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High dose psilocybin is associated with positive subjective effects in healthy volunteers

/ Mushrooms / Psilocybin, Papers, Psychology, Publications / / , , , , , ,

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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Mental health of a self-selected sample of psychedelic users and self-medication practices with psychedelics

/ LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / / ,

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

/ Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / / , , , ,

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

/ Ayahuasca, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications / / ,

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.
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Effects of psilocybin therapy on personality structure

/ Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / / , , , , , ,

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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Oxytocin receptor gene variations and socio-emotional effects of MDMA: A pooled analysis of controlled studies in healthy subjects

/ MDMA, Neuroscience, Papers, Psychology, Publications / / ,

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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Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

/ Ayahuasca, Depressive Disorders, Papers, Psychology, Publications / / , , , , , ,

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.

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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Psychedelics Promote Structural and Functional Neural Plasticity

/ Depressive Disorders, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / / , , , , , ,

Abstract

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders.
Ly, C., Greb, A. C., Cameron, L. P., Wong, J. M., Barragan, E. V., Wilson, P. C., … & Duim, W. C. (2018). Psychedelics Promote Structural and Functional Neural Plasticity. Cell reports, 23(11), 3170-3182. 10.1016/j.celrep.2018.05.022
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Cardiac arrest after ibogaine intoxication

/ Iboga / Ibogaine, Papers, Psychiatry & Medicine, Publications / / ,

Abstract

Ibogaine is a psychoactive herbal medication with alleged antiaddiction properties. We report a case of ibogaine intoxication mimicking Long-QT syndrome resulting in ventricular flutter and nearby cardiac arrest. A 61-year-old man experienced massive QT prolongation and ventricular flutter at a rate of 270 beats per minute requiring defibrillation after ingestion of a large dose of Ibogaine. The ingested dose of 65-70 mg/kg represents the highest survived ibogaine dose reported to date. As a result of the long plasma half-life of ibogaine, it took 7 days for the patient’s QT interval to normalize.

Steinberg, C., & Deyell, M. W. (2018). Cardiac arrest after ibogaine intoxication. Journal of arrhythmia, 34(4), 455-457.,  10.1002/joa3.12061

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Dark Classics in Chemical Neuroscience: Mescaline

/ Biology & Ethnobotany, Humanities & Art, Mescaline / Cacti, Neuroscience, Papers, Psychology, Publications / / ,

Abstract

Archeological studies in the United States, Mexico, and Peru suggest that mescaline, as a cactus constituent, has been used for more than 6000 years. Although it is a widespread cactus alkaloid, it is present in high concentrations in few species, notably the North American peyote ( Lophophora williamsii) and the South American wachuma ( Trichocereus pachanoi, T. peruvianus, and T. bridgesii). Spanish 16th century chroniclers considered these cacti “diabolic”, leading to their prohibition, but their use persisted to our days and has been spreading for the last 150 years. In the late 1800s, peyote attracted scientific attention; mescaline was isolated, and its role in the psychedelic effects of peyote tops or “mescal buttons” was demonstrated. Its structure was established by synthesis in 1929, and alternative routes were developed, providing larger amounts for pharmacological and biosynthetic research. Although its effects are attributed mainly to its action as a 5-HT2Aserotonin receptor agonist, mescaline binds in a similar concentration range to 5-HT1A and α2A receptors. It is largely excreted unchanged in human urine, and its metabolic products are apparently unrelated to its psychedelic properties. Its low potency is probably responsible for its relative neglect by recreational substance users, as the successful search for structure-activity relationships in the hallucinogen field focused largely on finding more potent analogues. Renewed interest in the possible therapeutic applications of psychedelic drugs may hopefully lead to novel insights regarding the commonalities and differences between the actions of individual classic hallucinogens.
Cassels, B., & Sáez-Briones, P. (2018). Dark Classics in Chemical Neuroscience: Mescaline. ACS chemical neuroscience. 10.1021/acschemneuro.8b00215
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Journal Club #28: Efficacy and Safety of Psilocybin in Treatment-Resistant Depression: Results of the EPIsoDE Trial - October 6

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