
Julkaisu:Neuropharmacology
Tiivistelmä: Scientific curiosity and fascination have played a key role in human research with psychedelics along with the hope that perceptual alterations and heightened insight could benefit well-being and play a role in the treatment of various neuropsychiatric disorders. These motivations need to be tempered by a realistic assessment of the hurdles to be cleared for therapeutic use. Development of a psychedelic drug for treatment of a serious psychiatric disorder presents substantial although not insurmountable challenges. While the varied psychedelic agents described in this chapter share some properties, they have a range of pharmacologic effects that are reflected in the gradation in intensity of hallucinogenic effects from the classical agents to DMT, MDMA, ketamine, dextromethorphan and new drugs with activity in the serotonergic system. The common link seems to be serotonergic effects modulated by NMDA and other neurotransmitter effects. The range of hallucinogens suggest that they are distinct pharmacologic agents and will not be equally safe or effective in therapeutic targets. Newly synthesized specific and selective agents modeled on the legacy agents may be worth considering. Defining therapeutic targets that represent unmet medical need, addressing market and commercial issues, and finding treatment settings to safely test and use such drugs make the human testing of psychedelics not only interesting but also very challenging.
Yhdiste:Psykedeelit yleisesti, LSD, psilosybiini, MDMA
Aihe:Yleiset vaikutukset, farmakologia
Menetelmät:Kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit:
DOI:10.1016/j.neuropharm.2017.11.029
URL: https://www.sciencedirect.com/science/article/pii/S00283908173054...


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/


Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. (Carhart-Harris RL, Roseman L, Bolstridge M, Demetriou L, Pan.., 2017)
Julkaisu:Scientific Reports
Tiivistelmä: Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD).

Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC.

These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other 'psychedelics' yet were related to clinical outcomes. A 'reset' therapeutic mechanism is proposed.
Yhdiste:Psilosybiini
Aihe:Yleiset vaikutukset, aivotutkimus
Menetelmät:fMRI
Otoskoko:16
Muuta:
Tagit:
DOI:10.1038/s41598-017-13282-7
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640601/


Psychedelics. (Nichols DE, 2016)
Julkaisu:Pharmacological Reviews
Tiivistelmä: Psychedelics (serotonergic hallucinogens) are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. They are generally considered physiologically safe and do not lead to dependence or addiction. Their origin predates written history, and they were employed by early cultures in many sociocultural and ritual contexts

After the virtually contemporaneous discovery of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD)-25 and the identification of serotonin in the brain, early research focused intensively on the possibility that LSD and other psychedelics had a serotonergic basis for their action.

Today there is a consensus that psychedelics are agonists or partial agonists at brain serotonin 5-hydroxytryptamine 2A receptors, with particular importance on those expressed on apical dendrites of neocortical pyramidal cells in layer V. Several useful rodent models have been developed over the years to help unravel the neurochemical correlates of serotonin 5-hydroxytryptamine 2A receptor activation in the brain, and a variety of imaging techniques have been employed to identify key brain areas that are directly affected by psychedelics.

Recent and exciting developments in the field have occurred in clinical research, where several double-blind placebo-controlled phase 2 studies of psilocybin-assisted psychotherapy in patients with cancer-related psychosocial distress have demonstrated unprecedented positive relief of anxiety and depression. Two small pilot studies of psilocybin-assisted psychotherapy also have shown positive benefit in treating both alcohol and nicotine addiction. Recently, blood oxygen level-dependent functional magnetic resonance imaging and magnetoencephalography have been employed for in vivo brain imaging in humans after administration of a psychedelic, and results indicate that intravenously administered psilocybin and LSD produce decreases in oscillatory power in areas of the brain's default mode network.
Yhdiste:Psykedeelit yleisesti, LSD, psilosybiini
Aihe:Yleiset vaikutukset
Menetelmät:Kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit:
DOI:10.1124/pr.115.011478
URL: http://pharmrev.aspetjournals.org/content/68/2/264.long


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...


