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Shrooms or magic mushrooms are slang terms used to refer to mushrooms containing psilocybin that people use to get high. Shrooms can include a variety of naturally-occurring mushrooms. They are often dried and crushed before being smoked, packed into small capsules, or brewed with tea for consumption.

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Psilocybin is a classic psychedelic compound that may have efficacy for the treatment of mood and substance use disorders. Acute psilocybin effects include reduced negative mood, increased positive mood, and reduced amygdala response to negative affective stimuli.

Psilocybin (magic mushrooms)

However, no study has investigated the long-term, enduring impact of psilocybin on negative affect and associated brain function. One-week post-psilocybin, negative affect and amygdala response to facial affect stimuli were reduced, whereas positive affect and dorsal lateral prefrontal and medial orbitofrontal cortex responses to emotionally-conflicting stimuli were increased.

One-month post-psilocybin, negative affective and amygdala response to facial affect stimuli returned to baseline levels while positive affect remained elevated, and trait anxiety was reduced. Finally, the of ificant resting-state functional connections across the brain increased from baseline to 1-week and 1-month post-psilocybin.

These preliminary findings suggest that psilocybin may increase emotional and brain plasticity, and the reported findings support the hypothesis that negative affect may be a therapeutic target for psilocybin. Studies suggest that psilocybin, a classic psychedelic drug serotonin 2A or 5-HT 2A receptor partial agonistmay have efficacy for the treatment of depression and anxiety 123tobacco use disorder 45and alcohol use disorder 67.

Reduction of Side effects of psilocybin symptoms has been shown to last up to 3 36 12and 12 8 months after 1 to 3 psilocybin administrations. Despite these promising advances, the neural and psychological mechanisms underlying the enduring therapeutic effects of psychedelic drugs are not well-understood. Two possibly interactive trans-diagnostic targets that may be affected by psilocybin are negative affect and brain network plasticity.

Increased negative affect, reduced positive affect, and hypersensitivity to negatively biased information are hallmarks of mood disorders 910 Negative affect is also a core component of the cycle of addiction in which craving and withdrawal symptoms experienced after intoxication lead to preoccupation, anticipation, and re-administration of drugs of abuse The amygdala has been shown in clinical and preclinical models to track the salience of stimuli in the environment 1314 and is highly responsive to negative emotional stimuli 1516 Abnormally high amygdala reactivity to negative affective stimuli has been implicated in the pathophysiology of depression Areas within the anterior cingulate cortex ACC are understood to monitor cognitive conflict 19202122are involved in the appraisal and expression of negative emotion 22respond to distress levels associated with pain 23 and negative social affect 24and have been implicated in negative rumination and depression Both amygdala and ACC dysfunction have been implicated in the pathophysiology of substance use disorders 12 and have specifically been implicated in supporting aberrant negative affect in these disorders.

Psychedelic drugs have been shown to acutely reduce processing of negative affective stimuli 26 while increasing positive mood in humans Side effects of psilocybin In behavioral paradigms, psychedelics have been shown to reduce sensitivity during encoding of fearful faces 29recognition of negative facial expressions 30and response to negative stimuli in an emotional inhibition task Functional magnetic resonance imaging fMRI studies have found that psilocybin acutely reduces amygdala activity and connectivity when viewing negative emotional facial expressions 2831 Psilocybin has also been found to acutely decrease activity in the ACC during resting state 33 and during autobiographical memory recall If acute effects of psychedelic drugs on affect and the associated neurobiology are sustained Side effects of psilocybin other acute effects of these drugs have resolved, these sustained effects may reveal a trans-diagnostic mechanism of the enduring therapeutic effects of psychedelics.

Available neuroimaging evidence may be interpreted to suggest that acute effects of psychedelic drugs on emotion perception e. However, changes in emotion perception and positive and negative affect that are observed with psychedelic drugs could also reasonably result from changes in the top-down control of emotion that could lead to observed effects as down-streamand recent qualitative and self-report evidence supports this. A recent survey demonstrated that although psychedelics were Side effects of psilocybin thought to reduce physiological components of craving and withdrawal, they may have reduced the affective components of craving and withdrawal Additional evidence abounds for a possible role of psychedelics in acutely decreasing resting-state connectivity within the default mode network DMN 333940and between and within a of sensory and cognitive brain networks 41 Two reports have also provided evidence for a post-acute change in DMN connectivity after psilocybin administration, which was shown to be decreased two days after psilocybin in a cohort of long-term meditators 43 and paradoxically increased one day after psilocybin in patients with treatment-resistant depression These findings argue for a potential neuroplastic effect of psilocybin on brain network function, loosely consistent with both in vitro and in vivo evidence for increased neuritogenesis and spinogenesis in cortical neurons in response to a wide range of classic, 5-HT 2A receptor agonist psychedelics Plasticity within higher-order cortical brain networks may allow for increased modulation of affect by top-down cognitive circuits.

