An exploratory study of the safety profile and neurocognitive function after single doses of mitragynine in humans.

Rationale: Despite the growing scientific interest on mitragynine, the primary alkaloid in kratom (Mitragyna Speciosa), there is a lack of clinical trials in humans.

Objectives: This phase 1 study aimed to evaluate mitragynine's safety profile and acute effects on subjective drug experience, neurocognition, and pain tolerance.

Methods: A placebo-controlled, single-blind, within-subjects study was conducted in two parts.

Safety and cognitive pharmacodynamics following dose escalations with 3-methylmethcathinone (3-MMC): a first in human, designer drug study.

3-Methylmethcathinone (3-MMC) is a designer drug that belongs to the group of synthetic cathinones. The compound has been scheduled in many jurisdictions because of public health concerns associated with excessive use. To date, there are no clinical studies that have evaluated the risk profile of 3-MMC in the recreational range of low to moderate doses.

Visual hallucinations originating in the retinofugal pathway under clinical and psychedelic conditions.

Psychedelics like LSD (Lysergic acid diethylamide) and psilocybin are known to modulate perceptual modalities due to the activation of mostly serotonin receptors in specific cortical (e.g., visual cortex) and subcortical (e.

Effects of psychedelic microdosing versus conventional ADHD medication use on emotion regulation, empathy, and ADHD symptoms in adults with severe ADHD symptoms: A naturalistic prospective comparison study.

Adults with attention-deficit hyperactivity disorder (ADHD) often struggle with emotion regulation (ER), impacting their empathic skills and relationships. ADHD medication might not be as effective for ER issues as for ADHD symptoms. Microdosing (MD) psychedelics has shown promise for ADHD treatment and previous studies reported social-emotional benefits.

Trait mindfulness and personality characteristics in a microdosing ADHD sample: a naturalistic prospective survey study.

Background: Microdosing (MD), repeatedly taking psychedelics in small, non-hallucinogenic amounts, has been practiced by individuals to relieve attention deficit hyperactivity disorder (ADHD) symptoms. Generally, adults diagnosed with ADHD have lower levels of mindfulness and differ in personality structure from non-ADHD adults. How MD affects mindfulness and personality in adults with ADHD remains unexplored.

A Preliminary Inventory of Kratom Products and Vendors on the Darknet and Cryptomarkets.

In recent years, the online sale of kratom (), a Southeast Asian plant with both medicinal and psychoactive properties, has raised health concerns mainly due to the uncontrolled diffusion of adulterated kratom-related products. This exploratory study provides, for the first time, a snapshot of the availability of kratom products on the darknet which has been further validated by data searches on the surface web. A total of 231 listings of kratom across 23 darknet marketplaces were identified between March 2020 and October 2021.

MDMA-assisted psychotherapy for PTSD: Growing evidence for memory effects mediating treatment efficacy.

The application of MDMA in conjunction with psychotherapy has in recent years seen a resurgence of clinical, scientific, and public interest in the treatment of posttraumatic stress disorder (PTSD). Clinical trials have shown promising safety and efficacy, but the mechanisms underlying this treatment form remain largely unestablished. This article explores recent preclinical and clinical evidence suggesting that the treatment's efficacy may be influenced by the mnemonic effects of MDMA.

Potential analgesic effects of psychedelics on select chronic pain conditions: A survey study.

Background: Chronic pain is a major cause of suffering and disability and is often associated with psychiatric complications. Current treatments carry the risk of severe side effects and may lead to limited or no relief at all in a relevant portion of this patient population. Preliminary evidence suggests that classical psychedelics (e.

Clinical Implications of Kratom () Use: a Literature Review.

Purpose Of Review: This work aims to provide an up-to-date review of the preclinical and clinical scientific literature on the therapeutic value of kratom to better understand the underlying mechanisms related to its use and inform future therapeutic applications.

Recent Findings: A growing number of studies, mainly of cross-sectional nature, describe the widespread use of kratom by individuals to self-treat pain, psychiatric symptoms, and substance use disorders (SUD) outside a controlled clinical setting. Preclinical evidence suggests kratom is effective as an analgesic agent and might decrease the self-administration of other drugs.

Assessment of the Acute Effects of 2C-B vs. Psilocybin on Subjective Experience, Mood, and Cognition.

2,5-dimethoxy-4-bromophenethylamine (2C-B) is a hallucinogenic phenethylamine derived from mescaline. Observational and preclinical data have suggested it to be capable of producing both subjective and emotional effects on par with other classical psychedelics and entactogens. Whereas it is the most prevalently used novel serotonergic hallucinogen to date, it's acute effects and distinctions from classical progenitors have yet to be characterized in a controlled study.

Decreases in State and Trait Anxiety Post-psilocybin: A Naturalistic, Observational Study Among Retreat Attendees.

Anxiety disorders are the most common type of psychiatric disorders among Western countries. Evidence-based treatment modalities including pharmacological and cognitive-behavioral therapy result in deficient treatment responses. Historical and recent research suggests psychedelic drugs may be efficacious in alleviating anxiety-related symptoms among healthy and clinical populations.

Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls.

Psilocybin microdosing involves repeated self-administration of mushrooms containing psilocybin at doses small enough to not impact regular functioning. Microdose practices are diverse and include combining psilocybin with substances such as lion's mane mushrooms (Hericium erinaceus; HE) and niacin (vitamin-B3). Public uptake of microdosing has outpaced evidence, mandating further prospective research.

