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Self-Rated Effectiveness of Microdosing With Psychedelics for Mental and Physical Health Problems Among Microdosers

September 13, 2019 / Anthropology & Sociology, Anxiety Disorders / PTSD, Papers, Psychology, Publications / By / , , ,

Abstract

Background: There is a growing interest in the use of psychedelic substances for health related purposes, including symptom relief for disorders like anxiety, depression, and pain. Although the focus of recent clinical trials has been on high doses of these substances, anecdotal evidence suggests that low (micro) doses are also effective, and may be more suitable for certain conditions. Nonetheless, empirical evidence regarding the efficacy of microdosing with psychedelics for symptomatic relief is lacking. The present study aimed to investigate, by means of an online questionnaire, the self-rated effectiveness (SRE) of microdosing with psychedelics (MDP) for mental and physiological disorders compared to the conventional prescribed treatment and to regular doses of psychedelics. Methods: An online questionnaire was launched on several websites and fora between March and July 2018. Respondents who had consented, were 18 years of age or older, had experience with microdosing and were diagnosed with at least one mental or physiological disorder by a medical doctor or therapist (N = 410; 7.2%) were included in the analyses. Odds ratio were calculated to compare the SRE of MDP with conventional treatment, and regular psychedelic doses for mental and physiological diagnoses for each of the three effectiveness questions (“Did it work,” “Symptom disappear,” “Quality of life improved”). Results: Odds ratio showed that SRE of MDP was significantly higher compared to that of conventional treatments for both mental and physiological diagnoses; and that these effects were specific for ADHD/ADD and anxiety disorders. In contrast, SRE of MDP was lower compared to that of higher, regular psychedelic doses for mental disorders such as anxiety and depression, while for physiological disorders no difference was shown. Conclusion: This study demonstrates that SRE of MDP to alleviate symptoms of a range of mental or physiological diagnoses is higher compared to conventionally offered treatment options, and lower than regular (‘full’) psychedelic doses. Future RCTs in patient populations should objectively assess the effectivity claims of psychedelics, and whether these are dose related, disorder specific, and superior to conventional treatments.

Hutten, N. R., Mason, N. L., Dolder, P. C., & Kuypers, K. P. (2019). Self-rated effectiveness of microdosing with psychedelics for mental and physical health problems amongst microdosers. Frontiers in psychiatry, 10, 672. 10.3389/fpsyt.2019.00672

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The Impact of Childhood Maltreatment on Intravenous Ketamine Outcomes for Adult Patients with Treatment-Resistant Depression

September 11, 2019 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Publications / By / , , , ,

Abstract

Childhood maltreatment is associated with a poor treatment response to conventional antidepressants and increased risk for treatment-resistant depression (TRD). The N-methyl-D-aspartate receptor (NDMAR) antagonist ketamine has been shown to rapidly improve symptoms of depression in patients with TRD. It is unknown if childhood maltreatment could influence ketamine’s treatment response. We examined the relationship between childhood maltreatment using the Childhood Trauma Questionnaire (CTQ) and treatment response using the Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR) in TRD patients receiving intravenous ketamine at a community outpatient clinic. We evaluated treatment response after a single infusion (n = 115) and a course of repeated infusions (n = 63). Repeated measures general linear models and Bayes factor (BF) showed significant decreases in QIDS-SR after the first and second infusions, which plateaued after the third infusion. Clinically significant childhood sexual abuse, physical abuse, and cumulative clinically significant maltreatment on multiple domains (maltreatment load) were associated with better treatment response to a single and repeated infusions. After repeated infusions, higher load was also associated with a higher remission rate. In contrast to conventional antidepressants, ketamine could be more effective in TRD patients with more childhood trauma burden, perhaps due to ketamine’s proposed ability to block trauma-associated behavioral sensitization.

