Altered Rationality? Integrating Psychedelic Experiences Into Rational Thinking Through the Critical Anchor Approach

Lucas F. Borkel, Tobias Fernandez- Borkel, Jaime Rojas-Hernández, Domingo J. Quintana- Hernández, Elisa Hernández-Álvarez, Luis Alberto Henríquez-Hernández

DOI: https://doi.org/10.1353/ppp.0.a973595

This paper examines delusions and psychedelic experiences as sources of both epistemic risk and benefit. Although these states are often seen as irrational or pathological, the paper explores their potential epistemic and psychological benefits, such as fostering emotional adaptation and creativity. The paper cautions against interpreting subjective experiences as metaphysical truths, which risks epistemic overreach and social disconnection. By introducing the Critical Anchor Approach, which emphasizes meta-consciousness, critical thinking, epistemic humility and the adoption of phenomenal rather than metaphysical interpretations to integrate insights from altered states, this paper offers a framework for synthesizing transformative insights within rational and empirical boundaries.

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Preliminary Findings on Low-Dose 1cp-LSD for Canine Anxiety: Exploring the Role of Owner Neuroticism and Psychopathology

​Elisa Hernández-Álvarez, Jaime Rojas-Hernández, Lucas F. Borkel, Domingo J. Quintana-Hernández, Tobías Fernández-Borkel, Luis Alberto Henríquez-Hernández

​DOI: https://doi.org/10.3390/vetsci12090872

This study explored whether small oral doses of 1cp-LSD, a legal prodrug of LSD, could help reduce anxiety in dogs. Seven anxious dogs were treated over 30 days, and their anxiety levels were evaluated before, after, and one month following treatment. An additional dog, whose anxiety was perceived by the owner but did not meet clinical criteria, received a placebo. This case was included for observational purposes only and was not part of the formal analysis. The results showed that dogs treated with higher doses of 1cp-LSD experienced greater reductions in anxiety, especially in separation-related behaviors. Notably, dogs whose owners scored higher on measures of hostility, interpersonal sensitivity, and paranoid ideation showed smaller reductions in anxiety. These findings suggest that low-dose psychedelics may have therapeutic potential for anxious pets, and that an owner’s emotional state can influence treatment success. Although the study involved a small number of animals, no adverse effects were observed, and improvements appeared to last beyond the treatment period. More research is needed, but this early work offers insight into new ways of supporting animal welfare through novel therapies.

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The Causal Role of Consciousness in Psychedelic Therapy for Treatment-Resistant Depression: Hypothesis and Proposal

Tobías Fernández-Borkel, Lucas F. Borkel, Jaime Rojas-Hernández, Elisa Hernández-Álvarez, Domingo J. Quintana-Hernández, Ludovica G. Ponti, Luis Alberto Henríquez-Hernández

​DOI: https://doi.org/10.1021/acsptsci.5c00445

​The therapeutic potential of psychedelic substances, particularly psilocybin, for treatment-resistant depression (TRD) has garnered considerable attention. However, the necessity of subjective psychedelic experiences for therapeutic efficacy remains unclear, creating a critical gap in the field. To determine whether subjective psychedelic experiences induced by psilocybin are required for its antidepressant effects or whether these effects are mediated solely by neurobiological actions independent of consciousness. We propose a randomized controlled trial with three groups: (P) Psilocybin (25 mg oral dose with guided therapeutic integration), (P+A) Psilocybin under propofol-induced general anesthesia (eliminating subjective experiences), and (X+A) Propofol-induced anesthesia with placebo (with no psilocybin). Clinical assessments of depression and anxiety, combined with fMRI-based brain connectivity analysis (including fractal complexity, brain entropy, and network dynamics), will be conducted at baseline, postintervention, and during follow-ups. The proposed study protocol expects distinct therapeutic outcomes across groups. Superior improvements in depression and anxiety symptoms are anticipated in the conscious psilocybin group (P) compared to both anesthetized groups (P+A) and (X+A). Additionally, increased brain connectivity measures in fractal complexity and entropy are hypothesized to correlate positively with therapeutic improvements, particularly pronounced in the conscious condition. Isolating subjective experiences through anesthesia, aims to determine whether conscious psychedelic experiences play a causal role in therapeutic outcomes. Results have significant implications for clinical protocols, treatment guidelines, and the broader theoretical understanding of consciousness and its relationship to mental health.

