scholarly journals LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ramona M. Rodriguiz ◽  
Vineet Nadkarni ◽  
Christopher R. Means ◽  
Vladimir M. Pogorelov ◽  
Yi-Ting Chiu ◽  
...  
Keyword(s):  
Serotonin Receptor ◽  
Lysergic Acid ◽  
Clinical Use ◽  
Beneficial Effects ◽  
Nicotine Abuse ◽  
Psychedelic Drugs ◽  
Motor Activities ◽  
Drug Actions ◽  
Psychedelic Drug ◽  
Anxiety Depression

AbstractRecent evidence suggests that psychedelic drugs can exert beneficial effects on anxiety, depression, and ethanol and nicotine abuse in humans. However, their hallucinogenic side-effects often preclude their clinical use. Lysergic acid diethylamide (LSD) is a prototypical hallucinogen and its psychedelic actions are exerted through the 5-HT2A serotonin receptor (5-HT2AR). 5-HT2AR activation stimulates Gq- and β-arrestin- (βArr) mediated signaling. To separate these signaling modalities, we have used βArr1 and βArr2 mice. We find that LSD stimulates motor activities to similar extents in WT and βArr1-KO mice, without effects in βArr2-KOs. LSD robustly stimulates many surrogates of psychedelic drug actions including head twitches, grooming, retrograde walking, and nose-poking in WT and βArr1-KO animals. By contrast, in βArr2-KO mice head twitch responses are low with LSD and this psychedelic is without effects on other surrogates. The 5-HT2AR antagonist MDL100907 (MDL) blocks the LSD effects. LSD also disrupts prepulse inhibition (PPI) in WT and βArr1-KOs, but not in βArr2-KOs. MDL restores LSD-mediated disruption of PPI in WT mice; haloperidol is required for normalization of PPI in βArr1-KOs. Collectively, these results reveal that LSD’s psychedelic drug-like actions appear to require βArr2.

scholarly journals Genetic deletion of β-arrestin 2 modulates LSD-stimulated behaviors in mice

2021 ◽  
Author(s):  
Ramona M. Rodriguiz ◽  
Vineet Nadkarni ◽  
Christopher R. Means ◽  
Vladimir M. Pogorelov ◽  
Yi-Ting Chiu ◽  
...  
Keyword(s):  
Serotonin Receptor ◽  
Beneficial Effects ◽  
Nicotine Abuse ◽  
Head Twitches ◽  
Psychedelic Drugs ◽  
Motor Activities ◽  
Drug Actions ◽  
Psychedelic Drug ◽  
Genetic Deletion ◽  
Anxiety Depression

Abstract Recent evidence suggests that psychedelic drugs can exert beneficial effects on anxiety, depression, and ethanol and nicotine abuse in humans. However, their hallucinogenic side-effects often preclude their clinical use. Lysergic acid diethylamide (LSD) is a prototypical hallucinogen and its psychedelic actions are exerted through the 5-HT2A serotonin receptor (5-HT2AR). 5-HT2AR activation stimulates Gq- and β-arrestin- (βArr) mediated signaling. To separate these signaling modalities, we have used βArr1 and βArr2 mice. We find that LSD stimulates motor activities to similar extents in WT and βArr1-KO mice, with non-significant effects in βArr2-KOs. LSD robustly stimulates many surrogates of psychedelic drug actions including head twitches, grooming, retrograde walking, and nose-poking in WT and βArr1-KO animals. By contrast, LSD slightly stimulates head twitches in βArr2-KO mice, without effects on other surrogates. The 5-HT2AR antagonist MDL100907 (MDL) blocks these LSD effects. LSD also disrupts prepulse inhibition (PPI) in WT and βArr1-KOs; PPI is unaffected in βArr2-KOs. MDL restores PPI in WT mice, but this antagonist is without effect and haloperidol is required in βArr1-KOs. Collectively, these results reveal that LSD’s psychedelic drug-like actions appear to require βArr2.

scholarly journals LSD’s effects are differentially modulated in arrestin knockout mice

2021 ◽  
Author(s):  
Ramona M. Rodriguiz ◽  
Vineet Nadkarni ◽  
Christopher R. Means ◽  
Yi-Ting Chiu ◽  
Bryan L. Roth ◽  
...  
Keyword(s):  
Serotonin Receptor ◽  
Temperature Response ◽  
Beneficial Effects ◽  
Nicotine Abuse ◽  
Head Twitches ◽  
Way 100635 ◽  
Psychedelic Drugs ◽  
Motor Activities ◽  
Drug Actions ◽  
Psychedelic Drug

