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Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer
... 36 The restrictions extend to other 5-HT 2A agonists, limiting adjacent lines of research which may improve the mechanistic understanding of psychedelics. 4,43,56 Even once legislative hurdles are overcome, it is difficult to source pharmaceutical-grade psychedelics for research. Manufacturers face numerous hurdles in the development of psychedelics, leading to high costs of custom synthesis that is often too extensive for research grants, $12,000 per gram of psilocybin, for example. ...
... Manufacturers face numerous hurdles in the development of psychedelics, leading to high costs of custom synthesis that is often too extensive for research grants, $12,000 per gram of psilocybin, for example. 56 Together, numerous political and legal barriers continue to impact the ability to conduct psychedelic research. ...
Psychedelics are a group of psychoactive substances that alter consciousness and produce marked shifts in sensory perception, cognition, and mood. Although psychedelics have been used by indigenous communities for centuries, they have only recently been investigated as an adjunctive therapeutic tool in psychotherapy. Since the early twentieth century, psychedelic-assisted psychotherapy has been explored for the treatment of several neuropsychiatric conditions characterized by rigid thought patterns and treatment resistance. However, this rapidly emerging field of neuroscience has evolved alongside opposition in several areas, including the affiliation with mid-twentieth century counterculture movements, media sensationalization, legislative restriction, and scientific criticisms such as “breaking the blind” and “excessive enthusiasm.” This perspective article explores the historical opposition to psychedelic research and the implications for the credibility of the field. In the midst of psychedelic drug policy reform, drawing lessons from historical events will contribute to clinical research efforts in psychiatry.
... Recent clinical trials have suggested therapeutic potential for classic psychedelics, defined as serotonin 2A receptor (5-HT 2A R) agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin (Johnson et al., 2019). Studies of these substances have demonstrated preliminary evidence of potential benefits for several conditions, including major depressive disorder (Carhart-Harris et al., 2016Davis et al., 2021;D'Souza et al., 2022;Goodwin et al., 2023;Raison et al., 2023), end-of-life anxiety and depression (Griffiths et al., 2016;Grob et al., 2011;Muttoni et al., 2019;Ross et al., 2016), and substance use disorder (Bogenschutz et al., 2015(Bogenschutz et al., , 2022Johnson et al., 2014Johnson et al., , 2017. While there appear to be both short-and long-term benefits from psychedelic experiences in clinical and nonclinical contexts, there are also short-and long-term risks associated with psychedelic use. ...
Background
As classic psychedelics’ therapeutic potential is studied and their popularity continues to rise, it is important to establish their relative risks and benefits. Previous surveys have tended to use convenience sampling on social media, select participants who have had either extremely positive or negative effects, and have not compared the risk/benefit profile of psychedelics to other substances.
Aims
To address these limitations, we gathered samples from an opt-in panel service using quota-based sampling to approximate demographics representing US Census data, did not pre-specify positive or negative experiences, and compared experiences with psychedelics to those with cannabis.
Methods
We conducted two studies, one using a between-subjects design ( n = 743) and one using a within-subjects design ( n = 514), in which participants recruited from an opt-in panel service reflected on prior experience with psychedelics or cannabis and indicated self-reported risks and benefits associated with their experience.
Results
Results indicated that first or most memorable psychedelic experiences were associated with greater acute challenging effects and persisting negative effects than first or most memorable cannabis experiences, but psychedelic experiences were also associated with greater positive acute and persisting effects. Common predictors of negative and positive acute and persisting effects with psychedelics included various experience qualities (e.g., dose level, presence of others) and individual differences (e.g., religiosity, personality), though only to a small degree.
Conclusions
These findings on psychedelic experiences provide a more nuanced characterization of risks and benefits and their predictors.
... Due to their established and potential novel therapeutic effects, serotonergic psychedelics have become a focal point of current psychopharmacological research [1]. Clinical trials have demonstrated promising effects of these compounds in alleviating anxiety and depression [2][3][4], treating substance abuse [5][6][7][8], and managing obsessive-compulsive 'wet dog shake' [16]. However, for simplicity, we will use the term 'head-twitch response' throughout this paper. ...
Serotonergic psychedelics, which display a high affinity and specificity for 5-HT2A receptors like 2,5-dimethoxy-4-iodoamphetamine (DOI), reliably induce a head-twitch response in rodents characterized by paroxysmal, high-frequency head rotations. Traditionally, this behavior is manually counted by a trained observer. Although automation could simplify and facilitate data collection, current techniques require the surgical implantation of magnetic markers into the rodent’s skull or ear.
