Tieteelliset julkaisut

Tulokset kategoriasta aihe hakusanalla farmakologia. Takaisin


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...


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


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, farmakologia
Menetelmät:Kirjallisuuskatsaus
Otoskoko:0
Muuta:
Tagit:
DOI:10.1016/j.euroneuro.2013.12.006
URL: https://www.europeanneuropsychopharmacology.com/article/S0924-977...


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


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