ABSTRACTRecent evidence suggests that psychedelic drugs can exert beneficial effects on anxiety, depression, and ethanol and nicotine abuse in humans. However, the hallucinogenic side-effects of psychedelics often preclude their clinical use. Lysergic acid diethylamide (LSD) is a prototypical hallucinogen and its psychedelic actions are exerted through the 5-HT2A serotonin receptor (5-HT2AR). 5-HT2AR activation stimulates Gq- and β-arrestin-(βArr) mediated signaling. To separate effects of these signaling modes, we have used βArr1 and βArr2 mice. We find that LSD stimulates motor activities to similar extents in WT and βArr1-KO mice, with non-significant effects in βArr2-KOs. LSD robustly stimulates many surrogates of psychedelic drug actions including head twitches, grooming, retrograde walking, and nose poking in WT and βArr1-KO animals. In contrast, LSD only slightly stimulates head twitches in βArr2-KO mice, without effects on retrograde walking or nose poking. The 5-HT2AR antagonist MDL100907 (MDL) blocks these LSD effects. LSD also disrupts prepulse inhibition (PPI) in WT and βArr1-KOs; PPI is unaffected in βArr2-KOs. MDL restores PPI in WT mice, but this antagonist is without effect and haloperidol is required in βArr1-KOs. LSD produces a biphasic body-temperature response in WT mice, a monophasic response in βArr1-KOs, and is without effect in βArr2 mutants. Both MDL and the 5-HT1AR antagonist, WAY 100635 (WAY), block the effects of LSD on body temperatures in WT mice, whereas WAY is effective in βArr1-KOs. Collectively, these results reveal that LSD produces diverse behavioral effects through βArr1 and βArr2, and that LSD’s psychedelic drug-like actions appear to require βArr2.

scholarly journals Improved colour blindness symptoms associated with recreational psychedelic use: Results from the Global Drug Survey 2017

2020 ◽  
Vol 6 ◽  
pp. 205032452094234
Author(s):  
JEC Anthony ◽  
A Winstock ◽  
JA Ferris ◽  
DJ Nutt
Keyword(s):  
Preliminary Data ◽  
Lysergic Acid ◽  
Lysergic Acid Diethylamide ◽  
Colour Perception ◽  
Neural Connections ◽  
Drug Ingestion ◽  
Cortical Areas ◽  
Psychedelic Drugs ◽  
Psychedelic Drug ◽  
Colour Blindness

It is well documented that psychedelic drugs can have a profound effect on colour perception. After previous research involving psychedelic drug ingestion, several participants had written to the authors describing how symptoms of their colour blindness had improved. The Global Drugs Survey runs the world’s largest annual online drug survey. In the Global Drugs Survey 2017, participants reporting the use of lysergic acid diethylamide or psilocybin in the last 12 months were asked,    We have received reports from some people with colour-blindness that this improves after they use psychedelics. If you have experienced such an effect can you please describe it in the box below, say what drug you took and how long the effect lasted. We received 47 responses that could be usefully categorised of which 23 described improved colour blindness. Commonly cited drugs were LSD and psilocybin; however, several other psychedelic compounds were also listed. Some respondents cited that the changes in colour blindness persisted, from a period of several days to years. Improved colour blindness may be a result of new photisms experienced in the psychedelic state aligning with pre-existing concepts of colour to be ascribed a label. Connections between visual and linguistic cortical areas may be enhanced due to disorder in the brain’s neural connections induced by psychedelics allowing these new photisms and concepts to become linked. This paper provides preliminary data regarding improved colour blindness accompanying recreational psychedelic use which may be further investigated in future iterations of the Global Drugs Survey or in a stand-alone Global Drugs Survey-managed psychedelics survey.

scholarly journals Pharmacologic analysis of non-synonymous coding 5-HT2A SNPs reveals alterations psychedelic drug potencies and efficacies

2021 ◽  
Author(s):  
Gavin Schmitz ◽  
Jeffrey DiBerto ◽  
Manish Jain ◽  
Bryan L Roth
Keyword(s):  
Random Sequence ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Synonymous Snps ◽  
Sequence Variations ◽  
Psychedelic Drugs ◽  
In Vitro Pharmacology ◽  
Drug Actions ◽  
Psychedelic Drug

Serotonin (5-Hydroxytryptamine; 5-HT) 2A receptor (5-HT2AR) signaling is essential for the actions of classical psychedelic drugs. In this study, we examined whether random sequence variations in the gene (single nucleotide polymorphisms, SNPs) encoding the 5-HT2AR affect the signaling of four commonly used psychedelic drugs. We examined the in vitro pharmacology of seven non-synonymous SNPs, which give rise to S12N, T25N, D48N, I197V, A230T, A447V, and H452Y variant 5-HT2A serotonin receptors. We found that these non-synonymous SNPs exert statistically significant, although modest, effects on the efficacy and potency of four therapeutically relevant hallucinogens. Significantly, the in vitro pharmacological effects of the SNPs drug actions at 5-HT2AR are drug specific.

