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JAMA Oncology Jun 2023
Topics: Humans; Psilocybin; Depression; Depressive Disorder, Major; Neoplasms; Patients
PubMed: 37052904
DOI: 10.1001/jamaoncol.2023.0351 -
Nature Medicine Aug 2023Anorexia nervosa (AN) is a deadly illness with no proven treatments to reverse core symptoms and no medications approved by the US Food and Drug Administration. Novel...
Anorexia nervosa (AN) is a deadly illness with no proven treatments to reverse core symptoms and no medications approved by the US Food and Drug Administration. Novel treatments are urgently needed to improve clinical outcomes. In this open-label feasibility study, 10 adult female participants (mean body mass index 19.7 kg m; s.d. 3.7) who met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for AN or pAN (partial remission) were recruited to a study conducted at an academic clinical research institute. Participants received a single 25-mg dose of synthetic psilocybin in conjunction with psychological support. The primary aim was to assess safety, tolerability and feasibility at post-treatment by incidences and occurrences of adverse events (AEs) and clinically significant changes in electrocardiogram (ECG), laboratory tests, vital signs and suicidality. No clinically significant changes were observed in ECG, vital signs or suicidality. Two participants developed asymptomatic hypoglycemia at post-treatment, which resolved within 24 h. No other clinically significant changes were observed in laboratory values. All AEs were mild and transient in nature. Participants' qualitative perceptions suggest that the treatment was acceptable for most participants. Results suggest that psilocybin therapy is safe, tolerable and acceptable for female AN, which is a promising finding given physiological dangers and problems with treatment engagement. ClinicalTrials.gov identifier NCT04661514 .
Topics: Adult; Humans; Female; Psilocybin; Anorexia Nervosa; Feasibility Studies; Body Mass Index; Treatment Outcome
PubMed: 37488291
DOI: 10.1038/s41591-023-02455-9 -
Proceedings of the National Academy of... Feb 2012Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about... (Clinical Trial)
Clinical Trial
Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.
Topics: Adult; Arteries; Brain; Brain Mapping; Cerebrovascular Circulation; Female; Hallucinogens; Humans; Magnetic Resonance Imaging; Male; Oxygen; Perfusion; Prefrontal Cortex; Psilocybin; Spin Labels
PubMed: 22308440
DOI: 10.1073/pnas.1119598109 -
Psychopharmacology Mar 2004Serotonin (5-Hydroxytryptamine, 5-HT) receptors play an important role in perception, affect regulation and attention. Pharmacological challenge with the 5-HT(2A)... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
RATIONALE
Serotonin (5-Hydroxytryptamine, 5-HT) receptors play an important role in perception, affect regulation and attention. Pharmacological challenge with the 5-HT(2A) 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") microg/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 60 min 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.
Topics: Adult; Affect; Analysis of Variance; Attention; Blood Pressure; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heart Rate; Humans; Male; Psilocybin
PubMed: 14615876
DOI: 10.1007/s00213-003-1640-6 -
Journal of Psychopharmacology (Oxford,... Nov 2014Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To... (Clinical Trial)
Clinical Trial
Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-week smoking cessation treatment protocol. Participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. Biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up. The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies (typically <35%). Although the open-label design does not allow for definitive conclusions regarding the efficacy of psilocybin, these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models. The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction.
Topics: Attitude; Behavior, Addictive; Biomarkers; Carbon Monoxide; Cognitive Behavioral Therapy; Combined Modality Therapy; Cotinine; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Nicotinic Agonists; Pilot Projects; Psilocybin; Serotonin Receptor Agonists; Smoking Cessation; Tobacco Use Disorder; Treatment Outcome
PubMed: 25213996
DOI: 10.1177/0269881114548296 -
Therapeutic role of psilocybin and 3,4-methylenedioxymethamphetamine in trauma: A literature review.World Journal of Psychiatry May 2023With the Food and Drug Administration designation in 2017 of 3,4-methylenedioxymethamphetamine (MDMA) as a breakthrough therapy in post-traumatic stress disorder and... (Review)
Review
With the Food and Drug Administration designation in 2017 of 3,4-methylenedioxymethamphetamine (MDMA) as a breakthrough therapy in post-traumatic stress disorder and psilocybin in treatment-resistant depression, psychedelic drugs have continued to garner the attention of researchers and clinicians for their promise of unmatched, rapid improvement in a multitude of psychiatric conditions. Classic psychedelic drugs including psilocybin, lysergic acid diethylamide, and ayahuasca, as well as non-classic drugs such as MDMA and ketamine, are currently being investigated for a potential therapeutic role in trauma, depressive disorders, and other psychopathologies. However, psilocybin and MDMA each have a functional profile well-suited for integration with psychotherapy. The present review focuses on psilocybin and MDMA in psychedelic-assisted therapy (PAT), as these studies compose most of the literature pool. In this review, we discuss the current and future uses of psychedelic drugs, with an emphasis on the role of MDMA and psilocybin in PAT in the setting of trauma and related comorbidities on the efficacy of psychedelic drugs across multiple psychiatric disorders. The article concludes with thoughts for future research, such as incorporating wearables and standardization of symptom scales, therapy styles, and assessment of adverse drug reactions.
