The Future for Psychedelic Agents in the Treatment of Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) treatment options, including the potential use of psychedelic-assisted therapy, are reviewed. Traditional PTSD treatment remains ineffective for many, and includes, trauma focused cognitive behavioral therapy, eye movement desensitization and remodeling, and selective serotonin reuptake inhibitors. Evidence has shown that with further supportive research, psychedelic-assisted therapy may offer an alternative treatment option.

Pilot study of single-dose psilocybin for serotonin reuptake inhibitor-resistant body dysmorphic disorder.

OBJECTIVE: Body dysmorphic disorder (BDD) is an often-severe condition in which individuals are preoccupied by misperceptions of their appearance as defective or ugly. Only serotonin reuptake inhibitors and cognitive-behavioral therapy have been demonstrated efficacious in randomized controlled trials. Psilocybin is a psychedelic drug with growing evidence for safety and efficacy in treatment of depression. This study aimed to pilot test the feasibility, tolerability, safety, and efficacy of psilocybin treatment of adults with BDD. METHODS: In this open-label trial, 12 adults (8 women, 4 men) with moderate-to-severe non-delusional BDD that had been unresponsive to at least one serotonin reuptake inhibitor trial received a single oral dose of psilocybin 25 mg. There was no control group. Psychological support was provided before, during, and after the dosing session. The primary outcome measure for efficacy was the Yale-Brown Obsessive Compulsive Disorder Scale Modified for BDD (BDD-YBOCS) score during 12 weeks of assessments after dosing. RESULTS: All participants completed dosing and all follow-up assessments. BDD-YBOCS scores decreased significantly over 12 weeks of follow-up (p < .001) with a large effect size (partial eta squared = 0.54), and significant changes from baseline were present at week 1 and persisted through week 12. Secondary efficacy measures of BDD symptoms, conviction of belief, negative affect, and disability also improved significantly, and no serious adverse events occurred. At week 12, seven participants (58%) were rated responders, based on ≥30% decrease in BDD-YBOCS. CONCLUSION: This study provides promising preliminary support for psilocybin as a treatment of BDD, warranting future controlled studies.

The effect of psilocybin on personality

As classic psychedelics are increasingly legalized and reintroduced into the psychotherapeutic frame, a deeper understanding of their effect on personality and overall wellbeing - as well as their clinical contraindications and potential pitfalls - will prove essential. As a result, this study represents a preliminary investigation into the effect of psilocybin exposure on a range of personality constructs.Methods: Data was collected through a collaboration with The Psychedelic Society, an organization that legally administers psilocybin in the Netherlands to self-selecting retreat attendees who have been screened for mental health disorders in accordance with Johnson et al.'s (2008) widely accepted safety guidelines. Participants completed the following measures via online questionnaire the day before psilocybin exposure, two days after psilocybin exposure, and at a one-month follow-up: Brief Symptom Inventory (BSI), Experiences in Close Relationships-Revised (ECR-R), Mentalization Scale (MentS), Inventory of Personality Organization (IPO), Pathological Narcissism Inventory (PNI), Pro-Environmental Behavior (PEB) and the Ryff Scale of Psychological Well-Being (Ryff). As rigorous double-blind clinical studies have linked psychedelic-occasioned mystical experiences to sustained improvement in personality-related domains (Maclean et al., 2011;Griffiths et al., 2006;Griffiths et al., 2008, Griffiths et al., 2011), the Mystical Experience Questionnaire (MEQ) was also administered. Lastly, participants provided self-report responses to open-ended questions regarding subjective experiences following psilocybin exposure. Results: Due to the Covid-19 pandemic, data collection was prematurely cut short, and only preliminary conclusions can be drawn. Those provisional conclusions include significantly improved overall symptomatology (BSI GSI), identity diffusion (IPO-ID) and reality testing (IPO-RT) following psilocybin exposure. Significant interactions were also identified for primitive defenses (IPO-PD) and narcissistic grandiosity (PNI-G), with the non-mystical experience group trending toward improvement, and the mystical-experience group remaining largely unchanged over time. Due to methodological constraints encountered, these findings remain preliminary. Nevertheless, the presence of multiple significant findings (however nascent) within the context of so few participants suggests the possibility of more robust findings in the context of a larger sample size. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Psychedelic science in post-COVID-19 psychiatry.

