OPEN Foundation

Menu

Author name: OPEN Foundation

Neurochemical and Behavioral Profiling in Male and Female Rats of the Psychedelic Agent 25I-NBOMe

/ LSD, MDMA, Neuroscience, Papers, Publications / / , , , , , ,

Abstract

4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe), commonly called “N-Bomb,” is a synthetic phenethylamine with psychedelic and entactogenic effects; it was available on the Internet both as a legal alternative to lysergic acid diethylamide (LSD) and as a surrogate of 3,4-methylenedioxy-methamphetamine (MDMA), but now it has been scheduled among controlled substances. 25I-NBOMe acts as full agonist on serotonergic 5-HT2A receptors. Users are often unaware of ingesting fake LSD, and several cases of intoxication and fatalities have been reported. In humans, overdoses of “N-Bomb” can cause tachycardia, hypertension, seizures, and agitation. Preclinical studies have not yet widely investigated the rewarding properties and behavioral effects of this compound in both sexes. Therefore, by in vivo microdialysis, we evaluated the effects of 25I-NBOMe on dopaminergic (DA) and serotonergic (5-HT) transmissions in the nucleus accumbens (NAc) shell and core, and the medial prefrontal cortex (mPFC) of male and female rats. Moreover, we investigated the effect of 25I-NBOMe on sensorimotor modifications as well as body temperature, nociception, and startle/prepulse inhibition (PPI). We showed that administration of 25I-NBOMe affects DA transmission in the NAc shell in both sexes, although showing different patterns; moreover, this compound causes impaired visual responses in both sexes, whereas core temperature is heavily affected in females, and the highest dose tested exerts an analgesic effect prominent in male rats. Indeed, this drug is able to impair the startle amplitude with the same extent in both sexes and inhibits the PPI in male and female rats. Our study fills the gap of knowledge on the behavioral effects of 25I-NBOMe and the risks associated with its ingestion; it focuses the attention on sex differences that might be useful to understand the trend of consumption as well as to recognize and treat intoxication and overdose symptoms.

Miliano, C., Marti, M., Pintori, N., Castelli, M. P., Tirri, M., Arfè, R., & De Luca, M. A. (2019). Neurochemical and Behavioral Profiling in Male and Female Rats of the Psychedelic Agent 25I-NBOMe. Frontiers in Pharmacology, 10., 10.3389/fphar.2019.01406
Link to full text

Neurochemical and Behavioral Profiling in Male and Female Rats of the Psychedelic Agent 25I-NBOMe Read More »

4-MeO-PCP and 3-MeO-PCMo, new dissociative drugs, produce rewarding and reinforcing effects through activation of mesolimbic dopamine pathway and alteration of accumbal CREB, deltaFosB, and BDNF levels

/ Neuroscience, Papers, Pharmacology & Chemistry, Psychiatry & Medicine, Publications, Substance Use Disorder / / , , , , , ,

Abstract

Rationale: A high number of synthetic dissociative drugs continue to be available through online stores, leading to their misuse. Recent inclusions in this category are 4-MeO-PCP and 3-MeO-PCMo, analogs of phencyclidine. Although the dissociative effects of these drugs and their recreational use have been reported, no studies have investigated their abuse potential.

Objectives: To examine their rewarding and reinforcing effects and explore the mechanistic correlations.

Methods: We used conditioned place preference (CPP), self-administration, and locomotor sensitization tests to assess the rewarding and reinforcing effects of the drugs. We explored their mechanism of action by pretreating dopamine receptor (DR) D1 antagonist SCH23390 and DRD2 antagonist haloperidol during CPP test and investigated the effects of 4-MeO-PCP and 3-MeO-PCMo on dopamine-related proteins in the ventral tegmental area and nucleus accumbens. We also measured the levels of dopamine, phosphorylated cyclic-AMP response element-binding (p-CREB) protein, deltaFosB, and brain-derived neurotrophic factor (BDNF) in the nucleus accumbens. Additionally, we examined the effects of both drugs on brain wave activity using electroencephalography.

Results: While both 4-MeO-PCP and 3-MeO-PCMo induced CPP and self-administration, only 4-MeO-PCP elicited locomotor sensitization. SCH23390 and haloperidol inhibited the acquisition of drug CPP. 4-MeO-PCP and 3-MeO-PCMo altered the levels of tyrosine hydroxylase, DRD1, DRD2, and dopamine, as well as that of p-CREB, deltaFosB, and BDNF. All drugs increased the delta and gamma wave activity, whereas pretreatment with SCH23390 and haloperidol inhibited it.