Participants completed the Big Five Inventory BFI 51 and the Tellegen Absorption Scale TAS 52 one day before and one month after psilocybin, and responses were compared between time points to investigate the enduring effect of psilocybin on personality. One day before, one week after, and one month after psilocybin, participants also underwent fMRI measurements during rest and during the completion of three separate emotion processing tasks the emotion discrimination task 15the emotion recognition task 53and an emotional conflict Stroop task Functional connectomes calculated from resting-state scans were compared between time points to determine the enduring effects of psilocybin on Side effects of psilocybin network connectivity.

POMS depression was ificantly greater at 1 month post-psilocybin compared to 1 week post-psilocybin. Ratings of trait anxiety were reduced 1-month post-psilocybin compared to baseline.

Psilocybin (magic mushrooms)

Post-hoc tests Side effects of psilocybin 1 demonstrated that DPES scores were ificantly greater both 1 week and 1 month after psilocybin compared to baseline. Descriptive statistics for all self-report measures are presented in Supplementary Information Table S1.

Response accuracy in the emotion recognition task was near ceiling for all emotional facial at all timepoints mean accuracy No effect of emotional condition or interaction between timepoint and emotional condition in any ROI was observed. Post-hoc comparisons Fig. Individual data for amygdala response in the emotion recognition task are presented in Supplementary Information Fig.

Exploratory associations between changes in self-report affect across time and changes in amygdala response across time in the emotion recognition task are also presented in Supplementary Information Figs.

S2 — S4. No effects were observed in whole-brain voxel-wise analysis of the emotion recognition task. Longitudinal effects of a single high dose of psilocybin on amygdala and anterior cingulate response to facial emotional Side effects of psilocybin. Each panel of the figure presents contrast values for a different region of interest.

Error bars are standard error. Dark blue bars plot values for baseline, turquoise bars plot values for 1 week post-psilocybin, and yellow bars for 1 month post-psilocybin. ACC: anterior cingulate cortex. Performance accuracy during the emotion discrimination task was near ceiling at baseline No differences were observed in amygdala or ACC response to the emotion discrimination task, between baseline, 1 week, or 1 month time points, and no ificant effects were observed in whole-brain voxel-wise analyses of the emotion discrimination task.

Participants performed at ceiling across all timepoints in the emotional conflict Stroop task No main effect of timepoint or interaction between timepoint and condition was observed in behavioral data. No effect of task condition or time point on amygdala or ACC response was observed in ROI analyses for the emotional conflict Stroop task. However, whole-brain voxel-wise analysis of the emotional conflict Stroop task identified ificant findings. It has been shown that trial-to-trial changes in task condition can alter cognitive control processes, with the greatest interference effects in Stroop-like paradigms being found in incongruent trials that follow congruent trials 19 Longitudinal effects of a single high dose of psilocybin on brain response to high conflict trials in the emotional conflict Stroop task.

Each panel contains sagittal, coronal, and axial slices that display the ificant clusters that were observed in the whole-brain general linear model analysis, with the in-plane coordinate for a given slice found in the top left-hand corner of each slice. ificant clusters in each slice are circled in yellow. CI: an incongruent Stroop trial that followed a congruent Stroop trial — this is a high-demand trial, as the trial involves both incongruent emotional information as well as a response-switch from responding Side effects of psilocybin a congruent trial to responding to an incongruent trial; CC: a congruent Stroop trial that followed another congruent Stroop trial — this is a low-demand trial, as the trial involves Side effects of psilocybin emotional stimuli and does not require response-switching from the trial.

Out of 35, possible functional connections in the Shen atlas 56were ificantly different from zero after Bonferroni correction for at least one time point.

Emotions and brain function are altered up to one month after a single high dose of psilocybin

Functional connectivity increased across the brain from baseline to 1 week after psilocybin greater connectivity strength for 38 edges and less for 10 edges and this pattern persisted at one month greater connectivity strength for 29 edges and less for 18 edges at 1 month; Fig.