The medium- to long-term consequences of COVID-19 are not yet known, though an increase in mental health problems are predicted. Multidisciplinary strategies across socio-economic and psychological levels may be needed to mitigate the mental health burden of COVID-19. Preliminary evidence from the rapidly progressing field of psychedelic science shows that psilocybin therapy offers a promising transdiagnostic treatment strategy for a range of disorders with restricted and maladaptive habitual patterns of cognition and behaviour, notably depression, addiction and obsessive compulsive disorder. The COMPASS Pathways (COMPASS) phase 2b double-blind trial of psilocybin therapy in antidepressant-free, treatment-resistant depression (TRD) is underway to determine the safety, efficacy and optimal dose of psilocybin. Results from the Imperial College London Psilodep-RCT comparing the efficacy and mechanisms of action of psilocybin therapy to the selective serotonin reuptake inhibitor (SSRI) escitalopram will soon be published. However, the efficacy and safety of psilocybin therapy in conjunction with SSRIs in TRD is not yet known. An additional COMPASS study, with a centre in Dublin, will begin to address this question, with potential implications for the future delivery of psilocybin therapy. While at a relatively early stage of clinical development, and notwithstanding the immense challenges of COVID-19, psilocybin therapy has the potential to play an important therapeutic role for various psychiatric disorders in post-COVID-19 clinical psychiatry.

Death risk: Lack of movement: The ignored pandemic of digitalization escalates the COVID-19 crisis

Data analysis from diverse medical fields suggests that we have reached a tipping point in the digitalization dynamic through the ongoing COVID-19 crisis, leading to an escalation of physical inactivity and related diseases. The lack of prioritization of physical activity designed to intervene against obesity, diabetes, loneliness, depression, anxiety disorders and suicide risk could destabilize our current global health system beyond rehabilitation. To counteract this, the author outlines the basis for a sustainable solution to best integrate physical activity into work, daily life and education. In addition, he highlights the potential benefits of combining exercise training with microdosing of psilocybin or of active ingredient essences of psilocybin-containing mushrooms. The article also shows that the integration of mindfulness-based practice and neuroplastic movement practice is a necessity and a competitive advantage for the future. © 2021 Intellect Ltd Article. English language.

Psychoactive Drugs in the Management of Post Traumatic Stress Disorder: A Promising New Horizon.

Post-traumatic stress disorder (PTSD) is an anxiety disorder that often presents after exposure to a traumatic, life-threatening event. Experiencing a traumatic event is not rare, with inciting incidents ranging from being burglarized to politically motivated genocide. While traditional psychopharmacology and psychotherapy are the mainstays of the treatment of PTSD currently, psychoactive drugs (otherwise known as psychedelics) are being explored for their novel role in the treatment of PTSD patients. Psychoactive drugs such as MDMA, ketamine, and psilocybin have been shown to specifically target and decrease fear and anxiety pathways in the brain. These unique properties hold the potential to be utilized in addressing symptoms of trauma in those with refractory or treatment-resistant PTSD. Historically, federal and state laws have restricted research into how psychoactive drugs can be used to treat mental illness due to the widespread belief that these drugs present more harm than benefit. However, the current shift in public opinion on psychedelics has propelled research to look into the benefits of these drugs for patients with mental illness. This article aims to discuss the mechanisms of how MDMA, ketamine, and psilocybin work in the PTSD brain, as well as their beneficial role in treatment.

HERBAL RESOURCES IN THE MEDICATION OF DEPRESSION DURING PANDEMIC COVID-19

Depression has long been recognized as a major public health problem. Fear and anxiety associated with the high morbidity and mortality of COVID-19 have increased risk factors for mental health decline. A high prevalence of psychiatric disorders has been documented in individuals who have been directly or indirectly exposed to life-threatening situations. Current evidence suggests decompensation of pre-existing psychiatric disorders, increasing levels of depression, anxiety, and worry, and increased suicide as sequelae of COVID-19. Patients with COVID-19 are particularly vulnerable because psychopathologies can be exacerbated by coronaviruses, either through direct viral infection of the central nervous system or indirectly through an immune response. It, therefore, seems expedient to search for alternative methods of prevention, treatment, or supportive treatment of depression, especially since conventional pharmacotherapies and psychotherapies are only partially effective. Beneficial antidepressant effects have been observed after the application of spice plants as well as some mushrooms and herbs containing complex active components or phytochemicals. Their use in adjunctive therapy against depression, especially in the period of difficulties related to the functioning of COVID-19 oriented health care, seems to be an interesting alternative. The aim of the present study was to analyze the usefulness of Sceletium tortuo??Hericium erinaceus (Bull.:Fr.) Pers. and plant materials with psychedelic activity such as psilocybin and ayahuasca in reducing symptoms associated with depression.

