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. METHODS: A systematic literature search using PubMed and the Medline database was conducted between April and November 2020. RESULTS: Both preclinical (N = 57) and clinical (N = 18) studies emerged from our search. Preclinical data indicated a therapeutic value in terms of acute/chronic pain (N = 23), morphine/ethanol withdrawal, and dependence (N = 14), among other medical conditions (N = 26). Clinical data included interventional studies (N = 2) reporting reduced pain sensitivity, and observational studies (N = 9) describing the association between kratom's chronic (daily/frequent) use and safety issues, in terms of health consequences (e.g., learning impairment, high cholesterol level, dependence/withdrawal). CONCLUSIONS: Although the initial (pre)clinical evidence on kratom's therapeutic potential and its safety profile in humans is encouraging, further validation in large, controlled clinical trials is required.

Motives and Side-Effects of Microdosing With Psychedelics Among Users.

BACKGROUND: Microdosing with psychedelics has gained considerable media attention where it is portrayed as a performance enhancer, especially popular on the work floor. While reports are in general positive, scientific evidence about potential negative effects is lacking aside from the prevalence and motives for use. The present study addressed this gap by surveying psychedelic users about their experience with microdosing including their dosing schedule, motivation, and potential experienced negative effects. METHODS: An online questionnaire was launched on several websites and fora between March and July 2018. Respondents who had consented, were 18 years of age or older, and had experience with microdosing were included in the analyses. RESULTS: In total, 1116 of the respondents were either currently microdosing (79.5%) or microdosed in the past (20.5%). Lysergic acid diethylamide (10 mcg) and psilocybin (0.5 g) were the most commonly used psychedelics with a microdosing frequency between 2 and 4 times per week. The majority of users, however, were oblivious about the consumed dose. Performance enhancement was the main motive to microdose (37%). The most reported negative effects were of psychological nature and occurred acutely while under the influence. CONCLUSION: In line with media reports and anecdotes, the majority of our respondents microdosed to enhance performance. Negative effects occurred mostly acutely after substance consumption. However, the main reason to have stopped microdosing was that it was not effective. Future experimental placebo-controlled studies are needed to test whether performance enhancement can be quantified and to assess potential negative effects after longer term microdosing.

Independent elevation of peripheral oxytocin concentrations and reduction in cognitive empathy during 4-fluoroamphetamine intoxication.

OBJECTIVES: 4-Fluoroamphetamine (4-FA) is a novel psychoactive substance with a pharmacological profile and reported subjective effects (e.g., empathy) intermediate between 3,4-methylenedioxymethamphetamine (MDMA) and amphetamine. Studies have shown that MDMA and amphetamine increase emotional empathy without affecting cognitive empathy; MDMA simultaneously leads to elevated levels of oxytocin, unrelated to its behavioral effects. The aim of the present study was to assess the reported enhancement of empathy by 4-FA, to assess its effects on oxytocin, and to test potential associations between both. METHODS: Twelve healthy poly-drug users were included in a double-blind placebo-controlled two-way crossover study. Treatments were 4-FA (100 mg) and placebo; empathy was assessed by means of the multifaceted empathy test, and blood samples were taken before and after treatment administration to determine oxytocin concentrations. RESULTS: 4-FA reduced cognitive empathy, whereas emotional empathy was left unaffected. One hour after treatment, plasma oxytocin levels were significantly increased compared with placebo. Behavioral and hormonal effects were unrelated. CONCLUSION: Although 4-FA shares its pharmacological mechanism with MDMA and amphetamine, current findings seem to indicate that it affects empathy differently. The 4-FA-induced increase in oxytocin levels was independent of behavioral effects, which confirms previous findings that drug-induced effects on peripheral oxytocin levels are not associated with empathy.

Brain reactivity to alcohol and cannabis marketing during sobriety and intoxication.

Drugs of abuse stimulate striatal dopamine release and activate reward pathways. This study examined the impact of alcohol and cannabis marketing on the reward circuit in alcohol and cannabis users while sober and intoxicated. It was predicted that alcohol and cannabis marketing would increase striatal activation when sober and that reward sensitivity would be less during alcohol and cannabis intoxication. Heavy alcohol (n = 20) and regular cannabis users (n = 21) participated in a mixed factorial study involving administration of alcohol and placebo in the alcohol group and cannabis and placebo in the cannabis group. Non-drug users (n = 20) served as between group reference. Brain activation after exposure to alcohol and cannabis marketing movies was measured using functional magnetic resonance imaging and compared between groups while sober and compared with placebo while intoxicated. Implicit alcohol and cannabis cognitions were assessed by means of a single-category implicit association test. Alcohol and cannabis marketing significantly increased striatal BOLD activation across all groups while sober. Striatal activation however decreased during intoxication with alcohol and cannabis. Implicit associations with cannabis marketing cues were significantly more positive in alcohol and cannabis users as compared with non-drug using controls. Public advertising of alcohol or cannabis use elicits striatal activation in the brain's reward circuit. Reduction of marketing would reduce brain exposure to reward cues that motivate substance use. Conversely, elevated dopamine levels protect against the reinforcing potential of marketing.

