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Introduktion: Depression är en vanlig psykisk sjukdom som påverkar patientenslivskvalitet negativt. Symtomatisk kan depression orsaka att patienten känna sig ledsen,orolig, tom, hopplös, rastlös och ännu allvarligare kan depressiva patienter försökaeller lyckas begå självmord. En av de vanligaste hypoteserna gällande anledningen tillförekomst av depression är monoaminhypotesen. Det innebär att förändring i nivåer aven eller flera monoaminer som serotonin, dopaminoch noradrenalin resulterar i depression. Psilocybin är en prodrog av psilocin och äricke-selektivt serotoninreceptor agonist. Det innebär att psilocin binder till 5-HT1A-, 5-HT2A- och 5-HT2C-receptorer med måttlig till hög affinitet. Studier visaratt psilocybin är effektivt för att minska symtomen på tvångssyndrom och har effekt påångest. Syfte: Syftet med detta arbete är att undersöka om psilocybin kan minska symtom hospatienter som lider av depression.   Metod: Detta arbete är en systematisk översiktsstudie. Artikelsökning utfördes idatabasen PubMed mellan den 12:e september till den 10:e oktober 2021 med filtret“Clinical Trial”, med sökordet ”psilocybin and depression symptom”. Sökningengav fjorton träffar och sex vetenskapliga originalartiklar somuppfyllde samtliga inklusionskriterierna valdes ut.   Resultat: De sex utvalda studierna visar att psilocybin har en statistiskt signifikanteffekt på depressionssymtomen. Det innebär att de utvalda studierna visaratt psilocybin kan signifikant minska symtom hos patienter som lider av depression.   Slutsats: Resultaten i detta arbete tyder på att psilocybin kan minskadepressionssymtom. Däremot är det svårt att säkerställa trovärdigheten av resultatet pågrund av att psykoterapi gavs till patienterna vid samma tidpunkt som psilocybinbehandlingen pågick vilket gjorde det svårt att skilja på hur stor del av minskningen idepressionssymtomen som berodde enbart på psilocybin. Därför kanen randomiserad dubbelblindstudie med en stor provstorlek vara nödvändig.

Depression is a potentially life-threatening disease that is one of the leading causes of disability in the world. In 2017, more than 300 million people suffered from depression. That equates to about 4.4% of the world's population, making it the world's second most common public health disease after cardiovascular disease. About 50% who are treated for depression develop unipolar treatment-resistant depression, a type of severe persistent depression in which conventional methods or drugs do not have effect.  Psilocybin is a tryptamine found in a variety of species of psychedelic mushrooms. Psilocybin is a prodrug that breaks down into the active substance psilocin which interacts with serotonin receptors and produces psychoactive effects. Psilocybin is classified as a schedule I drug in most of the world and is therefore not considered to have any medical value. Psilocybin has been researched intensively in recent years, mainly focusing on its potential antidepressant effect. Psilocybin's effects have been widely covered in English literature but hardly at all in Swedish literature. This bachelor thesis will hopefully fill that gap and encourage more research on the subject here in Sweden. The purpose of this bachelor thesis was to evaluate, based on published studies, whether psilocybin potentially can have an effective, safe, and long-lasting antidepressant effect on depressive symptoms. Six studies are presented, and the results indicate that that 20–30 mg of psilocybin together with psychological support in an optimal environment can potentially have a long-acting, safe, and effective antidepressant effect on adult people with moderate to severe unipolar depression. Based on these results, the drug classification of psilocybin should be questioned and investigated.

Major depression disorder is increasing globally, causing great personal suffering and economic burdens to society. Current antidepressant medications are not sufficiently able to treat all cases of depression and are often associated with troubling side effects. There is a great need for the development of novel treatments, and classic psychedelic drugs are currently being investigated with new interest. The legal status has hindered research, but promising results from pioneering studies on the antidepressant effect of psilocybin have recently given psilocybin breakthrough therapy status, allowing further research to occur more freely. This systematic review aims to investigate the literature available on psilocybin’s effect on major depressive disorder. Five studies were selected according to set inclusion and exclusion criteria. Results are suggesting that psilocybin combined with psychological support is a fast-acting antidepressant agent, able to produce a sustained decrease in symptoms of depression with minimal side effects. However, current studies come with several limitations and further research is needed before the antidepressant effect of psilocybin can be stated as a fact.

The aim of this systematic review is to present the current literature on the therapeutic potential of the classic psychedelic compound psilocybin for depressive disorders and the neurocognitive mechanisms involved recorded with functional magnetic resonance imaging (fMRI). A comprehensive literature search was conducted in the electronic databases Web of Science, Scopus and Medline EBSCO using a Boolean search string containing the keywords psilocybin, depression, fMRI, MRI and PET. Our inclusion criteria require original neuroimaging research articles published in scientific peer-reviewed journals involving participants diagnosed with depression receiving psilocybin in conjunction with psychological support. Five articles were identified including a total of 104 participants with depression and 75 who received treatment, resulting in significant reduction of depressive symptoms associated with observable changes in neural activity. Specifically reduced cerebral blood flow (CBF) in amygdala, decreased brain modularity along with functional changes in default mode network (DMN), executive network (EN), salience network (SN), decrease in functional connectivity (FC) between ventromedial prefrontal cortex (vmPFC) to amygdala and increased amygdala reactivity to fearful faces. Limitations of our systematic review include a currently limited amount of articles published and thus lack of control groups in most studies. The current evidence indicates that the therapeutic potential of psilocybin-assisted therapy may provide fast acting and efficient amelioration of depressive symptoms and the effects may be mediated by neurocognitive changes acute and post-treatment. The preliminary results warrants further research in order to optimize treatment and establish safety and efficacy long term.

