Psilocybin and Mental Health–Don't Lose Control
Barnby, J. M., & Mehta, M. A. (2018). Psilocybin and Mental Health-Don’t Lose Control. Frontiers in Psychiatry, 9, 293. 10.3389/fpsyt.2018.00293
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Scienitific Discipline
Rapid antidepressant effect of S-ketamine in schizophrenia.
Abstract
Rapid anti-suicidal and antidepressant effects of ketamine have repeatedly been confirmed in unipolar and bipolar depression. Although meaningful antidepressant efficacy of ketamine has also been shown in depressed patients with a history of psychotic symptoms, its administration in psychotic disorders has largely been neglected due to its potential to exacerbate dissociative or psychotic symptoms. Presenting a case of a young female inpatient suffering from schizophrenia with a severe post-psychotic depression, we demonstrate a robust anti-suicidal and antidepressant effect of S-ketamine infusions administered thrice weekly for 3 weeks in total. Importantly, no relevant psychotic or dissociative symptoms occurred during the whole augmentation treatment period leading to a sustained remission of depressive symptoms and suicidality. Our safe and effective experience with intravenous S-ketamine might encourage researchers and clinicians to widen its administration range beyond the diagnosis of depression to enrich the current knowledge of ketamine effects in psychotic disorders.
Bartova, L., Papageorgiou, K., Milenkovic, I., Dold, M., Weidenauer, A., Willeit, M., … & Kasper, S. (2018). Rapid antidepressant effect of S-ketamine in schizophrenia. European Neuropsychopharmacology, 28(8), 980-982., 10.1016/j.euroneuro.2018.05.007
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Bartova, L., Papageorgiou, K., Milenkovic, I., Dold, M., Weidenauer, A., Willeit, M., … & Kasper, S. (2018). Rapid antidepressant effect of S-ketamine in schizophrenia. European Neuropsychopharmacology, 28(8), 980-982., 10.1016/j.euroneuro.2018.05.007
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Positive psychology in the investigation of psychedelics and entactogens: A critical review
Abstract
RATIONALE:
We reviewed the concepts and empirical findings in studies with psychedelics and entactogens related to positive psychology – the study of healthy human functioning, well-being and eudaemonia. It is an unresolved question how beneficial effects of psychedelics and entactogens are related to the potential risks of these substances – particularly in non-clinical settings.
METHODS:
We searched in PubMed, PsychINFO and the Cochrane Library for controlled clinical and epidemiological studies which applied concepts from positive psychology. We included N = 77 eligible studies with 9876 participants published before November 1st, 2017: (1) quantitative studies (N = 54), (2) preliminary or exploratory studies and reviews not including meta-analyses (N = 17), and (3) studies evidencing primarily negative results (N = 6).
RESULTS:
Positive psychology concepts have been applied for measuring effects of clinical trials, recreational and ceremonial use of psychedelics and entactogens. Psychedelics and entactogens were shown to produce acute and long-term effects on mood, well-being, prosocial behaviours, empathy, cognitive flexibility, creativity, personality factors like openness, value orientations, nature-relatedness, spirituality, self-transcendence and mindfulness-related capabilities.
CONCLUSIONS:
There is preliminary evidence for beneficial effects of psychedelics and entactogens on measures of positive psychology in clinical and healthy populations, however their sustainability remains largely unresolved. The reported results must be considered preliminary due to methodological restrictions. Since longitudinal data on both positive and adverse effects of psychedelics are lacking, more rigorous and standardized measures from positive psychology should be applied in less biased populations with prospective longitudinal designs to carefully assess the benefit-risk-ratio.
Jungaberle, H., Thal, S., Zeuch, A., Rougemont-Bücking, A., von Heyden, M., Aicher, H., & Scheidegger, M. (2018). Positive psychology in the investigation of psychedelics and entactogens: A critical review. Neuropharmacology. 10.1016/j.neuropharm.2018.06.034
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We reviewed the concepts and empirical findings in studies with psychedelics and entactogens related to positive psychology – the study of healthy human functioning, well-being and eudaemonia. It is an unresolved question how beneficial effects of psychedelics and entactogens are related to the potential risks of these substances – particularly in non-clinical settings.
METHODS:
We searched in PubMed, PsychINFO and the Cochrane Library for controlled clinical and epidemiological studies which applied concepts from positive psychology. We included N = 77 eligible studies with 9876 participants published before November 1st, 2017: (1) quantitative studies (N = 54), (2) preliminary or exploratory studies and reviews not including meta-analyses (N = 17), and (3) studies evidencing primarily negative results (N = 6).
