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BackgroundPast research reports a positive relationship between experience with classic serotonergic psychedelics and nature relatedness (NR). However, these studies typically do not distinguish between different psychedelic compounds, which have a unique psychopharmacology and may be used in specific contexts and with different intentions. Likewise, it is not clear whether these findings can be attributed to substance use per se or unrelated variables that differentiate psychedelic users from nonusers.AimsThe present study was designed to determine the relative degree to which lifetime experience with different psychedelic substances is predictive of self-reported NR among psychedelic-experienced users.MethodsWe conducted a combined reanalysis of five independent datasets (N = 3817). Using standard and regularized regression analyses, we tested the relationship between degree of experience with various psychedelic substances (binary and continuous) and NR, both within a subsample of psychedelic-experienced participants as well as the complete sample including psychedelic-naïve participants.Results/outcomesAmong people experienced with psychedelics, only past use of psilocybin (versus LSD, mescaline, Salvia divinorum, ketamine, and ibogaine) was a reliable predictor of NR and its subdimensions. Weaker, less reliable results were obtained for the pharmacologically similar N,N-dimethyltryptamine (DMT). Results replicate when including psychedelic-naïve participants. In addition, among people exclusively experience with psilocybin, use frequency positively predicted NR.Conclusions/interpretationResults suggest that experience with psilocybin is the only reliable (and strongest) predictor of NR. Future research should focus on psilocybin when investigating effects of psychedelic on NR and determine whether pharmacological attributes or differences in user expectations/use settings are responsible for this observation.

A topic of growing interest in computational neuroscience is the discovery of fundamental principles underlying global dynamics and the self-organization of the brain. In particular, the notion that the brain operates near criticality has gained considerable support, and recent work has shown that the dynamics of different brain states may be modeled by pairwise maximum entropy Ising models at various distances from a phase transition, i.e., from criticality. Here we aim to characterize two brain states (psychedelics-induced and placebo) as captured by functional magnetic resonance imaging (fMRI), with features derived from the Ising spin model formalism (system temperature, critical point, susceptibility) and from algorithmic complexity. We hypothesized, along the lines of the entropic brain hypothesis, that psychedelics drive brain dynamics into a more disordered state at a higher Ising temperature and increased complexity. We analyze resting state blood-oxygen-level-dependent (BOLD) fMRI data collected in an earlier study from fifteen subjects in a control condition (placebo) and during ingestion of lysergic acid diethylamide (LSD). Working with the automated anatomical labeling (AAL) brain parcellation, we first create "archetype" Ising models representative of the entire dataset (global) and of the data in each condition. Remarkably, we find that such archetypes exhibit a strong correlation with an average structural connectome template obtained from dMRI (r = 0.6). We compare the archetypes from the two conditions and find that the Ising connectivity in the LSD condition is lower than in the placebo one, especially in homotopic links (interhemispheric connectivity), reflecting a significant decrease of homotopic functional connectivity in the LSD condition. The global archetype is then personalized for each individual and condition by adjusting the system temperature. The resulting temperatures are all near but above the critical point of the model in the para

Psychedelic drugs, including lysergic acid diethylamide (LSD) and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of relevance to the psychedelic experience, mediating both acute alterations in consciousness and long-term effects. However, no clear mechanistic explanation for this entropy increase has been put forward so far. We sought to do this here by building upon a recent whole-brain model of serotonergic neuromodulation, to study the entropic effects of 5HT2A-R activation. Our results reproduce the overall entropy increase observed in previous experiments in vivo, providing the first model-based explanation for this phenomenon. We also found that entropy changes were not uniform across the brain: entropy increased in all regions, but the larger effect were localised in visuo-occipital regions. Interestingly, at the whole-brain level, this reconfiguration was not well explained by 5HT2A-R density, but related closely to the topological properties of the brain's anatomical connectivity. These results help us understand the mechanisms underlying the psychedelic state and, more generally, the pharmacological modulation of whole-brain activity.

