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Pharmacology & Therapeutics Nov 2022Post-traumatic stress disorder (PTSD), characterized by abnormally persistent and distressing memories, is a chronic debilitating condition in need of new treatment... (Review)
Review
Post-traumatic stress disorder (PTSD), characterized by abnormally persistent and distressing memories, is a chronic debilitating condition in need of new treatment options. Current treatment guidelines recommend psychotherapy as first line management with only two drugs, sertraline and paroxetine, approved by U.S. Food and Drug Administration (FDA) for treatment of PTSD. These drugs have limited efficacy as they only reduce symptoms related to depression and anxiety without producing permanent remission. PTSD remains a significant public health problem with high morbidity and mortality requiring major advances in therapeutics. Early evidence has emerged for the beneficial effects of psychedelics particularly in combination with psychotherapy for management of PTSD, including psilocybin, MDMA, LSD, cannabinoids, ayahuasca and ketamine. MDMA and psilocybin reduce barrier to therapy by increasing trust between therapist and patient, thus allowing for modification of trauma related memories. Furthermore, research into the memory reconsolidation mechanisms has allowed for identification of various pharmacological targets to disrupt abnormally persistent memories. A number of pre-clinical and clinical studies have investigated novel and re-purposed pharmacological agents to disrupt fear memory in PTSD. Novel therapeutic approaches like neuropeptide Y, oxytocin, cannabinoids and neuroactive steroids have also shown potential for PTSD treatment. Here, we focus on the role of fear memory in the pathophysiology of PTSD and propose that many of these new therapeutic strategies produce benefits through the effect on fear memory. Evaluation of recent research findings suggests that while a number of drugs have shown promising results in preclinical studies and pilot clinical trials, the evidence from large scale clinical trials would be needed for these drugs to be incorporated in clinical practice.
Topics: United States; Humans; Stress Disorders, Post-Traumatic; N-Methyl-3,4-methylenedioxyamphetamine; Psilocybin; Fear; Cannabinoids
PubMed: 35489438
DOI: 10.1016/j.pharmthera.2022.108195 -
Revista Brasileira de Psiquiatria (Sao... 2021
Topics: Combined Modality Therapy; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Psychotherapy; Stress Disorders, Post-Traumatic
PubMed: 33053043
DOI: 10.1590/1516-4446-2020-0020 -
Psychopharmacology Mar 2019Current prevalence estimates of synthetic cathinone ("bath salt") use may be underestimates given that traditional metrics (e.g., surveys, urinalysis) often fail to... (Review)
Review
RATIONALE
Current prevalence estimates of synthetic cathinone ("bath salt") use may be underestimates given that traditional metrics (e.g., surveys, urinalysis) often fail to capture the emergent issue of synthetic cathinone adulteration of more common illegal drugs, such as ecstasy (3,4-methylenedioxymethamphetamine).
OBJECTIVES
This review examines the evolution of synthetic cathinones and prevalence of use over the past decade in the United States. We also review methods of self-report and biological testing of these compounds as well as adverse outcomes associated with adulterated drug use.
RESULTS
Synthetic cathinone use emerged in the United States by 2009 with use associated with tens of thousands of poisonings. Reported poisonings and self-reported use have substantially decreased over the past five years. However, our review suggests that current estimates of use are underestimates due to underreporting stemming primarily from unknown or unintentional use of adulterated formulations of relatively popular illegal drugs, such as ecstasy.
CONCLUSIONS
While intentional synthetic cathinone use has decreased in recent years, evidence suggests that prevalence of use is underestimated. Testing of drugs and/or biological specimens can improve the accuracy of synthetic cathinone use estimates. Furthermore, we advocate that researchers and clinicians should become better aware that exposure to these potent compounds (e.g., as adulterants) often occurs unknowingly or unintentionally. To improve our understanding of synthetic cathinone adulteration, research utilizing a combinatorial approach (survey and biological testing) will help more accurately estimate the prevalence and impact of this public health issue.
