OPEN Foundation

Anxiety disorders / PTSD

Psychedelics not linked to mental health problems or suicidal behavior: A population study

Abstract

A recent large population study of 130,000 adults in the United States failed to find evidence for a link between psychedelic use (lysergic acid diethylamide, psilocybin or mescaline) and mental health problems. Using a new data set consisting of 135,095 randomly selected United States adults, including 19,299 psychedelic users, we examine the associations between psychedelic use and mental health. After adjusting for sociodemographics, other drug use and childhood depression, we found no significant associations between lifetime use of psychedelics and increased likelihood of past year serious psychological distress, mental health treatment, suicidal thoughts, suicidal plans and suicide attempt, depression and anxiety. We failed to find evidence that psychedelic use is an independent risk factor for mental health problems. Psychedelics are not known to harm the brain or other body organs or to cause addiction or compulsive use; serious adverse events involving psychedelics are extremely rare. Overall, it is difficult to see how prohibition of psychedelics can be justified as a public health measure.

Johansen, P. Ø., & Krebs, T. S. (2015). Psychedelics not linked to mental health problems or suicidal behavior: A population study. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881114568039
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Peak experiences and the afterglow phenomenon: When and how do therapeutic effects of hallucinogens depend on psychedelic experiences?

Abstract

Interest in the therapeutic potential of psychedelic substances has recently resumed. During an early phase of human psychedelic research, their therapeutic application in different pathologies had been suggested, and the first evidence for efficacy was provided. The range of recent clinical applications of psychedelics spans from cluster headaches and obsessive-compulsive disorder to addiction and the treatment of fear and anxiety in patients suffering from terminal illness, indicating potentially different therapeutic mechanisms. A variety of approaches in psychotherapy emphasize subjective experiences, such as so-called peak experiences or afterglow phenomena, as differentially mediating therapeutic action. This review aims to re-evaluate earlier and recent concepts of how psychedelic substances may exert beneficial effects. After a short outline of neurophenomenological aspects, we discuss different approaches to how psychedelics are used in psychotherapy. Finally, we summarize evidence for the relationship between subjective experiences and therapeutic success. While the distinction between pharmacological and psychological action obviously cannot be clear-cut, they do appear to contribute differently from each other when their effects are compared with regard to pathologies.

Majić, T., Schmidt, T. T., & Gallinat, J. (2015). Peak experiences and the afterglow phenomenon: When and how do therapeutic effects of hallucinogens depend on psychedelic experiences? Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881114568040
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Classic psychedelic use is associated with reduced psychological distress and suicidality

A8_thumbnail_500x400In a population-based survey study that was published earlier this month, an association was found between the use of classic psychedelics and reduced psychological distress and suicidality [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][1]. The researchers included the data of 191.382 individuals that participated in the annual National Survey on Drug Use and Health (NSDUH) [2] between 2008 and 2012, and made a comparison between the psychological well being of classic psychedelic users and non-users. Classic psychedelic users were categorized as such if they met the criteria of having used ayahuasca, mescaline, LSD, peyote or San Pedro and/or psilocybin at least once in their lifetime. To rule out the possibility that differences between the groups of users and non-users could be attributed to factors other than classic psychedelics, the researchers statistically controlled the demographical factors age, gender, ethno-racial identity, educational attainment, annual household income, marital status, self-reported risky behavior and lifetime illicit drug use. No solid claim can be made about causality from this correlation, but the results are in line with earlier hypotheses that the effects of psychedelics may have qualities that could be helpful in modulating suicide risk [3]. As a current estimate, about 7% of the population worldwide suffers from mental health disorders [4]. The results of this study are a hopeful answer to the request from the National Action Alliance for Suicide Prevention (2014) to develop novel interventions that aim at suicide prevention.