Depression is a mental illness that is characterized by a depressed mood, reduced energy levels, loss of interest in activities, and decreased concentration. It is the biggest cause behind the approximately 800 000 suicides committed every year, and one of the largest contributors to global disability. Between 12-55% of all patients suffering from depression do not experience improvement of symtoms after two or more pharmaceutical treatments. Even when the treatments do work, it often takes several weeks for them to acheive full effect.In recent years, research on the antidepressant effects of the controlled substance psilocybin has resumed after a long hiatus. Psilocybin is a psychedelic substance with hallucinogenic, mind-altering properties. It occurs naturally in several species of mushrooms, and has a long history of usage in spiritual rituals by native populations of South America. After ingestion, psilocybin is converted to its active form, psilocin, by enzymes found in the body. Psilocin has a structure similar to serotonin, and the hallucionogenic effects are mediated by psilocin binding to serotonin receptors. The mechanism behind the potential antidepressant effects is not yet fully known, but believed to involve several pathways.This bachelor´s thesis aimed to, through reviewing literature, examine whether psilocybin can constitute a safe and effective treatment for depression. Six scientific studies on the topic were chosen from the databases PubMed and ScienceDirect to be presented in this thesis. All of the chosen studies used established rating scales to evaluate the degree of depressive symtoms before and after one to two doses of psilocybin.The results from the analysed studies indicate that psilocybin, when combined with psychological support, has the potential to constitute a safe and effective treatment for depression. This presupposes that 20-30 mg is administrated in a safe environment with professionally trained indivuduals present. The effect also appears to be long-lasting after only one to two doses, with twelve months being the longest observed period of effect. The number of participants in the studies were however too low to draw any definitive conclusions regarding either effect, safety nor period of effect. More studies with larger study populations are needed to further examine these aspects, and more comparisons with other treatment options are called for.

Psychedelics—also known as hallucinogens and entheogens—comprise a family of psychoactive molecules that are both found in nature and synthetically engineered in the lab. As a class, psychedelic compounds produce phenomenologically complex and novel experiences that have recently captured the attention of mental health clinicians and researchers. However, psychedelic clinical research and treatment remain limited, with most studies exploring the efficacy and safety of protocols for individuals with anxiety, depression, substance use, and posttraumatic stress disorder (PTSD), while individuals with personal or familial histories of psychosis, psychotic disorders, and bipolar disorder are mostly excluded from treatment and research. The overarching objectives of this thesis included determining 1) whether excluding this group from psychedelic clinical research is justified, 2) when psychedelic drug administration and psychedelic-assisted psychotherapy (PAP) may be contraindicated for this group, 3) if people with a history of psychosis or a psychotic disorder may be able to treat their psychotic symptoms with PAP, 4) if people with a history of psychosis or psychotic disorder may be able to treat their co-morbid conditions like anxiety, depression, substance use, or PTSD with PAP, 5) what a PAP treatment protocol for this group could look like 6) how individuals with reported histories of psychosis and psychotic disorders describe their experiences of psychedelic drug use and 7) whether naturalistic psychedelic use has an overall positive or negative effect on emotional well-being and psychological functioning for this group. Results from the first study—a qualitative study with experts in medicine, mental health, and psychedelics—suggest that certain individuals with histories of psychosis and psychotic disorders may benefit from PAP under the right conditions, such as when psychosis is etiologically connected to traumatic events, when the protocol offers extensive support for the patient, and when psychosis is not the result of amphetamine use or medical conditions such as epilepsy. Moreover, results suggest that the effects of the specific psychedelic that is administered must be carefully considered and support outside of therapy must also be assessed. Other factors such as personality traits, ability to form rapport with a guide or sitter, symptom severity, specific symptom endorsement, symptom duration, age, the presence of physiopathology and more must also be taken into consideration. For the second study, a cross-sectional, retrospective, phenomenological survey report was administered to individuals who reported a history of one or more psychotic experiences and/or diagnosis of a psychotic condition who also had at least one psychedelic drug experience in their lifetime. The survey asked participants to describe one memorable instance of psychedelic drug use and found that in a sample of 100, most individuals (n=88) describe some degree of personal growth resulting from their experience. Many also describe mystical-type experiences, gaining insight or awareness during their experience, heightened appreciation for life, and improved mental health and emotional well-being. Descriptions of symptomatic relief included reduced paranoid thinking, changes in relationships with symptoms, and decreased suicidal ideation. Approximately 11% of the sample described negative experiences including perseverating psychological impairment, symptom exacerbation, and psychedelic-induced suicidality. A slightly larger portion of the sample described mixed-type experiences, i.e., experiencing positive and negative effects alongside each other. The findings of these studies fill a major gap in the literature by suggesting that individuals with histories of psychotic symptoms and disorders may be able to partake in psychedelic studies and treatment under certain circumstances. This is because experts have explicitly stated that psychedelic use is not necessarily contraindicated for everyone with psychotic conditions and symptoms, but rather that most PAP protocols for anxiety, depression and other conditions do not offer enough support. At the same time, exclusion criteria are required by the FDA. Additionally, survey reports from individuals with lived experiences of psychosis further back the position that PAP could be a viable treatment option for this group through their survey reports. Specifically, the high prevalence of positive and therapeutic experiences with psychedelics in naturalistic settings suggests that clinically supervised psychedelic drug use may generate similar or even better outcomes for this population. Although a minority had adverse experiences, it remains to be studied as to whether similar effects might be experienced at a similar rate or similar degree of frequency in clinical studies, which utilize harm reduction strategies, maximize safety, and implement preparatory and integration sessions, elements which were notably absent from reports of adverse experiences in the survey. Results also shed light on what a psychedelic treatment protocol could look like for this group, and how individuals with histories of psychotic experiences and diagnosed psychotic conditions describe their experiences of psychedelic use and the effects of psychedelic drugs on their emotional and psychological functioning.