This study aimed to assess the feasibility of a marker-less workflow for detecting head-twitch responses using deep learning algorithms. High-speed videos were analyzed using the DeepLabCut neural network to track head movements, and the Simple Behavioral Analysis (SimBA) toolkit was employed to build models identifying specific head-twitch responses.
In studying DOI (0.3125–2.5 mg/kg) effects, the deep learning algorithm workflow demonstrated a significant correlation with human observations. As expected, the preferential 5-HT2A receptor antagonist ketanserin (0.625 mg/kg) attenuated DOI (1.25 mg/kg)-induced head-twitch responses. In contrast, the 5-HT5A receptor antagonists SB 699,551 (3 and 10 mg/kg), and ASP 5736 (0.01 and 0.03 mg/kg) failed to do so.
Previous drug discrimination studies demonstrated that the 5-HT5A receptor antagonists attenuated the interoceptive cue of a potent hallucinogen LSD, suggesting their anti-hallucinatory effects. Nonetheless, the present results were not surprising and support the head-twitch response as selective for 5-HT2A and not 5-HT5A receptor activation. We conclude that the DeepLabCut and SimBA toolkits offer a high level of objectivity and can accurately and efficiently identify compounds that induce or inhibit head-twitch responses, making them valuable tools for high-throughput research.
... Further psilocybin has shown significant improvement in the quality of life. The mystical effect of psilocybin showed that cancer patients were able to overcome the anxiety and depressant even after the 6-month follow-up 29 . ...
Cancer patients are more vulnerable to developing psychiatric disorders like anxiety and depression. These conditions give an additional burden leading to poor quality of life. The available antidepressant and antianxiety drugs are not very useful in improving quality of life by reducing anxiety and depressive episodes. Therefore, there is a need for good drugs to alleviate the psychiatric problems among cancer patients. The recent reviews deal with the pharmacodynamics, pharmacokinetics and efficacy of psilocybin in the treatment of patients suffering from anxiety and depression.
A presente pesquisa pretende deslindar de qual modo a retomada de pesquisas com substâncias alucinógenas podem corroborar, a princípio, na amplificação do direito à morte digna. Outrossim, vislumbra-se averiguar quais são os possíveis impactos das novas descobertas atinentes à Medicina Psicodélica para a humanidade, máxime no que tange aos pacientes terminais, mas também, impende-se investigar a dinâmica existente entre o avanço das pesquisas com substâncias psicoativas e a melhoria no bem-estar dos enfermos
Importance
The psychological morbidity experienced by physicians, advanced practice practitioners (APPs), and nurses from working during the COVID-19 pandemic includes burnout, depression, and posttraumatic stress disorder (PTSD).
Objective
To investigate whether psilocybin therapy could improve symptoms of depression, burnout, and PTSD in US clinicians who developed these symptoms from frontline clinical work during the pandemic.
Design, Setting, and Participants
This double-blind randomized clinical trial enrolled participants from February to December 2022. Participants included physicians, APPs, and nurses who provided frontline care for more than 1 month during the pandemic and had no prepandemic mental health diagnoses but had moderate or severe symptoms of depression at enrollment. Participants were randomly assigned to either the psilocybin or niacin arm. Data analysis was conducted between December 2023 and May 2024 and was based on the intention-to-treat principle.
Intervention
One intervention episode consisted of 2 preparation visits, 1 medication session, and 3 integration visits. At the medication session, participants received psilocybin, 25 mg, or niacin, 100 mg, orally.
Main Outcome and Measures
The primary outcome was a change from baseline (preparation 1 session) to day 28 (after medication administration) in symptoms of depression as measured by the clinician-administered Montgomery-Asberg Depression Rating Scale (MADRS) used by blinded raters. The secondary outcomes were a change in symptoms of burnout (measured with the Stanford Professional Fulfillment Index [SPFI]) and symptoms of PTSD (measured with the Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [PCL-5]).
Results
A total of 30 clinicians (15 females [50%]; mean [range] age, 38 [29-60] years) participated, of whom 15 were randomly assigned to receive psilocybin and 15 to receive niacin. The mean change in symptoms of depression (MADRS scores) from preparation 1 session to day 28 was −21.33 (7.84) in the psilocybin arm compared with −9.33 (7.32) in the niacin arm, with a mean difference between arms of −12.00 (95% CI, −17.67 to −6.33; P < .001), a decrease in MADRS scores indicating improvement. The mean change in SPFI scores from preparation 1 session to day 28 showed a numerically larger improvement in symptoms of burnout in the psilocybin compared with the niacin arm (−6.40 [5.00] vs −2.33 [5.97]; P = .05) but was not statistically significant. Since the SPFI score change did not reach statistical significance, the PCL-5 score change was evaluated descriptively. The mean change in PCL-5 scores showed a numerically larger decrease in symptoms of PTSD from preparation 1 session to day 28 in the psilocybin vs the niacin arm (−16.67 [15.04] vs −6.73 [10.69]), but this difference was not statistically tested.