 
[1] Hendricks et al. (2015).
[2] The NSDUH survey is the annual survey that is conducted by the United States Department of Health and Human Services. The survey aims at estimating the prevalence of substance use and mental illnesses.
[3] An extensive overview of earlier research can be found in the third and fourth paragraph of the article of Hendricks et al. (2015).
[4] This is based on the estimate of the World Health Organization (2001) that about half a billion people worldwide experience mental health problems and that the current world population is estimated at 7.2 billion (United States Census Bureau, 2015)
 
References

Hendricks, P. S., Thorne, C. B., Clark, C. B., Coombs, D. W., & Johnson, M. W. (2015). Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. Journal of Psychopharmacology. [Abstract]
National Action Alliance for Suicide Prevention: Research Prioritization Task Force (2014). A prioritized research agenda for suicide prevention: An action plan to save lives. National Institute of Mental Health and the Research Prioritization Task Force, Rockville, Maryland.
United States Census Bureau (2015). U.S. and World Population Clock. As retrieved on January 17. from http://www.census.gov/popclock/
World Health Organization (2001). The World health report 2001: Mental health: New understanding, new hope. Geneva, Switzerland: World Health Organization[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population

Abstract

Mental health problems are endemic across the globe, and suicide, a strong corollary of poor mental health, is a leading cause of death. Classic psychedelic use may occasion lasting improvements in mental health, but the effects of classic psychedelic use on suicidality are unknown. We evaluated the relationships of classic psychedelic use with psychological distress and suicidality among over 190,000 USA adult respondents pooled from the last five available years of the National Survey on Drug Use and Health (2008–2012) while controlling for a range of covariates. Lifetime classic psychedelic use was associated with a significantly reduced odds of past month psychological distress (weighted odds ratio (OR)=0.81 (0.72–0.91)), past year suicidal thinking (weighted OR=0.86 (0.78–0.94)), past year suicidal planning (weighted OR=0.71 (0.54–0.94)), and past year suicide attempt (weighted OR=0.64 (0.46–0.89)), whereas lifetime illicit use of other drugs was largely associated with an increased likelihood of these outcomes. These findings indicate that classic psychedelics may hold promise in the prevention of suicide, supporting the view that classic psychedelics’ most highly restricted legal status should be reconsidered to facilitate scientific study, and suggesting that more extensive clinical research with classic psychedelics is warranted.

Hendricks, P. S., Thorne, C. B., Clark, C. B., Coombs, D. W., & Johnson, M. W. (2015). Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881114565653

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Making a medicine out of MDMA

Abstract

From its first use 3,4,-methylenedioxymethamphetamine (MDMA) has been recognised as a drug with therapeutic potential. Research on its clinical utility stopped when it entered the recreational drug scene but has slowly resurrected in the past decade. Currently there is enough evidence for MDMA to be removed from its Schedule 1 status of ‘no medical use’ and moved into Schedule 2 (alongside other misused but useful medicines such as heroin and amphetamine). Such a regulatory move would liberate its use as a medicine for patients experiencing severe mental illnesses such as treatment-resistant post-traumatic stress disorder.

Sessa, B., & Nutt, D. (2015). Making a medicine out of MDMA. The British Journal of Psychiatry, 206, 4-6. https://dx.doi.org/10.1192/bjp.bp.114.152751

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Psilocybin and Obsessive Compulsive Disorder

Abstract

Obsessive Compulsive Disorder (OCD) is a psychiatric disorder with considerable morbidity and mortality. This condition disables many individuals and is often refractory to treatment. Research suggests that serotonin plays a role in OCD symptom reduction. We present a case of an individual who successfully used psilocybin, a serotonergic agent, to reduce the core symptoms of OCD for several years. Although not endorsing this form of treatment, we feel that the successful use of this agent highlights the role of serotonergic factors in OCD and the need for further, legitimate research into the value of psilocybin in the treatment of anxiety disorders.

Wilcox, J. A. (2014). Psilocybin and Obsessive Compulsive Disorder. Journal of psychoactive drugs, 46(5), 393-395. https://dx.doi.org/10.1080/02791072.2014.963754

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LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects

Abstract

Objective: A recently published study showed the safety and efficacy of LSD-assisted psychotherapy in patients with anxiety associated with life-threatening diseases. Participants of this study were included in a prospective follow-up.

