OPEN Foundation

Day: 14 February 2017

Altered Insula Connectivity Under MDMA

February 14, 2017 / MDMA, Neuroscience, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , , , , , ,

Abstract

Recent work with noninvasive human brain imaging has started to investigate the effects of 3, 4-methylenedioxymethamphetamine (MDMA) on large-scale patterns of brain activity. MDMA, a potent monoamine-releaser with particularly pronounced serotonin- releasing properties, has unique subjective effects that include: marked positive mood, pleasant/unusual bodily sensations and pro-social, empathic feelings. However, the neurobiological basis for these effects is not properly understood, and the present analysis sought to address this knowledge gap. To do this, we administered MDMA-HCl (100 mg p.o.) and, separately, placebo (ascorbic acid) in a randomized, double-blind, repeated-measures design with twenty-five healthy volunteers undergoing fMRI scanning. We then employed a measure of global resting-state functional brain connectivity and follow-up seed-to-voxel analysis to the fMRI data we acquired. Results revealed decreased right insula/salience network functional connectivity under MDMA. Furthermore, these decreases in right insula/salience network connectivity correlated with baseline trait anxiety and acute experiences of altered bodily sensations under MDMA. The present findings highlight insular disintegration (ie, compromised salience network membership) as a neurobiological signature of the MDMA experience, and relate this brain effect to trait anxiety and acutely altered bodily sensations-both of which are known to be associated with insular functioning.

Walpola, I. C., Nest, T., Roseman, L., Erritzoe, D., Feilding, A., Nutt, D. J., & Carhart-Harris, R. L. (2017). Altered Insula Connectivity Under MDMA. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology. 10.1038/npp.2017.35
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Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide in Healthy Subjects

February 14, 2017 / LSD, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , , , , ,

Abstract

Background and Objective: Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. The aim of the present study was to characterize the pharmacokinetics and exposure–response relationship of oral LSD.

Methods: We analyzed pharmacokinetic data from two published placebo-controlled, double-blind, cross-over studies using oral administration of LSD 100 and 200 µg in 24 and 16 subjects, respectively. The pharmacokinetics of the 100-µg dose is shown for the first time and data for the 200-µg dose were reanalyzed and included. Plasma concentrations of LSD, subjective effects, and vital signs were repeatedly assessed. Pharmacokinetic parameters were determined using compartmental modeling. Concentration-effect relationships were described using pharmacokinetic-pharmacodynamic modeling.

Results: Geometric mean (95% confidence interval) maximum plasma concentration values of 1.3 (1.2–1.9) and 3.1 (2.6–4.0) ng/mL were reached 1.4 and 1.5 h after administration of 100 and 200 µg LSD, respectively. The plasma half-life was 2.6 h (2.2–3.4 h). The subjective effects lasted (mean ± standard deviation) 8.2 ± 2.1 and 11.6 ± 1.7 h for the 100- and 200-µg LSD doses, respectively. Subjective peak effects were reached 2.8 and 2.5 h after administration of LSD 100 and 200 µg, respectively. A close relationship was observed between the LSD concentration and subjective response within subjects, with moderate counterclockwise hysteresis. Half-maximal effective concentration values were in the range of 1 ng/mL. No correlations were found between plasma LSD concentrations and the effects of LSD across subjects at or near maximum plasma concentration and within dose groups.

Conclusions: The present pharmacokinetic data are important for the evaluation of clinical study findings (e.g., functional magnetic resonance imaging studies) and the interpretation of LSD intoxication. Oral LSD presented dose-proportional pharmacokinetics and first-order elimination up to 12 h. The effects of LSD were related to changes in plasma concentrations over time, with no evidence of acute tolerance.

Dolder, P. C., Schmid, Y., Steuer, A. E., Kraemer, T., Rentsch, K. M., Hammann, F., & Liechti, M. E. (2017). Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide in Healthy Subjects. Clinical Pharmacokinetics, 1-12. 10.1007/s40262-017-0513-9

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The association of psychedelic use and opioid use disorders among illicit users in the United States

February 14, 2017 / Addiction, Other substances, Papers, Psychology, Publications / By / , , , , ,

Abstract

Background: Preliminary studies show psychedelic compounds administered with psychotherapy are potentially effective and durable substance misuse interventions. However, little is known about the association between psychedelic use and substance misuse in the general population. This study investigated the association between psychedelic use and past year opioid use disorders within illicit opioid users.

Methods: While controlling for socio-demographic covariates and the use of other substances, the relationship between classic psychedelic use and past year opioid use disorders was analyzed within 44,000 illicit opioid users who completed the National Survey on Drug Use and Health from 2008 to 2013.

Results: Among respondents with a history of illicit opioid use, psychedelic drug use is associated with 27% reduced risk of past year opioid dependence (weighted risk ratio = 0.73 (0.60–0.89) p = 0.002) and 40% reduced risk of past year opioid abuse (weighted risk ratio = 0.60 (0.41–0.86) p = 0.006). Other than marijuana use, which was associated with 55% reduced risk of past year opioid abuse (weighted risk ratio = 0.45 (0.30–0.66) p < 0.001), no other illicit drug was associated with reduced risk of past year opioid dependence or abuse.

Conclusion: Experience with psychedelic drugs is associated with decreased risk of opioid abuse and dependence. Conversely, other illicit drug use history is largely associated with increased risk of opioid abuse and dependence. These findings suggest that psychedelics are associated with positive psychological characteristics and are consistent with prior reports suggesting efficacy in treatment of substance use disorders.

Pisano, V. D., Putnam, N. P., Kramer, H. M., Franciotti, K. J., Halpern, J. H., & Holden, S. C. (2017). The association of psychedelic use and opioid use disorders among illicit users in the United States. Journal of Psychopharmacology, 0269881117691453.

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30 April - Q&A with Rick Strassman

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