BackgroundKetamine and its enantiomers are widely researched and increasingly used to treat mental disorders, especially treatment-resistant depression. The phenomenology of ketamine-induced... Show moreBackgroundKetamine and its enantiomers are widely researched and increasingly used to treat mental disorders, especially treatment-resistant depression. The phenomenology of ketamine-induced experiences and their relation to its psychotherapeutic potential have not yet been systematically investigated.AimsTo describe the phenomenology of patient experiences during oral esketamine treatment for treatment-resistant depression (TRD) and to explore the potential therapeutic relevance of these experiences.MethodsIn-depth interviews were conducted with 17 patients after a 6-week, twice-weekly ‘off label’ generic oral esketamine (0.5–3.0mg/kg) treatment program. Interviews explored participants’ perspectives, expectations, and experiences with oral esketamine treatment. Audio interviews were transcribed and analyzed using an Interpretative Phenomenological Analysis (IPA) framework.ResultsThe effects of ketamine were highly variable, and psychological distress was common in most patients. Key themes included (a) perceptual effects (auditory, visual, proprioceptive), (b) detachment (from body, self, emotions, and the world), (c) stillness and openness, (d) mystical-type effects (transcendence, relativeness, spirituality), and (e) fear and anxiety. Key themes related to post-session reports included (a) feeling hungover and fatigued, and (b) lifting the blanket: neutralizing mood effects.ConclusionPatients reported several esketamine effects with psychotherapeutic potential, such as increased openness, detachment, an interruption of negativity, and mystical-type experiences. These experiences deserve to be explored further to enhance treatment outcomes in patients with TRD. Given the frequency and severity of the perceived distress, we identify a need for additional support in all stages of esketamine treatment. Show less
Standardization and reduction of variation is key to behavioural screening of animal models in toxicological and pharmacological studies. However, individual variation in behavioural and... Show moreStandardization and reduction of variation is key to behavioural screening of animal models in toxicological and pharmacological studies. However, individual variation in behavioural and physiological phenotypes remains in each laboratory population and can undermine the understanding of toxicological and pharmaceutical effects and their underlying mechanisms. Here, we used zebrafish (ABTL-strain) larvae to explore individual consistency in activity level and emergence time, across subsequent days of early development (6-8 dpf). We also explored the correlation between these two behavioural parameters. We found inter-individual consistency over time in activity level and emergence time, but we did not find a consistent correlation between these parameters. Subsequently, we investigated the impact of variation in activity level on the effect of a 1% ethanol treatment, suitable for our proof-of-concept case study about whether impact from pharmacological treatments might be affected by inter-individual variation in basal locomotion. The inter-individual consistency over time in activity level did not persist in this test. This was due to the velocity change from before to after exposure, which turned out to be a dynamic individual trait related to basal activity level: low-activity individuals raised their swimming velocity, while high-activity individuals slowed down, yielding diametrically opposite response patterns to ethanol exposure. We therefore argue that inter-individual consistency in basal activity level, already from 6 dpf, is an important factor to take into account and provides a practical measure to improve the power of statistical analyses and the scope for data interpretation from behavioural screening studies. Show less
Elk, M. van; Fejer, G.; Lempe, P.; Prochazkova, L.; Kuchar, M.; Hakova, K.; Marschall, J. 2021
Rationale and objective The aim of this study was to investigate the possible facilitating effect of the partial NMDA receptor agonist D-cycloserine (DCS) on memory consolidation of conditioned... Show moreRationale and objective The aim of this study was to investigate the possible facilitating effect of the partial NMDA receptor agonist D-cycloserine (DCS) on memory consolidation of conditioned sexual responses and to examine the capability of DCS to reduce context-specificity of learning. Methods In a randomized placebo-controlled double-blind trial, 50 healthy females were exposed to a differential conditioning procedure. Two pictures of a male abdomen were used as conditional stimuli (CSs), of which one (the CS+) was followed by the unconditional stimulus (US), a genital vibrotactile stimulus. After the conditioning session on day 1, participants received either 125 mg of DCS or a placebo. The effects of DCS on affect, sexual arousal and US expectancy in response to the CS+ and CS- were examined 24 h after the conditioning procedure. Results A main effect of DCS was found on affect at the first test trials (p = 0.04, eta(2)(p) = 0.09), and a similar non-significant but trend level effect was found for sexual arousal (p = 0.06, eta(2)(p) = 0.07), which appeared to persist over a longer time (p = 0.07, eta(2)(p) = 0.08). Unexpectedly, ratings of positive affect and sexual arousal in response to both the CS+ and the CS- were higher in the DCS condition compared to the control condition, possibly indicating that DCS administration reduced stimulus specificity. Since the results did not show clear evidence for context learning, we were not able to test effects on context-specificity of learning. Conclusion Although largely inconclusive, the results provide tentative support for a facilitating effect of DCS on affect and sexual arousal in response to stimuli that were presented in a sexual conditioning procedure, however, no conclusions can be drawn about effects of DCS on sexual reward learning, since the design and results do not lend themselves to unambiguous interpretation. Show less
