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Therapeutic Application

Capturing the different health conditions that PAP may adress

Harmine produces antidepressant-like effects via restoration of astrocytic functions

June 15, 2017 / Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Depression is a world-wide disease with no effective therapeutic methods. Increasing evidence indicates that astrocytic pathology contributes to the formation of depression. In this study, we investigated the effects of harmine, a natural β-carboline alkaloid and potent hallucinogen, known to modulate astrocytic glutamate transporters, on chronic unpredictable stress (CUS)-induced depressive-like behaviors and astrocytic dysfunctions. Results showed that harmine treatment (10, 20 mg/kg) protected the mice against the CUS-induced increases in the immobile time in the tail suspension test (TST) and forced swimming test (FST), and also reversed the reduction in sucrose intake in the sucrose preference experiment. Harmine treatment (20 mg/kg) prevented the reductions in brain-derived neurotrophic factor (BDNF) protein levels and hippocampal neurogenesis induced by CUS. In addition, harmine treatment (20 mg/kg) increased the protein expression levels of glutamate transporter 1 (GLT-1) and prevented the CUS-induced decreases in glial fibrillary acidic protein (GFAP) protein expressions in the prefrontal cortex and hippocampus, suggesting that restoration of astrocytic functions may be a potential mechanism underlying the antidepressant-like effects of harmine. This opinion was proved by the results that administration of mice with l-Alpha-Aminoadipic Acid (L-AAA), a gliotoxin specific for astrocytes, attenuated the antidepressant-like effects of harmine, and prevented the improvement effects of harmine on BDNF protein levels and hippocampal neurogenesis. These results provide further evidence to confirm that astrocytic dysfunction contributes critically to the development of depression and that harmine exerts antidepressant-like effects likely through restoration of astrocytic functions.

Liu, F., Wu, J., Gong, Y., Wang, P., Zhu, L., Tong, L. J., … & Huang, C. (2017). Harmine produces antidepressant-like effects via restoration of astrocytic functions. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 10.1016/j.pnpbp.2017.06.012
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Cancer at the Dinner Table: Experiences of Psilocybin-Assisted Psychotherapy for the Treatment of Cancer-Related Distress

June 14, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Recent randomized controlled trials of psilocybin-assisted psychotherapy for patients with cancer suggest that this treatment results in large-magnitude reductions in anxiety and depression as well as improvements in attitudes toward disease progression and death, quality of life, and spirituality. To better understand these findings, we sought to identify psychological mechanisms of action using qualitative methods to study patient experiences in psilocybin-assisted psychotherapy. Semistructured interviews were conducted with 13 adult participants with clinically elevated anxiety associated with a cancer diagnosis who received a single dose of psilocybin under close clinical supervision. Transcribed interviews were analyzed using interpretative phenomenological analysis, which resulted in 10 themes, focused specifically on cancer, death and dying, and healing narratives. Participants spoke to the anxiety and trauma related to cancer, and perceived lack of available emotional support. Participants described the immersive and distressing effects of the psilocybin session, which led to reconciliations with death, an acknowledgment of cancer’s place in life, and emotional uncoupling from cancer. Participants made spiritual or religious interpretations of their experience, and the psilocybin therapy helped facilitate a felt reconnection to life, a reclaiming of presence, and greater confidence in the face of cancer recurrence. Implications for theory and clinical treatment are discussed.
Swift, T. C., Belser, A. B., Agin-Liebes, G., Devenot, N., Terrana, S., Friedman, H. L., … & Ross, S. (2017). Cancer at the Dinner Table: Experiences of Psilocybin-Assisted Psychotherapy for the Treatment of Cancer-Related Distress. Journal of Humanistic Psychology, 0022167817715966.
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Potential Therapeutic Effects of Psilocybin

June 5, 2017 / Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / ,

Abstract

Psilocybin and other 5-hydroxytryptamine2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.
Johnson, M. W., & Griffiths, R. R. (2017). Potential Therapeutic Effects of Psilocybin. Neurotherapeutics, 1-7. 10.1007/s13311-017-0542-y
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Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy

