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Therapeutic Application

Capturing the different health conditions that PAP may adress

Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review

September 22, 2017 / Anxiety Disorders / PTSD, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , ,

Abstract

Anxiety and depression are some of the most common psychiatric symptoms of patients suffering with life-threatening diseases, often associated with a low quality of life and a poor overall prognosis. 5-HT2A-receptor agonists (serotonergic hallucinogens, ‘psychedelics’) like lysergic acid diethylamide (LSD) and psilocybin were first investigated as therapeutic agents in the 1960s. Recently, after a long hiatus period of regulatory obstacles, interest in the clinical use of these substances has resumed. The current article provides a systematic review of studies investigating psychedelics in the treatment of symptoms of existential distress in life-threatening diseases across different periods of research, highlighting how underlying concepts have developed over time. A systematic search for clinical trials from 1960 to 2017 revealed 11 eligible clinical trials involving a total number of N=445 participants, of which 7 trials investigated the use of lysergic acid diethylamide (LSD) (N=323), 3 trials investigated the use of psilocybin (N=92), and one trial investigated the use of dipropyltryptamine (DPT) (N=30). The 4 more recent randomized controlled trials (RCTs) (N=104) showed a significantly higher methodological quality than studies carried out in the 1960s and 1970s. Evidence supports that patients with life threatening diseases associated with symptoms of depression and anxiety benefit from the anxiolytic and antidepressant properties of serotonergic hallucinogens. Some studies anecdotally reported improvements in patients´ quality of life and reduced fear of death. Moreover, low rates of side effects were reported in studies that adhered to safety guidelines. Further studies are needed to determine how these results can be transferred into clinical practice.
Reiche, S., Hermle, L., Gutwinski, S., Jungaberle, H., Gasser, P., & Majić, T. (2017). Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 10.1016/j.pnpbp.2017.09.012
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Does psychedelic drug use reduce risk of suicidality? Evidence from a longitudinal community-based cohort of marginalised women in a Canadian setting

September 21, 2017 / Anthropology & Sociology, Depressive Disorders, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

OBJECTIVE:
This study aimed to longitudinally investigate whether ever having used a psychedelic drug can have a protective effect on incidence of suicidality among marginalised women.
DESIGN:
Longitudinal community-based cohort study.
SETTING:
Data were drawn from a prospective, community-based cohort of marginalised women in Metro Vancouver, Canada.
PARTICIPANTS:
766 women completed the baseline questionnaire between January 2010 and August 2014. Participants who did not report suicidality at baseline and who completed at least one follow-up visit were included.
MAIN OUTCOME MEASURE:
Extended Cox regression was used to model predictors of new suicidality (suicide ideation or attempts) over 54-month follow-up.
RESULTS:
Nearly half (46%; n=355) of participants reported prior suicidality and were thus excluded from the present analyses. Of 290 women eligible at baseline, 11% (n=31) reported recent suicidality during follow-up, with an incidence density of 4.42 per 100 person-years (95% CI 3.10 to 6.30). In multivariable analysis, reported lifetime psychedelic drug use was associated with a 60% reduced hazard for suicidality (adjusted HR (AHR) 0.40; 95% CI 0.17 to 0.94). Crystal methamphetamine use (AHR 3.25; 95% CI 1.47 to 7.21) and childhood abuse (AHR 3.54; 95% CI 1.49 to 8.40) remained independent predictors of suicidality.
CONCLUSION:
The high rate of suicidality identified in this study is of major concern. Alongside emerging evidence on the potential of psychedelic-assisted therapy to treat some mental illness and addiction issues, our findings demonstrate that naturalistic psychedelic drug use is independently associated with reduced suicidality, while other illicit drug use and childhood trauma predispose women to suicidality. While observational, this study supports calls for further investigation of the therapeutic utility of psychedelic drugs in treating poor mental health and promoting mental wellness.
Argento, E., Strathdee, S. A., Tupper, K., Braschel, M., Wood, E., & Shannon, K. (2017). Does psychedelic drug use reduce risk of suicidality? Evidence from a longitudinal community-based cohort of marginalised women in a Canadian setting. BMJ open, 7(9), e016025. 10.1136/bmjopen-2017-016025
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Psychoactive substances as a last resort—a qualitative study of self-treatment of migraine and cluster headaches

September 5, 2017 / Anthropology & Sociology, Headache Pain and Neurological Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology / By / , ,

Abstract

Background

Treatment resistant cluster headache and migraine patients are exploring alternative treatments online. The aim of this study was to improve comprehension regarding the use of non-established or alternative pharmacological treatments used by sufferers of cluster headaches and migraines.