Topics: Alkaloids; Central Nervous System Stimulants; Drug Contamination; Humans; Illicit Drugs; N-Methyl-3,4-methylenedioxyamphetamine; Poison Control Centers; Prevalence; Self Report; Substance-Related Disorders; Surveys and Questionnaires; Synthetic Drugs; United States
PubMed: 30338489
DOI: 10.1007/s00213-018-5066-6 -
Tidsskrift For Den Norske Laegeforening... May 2022
Topics: Dangerous Behavior; Hallucinogens; Humans; N-Methyl-3,4-methylenedioxyamphetamine
PubMed: 35635415
DOI: 10.4045/tidsskr.22.0309 -
Neuropsychopharmacology : Official... Dec 2023There is renewed interest in the use of lysergic acid diethylamide (LSD) in psychiatric research and practice. Although acute subjective effects of LSD are mostly... (Randomized Controlled Trial)
Randomized Controlled Trial
There is renewed interest in the use of lysergic acid diethylamide (LSD) in psychiatric research and practice. Although acute subjective effects of LSD are mostly positive, negative subjective effects, including anxiety, may occur. The induction of overall positive acute subjective effects is desired in psychedelic-assisted therapy because positive acute experiences are associated with greater therapeutic long-term benefits. 3,4-Methylenedioxymethamphetamine (MDMA) produces marked positive subjective effects and is used recreationally with LSD, known as "candyflipping." The present study investigated whether the co-administration of MDMA can be used to augment acute subjective effects of LSD. We used a double-blind, randomized, placebo-controlled, crossover design with 24 healthy subjects (12 women, 12 men) to compare the co-administration of MDMA (100 mg) and LSD (100 µg) with MDMA and LSD administration alone and placebo. Outcome measures included subjective, autonomic, and endocrine effects and pharmacokinetics. MDMA co-administration with LSD did not change the quality of acute subjective effects compared with LSD alone. However, acute subjective effects lasted longer after LSD + MDMA co-administration compared with LSD and MDMA alone, consistent with higher plasma concentrations of LSD (C and area under the curve) and a longer plasma elimination half-life of LSD when MDMA was co-administered. The LSD + MDMA combination increased blood pressure, heart rate, and pupil size more than LSD alone. Both MDMA alone and the LSD + MDMA combination increased oxytocin levels more than LSD alone. Overall, the co-administration of MDMA (100 mg) did not improve acute effects or the safety profile of LSD (100 µg). The combined use of MDMA and LSD is unlikely to provide relevant benefits over LSD alone in psychedelic-assisted therapy. Trial registration: ClinicalTrials.gov identifier: NCT04516902.
Topics: Male; Humans; Female; N-Methyl-3,4-methylenedioxyamphetamine; Hallucinogens; Healthy Volunteers; Lysergic Acid Diethylamide; Double-Blind Method; Cross-Over Studies
PubMed: 37258715
DOI: 10.1038/s41386-023-01609-0 -
Acta Paediatrica (Oslo, Norway : 1992) Oct 2014Paediatric hyponatraemia is usually caused by an excess of antidiuretic hormone and may lead to serious neurological complications. It is challenging for clinicians to... (Review)
Review
AIM
Paediatric hyponatraemia is usually caused by an excess of antidiuretic hormone and may lead to serious neurological complications. It is challenging for clinicians to differentiate between conditions causing excess water and salt loss. This review analyses individual causes of hyponatraemia and focuses on optimal diagnostic algorithms and treatment strategies.
CONCLUSION
Correct evaluation of hyponatraemia requires proper understanding of the aetiology and appropriate management calls for a detailed history, physical examination and specific laboratory investigations.
Topics: Child; Exercise; Humans; Hyponatremia; Inappropriate ADH Syndrome; N-Methyl-3,4-methylenedioxyamphetamine; Water; Water Intoxication; Water-Electrolyte Balance
PubMed: 24862500
DOI: 10.1111/apa.12705 -
Current Psychiatry Reports Oct 2023This review discusses the current and projected landscape of psychedelic-assisted therapy (PAT), with a focus on clinical, legal, and implementation considerations in... (Review)
Review
PURPOSE OF REVIEW
This review discusses the current and projected landscape of psychedelic-assisted therapy (PAT), with a focus on clinical, legal, and implementation considerations in Department of Defense (DoD) and Department of Veterans Affairs (VA) healthcare systems.
RECENT FINDINGS
3,4-Methylenedioxymethamphetamine (MDMA)- and psilocybin-assisted therapy have shown promising outcomes in efficacy, safety, tolerability, and durability for PTSD and depression, respectively. MDMA-assisted therapy is already approved by the Food and Drug Administration (FDA) on an Expanded Access ("compassionate use") basis for PTSD, with full approval projected for 2024. Psilocybin-assisted therapy is projected to be FDA-approved for depression soon thereafter. Other psychedelics are in earlier stages of development. The VA is currently conducting PAT clinical trials. Although there are clear legal pathways for the VA and DoD to conduct PAT trials, a number of implementation barriers exist, such as the very high number of clinical hours necessary to treat each patient, resource requirements to support treatment infrastructure, military-specific considerations, and the high level of evidence necessary for PAT to be recommended in clinical practice guidelines. Ongoing considerations are whether and how PAT will be made available to VA and DoD beneficiaries, feasibility and cost-effectiveness, and ethical safeguards that must be implemented to prioritize access to PAT given the likelihood of extremely limited initial availability. However, with imminent FDA approval of PATs and considerable national interest in these treatments, DoD and VA policymakers must be prepared with clearly delineated policies and plans for how these healthcare systems will approach PAT.