The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms. (Barrett FS, Bradstreet MP, Leoutsakos JS, Johnson MW, Griffi.., 2016)
Julkaisu:Journal of Psychopharmacology
Tiivistelmä: Acute adverse psychological reactions to classic hallucinogens ("bad trips" or "challenging experiences"), while usually benign with proper screening, preparation, and support in controlled settings, remain a safety concern in uncontrolled settings (such as illicit use contexts). Anecdotal and case reports suggest potential adverse acute symptoms including affective (panic, depressed mood), cognitive (confusion, feelings of losing sanity), and somatic (nausea, heart palpitation) symptoms.

Responses to items from several hallucinogen-sensitive questionnaires (Hallucinogen Rating Scale, the States of Consciousness Questionnaire, and the Five-Dimensional Altered States of Consciousness questionnaire) in an Internet survey of challenging experiences with the classic hallucinogen psilocybin were used to construct and validate a Challenging Experience Questionnaire.

The stand-alone Challenging Experience Questionnaire was then validated in a separate sample. Seven Challenging Experience Questionnaire factors (grief, fear, death, insanity, isolation, physical distress, and paranoia) provide a phenomenological profile of challenging aspects of experiences with psilocybin. Factor scores were associated with difficulty, meaningfulness, spiritual significance, and change in well-being attributed to the challenging experiences. The factor structure did not differ based on gender or prior struggle with anxiety or depression.

The Challenging Experience Questionnaire provides a basis for future investigation of predictors and outcomes of challenging experiences with classic hallucinogens.
Yhdiste:Psykedeelit yleisesti
Aihe:Yleiset vaikutukset
Menetelmät:Kyselytutkimus, kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit:
DOI:10.1177/0269881116678781
URL: http://journals.sagepub.com/doi/abs/10.1177/0269881116678781


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...


Classical hallucinogens and neuroimaging: A systematic review of human studies: Hallucinogens and neuroimaging. (Dos Santos RG, Osório FL, Crippa JAS, Hallak JEC, 2016)
Julkaisu:Neuroscience and Biobehavioural Reviews
Tiivistelmä: Serotonergic hallucinogens produce alterations of perceptions, mood, and cognition, and have anxiolytic, antidepressant, and antiaddictive properties. These drugs act as agonists of frontocortical 5-HT2A receptors, but the neural basis of their effects are not well understood. Thus, we conducted a systematic review of neuroimaging studies analyzing the effects of serotonergic hallucinogens in man.

Studies published in the PubMed, Lilacs, and SciELO databases until 12 April 2016 were included using the following keywords: "ayahuasca", "DMT", "psilocybin", "LSD", "mescaline" crossed one by one with the terms "mri", "fmri", "pet", "spect", "imaging" and "neuroimaging". Of 279 studies identified, 25 were included.

Acute effects included excitation of frontolateral/frontomedial cortex, medial temporal lobe, and occipital cortex, and inhibition of the default mode network. Long-term use was associated with thinning of the posterior cingulate cortex, thickening of the anterior cingulate cortex, and decreased neocortical 5-HT2A receptor binding.

Despite the high methodological heterogeneity and the small sample sizes, the results suggest that hallucinogens increase introspection and positive mood by modulating brain activity in the fronto-temporo-parieto-occipital cortex.
Yhdiste:Psykedeelit yleisesti, ayahuasca, psilosybiini, LSD
Aihe:Aivotutkimus, yleiset vaikutukset, farmakologia
Menetelmät:Kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit:
DOI:10.1016/j.neubiorev.2016.10.026
URL: https://www.sciencedirect.com/science/article/pii/S01497634163023...


The current state of research on ayahuasca: A systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging. (Dos Santos RG, Balthazar FM, Bouso JC, Hallak JE, 2016)
Julkaisu:Journal of Psychopharmacology
Tiivistelmä: RATIONALE:
In recent decades, the use of ayahuasca (AYA) - a β-carboline- and dimethyltryptamine-rich hallucinogenic botanical preparation traditionally used by Northwestern Amazonian tribes for ritual and therapeutic purposes - has spread from South America to Europe and the USA, raising concerns about its possible toxicity and hopes of its therapeutic potential. Thus, it is important to analyze the acute, subacute, and long-term effects of AYA to assess its safety and toxicity.

OBJECTIVES:
The purpose of this study was to conduct a systematic review of human studies assessing AYA effects on psychiatric symptoms, neuropsychological functioning, and neuroimaging.