Methods

A qualitative thematic analysis of the users’ own accounts presented in online forum discussions were conducted. The forum boards https://shroomery.org/, http://bluelight.org, and https://clusterbusters.org/ met the inclusion criteria and were used for the study.

Results

The analysis resulted in six themes: a desperate need for effective treatments; the role of the forum—finding alternative treatments and community support; alternative treatment substances; dosage and regimens; effects and treatment results; and adverse effects. The results provide an insight into why, how, and by which substances and methods sufferers seek relief from cluster headache and migraines.

Conclusions

These patients are in a desperate and vulnerable situation, and illicit psychoactive substances are often considered a last resort. There appeared to be little or no interest in psychoactive effects per se as these were rather tolerated or avoided by using sub-psychoactive doses. Primarily, psilocybin, lysergic acid diethylamide, and related psychedelic tryptamines were reportedly effective for both prophylactic and acute treatment of cluster headache and migraines. Treatment results with cannabis were more unpredictable. No severe adverse events were reported, but it was observed how desperation sometimes spurred risky behavior when obtaining and testing various treatment alternatives. The forum discourse mainly revolved around maximizing treatment results and minimizing potential harms.

Andersson, M., Persson, M., & Kjellgren, A. (2017). Psychoactive substances as a last resort—a qualitative study of self-treatment of migraine and cluster headaches. Harm Reduction Journal, 14(1), 60. 10.1186/s12954-017-0186-6

Assessing the psychedelic “after-glow” in ayahuasca users: post-acute neurometabolic and functional connectivity changes are associated with enhanced mindfulness capacities

September 1, 2017 / Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

BACKGROUND:
Ayahuasca is a plant tea containing the psychedelic 5-HT2A agonist N,N-dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism. Post-acutely, ayahuasca potentiates mindfulness capacities in volunteers and induces rapid and sustained antidepressant effects in treatment-resistant patients. However, the mechanisms underlying these fast and maintained effects are poorly understood. Here, we investigated in an open-label uncontrolled study in 16 healthy volunteers ayahuasca-induced post-acute neurometabolic and connectivity modifications and their association with mindfulness measures.
METHODS:
Using 1H-magnetic resonance spectroscopy and functional connectivity, we compared baseline and post-acute neurometabolites and seed-to-voxel connectivity in the posterior and anterior cingulate cortex after a single ayahuasca dose.
RESULTS:
Magnetic resonance spectroscopy showed post-acute reductions in glutamate+glutamine, creatine, and N-acetylaspartate+N-acetylaspartylglutamate in the posterior cingulate cortex. Connectivity was increased between the posterior cingulate cortex and the anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. Glutamate+glutamine reductions correlated with increases in the “nonjudging” subscale of the Five Facets Mindfulness Questionnaire. Increased anterior cingulate cortex-medial temporal lobe connectivity correlated with increased scores on the self-compassion questionnaire. Post-acute neural changes predicted sustained elevations in nonjudging 2 months later.
CONCLUSIONS:
These results support the involvement of glutamate neurotransmission in the effects of psychedelics in humans. They further suggest that neurometabolic changes in the posterior cingulate cortex, a key region within the default mode network, and increased connectivity between the anterior cingulate cortex and medial temporal lobe structures involved in emotion and memory potentially underlie the post-acute psychological effects of ayahuasca.
Sampedro, F., de la Fuente Revenga, M., Valle, M., Roberto, N., Domínguez-Clavé, E., Elices, M., … & Friedlander, P. (2017). Assessing the psychedelic “after-glow” in ayahuasca users: post-acute neurometabolic and functional connectivity changes are associated with enhanced mindfulness capacities. International Journal of Neuropsychopharmacology. 10.1093/ijnp/pyx036
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Assessing the psychedelic "after-glow" in ayahuasca users: post-acute neurometabolic and functional connectivity changes are associated with enhanced mindfulness capacities

October 24, 2021 / Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Background:

Ayahuasca is a plant tea containing the psychedelic 5-HT2A agonist N,N-dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism. Post-acutely, ayahuasca potentiates mindfulness capacities in volunteers and induces rapid and sustained antidepressant effects in treatment-resistant patients. However, the mechanisms underlying these fast and maintained effects are poorly understood. Here, we investigated in an open-label uncontrolled study in 16 healthy volunteers ayahuasca-induced post-acute neurometabolic and connectivity modifications and their association with mindfulness measures.