Conclusions and Relevance
This randomized clinical trial found that psilocybin therapy resulted in a significant, sustained reduction in symptoms of depression experienced by clinicians after frontline work during the COVID-19 pandemic. The findings establish psilocybin therapy as a new paradigm of treatment for this postpandemic condition.
Trial Registration
ClinicalTrials.gov Identifier: NCT05163496
Background
Persons with schizophrenia are excluded from psychedelic-assisted therapy due to concerns about the risk of triggering or worsening psychosis. However, there is limited meta-analytic data on the risk of psychedelic-induced psychosis in individuals with pre-existing psychotic disorders.
Methods
We conducted a systematic review, meta-analysis, and overview of reviews to assess the incidence of psychedelic-induced psychosis and symptom exacerbation in schizophrenia. Our pre-registered protocol (CRD42023399591) covered: LSD, psilocybin, mescaline, DMT, and MDMA, using data from Embase, PubMed, PsyARTICLES, PsyINFO, and trial registries up to November 2023. A random-effects model was used to calculate psychosis incidence, with standardized assessments of study quality.
Results
From 131 publications, we analyzed 14 systematic reviews, 20 reviews, 35 randomized-controlled trials (RCTs), 10 case-control studies, 30 uncontrolled trials (UCTs), and 22 cohort studies, most of which were low quality. Meta-analysis of nine studies showed an incidence of psychedelic-induced psychosis at 0.002% in population studies, 0.2% in UCTs, and 0.6% in RCTs. In UCTs including individuals with schizophrenia, 3.8% developed long-lasting psychotic symptoms. Of those with psychedelic-induced psychosis, 13.1% later developed schizophrenia. Sensitivity analyses confirmed the results.
Conclusion
In summary, the reviewed evidence suggests that schizophrenia might not be a definite exclusion criterion for clinical trials exploring safety and efficacy of psychedelics for treatment-resistant depression and negative symptoms. However, given the low quality and limited number of studies, more high-quality research is needed, and a conservative approach is recommended until further data is available.
Following a decades-long decline in psychedelic research resulting from social, political, and legislative factors, there has been greatly renewed interest in these compounds' ability to treat psychiatric disorders. Classic psychedelics, encompassing both natural and synthetic psychoactive compounds, are characterized by their action as agonists or partial agonists of serotonin 5-hydroxytryptamine 2A receptors. In this comprehensive review, we summarize the latest clinical trials of classic psychedelics on depression and anxiety, attending to the patient demographics and methodology of each study. Overall, studies published since 2020 affirm the potential for classic psychedelics to treat major depressive disorder, treatment-resistant depression, bipolar II, and anxiety-spectrum disorders. However, findings are limited by short follow-up durations and nonstandard dosing and study designs. Given that many of the studies identified were post hoc analyses or follow-up studies from a select few parent studies, it is recommended that more original research be undertaken, with more diverse and larger sample sizes, standardized methodologies including blinding assessment, and long-term follow-up to identify duration of benefits and adverse reactions. It is also important to consider the role of psychological support and the therapeutic alliance in the psychedelic treatment of psychiatric disorders.
Psilocybin mushrooms, also known as "magic mushrooms," have garnered significant attention for their psychoactiveproperties and potential therapeutic applications. This review explores the comprehensive morphology, pharmacognosticproperties, and pharmacological activities of psilocybin-producing fungi. The unique morphological characteristics of thesemushrooms, including their microscopic structure and macroscopic features, contribute to their identification and classificationwithin various Psilocybe species. The pharmacognostic analysis delves into the identification, sourcing, and quality control ofthese fungi, essential for therapeutic and research applications. Moreover, the pharmacological profile of psilocybin, the primarybioactive compound, is discussed in detail, highlighting its mechanism of action, therapeutic potential in mental healthtreatments, and effects on the central nervous system. With an increasing body of evidence supporting the therapeutic potentialof psilocybin in managing depression, anxiety, and other mental health disorders, this paper provides a foundationalunderstanding for future research and clinical applications. Ultimately, this review aims to bridge the gap between traditionalknowledge and modern scientific insights, contributing to the broader understanding of psilocybin mushrooms' potential astherapeutic agents.
Psychedelic compounds continue gaining scientific and regulatory traction as potential new treatments for psychiatric disorders. While most psychiatrists will likely not work directly with these compounds, psychedelic research practices provide insights that may improve conventional psychiatric care. Through its emphasis on ‘set and setting’ (mindset and environment, respectively), psychedelic research highlights the importance of non-pharmacologic factors maximizing therapeutic outcomes. While psychedelics and serotonergic antidepressants are distinctly different in their subjective experience, new findings suggest mechanistic overlap between them. Both have been found to modulate neurotrophins, enhance neuroplasticity, and reopen critical periods of learning, molded by the environmental context in which they are administered.
