scholarly journals Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin

2020 ◽  
Vol 45 (12) ◽  
pp. 2003-2011 ◽  
Author(s):  
N. L. Mason ◽  
K. P. C. Kuypers ◽  
F. Müller ◽  
J. Reckweg ◽  
D. H. Y. Tse ◽  
...  

Abstract There is growing interest in the therapeutic utility of psychedelic substances, like psilocybin, for disorders characterized by distortions of the self-experience, like depression. Accumulating preclinical evidence emphasizes the role of the glutamate system in the acute action of the drug on brain and behavior; however this has never been tested in humans. Following a double-blind, placebo-controlled, parallel group design, we utilized an ultra-high field multimodal brain imaging approach and demonstrated that psilocybin (0.17 mg/kg) induced region-dependent alterations in glutamate, which predicted distortions in the subjective experience of one’s self (ego dissolution). Whereas higher levels of medial prefrontal cortical glutamate were associated with negatively experienced ego dissolution, lower levels in hippocampal glutamate were associated with positively experienced ego dissolution. Such findings provide further insights into the underlying neurobiological mechanisms of the psychedelic, as well as the baseline, state. Importantly, they may also provide a neurochemical basis for therapeutic effects as witnessed in ongoing clinical trials.

2021 ◽  
Author(s):  
Suhas Ganesh ◽  
Jose Cortes-Briones ◽  
Ashley M Schnakenberg Martin ◽  
Patrick D Skosnik ◽  
Deepak Cyril D'Souza ◽  
...  

Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the principal phyto-cannabinoids in the cannabis plant. The differential and possibly antagonistic effects of these compounds on specific brain and behavioral responses, and the mechanisms underlying their effects have generated extensive interest in pre-clinical and clinical neuroscience investigations. In this double-blind randomized placebo-controlled counterbalanced human laboratory experiment, we examined the effects of three different dose ratios of CBD: THC (1:1, 2:1 and 3:1) on neural noise, an electrophysiological biomarker of psychosis known to be sensitive to cannabinoids as well as subjective and psychotomimetic effects. Interestingly, the lowest CBD:THC ratio (1:1) resulted in maximal attenuation of both THC induced psychotomimetic effects (PANSS positive - ATS = 7.83, df = 1, pcorr = 0.015) and neural noise (ATS = 8.83, df = 1, pcorr = 0.009) with an inverse-linear dose response relationship. Further, in line with previous studies, addition of CBD did not reduce the subjective experience of THC induced high (p > 0.05 for all CBD doses). These novel results demonstrate that CBD attenuates THC induced subjective and objective effects relevant to psychosis- but in a dose/ratio dependent manner. Given the increasing global trend of cannabis liberalization and application for medical indications, these results assume considerable significance given the potential dose related interactions of these key phyto-cannabinoids.


2005 ◽  
Vol 20 (2) ◽  
pp. 92-95 ◽  
Author(s):  
JR Calabrese ◽  
DJ Rapport ◽  
EA Youngstrom ◽  
K. Jackson ◽  
S. Bilali ◽  
...  

AbstractThe rapid cycling variant of bipolar disorder is defined as the occurrence of four periods of either manic or depressive illness within 12 months. Patients suffering from this variant of bipolar disorder have an unmet need for effective treatment. This review examines two major studies in an attempt to update understanding of the current therapies available to treat rapid cycling patients. The first trial compares lamotrigine versus placebo in 182 patients studied for 6 months. The second is a recently completed, 20-month trial comparing divalproate and lithium in 60 patients. Both trials had a double-blind, randomized parallel-group design. The data from the latter study indicate that there are no large differences in efficacy between lithium and divalproate in the long-term treatment of rapid cycling bipolar disorder. In addition, lamotrigine has the potential to complement the spectrum of lithium and divalproate through its greater efficacy for depressive symptoms.


2020 ◽  
Author(s):  
Sara Ruth Westbrook ◽  
Lauren Carrica ◽  
Asia Banks ◽  
Joshua Michael Gulley

Adolescent use of amphetamine and its closely related, methylated version methamphetamine, is alarmingly high in those who use drugs for nonmedical purposes. This raises serious concerns about the potential for this drug use to have a long-lasting, detrimental impact on the normal development of the brain and behavior that is ongoing during adolescence. In this review, we explore recent findings from both human and laboratory animal studies that investigate the consequences of amphetamine and methamphetamine exposure during this stage of life. We highlight studies that assess sex differences in adolescence, as well as those that are designed specifically to address the potential unique effects of adolescent exposure by including groups at other life stages (typically young adulthood). We consider epidemiological studies on age and sex as vulnerability factors for developing problems with the use of amphetamines, as well as human and animal laboratory studies that tap into age differences in use, its short-term effects on behavior, and the long-lasting consequences of this exposure on cognition. We also focus on studies of drug effects in the prefrontal cortex, which is known to be critically important for cognition and is among the later maturing brain regions. Finally, we discuss important issues that should be addressed in future studies so that the field can further our understanding of the mechanisms underlying adolescent use of amphetamines and its outcomes on the developing brain and behavior.


