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Nutrients Sep 2021Sleep is an essential component of overall human health but is so tightly regulated that when disrupted can cause or worsen certain ailments. An important part of this... (Review)
Review
Sleep is an essential component of overall human health but is so tightly regulated that when disrupted can cause or worsen certain ailments. An important part of this process is the presence of the well-known hormone, melatonin. This compound assists in the governing of sleep and circadian rhythms. Previous studies have postulated that dysregulation of melatonin rhythms is the driving force behind sleep and circadian disorders. A computer-aided search spanning the years of 2015-2020 using the search terms melatonin, circadian rhythm, disorder yielded 52 full text articles that were analyzed. We explored the mechanisms behind melatonin dysregulation and how it affects various disorders. Additionally, we examined associated therapeutic treatments including bright light therapy (BLT) and exogenous forms of melatonin. We found that over the past 5 years, melatonin has not been widely investigated in clinical studies thus there remains large gaps in its potential utilization as a therapy.
Topics: Animals; Biosynthetic Pathways; Circadian Rhythm; Humans; Light; Melatonin; Transcription, Genetic
PubMed: 34684482
DOI: 10.3390/nu13103480 -
Molecules (Basel, Switzerland) May 2021The psychedelic effects of some plants and fungi have been known and deliberately exploited by humans for thousands of years. Fungi, particularly mushrooms, are the... (Review)
Review
The psychedelic effects of some plants and fungi have been known and deliberately exploited by humans for thousands of years. Fungi, particularly mushrooms, are the principal source of naturally occurring psychedelics. The mushroom extract, psilocybin has historically been used as a psychedelic agent for religious and spiritual ceremonies, as well as a therapeutic option for neuropsychiatric conditions. Psychedelic use was largely associated with the "hippie" counterculture movement, which, in turn, resulted in a growing, and still lingering, negative stigmatization for psychedelics. As a result, in 1970, the U.S. government rescheduled psychedelics as Schedule 1 drugs, ultimately ending scientific research on psychedelics. This prohibition on psychedelic drug research significantly delayed advances in medical knowledge on the therapeutic uses of agents such as psilocybin. A 2004 pilot study from the University of California, Los Angeles, exploring the potential of psilocybin treatment in patients with advanced-stage cancer managed to reignite interest and significantly renewed efforts in psilocybin research, heralding a new age in exploration for psychedelic therapy. Since then, significant advances have been made in characterizing the chemical properties of psilocybin as well as its therapeutic uses. This review will explore the potential of psilocybin in the treatment of neuropsychiatry-related conditions, examining recent advances as well as current research. This is not a systematic review.
Topics: Biomedical Research; Clinical Studies as Topic; Hallucinogens; Humans; Mental Disorders; Molecular Structure; Neoplasms; Psilocybin
PubMed: 34063505
DOI: 10.3390/molecules26102948 -
Neuropsychopharmacology : Official... Jan 2023Classic psychedelics, such as LSD, psilocybin, and the DMT-containing beverage ayahuasca, show some potential to treat depression, anxiety, and addiction. Importantly,... (Review)
Review
Classic psychedelics, such as LSD, psilocybin, and the DMT-containing beverage ayahuasca, show some potential to treat depression, anxiety, and addiction. Importantly, clinical improvements can last for months or years after treatment. It has been theorized that these long-term improvements arise because psychedelics rapidly and lastingly stimulate neuroplasticity. The focus of this review is on answering specific questions about the effects of psychedelics on neuroplasticity. Firstly, we review the evidence that psychedelics promote neuroplasticity and examine the cellular and molecular mechanisms behind the effects of different psychedelics on different aspects of neuroplasticity, including dendritogenesis, synaptogenesis, neurogenesis, and expression of plasticity-related genes (e.g., brain-derived neurotrophic factor and immediate early genes). We then examine where in the brain psychedelics promote neuroplasticity, particularly discussing the prefrontal cortex and hippocampus. We also examine what doses are required to produce this effect (e.g., hallucinogenic doses vs. "microdoses"), and how long purported changes in neuroplasticity last. Finally, we discuss the likely consequences of psychedelics' effects on neuroplasticity for both patients and healthy people, and we identify important research questions that would further scientific understanding of psychedelics' effects on neuroplasticity and its potential clinical applications.
