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Current Topics in Behavioral... 2022Classic psychedelics, including psilocybin, lysergic acid diethylamide (LSD), dimethyltryptamine, and mescaline, and entactogens/empathogens, especially...
Classic psychedelics, including psilocybin, lysergic acid diethylamide (LSD), dimethyltryptamine, and mescaline, and entactogens/empathogens, especially 3,4-methylenedioxymethamphetamine, have received renewed attention in psychiatric research and may be developed into medications for such indications as anxiety, depression, cluster headache, and posttraumatic stress disorder, among others. However, identifying proper doses is crucial. Controlled study data on dosing using well-characterized pharmaceutical formulations of the substances are scarce. The dose equivalence of different substances, dose-response effects, and subjective effects of different doses are of great interest and practically important for their clinical use in psychotherapy. Furthermore, the so-called microdosing of psychedelics has recently gained popularity, and the first placebo-controlled studies of LSD have been published. This chapter discusses different aspects of psychedelic dosing, including pharmaceutical aspects, definitions and characteristics of different doses, including microdoses, aspects of personalized dosing, and non-pharmacological factors, that can influence the response to psychedelics.
Topics: Hallucinogens; Lysergic Acid Diethylamide; N-Methyl-3,4-methylenedioxyamphetamine; Pharmaceutical Preparations; Psilocybin
PubMed: 34734392
DOI: 10.1007/7854_2021_270 -
Revista de Investigacion Clinica;... 2023This review focuses on the effects and mechanisms of action of amphetamine-type stimulants (ATS) and their adverse effects on the cardiovascular, nervous, and immune... (Review)
Review
This review focuses on the effects and mechanisms of action of amphetamine-type stimulants (ATS) and their adverse effects on the cardiovascular, nervous, and immune systems. ATS include amphetamine (AMPH), methamphetamine (METH, "crystalmeth," or "ice"), methylenedioxymethamphetamine (MDMA, "ecstasy," or "Molly"), MDMA derivatives (e.g., methylenedioxyamphetamine [MDA] and methylenedioxy-N-ethylamphetamine [MDEA]), khat, and synthetic cathinones. The first section of this paper presents an overview of the historical aspects of ATS use, their initial clinical use, and regulations. The second part reviews the acute and chronic impact and the most salient clinical effects of ATS on the central nervous and cardiovascular systems, skin, and mouth. The chemical structure, pharmacokinetics, and classic and non-canonical pharmacological actions are covered in the third section, briefly explaining the mechanisms involved. In addition, the interactions of ATS with the central and peripheral immune systems are reviewed. The last section presents data about the syndemic of ATS and opioid use in the North American region, focusing on the increasing adulteration of METH with fentanyl.
Topics: Humans; Amphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Central Nervous System Stimulants; 3,4-Methylenedioxyamphetamine; Methamphetamine
PubMed: 37441770
DOI: 10.24875/RIC.23000110 -
European Journal of Pharmacology Jul 20213,4-methylenedioxymethamphetamine or MDMA (known as "ecstasy") is a recreational drug of abuse, popular worldwide for its distinctive psychotropic effects. Currently,... (Review)
Review
3,4-methylenedioxymethamphetamine or MDMA (known as "ecstasy") is a recreational drug of abuse, popular worldwide for its distinctive psychotropic effects. Currently, the therapeutic potential of MDMA in psychotherapy has attracted a lot of interest from the scientific community, despite the multitude of effects that this drug of abuse elicits on the human body. While neuronal effects have been the most studied, cardiovascular effects have also been described, as increased blood pressure and heart rate are the most recognizable. However, other effects have also been described at the cardiac (impaired cardiac contractile function, arrhythmias, myocardial necrosis and valvular heart disease) and vascular (vasoconstriction, disruption of vascular integrity and altered haemostasis) levels. Several mechanisms have been proposed, from the interaction with monoamine transporters and receptors to the promotion of oxidative stress or the activation of matrix metalloproteinases (MMPs). This review provides an overview of the cardiovascular implications of MDMA intake and underlying mechanisms, relevant when considering its consumption as drug of abuse but also when considering its therapeutic potential in psychiatry. Moreover, the risk/benefit ratio of the therapeutic use of MDMA remains to be fully elucidated from a cardiovascular standpoint, particularly in patients with underlying cardiovascular disease.
