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Therapeutic Application

Capturing the different health conditions that PAP may adress

Psilocybin with psychological support for treatment-resistant depression: six-month follow-up

November 8, 2017 / Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Rationale

Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy.

Objectives

Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression.

Methods

Twenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure.

Results

Treatment was generally well tolerated. Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen’s d = 2.2 at week 1 and 2.3 at week 5, both p < 0.001); nine and four patients met the criteria for response and remission at week 5. Results remained positive at 3 and 6 months (Cohen’s d = 1.5 and 1.4, respectively, both p < 0.001). No patients sought conventional antidepressant treatment within 5 weeks of psilocybin. Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience.

Conclusions

Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort. Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomised control trials.

Carhart-Harris, R. L., Bolstridge, M., Day, C. M. J., Rucker, J., Watts, R., Erritzoe, D. E., … & Rickard, J. A. (2017). Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology, 1-10. 10.1007/s00213-017-4771-x
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Why MDMA therapy for alcohol use disorder? And why now?

November 7, 2017 / MDMA, Papers, Psychology, Publications, Substance Use Disorder / By /

Abstract

Alcohol use disorder represents a serious clinical, social and personal burden on its sufferers and a significant financial strain on society. Current treatments, both psychological and pharmacological are poor, with high rates of relapse after medical detoxification and dedicated treatment programs. The earliest historical roots of psychedelic drug-assisted psychotherapy in the 1950s were associated with Lysergic acid diethylamide (LSD)-assisted psychotherapy to treat what was then called, alcoholism. But results were varied and psychedelic therapy with LSD and other ‘classical’ psychedelics fell out of favour in the wake of socio-political pressures and cultural changes. A current revisiting of psychedelic clinical research is now targeting substance use disorders – and particularly alcohol use disorder – again. 3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy has never been formally explored as a treatment for any form of substance use disorder. But in recent years MDMA has risen in prominence as an agent to treat posttraumatic stress disorder (PTSD). With its unique receptor profile and a relatively well-tolerated subjective experience of drug effects when used clinically, MDMA Therapy is ideally suited to allow a patient to explore and address painful memories without being overwhelmed by negative affect. Given that alcohol use disorder is so often associated with early traumatic experiences, the author is proposing in a current on-going UK-based study that patients with alcohol use disorder who have undergone a medical detoxification from alcohol might benefit from a course of MDMA-assisted psychotherapy.

Sessa, B. (2017). Why MDMA therapy for alcohol use disorder? And why now?. Neuropharmacology. 10.1016/j.neuropharm.2017.11.004
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Dying to live: The power of transcendence in the treatment of existential anxiety

November 2, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

There is a notable lack of effective treatments and therapies available for the treatment of existential anxiety. There are, however, a number of avenues worthy of more attention, all experiential or using insights gained from experiences. Such experiences include near-death experiences (NDEs), out-of-body experiences (OBEs) and those yielded by classical psychedelics such as psilocybin. Of these, the psychedelics may have a particular utility when it comes to the treatment of existential anxiety. Psychedelics are currently undergoing a long-overdue scientific research renaissance, and there has been some highly promising research utilizing psilocybin in the treatment of existential anxiety and depression in terminally ill cancer patients, yielding compelling and robust findings. A single dose of psilocybin produced immediate and sustained decreases in anxiety and depression and improvements in outlook and life meaning in an overwhelming majority of study participants. At sufficient doses, psychedelics can occasion mystical-type experiences, and it appears this is intimately tied to their long-term psychotherapeutic efficacy. There is some intriguing overlap in aftereffects reported by those who have undergone mystical experiences via psychedelics, NDEs, and OBEs. An interesting property of the NDE is that the psychological changes appear to be mentally contagious, so that one may reap the benefits of the experience without incurring the risk of experiencing one. A common thread and apparently psychotherapeutic element linking these experiences is the experience of being disembodied and of transcending the limits of the body.
Gandy, S. (2017). Dying to live: The power of transcendence in the treatment of existential anxiety. Threshold: Journal of Interdisciplinary Consciousness Studies, 1(2), 25-36.
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Antidepressant Response and Dissociative Effects After Ketamine Treatment: Two Sides of the Same Coin?