The research and use of psychedelic medicines to treat common mental health disorders has increased substantially in the past 2 decades. At the same time, knowledge is relatively uncommon among midwives regarding (1) the relative benefits of psychedelic-assisted therapy, (2) best practices associated with the delivery of psychedelic-assisted therapy, and (3) responsible integration of this potentially useful intervention into mental health treatment plans. The purpose of this review is to describe current applications of psychedelic medicines to treat common mental health disorders, to describe the current legal status of these medicines used in this context, and to explore the potential for midwifery practice in this area with further training. This article also addresses the disparities regarding LGBTQIA+ and BIPOC populations in relation to this topic and their historical exclusion from research and treatment access in this field.

Psychedelics including lysergic acid diethylamide (LSD) and psilocybin temporarily alter subjective experience through their neurochemical effects. Serotonin 2a (5-HT2a) receptor agonism by these compounds is associated with more diverse (entropic) brain activity. We postulate that this increase in entropy may arise in part from a flattening of the brain's control energy landscape, which can be observed using network control theory to quantify the energy required to transition between recurrent brain states. Using brain states derived from existing functional magnetic resonance imaging (fMRI) datasets, we show that LSD and psilocybin reduce control energy required for brain state transitions compared to placebo. Furthermore, across individuals, reduction in control energy correlates with more frequent state transitions and increased entropy of brain state dynamics. Through network control analysis that incorporates the spatial distribution of 5-HT2a receptors (obtained from publicly available positron emission tomography (PET) data under non-drug conditions), we demonstrate an association between the 5-HT2a receptor and reduced control energy. Our findings provide evidence that 5-HT2a receptor agonist compounds allow for more facile state transitions and more temporally diverse brain activity. More broadly, we demonstrate that receptor-informed network control theory can model the impact of neuropharmacological manipulation on brain activity dynamics.

Psychedelic microdosing describes the ingestion of near-threshold perceptible doses of classic psychedelic substances. Anecdotal reports and observational studies suggest that microdosing may promote positive mood and well-being, but recent placebo-controlled studies failed to find compelling evidence for this. The present study collected web-based mental health and related data using a prospective (before, during and after) design. Individuals planning a weekly microdosing regimen completed surveys at strategic timepoints, spanning a core four-week test period. Eighty-one participants completed the primary study endpoint. Results revealed increased self-reported psychological well-being, emotional stability and reductions in state anxiety and depressive symptoms at the four-week primary endpoint, plus increases in psychological resilience, social connectedness, agreeableness, nature relatedness and aspects of psychological flexibility. However, positive expectancy scores at baseline predicted subsequent improvements in well-being, suggestive of a significant placebo response. This study highlights a role for positive expectancy in predicting positive outcomes following psychedelic microdosing and cautions against zealous inferences on its putative therapeutic value.

The ergoline d-lysergic acid diethylamide (LSD) is one of the most potent psychedelic drugs. 1-Acetyl-LSD (ALD-52), a derivative of LSD containing an acetyl group on the indole nitrogen, also produces psychedelic effects in humans and has about the same potency as LSD. Recently, several other 1-acyl-substitued LSD derivatives, including 1-propanoyl-LSD (1P-LSD) and 1-butanoyl-LSD (1B-LSD), have appeared as designer drugs. Although these compounds are assumed to act as prodrugs for LSD, studies have not specifically tested this prediction. The present investigation was conducted to address the gap of information about the pharmacological effects and mechanism-of-action of 1-acyl-substituted LSD derivatives. Competitive binding studies and calcium mobilization assays were performed to assess the interaction of ALD-52, 1P-LSD, and 1B-LSD with serotonin 5-HT2 receptor subtypes. A receptorome screening was performed with 1B-LSD to assess its binding to other potential targets. Head twitch response (HTR) studies were performed in C57BL/6J mice to assess in vivo activation of 5-HT2A (the receptor thought to be primarily responsible for hallucinogenesis). Finally, liquid chromatography/ion-trap mass spectrometry (LC/MS) was used to quantify plasma levels of LSD in Sprague-Dawley rats treated with ALD-52 and 1P-LSD. 1-Acyl-substitution reduced the affinity of LSD for most monoamine receptors, including 5-HT2A sites, by one to two orders of magnitude. Although LSD acts as an agonist at 5-HT2 subtypes, ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists in Ca2+-mobilization assays. Despite the detrimental effect of 1-acyl substitution on 5-HT2A affinity and efficacy, 1-acyl-substitued LSD derivatives induce head twitches in mice with relatively high potency. High levels of LSD were detected in the plasma of rats after subcutaneous administration of ALD-52 and 1P-LSD, demonstrating these compounds are rapidly and efficiently deacylated in vivo. These findings are

