1,409 results on '"Psychedelic"'
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2. Examining differences in the effects and contexts of naturalistic psilocybin use for White participants vs. Participants of Color: A longitudinal online survey study
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Jones, Grant, Lowe, Matthew X., Nayak, Sandeep, Sepeda, Nathan, Kettner, Hannes, Carhart-Harris, Robin, Jackson, Heather, and Garcia-Romeu, Albert
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- 2025
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3. Modifications épigénétiques dans l’addiction à l’alcool et perspectives thérapeutiques
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Pierrefiche, Olivier
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- 2025
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4. Low (micro)doses of 2,5-dimethoxy-4-propylamphetamine (DOPR) increase effortful motivation in low-performing mice
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Noback, Michael, Kenton, Johnny A., Klein, Adam K., Hughes, Zoë A., Kruegel, Andrew C., Schmid, Yasmin, Halberstadt, Adam L., and Young, Jared W.
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- 2025
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5. A systematic review of participant diversity in psychedelic-assisted psychotherapy trials
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Haft, Stephanie L., Downey, Amanda E., Raymond-Flesch, Marissa, Fernandes-Osterhold, Gisele, Bradley, Ellen R., O'Donovan, Aoife, and Woolley, Joshua
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- 2025
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6. The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression
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Goodwin, Guy M., Aaronson, Scott T., Alvarez, Oscar, Carhart-Harris, Robin, Chai-Rees, Jamie, Croal, Megan, DeBattista, Charles, Dunlop, Boadie W., Feifel, David, Hellerstein, David J., Husain, Muhammad I., Kelly, John R., Kirlic, Namik, Licht, Rasmus W., Marwood, Lindsey, Meyer, Thomas D., Mistry, Sunil, Nowakowska, Ania, Páleníček, Tomáš, Repantis, Dimitris, Schoevers, Robert A., Simmons, Hollie, Somers, Metten, Teoh, Emma, Tsai, Joyce, Wahba, Mourad, Williams, Sam, Young, Allan H., Young, Matthew B., Zisook, Sidney, and Malievskaia, Ekaterina
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- 2025
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7. Prophylactic effects of arketamine, but not hallucinogenic psychedelic DOI nor non-hallucinogenic psychedelic analog lisuride, in lipopolysaccharide-treated mice and mice exposed to chronic restrain stress
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Liu, Guilin, Ma, Li, Qu, Youge, Wan, Xiayun, Xu, Dan, Zhao, Mingming, Murayama, Rumi, and Hashimoto, Kenji
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- 2023
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8. Psychotomimetic compensation versus sensitization.
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Brouwer, Ari, Carhart-Harris, Robin, and Raison, Charles
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psychedelic ,psychosis ,pychotomimetic ,schizophrenia ,sensitization ,stress ,substance use ,Humans ,Hallucinogens ,Animals ,Stress ,Psychological ,Psychoses ,Substance-Induced ,Neurotransmitter Agents - Abstract
It is a paradox that psychotomimetic drugs can relieve symptoms that increase risk of and cooccur with psychosis, such as attention and motivational deficits (e.g., amphetamines), pain (e.g., cannabis) and symptoms of depression (e.g., psychedelics, dissociatives). We introduce the ideas of psychotomimetic compensation and psychotomimetic sensitization to explain this paradox. Psychotomimetic compensation refers to a short-term stressor or drug-induced compensation against stress that is facilitated by engagement of neurotransmitter/modulator systems (endocannabinoid, serotonergic, glutamatergic and dopaminergic) that mediate the effects of common psychotomimetic drugs. Psychotomimetic sensitization occurs after repeated exposure to stress and/or drugs and is evidenced by the gradual intensification and increase of psychotic-like experiences over time. Theoretical and practical implications of this model are discussed.
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- 2024
9. Psychedelics and the inner healer: Myth or mechanism?
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Peill, Joseph, Marguilho, Miriam, Erritzoe, David, Barba, Tommaso, Greenway, Kyle, Rosas, Fernando, Timmermann, Christopher, and Carhart-Harris, Robin
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Healing ,Telos ,automatic ,psychedelic ,Humans ,Hallucinogens ,Psilocybin ,Double-Blind Method ,Adult ,Male ,Female ,Middle Aged ,Depression ,Young Adult ,Dose-Response Relationship ,Drug - Abstract
BACKGROUND: Reference to an intrinsic healing mechanism or an inner healer is commonplace amongst psychedelic drug-using cultures. The inner healer refers to the belief that psychedelic compounds, plants or concoctions have an intrinsically regenerative action on the mind and brain, analogous to intrinsic healing mechanisms within the physical body, for example, after sickness or injury. AIMS: Here, we sought to test and critique this idea by devising a single subjective rating item pertaining to perceived inner healing effects. METHODS: The item was issued to 59 patients after a single high (25 mg, n = 30) or placebo (1 mg, n = 29) dose of psilocybin in a double-blind randomised controlled trial of psilocybin for depression. RESULTS: Inner healer scores were higher after the high versus placebo dose of psilocybin (t = 3.88, p
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- 2024
10. The Relationship Between Changes in Mindfulness and Subsequent Changes in Well-Being Following Psychedelic Use: Prospective Cohort Study.
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Kettner, Hannes, Jones, Grant, Herrmann, Felipe, Bear, Adam, and Carhart-Harris, Robin
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anxiety ,depression ,drug ,drugs ,hallucinogen ,hallucinogens ,meditation ,mental health ,mindfulness ,observational ,psychedelic ,psychedelics ,substance use ,survey ,surveys ,web-based survey - Abstract
This study demonstrates that changes in mindfulness predict subsequent changes in well-being in a data set including individuals who recently engaged in psychedelic use.
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- 2024
11. Long-Term Mental Health and Wellbeing Outcomes Associated with Naturalistic Ayahuasca Consumption.
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Pagni, B.A., Halman, A., Sarris, J., Chenhall, R., Bogenschutz, M.P., and Perkins, D.
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The durability of ayahuasca’s effects on mental health and the influence of clinical diagnoses on therapeutic response is unclear. Adults with no prior exposure to ayahuasca (
n = 66) participating in neo-shamanic ayahuasca ceremonies completed questionnaires at baseline, 7 days, and 1, 6, and 12 months. Mixed models were used to characterize temporal trajectories in mental health, alcohol and cannabis use, affect, personality, spirituality, and relationships and examine the longevity of effects in individuals with and without a depressive or anxiety disorder. After multiple comparison correction, ayahuasca use was associated with decreases in depression, anxiety, stress, negative affect, negative emotionality, acceptance of external influence, and self-alienation at all time points. Improvements in mental health, self-efficacy, and spirituality were observed up to 12 months post-ceremony. Individuals with depression and anxiety diagnoses maintained significant symptom reductions, whereas those without a diagnosis experienced short-term benefits. Decreases in alcohol and cannabis use were only observed at month 1. Naturalistic ayahuasca use was associated with persisting improvements in mental health and wellbeing, with the largest magnitude of symptom reduction observed in those diagnosed with a depressive or anxiety disorder. Differing trajectories of change were identified across psychological constructs, suggestive of both enhancement and attenuation of gains over time. [ABSTRACT FROM AUTHOR]- Published
- 2025
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12. Quantitative analysis of recreational psychoactive mushroom gummies in Portland, Oregon.
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Correia, Matthew S., Gonzaga, Mikayla J., Temple, Courtney, and Gerona, Roy R.
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AbstractIntroductionMethodsResultsDiscussionConclusionsIn November 2020, Oregon passed Measures 109 and 110 altering the legal landscape for psychoactive substances by regulating psilocybin use and decriminalizing possession of Schedule I substances. This coincided with the growth of the commercial nootropic (cognitive enhancers) mushroom industry, including products such as mushroom gummies marketed for “legal highs.” Despite these product claims, concerns have been raised about their safety profile. Our study aimed to assess the accuracy of labeling of these products and quantify their psychoactive contents.Eight gummy products were procured from seven different smoke and vape shops in Portland, Oregon. Gummy samples were homogenized and analyzed using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Products were screened for psychoactive compounds, including psilocybin, psilocin, and their analogues, as well as for purported
Amanita muscaria derivatives. Quantitative analysis of identified compounds was performed using isotope dilution.Neither ibotenic acid nor muscimol, the active components ofAmanita muscaria , were detected in the two products claiming to containAmanita muscaria extracts. However, these products contained psilocin and tryptamine derivatives. One product labeled as psilocybin-free tested positive for psilocybin. Another sample claiming to be nootropic contained undisclosed Δ9-tetrahydrocannabinol. Overall, seven of the eight products contained psilocin, and six contained 4-acetoxy-N,N,dimethyltryptamine. Other detected compounds included various tryptamine congeners and kavalactones.Labeling was inaccurate and inconsistent in many of the products examined. Users are likely to experience psychoactive symptoms considering the concentrations of xenobiotics determined. Serotonergic effects are expected from products containing tryptamine derivatives, including those inaccurately labeled as containingAmanita muscaria extracts.The labeling of psychoactive mushroom gummies we tested was overall inaccurate. Products suggestingAmanita muscaria content instead contained serotonergic tryptamines, including some which falsely claimed to be free of psilocybin. [ABSTRACT FROM AUTHOR]- Published
- 2025
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13. Sex Differences in Religious Beliefs Before and After an Entity Encounter During an Ayahuasca Experience.