O’Brien, B., Lijffijt, M., Wells, A., Swann, A. C., & Mathew, S. J. (2019). The impact of childhood maltreatment on intravenous ketamine outcomes for adult patients with treatment-resistant depression. Pharmaceuticals, 12(3), 133., 10.3390/ph12030133
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Exploring ayahuasca‐assisted therapy for addiction: A qualitative analysis of preliminary findings among an Indigenous community in Canada

September 5, 2019 / Ayahuasca, Papers, Psychology, Publications, Substance Use Disorder / By / , , , ,

Abstract

Introduction and Aims

A previous observational study of ayahuasca‐assisted therapy demonstrated statistically significant reductions in self‐reported problematic cocaine use among members of an Indigenous community in Canada. This paper aims to qualitatively explore the impact of ayahuasca‐assisted therapy on addiction and other substance use‐related outcomes and elucidate the lived experiences of participants.

Design and Methods

Qualitative interviews were conducted with 11 adult Indigenous participants of the ayahuasca‐assisted ‘Working with Addiction and Stress’ ceremonial retreats (June–September 2011). Semi‐structured interviews assessed experiences of participants following the retreats at 6‐month follow up. Thematic analysis of interview transcripts was conducted.

Results

Narratives revealed that the retreats helped participants identify negative thought patterns and barriers related to their addiction in ways that differed from conventional therapies. All participants reported reductions in substance use and cravings; eight participants reported complete cessation of at least one substance at follow up. Increased connectedness with self, others and nature/spirit was described as a key element associated with reduced substance use and cravings.

Discussion and Conclusions

This analysis expands upon prior quantitative results highlighting the therapeutic potential of ayahuasca‐assisted therapy and provides important contextual insights into why ayahuasca‐assisted therapy may have been beneficial for members of an Indigenous community seeking to address their problematic use of substances. Given limited efficacy of conventional treatments for resolving addiction issues, further research should investigate the role of ayahuasca and other psychedelic‐assisted therapies in enhancing connectedness and other key factors that may improve well‐being and reduce harmful substance use

Argento, E., Capler, R., Thomas, G., Lucas, P., & Tupper, K. W. (2019). Exploring ayahuasca‐assisted therapy for addiction: A qualitative analysis of preliminary findings among an Indigenous community in Canada. Drug and alcohol review.

Hallucinogens and Their Therapeutic Use: A Literature Review

September 1, 2019 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, DMT, Iboga / Ibogaine, Ketamine, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

The exploration of possible therapeutic benefits of hallucinogenic substances has undergone a revitalization in the past decade. This literature review investigated the published literature regarding the psychotherapeutic uses of hallucinogens in psychiatric disorders. The results showed that a variety of substances have been evaluated in the treatment of psychiatric disorders, including ayahuasca, ibogaine, ketamine, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, and psilocybin. The conditions treated ranged from depression to autism, with the largest volume of research dedicated to substance use disorders. The majority of studies that were reviewed demonstrated significant associations with improvement in the conditions investigated. However, it was difficult to draw definitive conclusions as most studies suffered from small sample sizes, inconsistent measures, and poor study design. To properly assess the risks and potential benefits of hallucinogens in psychiatric treatment, there is a need for well designed, standardized studies that demonstrate the impact of hallucinogenic substances on psychiatric conditions.

BEGOLA, M. J., & SCHILLERSTROM, J. E. (2019). Hallucinogens and Their Therapeutic Use: A Literature Review. Journal of Psychiatric Practice®, 25(5), 334-346., 10.1097/PRA.0000000000000409
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Repeated ketamine injections in synergy with antidepressants for treating refractory depression: A case showing 6-month improvement.