November 1, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , ,

Abstract

In recent years, there has been growing interest in research on N-methyl-d-aspartate (NMDA) antagonists as rapid-acting agents for treating depression1 and related suicidal ideation.2 Ketamine has shown preliminary efficacy for the rapid treatment of both unipolar and bipolar depression, although it has been also associated with high rates of dissociative and psychotomimetic symptoms, especially within 60 minutes after the infusion.3 For this reason, we read with great interest the update recently published in JCP4 that synthesized issues related to efficacy, adverse effects, and mechanism of action of ketamine for treating depression. In particular, in analyzing ketamine-related adverse effects, this overview highlighted that subanesthetic doses of ketamine may induce dissociative and psychotomimetic symptoms, although these effects are often mild and short-lasting.4 In addition, the authors of a recent review5 suggest that intranasal route of administration and lower doses of ketamine, as well as alternative NMDA-modulating agents, all might mitigate dissociative and psychotomimetic effects.

However, ketamine-induced dissociative symptoms, whether therapeutic or side effects, may deserve additional insight. Findings from a randomized controlled trial6 showed that significant, though transient, dissociative effects can occur after ketamine infusion in about 1 out of 5 subjects with treatment-resistant depression. However, a significant correlation between dissociative symptoms 40 minutes after ketamine infusion and improvement in depressive symptoms (230 minutes and 7 days after infusion) has been reported in subjects with treatment-resistant major depressive or bipolar disorder.7 Among the potential mediators tested, only dissociative effects predicted a robust and sustained antidepressant response attributable to ketamine. This issue may well be supported by a biological rationale, since dissociative symptoms may be the consequence of the enhancement of glutamate release induced by ketamine.7 In addition, a recent study based on a retrospective chart review8 evaluating efficacy and safety of intravenous subanesthetic doses of esketamine in 27 subjects with treatment-resistant or bipolar depression found that mild to severe dissociative symptoms occurred in about one tenth of subjects. Nevertheless, 2 out of 3 subjects with dissociative symptoms remitted from depression within 3 weeks after esketamine infusion. Thus, also in this case, it seems that ketamine-related dissociation and therapeutic efficacy might be linked, possibly as “two sides of the same coin.” Nonetheless, available evidence is limited and not conclusive, since other studies, although based on small sample sizes, showed that dissociative symptoms were not correlated with changes in depression scores9 or could be even associated with suicidal ideation.10 Although a number of different factors involved in the efficacy of ketamine can be hypothesized,11 including induced psychotomimetic effects,12 the mechanisms of its antidepressant activity are far from being fully understood. In particular, it should be elucidated if transient dissociative effects induced by ketamine should be considered physiological conditions linked to antidepressant response, rather than intrinsic side effects that could decrease clinical confidence in terms of tolerability. Research should clarify strategies that can decrease ketamine-induced dissociative effects5 while not challenging its promising antidepressant properties.

Bartoli, F., Clerici, M., & Carrà, G. (2017). Antidepressant Response and Dissociative Effects After Ketamine Treatment: Two Sides of the Same Coin?. The Journal of clinical psychiatry, 78(9), e1318. 10.4088/JCP.17lr11789
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Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression

October 30, 2017 / Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Rationale

Depressed patients robustly exhibit affective biases in emotional processing which are altered by SSRIs and predict clinical outcome.

Objectives

The objective of this study is to investigate whether psilocybin, recently shown to rapidly improve mood in treatment-resistant depression (TRD), alters patients’ emotional processing biases.

Methods

Seventeen patients with treatment-resistant depression completed a dynamic emotional face recognition task at baseline and 1 month later after two doses of psilocybin with psychological support. Sixteen controls completed the emotional recognition task over the same time frame but did not receive psilocybin.

Results

We found evidence for a group × time interaction on speed of emotion recognition (p = .035). At baseline, patients were slower at recognising facial emotions compared with controls (p < .001). After psilocybin, this difference was remediated (p = .208). Emotion recognition was faster at follow-up compared with baseline in patients (p = .004, d = .876) but not controls (p = .263, d = .302). In patients, this change was significantly correlated with a reduction in anhedonia over the same time period (r = .640, p = .010).

