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-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 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 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.

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.

Flashbacks and schizophrenia

1993 ◽  
Vol 10 (1) ◽  
pp. 37-39 ◽  
Author(s):  
Hazim Obaydi
Keyword(s):  
Drug Misuse ◽  
Psychotic Experience ◽  
Psychedelic Drugs ◽  
Psychedelic Drug ◽  
Perceptual Changes

AbstractThree cases of schizophrenia (DSM-III-R) (l), whilst responding to treatment, exhibit a group of symptoms which had the essential features of “flashbacks”, as described in relation to psychedelic drugs, though there was no evidence of psychedelic drug misuse. Symptoms were characterised by memory flashes of the original psychotic experience, followed immediately by very brief re-experiencing of earlier symptoms, including visual perceptual changes in clear consciousness and full insight. Symptoms were less clear, less severe, but more distressing, than the original episodes. Symptoms were triggered by stress/anxiety, and relieved by an anxiolytic. The association of flashbacks with schizophrenia is discussed.

scholarly journals Long-lasting beneficial effects of central serotonin receptor 7 stimulation in female mice modeling Rett syndrome

2015 ◽  
Vol 9 ◽  
Author(s):  
Bianca De Filippis ◽  
Valentina Chiodi ◽  
Walter Adriani ◽  
Enza Lacivita ◽  
Cinzia Mallozzi ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Serotonin Receptor ◽  
Female Mice ◽  
Beneficial Effects

scholarly journals Psychedelic drugs—a new era in psychiatry?

2019 ◽  
Vol 21 (2) ◽  
pp. 139-147 ◽  
Keyword(s):  
Psychiatric Research ◽  
European Medicines Agency ◽  
Post Traumatic Stress ◽  
Phase 3 ◽  
New Era ◽  
Psychedelic Drugs ◽  
Post Traumatic ◽  
Resistant Depression ◽  
Anxiety Depression ◽  
Recreational Use

This article covers the renaissance of classical psychedelic drugs such as psilocybin and LSD plus 3,4-methylene dioxymethamphetamine (MDMA—ecstasy) in psychiatric research. These drugs were used quite extensively before they became prohibited. This ban had little impact on recreational use, but effectively stopped research and clinical treatments, which up to that point had looked very promising in several areas of psychiatry. In the past decade a number of groups have been working to re-evaluate the utility of these substances in medicine. So far highly promising preliminary data have been produced with psilocybin in anxiety, depression, smoking, alcoholism, and with MDMA for post-traumatic stress disorder (PTSD) and alcoholism. These findings have led to the European Medicines Agency approving psilocybin for a phase 3 study in treatment-resistant depression and the Food and Drug Administration for PTSD with MDMA. Both trials should read out in 2020, and if the results are positive we are likely to see these medicines approved for clinical practice soon afterwards.

scholarly journals Cross-Sectional Associations Between Lifetime Use of Psychedelic Drugs and Psychometric Measures During the COVID-19 Confinement: A Transcultural Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Dóra Révész ◽  
Genís Ona ◽  
Giordano N. Rossi ◽  
Juliana M. Rocha ◽  
Rafael G. dos Santos ◽  
...  
Keyword(s):  
Mental Health ◽  
Social Support ◽  
Psychological Distress ◽  
Drug Users ◽  
Protective Factor ◽  
Effective Measure ◽  
Psychedelic Drugs ◽  
Psychedelic Drug ◽  
Prospective Longitudinal ◽  
The Impact

Background: One of the main public health strategies adopted at the beginning of the COVID-19 pandemic consisted of implementing strict lockdowns to stop the transmission of the virus. Despite being an effective measure, the confinement and the associated social isolation create a stressful, potentially lengthy situations that has been proven to have several psychological consequences. Given the potential benefits that certain psychedelic drugs have shown for the treatment of psychological disorders, this study aimed to assess the impact of lifetime psychedelic drug use on mental health in relation to the first strict lockdown adopted by various countries (April-July 2020).Methods: Subjects completed an online survey that inquired about sociodemographic factors, activities, and lifestyle factors during confinement, as well as health and mental health related factors. Subjects were asked about their lifetime use of psychedelic drugs (MDMA, ayahuasca, psilocybin-containing mushrooms, LSD, peyote, San Pedro, Bufo alvarius or 5-MeO-DMT, and others), being classified as regular users (more than once per 6 months), occasional users, or non-users. The survey included psychometric tests used to assess psychological distress, peritraumatic stress, social support, psychopathological symptoms, and personality. Linear regressions were performed with psychedelic drug users as the independent variable and psychometric factors as the outcomes, while correcting for age, gender, language, religion, spirituality, and use of non-psychedelic drugs.Results: The study included 2,974 English, Portuguese, and Spanish speakers (497 regular users of psychedelic drugs, 606 occasional users, and 1,968 non-users). On average, respondents were 36 years old and 70% were female. Psychedelic drug users, especially regular ones, reported less psychological distress, less peritraumatic stress, and more social support. Regarding personality measures, psychedelic drug users scored higher on the novelty-seeking and self-transcendence scales, and lower on cooperativeness.Conclusion: Our findings showed that regular users of psychedelic drugs had less psychological stress and some personality differences when compared to occasional users and non-users. This suggests that either the use of psychedelics might be a protective factor itself or people with certain previous traits are more prone to frequently using psychedelic drugs. Future prospective longitudinal research should investigate the underlying processes observed in this study to develop consistent hypotheses.

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