August 30, 2019 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

WHAT IS KNOWN AND OBJECTIVE:
Some patients with refractory depression who fail to respond to rapid injection of standard-dose ketamine are injected with high doses, but the safety and efficacy of this practice are unclear.
CASE DESCRIPTION:
A 57-year-old woman with refractory depression whose symptoms did not improve after 20-seconds intravenous injection of 0.5 mg/kg ketamine went into remission following eight, 1-minute intravenous injections of 1 mg/kg ketamine delivered over a 4-week period. By 6-month follow-up, no significant adverse events had occurred and cognitive function had improved.
WHAT IS NEW AND CONCLUSION:
High-dose intravenous injections of ketamine may stably improve depressive symptoms and cognitive function in patients with refractory depression who do not respond to rapid intravenous injection of standard-dose ketamine. The high-dose treatment appears to be associated with only mild side effects.
Wang, M., Xiong, Z., Su, B., Wang, L., Li, Z., Yang, Y., & Fang, J. (2019). Repeated ketamine injections in synergy with antidepressants for treating refractory depression: A case showing 6-month improvement. Journal of clinical pharmacy and therapeutics., https://doi.org/10.1111/jcpt.13041
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Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism.

August 29, 2019 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

We recently reported that naltrexone blocks antidepressant effects of ketamine in humans, indicating that antidepressant effects of ketamine require opioid receptor activation. However, it is unknown if opioid receptors are also involved in ketamine’s antisuicidality effects. Here, in a secondary analysis of our recent clinical trial, we test whether naltrexone attenuates antisuicidality effects of ketamine. Participants were pretreated with naltrexone or placebo prior to intravenous ketamine in a double-blinded crossover design. Suicidality was measured with the Hamilton Depression Rating Scale item 3, Montgomery-Åsberg Depression Rating Scale item 10, and Columbia Suicide Severity Rating Scale. In the 12 participants who completed naltrexone and placebo conditions, naltrexone attenuated the antisuicidality effects of ketamine on all three suicidality scales/subscales (linear mixed model, fixed pretreatment effect, p < 0.01). Results indicate that opioid receptor activation plays a significant role in the antisuicidality effects of ketamine.
Williams, N. R., Heifets, B. D., Bentzley, B. S., Blasey, C., Sudheimer, K. D., Hawkins, J., … & Schatzberg, A. F. (2019). Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism. Molecular psychiatry, 1-8., https://doi.org/10.1038/s41380-019-0503-4
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Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders

August 27, 2019 / Anxiety Disorders / PTSD, Ketamine, MDMA, Papers, Psychiatry & Medicine, Publications / By / ,

Abstract

Current medication for anxiety disorders is suboptimal in terms of efficiency and tolerability, highlighting the need for improved drug treatments. In this review an overview of drugs being studied in different phases of clinical trials for their potential in the treatment of fear-, anxiety- and trauma-related disorders is presented. One strategy followed in drug development is refining and improving compounds interacting with existing anxiolytic drug targets, such as serotonergic and prototypical GABAergic benzodiazepines. A more innovative approach involves the search for compounds with novel mechanisms of anxiolytic action using the growing knowledge base concerning the relevant neurocircuitries and neurobiological mechanisms underlying pathological fear and anxiety. The target systems evaluated in clinical trials include glutamate, endocannabinoid and neuropeptide systems, as well as ion channels and targets derived from phytochemicals. Examples of promising novel candidates currently in clinical development for generalised anxiety disorder, social anxiety disorder, panic disorder, obsessive compulsive disorder or post-traumatic stress disorder include ketamine, riluzole, xenon with one common pharmacological action of modulation of glutamatergic neurotransmission, as well as the neurosteroid aloradine. Finally, compounds such as D-cycloserine, MDMA, L-DOPA and cannabinoids have shown efficacy in enhancing fear-extinction learning in humans. They are thus investigated in clinical trials as an augmentative strategy for speeding up and enhancing the long-term effectiveness of exposure-based psychotherapy, which could render chronic anxiolytic drug treatment dispensable for many patients. These efforts are indicative of a rekindled interest and renewed optimism in the anxiety drug discovery field, after decades of relative stagnation.

Sartori, S. B., & Singewald, N. (2019). Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders. Pharmacology & therapeutics, 107402., 10.1016/j.pharmthera.2019.107402
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Ketamine and depression: a narrative review.