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.g., thalamus) regions of the brain. In the visual domain, these psychedelic modulations often result in peculiar disturbances of viewed objects and light and sometimes even in hallucinations of non-existent environments, objects, and creatures. Although the underlying processes are poorly understood, research conducted over the past twenty years on the subjective experience of psychedelics details theories that attempt to explain these perceptual alterations due to a disruption of communication between cortical and subcortical regions. However, rare medical conditions in the visual system like Charles Bonnet syndrome that cause perceptual distortions may shed new light on the additional importance of the retinofugal pathway in psychedelic subjective experiences. Interneurons in the retina called amacrine cells could be the first site of visual psychedelic modulation and aid in disrupting the hierarchical structure of how humans perceive visual information. This paper presents an understanding of how the retinofugal pathway communicates and modulates visual information in psychedelic and clinical conditions. Therefore, we elucidate a new theory of psychedelic modulation in the retinofugal pathway.

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. Two online prospective studies investigated MD effects on ER and empathy in adults with severe ADHD symptoms across three assessments: baseline, two-, and four-week post-initiation. Study 1 examined adults initiating MD on their own (n = 233, n = 64, and n = 44) and found positive effects on ER (cognitive reappraisal and expressive suppression) and aspects of empathy (perspective-taking and personal distress). Study 2, including a control group and an ADHD symptom scale, compared individuals only MD (n = 180, n = 50, and n = 38) to individuals using conventional ADHD medication (n = 37, n = 27, and n = 28). After 4 weeks, ADHD symptoms were lower in the MD group. Only improvements in expressive suppression persisted after adding the control group. This study indicates the positive effects of MD psychedelics on ADHD symptoms and ER in adults with severe ADHD symptoms while lacking evidence for effects on empathy.

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.g. LSD and psilocybin) may have analgesic effects in healthy volunteers, and in certain chronic pain conditions and observational studies reveal that they are used in naturalistic settings as a means to manage pain. METHODS: In order to gain insight on the effectiveness of such compounds in chronic pain conditions, we set up a survey addressed to chronic pain patients inquiring about psychedelic use and the relief levels achieved with both conventional treatments, full psychedelic doses and microdoses. We analysed data related to five conditions selected based on diagnostic homogeneity within each of them: fibromyalgia, arthritis, migraine, tension-type headache and sciatica. RESULTS: Except for sciatica, volunteers reported that psychedelics led to better pain relief compared to conventional medication in all examined conditions. More specifically, full doses performed better than conventional medication. Microdoses led to significantly better relief compared to conventional medication in migraines and achieved comparable relief in the remaining three categories. Implications for future research are discussed. CONCLUSIONS: Full doses and microdoses may hold value in the treatment of some specific chronic pain conditions. SIGNIFICANCE: Psychedelic substances are receiving increasing attention from the scientific literature because of evidence showing beneficial effects on several measures related to mental health in clinical samples and healthy volunteers samples. Previous evidence suggests that people suffering from chronic pain are using psychedelics to seek relief and the present paper presents the results of a survey study investigating their use and analgesic effects among individuals suffering from fibromyalgia, arthritis, migraine, tension-type headache and sciatica.

Inter-individual variability in neural response to low doses of LSD.

The repeated use of small doses of psychedelics (also referred to as "microdosing") to facilitate benefits in mental health, cognition, and mood is a trending practice. Placebo-controlled studies however have largely failed to demonstrate strong benefits, possibly because of large inter-individual response variability. The current study tested the hypothesis that effects of low doses of LSD on arousal, attention and memory depend on an individual's cognitive state at baseline. Healthy participants (N = 53) were randomly assigned to receive repeated doses of LSD (15 mcg) or placebo on 4 occasions divided over 2 weeks. Each treatment condition also consisted of a baseline and a 1-week follow-up visit. Neurophysiological measures of arousal (resting state EEG), pre-attentive processing (auditory oddball task), and perceptual learning and memory (visual long-term potentiation (LTP) paradigm) were assessed at baseline, dosing session 1 and 4, and follow-up. LSD produced stimulatory effects as reflected by a reduction in resting state EEG delta, theta, and alpha power, and enhanced pre-attentive processing during the acute dosing sessions. LSD also blunted the induction of LTP on dosing session 4. Stimulatory effects of LSD were strongest in individuals with low arousal and attention at baseline, while inhibitory effects were strongest in high memory performers at baseline. Decrements in delta EEG power and enhanced pre-attentive processing in the LSD treatment condition were still present during the 1-week follow-up. The current study demonstrates across three cognitive domains, that acute responses to low doses of LSD depend on the baseline state and provides some support for LSD induced neuroadaptations that sustain beyond treatment.

