Acute effects of MDMA on trust, cooperative behaviour and empathy: A double-blind, placebo-controlled experiment

Background: 3,4-Methylenedioxymethamphetamine (MDMA) is being actively researched as an adjunct to psychotherapy. It may be beneficial to trust, empathy and cooperative behaviour due to its acute prosocial effects. Aim: To test (a) the acute effects of MDMA on measures of empathy, trust and cooperative behaviour, and (b) subacute changes in mood three days after MDMA administration. Methods: Twenty-five participants ( n=7 female), participated in this double-blind, repeated-measures, placebo-controlled experiment. Participants attended two acute sessions, one week apart. Each acute session was followed by a subacute session three days later. Participants received placebo (100 mg ascorbic acid) during one acute session, and MDMA (100 mg MDMA-HCl) at the other, with order counterbalanced. Participants completed the following tasks assessing prosocial behaviour: a trust investment task, a trustworthy face rating task, an empathic stories task, a public project game, a dictator game and an ultimatum game. Participants reported subjective effects. Blood was taken pre-drug, 2 and 4 hours post-drug, and tested for plasma MDMA levels. Results: MDMA acutely increased self-reported ‘closeness to others’ and ‘euphoria’ and increased plasma concentrations of MDMA. MDMA did not significantly change task-based empathy, trust or cooperative behaviour. Using Bayesian analyses, we found evidence that MDMA and placebo did not differ in their effects on empathy and cooperative behaviour. MDMA did not significantly change subacute mood and this was supported by our Bayesian analyses. Conclusion: Despite augmentation in plasma MDMA levels and subjective drug effects, we found no increase in prosocial behaviour in a laboratory setting.

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Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects

Neuropsychopharmacology ◽

10.1038/s41386-019-0569-3 ◽

2019 ◽

Vol 45 (3) ◽

pp. 462-471 ◽

Cited By ~ 19

Author(s):

Friederike Holze ◽

Patrick Vizeli ◽

Felix Müller ◽

Laura Ley ◽

Raoul Duerig ◽

...

Keyword(s):

Healthy Subjects ◽

Mystical Experience ◽

Subjective Effects ◽

Plasma Concentrations ◽

Drug Effects ◽

Psychotherapy Research ◽

Dose Finding ◽

Controlled Study ◽

Acute Effects ◽

Double Blind

AbstractLysergic acid diethylamide (LSD) is a classic psychedelic, 3,4-methylenedioxymethamphetamine (MDMA) is an empathogen, and d-amphetamine is a classic stimulant. All three substances are used recreationally. LSD and MDMA are being investigated as medications to assist psychotherapy, and d-amphetamine is used for the treatment of attention-deficit/hyperactivity disorder. All three substances induce distinct acute subjective effects. However, differences in acute responses to these prototypical psychoactive substances have not been characterized in a controlled study. We investigated the acute autonomic, subjective, and endocrine effects of single doses of LSD (0.1 mg), MDMA (125 mg), d-amphetamine (40 mg), and placebo in a randomized, double-blind, cross-over study in 28 healthy subjects. All of the substances produced comparable increases in hemodynamic effects, body temperature, and pupil size, indicating equivalent autonomic responses at the doses used. LSD and MDMA increased heart rate more than d-amphetamine, and d-amphetamine increased blood pressure more than LSD and MDMA. LSD induced significantly higher ratings on the 5 Dimensions of Altered States of Consciousness scale and Mystical Experience Questionnaire than MDMA and d-amphetamine. LSD also produced greater subjective drug effects, ego dissolution, introversion, emotional excitation, anxiety, and inactivity than MDMA and d-amphetamine. LSD also induced greater impairments in subjective ratings of concentration, sense of time, and speed of thinking compared with MDMA and d-amphetamine. MDMA produced greater ratings of good drug effects, liking, high, and ego dissolution compared with d-amphetamine. d-Amphetamine increased ratings of activity and concentration compared with LSD. MDMA but not LSD or d-amphetamine increased plasma concentrations of oxytocin. None of the substances altered plasma concentrations of brain-derived neurotrophic factor. These results indicate clearly distinct acute effects of LSD, MDMA, and d-amphetamine and may assist the dose-finding in substance-assisted psychotherapy research.