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Xin, Yitong, Griffiths, Roland R., and Davis, Alan K.
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RELIGIOUS differences , *INTERNET surveys , *ATHEISM , *SPIRITUALITY , *AGNOSTICISM - Abstract
An interesting aspect of entity encounters during psychedelic experiences is their ability to transform one’s religious beliefs. However, little is known about sex differences in these transformations. This study investigates sex differences in changes in religious beliefs before and after an entity encounter among ayahuasca users. Data were collected via an anonymous Internet-based survey (
N = 415;M age = 38.53,SD = 11.39; male = 60.5%). Descriptive analyses, binary logistic regression, and two-proportion z-tests were conducted. Before the entity encounter, males were significantly more likely to identify as atheists (OR = 2.889,p = .001) and less likely to identify as having religious beliefs (OR = 0.453,p < .001) compared to females. After the entity encounter, no significant sex differences in religious beliefs were found (p s >0.05). Comparing changes before and after the experience, both sex groups showed decreases in atheism and agnosticism and increases in religious beliefs, with males exhibiting larger changes. Specifically, the proportion of males identifying as religious significantly increased from before to after the entity encounter (z = 3.49,p < .001), whereas the increase for females was not statistically significant. Findings suggest sex is associated with perceived changes in religious beliefs among ayahuasca users reporting an entity encounter, highlighting the importance of considering sex in psychedelic research and its impact on spirituality and related outcomes. [ABSTRACT FROM AUTHOR]- Published
- 2025
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14. Evaluating the value and risks of psychedelics for psychiatric medicine: a clinical perspective.
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Marazziti, Donatella, Weiss, Francesco, Gurrieri, Riccardo, Russomanno, Gerardo, Gambini, Matteo, Magnesa, Anna, Coccoglioniti, Andrea, and Perugi, Giulio
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Introduction: After a long period of obscurantism, a possible role of psychedelics in clinical practice has progressively become a tangible perspective during the last two decades. However, the resounding enthusiasm linked to such 'psychedelic renaissance' runs the risk to unduly minimize the possible hazards associated with these compounds, while expanding their alleged benefits to improbable panacea-like proportions. In order to avoid mystifying or demonizing the properties of 5-HT2a agonists on emotional grounds, this subject requires a strictly unprejudiced and cautious approach to the evidence. Areas covered: In this article, the authors attempted to comprehensively analyze the available literature to provide a balanced overview of the possible benefits of psychedelics in healthcare, taking into account their potential risks. Expert opinion: To date, psychedelics have shown a therapeutic potential in a wide range of conditions, with a seemingly limited risk of inducing adverse reactions, including abuse and dependence, when administered in a controlled environment by specialized personnel. In any case, although several questions remain unanswered before drawing firm conclusions, further studies are needed to establish which conditions and subjects could benefit from psychedelics and which patients bear the greater risk of adversities. [ABSTRACT FROM AUTHOR]
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- 2025
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15. Experimental Test of Perceptions of Psychedelics by Therapeutic and Recreational Use.
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Kiniry, Mackenzie T., Magnan, Renee E., Elder, Sarah N., and Ladd, Benjamin O.
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PUBLIC opinion , *PERCEPTION testing , *MEDICAL communication , *PHARMACEUTICAL policy , *SUBSTANCE abuse - Abstract
Recent research on the potential therapeutic value of psychedelic substances has led to changes in media representation and drug policy in some U.S. states. Yet, little is known about lay perceptions of these substances. The current study aimed to describe health perceptions of psychedelic substances, test differences in perceptions of therapeutic vs. recreational use of psychedelic substances, and determine if such perceptions vary by use experience. Participants (
N = 309) completed an online within-subjects experiment in which they responded to measures of positive and negative perceptions of therapeutic and recreational use of psychedelics. Endorsement of positive and negative health perceptions of psychedelics was moderate to strong. Recreational use was perceived as having more negative health consequences, while therapeutic use was perceived as having more positive health consequences. Participants who reported lifetime psychedelic use (40.7%) perceived both recreational and therapeutic uses as having more positive health consequences, and this pattern was consistent across most perception domains. The outcomes suggest that public perceptions of use may change based on reason for use. This information may aid in filling current gaps in knowledge and identifying potential targets for public health communications, and such approaches may benefit from considering prior use experience. [ABSTRACT FROM AUTHOR]- Published
- 2025
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16. The association between study design and antidepressant effects in psychedelic-assisted therapy: A meta-analysis.
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Li, Jia-Ru, Chiang, Kuo-Tung, Kao, Yu-Chen, Yu, Chia-Ling, Yang, Fu-Chi, Liang, Chih-Sung, and Hsu, Tien-Wei
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LSD (Drug) , *PSILOCYBIN , *MENTAL depression , *HALLUCINOGENIC drugs , *ECSTASY (Drug) - Abstract
Different study designs of psychedelic trials may impact the blinding and expectance, leading to biased treatment effects. This study aimed to examine the association between antidepressant efficacy and study designs in psychedelic trials. Six databases were systematically searched. Eligible trials were required to investigate the efficacy of psychedelics (psilocybin, lysergic acid diethylamide [LSD], 3,4-Methylenedioxymethamphetamine [MDMA], and ayahuasca) in adult patients with depressive symptoms. We only considered oral psychedelic-assisted therapy without concomitant use of antidepressants. The primary outcome was the change in depressive symptoms. There were five study designs of psychedelic trials, including non-active-drug-as-placebo, active-drug-as-placebo, waitlist-as-control, fixed-order, and pre-post designs. In non-active-drug -as-placebo design, psilocybin (k = 4, Hedges' g [g] = 0.87, 95 % confidence intervals[CIs] = 0.58 to 1.16) and MDMA (k = 2, g = 0.65, 95%CIs = 0.26 to 1.05) were associated with large and medium effect sizes, respectively. In active-drug-as-placebo design, both psilocybin (k = 2, g = 0.71, 95%CIs = −0.01 to 1.43) and MDMA (k = 3, g = 0.53, 95%CIs = −0.23 to 1.28) were not statistically significant. In pre-post single-arm (k = 3, g = 2.51, 95%CIs = 1.00 to 4.02) and waitlist-as-control (k = 1, g = 2.88, 95%CIs = 1.75 to 4.00) designs, psilocybin showed a large effect size of antidepressant effect. Ayahuasca also showed a large effect size in both pre-post (k = 2, g = 1.88, 95%CIs = 1.18 to 2.57) and non-active-drug-as-placebo (k = 1, g = 1.60, 95%CIs = 0.84 to 2.36) designs. LSD was associated with a significant antidepressant effect only in non-active-drug-as-placebo design (k = 1, g = 1.49, 95%CIs = 0.80 to 2.17) but not in active-drug-as-placebo design (k = 1, g = 0.44, 95%CIs = −0.90 to 1.78). The antidepressant effects of psychedelics may be overestimated in studies with pre-post single-arm, non-active-drugs-as placebo, and waitlist-control designs. Restricted sample size, difficulty with establishing blinding for participants, and over expectancy limit the estimation of the antidepressant effect of psychedelic-assisted therapy. • The antidepressant effects of psychedelics may be overestimated in studies with pre-post single-arm, non-active-drugs-as placebo, or waitlist-control designs. • In non-active-drug-as-placebo design, psilocybin, MDMA, and LSD were associated with better efficacy than placebo. • In active-drug-as-placebo design, psilocybin MDMA, and LSD were not significantly associated with better efficacy than placebo. • In meta-regression, we identified that the higher dose of psilocybin is associated with a better antidepressant effect. [ABSTRACT FROM AUTHOR]
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- 2025
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17. Multidimensional Personality Changes Following Psilocybin-Assisted Therapy in Patients With Alcohol Use Disorder: Results From a Double-Blind, Placebo-Controlled Clinical Trial.
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Pagni, Broc A., Zeifman, Richard J., Mennenga, Sarah E., Carrithers, Brennan M., Goldway, Noam, Bhatt, Snehal, O'Donnell, Kelley C., Ross, Stephen, and Bogenschutz, Michael P.