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Evaluating the Potential of Microdosing 1cp-LSD for the Treatment of Canine Anxiety: A One-Month Case Study

Elisa Hernández-Álvarez, Lucas F. Borkel, Jaime Rojas-Hernández, Domingo J. Quintana-Hernández, Ignacio García-Serrano, Tobías Fernández-Borkel, Manuel Zumbado, Luis Alberto Henríquez-Hernández

DOI: https://doi.org/10.1002/vms3.70486

​This pilot study explored the potential of microdosing 1-cyclopropionyl-d-lysergic acid diethylamide (1cp-LSD) to treat canine anxiety. A single-case study was conducted on a 13-year-old female dog with severe separation anxiety, who was treated with 5 µg of 1cp-LSD every 3 days for a month. Anxiety was assessed before, after, and 1 month following treatment using a validated questionnaire. The owner's attachment style was assessed using a validated scale. The dog's anxiety score significantly decreased from 29 (severe) to 14 (moderate) after treatment. A reduction in anxiety levels was observed, characterized by decreased destructive behaviour and shorter durations of vocalization. This improvement was sustained 1 month following treatment, although vocalization frequency increased. These findings suggest potential therapeutic efficacy of microdosing 1cp-LSD in managing canine anxiety; however, the absence of a control group makes it difficult to determine whether the observed effects are due to 1cp-LSD, owner bias, or natural variability in the dog's behaviour. Additional studies with blinded protocols and larger sample sizes are necessary to validate these findings and further explore the impact of owner attachment on canine anxiety.​

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Therapeutic benefit versus epistemic risk: Need for empirical research in psychedelic epistemology

Lucas F. Borkel, Jaime Rojas-Hernández, Domingo J. Quintana-Hernández, Luis Alberto Henríquez-Hernández

DOI: https://doi.org/10.1016/j.jpsychires.2025.05.039

This paper highlights the ethical and epistemic challenges posed by psychedelic therapy and vindicates the importance of epistemology in the clinical and psychotherapeutic setting. Despite their relative physiological and psychological safety, these substances can induce changes in the beliefs of those who use them, such as paranormal beliefs. To explain the changes in beliefs, we introduced the concept of epistemic criteria (i.e., the principles individuals use to validate and justify their beliefs) and hypothesized that psychedelics may alter beliefs by modifying epistemic criteria. Further research should be conducted to determine this potential and under-researched risk of psychedelic therapy.

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Pattern of psychedelic substance use: a comparison between populations in Spain and South America using the Psychedelic Use Scale (PUS)

Jaime Rojas-Hernández, Lucas F. Borkel, Domingo J. Quintana-Hernández, Ángelo Santana del Pino & ​Luis Alberto Henríquez-Hernández

DOI: https://doi.org/10.1007/s12144-024-07017-x

Psychedelic use has increased in the last decade. However, it is unclear whether the cultural background of the consumers exerts any influence. The aim of the present study was to determine the pattern of psychedelic use in Spain and Spanish-speaking populations in South America and compare these consumption patterns to understand the use of these substances in two culturally distinct populations. The Psychedelic Use Scale (PUS) was administered via the Google Surveys platform between September and November 2022. 735 participants were selected using a non-probability purposive sampling technique. The study received ethics approval from the local ethics committee. Psilocybin was the most used substance. MDMA was more frequently consumed in the Spanish population (78.5 vs. 37.1%), while mescaline was more commonly used among participants from South America (31.9 vs. 24.0%), mainly among males (P < 0.05). Among the Spanish population, MDMA was the most commonly combined psychedelic; for the South American population, LSD was the substance most frequently combined, highlighting the predominant recreational use of this substance. DMT predicted the most adverse effects during consumption, whereas MDMA predicted the most adverse effects after consumption. Age was as a risk factor for the development of adverse effects, with a significant increase in risk observed in individuals under 30 years of age (OR = 2.01, CI95% 1.1–3.6). In conclusion, the pattern of psychedelic substance use differed between both populations, highlighting the necessity for comprehensive studies. This is especially crucial in light of the social shifts stemming from the ongoing psychedelic renaissance.