Conclusions

Psilocybin with psychological support appears to improve processing of emotional faces in treatment-resistant depression, and this correlates with reduced anhedonia. Placebo-controlled studies are warranted to follow up these preliminary findings.

Stroud, J. B., Freeman, T. P., Leech, R., Hindocha, C., Lawn, W., Nutt, D. J., … & Carhart-Harris, R. L. (2017). Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression. Psychopharmacology, 1-8. 10.1007/s00213-017-4754-y
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Subjective effectiveness of ibogaine treatment for problematic opioid consumption: Short- and long-term outcomes and current psychological functioning

October 17, 2017 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / , , , ,

Abstract

Background and aims

Very few studies have reported the effectiveness of ibogaine as a treatment for chronic opioid use. Therefore, this study evaluated the acute subjective effects of ibogaine, outcomes on problematic opioid consumption, and the long-term associations with psychological functioning.

Methods

Using online data collection, 88 patients who received ibogaine treatment in Mexico between 2012 and 2015 completed our survey.

Results

Most participants (72%) had used opioids for at least 4 years and 69% reported daily use. Most (80%) indicated that ibogaine eliminated or drastically reduced withdrawal symptoms. Fifty percent reported that ibogaine reduced opioid craving, some (25%) reporting a reduction in craving lasting at least 3 months. Thirty percent of participants reported never using opioids again following ibogaine treatment. And over one half (54%) of these abstainers had been abstinent for at least 1 year, with 31% abstinent for at least 2 years. At the time of survey, 41% of all participants reported sustained abstinence (>6 months). Although 70% of the total sample reported a relapse following treatment, 48% reported decreased use from pretreatment levels and an additional 11% eventually achieved abstinence. Treatment responders had the lowest rates of depressive and anxious symptoms, the highest levels of subjective well-being and rated their ibogaine treatment as more spiritually meaningful compared with treatment non-responders.

Conclusion

The results suggest that ibogaine is associated with reductions in opioid use, including complete abstinence, and has long-term positive psychological outcomes. Future research should investigate the efficacy of ibogaine treatment using rigorous longitudinal and controlled designs.

Davis, A. K., Barsuglia, J. P., Windham-Herman, A. M., Lynch, M., & Polanco, M. (2017). Subjective effectiveness of ibogaine treatment for problematic opioid consumption: Short-and long-term outcomes and current psychological functioning. Journal of Psychedelic Studies, (0), 1-9. 10.1556/2054.01.2017.009
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Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms

October 13, 2017 / Depressive Disorders, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. A ‘reset’ therapeutic mechanism is proposed.
Carhart-Harris, R. L., Roseman, L., Bolstridge, M., Demetriou, L., Pannekoek, J. N., Wall, M. B., … & Leech, R. (2017). Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific reports, 7(1), 13187. 10.1038/s41598-017-13282-7
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Separating the agony from ecstasy: R(-)-3,4-methylenedioxymethamphetamine has prosocial and therapeutic-like effects without signs of neurotoxicity in mice

