psychoactive effects
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2021 ◽  
Vol 12 ◽  
Author(s):  
Pascal Michael ◽  
David Luke ◽  
Oliver Robinson

Introduction:N,N-dimethyltryptamine (DMT) is an endogenous serotonergic psychedelic capable of producing radical shifts in conscious experience. Increasing trends in its use, as well as new trials administering DMT to patients, indicate the growing importance of a thorough elucidation of the qualitative content, over and above structure, which the drug occasions. This is particularly in light of the hyper-real, otherworldly, and often ontologically challenging yet potentially transformative, nature of the experience, not least encounters with apparently non-self social agents. Laboratory studies have been limited by clinical setting and lacking qualitative analyses of experiential content, while online surveys’ limitations lie in retrospective design, uncontrolled use, and both of which not guaranteeing ‘breakthrough’ experiences, i.e., producing very strong psychoactive effects.Methods: We report on the first naturalistic field study of DMT use including its qualitative analysis. Screened, healthy, anonymised and experienced DMT users were observed during their non-clinical use of the drug at home (40–75 mg inhaled). In-depth semi-structured interviews (inspired by the micro-phenomenological technique) were employed immediately after their experience. This paper reports on the thematic analysis of one major domain of the breakthrough experiences elicited, the ‘other’. Thirty-six post-DMT experience interviews with mostly Caucasian (83%) males (eight female) of average 37 years were predominantly inductively coded.Results: Invariably, profound and highly intense experiences occurred. The first overarching category comprised the encounter with other ‘beings’ (94% of reports), encompassing super-ordinate themes including the entities’ role, appearance, demeanour, communication and interaction; while the second overarching category comprised experiences of emerging into other ‘worlds’ (100% of reports), encompassing super-ordinate themes of the scene, the contents and quality of the immersive spaces. Many further mid-level themes and subthemes also illuminate the rich content of the DMT experience.Discussion: The present study provides a systematic and in-depth analysis of the nuanced content of the otherworldly encounter within the breakthrough DMT experience, as well as elaborating on the resonances both with previous DMT studies focusing on entity encounters and other types of extraordinary experiences entailing such encounters. These include the alien abduction, folkloric, shamanic and near-death experience. Putative neural mechanisms of these features of the DMT experience and its promise as a psychotherapeutic agent are discussed in light of such findings.


2021 ◽  
Vol 12 ◽  
Author(s):  
Johannes Reckweg ◽  
Natasha L. Mason ◽  
Cees van Leeuwen ◽  
Stefan W. Toennes ◽  
Theis H. Terwey ◽  
...  

5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) is a tryptamine with ultra-rapid onset and short duration of psychedelic effects. Prospective studies for other tryptamines have suggested beneficial effects on mental health outcomes. In preparation for a study in patients with depression, the present study GH001-HV-101 aimed to assess the impact of four different dose levels of a novel vaporized 5-MeO-DMT formulation (GH001) administered via inhalation as single doses of 2 (N = 4), 6 (N = 6), 12 (N = 4) and 18 mg (N = 4), and in an individualized dose escalation regimen (N = 4) on the safety, tolerability, and the dose-related psychoactive effects in healthy volunteers (N = 22). The psychedelic experience was assessed with a novel Peak Experience Scale (PES), the Mystical Experience Questionnaire (MEQ), the Ego Dissolution Inventory (EDI), the Challenging Experience Questionnaire (CEQ), and the 5-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). Further aims were to assess the impact of 5-MeO-DMT on cognitive functioning, mood, and well-being. Higher doses of 5-MeO-DMT produced significant increments in the intensity of the psychedelic experience ratings as compared to the lowest 2 mg dose on all questionnaires, except the CEQ. Prominent effects were observed following single doses of 6, 12, and 18 mg on PES and MEQ ratings, while maximal effects on PES, MEQ, EDI, and 5D-ASC ratings were observed following individualized dose escalation of 5-MeO-DMT. Measures of cognition, mood, and well-being were not affected by 5-MeO-DMT. Vital signs at 1 and 3 h after administration were not affected and adverse events were generally mild and resolved spontaneously. Individualized dose escalation of 5-MeO-DMT may be preferable over single dose administration for clinical applications that aim to maximize the experience to elicit a strong therapeutic response.