Psychedelic-Assisted Psychotherapy-A Systematic Review of Associated Psychological Interventions.

Modern clinical research on psychedelics is generating interesting outcomes in a wide array of clinical conditions when psychedelic-assisted psychotherapy is delivered to appropriately screened participants and in controlled settings. Still, a number of patients relapse or are less responsive to such treatments. Individual and contextual factors (i.

Don't be afraid, try to meditate- potential effects on neural activity and connectivity of psilocybin-assisted mindfulness-based intervention for social anxiety disorder: A systematic review.

Background: Current first-line treatment for social anxiety disorder (SAD), one of the most prevalent anxiety disorders, is limited in its efficacy. Hence, novel treatment approaches are urgently needed. The current review suggests a combination of meditation-based interventions and the administration of a psychedelic as a future alternative treatment approach.

A Comparison of Acute Neurocognitive and Psychotomimetic Effects of a Synthetic Cannabinoid and Natural Cannabis at Psychotropic Dose Equivalence.

Due to differences in potency, efficacy, and affinity for CB1 receptors, similarities and differences in psychoactive effect profiles of natural cannabis and synthetic cannabinoids (SCs) cannot reliably be derived from equipotent dose comparisons. Instead, the current study proposes to compare the intrinsic psychoactive effects of natural cannabis (THC) and an SC, JWH-018, at psychotropic dose equivalence. Participants from two placebo-controlled studies were matched for their levels of subjective high to compare neurocognitive and psychotomimetic effects of THC and JWH-018.

Self-Rated Recovery and Mood Before and After Resistance Training and Muscle Microcurrent Application.

Background: Resistance training (RT) can offer beneficial physiological and psychological effects. The regular continuation of this exercise can be accomplished by improving the recovery and mood after a workout. Frequency-specific microcurrent (microstimulation) might offer a solution here as it has been shown to improve physical injuries, mood state, and sleep.

Adults who microdose psychedelics report health related motivations and lower levels of anxiety and depression compared to non-microdosers.

The use of psychedelic substances at sub-sensorium 'microdoses', has gained popular academic interest for reported positive effects on wellness and cognition. The present study describes microdosing practices, motivations and mental health among a sample of self-selected microdosers (n = 4050) and non-microdosers (n = 4653) via a mobile application. Psilocybin was the most commonly used microdose substances in our sample (85%) and we identified diverse microdose practices with regard to dosage, frequency, and the practice of stacking which involves combining psilocybin with non-psychedelic substances such as Lion's Mane mushrooms, chocolate, and niacin.

Persisting Effects of Ayahuasca on Empathy, Creative Thinking, Decentering, Personality, and Well-Being.

Naturalistic and placebo-controlled studies have suggested that ayahuasca, a traditional Amazonian beverage, could be helpful in the treatment of psychopathologies like depression and anxiety disorders by changing otherwise disturbed cognitive and emotional processes. To better understand its full therapeutic potential, one way is to study the effects on processes like flexible thinking, empathy, and well-being, which are normally compromised in stress-related psychopathologies. Volunteers attending ayahuasca ceremonies were asked to complete a test battery at three separate occasions: baseline, the morning after, and 1 week after the ceremony.

Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics.

Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce cognitive, antidepressant, anxiolytic, and antiaddictive effects suggested to arise from biological changes similar to conventional antidepressants or the rapid-acting substance ketamine. The proposed route is by inducing brain neuroplasticity.

The effect of intranasally administered oxytocin on observed social behavior in social anxiety disorder.

Research has shown that patients with a social anxiety disorder (SAD) show social performance deficits. These deficits are a maintaining factor in SAD, as mending social behavior improves interpersonal judgments and reduces social anxiety. Thus finding ways to enhance social behavior is evidently of importance in the treatment of SAD.

A systematic review of (pre)clinical studies on the therapeutic potential and safety profile of kratom in humans.

Introduction: Kratom (Mitragyna speciosa) is a tropical plant traditionally used as an ethnomedicinal remedy for several conditions in South East Asia. Despite the increased interest in its therapeutical benefits in Western countries, little scientific evidence is available to support such claims, and existing data remain limited to kratom's chronic consumption.

Objective: Our study aims to investigate (pre)clinical evidence on the efficacy of kratom as a therapeutic aid and its safety profile in humans.

Low Doses of LSD Acutely Increase BDNF Blood Plasma Levels in Healthy Volunteers.

Despite preclinical evidence for psychedelic-induced neuroplasticity, confirmation in humans is grossly lacking. Given the increased interest in using low doses of psychedelics for psychiatric indications and the importance of neuroplasticity in the therapeutic response, this placebo-controlled within-subject study investigated the effect of single low doses of LSD (5, 10, and 20 μg) on circulating BDNF levels in healthy volunteers. Blood samples were collected every 2 h over 6 h, and BDNF levels were determined afterward in blood plasma using ELISA.

Psychotomimetic symptoms after a moderate dose of a synthetic cannabinoid (JWH-018): implications for psychosis.

Background: Synthetic cannabinoids (SCs) are the largest class of novel psychoactive substances (NPS) and are associated with an increased risk of overdosing and adverse events such as psychosis. JWH-018 is one of the earliest SCs and still widely available in large parts of the world. Controlled studies to assess the safety and behavioural profiles of SCs are extremely scarce.