Fungi as a source of bioactive molecules for the development of longevity medicines.

Age-related loss of function brings age-related disease, and therefore it is of primary importance to search for interventions that can help minimize detrimental symptoms people deal with in old age. Fungi have always been given a great deal of attention and reverence in traditional medical practices for their ability to minimize harmful symptoms of diseases. More recently, the role of fungi in influencing healthspan and lifespan is being directly studied in the lab. To treat animal model organisms with fungi-derived molecules, extractions from different life cycle stages of fungi are performed. This includes mycelium (the vegetative stage), sporocarps (the reproductive stage), or spores (the end product of the reproductive stage), and each stage provides a variety of bioactive compounds. These bioactive compounds include glycoproteins, polysaccharides, triterpenoids, meroterpenoids, sesquiterpenoids, steroids, alkaloids, benzopyran derivatives, and benzoic acid derivatives, amongst others. In this work, we review evidence that fungal extracts from multiple species can have beneficial effects on the lifespan and healthspan of model organisms, such as C. elegans worms, D. melanogaster flies, and M. musculus mice. We cover extraction methods and lifespan effects of Ganoderma lucidum (i.e. Reishi), Lentinula edodes (i.e. Shiitake), the genus Auricularia (i.e. jelly ear mushrooms), the genera Cordyceps and Ophiocordyceps (e.g. the caterpillar fungi), Hericium erinaceus (i.e. Lion's mane), the mold genus Monascus, and also Inonotus obliquus (i.e. Chaga), Grifola frondosa (i.e. Maitake or hen-of-the-woods), the genus Pleurotus (e.g. oyster mushrooms), and Agaricus subrufescens (i.e. the almond mushroom). We propose that further research on fungal extracts will provide a greater picture of the role fungi-derived bioactive molecules can have in developing longevity and neuroprotective medicines for humans.

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. Aim: This study aimed to investigate the effects of 4 weeks of MD on mindfulness and personality traits in adults diagnosed with ADHD and those experiencing severe ADHD symptoms. It was expected that mindfulness and the personality traits conscientiousness, extraversion, agreeableness, and openness would increase and neuroticism would decrease after 4 weeks of MD compared to baseline. It was explored if using conventional ADHD medication alongside MD and/or having comorbidities influenced MD-induced effects. Methods: An online prospective naturalistic design was used to measure participants before MD initiation and 2 and 4 weeks later. Validated self-report measures were used assessing mindfulness (15-item Five Facet Mindfulness Questionnaire) and personality traits (10-item version of the Big Five Inventory) at three time points. Results: The sample included n = 233, n = 66, and n = 44 participants at the three time points, respectively. Trait mindfulness, specifically description and non-judging of inner experience, was increased, and neuroticism was decreased after 4 weeks of MD compared to baseline. The remaining personality traits remained unchanged. Using conventional medication and/or having comorbid diagnoses did not change the MD-induced effects on mindfulness and personality traits after 4 weeks. Conclusion: MD induced changes in otherwise stable traits. Future placebo-controlled studies are warranted to confirm whether these changes occur in a controlled setting.

Clinical Implications of Kratom (Mitragyna speciosa) 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. A randomized controlled trial has further supported kratom's therapeutic value as an analgesic. Investigations in nonclinical samples of long-term kratom users also indicate its therapeutic benefit in managing SUD symptoms (e.g., craving) and long-term or acute symptoms (e.g., withdrawal) for alcohol, opioids, and other illicit drugs. However, episodes of kratom-related intoxications have also been reported, often due to the adulteration and the contamination of kratom products mainly sold online or mixed toxicities when consumed outside clinical and traditional settings. Summary: Evidence on the clinical implications of kratom use is still limited and uncertain, with kratom research constantly evolving. Therefore, further randomized trials are needed.

Investigation of self-treatment with lysergic acid diethylamide and psilocybin mushrooms: Findings from the Global Drug Survey 2020.