Planta Medica ◽  
2021 ◽  
Author(s):  
Matteo Politi ◽  
Giorgia Tresca ◽  
Luigi Menghini ◽  
Claudio Ferrante

AbstractThe herbal preparation ayahuasca has been an important part of ritual and healing practices, deployed to access invisible worlds in several indigenous groups in the Amazon basin and among mestizo populations of South America. The preparation is usually known to be composed of two main plants, Banisteriopsis caapi and Psychotria viridis, which produce both hallucinogenic and potent purging and emetic effects; currently, these are considered its major pharmacological activities. In recent decades, the psychoactive and visionary effect of ayahuasca has been highly sought after by the shamanic tourism community, which led to the popularization of ayahuasca use globally and to a cultural distancing from its traditional cosmological meanings, including that of purging and emesis. Further, the field of ethnobotany and ethnopharmacology has also produced relatively limited data linking the phytochemical diversity of ayahuasca with the different degrees of its purging and emetic versus psychoactive effects. Similarly, scientific interest has also principally addressed the psychological and mental health effects of ayahuasca, overlooking the cultural and pharmacological importance of the purging and emetic activity. The aim of this review is therefore to shed light on the understudied purging and emetic effect of ayahuasca herbal preparation. It firstly focuses on reviewing the cultural relevance of emesis and purging in the context of Amazonian traditions. Secondly, on the basis of the main known phytochemicals described in the ayahuasca formula, a comprehensive pharmacological evaluation of their emetic and purging properties is presented.


2021 ◽  
Vol 27 ◽  
Author(s):  
Sara Malaca ◽  
Francesco Paolo Busardò ◽  
Giulio Nittari ◽  
Ascanio Sirignano ◽  
Giovanna Ricci

Background: Over the past few years, an emerging number of new psychoactive substances (NPSs) entered the illicit market. NPSs are designed to resemble the effects of classical drugs of abuse, reinforcing their effects and duration. Among the most abused NPS, synthetic cannabinoids are cannabinoid receptor agonists (SCRAs) and mimic the effect of the main psychotropic phytocannabinoid Δ9-tetrahydrocannabinol (THC). Methods: We herein reviewed the international literature to provide available information on the newest SCRAs generation. Results: Compared to the previous SCRAs generations, the structures of the last generation result in increased affinity for and efficacy at cannabinoid CB1 receptors, which are thought to be mainly responsible for the psychoactive effects of THC and its analogues. Accordingly, these more potent cannabimimetic effects may increase the number of adverse reactions such as neurological disorders (e.g., psychosis, agitation, irritability, paranoia, confusion, and anxiety), psychiatric episodes (e.g., hallucinations, delusions, self-harm), other physical conditions (e.g., tachycardia, hypertension, arrhythmia, chest pain, nausea, vomiting, and fever) and deaths. In the last decade, more than a hundred SCRAs from different chemical classes emerged on the illicit web market. SCRAs have been thoroughly studied: they were physico-chemically characterized and pharmaco-toxicological characteristics were investigated. The last SCRAs generations include increasingly potent and toxic compounds, posing a potential health threat to consumers. Conclusion: From November 2017 to February 2021, at least 20 new “fourth-generation” SCRAs were formally reported to international drug agencies. Our understanding about the neurotoxicity of these compounds is still limited due to the lack of global data, but their potency and their toxicity are likely higher than those of the previous generations.


Medicina ◽  
2021 ◽  
Vol 57 (10) ◽  
pp. 1107
Author(s):  
Katie Pizzolato ◽  
David Thacker ◽  
Nicole Del Toro-Pagán ◽  
Abeer Hanna ◽  
Jacques Turgeon ◽  
...  

Cannabis products that contain the tetrahydrocannabinol (THC) cannabinoid are emerging as promising therapeutic agents for the treatment of medical conditions such as chronic pain. THC elicits psychoactive effects through modulation of dopaminergic neurons, thereby altering levels of dopamine in the brain. This case report highlights the complexity associated with medicinal cannabis and the health risks associated with its use. A 57-year-old male with Parkinson’s disease was experiencing worsening tremors and vivid hallucinations despite therapy optimization attempts. It was discovered that the patient took cannabis for chronic back pain, and a pharmacogenomics (PGx) test indicated the presence of variants for the COMT and HTR2A genes. These variants could increase dopamine levels and predispose patients to visual hallucinations. Once the cannabis was discontinued, the patient’s hallucinations began to slowly dissipate. Cannabis use continues to expand as it gains more acceptance legally and medicinally, but cannabis can affect the response to drugs. This patient case suggests that cannabis use in combination with dopamine-promoting drugs, especially in a patient with genetic variants, can increase the risk for vivid hallucinations. These conditions support the importance of considering herb–drug interactions and PGx data when performing a medication safety review.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mihai Avram ◽  
Helena Rogg ◽  
Alexandra Korda ◽  
Christina Andreou ◽  
Felix Müller ◽  
...  