RESULTS:
Positive psychology concepts have been applied for measuring effects of clinical trials, recreational and ceremonial use of psychedelics and entactogens. Psychedelics and entactogens were shown to produce acute and long-term effects on mood, well-being, prosocial behaviours, empathy, cognitive flexibility, creativity, personality factors like openness, value orientations, nature-relatedness, spirituality, self-transcendence and mindfulness-related capabilities.
CONCLUSIONS:
There is preliminary evidence for beneficial effects of psychedelics and entactogens on measures of positive psychology in clinical and healthy populations, however their sustainability remains largely unresolved. The reported results must be considered preliminary due to methodological restrictions. Since longitudinal data on both positive and adverse effects of psychedelics are lacking, more rigorous and standardized measures from positive psychology should be applied in less biased populations with prospective longitudinal designs to carefully assess the benefit-risk-ratio.
Jungaberle, H., Thal, S., Zeuch, A., Rougemont-Bücking, A., von Heyden, M., Aicher, H., & Scheidegger, M. (2018). Positive psychology in the investigation of psychedelics and entactogens: A critical review. Neuropharmacology. 10.1016/j.neuropharm.2018.06.034
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High dose psilocybin is associated with positive subjective effects in healthy volunteers
Abstract
AIM:
The aim of the current study was to investigate the relationship between escalating higher doses of psilocybin and the potential psilocybin occasioned positive subjective effects.
METHODS:
Healthy participants ( n=12) were given three escalating doses of oral psilocybin (0.3 mg/kg; 0.45 mg/kg; 0.6 mg/kg) or (18.8-36.6 mg; 27.1-54.0 mg; 36.3-59.2 mg) a minimum of four weeks apart in a supervised setting. Blood and urine samples, vital signs, and electrocardiograms were obtained. Subjective effects were assessed using the Mystical Experience Questionnaire and Persisting Effects Questionnaire.
RESULTS:
There was a significant linear dose-related response in Mystical Experience Questionnaire total score and the transcendence of time and space subscale, but not in the rate of a complete mystical experience. There was also a significant difference between dose 3 compared to dose 1 on the transcendence of time and space subscale, while no dose-related differences were found for Mystical Experience Questionnaire total scores or rate of a mystical experience. Persisting Effects Questionnaire positive composite scores 30 days after completion of the last dose were significantly higher than negative composite scores. Persisting Effects Questionnaire results revealed a moderate increase in sense of well-being or life satisfaction on average that was associated with the maximum Mystical Experience Questionnaire total score. Pharmacokinetic measures were associated with dose but not with Mystical Experience Questionnaire total scores or rate of a mystical experience.
CONCLUSIONS:
High doses of psilocybin elicited subjective effects at least as strong as the lower doses and resulted in positive persisting subjective effects 30 days after, indicating that a complete mystical experience was not a prerequisite for positive outcomes.
Nicholas, C. R., Henriquez, K. M., Gassman, M. C., Cooper, K. M., Muller, D., Hetzel, S., … & Hutson, P. R. (2018). High dose psilocybin is associated with positive subjective effects in healthy volunteers. Journal of Psychopharmacology, 0269881118780713.
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The aim of the current study was to investigate the relationship between escalating higher doses of psilocybin and the potential psilocybin occasioned positive subjective effects.
METHODS:
Healthy participants ( n=12) were given three escalating doses of oral psilocybin (0.3 mg/kg; 0.45 mg/kg; 0.6 mg/kg) or (18.8-36.6 mg; 27.1-54.0 mg; 36.3-59.2 mg) a minimum of four weeks apart in a supervised setting. Blood and urine samples, vital signs, and electrocardiograms were obtained. Subjective effects were assessed using the Mystical Experience Questionnaire and Persisting Effects Questionnaire.
RESULTS:
There was a significant linear dose-related response in Mystical Experience Questionnaire total score and the transcendence of time and space subscale, but not in the rate of a complete mystical experience. There was also a significant difference between dose 3 compared to dose 1 on the transcendence of time and space subscale, while no dose-related differences were found for Mystical Experience Questionnaire total scores or rate of a mystical experience. Persisting Effects Questionnaire positive composite scores 30 days after completion of the last dose were significantly higher than negative composite scores. Persisting Effects Questionnaire results revealed a moderate increase in sense of well-being or life satisfaction on average that was associated with the maximum Mystical Experience Questionnaire total score. Pharmacokinetic measures were associated with dose but not with Mystical Experience Questionnaire total scores or rate of a mystical experience.