Topics: Animals; Blood Pressure; Blood Vessels; Cardiovascular System; Heart; Heart Rate; Humans; N-Methyl-3,4-methylenedioxyamphetamine
PubMed: 33971177
DOI: 10.1016/j.ejphar.2021.174156 -
Expert Opinion on Drug Metabolism &... Feb 2018MDMA, 3,4-methylenedioxymethamphetamine, is a synthetic phenethylamine derivative with structural and pharmacological similarities to both amphetamines and mescaline.... (Review)
Review
MDMA, 3,4-methylenedioxymethamphetamine, is a synthetic phenethylamine derivative with structural and pharmacological similarities to both amphetamines and mescaline. MDMA produces characteristic amphetamine-like actions (euphoria, well-being), increases empathy, and induces pro-social effects that seem to motivate its recreational consumption and provide a basis for its potential therapeutic use. Areas covered: The aim of this review is to present the main interindividual determinants in MDMA pharmacodynamics. The principal sources of pharmacodynamic variability are reviewed, with special emphasis on sex-gender, race-ethnicity, genetic differences, interactions, and MDMA acute toxicity, as well as possible therapeutic use. Expert opinion: Acute MDMA effects are more pronounced in women than they are in men. Very limited data on the relationship between race-ethnicity and MDMA effects are available. MDMA metabolism includes some polymorphic enzymes that can slightly modify plasma concentrations and effects. Although a considerable number of studies exist about the acute effects of MDMA, the small number of subjects in each trial limits evaluation of the different interindividual factors and does not permit a clear conclusion about their influence. These issues should be considered when studying possible MDMA therapeutic use.
Topics: Animals; Drug Interactions; Ethnicity; Female; Hallucinogens; Humans; Male; N-Methyl-3,4-methylenedioxyamphetamine; Racial Groups; Serotonin Agents; Sex Factors; Substance-Related Disorders
PubMed: 29303006
DOI: 10.1080/17425255.2018.1424832 -
ACS Chemical Neuroscience Oct 2018Better known as "ecstasy", 3,4-methylenedioxymethamphetamine (MDMA) is a small molecule that has played a prominent role in defining the ethos of today's teenagers and... (Review)
Review
Better known as "ecstasy", 3,4-methylenedioxymethamphetamine (MDMA) is a small molecule that has played a prominent role in defining the ethos of today's teenagers and young adults, much like lysergic acid diethylamide (LSD) did in the 1960s. Though MDMA possesses structural similarities to compounds like amphetamine and mescaline, it produces subjective effects that are unlike any of the classical psychostimulants or hallucinogens and is one of the few compounds capable of reliably producing prosocial behavioral states. As a result, MDMA has captured the attention of recreational users, the media, artists, psychiatrists, and neuropharmacologists alike. Here, we detail the synthesis of MDMA as well as its pharmacology, metabolism, adverse effects, and potential use in medicine. Finally, we discuss its history and why it is perhaps the most important compound for the future of psychedelic science-having the potential to either facilitate new psychedelic research initiatives, or to usher in a second Dark Age for the field.
Topics: Hallucinogens; History, 20th Century; History, 21st Century; Humans; N-Methyl-3,4-methylenedioxyamphetamine
PubMed: 30001118
DOI: 10.1021/acschemneuro.8b00155 -
Neurochemistry International Feb 20223,4-methylenedioxymethamphetamine (MDMA) is a world-wide abused psychostimulant, which has the neurotoxic effects on dopaminergic and serotonergic neurons in both... (Review)
Review
3,4-methylenedioxymethamphetamine (MDMA) is a world-wide abused psychostimulant, which has the neurotoxic effects on dopaminergic and serotonergic neurons in both rodents and non-human primates. Adenosine acts as a neurotransmitter in the brain through the activation of four specific G-protein-coupled receptors and it acts as a neuromodulator of dopamine neurotransmission. Recent studies suggest that stimulation of adenosine receptors oppose many behavioral effects of methamphetamines. This review summarizes the specific cellular mechanisms involved in MDMA neuroinflammatory effects, along with the protective effects of adenosine receptors.
Topics: Animals; Brain; Central Nervous System Stimulants; Dopamine; Inflammation; N-Methyl-3,4-methylenedioxyamphetamine; Receptors, Purinergic P1
PubMed: 34990730
DOI: 10.1016/j.neuint.2021.105275 -
Laeknabladid May 2024MDMA is a potential novel treatment for post-traumatic stress disorder (PTSD). Our goal is to review current knowledge on MDMA and its use in MDMA-assisted psychotherapy... (Review)
Review
MDMA is a potential novel treatment for post-traumatic stress disorder (PTSD). Our goal is to review current knowledge on MDMA and its use in MDMA-assisted psychotherapy for PTSD. Literature searches were done on PubMed, Web of Science and Google Scholar and references reviewed in identified articles. MDMA-assisted therapy for PTSD usually consists of a few preparatory sessions before two or three sessions where one or two oral doses of MDMA are given along with supportive psychotherapy. The therapy is delivered in the presence of two therapists for about eight hours each time. In addition, the patient receives up to 9 integrative sessions in due course. This use of MDMA as a part of psychotherapy for PTSD is proposed to lessen the psychological distress that often arises in the processing of traumatic events to facilitate the treatment process and reduce the risk of drop-out. Recent studies indicate that MDMA-assisted psychotherapy reduces PTSD symptoms and is generally well tolerated. These studies are necessary if this MDMA-assisted treatment is to be approved by licensing authorities. There is an urgent need for new effective treatments for PTSD and for comparisons between this MDMA-assisted psychotherapy and currently approved psychotherapies with and without MDMA-use.