The modern psychiatric crisis has become a global epidemic as the prevalence of psychiatric disorders continues to rise. These numbers have only been exacerbated by the COVID-19 pandemic, and the long-term psychological effects resulting from the social isolation and fear of the disease have yet to be seen. Those already suffering from psychiatric disorders have limited options for treatment, as current therapeutic methods for mood, anxiety, and substance use disorders demonstrate high failure rates with many individuals suffering from treatment resistance. Individuals that do respond to modern therapies typically require treatment for several weeks or months, occasionally even years, before experiencing any reductions in their symptoms. Tryptamine psychedelics have been used for millennia by indigenous cultures through highly ritualized religious ceremonies to purge individuals of disease and offer spiritual guidance, however their application within modern medicine did not begin until Albert Hofmann’s discovery of LSD in 1938. The next several decades saw an explosion in clinical studies involving tryptamine psychedelics showcasing their ability to demonstrate immediate treatment after single doses in individuals suffering from diseases such as depression and PTSD, however research and clinical practices came to a halt after the passing of the Controlled Substances Act of 1970. As renewed interest in psychedelic medicine continues to grow, this review details the therapeutic potential of tryptamine psychedelics while exploring their current status within clinical trials.

Mikrodosering av psykedeliska droger är den senaste trenden som verkar ha fått en stor spridning, främst bland unga människor för att uppnå ökad produktivitet och kreativitet, men även för att uppnå allmän psykisk hälsa. Denna uppsats lägger fokus på lysergsyradietylamid (LSD) och psilocybin (magic mushroom). Mikrodosering innebär att användaren tar en väldigt låg dos av substansen. Dosen ger ingen psykedelisk effekt, d.v.s. inga visuella effekter, inget förändrat medvetandetillstånd,och ingen förändrad tids-eller rumsuppfattning. Deltagare (n=201) besvarade en elektronisk enkät som distribuerades i olika forum med intresse för psykedeliska substanser. I denna deskriptiva sambandsstudie undersöktes motiveringen av att mikrodosera LSD-och psilocybin, samt vilka positiva och negativa effekter mikrodosering av dessa substanser har på den psykiska hälsan.Deltagare uppgav upplevd minskad depression, ångest och stress, men att det inte var den primära anledningen till att de mikrodoserade trots att 62% hade självdiagnostiserat sig med någon form av upplevd ohälsa. De primära motiven med att mikrodosera, som angavs i enkäten, var att förbättra den allmänna hälsan, samt för att nå ökad kreativitet och produktivitet. Trots upplevda negativa bieffekter under mikrodoseringscykeln uppgav majoriteten att de ville fortsätta att mikrodosera. På grund av urvalet är studieresultatet inte generaliserbart och efterföljande undersökningar med hypoteser och frågor är att föreslå.

Classic psychedelic substances, such as lysergic acid diethylamide and the active compound in magic mushrooms, psilocybin, are being studied again in a renaissance of psychedelic research. Psychedelic substances have profound effects on perception, emotion, and cognition, as well as the capacity to induce mystical-type experiences and ego-dissolution. Recent clinical studies indicate that these substances have positive effects on patient populations and healthy participants, both acutely and long-term. Neuroimaging studies show that psychedelics alter neural integration, by the disintegration of normally stable resting state networks, and increasing network connectivity between normally anticorrelated networks. This thesis will review the phenomenological characteristics of the psychedelic-induced altered state of consciousness, the therapeutic potential of the psychedelic-induced altered state of consciousness, and neuroimaging studies on the psychedelic state. Two theoretical accounts are compared on the brain basis of psychedelic-induced altered state of consciousness. From the recent research on psychedelics a novel theory of conscious states has evolved, the entropic brain theory. This theory will be compared to the integrated information theory, a well-established theory of consciousness within cognitive neuroscience.