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.

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.

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.

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.

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. Using a naturalistic, observational design, we followed psilocybin microdosers (n = 953) and non-microdosing comparators (n = 180) for approximately 30 days and identified small- to medium-sized improvements in mood and mental health that were generally consistent across gender, age and presence of mental health concerns, as we all as improvements in psychomotor performance that were specific to older adults. Supplementary analyses indicated that combining psilocybin with HE and B3 did not impact changes in mood and mental health. However, among older microdosers combining psilocybin, HE and B3 was associated with psychomotor improvements relative to psilocybin alone and psilocybin and HE. Our findings of mood and mental health improvements associated with psilocybin microdosing add to previous studies of psychedelic microdosing by using a comparator group and by examining the consistency of effects across age, gender, and mental health. Findings regarding the combination of psilocybin, HE and B3 are novel and highlight the need for further research to confirm and elucidate these apparent effects.

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.

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.

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. AIM: The current study was designed to assess the psychotomimetic effects of a moderate dose of JWH-018. METHODS: Twenty-four healthy participants (10 males, 14 females) entered a placebo-controlled, double blind, within-subjects trial and inhaled vapour of placebo or 75µg/kg bodyweight JWH-018. To ascertain a minimum level of intoxication, a booster dose of JWH-018 was administered on an as-needed basis. The average dose of JWH-018 administered was 5.52 mg. Subjective high, dissociative states (CADSS), psychedelic symptoms (Bowdle), mood (POMS) and cannabis reinforcement (SCRQ) were assessed within a 4.5-h time window after drug administration. RESULTS: JWH-018 caused psychedelic effects, such as altered internal and external perception, and dissociative effects, such as amnesia, derealisation and depersonalisation and induced feelings of confusion. CONCLUSION: Overall, these findings suggest that a moderate dose of JWH-018 induces pronounced psychotomimetic symptoms in healthy participants with no history of mental illness, which confirms that SCs pose a serious risk for public health.

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. Microdosers were generally similar to non-microdosing controls with regard to demographics, but were more likely to report a history of mental health concerns. Among individuals reporting mental health concerns, microdosers exhibited lower levels of depression, anxiety, and stress across gender. Health and wellness-related motives were the most prominent motives across microdosers in general, and were more prominent among females and among individuals who reported mental health concerns. Our results indicate health and wellness motives and perceived mental health benefits among microdosers, and highlight the need for further research into the mental health consequences of microdosing including studies with rigorous longitudinal designs.

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

Background: 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. Materials and Methods: 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. We included the constructs of creative thinking (measured by Picture Concept Test), empathy (Multifaceted Empathy Test), satisfaction with life (Satisfaction with Life Scale), decentering (Experiences Questionnaire), and personality (Big Five Inventory) into the test battery. Additionally, the psychedelic experience was quantified with the Persisting Effects Questionnaire, the Ego Dissolution Scale, and Visual Analogue Scales. Results: In total, 43 attendees (males = 22; females = 21) completed parts of the baseline assessment, 20 (males = 12; females = 8) completed assessments in the morning after the ceremony, and 19 (males = 14; females = 5) completed assessments at the 1-week follow-up. At one and 7 days post-ceremony, cognitive empathy, satisfaction with life, and decentering increased, while divergent thinking (Fluency corrected for Originality) decreased, when compared to baseline. Implicit emotional empathy increased at 1-week follow-up, whereas ratings of the trait neuroticism decreased. Conclusion: The study suggests that a single ingestion of ayahuasca in a social setting is associated with enhancement of subjective well-being, an enhanced ability to take an objective and non-judging stance towards the self (decentering), and the ability to correctly recognize emotions in others, compared to baseline, lasting up to 1 week post-ceremony. To understand the therapeutic potential related to these effects, further research with clinical populations is needed in which these effects can be assessed, including its link with therapeutic outcomes. Together, this will increase our understanding of the effectiveness and breadth of future therapeutic options.

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. This review attempts to summarize the evidence that psychedelics induce neuroplasticity by focusing on psychedelics' cellular and molecular neuroplasticity effects after single and repeated administration. When behavioral parameters are encountered in the selected studies, the biological pathways will be linked to the behavioral effects. Additionally, knowledge gaps in the underlying biology of clinical outcomes of psychedelics are highlighted. The literature searched yielded 344 results. Title and abstract screening reduced the sample to 35; eight were included from other sources, and full-text screening resulted in the final selection of 16 preclinical and four clinical studies. Studies (n = 20) show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment. Findings from the current review demonstrate that psychedelics induce molecular and cellular adaptations related to neuroplasticity and suggest those run parallel to the clinical effects of psychedelics, potentially underlying them. Future (pre)clinical research might focus on deciphering the specific cellular mechanism activated by different psychedelics and related to long-term clinical and biological effects to increase our understanding of the therapeutic potential of these compounds.