CONCLUSIONS:
High doses of psilocybin elicited subjective effects at least as strong as the lower doses and resulted in positive persisting subjective effects 30 days after, indicating that a complete mystical experience was not a prerequisite for positive outcomes.
Nicholas, C. R., Henriquez, K. M., Gassman, M. C., Cooper, K. M., Muller, D., Hetzel, S., … & Hutson, P. R. (2018). High dose psilocybin is associated with positive subjective effects in healthy volunteers. Journal of Psychopharmacology, 0269881118780713.
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Mental health of a self-selected sample of psychedelic users and self-medication practices with psychedelics
Abstract
Background
A substantial number of people worldwide suffer from mental health problems during their lifetime. First-line treatments are not effective for everybody. Recent studies suggest that psychedelic drugs have high therapeutic potential for a variety of mental disorders.
Aims
This survey study aimed to assess the tendency of psychedelic users to self-medicate with psychedelics and to compare the effectiveness of self-administered psychedelics to treat their disorder and the treatment offered by a medical professional.
Methods and results
In total, 1,967 respondents consented were ≥18 years and completed the questionnaire. The mean (±SD) age was 25.9 (8.7); 79% were males, 20% females, and 1% classified themselves as “other.” Almost half of the respondents (46%) indicated to have suffered/to be suffering from a mental disorder, with 77% being diagnosed by a medical professional. In 99% of the diagnosed cases, the treatment was offered; 77% searched for treatments outside a medical professional’s recommendation with 81% who had used/were using psychedelics to treat/cure symptoms. Self-administered psychedelic treatment had a higher likelihood of being efficacious, with higher symptoms reduction and larger quality of life improvement compared to treatment offered by a medical professional.
Conclusions
Lifetime prevalence of psychopathologies in the current sample of psychedelic drug users seemed to be higher than in the general population. Self-medication with psychedelics was not highly frequent; although when it occurred, it was rated as significantly more effective as treatment offered by a medical professional. Current findings support research exploring the potential of psychedelics in the treatment of psychopathologies.
Mason, N. L., & Kuypers, K. P. (2018). Mental health of a self-selected sample of psychedelic users and self-medication practices with psychedelics. Journal of Psychedelic Studies, 2(1), 45-52. 10.1556/2054.2018.006
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Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts
Abstract
Background:
Recent pilot trials suggest feasibility and potential efficacy of psychedelic-facilitated addiction treatment interventions. Fifteen participants completed a psilocybin-facilitated smoking cessation pilot study between 2009 and 2015.
Aims:
The aims of this study were as follows: (1) to identify perceived mechanisms of change leading to smoking cessation in the pilot study; (2) to identify key themes in participant experiences and long-term outcomes to better understand the therapeutic process.
Methods:
Participants were invited to a retrospective follow-up interview an average of 30 months after initial psilocybin sessions. Semi-structured interviews were conducted with 12 of the 15 participants. Data were analysed using thematic analysis.
Results:
Participants reported gaining vivid insights into self-identity and reasons for smoking from their psilocybin sessions. Experiences of interconnectedness, awe, and curiosity persisted beyond the duration of acute drug effects. Participants emphasised that the content of psilocybin experiences overshadowed any short-term withdrawal symptoms. Preparatory counselling, strong rapport with the study team, and a sense of momentum once engaged in the study treatment were perceived as vital additional factors in achieving abstinence. In addition, participants reported a range of persisting positive changes beyond smoking cessation, including increased aesthetic appreciation, altruism, and pro-social behaviour.
Conclusions:
The findings highlight the value of qualitative research in the psychopharmacological investigation of psychedelics. They describe perceived connections between drug- and non-drug factors, and provide suggestions for future research trial design and clinical applications.
Noorani, T., Garcia-Romeu, A., Swift, T. C., Griffiths, R. R., & Johnson, M. W. (2018). Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts. Journal of Psychopharmacology, 32(7), 756-769. 10.1177%2F0269881118780612
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Psychedelics and hypnosis: Commonalities and therapeutic implications
Abstract
BACKGROUND:
Recent research on psychedelics and hypnosis demonstrates the value of both methods in the treatment of a range of psychopathologies with overlapping applications and neurophenomenological features. The potential of harnessing the power of suggestion to influence the phenomenological response to psychedelics toward more therapeutic action has remained unexplored in recent research and thereby warrants empirical attention.
