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The International Journal on Drug Policy Jun 2024Despite advancements in policies governing psychedelic substances globally, our understanding of real-world psychedelic use and its variations across international...
OBJECTIVES
Despite advancements in policies governing psychedelic substances globally, our understanding of real-world psychedelic use and its variations across international jurisdictions remains limited. We implemented the Global Psychedelic Survey (GPS) to capture information about psychedelic consumer characteristics, access, and usage patterns around the world.
METHODS
The GPS was administered online in Spring 2023 to English-speaking adults (≥21 years) who use(d) psychedelics. We categorized survey responses into major catchment regions (Canada/US, Europe/UK, Australia/NZ, All Other). We used descriptive and bivariable statistics to characterize consumers' socio-demographic characteristics, psychedelic access sources, and usage patterns. We examined regional differences in psychedelic use patterns using multinomial logistic regression.
RESULTS
We analyzed 6379 responses from 85 countries including Canada/US (n = 4434), Europe/UK (n = 771), Australia/NZ (n = 864), and Other (n = 310). Psilocybin, LSD, and MDMA were the most used psychedelics and personal growth was the most common use motive across all catchments. There were significant regional differences in psychedelic use patterns, including types of psychedelics used (e.g., less ibogaine use in Europe/UK and Australia/NZ relative to Canada/US), frequency of use (e.g., lower frequency use in Australia/NZ relative to Canada/US), motivations for use (e.g., less therapeutic use in Europe/UK and Other relative to Canada/US), and types of dosing regimens (e.g., more "micro"-dosing in Canada/US).
DISCUSSION
In this large sample of adult psychedelic consumers from regions around the world, infrequent psychedelic use centered around life enhancement was common. Respondents indicated preference for legal access via quality-controlled sources. Jurisdictional differences in access and usage patterns likely reflect region-specific regulations and traditional practices. Further research should explore opportunities to increase representation of non-White respondents in psychedelic research via translation of studies into several languages and incorporation of culturally reflective, community-based study development.
PubMed: 38936219
DOI: 10.1016/j.drugpo.2024.104507 -
Psychiatry Research Jun 2024Treatment-Resistant Depression (TRD) challenges psychiatric treatment, with existing guidelines covering only a subset of augmentation strategies.
BACKGROUND
Treatment-Resistant Depression (TRD) challenges psychiatric treatment, with existing guidelines covering only a subset of augmentation strategies.
METHODS
A network meta-analysis following PRISMA guidelines examined the efficacy and safety of TRD treatments, analyzing 72 randomized controlled trials from eight databases, assessing response and remission rates, tolerability, and safety through the Cochrane Risk of Bias Tool and CINeMA framework.
FINDINGS
Including 12,105 participants, the analysis highlighted ECT, Ketamine, Esketamine, and Psilocybin as superior first-line treatments due to their optimal balance between effectiveness and tolerability. Brexpiprazole and Quetiapine showed no significant efficacy over placebo in response rates, while Esketamine and Psilocybin exhibited lower tolerability.
INTERPRETATION
The results advocate for ECT, Ketamine, Esketamine, and Psilocybin as preferred treatments for TRD, guiding clinical practice with evidence-based recommendations for enhancing treatment outcomes. This study underscores the importance of considering both efficacy and safety in selecting augmentation strategies for TRD.
PubMed: 38924903
DOI: 10.1016/j.psychres.2024.116018 -
Frontiers in Psychiatry 2024Resistance to traditional treatment methods is still a major obstacle in modern psychiatry. As a result, several studies are currently being conducted to find effective... (Review)
Review
Unlocking the healing power of psilocybin: an overview of the role of psilocybin therapy in major depressive disorder, obsessive-compulsive disorder and substance use disorder.
Resistance to traditional treatment methods is still a major obstacle in modern psychiatry. As a result, several studies are currently being conducted to find effective alternatives to traditional therapies. One of these alternatives is psilocybin, a psychedelic substance that has been tested in clinical trials as an adjunct to psychotherapy. These studies focus on patients with major depressive disorder (MDD), obsessive-compulsive disorder (OCD) and substance use disorder (SUD), particularly alcohol and nicotine dependence. This article looks at the current understanding of psilocybin, including data from clinical trials conducted, psilocybin's mechanism of action, its safety and the level of risk associated with it.