Method: 12 months after finishing LSD psychotherapy, 10 participants were tested for anxiety (STAI) and participated in a semi-structured interview. A Qualitative Content Analysis (QCA) was carried out on the interviews to elaborate about LSD effects and lasting psychological changes.

Results: None of the participants reported lasting adverse reactions. The significant benefits as measured with the STAI were sustained over a 12-month period. In the QCA participants consistently reported insightful, cathartic and interpersonal experiences, accompanied by a reduction in anxiety (77.8%) and a rise in quality of life (66.7%). Evaluations of subjective experiences suggest facilitated access to emotions, confrontation of previously unknown anxieties, worries, resources and intense emotional peak experiences à la Maslow as major psychological working mechanisms. The experiences created led to a restructuring of the person’s emotional trust, situational understanding, habits and world view.

Conclusions: LSD administered in a medically supervised psychotherapeutic setting can be safe and generate lasting benefits in patients with a life-threatening disease. Explanatory models for the therapeutic effects of LSD warrant further study.

Gasser, P., Kirchner, K., & Passie, T. (2014). LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881114555249
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Improvement in suicidal ideation after ketamine infusion: Relationship to reductions in depression and anxiety

Abstract

Objective

Suicide is a psychiatric emergency. Currently, there are no approved pharmacologic treatments for suicidal ideation. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that rapidly reduces suicidal ideation as well as depression and anxiety, but the dynamic between these symptoms is not known. The aim of this analysis was to evaluate whether ketamine has an impact on suicidal thoughts, independent of depressive and anxiety symptoms.

Methods

133 patients with treatment-resistant depression (major depressive disorder or bipolar I/II disorder) received a single subanesthetic infusion of ketamine (0.5 mg/kg over 40 min). Post-hoc correlations and linear mixed models evaluated the relationship between suicidal ideation and depression and anxiety symptoms using the Hamilton Depression Rating Scale (HAMD), Scale for Suicidal Ideation (SSI), Beck Depression Inventory (BDI), and Hamilton Anxiety Rating Scale (HAMA) focusing on 230 min post-infusion.

Results

At 230 min post-infusion, correlations between changes in suicidal ideation and depression ranged from 0.23 to 0.44 (p < .05), accounting for up to 19% in the variance of ideation change. Correlations with anxiety ranged from 0.23 to 0.40 (p < .05), accounting for similar levels of variance. Ketamine infusion was associated with significant reductions in suicidal ideation compared to placebo, when controlling for the effects of ketamine on depression (F1,587 = 10.31, p = .001) and anxiety (F1,567 = 8.54, p = .004).

Conclusions

Improvements in suicidal ideation after ketamine infusion are related to, but not completely driven by, improvements in depression and anxiety. Investigation of the specific effects of ketamine on suicidal thoughts is warranted.

Ballard, E. D., Ionescu, D. F., Voort, J. L. V., Niciu, M. J., Richards, E. M., Luckenbaugh, D. A., … & Zarate, C. A. (2014). Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety. Journal of psychiatric research, 58, 161-166. https://dx.doi.org/10.1016/j.jpsychires.2014.07.027

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Effects of ecstasy on cooperative behaviour and perception of trustworthiness: A naturalistic study

Abstract

Background: Acute recreational use of 3,4-methylenedioxymethamphetamine (MDMA; ‘ecstasy’) can promote pro-social effects which may alter interpersonal perceptions.

Aims: To explore such effects, this study investigated whether acute recreational use of ecstasy was associated with changes in individual perception of trustworthiness of people’s faces and co-operative behaviours.

Method: An independent group, repeated measures design was used in which 17 ecstasy users were tested on the night of drug use (day 0) and again three days later (day 3); 22 controls were tested on parallel days. On each day, participants rated the trustworthiness of 66 faces, carried out three co-operative behaviour tasks (public good; dictator; ultimatum game) and completed mood self-ratings.