BACKGROUND: Growing numbers of people are using psychedelics for personal psychotherapy outside clinical settings, but research on such use is scarce. AIMS: This study investigated the patterns of use, self-reported outcomes and outcome predictors of psychedelic 'self-treatment' of mental health conditions or specific worries/concerns in life. METHODS: We use data from the Global Drug Survey 2020, a large online survey on drug use collected between November 2019 and February 2020. In all, 3364 respondents reported their self-treatment experiences with lysergic acid diethylamide (N = 1996) or psilocybin mushrooms (N = 1368). The primary outcome of interest was the 17-item self-treatment outcome scale, items reflecting aspects of well-being, psychiatric symptoms, social-emotional skills, and health behaviours. RESULTS: Positive changes were observed across all 17 outcome items, with the strongest benefits on items related to insight and mood. Negative effects were reported by 22.5% of respondents. High intensity of psychedelic experience, seeking advice before treatment, treating with psilocybin mushrooms and treating post-traumatic stress disorder were associated with higher scores on the self-treatment outcome scale after averaging values across all 17 items. Younger age, high intensity of experience and treating with LSD were associated with increased number of negative outcomes. CONCLUSIONS: This study brings important insights into self-treatment practices with psychedelics in a large international sample. Outcomes were generally favourable, but negative effects appeared more frequent than in clinical settings. Our findings can help inform safe practices of psychedelic use in the community, and inspire clinical research. Future research can be improved with utilisation of prospective designs and additional predictive variables.

A Preliminary Inventory of Kratom (Mitragyna Speciosa) Products and Vendors on the Darknet and Cryptomarkets.

In recent years, the online sale of kratom (Mitragyna speciosa), 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. Among these, 40 were found actively sold across five markets by thirteen vendors. Listed items were mainly advertised as "safe" substitutes for medicinal products for the self-management of pain and other health conditions and offered in various forms (e.g., dry leaf powder, pills, capsules). Purchases were made using cryptocurrencies, with some vendors offering Pretty Good Privacy, and were shipped from Europe, Australia, the United States, and the United Kingdom. Goods sold by the same sellers also included illicit drugs and fraud-related products. Our study discovered a previously unknown diffusion of kratom products on the darknet mainly for self-treating a variety of medical conditions, suggesting the need for further research and immediate interventions to safeguard the well-being and health of kratom consumers.

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. We assessed for the first time the immediate acute subjective, cognitive, and cardiovascular effects of 2C-B (20 mg) in comparison to psilocybin (15 mg) and placebo in a within-subjects, double-blind, placebo-controlled study of 22 healthy psychedelic-experienced participants. 2C-B elicited alterations of waking consciousness of a psychedelic nature, with dysphoria, subjective impairment, auditory alterations, and affective elements of ego dissolution largest under psilocybin. Participants demonstrated equivalent psychomotor slowing and spatial memory impairments under either compound compared with placebo, as indexed by the Digit Symbol Substitution Test, Tower of London, and Spatial Memory Task. Neither compound produced empathogenic effects on the Multifaceted Empathy Test. 2C-B induced transient pressor effects to a similar degree as psilocybin. The duration of self-reported effects of 2C-B was shorter than that of psilocybin, largely resolving within 6 hours. Present findings support the categorization of 2C-B as a psychedelic of moderate experiential depth at doses given. Tailored dose-effect studies are needed to discern the pharmacokinetic dependency of 2C-B's experiential overlaps.

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. However, knowledge is lacking about the impact of microstimulation after RT on said parameters. The present study aimed to test the effects of RT and muscle-microstimulation on mood and physical recovery in healthy men after performing conventional deadlifts, which is a type of RT. Methods: The study was conducted according to a single-blind, randomized, placebo-controlled, and two-way crossover study. Twenty participants naïve to microstimulation (MS) engaged in RT twice on separate days. They were randomized to receive MS on 1 day and no microstimulation (Sham-MS) on another day. Before and after the workout and after their treatment (MS or Sham-MS), participants self-rated their mood state and mental and physical exhaustion levels. Results: Findings showed that MS increased the self-ratings of well-rested and sociable and, most importantly, reduced the feeling of exercise-induced exhaustion. There were no MS effects on ratings of feeling sad, happy, or exhausted, although the workout, independent of MS, negatively influenced the level of exhaustion. Conclusion: The combination of enhanced sociableness, reduced fatigue, and exercise-induced exhaustion after a workout, followed by microstimulation, has important implications for professional sporters and nonprofessionals who try to get the best result after a workout. Future studies using a double-blind approach including different types of exercises, different durations of programs, and both sexes can shed more light on the full potential of microstimulation after a workout on mood state and exercise-induced exhaustion.