Topics: Humans; Stress Disorders, Post-Traumatic; Treatment Outcome; Psychotherapy; N-Methyl-3,4-methylenedioxyamphetamine; Hallucinogens; Combined Modality Therapy
PubMed: 38713560
DOI: 10.17992/lbl.2024.05.793 -
Brain Research May 2020Mephedrone and MDMA are both constituents of party drugs, with mephedrone being relatively new compared to MDMA. This review compares current knowledge regarding the... (Comparative Study)
Comparative Study Review
Mephedrone and MDMA are both constituents of party drugs, with mephedrone being relatively new compared to MDMA. This review compares current knowledge regarding the patterns of usage and neuropsychobiological effects of both mephedrone and MDMA. Both drugs share common psychoactive effects, the duration of which is significantly shorter with mephedrone use, attributing towards a pattern of binge use among users. Both drugs have also been associated with adverse health, psychiatric, and neurocognitive problems. Whilst there is extensive research into the psychobiological problems induced by MDMA, the evidence for mephedrone is comparatively limited. The adverse effect profile of mephedrone appears to be less severe than that of MDMA. Users often believe it to be safer, although both drugs have been associated with overdoses. The neurotoxic potential of mephedrone appears to be low, whereas MDMA can cause long-term damage to the serotonergic system, although this needs further investigation. The abuse liability of mephedrone is significantly greater than that of MDMA, raising concerns regarding the impact of lifetime usage on users. Given that mephedrone is relatively new, the effects of long-term exposure are yet to be documented. Future research focused on lifetime users may highlight more severe neuropsychobiological effects from the drug.
Topics: Brain; Humans; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Neurotoxicity Syndromes
PubMed: 32087112
DOI: 10.1016/j.brainres.2020.146740 -
Anasthesiologie, Intensivmedizin,... Feb 2017This case presents the clinical treatment of a patient with severe MDMA intoxication. The history of stimulating psychotropic substances is presented as well as the...
This case presents the clinical treatment of a patient with severe MDMA intoxication. The history of stimulating psychotropic substances is presented as well as the modes of action of current party drugs. Data from the Austrian Drug Report indicate a tendency away from "hard drugs" towards the consumption of cannabis and amphetamine derivates. The lethal outcome in our case demonstrates the risk potential of these substances and underlines the necessity of aggressive resuscitation efforts.
Topics: Drug Overdose; Fatal Outcome; Hallucinogens; Humans; Male; N-Methyl-3,4-methylenedioxyamphetamine; Resuscitation; Young Adult
PubMed: 28222475
DOI: 10.1055/s-0042-118022 -
Journal of the Neurological Sciences Aug 2022Post-traumatic stress disorder (PTSD) is a debilitating mental illness with limited treatment options and a high treatment dropout rate. Psychedelics, often in... (Review)
Review
Post-traumatic stress disorder (PTSD) is a debilitating mental illness with limited treatment options and a high treatment dropout rate. Psychedelics, often in combination with psychotherapy, are now under investigation as a potential treatment option for a variety of psychiatric conditions including PTSD. This paper reviews the proposed mechanism of action for 3,4-Methylenedioxymethamphetamine (MDMA) and classical psychedelics such as psilocybin in treating PTSD, along with available clinical evidence, safety and side effects. MDMA-assisted psychotherapy is in FDA phase III clinical trials for PTSD and is purported to work by way of increased empathy and decreased amygdala activation during the therapeutic encounter and trauma processing. Classical psychedelics may create change by a subjective transformative experience along with an observable process of brain network alterations, though these substances have not been clinically studied in the context PTSD. In recent human-subject studies MDMA-assisted therapy resulted in significant improvement in PTSD symptoms with a good safety and side effect profile. There is not yet direct clinical evidence for classical psychedelics in treating PTSD, but the evidence supports such a trial. The studies to date have been relatively small, and participants are wellscreened for potential co-morbidities which could increase the risks of psychedelic treatment. Nonetheless, the data is promising for psychedelic-assisted treatment to become a much-needed treatment option for PTSD.
Topics: Combined Modality Therapy; Hallucinogens; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Psychotherapy; Stress Disorders, Post-Traumatic
PubMed: 35700643
DOI: 10.1016/j.jns.2022.120302