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ALCOHOLISM , *PERSONALITY , *ALCOHOL drinking , *PSILOCYBIN , *RANDOMIZED controlled trials , *PERSONALITY change - Abstract
Objective: Evidence suggests that psilocybin-assisted therapy (PAT) leads to durable shifts in personality structure. However, such changes have yet to be characterized in disorders of addiction. In this secondary analysis from a randomized controlled trial, the authors examined the effect of PAT on personality dimensions in patients with alcohol use disorder (AUD), hypothesizing that PAT would attenuate personality abnormalities in AUD and that reductions in trait impulsiveness would be associated with lower drinking. Methods: Eighty-four adults with AUD were randomized to two medication sessions of either psilocybin (N=44) or active placebo (diphenhydramine; N=40), received 12 weekly psychotherapy sessions, and completed follow-up for an additional 24 weeks. Changes in personality traits (week 36 vs. baseline) were assessed with the revised NEO Personality Inventory; daily alcohol consumption was quantified using the timeline followback. Results: Relative to the placebo group, the psilocybin group showed significant reductions in neuroticism and increases in extraversion and openness. Secondary analyses showed that reductions in neuroticism were driven by decreases in the facets depression, impulsiveness, and vulnerability; increases in openness were driven by increases in the facets openness toward feelings and fantasy. Across all participants, decreases in impulsiveness were associated with lower posttreatment alcohol consumption, and an exploratory analysis revealed that these associations were strongest among psilocybin-treated participants who continued moderate- or high-risk drinking prior to the first medication session. Conclusions: PAT elicited durable shifts in personality, suggesting normalization of abnormal personality trait expression in AUD. Further study is needed to clarify whether PAT exerts its beneficial effects by reducing impulsiveness or whether impulsive individuals inherently respond better to PAT. [ABSTRACT FROM AUTHOR]
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- 2025
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18. Healing, Harms, and Humility: Expanding the Scope of Psychedelic-Assisted Psychotherapy Research.
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O'Donnell, Kelley C., Grigsby, Jim, and Grob, Charles S.
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MENTAL health services , *PSYCHOTHERAPY , *REWARD (Psychology) , *PATIENTS' attitudes , *CULTURAL pluralism , *PSYCHOEDUCATION - Abstract
The article discusses the increasing research on psychedelic-assisted psychotherapy (PAP) and emphasizes the importance of epistemic humility in conducting and interpreting this research. It highlights the need to explore therapist-specific factors, psychotherapy process research, and the inclusion of diverse voices in PAP studies. The article calls for a broader range of methodologies and voices to be considered in the study of psychedelic compounds and treatments, with a focus on cultural sensitivity and ethical considerations. [Extracted from the article]
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- 2025
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19. Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm.
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MacConnel, Henry A, Earleywine, Mitch, and Radowitz, Steven
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POST-traumatic stress disorder , *SUICIDAL ideation , *KETAMINE , *PSYCHOTHERAPY , *STATUS (Law) - Abstract
Background: Traditional treatments for post-traumatic stress disorder (PTSD) often show limited success with high dropout. Ketamine, an N -methyl-D-aspartate antagonist known for rapid antidepressant effects, has decreased PTSD symptoms in some studies but not in others. Administering ketamine in ways that parallel psychedelic-assisted treatments—including preparatory, integration, sensory immersion, and psychotherapy sessions—could decrease PTSD symptoms meaningfully. Methods: A retrospective sample of 117 screened outpatients with elevated PTSD Checklist for DSM-5 (PCL-5) scores received intravenous ketamine in supportive environments. The protocol included preparation, intention-setting, and integration sessions accompanying at least six administrations. Administration sessions included eye shades and evocative music paralleling typical psychedelic therapy trials. Results: Mean PCL scores decreased from 52.54 (SD = 12.01) to 28.78 (SD = 16.61), d = 1.64. Patients tolerated treatment well, with no serious adverse events. Covariates, including age, gender, days between PCL assessments, number of psychiatric medications, and suicidal ideation were not significant moderators; concomitant psychotherapy did reach significance, d = 0.51. Of the 117 patients' final PCL scores, 88 (75.21%) measures suggested clinically meaningful improvement and 72 (61.54%) suggested remission of PTSD symptoms. Conclusion: Intravenous ketamine in supportive environments, with hallmarks of psychedelic therapy, preceded large reductions in PTSD symptoms. These results highlight ketamine's potential when delivered in this manner, suggesting environmental factors might account for some variation seen in previous work. Given the molecule's cost, minimal interaction with other psychiatric medications, and legal status, intravenous ketamine in a psychedelic paradigm may be a promising option for PTSD unresponsive to other treatments. [ABSTRACT FROM AUTHOR]
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- 2025
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20. Therapeutic Use of Psychedelics for Mental Disorders: A Systematized Review.
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Alyahya, Norah M. and Al Saleem, Eithar A.
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MENTAL health services , *PEOPLE with mental illness , *MENTAL illness , *EATING disorders , *POST-traumatic stress disorder - Abstract
In this review, studies focusing on the therapeutic use of psychedelics for treating mental health disorders published since 2010 have been examined. A systematic literature search was conducted using Medline and EBSCO. After extracting data from 19 papers, an analysis was performed. Critical evidence highlighting the effectiveness of psychedelic drugs in treating depression, anxiety, obsessive–compulsive disorder, drug addiction, and mental problems associated with terminal disease has been identified in the analyzed research. Guidelines for the safe administration of psychedelic therapy have been employed in all relevant primary studies. Nonetheless, mania and psychosis have been found to be linked to unfavorable outcomes. Although there has been a resurgence of research on the safety and effectiveness of psychedelics for a variety of mental health issues, the positive findings of this review reinforce the need for more comprehensive studies to better understand how psychedelics affect clients with mental illnesses. More studies are also required to examine the effectiveness of psychedelics in treating some mental illnesses, such as eating disorders, posttraumatic stress disorder, and personality disorders. [ABSTRACT FROM AUTHOR]
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- 2025
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21. THE AUDIOVISUAL AESTHETICS AND POLITICS OF GAYE SU AKYOL'S MUSIC.
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YILMAZ, Çağrı
- Abstract
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- 2025
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22. MDMA for PTSD and beyond: a new paradigm brings hope.
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Shannon, Scott and Geller, Jamarie
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MENTAL health services ,MEDICAL care ,PSYCHOTHERAPY ,ELECTROCONVULSIVE therapy ,TRANSCRANIAL magnetic stimulation - Published
- 2024
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23. Psilocybin-assisted psychotherapy for methamphetamine dependence: a case report involving daily methamphetamine use.
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Brett, Jonathan, Knock, Elizabeth, Watson, Kathy, Albert, Steven, Siefried, Krista J., and Guss, Jeffrey
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PSILOCYBIN ,NICOTINE addiction ,PSYCHOTHERAPY ,METHAMPHETAMINE ,MENTAL health - Abstract
Methamphetamine (MA) dependence leads to severe physical and psychological issues. Current treatments, including psychosocial therapies and residential rehabilitation, face limitations such as high relapse rates, cost, and accessibility issues. As a result, there is an urgent need for novel approaches to treat MA dependence that are effective, affordable, and accessible to patients. Psilocybin, the active component in numerous mushrooms of the Psilocybe genus, has shown potential for enhancing psychotherapy for various addiction and mental health issues due to its effects on perception, cognition, and affect. Psilocybin-assisted psychotherapy (PAT) has demonstrated initial safety and efficacy in treating alcohol, cocaine, and nicotine dependence. The case presented here describes a 36-year-old transwoman and daily MA user, who participated in a single-arm open-label clinical trial assessing feasibility and safety of PAT for MA dependence at St. Vincent's Hospital, Sydney. Following inpatient withdrawal management and one session of psilocybin-assisted therapy, she experienced significant cognitive and emotional shifts and sustained MA abstinence. She reported improved mental health over 3 months following treatment completion. She also noted increased self-esteem, mindfulness, and distress tolerance. This study suggests that PAT (following inpatient MA withdrawal management) may offer a scalable, safe, and effective approach for treating MA dependence. However, further research is required to confirm the generalisability and efficacy of PAT for broader populations of people using MA. It is encouraging that this participant, a daily MA user, showed improvements in mood and cognition, in addition to abstinence from MA. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Learning how to make use of dissociative therapies.
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Mathai, David S.
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Dissociative therapies are being increasingly explored for their psychiatric applications, although questions remain about how they work and how best to use them. In exploring these questions, this review highlights six key areas of clinical relevance: (1) The possible contributions of functional unblinding when interpreting efficacy data; (2) The degree to which the therapeutic effects of dissociative therapies can be distinguished from the transient forms of relief seen with recreational drug use; (3) Understanding the construct of dissociation as it is tasked with describing the function of dissociative drugs; (4) The investigation of subjective drug effects as predictors of therapeutic outcome; (5) Similarities and differences in the effects of dissociative and classic psychedelics; and (6) The anticipated need for judicious prescribing/deprescribing resources as dissociative therapies proliferate. [ABSTRACT FROM AUTHOR]
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- 2024
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25. The origin of 2,5‐dimethoxy‐4‐methylamphetamine (DOM, STP).