Contemporary research with classic psychedelic drugs (e.g., lysergic acid diethylamide (LSD) and psilocybin) is indebted to the twentieth-century researchers and clinicians who generated valuable clinical knowledge of these substances through experimentation. Several recent reviews that highlight the contributions of this early literature have focused on psychedelic-assisted individual psychotherapy modalities. None have attempted to systematically identify and compile experimental studies of psychedelic-assisted group therapy. In therapeutic settings, psychedelics were often used to enhance group therapy for a variety of populations and clinical indications. We report on the results of a systematic review of the published literature in English and Spanish on psychedelic-assisted group therapies. Publications are characterized by their clinical approach, experimental method, and clinical outcomes. Given the renewed interest in the clinical use of psychedelic medicines, this review aims to stimulate hypotheses to be tested in future research on psychedelic-assisted psychotherapy, group process, and interpersonal functioning.

Mikrodosering av psykedeliska droger är den senaste trenden som verkar ha fått en stor spridning, främst bland unga människor för att uppnå ökad produktivitet och kreativitet, men även för att uppnå allmän psykisk hälsa. Denna uppsats lägger fokus på lysergsyradietylamid (LSD) och psilocybin (magic mushroom). Mikrodosering innebär att användaren tar en väldigt låg dos av substansen. Dosen ger ingen psykedelisk effekt, d.v.s. inga visuella effekter, inget förändrat medvetandetillstånd,och ingen förändrad tids-eller rumsuppfattning. Deltagare (n=201) besvarade en elektronisk enkät som distribuerades i olika forum med intresse för psykedeliska substanser. I denna deskriptiva sambandsstudie undersöktes motiveringen av att mikrodosera LSD-och psilocybin, samt vilka positiva och negativa effekter mikrodosering av dessa substanser har på den psykiska hälsan.Deltagare uppgav upplevd minskad depression, ångest och stress, men att det inte var den primära anledningen till att de mikrodoserade trots att 62% hade självdiagnostiserat sig med någon form av upplevd ohälsa. De primära motiven med att mikrodosera, som angavs i enkäten, var att förbättra den allmänna hälsan, samt för att nå ökad kreativitet och produktivitet. Trots upplevda negativa bieffekter under mikrodoseringscykeln uppgav majoriteten att de ville fortsätta att mikrodosera. På grund av urvalet är studieresultatet inte generaliserbart och efterföljande undersökningar med hypoteser och frågor är att föreslå.

Classic psychedelic drugs (serotonin 2A, or 5HT2A, receptor agonists) have notable effects on music listening. In the current report, blood oxygen level-dependent (BOLD) signal was collected during music listening in 25 healthy adults after administration of placebo, lysergic acid diethylamide (LSD), and LSD pretreated with the 5HT2A antagonist ketanserin, to investigate the role of 5HT2A receptor signaling in the neural response to the time-varying tonal structure of music. Tonality-tracking analysis of BOLD data revealed that 5HT2A receptor signaling alters the neural response to music in brain regions supporting basic and higher-level musical and auditory processing, and areas involved in memory, emotion, and self-referential processing. This suggests a critical role of 5HT2A receptor signaling in supporting the neural tracking of dynamic tonal structure in music, as well as in supporting the associated increases in emotionality, connectedness, and meaningfulness in response to music that are commonly observed after the administration of LSD and other psychedelics. Together, these findings inform the neuropsychopharmacology of music perception and cognition, meaningful music listening experiences, and altered perception of music during psychedelic experiences.