Results: Acute ecstasy use was associated with increased face trustworthiness ratings and increased cooperative behaviour on the dictator and ultimatum games; on day 3 there were no group differences on any task. Self-ratings showed the standard acute ecstasy effects (euphoria, energy, jaw clenching) with negative effects (less empathy, compassion, more distrust, hostility) emerging on day 3.

Conclusions: Our findings of increased perceived trustworthiness and co-operative behaviours following use of ecstasy suggest that a single dose of the drug enhances aspects of empathy. This may in turn contribute to its popularity as a recreational drug and potentially to its enhancement of the therapeutic alliance in psychotherapy.

Stewart, L. H., Ferguson, B., Morgan, C. J. A., Swaboda, N., Jones, L., Fenton, R., … & Curran, H. V. (2014). Effects of ecstasy on cooperative behaviour and perception of trustworthiness: A naturalistic study. Journal of Psychopharmacology, 28(11), 1001-1008. https://dx.doi.org/10.1177/0269881114544775

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PTSD and MDMA in the ‘picture’

a5_ptsd_508With an upcoming fMRI study in the United Kingdom, an attempt is being made to outline the neurobiological mechanisms that are hypothesized to underlie the favorable outcome of MDMA-assisted psychotherapy in posttraumatic stress disorder (PTSD).

Earlier studies found that after just a few treatment sessions with MDMA in addition to psychotherapy, there was a significant short [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][1] and long [2] term improvement of PTSD symptomatology in patients that were resistant to regular psycho- and/or pharmacotherapy [3]. Up to today, not much is known about the factors that contribute to the success of this form of treatment. Several researchers suggest that MDMA, o.a. by temporarily reducing fear and by easing interpersonal contact, facilitate the therapy on a psychological level [4], but about the neurobiological foundations remains to be speculated.

By using fMRI, dr. Ben Sessa and his research team at Cardiff University will try to image the manifestation of MDMA in PTSD patients. To capture the effects of the compound in isolation, the patients will not receive any psychotherapy during this study.

The research proposal is currently waiting for approval of the Committee of Ethics.


 
[1] Mithoefer, Wagner, Mithoefer, Jerome, & Doblin (2011)
[2] Mithoefer et al. (2012)
[3] A similar study from Oehen, Traber, Widmer, & Schnyder (2013) did not reach significance on the primary measurement (p = .066), a diagnostic tool to assess PTSD symptomatology, though at a subjective level the patients indicated to have some relief from their former complaints. Bouso et al. (2008) couldn’t draw any firm conclusions on their data of the first MDMA-assisted psychotherapy study in PTSD, due to a sudden unexpected cancellation of the study and the consequencing small study sample.
[4] Bouso, Doblin, Farré, Alcázar, & Gómez-Jarabo (2008), Mithoefer et al. (2011), Oehen et al. (2013)
 
References
Bouso, J. C., Doblin, R., Farré, M., Alcázar, M. A., & Gómez-Jarabo, G. (2008). MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder. Journal of Psychoactive Drugs, 40(3), 225–36. doi:10.1080/02791072.2008.10400637
Mithoefer, M. C. M., Wagner, M. M. T., Mithoefer, A. A. T., Jerome, L., Martin, S. F., Yazar-Klosinski, B., … Doblin, R. (2012). Durability of improvement in posttraumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. Journal of Psychopharmacology (Oxford, England), 27, 28–39. doi:10.1177/0269881112456611
Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T., Jerome, L., & Doblin, R. (2011). The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Journal of psychopharmacology (Oxford, England) (Vol. 25, pp. 439–452). doi:10.1177/0269881110378371
Oehen, P., Traber, R., Widmer, V., & Schnyder, U. (2013). A randomized, controlled pilot study of MDMA (± 3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD). Journal of Psychopharmacology (Oxford, England), 27(1), 40–52. doi:10.1177/0269881112464827[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

22 May - Delivering Effective Psychedelic Clinical Trials

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