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Single-dose 1cp-LSD administration for canine anxiety: a pilot study

​Luis Alberto Henríquez-Hernández, Ignacio García-Serrano, Domingo J. Quintana-Hernández, Jaime Rojas-Hernández, Elisa Hernández-Álvarez, Manuel Zumbado, Tobías Fernández-Borkel & Lucas F. Borkel (2024) 

DOI: https://doi.org/10.1007/s11259-024-10542-6

https://link.springer.com/article/10.1007/s11259-024-10542-6

​Anxiety affects 14–20% of dogs. Pharmacological treatments often fail. Psychedelics have shown to be useful for anxiety and depression in humans, but their veterinary use remains unexplored. We aimed to determine the effects of low-dose 1-cyclopropionyl-d-lysergic acid diethylamide (1cp-LSD) administered in a single dose to a dog, to observe the effect and establish the safety of the substance. The patient was a 13-year-old female dog, weighing 13 kg, mixed breed, and spayed. A total of 5 µg was administered orally, equivalent to 0.38 µg/kg. The animal has had a history of separation related behavioral problems throughout her life. To objectively assess the degree of anxiety in the dog, a validated scale was utilized. The trial was scheduled at the house where the animal lives. The owner was present throughout the experience. Informed consent was obtained prior to the assay. The trial began at 12:15 p.m. on January 10, 2024, lasting for 5 and a half hours. The response to anxiety-inducing stimuli was equally anxious during the first two hours. From that point onwards, a significant change in the animal’s behavior was observed, with no signs/mild signs of anxiety. The trial concluded without any adverse effects on the animal. The patient did not show signs of having a psychedelic experience. This is the first time that a study of this nature has been conducted and reported in the canine species. 1cp-LSD proved to be safe and exerted the desired effect on the animal’s behavior, significantly reducing the patient’s anxiety.​

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Set and setting predict psychopathology, wellbeing and meaningfulness of psychedelic experiences: a correlational study

​Lucas F. Borkel, Jaime Rojas-Hernández, Luis Alberto Henríquez-Hernández, Ángelo Santana Del Pino & Domingo J. Quintana-Hernández (2023) Set and setting predict psychopathology, wellbeing and meaningfulness of psychedelic experiences: a correlational study, Expert Review of Clinical Pharmacology, DOI: 10.1080/17512433.2023.2295997

https://www.tandfonline.com/doi/full/10.1080/17512433.2023.2295997

​Background: In psychedelic therapy, the importance of set and setting is a fundamental but under-researched assumption. The aim of this study is to correlate variables of set (psychedelic use motivation) and setting (psychedelic use location and type of companion) with psychopathology, wellbeing and personality variables.

Research design and methods: A sample of 1022 participants of the Spanish-speaking population was collected through an online survey. A novel instrument, the Psychedelic Use Scale (PUS), was developed to measure substance use variables of LSD, mescaline, psilocybin, DMT, 5-Meo-DMT, ketamine, Salvia divinorum, ibogaine and MDMA. Various personality, well-being and psychopathology instruments were implemented to measure outcome variables.

Results: Growth motivations, natural settings and presence of significant others predicted less psychopathology, greater wellbeing and meaningfulness of psychedelic experiences, whereas problematic motivations predicted greater psychopathology, lower wellbeing and did not predict meaningfulness of psychedelic experiences.

Conclusions: Based on these results, we suggest experimental hypotheses for future clinical trials and longitudinal studies with potential clinical implications.

