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Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials.

January 21, 2020 / Depressive Disorders, LSD, Papers, Psychology, Publications, Substance Use Disorder / By / , , , ,

Abstract

Lysergic acid diethylamide (LSD) was studied from the 1950s to the 1970s to evaluate behavioral and personality changes, as well as remission of psychiatric symptoms in various disorders. LSD was used in the treatment of anxiety, depression, psychosomatic diseases and addiction. However, most of the studies were not performed under contemporary standards, and it has taken several decades for a resurgence of interest in LSD research and its therapeutic potential for psychiatry. The aim of this review is to identify controlled and randomized clinical trials that assess the potential use of LSD in psychiatry. PRISMA guidelines for systematic review were followed. A literature search of PubMed and Psychedelic bibliography from Multidisciplinary Association for Psychedelic Studies (MAPS) databases was performed as well as a manual search of references from evaluated studies. Only randomized-controlled clinical trials were included. Study quality was systematically calculated by using the Cochrane Collaboration Tool for assessing risk of bias. A final selection of 11 articles was made after considering inclusion and exclusion criteria. LSD was administered to 567 patients in a dose ranging from 20 to 800 mcg. Despite the design heterogeneity of clinical trials, positive results were observed, thus revealing the therapeutic potential of LSD to reduce psychiatric symptomatology, mainly in alcoholism. The vast majority of authors describe significant and positive short-term changes in patients, despite the fact that in some studies an important homogenization was observed between the LSD treatment group and control group at long-term follow-up. Multiple variables regarding LSD treatment therapeutic approach and quality of experience were revealed and related to therapeutic outcomes. LSD is revealed as a potential therapeutic agent in psychiatry; the evidence to date is strongest for the use of LSD in the treatment of alcoholism. Despite the difficulty of designing proper double blind clinical trials with this substance, new studies that conform to modern standards are necessary in order to strengthen our knowledge on its use and open new doors in the future.
Fuentes, J. J., Fonseca, F., Elices, M., Farre, M., & Torrens, M. (2019). Therapeutic use of LSD in psychiatry: A systematic review of randomized-controlled clinical trials. Frontiers in Psychiatry, 10, 943., https://doi.org/10.3389/fpsyt.2019.00943
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[From Adam to ecstacy; legal use of MDMA in the 1970s and 1980s]

January 18, 2020 / Humanities & Art, MDMA, Papers, Psychology, Publications / By

Abstract

MDMA is currently a controversial psychedelic in the Netherlands: it is banned under the Opium Act, but widely used as a recreational drug. According to the government, the normalization of MDMA must be combated, others argue in favour of legalization. Meanwhile, in recent years psychiatry has become interested in renewed therapeutic use of MDMA.<br/> AIM: To place the current discussion of MDMA in the context of recent history. What can we learn from the way MDMA was used in America and Western Europe in the period between the (re)discovery of the drug in the 1970s and its legal prohibition in the 1980s?<br/> METHOD: Survey of the literature on the history of MDMA, and additional source research.<br/> CONCLUSION: In the period before MDMA became illegal, its use was closely linked to the pursuit of self-actualisation in therapeutic, spiritual and recreational contexts. History shows that the meaning that people attach to a psychoactive substance like MDMA is highly dependent on the context of use. Like all drugs, MDMA also has multiple functionalities and ‘framings’. The psychoactive substance cannot be reduced to one valuation or essence.
Blok, G. (2020). From Adam to ecstacy; legal use of MDMA in the 1970s and 1980s. Tijdschrift Voor Psychiatrie, 62(8), 702-706., https://pubmed.ncbi.nlm.nih.gov/32816299/
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Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression

January 16, 2020 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / By / , , , , ,

Abstract

BACKGROUND:

Psilocybin has shown promise as a treatment for depression but its therapeutic mechanisms are not properly understood. In contrast to the presumed actions of antidepressants, we recently found increased amygdala responsiveness to fearful faces one day after open-label treatment with psilocybin (25 mg) in 19 patients with treatment-resistant depression, which correlated with treatment efficacy.