August 27, 2019 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / ,

Abstract

Depression is the third leading cause of disability in the world. Depressive symptoms may be reduced within several weeks after the start of conventional antidepressants, but treatment resistance concerns one-third of patients who fail to achieve recovery. Over the last 20 years, ketamine, an antagonist of the N-methyl-D-aspartate receptor, has been described to have antidepressant properties. A literature review was conducted through an exhaustive electronic search. It was restricted to Cochrane reviews, meta-analyses, and randomized controlled trials (RCTs) of ketamine for major depressive disorder and/or bipolar disorder. This review included two Cochrane reviews, 14 meta-analyses and 15 trials. Ketamine was studied versus placebo, versus other comparators and as an anesthetic adjuvant before electroconvulsive therapy. In 14 publications, ketamine provided a rapid antidepressant effect with a maximum efficacy reached at 24 hrs. Its effect lasted for 1-2 weeks after infusion, but a longer-term effect is little reported. Ketamine does not seem to improve depressive symptoms at the end of electroconvulsive sessions. Safety and tolerability profiles with ketamine at low single dose are generally good in depressed patients. However, there is a lack of data concerning ketamine with repeated administration at higher doses. The clinical use of ketamine is increasing. Intranasal (S)-ketamine has recently been approved for depression by the Food and Drug Administration. It could be a promising treatment in depressed patients with suicidal ideation. Collectively, the level of proof of efficacy remains low and more RCTs are needed to explore efficacy and safety issues of ketamine in depression.
Corriger, A., & Pickering, G. (2019). Ketamine and depression: a narrative review. Drug design, development and therapy, 13, 3051., https://doi.org/10.2147/DDDT.S221437
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Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for posttraumatic stress disorder: A systematic review and meta-analysis.

August 19, 2019 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , ,

Abstract

BACKGROUND:
Posttraumatic stress disorder (PTSD) is a common psychiatric condition that can develop following a traumatic experience. PTSD is associated with significant disability, a large economic burden, and despite the range of therapies to treat PTSD, response to antidepressants is limited. A growing body of clinical research suggests the efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in individuals with treatment-refractory PTSD.
AIM:
To assess the effectiveness and safety of MDMA-assisted psychotherapy for reducing symptoms of PTSD, a systematic review and meta-analysis was undertaken.
METHODS:
Six online databases were searched from inception to December 2018. Reference lists of relevant articles were manually searched as well as electronic sources of ongoing trials and conference proceedings. Researchers active in the subject were also contacted. Eligible studies included randomized and quasi-randomized clinical trials using MDMA-assisted psychotherapy for PTSD in comparison with other medications, placebo or no medication (supportive care). We used standard methodological procedures expected by the Cochrane Collaboration. Two authors assessed studies for inclusion and extracted data. Using random-effects meta-analysis with Cochrane’s Review Manager 5.3, we obtained standardized mean differences [SMD] and rate ratios [RR] for reduction in PTSD symptomatology.
RESULTS:
A total of 5 trials met inclusion criteria, totaling 106 participants (average age: 35-40 years, 70% female). Studies were rated as moderate in quality. MDMA-assisted psychotherapy demonstrated a high rate of clinical response (RR = 3.47, 95% CI: 1.70, 7.06), remission (RR = 2.63, 95% CI: 1.37, 5.02), with a large effect size at reducing the symptoms of PTSD (SMD = 1.30, 95% CI: 0.66, 1.94). Available evidence indicates that MDMA was well-tolerated, with few serious adverse events reported across studies.
CONCLUSIONS:
MDMA-assisted psychotherapy appears to be a potentially safe, effective, and durable treatment for individuals with chronic, treatment-refractory PTSD. However, future studies involving larger samples and longer durations of treatment and follow-up are warranted-and underway.
Bahji, A., Forsyth, A., Groll, D., & Hawken, E. R. (2019). Efficacy of 3, 4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for posttraumatic stress disorder: A systematic review and meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 109735., https://doi.org/10.1016/j.pnpbp.2019.109735
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