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Genetic influence of CYP2D6 on pharmacokinetics and acute subjective effects of LSD in a pooled analysis

Scientific Reports ◽

10.1038/s41598-021-90343-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Patrick Vizeli ◽

Isabelle Straumann ◽

Friederike Holze ◽

Yasmin Schmid ◽

Patrick C. Dolder ◽

...

Keyword(s):

Genetic Polymorphisms ◽

Healthy Subjects ◽

Phase 1 ◽

Subjective Effects ◽

Plasma Concentrations ◽

Psychiatric Research ◽

Acute Effects ◽

Double Blind ◽

Common Genetic Variants

AbstractLysergic acid diethylamide (LSD) is a classic psychedelic substance that is used recreationally and investigated in psychiatric research. There are no pharmacogenetic studies on LSD. In vitro metabolic studies indicate that several cytochrome P450 (CYP) isoforms (e.g., CYP2D6, CYP1A2, and CYP2C9) are involved in LSD metabolism, but in vivo data are scarce. The present study examined the influence of genetic polymorphisms of CYP genes on the pharmacokinetics and acute effects of LSD in healthy subjects. We identified common genetic variants of CYPs (CYP2D6, CYP1A2, CYP2C9, CYP2C19, and CYP2B6) in 81 healthy subjects who were pooled from four randomized, placebo-controlled, double-blind Phase 1 studies. We found that genetically determined CYP2D6 functionality significantly influenced the pharmacokinetics of LSD. Individuals with no functional CYP2D6 (i.e., poor metabolizers) had longer LSD half-lives and approximately 75% higher parent drug and main metabolite 2-oxo-3-hydroxy LSD area-under-the-curve blood plasma concentrations compared with carriers of functional CYP2D6. Non-functional CYP2D6 metabolizers also exhibited greater alterations of mind and longer subjective effect durations in response to LSD compared with functional CYP2D6 metabolizers. No effect on the pharmacokinetics or acute effects of LSD were observed with other CYPs. These findings indicate that genetic polymorphisms of CYP2D6 significantly influence the pharmacokinetic and subjective effects of LSD. Given the potential therapeutic use of psychedelics, including LSD, the role of pharmacogenetic tests prior to LSD-assisted psychotherapy needs to be further investigated.

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The acute effects of a low and high dose of oral l-arginine supplementation in young active males at rest

Applied Physiology Nutrition and Metabolism ◽

10.1139/h11-035 ◽

2011 ◽

Vol 36 (3) ◽

pp. 405-411 ◽

Cited By ~ 16

Author(s):

Scott C. Forbes ◽

Gordon J. Bell

Keyword(s):

Body Mass ◽

Repeated Measures ◽

Plasma Concentrations ◽

Insulin Response ◽

High Dose ◽

Placebo Condition ◽

Double Blind ◽

Physically Active ◽

Significant Difference ◽

Arginine Supplementation

l-arginine (2-amino-5-guanidinovaleric acid) is a conditionally essential amino acid. Intravenous (IV) administration of l-arginine invokes a large metabolic (nitrate/nitrite (NOx)) and hormonal (growth hormone (GH), insulin-like growth factor 1 (IGF-1), and insulin) response; however, research examining oral l-arginine supplementation is conflicting, potentially owing to dose. The purpose of this study was examine a low and high dose of oral l-arginine on blood l-arginine, NOx, GH, IGF-1, and insulin response. Fourteen physically active males (age: 25 ± 5 years; weight: 78.0 ± 8.5 kg; height: 179.4 ± 4.7 cm) volunteered to be in a randomized, double-blind, repeated-measures study. Following an overnight fast, an IV catheter was placed in a forearm vein and a resting blood sample was drawn at ∼0800 hours. Each subject was then provided 1 of 3 treatment conditions (placebo, low (0.075 g·kg–1 of body mass), or high (0.15 g·kg–1 of body mass of l-arginine)). Blood samples were drawn at 30, 60, 90, 120, and 180 min after consumption. l-arginine plasma concentrations significantly increased (p < 0.001) to a similar level at any time point in both the low- and high-dose conditions; there was no change over time in the placebo condition. There was no significant difference between conditions for NOx, GH, IGF-1, or insulin. Based on these findings, a low dose of l-arginine was just as effective at increasing plasma l-arginine concentrations as a high dose; however, neither dose was able to promote a significant increase in NOx, GH, IGF-1, or insulin at rest.