AIMS:

Aiming to further unravel the therapeutic mechanisms of psilocybin, the present study extends this basic activation analysis. We hypothesised changed amygdala functional connectivity, more precisely decreased amygdala-ventromedial prefrontal cortex functional connectivity, during face processing after treatment with psilocybin.

METHODS:

Psychophysiological interaction analyses were conducted on functional magnetic resonance imaging data from a classic face/emotion perception task, with the bilateral amygdala and ventromedial prefrontal cortex time-series as physiological regressors. Average parameter estimates (beta weights) of significant clusters were correlated with clinical outcomes at one week.

RESULTS:

Results showed decreased ventromedial prefrontal cortex-right amygdala functional connectivity during face processing post- (versus pre-) treatment; this decrease was associated with levels of rumination at one week. This effect was driven by connectivity changes in response to fearful and neutral (but not happy) faces. Independent whole-brain analyses also revealed a post-treatment increase in functional connectivity between the amygdala and ventromedial prefrontal cortex to occipital-parietal cortices during face processing.

CONCLUSION:

These results are consistent with the idea that psilocybin therapy revives emotional responsiveness on a neural and psychological level, which may be a key treatment mechanism for psychedelic therapy. Future larger placebo-controlled studies are needed to examine the replicability of the current findings.

Mertens, L. J., Wall, M. B., Roseman, L., Demetriou, L., Nutt, D. J., & Carhart-Harris, R. L. (2020). Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression. Journal of Psychopharmacology, 10.1177/0269881119895520
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Psilocybin Induces Time-Dependent Changes in Global Functional Connectivity

January 13, 2020 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / By / , , , , , ,

Abstract

Background

The use of psilocybin in scientific and experimental clinical contexts has triggered renewed interest in the mechanism of action of psychedelics. However, its time-dependent systems-level neurobiology remains sparsely investigated in humans.

Methods

We conducted a double-blind, randomized, counterbalanced, crossover study comprising 23 healthy human participants who received placebo and 0.2 mg/kg of psilocybin orally on 2 different test days. Participants underwent magnetic resonance imaging at 3 time points between administration and peak effects: 20 minutes, 40 minutes, and 70 minutes after administration. Resting-state functional connectivity was quantified via a data-driven global brain connectivity method and compared with cortical gene expression maps.

Results

Psilocybin reduced associative, but concurrently increased sensory, brain-wide connectivity. This pattern emerged over time from administration to peak effects. Furthermore, we showed that baseline connectivity is associated with the extent of psilocybin-induced changes in functional connectivity. Lastly, psilocybin-induced changes correlated in a time-dependent manner with spatial gene expression patterns of the 5-HT2A (5-hydroxytryptamine 2A) and 5-HT1A (5-hydroxytryptamine 1A) receptors.

Conclusions

These results suggest that the integration of functional connectivity in sensory regions and the disintegration in associative regions may underlie the psychedelic state and pinpoint the critical role of the serotonin 2A and 1A receptor systems. Furthermore, baseline connectivity may represent a predictive marker of the magnitude of changes induced by psilocybin and may therefore contribute to a personalized medicine approach within the potential framework of psychedelic treatment.

Preller, K. H., Duerler, P., Burt, J. B., Ji, J. L., Adkinson, B., Stämpfli, P., … & Anticevic, A. (2020). Psilocybin induces time-dependent changes in global functional connectivity: Psi-induced changes in brain connectivity. Biological Psychiatry., 10.1016/j.biopsych.2019.12.027
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In vivo effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in rodents: Drug discrimination and thermoregulation.