AIMS:
Here we aim to elucidate the phenomenological and neurophysiological similarities and dissimilarities between psychedelic states and hypnosis in order to revisit how contemporary knowledge may inform their conjunct usage in psychotherapy.
METHODS:
We review recent advances in phenomenological and neurophysiological research on psychedelics and hypnosis, and we summarize early investigations on the coupling of psychedelics and hypnosis in scientific and therapeutic contexts. Results/outcomes: We highlight commonalities and differences between psychedelics and hypnosis that point to the potential efficacy of combining the two in psychotherapy. We propose multiple research paths for coupling these two phenomena at different stages in the preparation, acute phase and follow-up of psychedelic-assisted psychotherapy in order to prepare, guide and integrate the psychedelic experience with the aim of enhancing therapeutic outcomes.
CONCLUSIONS/INTERPRETATION:
Harnessing the power of suggestion to modulate response to psychedelics could enhance their therapeutic efficacy by helping to increase the likelihood of positive responses, including mystical-type experiences.
Lemercier, C. E., & Terhune, D. B. (2018). Psychedelics and hypnosis: Commonalities and therapeutic implications. Journal of Psychopharmacology, 0269881118780714.
Link to full text
Recent research on psychedelics and hypnosis demonstrates the value of both methods in the treatment of a range of psychopathologies with overlapping applications and neurophenomenological features. The potential of harnessing the power of suggestion to influence the phenomenological response to psychedelics toward more therapeutic action has remained unexplored in recent research and thereby warrants empirical attention.
AIMS:
Here we aim to elucidate the phenomenological and neurophysiological similarities and dissimilarities between psychedelic states and hypnosis in order to revisit how contemporary knowledge may inform their conjunct usage in psychotherapy.
METHODS:
We review recent advances in phenomenological and neurophysiological research on psychedelics and hypnosis, and we summarize early investigations on the coupling of psychedelics and hypnosis in scientific and therapeutic contexts. Results/outcomes: We highlight commonalities and differences between psychedelics and hypnosis that point to the potential efficacy of combining the two in psychotherapy. We propose multiple research paths for coupling these two phenomena at different stages in the preparation, acute phase and follow-up of psychedelic-assisted psychotherapy in order to prepare, guide and integrate the psychedelic experience with the aim of enhancing therapeutic outcomes.
CONCLUSIONS/INTERPRETATION:
Harnessing the power of suggestion to modulate response to psychedelics could enhance their therapeutic efficacy by helping to increase the likelihood of positive responses, including mystical-type experiences.
Lemercier, C. E., & Terhune, D. B. (2018). Psychedelics and hypnosis: Commonalities and therapeutic implications. Journal of Psychopharmacology, 0269881118780714.
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Effects of psilocybin therapy on personality structure
Abstract
OBJECTIVE:
To explore whether psilocybin with psychological support modulates personality parameters in patients suffering from treatment-resistant depression (TRD).
METHOD:
Twenty patients with moderate or severe, unipolar, TRD received oral psilocybin (10 and 25 mg, one week apart) in a supportive setting. Personality was assessed at baseline and at 3-month follow-up using the Revised NEO Personality Inventory (NEO-PI-R), the subjective psilocybin experience with Altered State of Consciousness (ASC) scale, and depressive symptoms with QIDS-SR16.
RESULTS:
Neuroticism scores significantly decreased while Extraversion increased following psilocybin therapy. These changes were in the direction of the normative NEO-PI-R data and were both predicted, in an exploratory analysis, by the degree of insightfulness experienced during the psilocybin session. Openness scores also significantly increased following psilocybin, whereas Conscientiousness showed trend-level increases, and Agreeableness did not change.
CONCLUSION:
Our observation of changes in personality measures after psilocybin therapy was mostly consistent with reports of personality change in relation to conventional antidepressant treatment, although the pronounced increases in Extraversion and Openness might constitute an effect more specific to psychedelic therapy. This needs further exploration in future controlled studies, as do the brain mechanisms of postpsychedelic personality change.