Lysergic acid diethylamide (LSD) is perhaps one of the best-known psychoactive substances and many structural modifications of this prototypical lysergamide have been investigated. Several lysergamides were recently encountered as 'research chemicals' or new psychoactive substances (NPS). Although lysergic acid morpholide (LSM-775) appeared on the NPS market in 2013, there is disagreement in the literature regarding the potency and psychoactive properties of LSM-775 in humans. The present investigation attempts to address the gap of information that exists regarding the analytical profile and pharmacological effects of LSM-775. A powdered sample of LSM-775 was characterized by X-ray crystallography, nuclear magnetic resonance spectroscopy (NMR), gas chromatography mass spectrometry (GC-MS), high mass accuracy electrospray MS/MS, high performance liquid chromatography (HPLC) diode array detection, HPLC quadrupole MS, and GC solid-state infrared analysis. Screening for receptor affinity and functional efficacy revealed that LSM-775 acts as a nonselective agonist at 5-HT1A and 5-HT2A receptors. Head twitch studies were conducted in C57BL/6J mice to determine whether LSM-775 activates 5-HT2A receptors and produces hallucinogen-like effects in vivo. LSM-775 did not induce the head twitch response unless 5-HT1A receptors were blocked by pretreatment with the antagonist WAY-100,635 (1 mg/kg, subcutaneous). These findings suggest that 5-HT1A activation by LSM-775 masks its ability to induce the head twitch response, which is potentially consistent with reports in the literature indicating that LSM-775 is only capable of producing weak LSD-like effects in humans.

Because of the ethical and regulatory hurdles associated with human studies, much of what is known about the psychopharmacology of hallucinogens has been derived from animal models. However, developing reliable animal models has proven to be a challenging task due to the complexity and variability of hallucinogen effects in humans. This chapter focuses on three animal models that are frequently used to test the effects of hallucinogens on unconditioned behavior: head twitch response (HTR), prepulse inhibition of startle (PPI), and exploratory behavior. The HTR has demonstrated considerable utility in the neurochemical actions of hallucinogens. However, the latter two models have clearer conceptual bridges to human phenomenology. Consistent with the known mechanism of action of hallucinogens in humans, the behavioral effects of hallucinogens in rodents are mediated primarily by activation of 5-HT2A receptors. There is evidence, however, that other receptors may play secondary roles. The structure-activity relationships (SAR) of hallucinogens are reviewed in relation to each model, with a focus on the HTR in rats and mice.

Mikrodosering av psykedeliska droger är den senaste trenden som verkar ha fått en stor spridning, främst bland unga människor för att uppnå ökad produktivitet och kreativitet, men även för att uppnå allmän psykisk hälsa. Denna uppsats lägger fokus på lysergsyradietylamid (LSD) och psilocybin (magic mushroom). Mikrodosering innebär att användaren tar en väldigt låg dos av substansen. Dosen ger ingen psykedelisk effekt, d.v.s. inga visuella effekter, inget förändrat medvetandetillstånd,och ingen förändrad tids-eller rumsuppfattning. Deltagare (n=201) besvarade en elektronisk enkät som distribuerades i olika forum med intresse för psykedeliska substanser. I denna deskriptiva sambandsstudie undersöktes motiveringen av att mikrodosera LSD-och psilocybin, samt vilka positiva och negativa effekter mikrodosering av dessa substanser har på den psykiska hälsan.Deltagare uppgav upplevd minskad depression, ångest och stress, men att det inte var den primära anledningen till att de mikrodoserade trots att 62% hade självdiagnostiserat sig med någon form av upplevd ohälsa. De primära motiven med att mikrodosera, som angavs i enkäten, var att förbättra den allmänna hälsan, samt för att nå ökad kreativitet och produktivitet. Trots upplevda negativa bieffekter under mikrodoseringscykeln uppgav majoriteten att de ville fortsätta att mikrodosera. På grund av urvalet är studieresultatet inte generaliserbart och efterföljande undersökningar med hypoteser och frågor är att föreslå.