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Trout, Keeper and Daley, Paul F.
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The story of the 1967 appearance of the powerful psychedelic 2,5‐dimethoxy‐4‐methylamphetamine (DOM, STP) commonly omits details and often includes hyperbole and inaccuracies. It is well known how and when the drug was first distributed to the public for free by Owsley Stanley, but the role that Alexander Shulgin played in providing that material is not as well understood. In the interest of transparency and historical accuracy, this article attempts to present an accurate account of this well‐known but inadequately detailed event. It follows DOM's development as an experimental substance believed to hold potential promise in psychotherapeutic applications through its appearance as a street drug generating bad press and a lasting bad impression among the public. One of the more interesting questions is why Shulgin would have taken such an immense risk in releasing this material to clandestine operators. While DOM was still legal it was also Dow's intellectual property, so discovery of his involvement could have jeopardized his career. The escape is especially curious as all fingers would logically first point towards Shulgin as the source. Drawing from published and unpublished sources, the authors attempt to suggest answers. DOM rapidly faded into oblivion before human pharmacodynamics and pharmacokinetics could be established. In this account, the reader is informed of the potential value that the compound played in non‐clinical molecular neuroscience, elucidating receptor specificity of new drugs, and how mistaken warnings about combining DOM with chlorpromazine led to better non‐pharmacological drug crisis response. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Criticality supports cross-frequency cortical-thalamic information transfer during conscious states.
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Toker, Daniel, Müller, Eli, Miyamoto, Hiroyuki, Riga, Maurizio, Lladó-Pelfort, Laia, Yamakawa, Kazuhiro, Artigas, Francesc, Shine, James, Hudson, Andrew, Pouratian, Nader, and Monti, Martin
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anesthesia ,consciousness ,criticality ,epilepsy ,human ,mouse ,neuroscience ,physics of living systems ,psychedelic ,rat ,thalamus ,Humans ,Rats ,Mice ,Animals ,Consciousness ,Cerebral Cortex ,Hallucinogens ,Unconsciousness ,Thalamus ,Electroencephalography - Abstract
Consciousness is thought to be regulated by bidirectional information transfer between the cortex and thalamus, but the nature of this bidirectional communication - and its possible disruption in unconsciousness - remains poorly understood. Here, we present two main findings elucidating mechanisms of corticothalamic information transfer during conscious states. First, we identify a highly preserved spectral channel of cortical-thalamic communication that is present during conscious states, but which is diminished during the loss of consciousness and enhanced during psychedelic states. Specifically, we show that in humans, mice, and rats, information sent from either the cortex or thalamus via δ/θ/α waves (∼1-13 Hz) is consistently encoded by the other brain region by high γ waves (52-104 Hz); moreover, unconsciousness induced by propofol anesthesia or generalized spike-and-wave seizures diminishes this cross-frequency communication, whereas the psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) enhances this low-to-high frequency interregional communication. Second, we leverage numerical simulations and neural electrophysiology recordings from the thalamus and cortex of human patients, rats, and mice to show that these changes in cross-frequency cortical-thalamic information transfer may be mediated by excursions of low-frequency thalamocortical electrodynamics toward/away from edge-of-chaos criticality, or the phase transition from stability to chaos. Overall, our findings link thalamic-cortical communication to consciousness, and further offer a novel, mathematically well-defined framework to explain the disruption to thalamic-cortical information transfer during unconscious states.
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- 2024
27. Within-subject comparison of near-death and psychedelic experiences: acute and enduring effects.
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Martial, Charlotte, Carhart-Harris, Robin, and Timmermann, Christopher
- Subjects
impact ,memory ,near-death experience ,phenomenology ,psychedelic - Abstract
Mystical-like states of consciousness may arise through means such as psychedelic substances, but may also occur unexpectedly during near-death experiences (NDEs). So far, research studies comparing experiences induced by serotonergic psychedelics and NDEs, along with their enduring effects, have employed between-subject designs, limiting direct comparisons. We present results from an online survey exploring the phenomenology, attribution of reality, psychological insights, and enduring effects of NDEs and psychedelic experiences (PEs) in individuals who have experienced both at some point during their lifetime. We used frequentist and Bayesian analyses to determine significant differences and overlaps (evidence for null hypotheses) between the two. Thirty-one adults reported having experienced both an NDE (i.e. NDE-C scale total score ≥27/80) and a PE (intake of lysergic acid diethylamide, psilocybin/mushrooms, ayahuasca, N,N-dimethyltryptamine, or mescaline). Results revealed areas of overlap between both experiences for phenomenology, attribution of reality, psychological insights, and enduring effects. A finer-grained analysis of the phenomenology revealed a significant overlap in mystical-like effects, while low-level phenomena (sensory effects) were significantly different, with NDEs displaying higher scores of disembodiment and PEs higher scores of visual imagery. This suggests psychedelics as a useful model for studying mystical-like effects induced by NDEs, while highlighting distinctions in sensory experiences.
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- 2024
28. Psychedelic Renaissance
- Author
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Miranda, Jose
- Subjects
Psychedelic ,Substances ,Medicine ,Neuroplasticity ,Psychological Sciences - Abstract
Psychedelic substances, which were once categorized as Schedule 1 drugs, are gaining public attention for their potential to treat individuals with mental conditions. Every Schedule 1 drug was once considered to have no medicinal value, with the potential for high abuse, but recent research has suggested otherwise. LySergic acid Diethylamide (LSD) and MethyleneDioxy-MethAmphetamine (MDMA) are two Schedule 1 class substances, which have been studied on a diverse amount of subjects and shown to have positive benefits on the physical and mental psyche with no potential for addiction or bodily harm. Moreover, studies regarding neuroplasticity in humans displayed benefits in how the brain can restructure itself through new learning while under the influence of psychedelic substances. Psychedelic substances are becoming more accessible to scientists, who now have legal authority to conduct research regarding their advantages to further investigate the benefits and unfound knowledge. As new information about psychedelic substances progress, and are now being introduced to the public, regulations are needed in order to uphold public demand. Open source projects, which are accessible to the public, such as Golden Euphorics at goldeneuphorics.org, have already contributed to providing individuals with safe and reliable products. Although psychedelic substances have made a significant amount of progress in the realm of medicine, and psychological sciences, further research is required to ensure safety of the public.
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- 2024
29. Knowledge, attitudes, and concerns about psilocybin and MDMA as novel therapies among U.S. healthcare professionals
- Author
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Erin Wang, David S. Mathai, Natalie Gukasyan, Sandeep Nayak, and Albert Garcia-Romeu
- Subjects
Psychedelic ,Psilocybin ,MDMA ,Hallucinogen ,Attitudes ,Medicine ,Science - Abstract
Abstract Psychedelic-assisted therapy (PAT) with substances like psilocybin and MDMA has shown promise for conditions including depression and post-traumatic stress disorder. Psilocybin and MDMA may become approved medicines in the coming decade. This study assessed knowledge and attitudes regarding PAT among 879 U.S. healthcare professionals via anonymous online survey. Multivariable linear regression was used to identify predictors of openness to clinical use. Most participants (71.2%) were female and White (85.8%), with a mean (SD) age of 45.5 (12.7) years. Registered nurses (25.4%) and physicians (17.7%) comprised the largest professional groups. Respondents endorsed strong belief in therapeutic promise, and moderate openness to clinical use and support for legal access to both substances, with higher overall ratings for psilocybin compared to MDMA. Objective knowledge items revealed low knowledge of therapeutic uses, risks, and pharmacology. Primary concerns were lack of trained providers, financial cost, and potential contraindications. Prior psychedelic use, self-rated knowledge, younger age, and professional role predicted openness to clinical use of psilocybin and MDMA, with physicians reporting lower openness. As psychedelics continue to garner popular and scientific interest, results indicate a pressing need for additional formal training to provide balanced, evidence-based information from trusted sources.
- Published
- 2024
- Full Text
- View/download PDF
30. Neuroprotective effects of psilocybin in a rat model of stroke
- Author
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Seong-Jin Yu, Kuo-Jen Wu, Yu-Syuan Wang, Eunkyung Bae, Fabio Chianelli, Nicholas Bambakidis, and Yun Wang
- Subjects
Stroke ,Psilocybin ,BDNF ,Psychedelic ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurophysiology and neuropsychology ,QP351-495 - Abstract
Abstract Background Psilocybin is a psychedelic 5HT2A receptor agonist found in “magic mushrooms”. Recent studies have indicated that 5HT2A agonists, such as dimethyltryptamine, given before middle cerebral artery occlusion (MCAo), improve staircase behavior, increased BDNF expression, and reduce brain infarction in stroke rats. The objective of this study is to determine the protective effect of psilocybin in cellular and animal models of stroke. Methods Adult male and timed-pregnant Sprague-Dawley rats were used for this study. The neural protective effects of psilocybin were determined in primary rat cortical neurons and adult rats. Rats were subjected to a 60-min middle cerebral artery occlusion. Brain tissues were collected for histological and qRTPCR analysis. Results Psilocybin reduced glutamate-mediated neuronal loss in rat primary cortical neuronal cultures. Psilocybin-mediated protection in culture was antagonized by the BDNF inhibitor ANA12. Pretreatment with psilocybin reduced brain infarction and neurological deficits in stroke rats. Early post-treatment with psilocybin improved locomotor behavior, upregulated the expression of MAP2 and synaptophysin, and down-regulated the expression of IBA1 in the stroke brain. ANA12 significantly attenuated psilocybin-mediated reduction in brain infarction and improvements in locomotor behavior. Conclusions Psilocybin reduced brain infarction and improved locomotor behavior in stroke rats; the protective mechanisms involve regulating BDNF expression. Our data support a novel therapeutic approach of psilocybin in stroke.