January 13, 2020 / Anxiety Disorders / PTSD, MDMA, Papers, Pharmacology & Chemistry, Psychiatry & Medicine, Publications / By / , , ,

Abstract

BACKGROUND:

Recent clinical studies support the use of 3,4-methylenedioxymethamphetamine (MDMA) as an adjunct treatment for posttraumatic stress disorder (PTSD). Despite these promising findings, MDMA administration in controlled settings can increase blood pressure, heart rate, and body temperature. Previous studies indicate thatO-demethylated metabolites of MDMA contribute to its adverse effects. As such, limiting the conversion of MDMA to reactive metabolites may mitigate some of its adverse effects and potentially improve its safety profile for therapeutic use.

METHODS:

We compared the interoceptive and hyperthermic effects of a deuterium-substituted form of MDMA (d2-MDMA) to MDMA using rodent drug discrimination and biotelemetry procedures, respectively.

RESULTS:

Compared to MDMA, d2-MDMA produced full substitution for a 1.5 mg/kg MDMA training stimulus with equal potency and effectiveness in the drug discrimination experiment. In addition, d2-MDMA produced increases in body temperature that were shorter-lasting and of lower magnitude compared to equivalent doses of MDMA. Last, d2-MDMA and MDMA were equally effective in reversing the hypothermic effects of the selective 5-HT2A/2C antagonist ketanserin.

CONCLUSION:

These findings indicate that deuterium substitution of hydrogen at the methylenedioxy ring moiety does not impact MDMA’s interoceptive effects, and compared to MDMA, d2-MDMA has less potential for producing hyperthermic effects and likely has similar pharmacodynamic properties. Given that d2-MDMA produces less adverse effects than MDMA, but retains similar desirable effects that are thought to relate to the effective treatment of PTSD, additional investigations into its effects on cardiovascular functioning and pharmacokinetic properties are warranted.

Berquist, M. D., Leth-Petersen, S., Kristensen, J. L., & Fantegrossi, W. E. (2020). In vivo effects of 3, 4-methylenedioxymethamphetamine (MDMA) and its deuterated form in rodents: drug discrimination and thermoregulation. Drug and Alcohol Dependence, 107850., 10.1016/j.drugalcdep.2020.107850
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Antidepressant and neurocognitive effects of serial ketamine administration versus ECT in depressed patients

January 13, 2020 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Publications / By / , , , , , ,

Abstract

BACKGROUND:

While electroconvulsive therapy (ECT) is considered the gold standard for acute treatment of patients with otherwise treatment-resistant depression, ketamine has recently emerged as a fast-acting treatment alternative for these patients. Efficacy and onset of action are currently among the main factors that influence clinical decision making, however, the effect of these treatments on cognitive functions should also be a crucial point, given that cognitive impairment in depression is strongly related to disease burden and functional recovery. ECT is known to induce transient cognitive impairment, while little is known about ketamine’s impact on cognition. This study therefore aims to compare ECT and serial ketamine administration not only with regard to their antidepressant efficacy but also to acute neurocognitive effects.

METHODS:

Fifty patients suffering from depression were treated with either serial ketamine infusions or ECT. Depression severity and cognitive functions were assessed before, during, and after treatment.

RESULTS:

ECT and ketamine administration were equally effective, however, the antidepressant effects of ketamine occurred faster. Ketamine improved neurocognitive functioning, especially attention and executive functions, whereas ECT was related to a small overall decrease in cognitive performance.

CONCLUSIONS:

Due to its pro-cognitive effects and faster antidepressant effect, serial ketamine administration might be a more favorable short-term treatment option than ECT.

LIMITATIONS:

As this research employed a naturalistic study design, patients were not systematically randomized, there was no control group and patients received concurrent and partially changing medications during treatment.

CLINICAL TRIALS REGISTRATION:

Functional and Metabolic Changes in the Course of Antidepressive Treatment, https://clinicaltrials.gov/ct2/show/NCT02099630, NCT02099630.