Psychedelic substances are used for clinical applications(e.g., treatment of addictions, anxiety and depression) aswell as an investigative tool in neuroscientific research.Recently it has been proposed that the psychedelicphenomenon stems from the brain reaching an increasedentropic state. In this paper, we use the predictive codingframework to formalize the idea of an entropic brain. Wepropose that the increased entropic state is created whentop-down predictions in affected brain areas break up anddecompose into many more overly detailed predictions dueto hyper activation of 5-HT2A receptors in layer Vpyramidal neurons. We demonstrate that this novel, unifiedtheoretical account can explain the various and sometimescontradictory effects of psychedelics such as hallucination,heightened sensory input, synesthesia, increased trait ofopenness, ‘ego death’ and time dilation by up-regulation ofa variety of mechanisms the brain can use to minimizeprediction under the constraint of decomposed prediction.

Recent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) on the human brain but the underlying dynamics are not yet fully understood. Here we used 'connectome-harmonic decomposition', a novel method to investigate the dynamical changes in brain states. We found that LSD alters the energy and the power of individual harmonic brain states in a frequency-selective manner. Remarkably, this leads to an expansion of the repertoire of active brain states, suggestive of a general re-organization of brain dynamics given the non-random increase in co-activation across frequencies. Interestingly, the frequency distribution of the active repertoire of brain states under LSD closely follows power-laws indicating a re-organization of the dynamics at the edge of criticality. Beyond the present findings, these methods open up for a better understanding of the complex brain dynamics in health and disease.

What is the level of consciousness of the psychedelic state? Empirically, measures of neural signal diversity such as entropy and Lempel-Ziv (LZ) complexity score higher for wakeful rest than for states with lower conscious level like propofol-induced anesthesia. Here we compute these measures for spontaneous magnetoencephalographic (MEG) signals from humans during altered states of consciousness induced by three psychedelic substances: psilocybin, ketamine and LSD. For all three, we find reliably higher spontaneous signal diversity, even when controlling for spectral changes. This increase is most pronounced for the single-channel LZ complexity measure, and hence for temporal, as opposed to spatial, signal diversity. We also uncover selective correlations between changes in signal diversity and phenomenological reports of the intensity of psychedelic experience. This is the first time that these measures have been applied to the psychedelic state and, crucially, that they have yielded values exceeding those of normal waking consciousness. These findings suggest that the sustained occurrence of psychedelic phenomenology constitutes an elevated level of consciousness - as measured by neural signal diversity.