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. This double-blind, placebo-controlled study investigated the effect of an intranasal administration of the hormone oxytocin (24 IU) on social behavior and anxious appearance in SAD patients (N = 40) and healthy controls (N = 39). Forty minutes after oxytocin administration participants were submitted to two live social situations (i.e., a waiting room situation and a getting acquainted task). The participants ('self-rated') and observers ('observer-rated') scored participants' social behavior and anxious appearance. Participants also rated their positive and negative affect. Confirming the social performance deficits in SAD, observers regarded SAD patients as more anxious and less socially skilled than healthy controls. Results indicated oxytocin-induced improvement of observer-rated social behavior in SAD patients compared to placebo but only in the getting acquainted task. This effect was not perceived as such by patients themselves and did not improve their affect ratings. In conclusion, this study found support for the idea that oxytocin helps SAD patients to perform better in social interactions, although this improvement seemed context-dependent (i.e., only present in the getting-acquainted task) and 'not perceived by the patient.

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. The findings demonstrated an increase in BDNF blood plasma levels at 4 h (5 µg) and 6 h (5 and 20 µg) compared to that for the placebo. The finding that LSD acutely increases BDNF levels warrants studies in patient populations.

Intoxication by a synthetic cannabinoid (JWH-018) causes cognitive and psychomotor impairment in recreational cannabis users.

BACKGROUND: Smoking mixtures containing synthetic cannabinoids (SCs) have become very popular over the last years but pose a serious risk for public health. Limited knowledge is, however, available regarding the acute effects of SCs on cognition and psychomotor performance. Earlier we demonstrated signs of impairment in healthy volunteers after administering one of the first SCs, JWH-018, even though subjective intoxication was low. In the current study, we aimed to investigate the acute effects of JWH-018 on several cognitive and psychomotor tasks in participants who are demonstrating representative levels of acute intoxication. METHODS: 24 healthy cannabis-experienced participants took part in this placebo-controlled, cross-over study. Participants inhaled the vapor of 75 µg JWH-018/kg body weight and were given a booster dose if needed to induce a minimum level of subjective high. They were subsequently monitored for 4 h, during which psychomotor and cognitive performance, vital signs, and subjective experience were measured, and serum concentrations were determined. RESULTS: Maximum subjective high (average 64%) was reached 30 min after administration of JWH-018, while the maximum blood concentration was shown after 5 min (8 ng/mL). JWH-018 impaired motor coordination (CTT), attention (DAT and SST), memory (SMT), it lowered speed-accuracy efficiency (MFFT) and slowed down response speed (DAT). CONCLUSION: In accordance with our previous studies, we demonstrated acute psychomotor and cognitive effects of a relatively low dose of JWH-018.

Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants.

"Microdoses" of lysergic acid diethylamide (LSD) are used recreationally to enhance mood and cognition. Increasing interest has also been seen in developing LSD into a medication. Therefore, we performed a pharmacokinetic-pharmacodynamic study using very low doses of LSD. Single doses of LSD base (5, 10, and 20 µg) and placebo were administered in a double-blind, randomized, placebo-controlled crossover study in 23 healthy participants. Test days were separated by at least 5 days. Plasma levels of LSD and subjective effects were assessed up to 6 hours after administration. Pharmacokinetic parameters were determined using compartmental modeling. Concentration-subjective effect relationships were described using pharmacokinetic-pharmacodynamic modeling. Mean (95% confidence interval) maximal LSD concentrations were 151 pg/mL (127-181), 279 pg/mL (243-320), and 500 pg/mL (413-607) after 5, 10, and 20 µg LSD administration, respectively. Maximal concentrations were reached after 1.1 hours. The mean elimination half-life was 2.7 hours (1.5-6.2). The 5 µg dose of LSD elicited no significant acute subjective effects. The 10 µg dose of LSD significantly increased ratings of "under the influence" and "good drug effect" compared with placebo. These effects began an average of 1.1 hours after 10 µg LSD administration, peaked at 2.5 hours, and ended at 5.1 hours. The 20 µg dose of LSD significantly increased ratings of "under the influence," "good drug effects," and "bad drug effects." LSD concentrations dose-proportionally increased at doses as low as 5-20 µg and decreased with a half-life of 3 hours. The threshold dose of LSD base for psychotropic effects was 10 µg.