Psychedelics: Alternative and Potential Therapeutic Options for Treating Mood and Anxiety Disorders.

The word "psychedelic" (psyche (i.e., the mind or soul) and delos (i.e., to show)) has Greek origin and was first coined by psychiatrist Humphry Osmond in 1956, who had been conducting research on lysergic acid diethylamide (LSD) at the time. Psychedelic drugs such as N,N-DMT/DMT (N,N-dimethyltryptamine), 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), LSD (lysergic acid diethylamide), MDMA (3,4-methylenedioxymethamphetamine) and psilocybin have had significant value as an entheogen in spiritual, religious (shamanic) and sociocultural rituals in Central and South American cultures for thousands of years. In the 1960s, the globalization of these drugs and their subsequent spread outside of their indigenous, old-world cultures, led to the subsequent implementation of strict drug control laws in many Western countries. Even today, psychedelics are still classified as Schedule I drugs, resulting in a still lingering negative stigmatization/perception, vilification, and ultimate criminalization of psychedelics. This controversy still lingers and still limits scientific research and full medical acceptance. For many years up until recently, the spiritual, religious and medicinal value of these drugs could not be explored in a scientific context. More recently, a second wave of psychedelic research is now focusing on psychedelics as neuropharmaceuticals to treat alcohol and tobacco addiction, general mood and anxiety disorders and cancer-related depression. There is now a vast array of promising evidence-based data to confirm the years of anecdotal evidence of the medicinal values of psychedelics. Natural therapeutic alternatives such as psychedelic drugs may provide a safe and efficacious alternate to conventional drugs used to treat mood and anxiety disorders. In a Western context in particular, psychedelic drugs as therapeutic agents for mood and anxiety disorders are becoming increasingly of interest amidst increasing rates of such disorders globally, changing social constructions, the implementation of government regulations and increasing investment opportunities, that ultimately allow for the scientific study to generate evidenced-based data. Alternative psychotherapeutic interventions are gaining interest also, because of their low physiological toxicity, relatively low abuse potential, safe psychological effects, and no associated persisting adverse physiological or psychological effects during and after use. On the other hand, conventional psychotic drugs and anti-depressants are becoming less favorable because of their adverse side effects. Psychedelic neuropharmaceutical interventions may with medical oversight be the solution to conventional psychiatric disorders such as depression and anxiety, and an alternative to conventional psychiatric treatment options. This paper will review the therapeutic potential of psychedelic drugs as alternative therapeutic options for mood and anxiety disorders in a controlled, clinical setting, where the chances of adverse psychological episodes occurring are mitigated.

Development of an E. coli-based norbaeocystin production platform and evaluation of behavioral effects in rats.

Interest in the potential therapeutic efficacy of psilocybin and other psychedelic compounds has escalated significantly in recent years. To date, little is known regarding the biological activity of the psilocybin pathway intermediate, norbaeocystin, due to limitations around sourcing the phosphorylated tryptamine metabolite for in vivo testing. To address this limitation, we first developed a novel E. coli platform for the rapid and scalable production of gram-scale amounts of norbaeocystin. Through this process we compare the genetic and fermentation optimization strategies to that of a similarly constructed and previously reported psilocybin producing strain, uncovering the need for reoptimization and balancing upon even minor genetic modifications to the production host. We then perform in vivo measurements of head twitch response to both biosynthesized psilocybin and norbaeocystin using both a cell broth and water vehicle in Long-Evans rats. The data show a dose response to psilocybin while norbaeocystin does not elicit any pharmacological response, suggesting that norbaeocystin and its metabolites may not have a strong affinity for the serotonin 2A receptor. The findings presented here provide a mechanism to source norbaeocystin for future studies to evaluate its disease efficacy in animal models, both individually and in combination with psilocybin, and support the safety of cell broth as a drug delivery vehicle.

In Silico Studies on Psilocybin Drug Derivatives Against SARS-CoV-2 and Cytokine Storm of Human Interleukin-6 Receptor.