The question of how spatially organized activity in the visual cortex behaves during eyes-closed, lysergic acid diethylamide (LSD)-induced "psychedelic imagery" (e.g., visions of geometric patterns and more complex phenomena) has never been empirically addressed, although it has been proposed that under psychedelics, with eyes-closed, the brain may function "as if" there is visual input when there is none. In this work, resting-state functional connectivity (RSFC) data was analyzed from 10 healthy subjects under the influence of LSD and, separately, placebo. It was suspected that eyes-closed psychedelic imagery might involve transient local retinotopic activation, of the sort typically associated with visual stimulation. To test this, it was hypothesized that, under LSD, patches of the visual cortex with congruent retinotopic representations would show greater RSFC than incongruent patches. Using a retinotopic localizer performed during a nondrug baseline condition, nonadjacent patches of V1 and V3 that represent the vertical or the horizontal meridians of the visual field were identified. Subsequently, RSFC between V1 and V3 was measured with respect to these a priori identified patches. Consistent with our prior hypothesis, the difference between RSFC of patches with congruent retinotopic specificity (horizontal-horizontal and vertical-vertical) and those with incongruent specificity (horizontal-vertical and vertical-horizontal) increased significantly under LSD relative to placebo, suggesting that activity within the visual cortex becomes more dependent on its intrinsic retinotopic organization in the drug condition. This result may indicate that under LSD, with eyes-closed, the early visual system behaves as if it were seeing spatially localized visual inputs. Hum Brain Mapp 37:3031-3040, 2016. © 2016 Wiley Periodicals, Inc.

Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD's marked effects on the visual cortex did not significantly correlate with the drug's other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of "ego-dissolution" and "altered meaning," implying the importance of this particular circuit for the maintenance of "self" or "ego" and its processing of "meaning." Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.

Personality is known to be relatively stable throughout adulthood. Nevertheless, it has been shown that major life events with high personal significance, including experiences engendered by psychedelic drugs, can have an enduring impact on some core facets of personality. In the present, balanced-order, placebo-controlled study, we investigated biological predictors of post-lysergic acid diethylamide (LSD) changes in personality. Nineteen healthy adults underwent resting state functional MRI scans under LSD (75µg, I.V.) and placebo (saline I.V.). The Revised NEO Personality Inventory (NEO-PI-R) was completed at screening and 2 weeks after LSD/placebo. Scanning sessions consisted of three 7.5-min eyes-closed resting-state scans, one of which involved music listening. A standardized preprocessing pipeline was used to extract measures of sample entropy, which characterizes the predictability of an fMRI time-series. Mixed-effects models were used to evaluate drug-induced shifts in brain entropy and their relationship with the observed increases in the personality trait openness at the 2-week follow-up. Overall, LSD had a pronounced global effect on brain entropy, increasing it in both sensory and hierarchically higher networks across multiple time scales. These shifts predicted enduring increases in trait openness. Moreover, the predictive power of the entropy increases was greatest for the music-listening scans and when "ego-dissolution" was reported during the acute experience. These results shed new light on how LSD-induced shifts in brain dynamics and concomitant subjective experience can be predictive of lasting changes in personality. Hum Brain Mapp 37:3203-3213, 2016. © 2016 Wiley Periodicals, Inc.

Background: Estrogen has been reported to enhance well-being and quality of life during the climacteric phase. In women with an intact uterus estrogen treatment is always combined with progestins in order to protect the endometrium from hyperplasia and malignancies. However, in certain women the addition of progestins causes cyclicity in negative mood symptoms and physical symptoms similar to those encountered during ovulatory cycles in women with premenstrual dysphoric disorder (PMDD). The ovarian hormones estradiol and progesterone have profound effects on a number of neurotransmitter systems in the brain, such as the gamma aminobutyric acid (GABA) system and the serotonergic system. Progesterone metabolites, such as allopregnanolone and pregnanolone (also referred to as neurosteroids) modify the GABAA receptor in the central nervous system (CNS) and enhance GABAergic inhibitory transmission. Neurosteroid sensitivity in human studies can be studied by saccadic eye movement measurements using pharmacodynamic challenges with pregnanolone. Altered neurosteroid sensitivity has been suggested as a possible contributory factor to the progesterone/progestin-induced adverse mood effects of hormone replacement therapy (HRT). There is also evidence of estrogen treatment affecting the serotonergic system in postmenopausal women, although progestin addition has been less well studied. Aims and method: The aim was to investigate whether the negative mood symptoms experienced during the progestin or progesterone phase of HRT were associated with changes in neurosteroid sensitivity, or changes in platelet serotonin uptake site (transporter) and serotonin2A (5-HT2A) receptor binding. The intention was also to investigate whether hormonal changes during the normal menstrual cycle affect these peripheral serotonergic parameters. Postmenopausal women with climacteric symptoms were given HRT in two randomized, double-blinded, placebo-controlled crossover studies. The women received 2