Methods:

Using 1H-magnetic resonance spectroscopy and functional connectivity, we compared baseline and post-acute neurometabolites and seed-to-voxel connectivity in the posterior and anterior cingulate cortex after a single ayahuasca dose.

Results:

Magnetic resonance spectroscopy showed post-acute reductions in glutamate+glutamine, creatine, and N-acetylaspartate+N-acetylaspartylglutamate in the posterior cingulate cortex. Connectivity was increased between the posterior cingulate cortex and the anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. Glutamate+glutamine reductions correlated with increases in the “nonjudging” subscale of the Five Facets Mindfulness Questionnaire. Increased anterior cingulate cortex-medial temporal lobe connectivity correlated with increased scores on the self-compassion questionnaire. Post-acute neural changes predicted sustained elevations in nonjudging 2 months later.

Conclusions:

These results support the involvement of glutamate neurotransmission in the effects of psychedelics in humans. They further suggest that neurometabolic changes in the posterior cingulate cortex, a key region within the default mode network, and increased connectivity between the anterior cingulate cortex and medial temporal lobe structures involved in emotion and memory potentially underlie the post-acute psychological effects of ayahuasca. Sampedro, F., de la Fuente Revenga, M., Valle, M., Roberto, N., Domínguez-Clavé, E., Elices, M., … & Friedlander, P. (2017). Assessing the psychedelic “after-glow” in ayahuasca users: post-acute neurometabolic and functional connectivity changes are associated with enhanced mindfulness capacities. International Journal of Neuropsychopharmacology. 10.1093/ijnp/pyx036

A phenomenological analysis of the subjective experience elicited by ibogaine in the context of a drug dependence treatment

August 29, 2017 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

Objective

This report documents the phenomenology of the subjective experiences of 22 patients with substance-related disorders who were involved in a treatment combining cognitive–behavioral therapy and hospital sessions with ibogaine in Brazil.

Methods

Participants underwent a one-to-one semi-structured interview exploring the subjective effects of ibogaine. We employed interpretative phenomenological analysis to identify relevant phenomenological categories, including physical sensations, perceptual (visual, auditory, and olfactory), emotional, cognitive, and spiritual. Participants also compared ibogaine with other drugs used in life, including psychedelics like ayahuasca, psilocybin mushrooms, and lysergic acid diethylamide.

Results

The findings reveal that the subjective experience with ibogaine has similarities with other psychedelic substances, but also important differences. These include very strong and unpleasant physical effects as well as, at least in this patient population, a very difficult and challenging experience.

Conclusions

Overall, the descriptions involve heightened memory retrieval, specially related to drug abuse and the perception of one’s own future with or without drug use. Strong perceptual phenomena, especially dreamlike visions, were commonly reported. Based on Revonsuo’s evolutionary hypothesis for the function of dreams and of previous suggestions that ibogaine has oneiric properties, we suggest the subjective experience of drug-dependent patients elicited by ibogaine may be framed as simulations of threat and danger.

Schenberg, E. E., de Castro Comis, M. A., Alexandre, J. F. M., Tófoli, L. F., Chaves, B. D. R., & da Silveira, D. X. (2017). A phenomenological analysis of the subjective experience elicited by ibogaine in the context of a drug dependence treatment. Journal of Psychedelic Studies, (0), 1-10. 10.1556/2054.01.2017.007
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Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic

August 26, 2017 / Anxiety Disorders / PTSD, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

