OPEN Foundation

Therapeutic Application

Capturing the different health conditions that PAP may adress

Clinical potential of psilocybin as a treatment for mental health conditions

Abstract

Psilocybin, a classic hallucinogen, is a chemical produced by more than 100 species of mushrooms worldwide. It has high affinity for several serotonin receptors, including 5-HT1A, 5-HT2A, and 5-HT2C, located in numerous areas of the brain, including the cerebral cortex and thalamus. With legislation introduced in 1992, more work is being done to further understand the implications of psilocybin use in a number of disease states. Certain mental health disease states and symptoms have been studied, including depressed mood, anxiety disorders, obsessive-compulsive disorder, alcohol use disorder, and tobacco use disorder. This article provides an in-depth review of the study design and results of psilocybin in each of these conditions and discusses the clinical potential for use.

Daniel, J., & Haberman, M. (2017). Clinical potential of psilocybin as a treatment for mental health conditions. Mental Health Clinician, 7(1), 24-28. 10.9740/mhc.2017.01.024

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Treating drug dependence with the aid of ibogaine: A qualitative study

Abstract

Background: Substance use disorders are important contributors to the global burden of disease, but current treatments are not associated with high rates of recovery. The lack of approved and effective treatments is acutely problematic for psychostimulants like cocaine and crack cocaine. One promising alternative in the treatment of drug dependence in general and psychostimulants in particular is the use of the psychedelic alkaloid ibogaine combined with psychotherapy. This was recently shown to induce prolonged periods of abstinence in polydrug users, including psychostimulants. However, drug dependence treatments cannot be comprehensively evaluated with reductions in consumption alone, with current recommendations including secondary outcome measures like craving, family and social relationship, quality of life, and self-efficacy.

Methods: We therefore employed a directed approach to qualitative content analysis to evaluate the outcomes of a treatment combining ibogaine with cognitive-behavioral therapy based on data gathered from patient’s reports obtained in semi-structured interviews.

Main findings: The results revealed that patients benefited from the treatment in all the secondary outcomes, reporting decreases in craving and improvements in personal relationships, quality of life, and self-efficacy, thus supporting existing notions that treatments combining ibogaine and psychotherapy do have a therapeutic potential in the treatment of substance use disorders.

Schenberg, E. E., de Castro Comis, M. A., Alexandre, J. F. M., Chaves, B. D. R., Tófoli, L. F., & da Silveira, D. X. (2016). Treating drug dependence with the aid of ibogaine: A qualitative study. Journal of Psychedelic Studies, (0), 1-10. 10.1556/2054.01.2016.002

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Ketamine Mechanism of Action: Separating the Wheat from the Chaff

Abstract

(R,S)-ketamine (ketamine) exerts rapid (within hours) and robust (>60% response) antidepressant effects in severely ill-depressed patients who have failed conventional treatments (Zarate et al, 2006). This clinical finding has been paradigm-shifting as there is now tremendous hope that very ill-depressed patients can be treated in a matter of hours, rather than many weeks or months required for standard therapies to take effect (if they do at all).

Gould, T. D., Zanos, P., & Zarate, C. A. (2017). Ketamine Mechanism of Action: Separating the Wheat from the Chaff. Neuropsychopharmacology, 42(1), 368-369. 10.1038/npp.2016.210
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Ketamine accelerates fear extinction via mTORC1 signaling

Abstract

Impaired fear extinction contributes to the persistence of post-traumatic stress disorder (PTSD), and can be utilized for the study of novel therapeutic agents. Glutamate plays an important role in the formation of traumatic memories, and in the pathophysiology and treatment of PTSD, highlighting several possible drug targets. Recent clinical studies demonstrate that infusion of ketamine, a glutamate NMDA receptor antagonist, rapidly and significantly reduces symptom severity in PTSD patients. In the present study, we examine the mechanisms underlying the actions of ketamine in a rodent model of fear conditioning, extinction, and renewal. Rats received ketamine or saline 24 h after fear conditioning and were then subjected to extinction-training on each of the following three days. Ketamine administration enhanced extinction on the second day of training (i.e., reduced freezing behavior to cue) and produced a long-lasting reduction in freezing on exposure to cue plus context 8 days later. Additionally, ketamine and extinction exposure increased levels of mTORC1 in the medial prefrontal cortex (mPFC), a region involved in the acquisition and retrieval of extinction, and infusion of the selective mTORC1 inhibitor rapamycin into the mPFC blocked the effects of ketamine on extinction. Ketamine plus extinction also increased cFos in the mPFC and administration of a glutamate-AMPA receptor antagonist blocked the effects of ketamine. These results support the hypothesis that ketamine produces long-lasting mTORC1/protein synthesis and activity dependent effects on neuronal circuits that enhance the expression of extinction and could represent a novel approach for the treatment of PTSD.