Background: Estrogen has been reported to enhance well-being and quality of life during the climacteric phase. In women with an intact uterus estrogen treatment is always combined with progestins in order to protect the endometrium from hyperplasia and malignancies. However, in certain women the addition of progestins causes cyclicity in negative mood symptoms and physical symptoms similar to those encountered during ovulatory cycles in women with premenstrual dysphoric disorder (PMDD). The ovarian hormones estradiol and progesterone have profound effects on a number of neurotransmitter systems in the brain, such as the gamma aminobutyric acid (GABA) system and the serotonergic system. Progesterone metabolites, such as allopregnanolone and pregnanolone (also referred to as neurosteroids) modify the GABAA receptor in the central nervous system (CNS) and enhance GABAergic inhibitory transmission. Neurosteroid sensitivity in human studies can be studied by saccadic eye movement measurements using pharmacodynamic challenges with pregnanolone. Altered neurosteroid sensitivity has been suggested as a possible contributory factor to the progesterone/progestin-induced adverse mood effects of hormone replacement therapy (HRT). There is also evidence of estrogen treatment affecting the serotonergic system in postmenopausal women, although progestin addition has been less well studied. Aims and method: The aim was to investigate whether the negative mood symptoms experienced during the progestin or progesterone phase of HRT were associated with changes in neurosteroid sensitivity, or changes in platelet serotonin uptake site (transporter) and serotonin2A (5-HT2A) receptor binding. The intention was also to investigate whether hormonal changes during the normal menstrual cycle affect these peripheral serotonergic parameters. Postmenopausal women with climacteric symptoms were given HRT in two randomized, double-blinded, placebo-controlled crossover studies. The women received 2

Background: Estrogen has been reported to enhance well-being and quality of life during the climacteric phase. In women with an intact uterus estrogen treatment is always combined with progestins in order to protect the endometrium from hyperplasia and malignancies. However, in certain women the addition of progestins causes cyclicity in negative mood symptoms and physical symptoms similar to those encountered during ovulatory cycles in women with premenstrual dysphoric disorder (PMDD). The ovarian hormones estradiol and progesterone have profound effects on a number of neurotransmitter systems in the brain, such as the gamma aminobutyric acid (GABA) system and the serotonergic system. Progesterone metabolites, such as allopregnanolone and pregnanolone (also referred to as neurosteroids) modify the GABAA receptor in the central nervous system (CNS) and enhance GABAergic inhibitory transmission. Neurosteroid sensitivity in human studies can be studied by saccadic eye movement measurements using pharmacodynamic challenges with pregnanolone. Altered neurosteroid sensitivity has been suggested as a possible contributory factor to the progesterone/progestin-induced adverse mood effects of hormone replacement therapy (HRT). There is also evidence of estrogen treatment affecting the serotonergic system in postmenopausal women, although progestin addition has been less well studied. Aims and method: The aim was to investigate whether the negative mood symptoms experienced during the progestin or progesterone phase of HRT were associated with changes in neurosteroid sensitivity, or changes in platelet serotonin uptake site (transporter) and serotonin2A (5-HT2A) receptor binding. The intention was also to investigate whether hormonal changes during the normal menstrual cycle affect these peripheral serotonergic parameters. Postmenopausal women with climacteric symptoms were given HRT in two randomized, double-blinded, placebo-controlled crossover studies. The women received 2