scholarly journals Cannabinoid and Cannabinoid-Related Receptors in the Myenteric Plexus of the Porcine Ileum

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 263
Author(s):  
Andrea Toschi ◽  
Giorgia Galiazzo ◽  
Andrea Piva ◽  
Claudio Tagliavia ◽  
Gemma Mazzuoli-Weber ◽  
...  
Keyword(s):  
Myenteric Plexus ◽  
Serotonin Receptor ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Visceral Pain ◽  
Wide Distribution ◽  
Nerve Fibers ◽  
Enteric Neurons ◽  
Beneficial Effects ◽  
Anatomical Basis

An important piece of evidence has shown that molecules acting on cannabinoid receptors influence gastrointestinal motility and induce beneficial effects on gastrointestinal inflammation and visceral pain. The aim of this investigation was to immunohistochemically localize the distribution of canonical cannabinoid receptor type 1 (CB1R) and type 2 (CB2R) and the cannabinoid-related receptors transient potential vanilloid receptor 1 (TRPV1), transient potential ankyrin receptor 1 (TRPA1), and serotonin receptor 5-HT1a (5-HT1aR) in the myenteric plexus (MP) of pig ileum. CB1R, TRPV1, TRPA1, and 5-HT1aR were expressed, with different intensities in the cytoplasm of MP neurons. For each receptor, the proportions of the immunoreactive neurons were evaluated using the anti-HuC/HuD antibody. These receptors were also localized on nerve fibers (CB1R, TRPA1), smooth muscle cells of tunica muscularis (CB1R, 5-HT1aR), and endothelial cells of blood vessels (TRPV1, TRPA1, 5-HT1aR). The nerve varicosities were also found to be immunoreactive for both TRPV1 and 5-HT1aR. No immunoreactivity was documented for CB2R. Cannabinoid and cannabinoid-related receptors herein investigated showed a wide distribution in the enteric neurons and nerve fibers of the pig MP. These results could provide an anatomical basis for additional research, supporting the therapeutic use of cannabinoid receptor agonists in relieving motility disorders in porcine enteropathies.

Look of Life

2020 ◽  
pp. 364-375
Author(s):  
Vittoria Sichi ◽  
Giacomo Ercolani ◽  
Luca Franchini ◽  
Luca Golfari ◽  
Silvia Varani ◽  
...  
Keyword(s):  
Pilot Study ◽  
Cancer Patients ◽  
Primary Objective ◽  
Control Group ◽  
Emotional Wellbeing ◽  
Structured Interviews ◽  
Beneficial Effects ◽  
Pain Symptoms ◽  
Anxiety Depression ◽  
At Home

The use of virtual reality (VR) shows promising results in improving the emotional wellbeing of cancer patients, reducing anxiety, depression, and pain symptoms. No data exist concerning the use of VR in cancer patients assisted at home. The ANT Foundation decided to conduct a pilot study to test the use of VR in cancer patients assisted at home. Fifty-eight ANT patients were randomized and assigned to a control group that didn't use VR devices and to an experimental group that used them. The primary objective of the pilot study was to determine whether VR device could be a viable instrument in homecare patients. Furthermore, the aim of the study was to discover if VR could have beneficial effects on patients' quality of life as well as discover which kind of videos were more effective. The innovative aspect of this study was to test the use of VR directly at home of patients, proposing a use of VR that is compatible with the needs and the daily rhythms of families, and investigating its effectiveness through appropriate validated psychometric questionnaires and semi-structured interviews.

Changes During Weeks in Effects of Tricyclic Drugs on the Human Sleeping Brain

1972 ◽  
Vol 120 (559) ◽  
pp. 663-672 ◽  
Author(s):  
D. L. F. Dunleavy ◽  
Vlasta Brezinova ◽  
Ian Oswald ◽  
A. W. Maclean ◽  
M. Tinker
Keyword(s):  
Human Brain ◽  
Time Scale ◽  
Mode Of Action ◽  
Tricyclic Antidepressants ◽  
Brain State ◽  
Clinical Use ◽  
Brain Physiology ◽  
Brain Functions ◽  
Drug Actions ◽  
Brain Changes