Girgenti, M. J., Ghosal, S., LoPresto, D., Taylor, J. R., & Duman, R. S. (2017). Ketamine accelerates fear extinction via mTORC1 signaling. Neurobiology of Disease, 100, 1-8. 10.1016/j.nbd.2016.12.026
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Can 3,4,-methylenedioxymethamphetamine therapy be used to treat alcohol use disorder?

Treating people with alcohol use disorder has been an important target area for psychedelic research – both in the first studies of the 1950s and during the Psychedelic Renaissance of the last 10 years. To date, most studies have looked at the classical psychedelic drugs as adjuncts to psychotherapy; with attention paid to the psychospiritual aspect of the experience as a central therapeutic process in effecting abstinence from drinking. Psychotherapy assisted with 3,4,-methylenedioxymethamphetamine (MDMA) has never been explored for treating alcohol use disorder. However, MDMA has some unique pharmacological characteristics – particularly its capacity for reducing the fear response and facilitating engagement in therapy around past psychological trauma – that could make it a useful candidate for tackling the core features of alcohol use disorder. This paper briefly describes the burden of alcohol use disorders and the history of psychedelic-assisted psychotherapy in the field of addictions. It gives the theoretical and experimental justification for MDMA-assisted psychotherapy for treating people with alcohol use disorder and introduces a forthcoming study from Bristol and London, UK, exploring the role for MDMA in treating a person with this challenging condition.

Sessa, B. (2016). Can 3, 4,-methylenedioxymethamphetamine therapy be used to treat alcohol use disorder?. Journal of Psychedelic Studies, (0), 1-9. 10.1556/2054.01.2016.003
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The antiaddictive effects of ibogaine: A systematic literature review of human studies

Abstract

Background and aims: Ibogaine is a naturally occurring hallucinogenic alkaloid with a therapeutic potential for reducing drug craving and withdrawal. To the best of our knowledge, no systematic review was previously performed assessing these effects. Thus, we conducted a systematic literature review of human studies assessing the antiaddictive effects of ibogaine.

Methods: Papers published up to July 2, 2016 were included from PubMed, LILACS, and SciELO databases following a comprehensive search strategy and a pre-determined set of criteria for article selection.

Results: Two hundred and fifty-nine studies were identified, of which eight met the established criteria. Seven studies were open-label case series with ibogaine and one study was a randomized, placebo-controlled clinical trial with noribogaine. Case series suggest that a single dose or a few treatments with ibogaine may significantly reduce drug withdrawal, craving, and self-administration in dependent individuals lasting from 24 h to weeks or months. No significant effects of noribogaine on opiate/opioid withdrawal were observed in the clinical trial.

Conclusions: Considering the necessity of new drugs that may produce fast-acting and sustained effects in opiate/opioid and cocaine dependence, the potential beneficial effects of ibogaine/noribogaine should be further investigated in controlled trials.

dos Santos, R. G., Bouso, J. C., & Hallak, J. E. (2016). The antiaddictive effects of ibogaine: A systematic literature review of human studies. Journal of Psychedelic Studies, (0), 1-9. 10.1556/2054.01.2016.001

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A One-Dose Psychedelic Fix for Addiction?

Abstract

A drug that mimics ibogaine, a hallucinogen used underground for decades as an antiaddiction agent, is now being tested in clinical trials

The psychedelic drug ibogaine is known for two things: its reputation in some circles as a panacea for addiction and the visceral hallucinations it induces. Positive anecdotes abound from people who have sought out the illegal drug at underground clinics.

Jacobson, R. (2017). A One-Dose Psychedelic Fix for Addiction?. Scientific American Mind, 28(1), 10-11. 10.1038/scientificamericanmind0117-10

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Psilocybin: promising results in double-blind trials require confirmation by real-world evidence

Breckenridge, A., & Grobbee, D. E. (2016). Psilocybin: promising results in double-blind trials require confirmation by real-world evidence. Journal of psychopharmacology (Oxford, England), 30(12), 1218. 10.1177/0269881116675784
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