PubMed: 37303932
DOI: 10.5498/wjp.v13.i5.182 -
International Journal of Molecular... Dec 2023Psychedelics belong to the oldest psychoactive drugs. They arouse recent interest due to their therapeutic applications in the treatment of major depressive disorder,... (Review)
Review
Psychedelics belong to the oldest psychoactive drugs. They arouse recent interest due to their therapeutic applications in the treatment of major depressive disorder, substance use disorder, end-of-life anxiety,= and anxiety symptoms, and obsessive-compulsive disorder. In this review, the current state of preclinical research on the mechanism of action, neurotoxicity, and behavioral impact of psychedelics is summarized. The effect of selective 5-HT2A receptor agonists, 25I- and 25B-NBOMe, after acute and repeated administration is characterized and compared with the effects of a less selective drug, psilocybin. The data show a significant effect of NBOMes on glutamatergic, dopaminergic, serotonergic, and cholinergic neurotransmission in the frontal cortex, striatum, and nucleus accumbens. The increases in extracellular levels of neurotransmitters were not dose-dependent, which most likely resulted from the stimulation of the 5-HT2A receptor and subsequent activation of the 5-HT2C receptors. This effect was also observed in the wet dog shake test and locomotor activity. Chronic administration of NBOMes elicited rapid development of tolerance, genotoxicity, and activation of microglia. Acute treatment with psilocybin affected monoaminergic and aminoacidic neurotransmitters in the frontal cortex, nucleus accumbens, and hippocampus but not in the amygdala. Psilocybin exhibited anxiolytic properties resulting from intensification of GABAergic neurotransmission. The data indicate that NBOMes as selective 5-HT2A agonists exert a significant effect on neurotransmission and behavior of rats while also inducing oxidative DNA damage. In contrast to NBOMes, the effects induced by psilocybin suggest a broader therapeutic index of this drug.
Topics: Animals; Rats; Hallucinogens; Psilocybin; Depressive Disorder, Major; Receptor, Serotonin, 5-HT2A; Neurotransmitter Agents
PubMed: 38203411
DOI: 10.3390/ijms25010241 -
The Australian and New Zealand Journal... Jul 2023
Topics: Humans; Psilocybin; N-Methyl-3,4-methylenedioxyamphetamine; Hallucinogens; Mental Disorders
PubMed: 37161273
DOI: 10.1177/00048674231174171 -
Scientific Reports Nov 2021The use of psychedelic substances at sub-sensorium 'microdoses', has gained popular academic interest for reported positive effects on wellness and cognition. The...
The use of psychedelic substances at sub-sensorium 'microdoses', has gained popular academic interest for reported positive effects on wellness and cognition. The present study describes microdosing practices, motivations and mental health among a sample of self-selected microdosers (n = 4050) and non-microdosers (n = 4653) via a mobile application. Psilocybin was the most commonly used microdose substances in our sample (85%) and we identified diverse microdose practices with regard to dosage, frequency, and the practice of stacking which involves combining psilocybin with non-psychedelic substances such as Lion's Mane mushrooms, chocolate, and niacin. Microdosers were generally similar to non-microdosing controls with regard to demographics, but were more likely to report a history of mental health concerns. Among individuals reporting mental health concerns, microdosers exhibited lower levels of depression, anxiety, and stress across gender. Health and wellness-related motives were the most prominent motives across microdosers in general, and were more prominent among females and among individuals who reported mental health concerns. Our results indicate health and wellness motives and perceived mental health benefits among microdosers, and highlight the need for further research into the mental health consequences of microdosing including studies with rigorous longitudinal designs.
Topics: Adolescent; Adult; Anxiety; Cognition; Cross-Sectional Studies; Depression; Female; Hallucinogens; Humans; International Cooperation; Lysergic Acid Diethylamide; Male; Mental Health; Middle Aged; Motivation; Psilocybin; Surveys and Questionnaires; Young Adult
PubMed: 34795334
DOI: 10.1038/s41598-021-01811-4 -
Journal of Neurochemistry Jul 2022A confluence of factors has renewed interest in the scientific understanding and translational potential of psychedelic drugs such as lysergic acid diethylamide (LSD),... (Review)
Review
A confluence of factors has renewed interest in the scientific understanding and translational potential of psychedelic drugs such as lysergic acid diethylamide (LSD), mescaline, and psilocybin: the desire for additional approaches to mental health care, incremental progress in basic and clinical research, and the reconsideration and relaxation of existing drug policies. With the United States Food and Drug Administration's designation of psilocybin as a "Breakthrough Therapy" for treatment-resistant depression, a new path has been forged for the conveyance of psychedelics to the clinic. Essential to the further development of such applications, however, is a clearer understanding of how these drugs exert their effects at the molecular level. Here we review the current knowledge regarding the molecular details of psychedelic drug actions and suggest that these discoveries can facilitate new insights into their hallucinogenic and therapeutic mechanisms.
Topics: Hallucinogens; Lysergic Acid Diethylamide; Psilocybin; United States
PubMed: 34797943
DOI: 10.1111/jnc.15540