PURPOSE OF REVIEW:
Studies of the neurobiology and treatment of PTSD have highlighted many aspects of the pathophysiology of this disorder that might be relevant to treatment. The purpose of this review is to highlight the potential clinical importance of an often-neglected consequence of stress models in animals that may be relevant to PTSD: the stress-related loss of synaptic connectivity.
RECENT FINDINGS:
Here, we will briefly review evidence that PTSD might be a “synaptic disconnection syndrome” and highlight the importance of this perspective for the emerging therapeutic application of ketamine as a potential rapid-acting treatment for this disorder that may work, in part, by restoring synaptic connectivity. Synaptic disconnection may contribute to the profile of PTSD symptoms that may be targeted by novel pharmacotherapeutics.
Krystal, J. H., Abdallah, C. G., Averill, L. A., Kelmendi, B., Harpaz-Rotem, I., Sanacora, G., … & Duman, R. S. (2017). Synaptic loss and the pathophysiology of PTSD: implications for ketamine as a prototype novel therapeutic. Current Psychiatry Reports, 19(10), 74. 10.1007/s11920-017-0829-z
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Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) psychotherapy prolong the therapeutic effects of single ketamine infusion on post-traumatic stress disorder and comorbid depression: a pilot randomized, placebo-controlled, crossover clinical trial

August 2, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, Papers, Psychology / By / , , , , , ,

Abstract

Background and objectives: Trauma memories lay at the core in etiopathogenesis of post-traumatic stress disorder (PTSD). Using pharmacological and cognitive behavioral treatments that specifically target trauma memories can improve the outcome. Ketamine has been shown to rapidly improve symptoms in PTSD and comorbid depression, but unfortunately these effects are short-lived. Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) psychotherapy is a type of mindfulness based cognitive behavioral therapy that targets the trauma memories. TIMBER psychotherapy in combination with (R,S)-ketamine are increasingly used to treat PTSD and comorbid depression. This study aims to determine if the combination of (R,S)-ketamine chemotherapy and TIMBER psychotherapy would produce a positive synergistic response in patients with PTSD.
Design: This is a randomized, placebo-controlled, cross-over clinical study.
Methods: Because response to ketamine alone is short-lived, this study combined TIMBER with a single infusion of 0.5 mg/kg (R,S)-ketamine to sustain its therapeutic effects. Ten patients with chronic and refractory PTSD were randomly assigned to two groups (n = 5 each): TIMBER-K group patients received ketamine infusion in combination with 12 TIMBER sessions (3 sessions in the first week followed by 9 sessions conducted on a weekly basis) and TIMBER-P group patients received placebo (normal saline infusion) in combination with 12 TIMBER sessions. The patients in the TIMBER-P group were switched to those in the TIMBER-K group after they experienced a sustained relapse.
Outcome measures: PTSD Checklist (PCL), Clinician Administered PTSD Scale for DSM-IV (CAPS), the 17-item Hamilton Rating Scale for Depression (Ham-D-17, clinician rated), Beck Anxiety Inventory (BAI), and Montreal Cognitive Assessment (MoCA) at baseline and 8 hours after infusion were used to investigate if ketamine selectively affected trauma memories leaving the general memory intact. The mindfulness interventions in TIMBER were personalized based on subject’s scores on Assessment Scale for Mindfulness Interventions which was administered at baseline, and after 5 sessions and 9 sessions (completion) of TIMBER. In this study, scores on CAPS and PCL scales were the primary outcome measures.
Results: In the acute phase trial ( first 3 months after infusion), nine out of 10 subjects showed robust response in primary outcome measures (PCL and CAPS scores for PTSD) and in the secondary outcome measures (Ham-D-17 and Beck Anxiety Inventory for depression and anxiety respectively) with a sustained response of 31.78 ± 18.29 days. The TIMBER-K group had a more sustained response (33 ± 22.98 days) compared to the TIMBER-P group (25 ± 16.8 days, P = 0.545). After switch from TIMBER-P group to TIMBER-K, patients experienced significantly prolonged response (49 vs. 25 days, P = 0.028). There were no intolerable side effects or dropouts during the 18-month follow-up period.
Conclusion: TIMBER psychotherapy augmented with low dose (R,S)-ketamine prolongs the therapeutic effects of the later and may be a valuable treatment option for PTSD.
Pradhan, B. K., Wainer, I. W., Moaddel, R., Torjman, M. C., Goldberg, M., Sabia, M., … & Pumariega, A. J. (2017). Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) psychotherapy prolong the therapeutic effects of single ketamine infusion on post-traumatic stress disorder and comorbid depression: a pilot randomized, placebo-controlled, crossover clinical trial. Asia Pacific Journal of Clinical Trials: Nervous System Diseases, 2(3), 80. 10.4103/2542-3932.211589
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