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 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 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.

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 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.

In Vivo Assessment of the Midbrain Raphe Nuclear Regulation of Serotonin Release in the Hamster Suprachiasmatic Nucleus

1999 ◽  
Vol 81 (4) ◽  
pp. 1469-1477 ◽  
Author(s):  
Thomas E. Dudley ◽  
Lisa A. Dinardo ◽  
J. David Glass
Keyword(s):  
Suprachiasmatic Nucleus ◽  
In Vivo Microdialysis ◽  
Serotonin Release ◽  
Significant Inhibition ◽  
Serotonergic Activity ◽  
Way 100635 ◽  
Drug Actions ◽  
In Vivo Assessment ◽  
Stimulation Of

In vivo assessment of the midbrain raphe nuclear regulation of serotonin release in the hamster suprachiasmatic nucleus. Serotonin (5-HT) plays important regulatory roles in mammalian circadian timekeeping; however, little is known concerning the regulation of serotonergic activity in the circadian clock located in the suprachiasmatic nuclei (SCN). By using in vivo microdialysis to measure 5-HT release we demonstrated that electrical or pharmacological stimulations of the dorsal or median raphe nuclei (DRN and MRN, respectively) can alter basal release of 5-HT in the hamster SCN. There were similar increases in SCN 5-HT release after electrical stimulation of either the MRN or DRN, indicating that both could contribute to the serotonergic activity in the SCN. Systemic pretreatment with the 5-HT antagonist metergoline abolished DRN-induced SCN 5-HT release but had little effect on MRN-induced SCN 5-HT release, suggesting different pathways for these nuclei in regulating 5-HT output in the SCN. Microinjections of the 5-HT1A autoreceptor agonist 8-OH-DPAT or antagonist WAY 100635 into the MRN caused significant inhibition and stimulation of SCN 5-HT release, respectively. Both drugs had substantially less effect in the DRN. These differential drug actions indicate that somatodendritic 5-HT1A autoreceptors on MRN neurons provide the prominent raphe autoregulation of 5-HT output in the SCN. Collectively the current results are evidence that DRN as well as MRN neurons can contribute to the regulation of 5-HT release in the hamster SCN. On the basis of the current observations and those from recent anatomic tracing studies of serotonergic projections to SCN it is hypothesized that DRN input to the SCN could be mediated by a DRN → MRN → SCN pathway involving a 5-HT–sensitive multisynaptic interaction between the DRN and MRN neurons.

scholarly journals Lactation improves pancreatic β cell mass and function through serotonin production

2020 ◽  
Vol 12 (541) ◽  
pp. eaay0455
Author(s):  
Joon Ho Moon ◽  
Hyeongseok Kim ◽  
Hyunki Kim ◽  
Jungsun Park ◽  
Wonsuk Choi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Glucose Tolerance ◽  
Serotonin Receptor ◽  
Cell Function ◽  
Cell Mass ◽  
Β Cells ◽  
Β Cell ◽  
Beneficial Effects

Pregnancy imposes a substantial metabolic burden on women through weight gain and insulin resistance. Lactation reduces the risk of maternal postpartum diabetes, but the mechanisms underlying this benefit are unknown. Here, we identified long-term beneficial effects of lactation on β cell function, which last for years after the cessation of lactation. We analyzed metabolic phenotypes including β cell characteristics in lactating and non-lactating humans and mice. Lactating and non-lactating women showed comparable glucose tolerance at 2 months after delivery, but after a mean of 3.6 years, glucose tolerance in lactated women had improved compared to non-lactated women. In humans, the disposition index, a measure of insulin secretory function of β cells considering the degree of insulin sensitivity, was higher in lactated women at 3.6 years after delivery. In mice, lactation improved glucose tolerance and increased β cell mass at 3 weeks after delivery. Amelioration of glucose tolerance and insulin secretion were maintained up to 4 months after delivery in lactated mice. During lactation, prolactin induced serotonin production in β cells. Secreted serotonin stimulated β cell proliferation through serotonin receptor 2B in an autocrine and paracrine manner. In addition, intracellular serotonin acted as an antioxidant to mitigate oxidative stress and improved β cell survival. Together, our results suggest that serotonin mediates the long-term beneficial effects of lactation on female metabolic health by increasing β cell proliferation and reducing oxidative stress in β cells.

Sign in / Sign up

Export Citation Format

Share Document