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- 2024
- Full Text
- View/download PDF
31. ‘Mind-Revealing’ Psychedelic States: Psychological Processes in Subjective Experiences That Drive Positive Change
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Rúna F. E. Walther and Hein T. van Schie
- Subjects
psychedelic ,altered states of consciousness ,therapeutic change ,psychedelic-assisted therapy ,psychology ,mental health ,Therapeutics. Pharmacology ,RM1-950 - Abstract
This narrative review explores the utilization of psychedelic states in therapeutic contexts, deliberately shifting the focus from psychedelic substances back to the experiential phenomena which they induce, in alignment with the original meaning of the term “mind-manifesting”. This review provides an overview of various psychedelic substances used in modern therapeutic settings and ritualistic indigenous contexts, as well as non-pharmacological methods that can arguably induce psychedelic states, including breathwork, meditation, and sensory deprivation. While the occurrence of mystical experiences in psychedelic states seems to be the strongest predictor of positive outcomes, the literature of this field yields several other psychological processes, such as awe, perspective shifts, insight, emotional breakthrough, acceptance, the re-experiencing of memories, and certain aspects of challenging experiences, that are significantly associated with positive change. Additionally, we discuss in detail mystical experience-related changes in metaphysical as well as self-related beliefs and their respective contributions to observed outcomes. We conclude that a purely medical and neurobiological perspective on psychological health is reductive and should not overshadow the significance of phenomenological experiences in understanding and treating psychological issues that manifest in the subjective realities of human individuals.
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- 2024
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32. The phenomenology of psychedelic temporality: current knowledge, open questions, and clinical applications.
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Miceli McMillan, Riccardo, Reynolds, Jack, and Fernandez, Anthony
- Subjects
- *
PHENOMENOLOGY , *PATHOLOGICAL psychology , *OPEN-ended questions , *HALLUCINOGENIC drugs , *CLINICAL medicine - Abstract
Current evidence suggests that the efficacy of psychedelic therapy depends, in part, on the character of psychedelic experiences themselves. One pronounced aspect of psychedelic experiences is alterations to the experience of time, including reports of timelessness or transcending time. However, how we should interpret such reports remains unclear, and this lack of clarity has philosophical and clinical implications. For instance, “true” timelessness may be considered antithetical to having any experience at all, and descriptions of experiences involving “timelessness” are known to be diverse and of varying clinical significance. In this article, we utilize a phenomenological approach to the study of temporality to highlight ambiguities in current constructs used to assess psychedelic experiences. In doing so, we advance some preliminary phenomenological accounts of psychedelic therapy’s mechanisms of action, such as psychedelic temporality acting as a kind of counterpoint for depressive temporality. We conclude by outlining how a dedicated phenomenological research program can provide a nuanced map of psychedelic temporality, guiding future research in a manner that addresses both philosophical and clinical ambiguities. [ABSTRACT FROM AUTHOR]
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- 2024
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33. Knowledge, attitudes, and concerns about psilocybin and MDMA as novel therapies among U.S. healthcare professionals.
- Author
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Wang, Erin, Mathai, David S., Gukasyan, Natalie, Nayak, Sandeep, and Garcia-Romeu, Albert
- Abstract
Psychedelic-assisted therapy (PAT) with substances like psilocybin and MDMA has shown promise for conditions including depression and post-traumatic stress disorder. Psilocybin and MDMA may become approved medicines in the coming decade. This study assessed knowledge and attitudes regarding PAT among 879 U.S. healthcare professionals via anonymous online survey. Multivariable linear regression was used to identify predictors of openness to clinical use. Most participants (71.2%) were female and White (85.8%), with a mean (SD) age of 45.5 (12.7) years. Registered nurses (25.4%) and physicians (17.7%) comprised the largest professional groups. Respondents endorsed strong belief in therapeutic promise, and moderate openness to clinical use and support for legal access to both substances, with higher overall ratings for psilocybin compared to MDMA. Objective knowledge items revealed low knowledge of therapeutic uses, risks, and pharmacology. Primary concerns were lack of trained providers, financial cost, and potential contraindications. Prior psychedelic use, self-rated knowledge, younger age, and professional role predicted openness to clinical use of psilocybin and MDMA, with physicians reporting lower openness. As psychedelics continue to garner popular and scientific interest, results indicate a pressing need for additional formal training to provide balanced, evidence-based information from trusted sources. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
34. Meaningfulness and attachment: what dreams, psychosis and psychedelic states tell us about our need for connection.
- Author
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Fischman, Lawrence
- Subjects
SELF-organizing systems ,DREAMS ,SCHIZOPHRENIA ,PSYCHOSES ,HALLUCINOGENIC drugs - Abstract
The human need to find meaning in life and the human need for connection may be two sides of the same coin, a coin forged in the developmental crucible of attachment. Our need for meaningfulness can be traced to our developmental need for connection in the attachment relationship. The free energy principle dictates that in order to resist a natural tendency towards disorder self-organizing systems must generate models that predict the hidden causes of phenomenal experience. In other words, they must make sense of things. In both an evolutionary and ontogenetic sense, the narrative self develops as a model that makes sense of experience. However, the self-model skews the interpretation of experience towards that which is predictable, or already "known." One may say it causes us to "take things personally." Meaning is felt more acutely when defenses are compromised, when the narrative self is offline. This enables meaning-making that is less egocentrically motivated. Dreams, psychosis, and psychedelic states offer glimpses of how we make sense of things absent a coherent narrative self. This has implications for the way we understand such states, and lays bare the powerful reach of attachment in shaping what we experience as meaningful. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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35. Psychothérapie assistée par psychédéliques (PAP) : le modèle genevois.
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Seragnoli, Federico, Thorens, Gabriel, Penzenstadler, Louise, Furtado, Leonice, Buchard, Albert, Bachmann, Silke, Iuga, Radu, Khatcherian, Eugénie, Nowotarski, Adam, Sabe, Michel, Richard-Lepouriel, Hélène, Glangetas, Alban, Girani, Léa, Anastasova, Raya, Girardet, Alexis, Yang, Ray, Lécureux, Léo, Alaux, Sylvie, Mabilais, Cedric, and Amberger, Caroline
- Abstract
Dans cet article, nous avons pour objectif de décrire un modèle interdisciplinaire de psychothérapie assistée par psychédéliques (PAP) que nous avons développé dans un cadre institutionnel aux hôpitaux universitaires de Genève. La psychothérapie assistée par psychédéliques (PAP) est une approche psychothérapeutique exploitant l'altération de l'état de conscience induite par une substance psychédélique. Cette approche, longtemps négligée pour des raisons historiques non scientifiques, fait de nouveau l'objet de recherches grâce à des résultats préliminaires importants concernant son potentiel thérapeutique dans divers troubles mentaux. En Suisse, depuis 2014, il est possible d'obtenir des autorisations médicales exceptionnelles pour traiter des patients avec du LSD et de la psilocybine. Nous soutenons que l'altération de la conscience induite par les psychédéliques est un outil thérapeutique puissant qui pourrait être développé pour appuyer la psychothérapie traditionnelle basée sur le dialogue afin de relancer le processus psychothérapeutique. In this article, we aim to describe an interdisciplinary model for psychedelic assisted psychotherapy (PAP) that we have developed at the Geneva University Hospitals, in an institutional setting. Our model integrates the collaborative efforts of psychiatrists, psychologists, and nurses establishing a structured framework for administering PAP in a safe, controlled, and standardized manner. Psychedelic assisted psychotherapy (PAP) is a psychotherapeutic approach that utilizes the profound alteration of the state of consciousness induced by psychedelic substances to enhance therapeutic outcomes. This innovative approach, which has been neglected due to historical biases rather than empirical evidence, is now experiencing a renewed interest among clinicians. Contemporary research, equipped with advanced methodologies and a rigorous scientific approach, is showing significant therapeutic potential for a range of mental health disorders. In Switzerland, the legal framework authorizes the medicinal use since 2014 for exceptional authorizations for the medicinal use of LSD and psilocybin for therapeutic purposes, under strict regulations. We provide a comprehensive description of the PAP protocol implemented at the Geneva University Hospitals, beginning with its inception in September 2020. Our methodological outline includes the administrative and clinical selection criteria for patient eligibility; the preparatory sessions designed to introduce the patients with psychoeducation interventions and the analysis of intention and therapeutical objectives; the controlled administration of psychedelics in a supportive environment; and the integration sessions that follow psychedelic experiences. Our protocol emphasizes safety, ethical considerations, and the importance of a supportive therapeutic relationship throughout the process. We also describe questionnaires we use to qualify and assess the alteration in the state of consciousness, namely The Five Dimension Altered States of Consciousness (5AD-ASC) and the Mystical Experience Questionnaire (MEQ). Since the start of the program in September 2020 and up to February 2024, a total of 224 personal authorizations (114 LSD, 110 Psilocybin) have been issued to the Geneva University Hospital PAP team, for a total of 396 individual sessions. The core argument presented in this article is that the psychedelic-induced alteration of consciousness is a novel therapeutic tool, which works as a potent catalyst that can be synergistically combined with traditional dialogue-based psychotherapy. This combination has the potential to support the psychotherapeutic processes and enable breakthroughs in cases where conventional therapy has reached its limits. We discuss the implications of this approach, reflecting on both its challenges and its transformative potential within its clinical application. The conclusion of our article is an endorsement of the continued basic and clinical research on PAP. By presenting a detailed framework of the PAP process, including its preparatory, experiential, and integrative phases, we advocate for a structured and scientifically grounded exploration of its therapeutic efficacy. Our conclusion calls for a broader acceptance and integration of PAP within clinical practice, provided it is underpinned by ongoing research, ethical practice, and institutional support. [ABSTRACT FROM AUTHOR]
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- 2024
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36. Healing with Ayahuasca the Plant Teacher: Psychedelic Metaphoricity and Polyontologies.