Of the 29 edges that showed greater connectivity at 1 month post-psilocybin, 7 of these were the same edges as those that increased from baseline to 1 Side effects of psilocybin post-psilocybin, and these edges were evenly distributed across different brain lobes and networks. Changes in static functional connectivity did not follow any discernable network pattern Fig.

Longitudinal effects of a single high dose of psilocybin on the strength of static functional brain connectivity.

The left and right side of each panel represents left and right hemispheres of the brain, respectively. Each dot in the inner ring of dots in each hemisphere corresponds to a node or Side effects of psilocybin of interest within the brain, and the outer band of color provides a color code indicating the lobe of the brain within which each node resides. Color to lobe mapping is provided in the inset legend. Effects of psilocybin on edge-wise and network-based static functional connectivity.

Each row and each column represents a single node ROI as defined by the Shen node functional brain atlas The color of each off-diagonal cell in the connectome matrix represents the Pearson correlation value r for each edge between the given nodes in the brain.


Nodes are grouped together in rows and columns by network as defined in the Shen atlas, with black lines marking the border between networks in the matrix. Each row and column represents a single brain network as defined by the Shen node functional brain atlas The diagonal cells represent differences in within-network connectivity between time points, and off-diagonal cells represent differences in between-network connectivity between time points. Measures of dispersion of Side effects of psilocybin strengths within and between networks were unaffected across time points Figs.

S5 — S8. The current open-label pilot study identified four key sustained effects of a single high dose of psilocybin on affect and the neural correlates of affective processing.

First, negative affect was decreased 1 week post-psilocybin and returned to baseline levels at 1 month post-psilocybin. Second, there were decreases in amygdala responses to emotional stimuli 1 week post-psilocybin that rebounded at 1 month post-psilocybin. Third, there were increased responses in reward-learning, attention, and decision-making circuits 1 week post-psilocybin, and increased responses in somatosensory and fusiform gyrus 1 month post-psilocybin, during high-demand incongruent trials in the emotional conflict Stroop task.

Finally, there were global increases in functional connectivity at both 1 week and 1 month post-psilocybin. A notable feature of the current report is that the reported effects of psilocybin were observed well after psilocybin would have been eliminated from the body and beyond expected transient effects of receptor trafficking that may be occurring after psilocybin administration. The half-life of psilocybin and psilocin the active metabolite of psilocybin Side effects of psilocybin roughly 3 hours 5758indicating that over 50 half-lives of the drug had passed before the 1 week time point, ensuring elimination of the drug from each participant.

Rather than receptor trafficking or other residual pharmacological effects, the reported findings might better be explained by a neuroplastic period during which the neural processing Side effects of psilocybin affective stimuli is altered.

The sustained decreases in negative affective states and traits, increases in positive affective states and traits, and decreases in amygdala responses to emotional stimuli that were observed in this trial all resemble reported acute effects of psilocybin 27 The observed changes in MOFC, DLPFC, IFG, insula, parietal, and fusiform response to conflicting trials, however, are unexpected findings that may reveal a potential top-down mechanism underlying the sustained effects of psilocybin Side effects of psilocybin affect and brain function. The DLPFC is broadly implicated in a of tasks spanning the domains of working memory 60decision making 61and emotion regulation Hypoactive DLPFC response to emotional interference has been demonstrated in major depressive disorder, suggesting a deficit in the neural circuitry underlying emotion regulation and top-down control of emotionally conflicting information 63and this hypoactive response has been shown to recover with antidepressant treatment DLPFC has also been shown to exert top-down influence on amygdala response during emotion regulation Reduced DLPFC recruitment and enhanced amygdala recruitment during down-regulation of negative emotion have been identified across a range of disorders including mood and substance use disorders MOFC response is observed in a wide range of decision-making tasks 6667and may code the reward value of reinforcers, with an anterior-to-posterior gradient within the OFC suggesting that more abstract reinforcers elicit more anterior OFC response The observed increase in anterior MOFC Side effects of psilocybin 1 week post-psilocybin is consistent with increased sensitivity to the abstract reinforcer of positive emotional stimuli.

The amygdala and MOFC also have dense bidirectional structural connections that are understood to facilitate top-down modulation of salience detection and reward learning