2021 ◽  
pp. 35-55
Author(s):  
Om Prakash Yadav ◽  
Yojana Yadav ◽  
Shashwati Ray

2008 ◽  
Vol 193 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Mark R.C. Daglish ◽  
Tim M. Williams ◽  
Sue J. Wilson ◽  
Lindsay G. Taylor ◽  
Chin B. Eap ◽  
...  

BackgroundDrugs of dependence cause dopamine release in the rat striatum. Human neuroimaging studies have shown an increase in dopamine in the equivalent region in response to stimulants and other drugsAimsWe tested whether opioids provoke dopamine release and its relationship to the subjective experienceMethodIn two combined studies 14 heroin addicts on methadone maintenance treatment underwent two positron emission tomography brain scans of the dopamine system using [11C]-raclopride following an injection of placebo and either 50 mg intravenous diamorphine or 10 mg subcutaneous hydromorphone in a double-blind, random order designResultsBoth opioids produced marked subjective and physiological effects, but no measurable change in [11C]-raclopride bindingConclusionsThe absence of a dopamine response to opioid agonists contrasts with that found with stimulant drugs and suggests dopamine may not play the same role in addiction to opioids. This questions the role of dopamine in the subjective experience of heroin in opioid addicts


2020 ◽  
Author(s):  
Francisco J. Parada ◽  
Alejandra Rossi

Recent technological advancements encompassed under the Mobile Brain/Body Imaging (MoBI) framework, have produced exciting new experimental results linking mind, brain, and behavior. The main goal of the MoBI approach is to model brain and body dynamics during every-day, natural, real-life situations. However, even though considerable advances have been made in both hardware and software, technical and analytical conditions are not yet optimal. The MoBI approach is based on attaching synchronized, small, and lightweight neurobehavioral sensors to and around participants during behaviorally-measured structured, semi-structured, and unstructured settings. These sensors have yet to become fully unobtrusive or transparent. Even though a considerable technical and analytical gap still exists, acquisition of brain/body dynamics during real-world situations as well as in virtual, modified, and/or extended laboratory settings has been -in many cases- successful. Nevertheless, even if the technical/analytical gap is breached, novel hypotheses, measures, and experimental paradigms are needed in order to tackle MoBI’s ultimate goal: to model and understand cognition, behavior, and experience as it emerges and unfolds unto and from the world. Such a goal is not completely novel or unique to the MoBI framework; it is at the core of a long-standing scientific and philosophical challenge. The present work starts by briefly reviewing the historical origins of complexity in order to identify three “waves and ripples of complexity” derived from naturalist accounts to the historical brain/body problem. We furthermore argue for a current 4th wave. Finally, we offer the reader what we consider to be the main objective for the MoBI+4E framework in its quest for understanding the functional role of brain/body/world couplings in the emergence of cognition.


2014 ◽  
Vol 16 (3) ◽  
pp. 307-320 ◽  

Obesity is now epidemic worldwide. Beyond associated diseases such as diabetes, obesity is linked to neuropsychiatric disorders such as depression. Alarmingly maternal obesity and high-fat diet consumption during gestation/lactation may "program" offspring longterm for increased obesity themselves, along with increased vulnerability to mood disorders. We review the evidence that programming of brain and behavior by perinatal diet is propagated by inflammatory mechanisms, as obesity and high-fat diets are independently associated with exaggerated systemic levels of inflammatory mediators. Due to the recognized dual role of these immune molecules (eg, interleukin [IL]-6, 11-1β) in placental function and brain development, any disruption of their delicate balance with growth factors or neurotransmitters (eg, serotonin) by inflammation early in life can permanently alter the trajectory of fetal brain development. Finally, epigenetic regulation of inflammatory pathways is a likely candidate for persistent changes in metabolic and brain function as a consequence of the perinatal environment.


2020 ◽  
Author(s):  
Milena Rmus ◽  
Samuel McDougle ◽  
Anne Collins

Reinforcement learning (RL) models have advanced our understanding of how animals learn and make decisions, and how the brain supports some aspects of learning. However, the neural computations that are explained by RL algorithms fall short of explaining many sophisticated aspects of human decision making, including the generalization of learned information, one-shot learning, and the synthesis of task information in complex environments. Instead, these aspects of instrumental behavior are assumed to be supported by the brain’s executive functions (EF). We review recent findings that highlight the importance of EF in learning. Specifically, we advance the theory that EF sets the stage for canonical RL computations in the brain, providing inputs that broaden their flexibility and applicability. Our theory has important implications for how to interpret RL computations in the brain and behavior.


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