- Author
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Gearin, Alex K.
- Subjects
- *
SHAMANS , *HEALING , *ONTOLOGY , *ATHEISTS , *HALLUCINOGENIC drugs - Abstract
Shamans, neo-shamans, atheists, and others describe gaining special knowledge from drinking ayahuasca, supporting the cross-cultural idea of ayahuasca as a plant teacher. While secular enthusiasts interpret this metaphorically, animists and others take it literally. This article examines ontological collisions at a healing retreat in the Peruvian Amazon, considering Shipibo shamans and their international clients. It explores how embodied experiences, such as purging and visions, inform both literal and metaphorical views of healing and illness. By addressing incommensurable ontologies, the article highlights how a polyontological framework approaches ontological collision without necessarily privileging specific ways of knowing. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
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37. Psychology of mysticism: Toward a layered hierarchy model.
- Author
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Chen, Zhuo Job
- Subjects
- *
SELF-perception , *RELIGIOUS experience , *SPIRITUALISM , *CONSCIOUSNESS , *SPIRITUALITY , *MYSTICISM - Abstract
The studies of mysticism have traditionally emphasized a common core centered around experiences of ego dissolution and unity. However, this focus on a central set of experiences tends to downplay the non-central aspects, resulting in a limited understanding that may not encompass many other types of extraordinary experiences. This article proposes a layered hierarchy model of mysticism, which reverts to the fundamental definition of mysticism and resonates with the Jamesian characteristics of mysticism as noetic and ineffable. Consequently, an extended definition is put forth to characterize mysticism as the transcendence of perceived reality and the transformation of the perceiver. Within this proposed model, four layers of mysticism are delineated. Monistic Mysticism is characterized by the perception of oneness in all existence and the dissolution of selfhood, exemplified by perennialist mystical unity. Nondualistic Mysticism involves the recognition of a higher reality beyond the mundane world and the subjugation of the ego to an idealized divine, exemplified by religious experiences. Dualistic Mysticism encompasses a world of spirits in contrast to human reality, where the self detaches from and interacts with spiritual beings, exemplified by psychedelic experiences and spiritism. Pluralistic Mysticism entails numerous coexisting realities, and the self is understood to have many facets and boundless potentials, exemplified by psychic phenomena and non-physicalism. This expanded framework broadens the scope of mysticism and makes it a versatile tool for studying a wide range of human experiences under a unified framework. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
- View/download PDF
38. Substrate recognition by the 4‐hydroxytryptamine kinase PsiK in psilocybin biosynthesis.
- Author
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Rogge, Kai, Wagner, Tobias Johannes, Hoffmeister, Dirk, Rupp, Bernhard, and Werten, Sebastiaan
- Subjects
- *
BIOCHEMICAL substrates , *NATURAL products , *MUTAGENESIS , *AMINO acids , *PHOSPHORYLATION , *PSILOCYBIN - Abstract
Psilocybin, the natural hallucinogen from Psilocybe (magic) mushrooms, is a highly promising drug candidate for the treatment of depression and several other mental health conditions. Biosynthesis of psilocybin from the amino acid l‐tryptophan involves four strictly sequential modifications. The third of these, ATP‐dependent phosphorylation of the intermediate 4‐hydroxytryptamine, is catalysed by PsiK. Here we present a crystallographic analysis and a structure‐based mutagenesis study of this kinase, providing insight into its mode of substrate recognition. The results of our work will support future bioengineering efforts aimed at generating variants of psilocybin with enhanced therapeutic properties. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
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39. Neuroprotective effects of psilocybin in a rat model of stroke.
- Author
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Yu, Seong-Jin, Wu, Kuo-Jen, Wang, Yu-Syuan, Bae, Eunkyung, Chianelli, Fabio, Bambakidis, Nicholas, and Wang, Yun
- Subjects
CEREBRAL infarction ,LABORATORY rats ,PSILOCYBIN ,SPRAGUE Dawley rats ,ARTERIAL occlusions - Abstract
Background: Psilocybin is a psychedelic 5HT2A receptor agonist found in "magic mushrooms". Recent studies have indicated that 5HT2A agonists, such as dimethyltryptamine, given before middle cerebral artery occlusion (MCAo), improve staircase behavior, increased BDNF expression, and reduce brain infarction in stroke rats. The objective of this study is to determine the protective effect of psilocybin in cellular and animal models of stroke. Methods: Adult male and timed-pregnant Sprague-Dawley rats were used for this study. The neural protective effects of psilocybin were determined in primary rat cortical neurons and adult rats. Rats were subjected to a 60-min middle cerebral artery occlusion. Brain tissues were collected for histological and qRTPCR analysis. Results: Psilocybin reduced glutamate-mediated neuronal loss in rat primary cortical neuronal cultures. Psilocybin-mediated protection in culture was antagonized by the BDNF inhibitor ANA12. Pretreatment with psilocybin reduced brain infarction and neurological deficits in stroke rats. Early post-treatment with psilocybin improved locomotor behavior, upregulated the expression of MAP2 and synaptophysin, and down-regulated the expression of IBA1 in the stroke brain. ANA12 significantly attenuated psilocybin-mediated reduction in brain infarction and improvements in locomotor behavior. Conclusions: Psilocybin reduced brain infarction and improved locomotor behavior in stroke rats; the protective mechanisms involve regulating BDNF expression. Our data support a novel therapeutic approach of psilocybin in stroke. Highlights: Psilocybin reduced glutamate-mediated neuronal loss in primary cortical neuronal cultures. ANA12 reduced psilocybin-mediated protection in culture. Psilocybin reduced brain infarction, reduced neurological deficits, and increased locomotor behavior in stroke rats. Psilocybin enhanced the expression of MAP2 and synaptophysin, and down-regulated IBA1 in the stroke rat brain. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
40. Defined radio wave frequencies attenuate the head-twitch response in mice elicited by (±)-2,5-dimethoxy-4-iodoamphetamine.
- Author
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Vu, Mary O., Butters, B. Michael, Canal, Clinton E., and Figueroa, Xavier A.