Basso, L., Bönke, L., Aust, S., Gärtner, M., Heuser-Collier, I., Otte, C., … & Grimm, S. (2020). Antidepressant and neurocognitive effects of serial ketamine administration versus ECT in depressed patients. Journal of Psychiatric Research.,  10.1016/j.jpsychires.2020.01.002

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A Dangerous Method? Psychedelic Therapy at Modum Bad, Norway, 1961-76

January 13, 2020 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

After many years of disregard, the use of psychedelic drugs in psychiatric treatment has re-emerged in recent years. The prospect that psychedelics may again be integrated into mainstream psychiatry has aroused interest in long-forgotten research and experience from the previous phase of psychedelic therapy, which lasted from the late 1940s to the 1970s. This article will discuss one large-scale psychedelic therapy programme at Modum Bad Nervesanatorium, a psychiatric clinic which treated 379 inpatients with psychedelic drugs during the years 1961-76. The psychiatrists there initially regarded the psychedelic treatment as efficacious and without serious negative reactions, but reports of long-term harm have since surfaced. This article discusses how insights from Modum Bad might benefit the new generation of psychedelic treatment efforts.
Johnstad, P. G. (2020). A dangerous method? Psychedelic therapy at Modum Bad, Norway, 1961–76. History of Psychiatry, 31(2), 217-226., https://doi.org/10.1177%2F0957154X19894537
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Ayahuasca’s ‘afterglow’: improved mindfulness and cognitive flexibility in ayahuasca drinkers.

January 11, 2020 / Ayahuasca, Papers, Psychology, Publications / By / ,

Abstract

RATIONALE:
There is a growing body of evidence demonstrating the therapeutic potential of ayahuasca for treating depression and anxiety. However, the mechanisms of action involved in ayahuasca’s therapeutic effects are unclear. Mindfulness and cognitive flexibility may be two possible psychological mechanisms. Like other classic psychedelics, ayahuasca also leads to an ‘afterglow’ effect of improved subjective well-being that persists after the acute effects have subsided. This period may offer a window of increased therapeutic potential.
OBJECTIVE:
To explore changes in mindfulness and cognitive flexibility before and within 24 h after ayahuasca use.METHODS:
Forty-eight participants (54% female) were assessed on measures of mindfulness (Five Facets Mindfulness Questionnaire (FFMQ)), decentering (Experiences Questionnaire (EQ)), and cognitive flexibility (Cognitive Flexibility Scale (CFS)), and completed the Stroop and Wisconsin Picture Card Sorting Task (WPCST) before drinking ayahuasca, and again within 24 h.
RESULTS:
Mindfulness (FFMQ total scores and four of the five mindfulness facets: observe, describe, act with awareness, and non-reactivity) and decentering (EQ) significantly increased in the 24 h after ayahuasca use. Cognitive flexibility (CFS and WPCST) significantly improved in the 24 h after ayahuasca use. Changes in both mindfulness and cognitive flexibility were not influenced by prior ayahuasca use.
CONCLUSIONS:
The present study supports ayahuasca’s ability to enhance mindfulness and further reports changes in cognitive flexibility in the ‘afterglow’ period occur, suggesting both could be possible psychological mechanisms concerning the psychotherapeutic effects of ayahuasca. Given psychological gains occurred regardless of prior ayahuasca use suggests potentially therapeutic effects for both naïve and experienced ayahuasca drinkers.
Murphy-Beiner, A., & Soar, K. (2020). Ayahuasca’s ‘afterglow’: improved mindfulness and cognitive flexibility in ayahuasca drinkers. Psychopharmacology, 1-9., https://doi.org/10.1007/s00213-019-05445-3
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Ayahuasca's 'afterglow': improved mindfulness and cognitive flexibility in ayahuasca drinkers.