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. While both separate treatments show promise in the treatment of (other) clinical conditions, their combination has not yet been investigated in the treatment of psychopathologies. AIM: With a systematic literature review, we aim to identify the potential mechanisms by which combined psilocybin and mindfulness treatment could adjust anomalous neural activity underlying SAD and exert therapeutic effects. RESULTS: Thirty experimental studies investigating the neural effects of meditation or psilocybin treatment in healthy and patient samples were included. Findings suggest that psilocybin-assisted meditation interventions might change cognitive processes like biased attention to threat linked to SAD by modulating connectivity of the salience network, balancing the activity and connectivity of cortical-midline structures, and increasing frontoparietal control over amygdala reactivity. CONCLUSIONS: Future studies should investigate whether psilocybin-assisted mindfulness-based intervention can provide therapeutic benefits to SAD patients who are do not remit following conventional therapy.

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. At equal subjective intoxication levels, both drugs impaired psychomotor, divided attention, and impulse control, with no significant difference between the two drugs. Both drugs also caused significant psychotomimetic effects, but dissociative effects were considerably more pronounced for JWH-018 than THC. We conclude that psychotropic dose equivalence provides a uniform approach for comparing the neurocognitive and psychotomimetic profiles of CB1 agonists, which can also be applied to other drug classes.

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. The main aim of the present study was investigation of the effects of psilocybin-containing truffles, when taken in a supportive group setting, on ratings of state and trait anxiety across self-reported healthy volunteers. Attendees of psilocybin ceremonies were asked to complete a test battery at three separate occasions: before the ceremony (baseline), the morning after, and 1 week after the ceremony. The test battery included questionnaires assessing state and trait anxiety (State-Trait Anxiety Inventory), mindfulness capacities (Five Facet Mindfulness Questionnaire), and personality (Big Five Inventory). Additionally, the psychedelic experience was quantified with the Persisting Effects Questionnaire and the Ego Dissolution Inventory. The total amount of psilocybin-containing truffles consumed by each participant was recorded, and a sample of the truffles was analyzed to determine psilocin concentrations. Fifty-two attendees (males = 25; females = 25; others = 2) completed parts of the baseline assessment, 46 (males = 21; females = 24; others = 1) completed assessments the morning after the ceremony, and 23 (males = 10; females = 13) completed assessments at the 1-week follow-up. Average psilocin consumption across individuals was 27.1 mg. The morning after the ceremony, we observed medium reductions in anxiety measures (both state and trait) compared to baseline ( d ¯ = 6.4; p < 0.001 and d ¯ = 6; p = 0.014, respectively), which persisted over a 1-week period post-ceremony ( d ¯ = 6.7; p = 0.001 and d ¯ = 8.6; p = 0.004, respectively). At 1 week post-ceremony, the non-judging facet of the mindfulness scale was increased ( d ¯ = 1.5; p = 0.03), while the personality trait neuroticism decreased ( d ¯ = 5.2; p = 0.005), when compared to baseline. Additionally, we found ratings of ego dissolution (mean: 59.7, SD: 28.3) and changes in neuroticism to be the strongest predictors of reductions in state and trait anxiety, respectively. In sum, results suggest rapid and persisting (up to 1 week) anxiolytic effects in individuals with sub-clinical anxiety symptoms, which are related to the acute experience of ego dissolution, as well as lasting changes in trait neuroticism. Results also add support to the feasibility and potential efficacy of group sessions with psychedelics. To understand whether these effects extend to wider populations suffering from heightened anxiety, and the mechanisms involved, further experimental research is needed.

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.e., set and setting) seem to play a role in shaping the psychedelic experience and in determining clinical outcomes. These findings, coupled with data from literature on the effectiveness of psychotherapy, frame the therapeutic context as a potential moderator of clinical efficacy, highlighting the need to investigate how to functionally employ environmental and relational factors. In this review, we performed a structured search through two databases (i.e., PubMed/Medline and Scopus) to identify records of clinical studies on psychedelics which used and described a structured associated psychotherapeutic intervention. The aim is to construct a picture of what models of psychedelic-assisted psychotherapy are currently adopted in clinical research and to report on their clinical outcomes. Ad-hoc and adapted therapeutic methods were identified. Common principles, points of divergence and future directions are highlighted and discussed with special attention toward therapeutic stance, degree of directiveness and the potential suggestive effects of information provided to patients.