PubMed: 38919636
DOI: 10.3389/fpsyt.2024.1406888 -
ACS Chemical Neuroscience Jun 2024The extent of changes in functional connectivity (FC) within functional networks as a common feature across hallucinogenic drug classes is under-explored. This work...
The extent of changes in functional connectivity (FC) within functional networks as a common feature across hallucinogenic drug classes is under-explored. This work utilized fMRI to assess the dissociative hallucinogens Psilocybin, a classical serotonergic psychedelic, and Salvinorin-A, a kappa-opioid receptor (KOR) agonist, on resting-state FC in nonhuman primates. We highlight overlapping and differing influence of these substances on FC relative to the thalamus, claustrum, prefrontal cortex (PFC), default mode network (DMN), and DMN subcomponents. Analysis was conducted on a within-subject basis. Findings support the cortico-claustro-cortical network model for probing functional effects of hallucinogens regardless of serotonergic potential, with a potential key paradigm centered around the claustrum, PFC, anterior cingulate cortices (ACC), and angular gyrus relationship. Thalamo-cortical networks are implicated but appear dependent on 5-HTR activation. Acute desynchronization relative to the DMN for both drugs was also shown. Our findings provide a framework to understand broader mechanisms at which hallucinogens in differing classes may impact subjects regardless of the target receptor.
PubMed: 38916752
DOI: 10.1021/acschemneuro.4c00245 -
Journal of Palliative Medicine Jun 2024
PubMed: 38916613
DOI: 10.1089/jpm.2024.0066 -
Neurobiology of Learning and Memory Jun 2024Psilocybin may provide a useful treatment for mood disorders including anxiety and depression but its mechanisms of action for these effects are not well understood....
Psilocybin may provide a useful treatment for mood disorders including anxiety and depression but its mechanisms of action for these effects are not well understood. While recent preclinical work has begun to assess psilocybin's role in affective behaviors through innate anxiety or fear conditioning, there is scant evidence for its role in conflict between reward and punishment. The current study was designed to determine the impact of psilocybin on the learning of reward-punishment conflict associations, as well as its effects after learning, in male and female rats. We utilized a chained schedule of reinforcement that involved execution of safe and risky reward-guided actions under uncertain punishment. Different patterns of behavioral suppression by psilocybin emerged during learning versus after learning of risky action-reward associations. Psilocybin increased behavioral suppression in female rats as punishment associations were learned. After learning, psilocybin decreased behavioral suppression in both sexes. Thus, psilocybin produces divergent effects on action suppression during approach-avoidance conflict depending on when the conflict is experienced. This observation may have implications for its therapeutic mechanism of action.
PubMed: 38909970
DOI: 10.1016/j.nlm.2024.107954 -
Nature Communications Jun 2024Psychedelics have experienced renewed interest following positive clinical effects, however the neurobiological mechanisms underlying effects remain unclear. The...
Psychedelics have experienced renewed interest following positive clinical effects, however the neurobiological mechanisms underlying effects remain unclear. The paraventricular nucleus of the hypothalamus (PVN) plays an integral role in stress response, autonomic function, social behavior, and other affective processes. We investigated the effect of psilocin, the psychoactive metabolite of psilocybin, on PVN reactivity in Sprague Dawley rats. Psilocin increased stimulus-independent PVN activity as measured by c-Fos expression in male and female rats. Psilocin increased PVN reactivity to an aversive air-puff stimulus in males but not females. Reactivity was restored at 2- and 7-days post-injection with no group differences. Additionally, prior psilocin injection did not affect PVN reactivity following acute restraint stress. Experimental groups sub-classified by baseline threat responding indicate that increased male PVN reactivity is driven by active threat responders. These findings identify the PVN as a significant site of psychedelic drug action with implications for threat responding behavior.
Topics: Animals; Paraventricular Hypothalamic Nucleus; Male; Psilocybin; Rats, Sprague-Dawley; Female; Rats; Hallucinogens; Proto-Oncogene Proteins c-fos; Behavior, Animal; Stress, Psychological
PubMed: 38909051
DOI: 10.1038/s41467-024-49741-9 -
The Australian and New Zealand Journal... Jun 2024Despite rapid advances in psychedelic sciences and the increasing number of countries legalizing psychedelics for the treatment of mental illnesses, the attitudes,...