Topics: Humans; Hallucinogens; Psilocybin; Anxiety; Neuronal Plasticity; Anxiety Disorders
PubMed: 36123427
DOI: 10.1038/s41386-022-01389-z -
Neurologia Sep 2022Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in... (Review)
Review
Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in its use as a treatment for insomnia. Moreover, as production of the hormone decreases with age, in inverse correlation with the frequency of poor sleep quality, it has been suggested that melatonin deficit is at least partly responsible for sleep disorders. Treating this age-related deficit would therefore appear to be a natural way of restoring sleep quality, which is lost as patients age. However, despite the undeniable theoretical appeal of this approach to insomnia, little scientific evidence is available that supports any benefit of this substitutive therapy. Furthermore, the most suitable dose ranges and pharmaceutical preparations for melatonin administration are yet to be clearly defined. This review addresses the physiology of melatonin, the different pharmaceutical preparations, and data on its clinical usefulness.
Topics: Humans; Melatonin; Pharmaceutical Preparations; Sleep; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders
PubMed: 36064286
DOI: 10.1016/j.nrleng.2018.08.004 -
Drugs Jan 2022Cluster headache belongs to the group of trigeminal autonomic headaches. This review summarizes drug therapy of cluster attacks and prophylactic treatment.... (Review)
Review
Cluster headache belongs to the group of trigeminal autonomic headaches. This review summarizes drug therapy of cluster attacks and prophylactic treatment. Neurostimulation methods are not addressed. The therapy for acute cluster attacks includes inhalation of 100% oxygen, subcutaneous administration of sumatriptan, and intranasal application of sumatriptan or zolmitriptan. Bridging therapy, which is used until oral prophylactic therapy is effective, is performed either with oral prednisolone or with a pharmacological block of the major occipital nerves. Best documented drugs for preventive treatment of cluster headache are verapamil and lithium, and possibly effective drugs are gabapentin, topiramate, divalproex sodium, and melatonin. The efficacy of monoclonal antibodies to the calcitonin gene-related peptide so far has been only demonstrated for episodic cluster headache. Several drug therapies are being investigated including ketamine, onabotulinumtoxinA, lysergic acid, and sodium oxybate.
Topics: Cluster Headache; Drug Administration Routes; Humans; Lithium; Oxazolidinones; Oxygen Inhalation Therapy; Prednisolone; Serotonin 5-HT1 Receptor Agonists; Sumatriptan; Tryptamines; Verapamil
PubMed: 34919214
DOI: 10.1007/s40265-021-01658-z -
Psychedelics: Alternative and Potential Therapeutic Options for Treating Mood and Anxiety Disorders.Molecules (Basel, Switzerland) Apr 2022The word "psychedelic" (psyche (i.e., the mind or soul) and delos (i.e., to show)) has Greek origin and was first coined by psychiatrist Humphry Osmond in 1956, who had... (Review)
Review
The word "psychedelic" (psyche (i.e., the mind or soul) and delos (i.e., to show)) has Greek origin and was first coined by psychiatrist Humphry Osmond in 1956, who had been conducting research on lysergic acid diethylamide (LSD) at the time. Psychedelic drugs such as ,-DMT/DMT (,-dimethyltryptamine), 5-MeO-DMT (5-methoxy-,-dimethyltryptamine), LSD (lysergic acid diethylamide), MDMA (3,4-methylenedioxymethamphetamine) and psilocybin have had significant value as an entheogen in spiritual, religious (shamanic) and sociocultural rituals in Central and South American cultures for thousands of years. In the 1960s, the globalization of these drugs and their subsequent spread outside of their indigenous, old-world cultures, led to the subsequent implementation of strict drug control laws in many Western countries. Even today, psychedelics are still classified as Schedule I drugs, resulting in a still lingering negative stigmatization/perception, vilification, and ultimate criminalization of psychedelics. This controversy still lingers and still limits scientific research and full medical acceptance. For many years up until recently, the spiritual, religious and medicinal value of these drugs could not be explored in a scientific context. More recently, a second wave of psychedelic research is now focusing on psychedelics as neuropharmaceuticals to treat alcohol and tobacco addiction, general mood and anxiety disorders and cancer-related depression. There is now a vast array of promising evidence-based data to confirm the years of anecdotal evidence of the medicinal values of psychedelics. Natural therapeutic alternatives such as psychedelic drugs may provide a safe and efficacious alternate to conventional drugs used to treat mood and anxiety disorders. In a Western context in particular, psychedelic drugs as therapeutic agents for mood and anxiety disorders are becoming increasingly of interest amidst increasing rates of such disorders globally, changing social constructions, the implementation of government regulations and increasing investment opportunities, that ultimately allow for the scientific study to generate evidenced-based data. Alternative psychotherapeutic interventions are gaining interest also, because of their low physiological toxicity, relatively low abuse potential, safe psychological effects, and no associated persisting adverse physiological or psychological effects during and after use. On the other hand, conventional psychotic drugs and anti-depressants are becoming less favorable because of their adverse side effects. Psychedelic neuropharmaceutical interventions may with medical oversight be the solution to conventional psychiatric disorders such as depression and anxiety, and an alternative to conventional psychiatric treatment options. This paper will review the therapeutic potential of psychedelic drugs as alternative therapeutic options for mood and anxiety disorders in a controlled, clinical setting, where the chances of adverse psychological episodes occurring are mitigated.