- Subjects
- *
SEROTONIN receptors , *HALLUCINOGENIC drugs , *ELECTROMAGNETIC fields , *RADIO frequency , *RADIO waves , *PSILOCYBIN - Abstract
Results from clinical trials show that serotonergic psychedelics have efficacy in treating psychiatric disorders, where currently approved pharmacotherapies are inadequate. Developing psychedelic medicines, however, comes with unique challenges, such as tempering heightened anxiety associated with the psychedelic experience. We conceived a new strategy to potentially mitigate psychedelic effects with defined electromagnetic signals (ES). We recorded the electromagnetic fields emitted by the serotonin 2 receptor (5-HT2R) agonist (±)-2,5-dimethoxy-4-iodoamphetamine (DOI) and converted them to a playable WAV file. We then exposed the DOI WAV ES to mice to assess its effects on th DOI-elicited, 5-HT2AR dependent head-twitch response (HTR). The DOI WAV signal significantly attenuated the HTR in mice elicited by 0.1 and 0.3 mg/kg subcutaneous DOI (p < 0.05 and p < 0.01, respectively). A scrambled WAV signal did not affect the DOI-elicited HTR, suggesting specificity of the DOI WAV signal. These results provide evidence that defined ES could modulate the psychoactive effects of serotonergic psychedelics. We discuss putative explanations for the distinct effects of the DOI WAV signal in the context of previous studies that demonstrate ES's efficacy for treating other conditions, including pain and cancer. Plain Language Summary: Numerous clinical studies demonstrate that psychedelic drugs can treat psychiatric disorders. A challenge with psychedelic drugs is that they can elicit distressing experiences, which require psychological support in some patients. Recent developments have allowed for the recording of the electromagnetic shell or field of molecules in solution. These electromagnetic signals (ES) can be emitted (as a magnetic field) to emulate the effects of the recorded drug. By using ES, we have the potential to manage or mitigate the negative effects of a drug, simply by turning off the magnetic field. The main target of serotonergic psychedelic drugs is the serotonin receptor, 5-HT2A. A reliable and well-studied drug used in psychedelic research is (±)-2,5-dimethoxy-4-iodoamphetamine (DOI). DOI binds and activates the 5-HT2A receptor. DOI is known to elicit head twitching in mice (called the head-twitch response or HTR) that is indicative of 5-HT2A receptor activation. A recording of DOI was played to evaluate its effect on the head-twitch response in mice. Here we report that the DOI WAV signal decreased the head-twitch response observed after treating mice with the DOI drug. The effects were measurable, reproducible and demonstrated the ability of the DOI recording to dampen the head-twitch response. This WAV recording has the potential to interfere with the unwanted effects of psychedelics, making their use safer. [ABSTRACT FROM AUTHOR]
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- 2024
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41. Pharmacological and behavioural effects of tryptamines present in psilocybin‐containing mushrooms.
- Author
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Rakoczy, Ryan J., Runge, Grace N., Sen, Abhishek K., Sandoval, Oscar, Wells, Hunter G., Nguyen, Quynh, Roberts, Brianna R., Sciortino, Jon H., Gibbons, William J., Friedberg, Lucas M., Jones, J. Andrew, and McMurray, Matthew S.
- Subjects
- *
MONOAMINE oxidase , *DRUG target , *CELL imaging , *HALLUCINOGENIC drugs , *ALKALINE phosphatase - Abstract
Background and Purpose: Demand for new antidepressants has resulted in a re‐evaluation of the therapeutic potential of psychedelic drugs. Several tryptamines found in psilocybin‐containing "magic" mushrooms share chemical similarities with psilocybin. Early work suggests they may share biological targets. However, few studies have explored their pharmacological and behavioural effects. Experimental Approach: We compared baeocystin, norbaeocystin and aeruginascin with psilocybin to determine if they are metabolized by the same enzymes, similarly penetrate the blood–brain barrier, serve as ligands for similar receptors and modulate behaviour in rodents similarly. We also assessed the stability and optimal storage and handling conditions for each compound. Key Results: In vitro enzyme kinetics assays found that all compounds had nearly identical rates of dephosphorylation via alkaline phosphatase and metabolism by monoamine oxidase. Further, we found that only the dephosphorylated products of baeocystin and norbaeocystin crossed a blood–brain barrier mimetic to a similar degree as the dephosphorylated form of psilocybin, psilocin. The dephosphorylated form of norbaeocystin was found to activate the 5‐HT2A receptor with similar efficacy to psilocin and norpsilocin in in vitro cell imaging assays. Behaviourally, only psilocybin induced head twitch responses in rats, a marker of 5‐HT2A‐mediated psychedelic effects and hallucinogenic potential. However, like psilocybin, norbaeocystin improved outcomes in the forced swim test. All compounds caused minimal changes to metrics of renal and hepatic health, suggesting innocuous safety profiles. Conclusions and Implications: Collectively, this work suggests that other naturally occurring tryptamines, especially norbaeocystin, may share overlapping therapeutic potential with psilocybin, but without causing hallucinations. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
42. Meditating on psychedelics. A randomized placebo-controlled study of DMT and harmine in a mindfulness retreat.
- Author
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Meling, Daniel, Egger, Klemens, Aicher, Helena D, Jareño Redondo, Javier, Mueller, Jovin, Dornbierer, Joëlle, Temperli, Elijah, Vasella, Emilia A, Caflisch, Luzia, Pfeiffer, David J, Schlomberg, Jonas TT, Smallridge, John W, Dornbierer, Dario A, and Scheidegger, Milan
- Subjects
- *
MONOAMINE oxidase inhibitors , *DIMETHYLTRYPTAMINE , *MINDFULNESS , *PSYCHOMETRICS , *MEDITATION , *PSILOCYBIN - Abstract
Background: In recent years, both meditation and psychedelics have attracted rapidly increasing scientific interest. While the current state of evidence suggests the promising potential of psychedelics, such as psilocybin, to enhance meditative training, it remains equivocal whether these effects are specifically bound to psilocybin or if other classical psychedelics might show synergistic effects with meditation practice. One particularly promising candidate is N,N -dimethyltryptamine (DMT), an active ingredient of ayahuasca. Aim: This study aims to investigate the effect of the psychedelic substance DMT, combined with the monoamine oxidase inhibitor harmine (DMT-harmine), on meditative states, compared to meditation with a placebo. Method: Forty experienced meditators (18 females and 22 males) participated in a double-blind, placebo-controlled study over a 3-day meditation retreat, receiving either placebo or DMT-harmine. Participants' levels of mindfulness, compassion, insight, and transcendence were assessed before, during, and after the meditation group retreat, using psychometric questionnaires. Results: Compared to meditation with a placebo, meditators who received DMT and harmine self-attributed greater levels of mystical-type experiences, non-dual awareness, and emotional breakthrough during the acute substance effects and, when corrected for baseline differences, greater psychological insight 1 day later. Mindfulness and compassion were not significantly different in the DMT-harmine group compared to placebo. At 1-month follow-up, the meditators who received DMT and harmine rated their experience as significantly more personally meaningful, spiritually significant, and well-being-enhancing than the meditators who received placebo. Conclusion: Investigating the impact of DMT-harmine on meditators in a naturalistic mindfulness group retreat, this placebo-controlled study highlights the specific effects of psychedelics during meditation. Trial registration: ClinicalTrials.gov identifier NCT05780216. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
43. At-home, telehealth-supported ketamine treatment for depression: Findings from longitudinal, machine learning and symptom network analysis of real-world data.
- Author
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Mathai, David S., Hull, Thomas D., Vando, Leonardo, and Malgaroli, Matteo
- Subjects
- *
MENTAL health services , *MACHINE learning , *KETAMINE , *KETAMINE abuse , *DATA analysis , *MENTAL depression - Abstract
Improving safe and effective access to ketamine therapy is of high priority given the growing burden of mental illness. Telehealth-supported administration of sublingual ketamine is being explored toward this goal. In this longitudinal study, moderately-to-severely depressed patients received four doses of ketamine at home over four weeks within a supportive digital health context. Treatment was structured to resemble methods of therapeutic psychedelic trials. Patients receiving a second course of treatment were also examined. Symptoms were assessed using the Patient Health Questionnaire (PHQ-9) for depression. We conducted preregistered machine learning and symptom network analyses to investigate outcomes (osf.io/v2rpx). A sample of 11,441 patients was analyzed, demonstrating a modal antidepressant response from both non-severe (n = 6384, 55.8 %) and severe (n = 2070, 18.1 %) baseline depression levels. Adverse events were detected in 3.0–4.8 % of participants and predominantly neurologic or psychiatric in nature. A second course of treatment helped extend improvements in patients who responded favorably to initial treatment. Improvement was most strongly predicted by lower depression scores and age at baseline. Symptoms of Depressed mood and Anhedonia sustained depression despite ongoing treatment. This study was limited by the absence of comparison or control groups and lack of a fixed-dose procedure for ketamine administration. At-home, telehealth-supported ketamine administration was largely safe, well-tolerated, and associated with improvement in patients with depression. Strategies for combining psychedelic-oriented therapies with rigorous telehealth models, as explored here, may uniquely address barriers to mental health treatment. • Telehealth ketamine assisted treatment was safe and effective for 11,000+ patients. • Machine learning identified patient characteristics predicting symptoms improvement. • Temporal network suggested low mood and anhedonia as key in treatment non-response. • Primarily psychiatric adverse events underscored importance of behavioral support. • Telehealth-supported ketamine administration may help address barriers to treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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44. The Epidemiology of Psychedelic Use Among United States Military Veterans.