Background: Estrogen has been reported to enhance well-being and quality of life during the climacteric phase. In women with an intact uterus estrogen treatment is always combined with progestins in order to protect the endometrium from hyperplasia and malignancies. However, in certain women the addition of progestins causes cyclicity in negative mood symptoms and physical symptoms similar to those encountered during ovulatory cycles in women with premenstrual dysphoric disorder (PMDD). The ovarian hormones estradiol and progesterone have profound effects on a number of neurotransmitter systems in the brain, such as the gamma aminobutyric acid (GABA) system and the serotonergic system. Progesterone metabolites, such as allopregnanolone and pregnanolone (also referred to as neurosteroids) modify the GABAA receptor in the central nervous system (CNS) and enhance GABAergic inhibitory transmission. Neurosteroid sensitivity in human studies can be studied by saccadic eye movement measurements using pharmacodynamic challenges with pregnanolone. Altered neurosteroid sensitivity has been suggested as a possible contributory factor to the progesterone/progestin-induced adverse mood effects of hormone replacement therapy (HRT). There is also evidence of estrogen treatment affecting the serotonergic system in postmenopausal women, although progestin addition has been less well studied. Aims and method: The aim was to investigate whether the negative mood symptoms experienced during the progestin or progesterone phase of HRT were associated with changes in neurosteroid sensitivity, or changes in platelet serotonin uptake site (transporter) and serotonin2A (5-HT2A) receptor binding. The intention was also to investigate whether hormonal changes during the normal menstrual cycle affect these peripheral serotonergic parameters. Postmenopausal women with climacteric symptoms were given HRT in two randomized, double-blinded, placebo-controlled crossover studies. The women received 2

Background: Estrogen has been reported to enhance well-being and quality of life during the climacteric phase. In women with an intact uterus estrogen treatment is always combined with progestins in order to protect the endometrium from hyperplasia and malignancies. However, in certain women the addition of progestins causes cyclicity in negative mood symptoms and physical symptoms similar to those encountered during ovulatory cycles in women with premenstrual dysphoric disorder (PMDD). The ovarian hormones estradiol and progesterone have profound effects on a number of neurotransmitter systems in the brain, such as the gamma aminobutyric acid (GABA) system and the serotonergic system. Progesterone metabolites, such as allopregnanolone and pregnanolone (also referred to as neurosteroids) modify the GABAA receptor in the central nervous system (CNS) and enhance GABAergic inhibitory transmission. Neurosteroid sensitivity in human studies can be studied by saccadic eye movement measurements using pharmacodynamic challenges with pregnanolone. Altered neurosteroid sensitivity has been suggested as a possible contributory factor to the progesterone/progestin-induced adverse mood effects of hormone replacement therapy (HRT). There is also evidence of estrogen treatment affecting the serotonergic system in postmenopausal women, although progestin addition has been less well studied. Aims and method: The aim was to investigate whether the negative mood symptoms experienced during the progestin or progesterone phase of HRT were associated with changes in neurosteroid sensitivity, or changes in platelet serotonin uptake site (transporter) and serotonin2A (5-HT2A) receptor binding. The intention was also to investigate whether hormonal changes during the normal menstrual cycle affect these peripheral serotonergic parameters. Postmenopausal women with climacteric symptoms were given HRT in two randomized, double-blinded, placebo-controlled crossover studies. The women received 2

Studies of the available fluorometric assay procedures for LSD-25 are described for possible clinical application. Variability of plasma 'blank' background fluorescence values were found to prohibit the use of standard fluorometric procedures without modification. A little known fluorometric procedure is described which minimuzes this problem and maintains the sensitivity of the assay at the nanogram level. Modifications of this method are suggested which could increase the sensitivity of this method to the subnanogram level. (Author)

The effect of LSD on E. coli was examined as a test system for damage to genetic material. LSD had a dose-dependent effect on bacterial growth rate. This effect was not amplified by the DNA-repair inhibitor caffeine. The lowering of the growth rate by LSD was shown to be completely reversible upon dilution. LSD was shown to cause a dose dependent extension of the growth recovery lag due to UV damage. Caffeine caused a much larger extension of this lag time. (Author)