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179 Dasotraline in Children With Attention Deficit Hyperactivity Disorder: Results of a Randomized, Double-Blind, Placebo-Controlled Study

CNS Spectrums ◽

10.1017/s1092852918000615 ◽

2018 ◽

Vol 23 (1) ◽

pp. 102-103

Author(s):

Robert Goldman ◽

Lenard Adler ◽

Thomas Spencer ◽

Robert Findling ◽

Seth C. Hopkins ◽

...

Keyword(s):

Weight Loss ◽

Repeated Measures ◽

Mixed Model ◽

Rating Scale ◽

Plasma Concentrations ◽

Fixed Dose ◽

Controlled Study ◽

Double Blind ◽

Once Daily ◽

Stable Plasma

AbstractObjectivesOnce-daily dosing with dasotraline, a novel dopamine and norepinephrine reuptake inhibitor, achieves stable plasma concentrations over 24 hours with once-daily dosing. This study evaluated dasotraline in children aged 6–12 years (NCT02428088).MethodsPatients were randomized 1:1:1 to 6 weeks of once-daily, fixed-dose dasotraline 2 or 4 mg/day, or placebo. The primary efficacy endpoint was change from baseline (CFB) at Week 6 in ADHD Rating Scale Version IV – Home Version (ADHD RS-IV HV) total score, using a mixed model for repeated measures (MMRM) in the intent-to-treat (ITT) population. Secondary endpoints included Clinical Global Impression-Severity (CGI-S) score and safety endpoints.ResultsThe mean age of 342 randomized patients was 9.1 [SD: 1.9] years; 66.7% were male. Overall, 79% of patients completed the study. In the ITT population (N=336), ADHD RS-IV HV total score improved significantly with dasotraline 4 mg/day vs placebo(least squares [LS] mean [SE] CFB at Week 6: –17.53 [±1.31] vs –11.36 [±1.29], respectively, p<0.001; effect size [ES]: 0.48). Inattentiveness and hyperactivity/impulsivity subscale scores significantly improved with 4 mg/day vs placebo at Week 6 (p=0.001, p=0.003, respectively). Improvement in CGI-S score was statistically significant with dasotraline 4 mg/day vs placebo(LS mean [SE] CFB at Week 6: –1.39 [±0.12] vs –1.04 [±0.12], respectively, p=0.040; ES: 0.29). No significant improvement was observed on the ADHD RS-IV HV total score and the CGI-S score for dasotraline 2 mg/day vs placebo. The most frequent treatment-emergent AEs (≥5% and higher than placebo) were (2 mg/day; 4 mg/day; placebo): insomnia (15.3%; 21.7%; 4.3%, all terms combined), decreased appetite (12.6%; 21.7%; 5.2%), weight loss (5.4%; 8.7%; 0%), irritability (3.6%; 7.0%; 6.0%), nasopharyngitis (0.9%; 5.2%; 0.9%), and nausea (0%; 5.2%; 2.6%).ConclusionsCompared with placebo, dasotraline 4 mg/day significantly improved ADHD symptoms in children, as assessed by ADHD RS-IV HV total score and inattentiveness and hyperactivity/impulsivity subscale scores. Dasotraline was generally well tolerated; most common AEs were insomnia, decreased appetite, weight loss and irritability.Funding AcknowledgementsStudy sponsored by Sunovion Pharmaceuticals Inc.

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Absence of drug–drug interactions between γ-hydroxybutyric acid (GHB) and cobicistat

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkab359 ◽

2021 ◽

Author(s):

José Moltó ◽

Lucía Bailón ◽

Clara Pérez-Mañá ◽

Ester Papaseit ◽

Cristina Miranda ◽

...