- Author
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Davis, Alan K., Bates, Mark, Lund, Erik M., Sepeda, Nathan D., Levin, Adam W., Armstrong, Stacey B., Koffman, Robert, Hooyer, Katinka, and Yehuda, Rachel
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- *
MENTAL health services , *VETERANS , *VETERANS' health , *HALLUCINOGENIC drugs , *PSILOCYBIN ,UNITED States armed forces - Abstract
We sought to identify patterns of psychedelic use among United States military veterans, compare demographic variables and perspectives of those who did and did not report use, and characterize benefits and adverse outcomes associated with use. Respondents (
N = 426) were recruited to complete an online cross-sectional survey. Approximately one-half (51%) reported using psychedelics. Most did so for healing/treatment (70%) and/or spiritual purposes (48%), and most (85%) reported benefiting from use. Those who used psychedelics reported they would be more likely to use VA services (p < .001, d = 0.64) and to return to the VA for care (p < .001, d = 0.79) if psychedelic therapy was offered. Almost two-thirds (59%) reported adverse outcomes associated with use. Equivalent proportions rated their psychedelic experiences as beneficial among those who did (89%) and did not (81%) report adverse outcomes. Fewer adverse outcomes were associated with being older, using psilocybin, feeling prepared and confident in the reasons for use, being in a comfortable setting, and being able to “trust, let go, and be open” (Rc = 0.77;p < .001). Psychedelics may offer benefits but may also lead to adverse outcomes without proper preparation and support. Future research should examine the utility of psychedelic-based approaches for veteran mental health care. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
45. THC-O-Acetate: Scarce Evidence for a Psychedelic Cannabinoid.
- Author
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Kruger, Daniel J., Bone, Carlton CB, Meacham, Meredith C., Klein, Charles, and Kruger, Jessica S.
- Subjects
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TIME perception , *INTERNET forums , *SHORT-term memory , *RESEARCH personnel , *HALLUCINATIONS - Abstract
There is a growing interest in semi-synthetic cannabinoids, including THC-O-acetate (THC-Oac). Some cannabis marketers and users have claimed that THC-Oac produces psychedelic effects; the current study is the first to examine this claim. Researchers developed an online survey for THC-Oac consumers based on previous cannabis and psychedelic use surveys and in consultation with the moderator of an online forum. The survey assessed the experiential profile of THC-Oac and included items from the Mystical Experience Questionnaire (MEQ), an instrument for assessing psychedelic experiences. Participants reported a low to moderate level of cognitive distortions (altered sense of time, difficulties concentrating, difficulties with short-term memory) and few visuals or hallucinations. Participants' responses were significantly below the threshold for a complete mystical experience on all four MEQ dimensions. Participants who had used classic (5-HT2A agonist) psychedelics had lower scores on all MEQ dimensions. When asked directly, 79% responded that using THC-Oac is "not at all" or "a little" of a psychedelic experience. Some reports of psychedelic experiences may be due to expectations or contaminants. Those having prior experience with classic psychedelics had lower ratings of mystical experiences. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
46. Psychedelic‐assisted therapy for palliative care within a home treatment setting: A case report.
- Author
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Federico, Seragnoli, Geo, Martignoni, Entela, Martignoni, Bachmann, Silke, Elisa, Rabitti, Silvio, Cavuto, Zoë, Dubus, Louise, Penzenstadler, Gabriel, Thorens, Joël, Billieux, and Daniele, Zullino
- Subjects
- *
PSYCHOLOGICAL distress , *PLACEBOS , *PSILOCYBIN , *PALLIATIVE treatment , *PATIENT safety - Abstract
Key Clinical Message: This case study describes the feasibility and safety of psychedelic‐assisted therapy (PAT) as a home‐based intervention for a patient with throat cancer experiencing significant existential distress. The patient tolerated the intervention well. This case supports the feasibility and safety of PAT for patients with life‐threatening conditions in a home setting. Psychedelic‐assisted therapy (PAT), as it is practiced today, merges traditional psychotherapeutic techniques with the use of psychedelics such as LSD, psilocybin, or MDMA with the aim of unlocking deeper insights in patients and treating mental conditions that are resistant to other forms of therapy. The present case study describes the safety of PAT as a home‐based intervention for a patient with throat cancer experiencing significant existential distress. The patient tolerated the intervention well and was asked to report on measures of anxiety, depression, and distress related to his somatic condition. The observations provided by this clinical case report align with previous findings, suggesting that PAT can be safely applied to potentially provide relief from existential distress in patients with life‐threatening conditions. As this is a single‐case study, generalizations should be made cautiously. Moreover, placebo effects, expectancy effects, and the natural course of the disease may influence outcomes. Future research should consider controlled trials to ascertain the efficacy and safety of such interventions in diverse settings. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
47. Perspectives and preliminary experiences of psychedelics for the treatment of eating disorders: A systematic scoping review.
- Author
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Cuerva, Karolina, Spirou, Dean, Cuerva, Adrian, Delaquis, Chantal, and Raman, Jayanthi
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- *
PREVENTION of eating disorders , *PSYCHOTHERAPY , *PATIENT safety , *HALLUCINOGENIC drugs , *EATING disorders , *SYSTEMATIC reviews , *DRUG efficacy , *SOCIAL support , *PATIENTS' attitudes - Abstract
Objective: Research regarding the therapeutic application of psychedelics and psychedelic‐assisted psychotherapy in the treatment of eating disorders (EDs) has begun to emerge. This systematic scoping review aimed to map and synthesise the existing evidence regarding the participant reported efficacy and perspectives concerning psychedelics in the treatment of EDs, and to identify significant research gaps. Method: A systematic search was undertaken across several databases in accordance with Preferred Reporting Items for Systematic reviews and Meta‐Analyses extension for Scoping Reviews guidelines. Results: 1290 publications were identified, 1135 after duplicates removed, with 17 meeting full‐eligibility criteria. Overall, findings suggested that most participants reported experiencing a meaningful reduction in their ED symptoms and having positive experiences or an openness to explore psychedelics as a treatment for ED symptoms, although some noted concerns of adverse effects and the importance of having psychological support to increase safety and efficacy. Conclusions: While preliminary research suggests psychedelics and psychedelic‐assisted psychotherapy may be a viable treatment option for ED symptoms, further research with more robust research designs is required to increase confidence in its efficacy, generalisability, and safety as a therapeutic medium. Highlights: While research regarding the efficacy of psychedelics in the treatment of eating disorders (EDs) is still in its infancy, preliminary findings have been promising.Participants across the included studies reported largely positive experiences and an openness to explore the use of psychedelics and psychedelic‐assisted psychotherapy as a treatment modality for EDs. However, some participants noted concerns about potential adverse effects (AEs) and the importance of ensuring psychological support was provided before, during, and/or after a psychedelic treatment experience.There is currently not enough evidence to determine which psychedelic substances are most efficacious for therapeutic intervention for EDs. Further research is therefore needed, with more robust research methodologies. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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48. Jung, the Rebirth Motif and Psychedelics I: Documenting Jung's Contact with the British Pioneers.
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Hill, Ginny
- Subjects
- *
HALLUCINOGENIC drugs , *LSD (Drug) , *REINCARNATION , *PSYCHOTHERAPY , *PSYCHIATRISTS , *JUNGIAN psychology - Abstract
C. G. Jung wrote very little about psychedelic drugs and he took a sceptical view of them. However, he was sufficiently impressed by Aldous Huxley's 1954 account of taking mescaline, The Doors of Perception, to invite Huxley to visit him in Switzerland. Huxley declined Jung's invitation but Huxley's collaborator Humphry Osmond met Jung instead. This paper documents Jung's contact with the British pioneers of psychedelics research and presents the scant material illuminating his views about these drugs. It also determines the efforts of British psychiatrist Ronald Sandison, who was the first to develop an "explicitly Jungian approach" to psychedelic‐assisted psychotherapy (Hill, 2013), and it highlights a connection between Sandison's initiative and the Society of Analytical Psychology (SAP) through the involvement of two SAP members: Margot Cutner, Sandison's colleague, and Michael Fordham, who supervised a trainee working with one of Sandison's former patients. Despite Jung's objections to the use of psychedelics, Sandison and Cutner developed ground‐breaking protocols during the 1950s and they were among the first to document the phenomenon of "spiritual rebirth symbolized in the birth experience known to many LSD therapists" (Sandison, 2001). In two companion papers, I consider Jung's treatment of the rebirth motif in his commentary on The Tibetan Book of the Dead, which later became a central text in the psychedelic movement, and I chart the evolution in psychedelics research from an association with schizophrenia during the 1950s to the mystical paradigms of the 1960s and beyond. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
49. Vers une utilisation thérapeutique encadrée de la MDMA outre-Atlantique ?
- Author
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Naudon, Anne-Solène
- Abstract
Copyright of Actualités Pharmaceutiques is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2024
- Full Text
- View/download PDF
50. Psychédéliques et psychédélisme, tour d'horizon.
- Author
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Amrouche, Linda
- Abstract
Copyright of Actualités Pharmaceutiques is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2024
- Full Text
- View/download PDF
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