June 1, 2017 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , , , , ,

Abstract

A growing body of research suggests that traumatic events lead to persisting personality change characterized by increased neuroticism. Relevantly, enduring improvements in Post-Traumatic Stress Disorder (PTSD) symptoms have been found in response to 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. There is evidence that lasting changes in the personality feature of “openness” occur in response to hallucinogens, and that this may potentially act as a therapeutic mechanism of change. The present study investigated whether heightened Openness and decreased Neuroticism served as a mechanism of change within a randomized trial of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD. The Clinician-Administered PTSD Scale (CAPS) Global Scores and NEO PI-R Personality Inventory (NEO) Openness and Neuroticism Scales served as outcome measures. Results indicated that changes in Openness but not Neuroticism played a moderating role in the relationship between reduced PTSD symptoms and MDMA treatment. Following MDMA-assisted psychotherapy, increased Openness and decreased Neuroticism when comparing baseline personality traits with long-term follow-up traits also were found. These preliminary findings suggest that the effect of MDMA-assisted psychotherapy extends beyond specific PTSD symptomatology and fundamentally alters personality structure, resulting in long-term persisting personality change. Results are discussed in terms of possible mechanisms of psychotherapeutic change.
Wagner, M. T., Mithoefer, M. C., Mithoefer, A. T., MacAulay, R. K., Jerome, L., Yazar-Klosinski, B., & Doblin, R. (2017). Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy. Journal of Psychopharmacology, 0269881117711712.
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Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes

May 25, 2017 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

BACKGROUND:
Ibogaine is a monoterpene indole alkaloid used in medical and nonmedical settings for the treatment of opioid use disorder. Its mechanism of action is apparently novel. There are no published prospective studies of drug use outcomes with ibogaine.
OBJECTIVES:
To study outcomes following opioid detoxification with ibogaine.
METHODS:
In this observational study, 30 subjects with DSM-IV Opioid Dependence (25 males, 5 females) received a mean total dose of 1,540 ± 920 mg ibogaine HCl. Subjects used oxycodone (n = 21; 70%) and/or heroin (n = 18; 60%) in respective amounts of 250 ± 180 mg/day and 1.3 ± 0.94 g/day, and averaged 3.1 ± 2.6 previous episodes of treatment for opioid dependence. Detoxification and follow-up outcomes at 1, 3, 6, 9, and 12 months were evaluated utilizing the Subjective Opioid Withdrawal Scale (SOWS) and Addiction Severity Index Composite (ASIC) scores, respectively.
RESULTS:
SOWS scores decreased from 31.0 ± 11.6 pretreatment to 14.0 ± 9.8 at 76.5 ± 30 hours posttreatment (t = 7.07, df = 26, p < 0.001). At 1-month posttreatment follow-up, 15 subjects (50%) reported no opioid use during the previous 30 days. ASIC Drug Use and Legal and Family/Social Status scores were improved relative to pretreatment baseline at all posttreatment time points (p < .001). Improvement in Drug Use scores was maximal at 1 month, and subsequently sustained from 3 to 12 months at levels that did not reach equivalence to the effect at 1 month.
CONCLUSION:
Ibogaine was associated with substantive effects on opioid withdrawal symptoms and drug use in subjects for whom other treatments had been unsuccessful, and may provide a useful prototype for discovery and development of innovative pharmacotherapy of addiction.
Brown, T. K., & Alper, K. (2017). Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. The American Journal of Drug and Alcohol Abuse, 1-13. 10.1080/00952990.2017.1320802
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Therapeutic Applications of Classic Hallucinogens

May 18, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

This chapter reviews what is known about the therapeutic uses of the serotonergic or classic hallucinogens, i.e., psychoactive drugs such as LSD and psilocybin that exert their effects primarily through agonist activity at serotonin 2A (5HT2A) receptors. Following a review of the history of human use and scientific study of these drugs, the data from clinical research are summarized, including extensive work on the use of classic hallucinogens in the treatment of alcoholism and other addictions, studies of the use of LSD and psilocybin to relieve distress concerning death, particularly in patients with advanced or terminal cancer, and more limited data concerning the use of classic hallucinogens to treat mood and anxiety disorders. A survey of possible mechanisms of clinically relevant effects is provided. The well-established safety of classic hallucinogens is reviewed. To provide a clinical perspective, case summaries are provided of two individuals who received treatment in recent controlled trials of psilocybin: one being treated for alcoholism, the other suffering from anxiety and depression related to fear of death due to a cancer diagnosis. Although promising early phase research conducted from the 1950s through the early 1970s was discontinued before firm conclusions could be reached concerning the efficacy of any of the classic hallucinogens for any clinical condition, the research that was conducted in that era strongly suggests that classic hallucinogens have clinically relevant effects, particularly in the case of LSD treatment of alcoholism. In the past decade, clinical trials have resumed investigating the effects of classic hallucinogens in the treatment of existential distress in the face of cancer, and in the treatment of addictions including alcoholism and nicotine addiction. The studies that have been completed to date are not sufficient to establish efficacy, but the outcomes have been very encouraging, and larger trials, up to and including phase 3, are now underway or being planned. Although research has elucidated many of the acute neurobiological and psychological effects of classic hallucinogens on humans, animals, and in vitro systems, the mechanisms of clinically relevant persisting effects remain poorly understood.
Bogenschutz, M. P., & Ross, S. (2016). Therapeutic applications of classic hallucinogens. 10.1007/7854_2016_464
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Associations between Specific Dissociative Symptoms and Symptom Subsets and Anti-Depressant Response to Ketamine