October 6, 2017 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , , ,

Abstract

S,R(+/-)-3,4-methylenedioxymethamphetamine (SR-MDMA) is an amphetamine derivative with prosocial and putative therapeutic effects. Ongoing clinical trials are investigating it as a treatment for post-traumatic stress disorder (PTSD) and other conditions. However, its potential for adverse effects such as hyperthermia and neurotoxicity may limit its clinical viability. We investigated the hypothesis that one of the two enantiomers of SR-MDMA, R-MDMA, would retain the prosocial and therapeutic effects but with fewer adverse effects. Using male Swiss Webster and C57BL/6 mice, the prosocial effects of R-MDMA were measured using a social interaction test, and the therapeutic-like effects were assessed using a Pavlovian fear conditioning and extinction paradigm relevant to PTSD. Locomotor activity and body temperature were tracked after administration, and neurotoxicity was evaluated post-mortem. R-MDMA significantly increased murine social interaction and facilitated extinction of conditioned freezing. Yet, unlike racemic MDMA, it did not increase locomotor activity, produce signs of neurotoxicity, or increase body temperature. A key pharmacological difference between R-MDMA and racemic MDMA is that R-MDMA has much lower potency as a dopamine releaser. Pretreatment with a selective dopamine D1 receptor antagonist prevented SR-MDMA-induced hyperthermia, suggesting that differential dopamine signaling may explain some of the observed differences between the treatments. Together, these results indicate that the prosocial and therapeutic effects of SR-MDMA may be separable from the stimulant, thermogenic, and potential neurotoxic effects. To what extent these findings translate to humans will require further investigation, but these data suggest that R-MDMA could be a more viable therapeutic option for the treatment of PTSD and other disorders for which SR-MDMA is currently being investigated.
Curry, D. W., Young, M. B., Tran, A. N., Daoud, G. E., & Howell, L. L. (2018). Separating the agony from ecstasy: R (–)-3, 4-methylenedioxymethamphetamine has prosocial and therapeutic-like effects without signs of neurotoxicity in mice. Neuropharmacology, 128, 196-206. 10.1016/j.neuropharm.2017.10.003
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A retrospective study of ketamine administration and the development of acute or post-traumatic stress disorder in 274 war-wounded soldiers

October 3, 2017 / Anxiety Disorders / PTSD, Ketamine, Papers, Psychology, Publications / By / , , ,

Abstract

The objective of this study was to explore whether ketamine prevents or exacerbates acute or post-traumatic stress disorders in military trauma patients. We conducted a retrospective study of a database from the French Military Health Service, including all soldiers surviving a war injury in Afghanistan (2010-2012). The diagnosis of post-traumatic stress disorder was made by a psychiatrist and patients were analysed according to the presence or absence of this condition. Analysis included the following covariables: age; sex; acute stress disorder; blast injury; associated fatality; brain injury; traumatic amputation; Glasgow coma scale; injury severity score; administered drugs; number of surgical procedures; physical, neurosensory or aesthetic sequelae; and the development chronic pain. Covariables related to post-traumatic and acute stress disorders with a p ≤ 0.10 were included in a multivariable logistic regression model. The data from 450 soldiers were identified; 399 survived, of which 274 were analysed. Among these, 98 (36%) suffered from post-traumatic stress disorder and 89 (32%) had received ketamine. Fifty-four patients (55%) in the post-traumatic stress disorder group received ketamine vs. 35 (20%) in the no PTSD group (p < 0.001). The 89 injured soldiers who received ketamine had a median (IQR [range]) injury severity score of 5 (3-13 [1-26]) vs. 3 (2-4 [1-6] in the 185 patients who did not (p < 0.001). At multivariable analysis, only acute stress disorder and total number of surgical procedures were independently associated with the development of post-traumatic stress disorder. In this retrospective study, ketamine administration was not a risk factor for the development of post-traumatic stress disorder in the military trauma setting.
Mion, G., Le Masson, J., Granier, C., & Hoffmann, C. (2017). A retrospective study of ketamine administration and the development of acute or post‐traumatic stress disorder in 274 war‐wounded soldiers. Anaesthesia. 10.1111/anae.14079
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Psychedelic Drugs in Biomedicine

September 22, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Substance Use Disorder / By / , , , ,

Abstract

Psychedelic drugs, such as lysergic acid diethylamide (LSD), mescaline, and psilocybin, exert profound effects on brain and behavior. After decades of difficulties in studying these compounds, psychedelics are again being tested as potential treatments for intractable biomedical disorders. Preclinical research of psychedelics complements human neuroimaging studies and pilot clinical trials, suggesting these compounds as promising treatments for addiction, depression, anxiety, and other conditions. However, many questions regarding the mechanisms of action, safety, and efficacy of psychedelics remain. Here, we summarize recent preclinical and clinical data in this field, discuss their pharmacological mechanisms of action, and outline critical areas for future studies of psychedelic drugs, with the goal of maximizing the potential benefits of translational psychedelic biomedicine to patients.
Kyzar, E. J., Nichols, C. D., Gainetdinov, R. R., Nichols, D. E., & Kalueff, A. V. (2017). Psychedelic Drugs in Biomedicine. Trends in Pharmacological Sciences. 10.1016/j.tips.2017.08.003
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