METHODS:
Papers published until 16 December 2015 were included from PubMed, LILACS and SciELO databases following a comprehensive search strategy and pre-determined set of criteria for article selection.

RESULTS:
The review included 28 full-text articles. Acute AYA administration was well tolerated, increased introspection and positive mood, altered visual perceptions, activated frontal and paralimbic regions and decreased default mode network activity. It also improved planning and inhibitory control and impaired working memory, and showed antidepressive and antiaddictive potentials. Long-term AYA use was associated with increased cortical thickness of the anterior cingulate cortex and cortical thinning of the posterior cingulate cortex, which was inversely correlated to age of onset, intensity of prior AYA use, and spirituality. Subacute and long-term AYA use was not associated with increased psychopathology or cognitive deficits, being associated with enhanced mood and cognition, increased spirituality, and reduced impulsivity.

CONCLUSIONS:
Acute, subacute, and long-term AYA use seems to have low toxicity. Preliminary studies about potential therapeutic effects of AYA need replication due to their methodological limitations.
Yhdiste:Ayahuasca
Aihe:Yleiset vaikutukset, aivotutkimus, farmakologia
Menetelmät:Kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit:
DOI:10.1177/0269881116652578
URL: http://journals.sagepub.com/doi/abs/10.1177/0269881116652578


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


Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies.logical functioning, and neuroimaging. (Dos Santos RG, Osório FL, Crippa JA, Hallak JE, 2016)
Julkaisu:Revista brasileira de psiquiatria
Tiivistelmä: OBJECTIVE:
To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline).

METHODS:
Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection.

RESULTS:
Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression.

CONCLUSION:
Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.
Yhdiste:Ayahuasca
Aihe:Yleiset vaikutukset, masennus
Menetelmät:Kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit:
DOI:10.1590/1516-4446-2015-1701
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-4446...


Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects. (Schmid Y, Enzler F, Gasser P, Grouzmann E, Preller KH, Volle.., 2015)
Julkaisu:Biological Psychiatry
Tiivistelmä: BACKGROUND:
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.

METHODS:
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.

RESULTS:
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.

CONCLUSIONS:
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.
Yhdiste:LSD
Aihe:haitta-arvio, yleiset vaikutukset
Menetelmät:kaksoissokkoutettu, satunnaistettu, lumekontrolloitu, vaihtovuoroinen
Otoskoko:16
Muuta:
Tagit: LSD
DOI:10.1016/j.biopsych.2014.11.015
URL: https://www.biologicalpsychiatryjournal.com/article/S0006-3223(14...


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


Psilocybin–summary of knowledge and new perspectives (Tylš F, Páleníček T, Horáček J, 2014)
Julkaisu:European Neuropsychopharmacology
Tiivistelmä: Psilocybin, a psychoactive alkaloid contained in hallucinogenic mushrooms, is nowadays given a lot of attention in the scientific community as a research tool for modeling psychosis as well as due to its potential therapeutic effects. However, it is also a very popular and frequently abused natural hallucinogen.

This review summarizes all the past and recent knowledge on psilocybin. It briefly deals with its history, discusses the pharmacokinetics and pharmacodynamics, and compares its action in humans and animals. It attempts to describe the mechanism of psychedelic effects and objectify its action using modern imaging and psychometric methods. Finally, it describes its therapeutic and abuse potential.
Yhdiste:psilosybiini
Aihe:Yleiset vaikutukset
Menetelmät:kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit: farmakodynamiikka, farmakokinetiikka, psilosybiini
DOI:10.1016/j.euroneuro.2013.12.006
URL: https://www.ncbi.nlm.nih.gov/pubmed/24444771


Psilocybin - summary of knowledge and new perspectives. (Tylš F, Páleníček T, Horáček J, 2014)
Julkaisu:European Neuropsychopharmacology
Tiivistelmä: Psilocybin, a psychoactive alkaloid contained in hallucinogenic mushrooms, is nowadays given a lot of attention in the scientific community as a research tool for modeling psychosis as well as due to its potential therapeutic effects. However, it is also a very popular and frequently abused natural hallucinogen.