IntroductionTaking microdoses (a mere fraction of normal doses) of psychedelic substances, such as truffles, recently gained popularity, as it allegedly has multiple beneficial effects including... Show moreIntroductionTaking microdoses (a mere fraction of normal doses) of psychedelic substances, such as truffles, recently gained popularity, as it allegedly has multiple beneficial effects including creativity and problem-solving performance, potentially through targeting serotonergic 5-HT2A receptors and promoting cognitive flexibility, crucial to creative thinking. Nevertheless, enhancing effects of microdosing remain anecdotal, and in the absence of quantitative research on microdosing psychedelics, it is impossible to draw definitive conclusions on that matter. Here, our main aim was to quantitatively explore the cognitive-enhancing potential of microdosing psychedelics in healthy adults.MethodsDuring a microdosing event organized by the Dutch Psychedelic Society, we examined the effects of psychedelic truffles (which were later analyzed to quantify active psychedelic alkaloids) on two creativity-related problem-solving tasks: the Picture Concept Task assessing convergent thinking and the Alternative Uses Task assessing divergent thinking. A short version of the Ravens Progressive Matrices task assessed potential changes in fluid intelligence. We tested once before taking a microdose and once while the effects were expected to be manifested.ResultsWe found that both convergent and divergent thinking performance was improved after a non-blinded microdose, whereas fluid intelligence was unaffected.ConclusionWhile this study provides quantitative support for the cognitive-enhancing properties of microdosing psychedelics, future research has to confirm these preliminary findings in more rigorous placebo-controlled study designs. Based on these preliminary results, we speculate that psychedelics might affect cognitive metacontrol policies by optimizing the balance between cognitive persistence and flexibility. We hope this study will motivate future microdosing studies with more controlled designs to test this hypothesis. Show less
Rationale Cannabis users often claim that cannabis has the potential to enhance their creativity. Research suggests that aspects of creative performance might be improved when intoxicated with... Show moreRationale Cannabis users often claim that cannabis has the potential to enhance their creativity. Research suggests that aspects of creative performance might be improved when intoxicated with cannabis; however, the evidence is not conclusive. Objective The aim of this study was to investigate the acute effects of cannabis on creativity. Methods We examined the effects of administering a low (5.5 mg delta-9-tetrahydrocannabinol [THC]) or high (22 mg THC) dose of vaporized cannabis vs. placebo on creativity tasks tapping into divergent (Alternate Uses Task) and convergent (Remote Associates Task) thinking, in a population of regular cannabis users. The study used a randomized, double-blind, between-groups design. Results Participants in the high-dose group (n = 18) displayed significantly worse performance on the divergent thinking task, compared to individuals in both the low-dose (n = 18) and placebo (n = 18) groups. Conclusions The findings suggest that cannabis with low potency does not have any impact on creativity, while highly potent cannabis actually impairs divergent thinking. Show less
Veen, R. van der; Boshuizen, M.C.S.; Kloet, E.R. de 2013
Rationale Glucocorticoid hormones facilitate sensitization to repeated administration of psychostimulants, an effect that is mediated by glucocorticoid receptors (GRs). It is still unclear, however... Show moreRationale Glucocorticoid hormones facilitate sensitization to repeated administration of psychostimulants, an effect that is mediated by glucocorticoid receptors (GRs). It is still unclear, however, at which stage of psychomotor sensitization are stress and GR-mediated effects involved.Objectives In the present study, we have tested the hypothesis that GR-mediated effects during the phase of repeated amphetamine injections play a crucial role in the long-term expression of sensitization. For this purpose, we used DBA/2 mice, an inbred strain commonly used for the study of stress effects on psychostimulant sensitization.Methods Animals were treated with the GR antagonist mifepristone (200 mg/kg) at 2.5 h before each daily injection of amphetamine (2.5 mg/kg) or saline in a 5-day protocol. The amphetamine or saline injections were given in the home or a novel context. This was followed by a 2.5-week withdrawal period, without any drug delivery. Following the withdrawal period, two low-dose amphetamine challenges (1.25 mg/kg) were given subsequently, without additional mifepristone.Results The animals receiving amphetamine in the novel context showed a higher expression of sensitization at challenge as compared to those in the home condition. Mifepristone treatment influenced locomotor response to repeated amphetamine injections, but this effect during the initial phase did not affect the expression of sensitization after a withdrawal period.Conclusion Our results indicate that GR-related processes during the initial phase of sensitization are involved in, but not crucial for, the development of long-term sensitization. Show less
Rover, M. de; Brown, S.B.R.E.; Boot, N.; Hajcak, G.; Noorden, M.S. van; Wee, N.J.A. van der; Nieuwenhuis, S. 2012
RATIONALE Electrophysiological studies have identified a scalp potential, the late positive potential (LPP), which is modulated by the emotional intensity of observed stimuli. Previous work has... Show moreRATIONALE Electrophysiological studies have identified a scalp potential, the late positive potential (LPP), which is modulated by the emotional intensity of observed stimuli. Previous work has shown that the LPP reflects the modulation of activity in extrastriate visual cortical structures, but little is known about the source of that modulation. OBJECTIVES The present study investigated whether beta-adrenergic receptors are involved in the generation of the LPP. METHODS We used a genetic individual differences approach (experiment 1) and a pharmacological manipulation (experiment 2) to test the hypothesis that the LPP is modulated by the activation of β-adrenergic receptors. RESULTS In experiment 1, we found that LPP amplitude depends on allelic variation in the β1-receptor gene polymorphism. In experiment 2, we found that LPP amplitude was modulated by the β-blocker propranolol in a direction dependent on subjects' level of trait anxiety: In participants with lower trait anxiety, propranolol led to a (nonsignificant) decrease in the LPP modulation; in participants with higher trait anxiety, propranolol increased the emotion-related LPP modulation. CONCLUSIONS These results provide initial support for the hypothesis that the LPP reflects the downstream effects, in visual cortical areas, of β-receptor-mediated activation of the amygdala. Show less