May 15, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , ,

Abstract

Ketamine has been shown to produce rapid antidepressant effects in major depression and bipolar disorder. Due to ketamine’s glutamatergic properties, many patients report dissociative effects, which recent studies have shown to be associated with increased anti-depressant response. Thus we investigated the connection between distinct subscales of dissociation and differing treatment response.

Shovestul, B., Jaso, B., Luckenbaugh, D., Park, L., Niciu, M., & Zarate, C. (2017). 199-Associations between Specific Dissociative Symptoms and Symptom Subsets and Anti-Depressant Response to Ketamine. Biological Psychiatry, 81(10), S82-S83. 10.1016/j.biopsych.2017.02.212
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Ketamine as a Treatment for Adolescent Major Depressive Disorder

May 15, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , ,

Abstract

Nearly 1 in 4 adolescents will experience major depressive disorder (MDD). Suicide is the 3rd leading cause of death in this age group. 40% of adolescents with MDD fail to respond to initial treatment with selective serotonin reuptake inhibitors (SSRIs). Of that SSRI-resistant population, nearly half remain depressed despite alternate medication and psychotherapy. Thus, better treatments for adolescent depression are urgently needed. Subanesthetic doses of ketamine, an NMDA antagonist, produce rapid antidepressant and anti-suicidal effects in depressed adults. There are few case reports and no prospective controlled trials of ketamine for the treatment of adolescent MDD.

Dwyer, J., Sanacora, G., & Bloch, M. (2017). 1002-Ketamine as a Treatment for Adolescent Major Depressive Disorder. Biological Psychiatry, 81(10), S405. 10.1016/j.biopsych.2017.02.729
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Clinical Predictors of an Antisuicidal Response to Ketamine

May 15, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Suicide is one of the leading causes of death in the United States. Despite treatment efforts, the national suicide rate has increased in recent years. Currently, there are no pharmacological treatments for suicidal ideation (SI). For individuals experiencing a suicidal crisis, rapid acting medications may save lives. Recent studies suggest ketamine, a glutamate modulator, elicits rapid antisuicidal responses. We examined clinical factors that might predict ketamine’s antisuicidal response as a step towards understanding ketamine’s mechanism of action on suicidal thoughts.

Yarrington, J., Ballard, E., Luckenbaugh, D., Niciu, M., Lener, M., Kadriu, B., … & Zarate, C. (2017). 1004-Clinical Predictors of an Antisuicidal Response to Ketamine. Biological Psychiatry, 81(10), S406. 10.1016/j.biopsych.2017.02.731
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Mood Dependent Effects of Ketamine on REM Eye Movements in Patients with Treatment Resistant Depression (TRD)

May 15, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , ,

Abstract

Both REM and NREM sleep are dysregulated in depression. REM dysregulation in MDD is thought to be partially linked to a deficient inhibitory influence of Process-S, leading to increased REM density (RD) and short REM latency (RL). Consistent with its effects on enhanced synaptic plasticity, ketamine increases SWS and early night slow-wave activity (SWA) in patients with TRD. Here we extend the examination of ketamine effects on rapid mood improvement to RD, an important marker of REM sleep in depression.

Hejazi, N., Yu, K., Park, L., Duncan, W., & Zarate, C. (2017). 861-Mood Dependent Effects of Ketamine on REM Eye Movements in Patients with Treatment Resistant Depression (TRD). Biological Psychiatry, 81(10), S348-S349. 10.1016/j.biopsych.2017.02.586
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