Introduction
Psilocybin is a psychedelic prodrug compound produced by over 200 species of so called ‘’magic mushrooms’’. It is well known for the use in indigenous cultures in religious or spiritual contexts. Here, the mushrooms were used to induce a trance, produce visions, and communicate with the Gods.
Research into psychedelics began in the 1950’s after the discovery of LSD by Albert Hofmann. By 1965 there were more than 1000 clinical studies on the effects of LSD alone. Psilocybin and other psychedelics have been reported to have promising therapeutic effects in patients with anxiety disorders, alcohol addiction, OCD, and depression. However, psychedelics were also being used outside of scientific research and became more and more associated with the emerging counter culture in the 1960’s and 70’s. The media depicted them as highly dangerous which led to more concern about health issues and eventually the demonization of psychedelics (Vollenweider & Kometer, 2010). In 1971 the United Nations signed the Convention on Psychotropic Substances treaty, which severally limited the use of psychotropic drugs for scientific and medical purposes. Psychedelics have been classified under Schedule I drugs, meaning that they are illegal and have no accepted medical use. This treaty made it very hard to conduct research on the effects of these substances (Rucker et al., 2016).
Since the 1990’s the interest in clinical research with psychedelics has increased again. Over the last 10 years there have been a lot of pilot clinical studies on the effects of psychedelics on OCD, anxiety, addiction, and depression with promising results.
It has also been found that psilocybin is
Recent research.. effecten op depressie en TRD.
Antidepressant medication alone or in combination with cognitive behavioral therapy is proven to be effective for about 80% of patients suffering from depression. This leaves about .. patients who do not respond to any kind of treatment
Treatment-resistant depression = failure of at least 2 different medications within the current depressive episode.
Psilocybin in the brain & it’s effects
When ingested, psilocybin is broken down by the body to produce psilocin, which is the active compound responsible for the mind-altering effects. Psilocin is a non-selective serotonin 2A receptor agonist, and is structurally related to the neurotransmitter serotonin (5-HT). Psilocybin binds to serotonergic 5-HT2 receptors, primarily to 5-HT2A receptors, although other receptors are likely to be involved as well. Downregulation of 5-HT2A receptors is thought to mediate the antidepressant effects of antidepressants, and psilocybin probably mediates the effects of the 5-HT2A receptors (Mahapatra & Gupta, 2017). Serotonin has several functions, including the regulation of mood, arousal, appetite, and anxiety, but it is also involved in some cognitive functions as memory and learning. Drugs that alter the levels of serotonin, like SSRI’s or MAOI’s are used in the treatment of depression and anxiety disorders (World Health Organization, 2004).
The effects of psilocybin are very subjective and vary amongst individuals. It is dependent on various factors such as dosage, mindset, environment, and personal expectations and metabolism. The most common effects however include euphoria, visual and mental hallucinations, changes in perception, and an altered sense of time. These effects usually last from three to eight hours, very much depending on dosage and metabolism. Because of the altered perception in time the effects can seem to last a lot longer than eight hours.
Results
Subjective results
One study found that nearly all of the participants diagnosed with treatment-resistant depression showed a clinically significant response to the treatment. The most salient effect was a change in consciousness. After the treatment with psilocybin they felt a sense of mental freedom, whereas before treatment they felt like they were in a ‘’mental prison’’. They also described a feeling of being reset and many described a sense of mental clarity and a feeling of expanded mental space. These effects were most intense during the dose and lasted for weeks to several months after treatment (Watts, Day, Krzanowski, Nutt & Carhart-Harris, 2017).
Results using neuroimaging
A study by Carhart-Harris et al. (2011) on the effects of psilocybin using a task-free fMRI protocol found decreases in cerebral blood flow and BOLD signals in brain regions relevant for depression. They found significant CBF decreases after psilocybin in subcortical as well as cortical brain regions. These included the thalamus, putamen, hypothalamus, PPC, ACC, and mPFC, as well as other cortical regions. The decreases in CBF were correlated with the intensity of the subjective effects. The decreases in BOLD signal were consistent with the decreases in CBF, with decreases in the mPFC, ventral PCC, and putamen. Psilocybin also significantly decreased the positive coupling between the mPFC and the PCC. Depression is characterized by pessimistic cognition, and trait pessimism has been associated with abnormalities in 5-HT2A receptor stimulation, especially within the mPFC. It is known that activity and connectivity with the mPFC in higher in patients with depression, and this pattern normalizes after effective treatment. Here, the mPFC was deactivated and the magnitude of the deactivation was correlated with the subjective intensity of effects. These results therefore suggest a biological mechanism by which decreased mPFC activity via 5-HT2A receptor stimulation decreases the depressive symptoms (Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin).
A study by… examined the effects of 2 doses of psilocybine (10mg and 25mg, 7 days apart) on changes in brain function in patients with treatment-resistant depression using fMRI. They found that the mean depression score one day after treatment decreased with 8.1 points (QIDS-SR16), and 8.0 points after 5 weeks. All patients showed at least some decrease in depressive symtpoms after one week, and all but one still showed a decrease after 5 weeks.
Increased vmPFC resting state functional connectivity with the inferior-lateral parietal cortex predicted treatment response 5 weeks after dose. They also found that a significant decrease in parahippocampal-prefrontal cortex RSFC was predictive of the treatment response after 5 weeks. The intensity of peal experience was again predictive of the magnitude of the changes in RSFC. These results are consistent with the findings of Carhart-Harris et al. (2011) and the fact that decreased mPFC activity is correlated with a decrease in depressive symptoms.
A significant relationship was found between the decrease in depressive scores and reductions in amygdala CFB. This result is important, as increased amygdala blood flow and metabolism has previously been associated with depression. Other fMRI studies by Kraehenmann et al. (2015a) and kraehenmann et al. (2015b) found that amygdala activation in response to threat-related stimuli decreases after psilocybin. This effect was also found for the threat-induced modulation of top-down connectivity from the amygdala to the visual cortex. The amygdala has an important and central role in the perception and verwerking of emotions. Amygdala hyperactivity has consistently been found to be related to the negative mood of depressed patients. These findings suggest that psilocybin has a significant effect on the role that the amygdala plays in depression.