Keyword(s):

Drug Interactions ◽

Treatment Period ◽

Day Treatment ◽

Subjective Effects ◽

Plasma Concentrations ◽

Pharmacokinetic Parameters ◽

People Living With Hiv ◽

Hydroxybutyric Acid ◽

Ct Number ◽

Double Blind

Abstract Objectives Potential interactions between CYP3A4 inhibitors and γ-hydroxybutyric acid (GHB) have been suggested as a possible explanation for cases of GHB overdose in recent years among people living with HIV engaged in chemsex. Our objective was to assess the effect of cobicistat on the pharmacokinetics of GHB. Methods Fifteen healthy adults were enrolled in this randomized, double-blind, placebo-controlled, two-arm, crossover clinical trial. Participants underwent two 5 day treatment periods with at least a 1 week washout period between them. In each treatment period, participants received cobicistat (150 mg q24h orally) or matched placebo. On day 5 of each treatment period, participants were given a single oral dose of GHB (25 mg/kg). Plasma concentrations of GHB, subjective effects, blood pressure, heart rate and oxygen saturation were monitored for 5 h after dosing. GHB pharmacokinetic and pharmacodynamic parameters were calculated for each participant during each study period by non-compartmental analysis and were compared using linear mixed-effects models. The study was registered at https://www.clinicaltrialsregister.eu (Eudra-CT number 2019-002122-71) and at https://clinicaltrials.gov (NCT04322214). Results Ten participants completed the two study periods. No drug-related adverse events that necessitated subject withdrawal or medical intervention occurred during the study. Compared with placebo, none of the primary pharmacokinetic parameters of GHB was substantially changed by the administration of GHB with cobicistat. Similarly, no differences regarding subjective or physiological effects were observed when GHB was administered alone or with cobicistat. Conclusions Neither pharmacokinetic nor pharmacodynamic drug–drug interactions between cobicistat and GHB were identified in this study.

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A single serving of caffeinated coffee impairs postprandial glucose metabolism in overweight men

British Journal Of Nutrition ◽

10.1017/s0007114515002640 ◽

2015 ◽

Vol 114 (8) ◽

pp. 1218-1225 ◽

Cited By ~ 17

Author(s):

Tracey M. Robertson ◽

Michael N. Clifford ◽

Simon Penson ◽

Gemma Chope ◽

M. Denise Robertson

Keyword(s):

Glucose Metabolism ◽

Repeated Measures ◽

Postprandial Glucose ◽

Acute Effects ◽

Double Blind ◽

Beneficial Effects ◽

Decaffeinated Coffee ◽

Caffeinated Coffee ◽

Post Hoc ◽

Dose Dependent

AbstractPrevious studies regarding the acute effects of coffee on glycaemic control have used a single large dose of coffee, typically containing the caffeine equivalent of 2–4 servings of coffee. This study investigates whether the acute effects of coffee are dose-dependent, starting with a single serving. A total of ten healthy overweight males participated in a two-part randomised double-blind cross-over study. In the first part, they ingested 2, 4 or 8 g instant decaffeinated coffee (DC) dissolved in 400 ml water with caffeine added in proportion to the DC (total 100, 200 or 400 mg caffeine) or control (400 ml water) all with 50 g glucose. In the second part, they ingested the same amounts of DC (2, 4, 8 g) or control, but with a standard 100 mg caffeine added to each. Capillary blood samples were taken every 15 min for 2 h after each drink and glucose and insulin levels were measured. Repeated measures ANOVA on glucose results found an effect when caffeine was varied in line with DC (P=0·008). Post hoc analysis revealed that both 2 and 4 g DC with varied caffeine content increased the glycaemic response v. control. There was no effect of escalating doses of DC when caffeine remained constant at 100 mg. These results demonstrate that one standard serving of coffee (2 g) is sufficient to affect glucose metabolism. Furthermore, the amount of caffeine found in one serving (100 mg) is sufficient to mask any potential beneficial effects of increasing other components. No dose-dependent effect was found.

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Neuronally-Enriched Exosomal miR-27b Reveals Mechanism for Ibuprofen-Induced Acute Effects on Reward-Related Brain Processing in a Randomized, Placebo-Controlled, Double-Blind Trial

10.21203/rs.3.rs-803515/v1 ◽

2021 ◽

Author(s):

Kaiping Burrows ◽

Leandra K. Figueroa-Hall ◽

Rayus Kuplicki ◽

Jennifer L. Stewart ◽

Ahlam M. Alarbi ◽

...