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Hofmann vs. Paracelsus: Do Psychedelics Defy the Basics of Toxicology?—A Systematic Review of the Main Ergolamines, Simple Tryptamines, and Phenylethylamines

​Henríquez-Hernández, L. A., Rojas-Hernández, J., Quintana-Hernández, D. J., & Borkel, L. F. (2023). Hofmann vs. Paracelsus: do psychedelics defy the basics of toxicology?—a systematic review of the main ergolamines, simple tryptamines, and phenylethylamines. Toxics, 11(2), 148.

https://doi.org/10.3390/toxics11020148

https://www.mdpi.com/2305-6304/11/2/148

​Psychedelics are experiencing a strong renaissance and will soon be incorporated into clinical practice. However, there is uncertainty about how much harm they can cause at what doses. This review aimed to collect information on the health-hazardous doses of psychedelic substances, to be aware of the risks to which patients may be subjected. We focused on ergolamines, simple tryptamines, and phenylethylamines. We reviewed articles published in major medical and scientific databases. Studies reporting toxic or lethal doses in humans and animals were included. We followed PRISMA criteria for revisions. We identified 3032 manuscripts for inclusion. Of these, 33 were ultimately useful and gave relevant information about effects associated with high psychedelics doses. Despite having different molecular structures and different mechanisms of action, psychedelics are effective at very low doses, are not addictive, and are harmful at extremely high doses. For LSD and psilocybin, no dose has been established above which the lives of users are endangered. In contrast, MDMA appears to be the most dangerous substance, although reports are biased by recreational missuses. It seems that it is not only the dose that makes the poison. In the case of psychedelics, the set and setting make the poison.

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​Mindfulness Prevents Depression and Psychopathology in Elderly People with Mild to Moderate Alzheimer’s Disease: A Randomized Clinical Trial​
Quintana-Hernández, D. J., Rojas-Hernández, J., Santana-del Pino, A., Céspedes Suárez, C., Pellejero Silva, M., Miró-Barrachina, M. T., ... & Borkel, L. F. (2023). Mindfulness prevents depression and psychopathology in elderly people with mild to moderate Alzheimer’s disease: a randomized clinical trial. Journal of Alzheimer's Disease, (Preprint), 1-11.
DOI: 10.3233/JAD-220889
https://content.iospress.com/articles/journal-of-alzheimers-disease/jad220889

​Background: This longitudinal study addressed whether mindfulness practice prevents psychological and behavioral symptoms, especially mood disorders, in Alzheimer’s disease (AD).

​Objective: To assess the incidence of depression in the course of AD and to determine which non-pharmacological treatment (NPT) is most effective in preventing psychopathological symptoms.

Methods: We conducted a longitudinal, non-inferiority and equivalence randomized clinical trial, repeated-measures design, with a control group and three experimental treatments: mindfulness, cognitive stimulation, and relaxation. Each experimental group performed three weekly sessions for two years. The pharmacological treatment of all participants was donepezil (10 mg). Participants were patients with probable AD without diagnosed depression from the public neurology services of the Canary Health Service, Spain. Psychological evaluation was performed using the Geriatric Depression Scale (GDS), Hamilton Depression Rating Scale (HDRS), and Neuropsychiatric Inventory (NPI-Q). The statistical analysis included only patients who attended at least 75% of the sessions. A nonparametric, repeated-measures analysis was performed with Kruskal-Wallis H test and between-group differences with Mann-Whitney U test with Bonferroni correction (p < 0.008). Effect size was calculated with partial eta-squared.

Results: The results showed significant differences with large effect sizes (η2p>0.14) between mindfulness and the rest of the experimental groups as well as the control in the GDS, HDRS, and NPI-Q scales.

Conclusion: Compared to the other experimental groups, only mindfulness prevented the onset of depression and other psychopathologies in early-stage AD. Based on its effectiveness in maintaining cognitive functions and preventing psychopathology, we recommend mindfulness as the first-choice NPT for mild to moderate AD.