OBJECTIVE
Despite rapid advances in psychedelic sciences and the increasing number of countries legalizing psychedelics for the treatment of mental illnesses, the attitudes, knowledge and readiness of both mental health consumers and the general population remain largely unknown.
METHODS
A cross-sectional survey was conducted among Australians, targeting individuals with mental illness as potential mental health service users. A sub-sample of individuals free of mental illness was also surveyed to assess attitudes in the general population. Participants completed the Attitudes on Psychedelics Questionnaire, the Basic Knowledge of Psychedelics Test and a questionnaire by Corrigan et al. to capture attitudes toward psychedelic therapy by mental health service users.
RESULTS
Of the 502 respondents, 64.5% self-identified as having a mental illness. A significant proportion favored legalizing psychedelics for medical use (43%) and were open to their use (52.4%), yet fewer viewed their effects positively (24%) or considered them safe (33%). Most participants reported to be psychedelic naive (61%). Participants with mental illness had significantly more experience with psychedelics than participant free of mental illness (44.1% vs 29.7%). Experience, perceived knowledge and actual knowledge significantly predicted attitudes toward legalization, effects, risks and openness to psychedelics.
CONCLUSIONS
While a large proportion of Australians are in favor of legalizing psychedelics for medical purposes, concerns about safety remain. People with self-identified mental illness, those with previous recreational psychedelic experience and those with greater knowledge of psychedelics were more likely to have positive attitudes toward psychedelics and psychedelic-assisted therapy.
PubMed: 38907608
DOI: 10.1177/00048674241261779 -
Journal of Psychoactive Drugs Jun 2024Data on medication interactions with psychedelics are limited. Here we present what may be the first published report of a hypertensive emergency following the...
Data on medication interactions with psychedelics are limited. Here we present what may be the first published report of a hypertensive emergency following the combination of psilocybin mushrooms with a monoamine oxidase inhibitor (MAOI). A 42-year-old man with treatment-resistant major depressive disorder took 1 g of mushrooms, while prescribed tranylcypromine, extended-release dextroamphetamine-amphetamine, and other medications. Approximately half an hour later, he developed severe hypertension with chest pain, palpitations, and headache. Upon hospital presentation, the electrocardiogram demonstrated ST-elevation. The patient was diagnosed with a myocardial infarction and treated with lorazepam, nitroglycerin, and aspirin. He subsequently underwent emergency cardiac catheterization, which revealed no significant cardiac abnormalities. Following overnight hospitalization, he was discharged home with no lasting physical sequelae. Though data are few, past studies suggest that classic serotonergic psychedelics (5HT-2A receptor agonists) such as dimethyltryptamine (DMT), lysergic acid (LSD), and synthetic psilocybin should not produce hypertensive emergency when combined with MAOIs. We suspect phenylethylamine, found in and other species of psilocybin mushrooms, interacted with tranylcypromine and dextroamphetamine-amphetamine to produce this hypertensive emergency. Patients prescribed MAOIs should be warned of the potential for hypertensive emergency when consuming psilocybin mushrooms, particularly when also prescribed norepinephrine releasers such as dextroamphetamine-amphetamine.
PubMed: 38903003
DOI: 10.1080/02791072.2024.2368617 -
ACS Medicinal Chemistry Letters Jun 2024This Patent Highlight explores advancements in pharmacology, focusing on the novel delivery and application of psychoactive substances. It highlights the development of...
This Patent Highlight explores advancements in pharmacology, focusing on the novel delivery and application of psychoactive substances. It highlights the development of transdermal formulations for psychoactive alkaloids, neuroenhancement techniques to augment emotional responses, and the intravenous infusion of psilocybin or psilocin for various therapeutic purposes. Additionally, it delves into the characterization and potential uses of crystalline forms of tryptamine derivatives. These innovations signify significant progress in drug delivery systems, neurostimulation methods, and the therapeutic use of psychedelic compounds, potentially revolutionizing the treatment of psychological and neurological disorders.
PubMed: 38894903
DOI: 10.1021/acsmedchemlett.4c00181