Keyword(s):

Repeated Measures ◽

Monetary Incentive ◽

Reward Processing ◽

Acute Administration ◽

Acute Effects ◽

Double Blind ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Monetary Incentive Delay ◽

Brain Processing

Abstract This double-blind, randomized, repeated measures study evaluated whether acute administration of an anti-inflammatory drug modulates neuron-specific, inflammation-modulating microRNAs linked to macroscopic changes in reward processing. Twenty healthy subjects (10 females,10 males) completed a monetary incentive delay (MID) task and provided blood samples after administration of placebo, 200 mg, or 600 mg of ibuprofen. Neuronally-enriched exosomal microRNAs were extracted from plasma and sequenced. Results showed that: (1) 600 mg of ibuprofen exhibited higher miR-27b-3p, miR-320b, miR-23b and miR-203a-3p expression than placebo; (2) higher mir-27b-3p was associated with lower insula activation during MID loss anticipation; and (3) there was an inverse relationship between miR-27b-3p and MID gain anticipation in bilateral putamen during placebo, a pattern attenuated by both 200 mg and 600 mg of ibuprofen. Our findings indicate that miR-27b could be an important messaging molecule altered by anti-inflammatory drugs that relates to the processing of positive or negative valenced information.

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Vitamin B6 Supplementation Reduces Depression in College Women Taking Oral Contraceptives: A Randomized, Double-Blind Cross-Over Trial

Current Developments in Nutrition ◽

10.1093/cdn/nzaa067_040 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1813-1813

Author(s):

Carol Johnston ◽

Anne Curtin

Keyword(s):

College Women ◽

Beck Depression Inventory ◽

Repeated Measures ◽

Vitamin B6 ◽

Plasma Concentrations ◽

Mood States ◽

Control Treatment ◽

Anthropometric Measures ◽

Double Blind ◽

Increased Risk

Abstract Objectives Oral contraception (OC) use has been linked to an increased risk of depression in college women and to poor micronutrient status. Of note, when compared to non-OC users, OC users have a heightened risk of low plasma concentrations of vitamin B6, a cofactor in the tryptophan-serotonin pathway critical to mood regulation. The purpose of this crossover study was to determine whether vitamin B6 supplementation impacted mood states and depression in college women using OC. Methods Participants were healthy and between 18–25 y, did not smoke or use dietary supplements, and used OC (estrogen with progestin) consistently for at least one year prior to the start of the study. The 12-week, randomized, double-blind crossover trial (4-week treatment periods [B6: 100 mg/d or control: placebo pill/d] separated by a 4-week washout [no pills taken]) was approved by the university Institutional Review Board, and participants provided written consent. Anthropometric measures, blood sampling, and diet and mood assessments were completed at the start of the trial and at weeks 4, 8, and 12. Participants (n = 8) maintained normal exercise and eating patterns the duration of the study and recorded pill consumption daily. The Profile of Mood States (POMS) and Beck Depression Inventory were used to assess affect. Plasma pyridoxal 5′ phosphate (PLP) concentrations were quantified by enzymatic assay. Repeated measures ANOVA was used to assess treatment effects. Results Plasma PLP concentrations averaged 66 ± 32 nmol/L at the start of the trial; one participant presented with marginal vitamin B6 status (20–30 nmol/L). Average vitamin B6 intakes did not vary during the trial (1.2–1.4 mg/d); whereas, vitamin B6 status rose significantly following the B6 supplementation period compared to the other three timepoints. POMS scores were not impacted by treatment; however, Beck Depression Inventory scores were reduced 30% by B6 supplementation in comparison to the control treatment (P = 0.047). Conclusions These preliminary data support a growing literature suggesting the benefits of B6 supplementation for reducing depression in young women using OC. Funding Sources This study was supported in part by the Graduate and Professional Students Association and the Office of the Vice Provost for Research.

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113 Dasotraline for the Treatment of Moderate to Severe Binge Eating Disorder in Adults: Results From a Randomized, Double-Blind, Placebo-Controlled Study

CNS Spectrums ◽

10.1017/s1092852918000135 ◽

2018 ◽

Vol 23 (1) ◽

pp. 72-73 ◽

Cited By ~ 3

Author(s):

Bradford Navia ◽

James I. Hudson ◽

Susan L McElroy ◽

Anna I. Guerdjikova ◽

Ling Deng ◽

...