Various metabolites identified with therapeutic mushrooms have been found from different sources and are known to have antibacterial, antiviral, and anticancer properties. Over thousands soil growth-based mushroom metabolites have been discovered, and utilized worldwide to combat malignancy. In this study, psilocybin-mushroom that contains the psychedelic compounds such as psilacetin, psilocin, and psilocybine were screened and found to be inhibitors of SARS-CoV-2 Mprotease. It has been found that psilacetin, psilocin, and psilocybine bind to Mprotease with -6.0, -5.4, and -5.8 kcal/mol, respectively. Additionally, the psilacetin was found to inhibit human interleukin-6 receptors to reduce cytokine storm. The binding of psilacetin to Mprotease of SARS-CoV-2 and human interleukin-6 receptors changes the structural dynamics and Gibbs free energy patterns of proteins. These results suggested that psilocybin-mushroom could be utilized as viable potential chemotherapeutic agents for SARS-CoV-2.

The effect of psilocybin on personality

As classic psychedelics are increasingly legalized and reintroduced into the psychotherapeutic frame, a deeper understanding of their effect on personality and overall wellbeing - as well as their clinical contraindications and potential pitfalls - will prove essential. As a result, this study represents a preliminary investigation into the effect of psilocybin exposure on a range of personality constructs.Methods: Data was collected through a collaboration with The Psychedelic Society, an organization that legally administers psilocybin in the Netherlands to self-selecting retreat attendees who have been screened for mental health disorders in accordance with Johnson et al.'s (2008) widely accepted safety guidelines. Participants completed the following measures via online questionnaire the day before psilocybin exposure, two days after psilocybin exposure, and at a one-month follow-up: Brief Symptom Inventory (BSI), Experiences in Close Relationships-Revised (ECR-R), Mentalization Scale (MentS), Inventory of Personality Organization (IPO), Pathological Narcissism Inventory (PNI), Pro-Environmental Behavior (PEB) and the Ryff Scale of Psychological Well-Being (Ryff). As rigorous double-blind clinical studies have linked psychedelic-occasioned mystical experiences to sustained improvement in personality-related domains (Maclean et al., 2011;Griffiths et al., 2006;Griffiths et al., 2008, Griffiths et al., 2011), the Mystical Experience Questionnaire (MEQ) was also administered. Lastly, participants provided self-report responses to open-ended questions regarding subjective experiences following psilocybin exposure. Results: Due to the Covid-19 pandemic, data collection was prematurely cut short, and only preliminary conclusions can be drawn. Those provisional conclusions include significantly improved overall symptomatology (BSI GSI), identity diffusion (IPO-ID) and reality testing (IPO-RT) following psilocybin exposure. Significant interactions were also identified for primitive defenses (IPO-PD) and narcissistic grandiosity (PNI-G), with the non-mystical experience group trending toward improvement, and the mystical-experience group remaining largely unchanged over time. Due to methodological constraints encountered, these findings remain preliminary. Nevertheless, the presence of multiple significant findings (however nascent) within the context of so few participants suggests the possibility of more robust findings in the context of a larger sample size. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

The Therapeutic Potential of Psilocybin.

The psychedelic effects of some plants and fungi have been known and deliberately exploited by humans for thousands of years. Fungi, particularly mushrooms, are the principal source of naturally occurring psychedelics. The mushroom extract, psilocybin has historically been used as a psychedelic agent for religious and spiritual ceremonies, as well as a therapeutic option for neuropsychiatric conditions. Psychedelic use was largely associated with the "hippie" counterculture movement, which, in turn, resulted in a growing, and still lingering, negative stigmatization for psychedelics. As a result, in 1970, the U.S. government rescheduled psychedelics as Schedule 1 drugs, ultimately ending scientific research on psychedelics. This prohibition on psychedelic drug research significantly delayed advances in medical knowledge on the therapeutic uses of agents such as psilocybin. A 2004 pilot study from the University of California, Los Angeles, exploring the potential of psilocybin treatment in patients with advanced-stage cancer managed to reignite interest and significantly renewed efforts in psilocybin research, heralding a new age in exploration for psychedelic therapy. Since then, significant advances have been made in characterizing the chemical properties of psilocybin as well as its therapeutic uses. This review will explore the potential of psilocybin in the treatment of neuropsychiatry-related conditions, examining recent advances as well as current research. This is not a systematic review.