Topics: Anxiety Disorders; Hallucinogens; Humans; Lysergic Acid Diethylamide; N,N-Dimethyltryptamine; N-Methyl-3,4-methylenedioxyamphetamine; Psilocybin
PubMed: 35458717
DOI: 10.3390/molecules27082520 -
JAMA Jun 2021Migraine is common and can be associated with significant morbidity, and several treatment options exist for acute therapy. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Migraine is common and can be associated with significant morbidity, and several treatment options exist for acute therapy.
OBJECTIVE
To evaluate the benefits and harms associated with acute treatments for episodic migraine in adults.
DATA SOURCES
Multiple databases from database inception to February 24, 2021.
STUDY SELECTION
Randomized clinical trials and systematic reviews that assessed effectiveness or harms of acute therapy for migraine attacks.
DATA EXTRACTION AND SYNTHESIS
Independent reviewers selected studies and extracted data. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction or by using a fixed-effect model based on the Mantel-Haenszel method if the number of studies was small.
MAIN OUTCOMES AND MEASURES
The main outcomes included pain freedom, pain relief, sustained pain freedom, sustained pain relief, and adverse events. The strength of evidence (SOE) was graded with the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews.
FINDINGS
Evidence on triptans and nonsteroidal anti-inflammatory drugs was summarized from 15 systematic reviews. For other interventions, 115 randomized clinical trials with 28 803 patients were included. Compared with placebo, triptans and nonsteroidal anti-inflammatory drugs used individually were significantly associated with reduced pain at 2 hours and 1 day (moderate to high SOE) and increased risk of mild and transient adverse events. Compared with placebo, calcitonin gene-related peptide receptor antagonists (low to high SOE), lasmiditan (5-HT1F receptor agonist; high SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE), acetaminophen (moderate SOE), antiemetics (low SOE), butorphanol (low SOE), and tramadol in combination with acetaminophen (low SOE) were significantly associated with pain reduction and increase in mild adverse events. The findings for opioids were based on low or insufficient SOE. Several nonpharmacologic treatments were significantly associated with improved pain, including remote electrical neuromodulation (moderate SOE), transcranial magnetic stimulation (low SOE), external trigeminal nerve stimulation (low SOE), and noninvasive vagus nerve stimulation (moderate SOE). No significant difference in adverse events was found between nonpharmacologic treatments and sham.
CONCLUSIONS AND RELEVANCE
There are several acute treatments for migraine, with varying strength of supporting evidence. Use of triptans, nonsteroidal anti-inflammatory drugs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments was associated with improved pain and function. The evidence for many other interventions, including opioids, was limited.
Topics: Analgesics; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Antiemetics; Calcitonin Gene-Related Peptide Receptor Antagonists; Electric Stimulation Therapy; Ergot Alkaloids; Evidence-Based Medicine; Humans; Migraine Disorders; Pain Measurement; Serotonin Receptor Agonists; Tryptamines
PubMed: 34128998
DOI: 10.1001/jama.2021.7939 -
JAMA Network Open Oct 2021New therapeutic classes of migraine-specific treatment have been developed, including 5-hydroxytryptamine1F receptor agonists (lasmiditan) and calcitonin gene-related... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
New therapeutic classes of migraine-specific treatment have been developed, including 5-hydroxytryptamine1F receptor agonists (lasmiditan) and calcitonin gene-related peptide antagonists (rimegepant and ubrogepant).
OBJECTIVE
To compare outcomes associated with the use of lasmiditan, rimegepant, and ubrogepant vs triptans for acute management of migraine headaches.
DATA SOURCES
The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to March 5, 2020.
STUDY SELECTION
Double-blind randomized clinical trials examining current available migraine-specific acute treatments were included.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was applied to extract the data according to a predetermined list of variables of interest, and all network meta-analyses were conducted using a random-effects model.
MAIN OUTCOMES AND MEASURES
The primary outcome was the odds ratio (OR) for freedom from pain (hereafter referred to as pain freedom) at 2 hours after the dose, and the secondary outcomes were ORs for pain relief at 2 hours after the dose and any adverse events.