Erritzoe, D., Roseman, L., Nour, M. M., MacLean, K., Kaelen, M., Nutt, D. J., & Carhart‐Harris, R. L. (2018). Effects of psilocybin therapy on personality structure. Acta Psychiatrica Scandinavica. 10.1111/acps.12904
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To explore whether psilocybin with psychological support modulates personality parameters in patients suffering from treatment-resistant depression (TRD).
METHOD:
Twenty patients with moderate or severe, unipolar, TRD received oral psilocybin (10 and 25 mg, one week apart) in a supportive setting. Personality was assessed at baseline and at 3-month follow-up using the Revised NEO Personality Inventory (NEO-PI-R), the subjective psilocybin experience with Altered State of Consciousness (ASC) scale, and depressive symptoms with QIDS-SR16.
RESULTS:
Neuroticism scores significantly decreased while Extraversion increased following psilocybin therapy. These changes were in the direction of the normative NEO-PI-R data and were both predicted, in an exploratory analysis, by the degree of insightfulness experienced during the psilocybin session. Openness scores also significantly increased following psilocybin, whereas Conscientiousness showed trend-level increases, and Agreeableness did not change.
CONCLUSION:
Our observation of changes in personality measures after psilocybin therapy was mostly consistent with reports of personality change in relation to conventional antidepressant treatment, although the pronounced increases in Extraversion and Openness might constitute an effect more specific to psychedelic therapy. This needs further exploration in future controlled studies, as do the brain mechanisms of postpsychedelic personality change.
Erritzoe, D., Roseman, L., Nour, M. M., MacLean, K., Kaelen, M., Nutt, D. J., & Carhart‐Harris, R. L. (2018). Effects of psilocybin therapy on personality structure. Acta Psychiatrica Scandinavica. 10.1111/acps.12904
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Oxytocin receptor gene variations and socio-emotional effects of MDMA: A pooled analysis of controlled studies in healthy subjects
Abstract
Methylenedioxymethamphetamine (MDMA) increases oxytocin, empathy, and prosociality. Oxytocin plays a critical role in emotion processing and social behavior and has been shown to mediate the prosocial effects of MDMA in animals. Genetic variants, such as single-nucleotide polymorphisms (SNPs), of the oxytocin receptor (OXTR) may influence the emotional and social effects of MDMA in humans. The effects of common genetic variants of the OXTR (rs53576, rs1042778, and rs2254298 SNPs) on the emotional, empathogenic, and prosocial effects of MDMA were characterized in up to 132 healthy subjects in a pooled analysis of eight double-blind, placebo-controlled studies. In a subset of 53 subjects, MDMA produced significantly greater feelings of trust in rs1042778 TT genotypes compared with G allele carriers. The rs53576 and rs225498 SNPs did not moderate the subjective effects of MDMA in up to 132 subjects. None of the SNPs moderated MDMA-induced impairments in negative facial emotion recognition or enhancements in emotional empathy in the Multifaceted Empathy Test in 69 subjects. MDMA significantly increased plasma oxytocin concentrations. MDMA and oxytocin concentrations did not differ between OXTR gene variants. The present results provide preliminary evidence that OXTR gene variations may modulate aspects of the prosocial subjective effects of MDMA in humans. However, interpretation should be cautious due to the small sample size. Additionally, OXTR SNPs did not moderate the subjective overall effect of MDMA (any drug effect) or feelings of “closeness to others”.
Vizeli, P., & Liechti, M. E. (2018). Oxytocin receptor gene variations and socio-emotional effects of MDMA: A pooled analysis of controlled studies in healthy subjects. PloS one, 13(6), e0199384. 10.1371/journal.pone.0199384
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Vizeli, P., & Liechti, M. E. (2018). Oxytocin receptor gene variations and socio-emotional effects of MDMA: A pooled analysis of controlled studies in healthy subjects. PloS one, 13(6), e0199384. 10.1371/journal.pone.0199384
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Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial
Abstract
BACKGROUND:
Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.
METHODS:
To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.
RESULTS:
We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen’s d = 0.84; D2: Cohen’s d = 0.84; D7: Cohen’s d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054).
CONCLUSIONS:
To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression.
Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.
METHODS:
To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.
RESULTS:
We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen’s d = 0.84; D2: Cohen’s d = 0.84; D7: Cohen’s d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054).
CONCLUSIONS:
To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression.
Palhano-Fontes, F., Barreto, D., Onias, H., Andrade, K. C., Novaes, M. M., Pessoa, J. A., … & Tófoli, L. F. (2018). Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychological medicine, 1-9. 10.1017/S0033291718001356
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