This review summarizes all the past and recent knowledge on psilocybin. It briefly deals with its history, discusses the pharmacokinetics and pharmacodynamics, and compares its action in humans and animals. It attempts to describe the mechanism of psychedelic effects and objectify its action using modern imaging and psychometric methods. Finally, it describes its therapeutic and abuse potential.
Yhdiste:Psilosybiini
Aihe:Yleiset vaikutukset, farmakologia
Menetelmät:Kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit:
DOI:10.1016/j.euroneuro.2013.12.006
URL: https://www.europeanneuropsychopharmacology.com/article/S0924-977...


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


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/


The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. (Vollenweider FX, Kometer M, 2010)
Julkaisu:Nature Reviews. Neuroscience.
Tiivistelmä: After a pause of nearly 40 years in research into the effects of psychedelic drugs, recent advances in our understanding of the neurobiology of psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and ketamine have led to renewed interest in the clinical potential of psychedelics in the treatment of various psychiatric disorders. Recent behavioural and neuroimaging data show that psychedelics modulate neural circuits that have been implicated in mood and affective disorders, and can reduce the clinical symptoms of these disorders. These findings raise the possibility that research into psychedelics might identify novel therapeutic mechanisms and approaches that are based on glutamate-driven neuroplasticity.
Yhdiste:Psykedeelit yleisesti, LSD, psilosybiini
Aihe:Yleiset vaikutukset, farmakologia
Menetelmät:Kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit:
DOI:10.1038/nrn2884
URL: https://www.nature.com/articles/nrn2884


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:Seurantatutkimus tutkimuksesta Griffiths ym. (2006).
Tagit:
DOI:10.1177/0269881108094300
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050654/


The pharmacology of lysergic acid diethylamide: a review. (Passie T, Halpern JH, Stichtenoth DO, Emrich HM, Hintzen A, 2008)
Julkaisu:CNS Neuroscience & Therapeutics
Tiivistelmä: Lysergic acid diethylamide (LSD) was synthesized in 1938 and its psychoactive effects discovered in 1943. It was used during the 1950s and 1960s as an experimental drug in psychiatric research for producing so-called "experimental psychosis" by altering neurotransmitter system and in psychotherapeutic procedures ("psycholytic" and "psychedelic" therapy). From the mid 1960s, it became an illegal drug of abuse with widespread use that continues today. With the entry of new methods of research and better study oversight, scientific interest in LSD has resumed for brain research and experimental treatments.

Due to the lack of any comprehensive review since the 1950s and the widely dispersed experimental literature, the present review focuses on all aspects of the pharmacology and psychopharmacology of LSD. A thorough search of the experimental literature regarding the pharmacology of LSD was performed and the extracted results are given in this review. (Psycho-) pharmacological research on LSD was extensive and produced nearly 10,000 scientific papers.

The pharmacology of LSD is complex and its mechanisms of action are still not completely understood. LSD is physiologically well tolerated and psychological reactions can be controlled in a medically supervised setting, but complications may easily result from uncontrolled use by layman. Actually there is new interest in LSD as an experimental tool for elucidating neural mechanisms of (states of) consciousness and there are recently discovered treatment options with LSD in cluster headache and with the terminally ill.
Yhdiste:LSD
Aihe:Yleiset vaikutukset
Menetelmät:Kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit:
DOI:10.1111/j.1755-5949.2008.00059.x
URL: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1755-5949.2008....


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


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


The pharmacology of psilocybin. (Passie T, Seifert J, Schneider U, Emrich HM, 2002)
Julkaisu:Addiction Biology
Tiivistelmä: Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is the major psychoactive alkaloid of some species of mushrooms distributed worldwide. These mushrooms represent a growing problem regarding hallucinogenic drug abuse. Despite its experimental medical use in the 1960s, only very few pharmacological data about psilocybin were known until recently. Because of its still growing capacity for abuse and the widely dispersed data this review presents all the available pharmacological data about psilocybin.
Yhdiste:psilosybiini
Aihe:yleiset vaikutukset
Menetelmät:Kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit: kirjallisuuskatsaus, psilosybiini
DOI:10.1080/1355621021000005937
URL: https://www.ncbi.nlm.nih.gov/pubmed/14578010