The tricyclic antidepressants are established in therapy but not in mode of action. Effects on mouse or rat brain of single and relatively enormous doses provide the basis for theories. Yet it may be inferred that the clinical use of tricyclic antidepressants relies upon an induction of brain changes on a time-scale of weeks. Studies of tricyclic drug actions upon human brain physiology are as scanty as are easily-measurable human brain functions. Electrophysiological techniques, however, can conveniently be applied during one principal brain-state, namely sleep, when there is a relative freedom from uncontrollable extraneous variables.

scholarly journals The early use of MDMA (‘Ecstasy’) in psychotherapy (1977–1985)

2018 ◽  
Vol 4 ◽  
pp. 205032451876744 ◽  
Author(s):  
Torsten Passie
Keyword(s):  
United States ◽  
Group Therapy ◽  
The United States ◽  
Recreational Drug ◽  
Beneficial Effects ◽  
International Scale ◽  
Early Use ◽  
Psychedelic Drugs

3,4-Methylenedioxymethamphetamine (MDMA), also known as ecstasy, was first synthesized in 1912 but first reached widespread popularity as a legal alternative after the much sought-after recreational drug 3,4-methylenedioxy-amphetamine (MDA) was made illegal in 1970. Because of its benign, feeling-enhancing, and nonhallucinatory properties, MDMA was used by a few dozen psychotherapists in the United States between 1977 and 1985, when it was still legal. This article looks into the contexts and practices of its psychotherapeutic use during these years. Some of the guidelines, recommendations, and precautions developed then are similar to those that apply to psychedelic drugs, but others are specific for MDMA. It is evident from this review that the therapists pioneering the use of MDMA were able to develop techniques (and indications/counterindications) for individual and group therapy that laid the groundwork for the use of MDMA in later scientific studies. In retrospect, it appears that the perceived beneficial effects of MDMA supported a revival of psycholytic/psychedelic therapy on an international scale.

scholarly journals Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target

2018 ◽  
Vol 19 (9) ◽  
pp. 2516 ◽  
Author(s):  
Ewelina Piktel ◽  
Ilya Levental ◽  
Bonita Durnaś ◽  
Paul Janmey ◽  
Robert Bucki
Keyword(s):  
Therapeutic Target ◽  
Animal Studies ◽  
Recent Progress ◽  
Mechanisms Of Action ◽  
Current Data ◽  
Clinical Use ◽  
Plasma Gelsolin ◽  
Beneficial Effects ◽  
Potential Biomarker ◽  
Efficacy Of Treatment

Gelsolin, an actin-depolymerizing protein expressed both in extracellular fluids and in the cytoplasm of a majority of human cells, has been recently implicated in a variety of both physiological and pathological processes. Its extracellular isoform, called plasma gelsolin (pGSN), is present in blood, cerebrospinal fluid, milk, urine, and other extracellular fluids. This isoform has been recognized as a potential biomarker of inflammatory-associated medical conditions, allowing for the prediction of illness severity, recovery, efficacy of treatment, and clinical outcome. A compelling number of animal studies also demonstrate a broad spectrum of beneficial effects mediated by gelsolin, suggesting therapeutic utility for extracellular recombinant gelsolin. In the review, we summarize the current data related to the potential of pGSN as an inflammatory predictor and therapeutic target, discuss gelsolin-mediated mechanisms of action, and highlight recent progress in the clinical use of pGSN.

scholarly journals The Employment of Leukotriene Antagonists in Cutaneous Diseases Belonging to Allergological Field

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Eustachio Nettis ◽  
Maddalena D'Erasmo ◽  
Elisabetta Di Leo ◽  
Gianfranco Calogiuri ◽  
Vincenzo Montinaro ◽  
...  
Keyword(s):  
Chronic Urticaria ◽  
Atopic Eczema ◽  
Inflammatory Responses ◽  
Affinity Binding ◽  
Clinical Use ◽  
Leukotriene Antagonists ◽  
High Affinity Binding ◽  
Beneficial Effects ◽  
High Affinity ◽  
Proinflammatory Mediators

Leukotrienes (LTs) are potent biological proinflammatory mediators. LTC4, LTD4, and LTE4 are more frequently involved in chronic inflammatory responses and exert their actions binding to a cysteinyl-LT 1 (CysLT1) receptor and a cysteinyl-LT 2 (CysLT2) receptor. LTs receptor antagonists available for clinical use demonstrate high-affinity binding to the CysLT1 receptor. In this paper the employment of anti-LTs in allergic cutaneous diseases is analyzed showing that several studies have recently reported a beneficial effects of these agents (montelukast and zafirlukast as well as zileuton) for the treatment of some allergic cutaneous related diseases-like chronic urticaria and atopic eczema although their proper application remains to be established.

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