Keyword(s):

Placebo Group ◽

Eating Disorder ◽

Binge Eating ◽

Binge Eating Disorder ◽

Repeated Measures ◽

Plasma Concentrations ◽

Controlled Study ◽

Obsessive Compulsive ◽

Double Blind ◽

Secondary Endpoints

AbstractObjectivesBinge eating disorder (BED) is the most common eating disorder in the US, with a lifetime prevalence of 2.8%. Disturbances in reward circuitry have been implicated in its pathogenesis. Dasotraline is a novel and potent dopamine and norepinephrine reuptake inhibitor with slow absorption and a long half-life resulting in stable plasma concentrations over 24 hours with once-daily dosing. This study evaluated the efficacy and safety of flexibly-dosed dasotraline (4, 6, and 8 mg/day) vs placebo in adults with moderate to severe BED over a 12-week period (NCT02564588).MethodsKey inclusion criteria included moderate to severe BED based on a history of ≥2 binge eating days/week for ≥6 months prior to screening, and ≥3 binge eating days for each of2 weeks prior to randomization, as documented in participant’s binge eating diary. Patients were randomized 1:1 to flexibly-dosed dasotraline (4, 6, 8 mg/day) or placebo. Theprimary endpoint was change from baseline (CFB) in the number of binge eating days per week at Week 12. Key secondary endpoints were: CFB in Clinical Global Impression–Severity (CGI-S) Scale at Week 12; CFB in Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (YBOCS-BE) at Week 12; and the percentage ofsubjects with a 4-week cessation from binge eating prior to Week 12 or end of treatment (EOT). Except for 4-week cessation, the other three variables were analyzed using amixed model for repeated measures (MMRM).Results317 subjects (84% female) received ≥1 dose of study medication (mean age was 38.2 years; mean number of binge eating days per week, 4.25; mean CGI-S score, 4.5; mean BMI, 34.7). The MMRM analysis of CFB at Week 12 in the number of binge days/week yielded a significant mean difference of –0.99 (95% CI: –0.65 to –1.33; p<0.001) infavour of dasotraline (–3.74 in the dasotraline group vs –2.75 in the placebo group). All three key secondary endpoints were met at Week 12 or EOT: 46.5% of subjects in thedasotraline group achieved at least 4 consecutive weeks’ cessation from binge eating vs 20.6% in the placebo group (p<0.001); CFB in CGI-S and YBOCS-BE scores were also statistically significant in favour of dasotraline (p<0.001). The treatment-emergent adverse events (TEAEs) that occurred more frequently with dasotraline vs placebo at >2% incidence included: insomnia (44.6% vs 8.1%), dry mouth (27.4% vs 5.0%), decreased appetite (19.7% vs 6.9%), anxiety (17.8% vs 2.5%), nausea (12.7% vs 6.9%) and decreased body weight (12.1% vs 0%). Discontinuation due to AEs occurred in 11.5% of patients taking dasotraline vs 2.5% taking placebo.ConclusionsIn adults with moderate to severe BED, there were highly significant and clinically meaningful reductions with dasotraline vs placebo in the frequency of binge eating, global severity of illness, and obsessive-compulsive symptoms related to binge eating. These results suggest dasotraline may offer a novel, well-tolerated and efficacious treatmentfor BED.Funding AcknowledgementsStudy sponsored by Sunovion Pharmaceuticals Inc.

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Microevidence for microdosing with psilocybin mushrooms: a double-blind placebo-controlled study of subjective effects, behavior, creativity, perception, cognition, and brain activity

10.1101/2021.11.30.470657 ◽

2021 ◽

Author(s):

Federico Cavanna ◽

Stephanie Muller ◽

Laura Alethia de la Fuente ◽

Federico Zamberlan ◽

Matías Palmucci ◽

...

Keyword(s):

Subjective Experience ◽

Spectral Power ◽

Brain Activity ◽

Subjective Effects ◽

Controlled Study ◽

Acute Effects ◽

Theta Band ◽

Double Blind ◽

Double Blind Placebo ◽

Active Dose

AbstractThe use of low sub-hallucinogenic doses of psychedelics (“microdosing”) has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies limits our knowledge of microdosing and its effects. Moreover, research conducted in laboratory settings might fail to capture the motivation of individuals engaged in microdosing protocols. We recruited 34 individuals planning to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled design, we investigated the effects of 0.5 g dried mushrooms on subjective experience, behavior, creativity, perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, which could be explained by unblinding. For the other measurements, we observed either null effects or a trend towards cognitive impairment and, in the case of EEG, towards reduced theta band spectral power. Our findings support the possibility that expectation effects underlie at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.

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