January 11, 2020 / Ayahuasca, Papers, Psychology, Publications / By / ,

Abstract

RATIONALE:
There is a growing body of evidence demonstrating the therapeutic potential of ayahuasca for treating depression and anxiety. However, the mechanisms of action involved in ayahuasca’s therapeutic effects are unclear. Mindfulness and cognitive flexibility may be two possible psychological mechanisms. Like other classic psychedelics, ayahuasca also leads to an ‘afterglow’ effect of improved subjective well-being that persists after the acute effects have subsided. This period may offer a window of increased therapeutic potential.
OBJECTIVE:
To explore changes in mindfulness and cognitive flexibility before and within 24 h after ayahuasca use.METHODS:
Forty-eight participants (54% female) were assessed on measures of mindfulness (Five Facets Mindfulness Questionnaire (FFMQ)), decentering (Experiences Questionnaire (EQ)), and cognitive flexibility (Cognitive Flexibility Scale (CFS)), and completed the Stroop and Wisconsin Picture Card Sorting Task (WPCST) before drinking ayahuasca, and again within 24 h.
RESULTS:
Mindfulness (FFMQ total scores and four of the five mindfulness facets: observe, describe, act with awareness, and non-reactivity) and decentering (EQ) significantly increased in the 24 h after ayahuasca use. Cognitive flexibility (CFS and WPCST) significantly improved in the 24 h after ayahuasca use. Changes in both mindfulness and cognitive flexibility were not influenced by prior ayahuasca use.
CONCLUSIONS:
The present study supports ayahuasca’s ability to enhance mindfulness and further reports changes in cognitive flexibility in the ‘afterglow’ period occur, suggesting both could be possible psychological mechanisms concerning the psychotherapeutic effects of ayahuasca. Given psychological gains occurred regardless of prior ayahuasca use suggests potentially therapeutic effects for both naïve and experienced ayahuasca drinkers.
Murphy-Beiner, A., & Soar, K. (2020). Ayahuasca’s ‘afterglow’: improved mindfulness and cognitive flexibility in ayahuasca drinkers. Psychopharmacology, 1-9., https://doi.org/10.1007/s00213-019-05445-3
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Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer.

January 9, 2020 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

BACKGROUND:
A recently published randomized controlled trial compared single-dose psilocybin with single-dose niacin in conjunction with psychotherapy in participants with cancer-related psychiatric distress. Results suggested that psilocybin-assisted psychotherapy facilitated improvements in psychiatric and existential distress, quality of life, and spiritual well-being up to seven weeks prior to the crossover. At the 6.5-month follow-up, after the crossover, 60-80% of participants continued to meet criteria for clinically significant antidepressant or anxiolytic responses.
METHODS:
The present study is a long-term within-subjects follow-up analysis of self-reported symptomatology involving a subset of participants that completed the parent trial. All 16 participants who were still alive were contacted, and 15 participants agreed to participate at an average of 3.2 and 4.5 years following psilocybin administration.
RESULTS:
Reductions in anxiety, depression, hopelessness, demoralization, and death anxiety were sustained at the first and second follow-ups. Within-group effect sizes were large. At the second (4.5 year) follow-up approximately 60-80% of participants met criteria for clinically significant antidepressant or anxiolytic responses. Participants overwhelmingly (71-100%) attributed positive life changes to the psilocybin-assisted therapy experience and rated it among the most personally meaningful and spiritually significant experiences of their lives.
CONCLUSION:
These findings suggest that psilocybin-assisted psychotherapy holds promise in promoting long-term relief from cancer-related psychiatric distress. Limited conclusions, however, can be drawn regarding the efficacy of this therapy due to the crossover design of the parent study. Nonetheless, the present study adds to the emerging literature base suggesting that psilocybin-facilitated therapy may enhance the psychological, emotional, and spiritual well-being of patients with life-threatening cancer.
Agin-Liebes, G. I., Malone, T., Yalch, M. M., Mennenga, S. E., Ponté, K. L., Guss, J., … & Ross, S. (2020). Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. Journal of Psychopharmacology, 0269881119897615., https://doi.org/10.1177%2F0269881119897615
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