This paper will argue that by integrating insights from psychedelic research (particularly set and setting), depression treatment outcomes in traditional psychiatric settings can improve by optimizing non-pharmacological factors in treatment, including the provision of high-quality psychotherapy.
Rationale: Serotonin (5-Hydroxytryptamine, 5-HT) receptors play an important role in perception, affect regulation and attention. Pharmacological challenge with the 5-HT2A agonist psilocybin (PY) is useful in studying the neurobiological basis of cognition and consciousness. Objective: Investigation of dose-dependent effects of PY on psycho(patho)logical and physiological parameters. Methods: Eight subjects received placebo (PL), and 45 ("very low dose, VLD”), 115 ("low dose, LD”), 215 ("medium dose, MD”), and 315 ("high dose, HD”) μg/kg body weight PY. The "Altered States of Consciousness Rating Scale” (5D-ASC), the "Frankfurt Attention Inventory” (FAIR), and the "Adjective Mood Rating Scale” (AMRS) were used to assess the effects of PY on psycho(patho)logical core dimensions, attention, and mood. A 24-h electrocardiogram (EKG) was recorded and blood pressure was measured. Plasma concentrations of thyroid-stimulating hormone (TSH), prolactin (PRL), cortisol (CORT), adrenocorticotropic hormone (ACTH), and standard clinical chemical parameters were determined. Results: PY dose dependently increased scores of all 5D-ASC core dimensions. Only one subject reacted with transient anxiety to HD PY. Compared with PL, MD and HD PY led to a 50% reduction of performance in the FAIR test. "General inactivation”, "emotional excitability”, and "dreaminess” were the only domains of the AMRS showing increased scores following MD and HD PY. The mean arterial blood pressure (MAP) was moderately elevated only 60min following administration of HD PY. Neither EKG nor body temperature was affected by any dose of PY. TSH, ACTH, and CORT plasma levels were elevated during peak effects of HD PY, whereas PRL plasma levels were increased following MD and HD PY. Conclusion: PY affects core dimensions of altered states of consciousness and physiological parameters in a dose-dependent manner. Our study provided no cause for concern that PY is hazardous with respect to somatic health
https://heffter.org/docs/hrireview/01/chapter2.pdf
Understanding why some terminally ill patients desire a hastened death has become an important issue in palliative care and the debate regarding legalization of assisted suicide.
To assess the prevalence of desire for hastened death among terminally ill cancer patients and to identify factors corresponding to desire for hastened death. Design Prospective survey conducted in a 200-bed palliative care hospital in New York, NY.
Ninety-two terminally ill cancer patients (60% female; 70% white; mean age, 65.9 years) admitted between June 1998 and January 1999 for end-of-life care who passed a cognitive screening test and provided sufficient data to permit analysis.
Scores on the Schedule of Attitudes Toward Hastened Death (SAHD), a self-report measure assessing desire for hastened death among individuals with life-threatening medical illness.
Sixteen patients (17%) were classified as having a high desire for hastened death based on the SAHD and 15 (16%) of 89 patients met criteria for a current major depressive episode. Desire for hastened death was significantly associated with a clinical diagnosis of depression (P=.001) as well as with measures of depressive symptom severity (P<.001) and hopelessness (P<.001). In multivariate analyses, depression (P=.003) and hopelessness (P<.001) provided independent and unique contributions to the prediction of desire for hastened death, while social support (P=.05) and physical functioning (P=.02) added significant but smaller contributions.
Desire for hastened death among terminally ill cancer patients is not uncommon. Depression and hopelessness are the strongest predictors of desire for hastened death in this population and provide independent and unique contributions. Interventions addressing depression, hopelessness, and social support appear to be important aspects of adequate palliative care, particularly as it relates to desire for hastened death.
This Spring I received a long distance telephone call from Dean Samuel Miller, who invited me to give this year's Ingersoll Lecture on human immortality. Three days later, Dean Miller was dead. When I heard the sad news, I, as many of you no doubt, began to think about the way he had influenced me, especially during my theological training here at Harvard Divinity School. One of my most vivid memories was a point which he emphasized in his class on Religion and Literature. Sam Miller felt strongly that in our modern 20th century two of the most profound and important experiences of human life are becoming more and more insulated from everyday existence. These two experiences, birth and death, have the potential for affecting the character and quality of the rest of life. But in each instance, they are falling victim to modern technological efficiency and adding to the process of dehumanization rather than counteracting it.