Investigation of self-treatment with lysergic acid diethylamide and psilocybin mushrooms: Findings from the Global Drug Survey 2020.

BACKGROUND: Growing numbers of people are using psychedelics for personal psychotherapy outside clinical settings, but research on such use is scarce. AIMS: This study investigated the patterns of use, self-reported outcomes and outcome predictors of psychedelic 'self-treatment' of mental health conditions or specific worries/concerns in life. METHODS: We use data from the Global Drug Survey 2020, a large online survey on drug use collected between November 2019 and February 2020. In all, 3364 respondents reported their self-treatment experiences with lysergic acid diethylamide (N = 1996) or psilocybin mushrooms (N = 1368). The primary outcome of interest was the 17-item self-treatment outcome scale, items reflecting aspects of well-being, psychiatric symptoms, social-emotional skills, and health behaviours. RESULTS: Positive changes were observed across all 17 outcome items, with the strongest benefits on items related to insight and mood. Negative effects were reported by 22.5% of respondents. High intensity of psychedelic experience, seeking advice before treatment, treating with psilocybin mushrooms and treating post-traumatic stress disorder were associated with higher scores on the self-treatment outcome scale after averaging values across all 17 items. Younger age, high intensity of experience and treating with LSD were associated with increased number of negative outcomes. CONCLUSIONS: This study brings important insights into self-treatment practices with psychedelics in a large international sample. Outcomes were generally favourable, but negative effects appeared more frequent than in clinical settings. Our findings can help inform safe practices of psychedelic use in the community, and inspire clinical research. Future research can be improved with utilisation of prospective designs and additional predictive variables.

Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis.

BACKGROUND: Psychedelic therapy shows promise for Major Depressive Disorder, especially when treatment-resistant, as well as life-threatening illness distress. The objective of this systematic review, inclusive of meta-analysis, is to examine recent clinical research on the therapeutic effects of classic psychedelics on depressive symptoms. METHODS: Fourteen psychedelic therapy studies, utilising psilocybin, ayahuasca, or LSD, were systematically reviewed. For the meta-analysis, standardised mean differences were calculated for seven randomised controlled trials. RESULTS: The systematic review indicated significant short- and long-term reduction of depressive symptoms in all conditions studied after administration of psilocybin, ayahuasca, or LSD, with psychological support. In the meta-analysis, symptom reduction was significantly indicated in three timepoints out of four, including 1-day, 1-week, and 3-5 weeks, supporting the results of the systematic review, with the exception of the 6-8 weeks follow-up point which was less conclusive. LIMITATIONS: The absence of required data for 2 studies necessitated the less precise use of graphical extraction and imputation. The small sample size in all but one study negatively affected the statistical power. None of the studies had long-term follow-up without also utilising the cross-over method, which did not allow for long-term results to be included in the meta-review. CONCLUSIONS: This review indicates an association between psychedelic therapy and significant reduction of depressive symptoms at several time points. However, the small number of studies, and low sample sizes, calls for careful interpretation of results. This suggests the need for more randomised clinical trials of psychedelic therapy, with larger and more diverse samples.

Adverse experiences resulting in emergency medical treatment seeking following the use of lysergic acid diethylamide (LSD).

BACKGROUND: Recreational lysergic acid diethylamide (LSD) use is growing in popularity amid increasing research interest on psychedelics and their possible therapeutic potential yet; the potent psychotropic effects of LSD may result in adverse reactions and behaviour. AIMS: This study aimed to investigate the 12-month incidence and nature of LSD-related adverse experiences resulting in emergency medical treatment (EMT) seeking in an international sample of people reporting LSD use. METHODS: We use data from the 2017 Global Drug Survey - a large anonymous online survey on patterns of drug use conducted between November 2016 and January 2017. RESULTS: Out of 10,293 past-year LSD users, 102 (1.0%) reported seeking EMT, with a per-event risk estimate of 0.2%. Younger age, comorbid mental health conditions and higher frequency of use were associated with increased risk of EMT seeking. The most common symptoms were psychological, including anxiety, panic and confusion, with the most common explanatory factors cited by respondents being poor 'setting' and 'mindset'. Most responders reported feeling back to normal within 24 h, but 11 participants experienced persistent issues after 4 weeks. CONCLUSION: The results suggest that LSD is a relatively safe drug in recreational settings. Adverse reactions are typically short-lived, self-limiting and psychological in nature. Sub-optimal set and setting were commonly reported as suspected contributory factors. Within clinical settings, patient screening, preparatory sessions and supervision should reduce these acute risks considerably.

Adverse experiences resulting in emergency medical treatment seeking following the use of magic mushrooms.

BACKGROUND: Psilocybin-containing mushrooms are used for recreational, spiritual, self-development and therapeutic purposes. However, physiologically relatively nontoxic, adverse reactions are occasionally reported. AIMS: This study investigated the 12-month prevalence and nature of magic mushroom-related adverse reactions resulting in emergency medical treatment seeking in a global sample of people reporting magic mushroom use. METHODS: We use data from the 2017 Global Drug Survey - a large anonymous online survey on patterns of drug use conducted between November 2016 and January 2017. RESULTS: Out of 9233 past year magic mushroom users, 19 (0.2%) reported having sought emergency medical treatment, with a per-event risk estimate of 0.06%. Young age was the only predictor associated with higher risk of emergency medical presentations. The most common symptoms were psychological, namely anxiety/panic and paranoia/suspiciousness. Poor 'mindset', poor 'setting' and mixing substances were most reported reasons for incidents. All but one respondent returned back to normality within 24 h. CONCLUSIONS: The results confirm psilocybin mushrooms are a relatively safe drug, with serious incidents rare and short lasting. Providing harm-reduction information likely plays a key role in preventing adverse effects. More research is needed to examine the detailed circumstances and predictors of adverse reactions including rarer physiological reactions.

Ketamine's effect on inflammation and kynurenine pathway in depression: A systematic review.

BACKGROUND: Ketamine is a novel rapid-acting antidepressant with high efficacy in treatment-resistant patients. Its exact therapeutic mechanisms of action are unclear; however, in recent years its anti-inflammatory properties and subsequent downstream effects on tryptophan (TRP) metabolism have sparked research interest. AIM: This systematic review examined the effect of ketamine on inflammatory markers and TRP-kynurenine (KYN) pathway metabolites in patients with unipolar and bipolar depression and in animal models of depression. METHODS: MEDLINE, Embase, and PsycINFO databases were searched on October 2020 (1806 to 2020). RESULTS: Out of 807 initial results, nine human studies and 22 animal studies on rodents met the inclusion criteria. Rodent studies provided strong support for ketamine-induced decreases in pro-inflammatory cytokines, namely in interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α and indicated anti-inflammatory effects on TRP metabolism, including decreases in the enzyme indoleamine 2,3-dioxygenase (IDO). Clinical evidence was less robust with high heterogeneity between sample characteristics, but most experiments demonstrated decreases in peripheral inflammation including in IL-1ß, IL-6, and TNF-α. Preliminary support was also found for reduced activation of the neurotoxic arm of the KYN pathway. CONCLUSION: Ketamine appears to induce anti-inflammatory effects in at least a proportion of depressed patients. Suggestions for future research include investigation of markers in the central nervous system and examination of clinical relevance of inflammatory changes.