Modern Clinical Research on LSD

All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT2A receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry

Influence of context and setting on the mental health and wellbeing outcomes of ayahuasca drinkers: results of a large international survey

Ayahuasca is a traditional plant decoction containing N,N-dimethyltryptamine (DMT) and various β-carbolines including harmine, harmaline and tetrahydroharmine, which has been used ceremonially by Amazonian Indigenous groups for healing and spiritual purposes. Use of the brew has now spread far beyond its original context of consumption to North America, Europe and Australia in neo-shamanic settings as well as Christian syncretic churches. While these groups have established their own rituals and protocols to guide use, it remains unknown the extent to which the use of traditional or non-traditional practices may affect drinkers’ acute experiences, and longer term wellbeing and mental health outcomes. Hence, this study aimed to provide the first detailed assessment of associations between ceremony/ritual characteristics, additional support practices, and motivations for drinking, and mental health and wellbeing outcomes. The paper uses data from a large cross-sectional study of ayahuasca drinkers in more than 40 countries who had used ayahuasca in various contexts (n=6,877). It captured detailed information about participant demographics, patterns and history of ayahuasca drinking, the setting of consumption, and ritualistic practices employed. Current mental health status was captured via the Kessler 10 psychological distress scale and the mental health component score of the SF-12 Health Questionnaire, while reported change in prior clinically diagnosed anxiety or depression (n=1276) was evaluated using a (PGIC) Patient Global Impression of Change tool. Various intermediate outcomes were also assessed including perceived change in psychological wellbeing, number of personal self-insights attained, and subjective spiritual experience measured via the spirituality dimension of the Persisting Effects Questionnaire (PEQ) and Short Index of Mystical Orientation. Regression models identified a range of significant associations between set and setting variables, and intermediate and final mental health and wellbeing outcomes. A generalized structural equation model (GSEM) was then used to verify relationships and associations between endogenous, mediating and final outcome variables concurrently. The present study sheds new light on the influence of ceremonial practices, additional supports and motivations on the therapeutic effects of ayahuasca for mental health and wellbeing, and ways in which such factors can be optimized in naturalistic settings and clinical studies

Ayahuasca use and reported effects on depression and anxiety symptoms: An international cross-sectional study of 11,912 consumers

Background Ayahuasca is a psychoactive Amazonian brew which has emerging data indicating that it has antidepressant and anxiolytic properties. Methods This paper uses data from the Global Ayahuasca Project (GAP), which was undertaken across 2017-2020 and involved 11912 people, to examine the perceived effects of ayahuasca consumption on affective symptoms. The study focused on the subsample reporting depression or anxiety diagnoses at time of Ayahuasca consumption (n = 2011). Results Of participants reporting depression (n=1571) or anxiety (n=1125) at the time of consuming Ayahuasca, 78% reported that their depression was either ‘very much’ improved (46%), or ‘completely resolved’ (32%); while 70% of those with anxiety reported that their symptoms were ‘very much’ improved (54%), or ‘completely resolved’ (16%). A range of factors were associated with greater reported affective symptoms improvement, including subjective mystical experience, number of Ayahuasca sessions, and number of personal psychological insights experienced. 2.7% and 4.5% of drinkers with depression or anxiety, respectively, reported worsening of symptoms. Limitations This study is recognized as a cross-sectional analysis which cannot assess treatment efficacy. Selection bias may exist due to survey-respondents with favorable experience being potentially biased towards participation. Conclusions Drinkers of Ayahuasca in naturalistic settings perceived remarkable benefits for their affective symptoms in this survey assessment. There is no obvious evidence of negative mental health effects being associated with long-term consumption. Additional randomized controlled trial evidence is required to establish the efficacy of Ayahuasca in affective disorders, and to understand the worsened symptoms reported by a small percentage of drinkers