Summary: Two new studies consider the potential of using psychedelics to help treat depression. Imperial College London researchers report psilocybin, the active compound in magic mushrooms, can help to relieve symptoms of depression without the dulling of emotions associated with SSRIs. The researchers note the psychedelic experience could help to maintain long term mental health for those with treatment resistant depression.
Source: Imperial College London.
Imperial research suggests psilocybin can help relieve the symptoms of depression, without the ‘dulling’ of emotions linked with antidepressants.
Working out if someone is happy, angry or afraid, from the look on their face, is a skill we may take for granted.
For some people, however, such as those with chronic depression, this innate ability to pick up on and respond to emotional prompts like a facial expression can be disrupted, with the brain becoming oversensitive to negative stimuli.
While antidepressants drugs can help to combat the symptoms of depression for patients, they can dampen how the brain processes strong emotions – effectively turning down the dial on the hypersensitivity to negative emotions but also ‘blunting’ intense positive mood.
Now, findings from a small trial carried out at Imperial College London suggest that psychedelics, like magic mushrooms, may hold the key to sidestepping some of these effects in treating depression, by reviving the brain’s activity and effectively reconnecting patients with their emotions.
Previous research has shown that psilocybin – the active compound in magic mushrooms – may help to alleviate symptoms in patients with persistent depression by ‘resetting’ brain activity.
In a recent study, published in the journal Neuropharmacology, the Psychedelic Research Group at Imperial focused on the potential of the drug to change brain activity in key areas involved in emotional processing.
They found that after treatment with psilocybin, patients with depression who did not respond to conventional treatments, reported improvements in their mood and symptoms. However, the researchers also observed a stronger response to emotional faces (happy and fearful) with increased brain activity in an area called the amygdala – the almond-shaped region of the brain involved in processing emotions and which is known to play a role in depression.
According to the researchers, the findings suggest an alternative pathway to tackling the changes seen in the depressed brain, which could potentially avoid some of the side effects seen with ‘Prozac-like’ selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed antidepressants.
“Our findings are important as they reveal biological changes after psilocybin therapy and, more specifically, they suggest that increased emotional processing is crucial for the treatment to work,” explained Leor Roseman, first author of the study and a member of the Psychedelic Research Group.
Changing brain activity
In the small, open label trial – which means the patients knew what they were taking – a total of 20 volunteers with depression were recruited and asked not to take any antidepressant medication in the two weeks leading up to the trial. They were then given two oral doses of psilocybin alongside psychiatric support, receiving an initial low dose of the drug before taking a second, much stronger therapeutic dose a week later.
In order to capture changes in brain activity, 19 of the volunteers completed fMRI scans before and after the treatment. They were shown images of human faces that were either happy, scared or neutral, with the fMRI capturing their responses as changes in blood flow throughout different regions of the brain.
Following treatment, patients reported feeling emotionally re-connected and accepting, with one patient describing the experience as an ‘emotional purging’. Results from the scans revealed that patients had a stronger response to emotional faces (happy and fearful) following psilocybin treatment, particularly in the amygdala.
The authors highlight that while the findings are interesting, follow up studies are needed to confirm the effects are directly related to the drug, rather than other factors, such as the psychological support provided during the trial or stopping their SSRIs.
Larger trials are now planned by the group and their collaborators, in which patients with depression don’t know whether they are receiving psilocybin, an SSRI or placebo, and parallel studies will be done in healthy non-depressed people. These studies will also aim to find out if psychedelic therapy has any lasting impact on activity in the amygdala and emotional processing.
“Having a healthy control group in future studies should be helpful in answering some of these questions,” said Roseman. He added: “We also want to investigate how the amygdala responds a longer time after treatment, which will inform us about longer term effects – compared to the current study, which was only looked at one day after the therapy.”
In a second paper, published in the journal Frontiers in Pharmacology, Roseman and team used questionnaires to capture patients’ feelings about the quality of their experience under the psilocybin and how this related to their depressed changes.
One of the dimensions of experience the researchers looked at has been called the ‘mystical experience’, which includes any feelings of unity, a loss of boundaries of the self and transcending time and space during the treatment.
They found that the stronger a patient rated this experience, the greater their decreases in depressive symptoms weeks after treatment, suggesting the mystical element of their psychedelic experience may help them maintain long-term mental health.
Roseman adds that future trials with psychedelics may look at enhancing this aspect of the experience while reducing anxiety in order to improve the effectiveness of the therapy.
Building on its body of research to date, the group is now planning further studies which will compare psilocybin directly with a leading antidepressant for patients with treatment-resistant depression. Trials are set to begin in early 2018.
Source: Ryan O’Hare – Imperial College London
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is adapted from the Imperial College London news release.
Original Research: Full open access research for “Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression” by Leor Roseman, Lysia Demetriou, Matthew B. Wall, David J.,Nutt, and Robin L .Carhart-Harrisa in Neuropharmacology. Published online December 27 2017 doi:10.1016/j.neuropharm.2017.12.041
Abstract for “Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression” by Leor Roseman, David J. Nutt, and Robin L. Carhart-Harris in Frontiers in Pharmacology. Published online January 2018 doi:10.3389/fphar.2017.00974 (*Note* this research paper has been provisionally accepted. Full, open access paper will be published soon.)
Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression
Recent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments’ therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions.
“Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression” by Leor Roseman, Lysia Demetriou, Matthew B. Wall, David J.,Nutt, and Robin L .Carhart-Harrisa in Neuropharmacology. Published online December 27 2017 doi:10.1016/j.neuropharm.2017.12.041
Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression
Introduction: It is a basic principle of the ‘psychedelic’ treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would not.
Material and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10mg and 25mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-time and DED-by-time interactions were the primary outcomes of interest.
Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson’s correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC (p < 0.05).
Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. More specifically, future therapeutic work with psychedelics may consider investigating ways which enhance mystical-type experience and reduce anxiety, given the growing evidence that this serves the efficacy of the treatment model.
“Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression” by Leor Roseman, David J. Nutt, and Robin L. Carhart-Harris in Frontiers in Pharmacology. Published online January 2018 doi:10.3389/fphar.2017.00974