Topics: United States; Humans; Veterans; Hallucinogens; N-Methyl-3,4-methylenedioxyamphetamine; Psilocybin; United States Department of Veterans Affairs; Delivery of Health Care
PubMed: 37682446
DOI: 10.1007/s11920-023-01446-4 -
The British Journal of Psychiatry : the... Jan 2015From its first use 3,4,-methylenedioxymethamphetamine (MDMA) has been recognised as a drug with therapeutic potential. Research on its clinical utility stopped when it...
From its first use 3,4,-methylenedioxymethamphetamine (MDMA) has been recognised as a drug with therapeutic potential. Research on its clinical utility stopped when it entered the recreational drug scene but has slowly resurrected in the past decade. Currently there is enough evidence for MDMA to be removed from its Schedule 1 status of 'no medical use' and moved into Schedule 2 (alongside other misused but useful medicines such as heroin and amphetamine). Such a regulatory move would liberate its use as a medicine for patients experiencing severe mental illnesses such as treatment-resistant post-traumatic stress disorder.
Topics: Humans; N-Methyl-3,4-methylenedioxyamphetamine; Stress Disorders, Post-Traumatic
PubMed: 25561485
DOI: 10.1192/bjp.bp.114.152751 -
Neuroscience and Biobehavioral Reviews Jan 2019In this meta-analysis, we aimed to assess the evidence from neuroimaging studies for chronic alterations in the brains of MDMA users. The databases PubMed, Embase, and... (Meta-Analysis)
Meta-Analysis Review
In this meta-analysis, we aimed to assess the evidence from neuroimaging studies for chronic alterations in the brains of MDMA users. The databases PubMed, Embase, and Web of Science were searched for studies published from inception to August 24, 2018, without any language restriction. Sixteen independent studies comprising 356 MDMA users and 311 controls were included. Of these, five studies investigated frontal and occipital N-acetylaspartate/creatine and myo-inositol/creatine ratios, three studies assessed basal ganglia blood flow and ten studies investigated serotonin transporter (SERT) density in various regions. We found significantly decreased SERT density in eight of 13 investigated regions. Meta-regression indicated a positive association with abstinence, but none with lifetime episodes of use. Therefore, other variables (such as doses taken per occasion) might be more important determinants. Positive associations between time of abstinence and SERT density might indicate that these alterations are reversible to some extent. Furthermore, there were no significant differences between user and control groups in terms of neurochemical ratios in the frontal and occipital lobes and blood flow in the basal ganglia. Overall, MDMA user groups showed heavy use patterns and study quality was poor.
Topics: Amphetamine-Related Disorders; Brain; Hallucinogens; Humans; N-Methyl-3,4-methylenedioxyamphetamine
PubMed: 30439373
DOI: 10.1016/j.neubiorev.2018.11.004 -
International Review of Psychiatry... May 2021This review examines the role of trauma in psychiatric morbidity and analogous psychoneurobiological changes. Trauma is a necessary criterion for Post-Traumatic Stress... (Review)
Review
This review examines the role of trauma in psychiatric morbidity and analogous psychoneurobiological changes. Trauma is a necessary criterion for Post-Traumatic Stress Disorder (PTSD), however, trauma history is highly correlated with a variety of psychiatric conditions. Some evidence suggests that Major Depressive Disorder (MDD) is the most common psychiatric condition that arises following trauma. Approximately 50% of PTSD cases present with co-morbid MDD. Overlapping symptomatology and neurobiology between these conditions underlie the debate over whether these phenomena result from problematic nosology or whether comorbid MDD + PTSD is a distinct phenotype of trauma-related psychopathology. Regardless, similar treatment approaches have been employed historically, with varying success. The drug-assisted psychotherapy treatment model, which combines pharmacological and psychotherapeutic approaches, is currently being trialled as a novel treatment approach in psychiatry. Both psilocybin- and 3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy have received Food and Drug Administration 'breakthrough therapy' designation for the treatment of resistant MDD and PTSD, respectively. This paper reviews the therapeutic rationale of both psilocybin and MDMA for treating both trauma-related MDD and PTSD.
Topics: Depressive Disorder, Major; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Psilocybin; Stress Disorders, Post-Traumatic; Treatment Outcome
PubMed: 34121583
DOI: 10.1080/09540261.2021.1919062