RESULTS
A total of 64 randomized clinical trials were included (46 442 participants; 74%-87% women; age range, 36-43 years). Most of the included treatments were associated with reduced pain at 2 hours compared with placebo. Most triptans were associated with higher ORs for pain freedom at 2 hours compared with lasmiditan (range: OR, 1.72 [95% CI, 1.06-2.80] to OR, 3.40 [95% CI, 2.12-5.44]), rimegepant (range: OR, 1.58 [95% CI, 1.07-2.33] to OR, 3.13 [95% CI, 2.16-4.52]), and ubrogepant (range: OR, 1.54 [95% CI, 1.00-2.37] to OR, 3.05 [95% CI, 2.02-4.60]). Most triptans were associated with higher ORs for pain relief at 2 hours compared with lasmiditan (range: OR, 1.46 [95% CI, 1.09-1.96] to OR, 3.31 [95% CI, 2.41-4.55]), rimegepant (range: OR, 1.33 [95% CI, 1.01-1.76] to OR, 3.01 [95% CI, 2.33-3.88]), and ubrogepant (range: OR, 1.38 [95% CI, 1.02-1.88] to OR, 3.13 [95% CI, 2.35-4.15]). The comparisons between lasmiditan, rimegepant, and ubrogepant were not statistically significant for both pain freedom and pain relief at 2 hours. Lasmiditan was associated with the highest risk of any adverse events, and certain triptans (rizatriptan, sumatriptan, and zolmitriptan) were also associated with a higher risk of any adverse events than the calcitonin gene-related peptide antagonists.
CONCLUSIONS AND RELEVANCE
For pain freedom or pain relief at 2 hours after the dose, lasmiditan, rimegepant, and ubrogepant were associated with higher ORs compared with placebo but lower ORs compared with most triptans. However, the lack of cardiovascular risks for these new classes of migraine-specific treatments may offer an alternative to triptans.
Topics: Adult; Female; Humans; Male; Migraine Disorders; Tryptamines
PubMed: 34633423
DOI: 10.1001/jamanetworkopen.2021.28544 -
Current Neuropharmacology 2023The use of exogenous melatonin (exo-MEL) as a sleep-promoting drug has been under extensive debate due to the lack of consistency of its described effects. In this... (Review)
Review
The use of exogenous melatonin (exo-MEL) as a sleep-promoting drug has been under extensive debate due to the lack of consistency of its described effects. In this study, we conduct a systematic and comprehensive review of the literature on the chronobiotic, sleep-inducing, and overall sleep-promoting properties of exo-MEL. To this aim, we first describe the possible pharmacological mechanisms involved in the sleep-promoting properties and then report the corresponding effects of exo-MEL administration on clinical outcomes in: a) healthy subjects, b) circadian rhythm sleep disorders, c) primary insomnia. Timing of administration and doses of exo-MEL received particular attention in this work. The exo-MEL pharmacological effects are hereby interpreted in view of changes in the physiological properties and rhythmicity of endogenous melatonin. Finally, we discuss some translational implications for the personalized use of exo-MEL in the clinical practice.
Topics: Humans; Melatonin; Circadian Rhythm; Sleep
PubMed: 35176989
DOI: 10.2174/1570159X20666220217152617 -
International Journal of Molecular... Dec 2022Anxiety disorders are the most common mental diseases. Anxiety and the associated physical symptoms may disturb social and occupational life and increase the risk of... (Review)
Review
Anxiety disorders are the most common mental diseases. Anxiety and the associated physical symptoms may disturb social and occupational life and increase the risk of somatic diseases. The pathophysiology of anxiety development is complex and involves alterations in stress hormone production, neurosignaling pathways or free radical production. The various manifestations of anxiety, its complex pathophysiological background and the side effects of available treatments underlie the quest for constantly seeking therapies for these conditions. Melatonin, an indolamine produced in the pineal gland and released into the blood on a nightly basis, has been demonstrated to exert anxiolytic action in animal experiments and different clinical conditions. This hormone influences a number of physiological actions either via specific melatonin receptors or by receptor-independent pleiotropic effects. The underlying pathomechanism of melatonin's benefit in anxiety may reside in its sympatholytic action, interaction with the renin-angiotensin and glucocorticoid systems, modulation of interneuronal signaling and its extraordinary antioxidant and radical scavenging nature. Of importance, the concentration of this indolamine is significantly higher in cerebrospinal fluid than in the blood. Thus, ensuring sufficient melatonin production by reducing light pollution, which suppresses melatonin levels, may represent an endogenous neuroprotective and anxiolytic treatment. Since melatonin is freely available, economically undemanding and has limited side effects, it may be considered an additional or alternative treatment for various conditions associated with anxiety.
Topics: Animals; Melatonin; Anti-Anxiety Agents; Antioxidants; Free Radicals; Anxiety
PubMed: 36555831
DOI: 10.3390/ijms232416187