Psychiatry has a well-established tradition of comparing drug-induced experiences to psychotic symptoms, based on shared phenomena such as altered perceptions. The present review focuses on experiences induced by classic psychedelics, which are substances capable of eliciting powerful psychoactive effects, characterized by distortions/alterations of several neurocognitive processes (e.g., hallucinations). Herein we refer to such experiences as psychedelic states. Psychosis is a clinical syndrome defined by impaired reality testing, also characterized by impaired neurocognitive processes (e.g., hallucinations and delusions). In this review we refer to acute phases of psychotic disorders as psychotic states. Neuropharmacological investigations have begun to characterize the neurobiological mechanisms underpinning the shared and distinct neurophysiological changes observed in psychedelic and psychotic states. Mounting evidence indicates changes in thalamic filtering, along with disturbances in cortico-striato-pallido-thalamo-cortical (CSPTC)-circuitry, in both altered states. Notably, alterations in thalamocortical functional connectivity were reported by functional magnetic resonance imaging (fMRI) studies. Thalamocortical dysconnectivity and its clinical relevance are well-characterized in psychotic states, particularly in schizophrenia research. Specifically, studies report hyperconnectivity between the thalamus and sensorimotor cortices and hypoconnectivity between the thalamus and prefrontal cortices, associated with patients' psychotic symptoms and cognitive disturbances, respectively. Intriguingly, studies also report hyperconnectivity between the thalamus and sensorimotor cortices in psychedelic states, correlating with altered visual and auditory perceptions. Taken together, the two altered states appear to share clinically and functionally relevant dysconnectivity patterns. In this review we discuss recent findings of thalamocortical dysconnectivity, its putative extension to CSPTC circuitry, along with its clinical implications and future directions.


Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4458
Author(s):  
Marco Falasca ◽  
Mauro Maccarrone

Cannabinoids, active components of the plant Cannabis sativa, had been used for centuries in ancient medicine as therapeutic remedies for a variety of conditions, before becoming stigmatized due to their psychoactive effects [...]


Crisis ◽  
2021 ◽  
Author(s):  
John Stogner ◽  
Courtney Patterson

Abstract. Background: Case studies have linked synthetic cannabinoid (SC) use to suicide risk both during and following acute psychoactive effects. No study has explored whether a meaningful relationship exists between SC use and suicidal ideation, planning, and attempts within a generalizable sample. Aims: This work attempted to determine whether SC use is significantly associated with suicidal thoughts, planning, or attempts and whether the association between SC use and suicide may be stronger in certain demographic groups. Method: Cross-sectional self-report data from the Youth Risk Behavior Surveillance System were utilized. Logistic regression models were explored within a sample of 29,384 adolescents. Results: A clear connection emerged between SC use and suicidal thoughts and attempts. SC use and suicide risk were strongly related within the lesbian, gay, and bisexual and African Americans populations, even after controlling for depressive symptoms. Limitations: The study was cross-sectional and respondents may have underreported substance use or suicidal thoughts. Conclusion: Whether SC use has an impact on suicidal ideation directly, indirectly, or if it is simply a co-occurring phenomenon, it may serve as a flag of enhanced risk. Physicians must remain cognizant of the SC–suicide risk connection, particularly among African American and/or lesbian, gay, or bisexual patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
O. Merve Mollaahmetoglu ◽  
Johanna Keeler ◽  
Katherine J. Ashbullby ◽  
Eirini Ketzitzidou-Argyri ◽  
Meryem Grabski ◽  
...  

Background: The therapeutic benefits of ketamine have been demonstrated for a variety of psychiatric disorders. However, the role of ketamine induced psychoactive experiences in mediating the therapeutic effects is unclear. Despite the growing quantitative research on the efficacy of ketamine treatment, very few studies examined participant experiences of ketamine infusions in a treatment setting.Aims: The current study aimed to examine participant experiences of ketamine infusions and how these relate to therapeutic mechanisms in a clinical trial setting.Methods: We conducted semi-structured interviews with 12 participants who received up to three ketamine infusions (0.8 mg/kg) as part of a Phase II double blind, randomised controlled trial. The interviews explored participants' acute experiences of ketamine infusions, experiences of psychotherapy/education, and the lasting effects of the trial. The interviews were transcribed verbatim and analysed using thematic analysis.Results: Six key themes were identified. (1) Participants reported multifaceted motivations for trial participation. (2) The set and setting was found to be influential in determining acute ketamine experiences. The acute ketamine experiences included: (3) the inherent contradictions of the experience (e.g., dissociation vs feelings of connection), (4) rapidly fluctuating and changing experiences, (5) meaningful, mystical and spiritual experiences. Finally, the final theme (6) relates to the transformational effects of the infusions and the trial.Conclusion: Provided in a supportive and professional environment, ketamine treatment led to a significant change in relationship with alcohol. Ketamine induced ego dissolution and dissociation were reported to be related to the transformational effects on relationship with alcohol. The extent to which the acute psychoactive effects of ketamine mediate therapeutic effects on drinking outcomes remain to be investigated in the trial data. The acute effects of ketamine reported by our participants transcend its traditional conceptualisation as a “dissociative anaesthetic”; therefore, we suggest the development or use of new measures alongside ketamine infusions to fully capture the spectrum of these effects which may be crucial in its therapeutic and transformative effects.


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