Conclusion: Our results indicate that 4-MeO-PCP and 3-MeO-PCMo induce rewarding and reinforcing effects that are probably mediated by the mesolimbic dopamine system, suggesting an abuse liability in humans.

Abiero, A., Botanas, C. J., Custodio, R. J., Sayson, L. V., Kim, M., Lee, H. J., … & Cheong, J. H. (2020). 4-MeO-PCP and 3-MeO-PCMo, new dissociative drugs, produce rewarding and reinforcing effects through activation of mesolimbic dopamine pathway and alteration of accumbal CREB, deltaFosB, and BDNF levels. Psychopharmacology, 237(3), 757-772; 10.1007/s00213-019-05412-y

Link to full text

4-MeO-PCP and 3-MeO-PCMo, new dissociative drugs, produce rewarding and reinforcing effects through activation of mesolimbic dopamine pathway and alteration of accumbal CREB, deltaFosB, and BDNF levels Read More »

Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment

/ DMT, Neuroscience, Papers, Pharmacology & Chemistry, Psychiatry & Medicine, Publications / / , , , , ,

Abstract

Rationale

5-methoxy-N,N-dimethyltryptamine is a psychotropic substance found in various plant and animal species and is synthetically produced. 5-methoxy-N,N-dimethyltryptamine is used in naturalistic settings for spiritual exploration, recreation, or to address negative affect and mood problems. However, scientific knowledge on the effects of 5-methoxy-N,N-dimethyltryptamine in humans is scarce.

Objectives

The first objective was to assess the effects of inhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine on neuroendocrine markers. The second objective was to assess effects of the substance on affect and mindfulness. In addition, we assessed whether ratings of subjective measures were associated with changes in stress biomarkers (i.e., cortisol) and immune response (i.e., IL-6, CRP, IL-1β), as well as the acute psychedelic experience.

Methods

Assessments (baseline, immediately post-session, and 7-day follow-up) were made in 11 participants. Salivary samples were collected at baseline and post-session and analyzed by high-sensitivity enzyme-linked immunosorbent assay (ELISA).

Results

5-methoxy-N,N-dimethyltryptamine significantly increased cortisol levels and decreased IL-6 concentrations in saliva immediately post-session. These changes were not correlated to ratings of mental health or the psychedelic experience. Relative to baseline, ratings of non-judgment significantly increased, and ratings of depression decreased immediately post-session and at follow-up. Ratings of anxiety and stress decreased from baseline to 7-day follow-up. Participant ratings of the psychedelic experience correlated negatively with ratings of affect and positively with ratings of non-judgment.

Conclusion

Inhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine produced significant changes in inflammatory markers, improved affect, and non-judgment in volunteers. Future research should examine the effect of 5-methoxy-N,N-dimethyltryptamineamine with healthy volunteers in a controlled laboratory setting.

Uthaug, M. V., Lancelotta, R., Szabo, A., Davis, A. K., Riba, J., & Ramaekers, J. G. (2019). Prospective examination of synthetic 5-methoxy-N, N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment. Psychopharmacology, 1-13., 10.1007/s00213-019-05414-w
Link to full text

Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment Read More »

Neuropharmacological modulation of the aberrant bodily self through psychedelics

/ Depressive Disorders, DMT, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / / , ,

Abstract

As a continual source of sensory input and fundamental component of self-referential processing, the body holds an integral modulatory role in cognition. In a healthy state, predictive coding of multisensory integration promotes the construction of a coherent self. However, several psychiatric disorders comprise aberrant perceptions of the bodily self that are purported to involve discrepancies in the integration and updating of multisensory systems. Changes in functional connectivity of somatomotor and high-level association networks in these disorders could be successfully remediated through 5-HT2A receptor agonism via psychedelics. Reported alterations of bodily self-awareness during psychedelic experiences allude to a potentially central role of the bodily self. In this article, we bridge the domains of (aberrant) bodily self-awareness and psychedelics by discussing the predictive coding mechanisms underlying the bodily self and psychedelics. Furthermore, we propose that psychedelically-induced desynchronization of predictive coding might involve modulation of somatomotor, sensorimotor, and high-level association networks that could remediate aberrant perceptions of the bodily self.

Ho, J. T., Preller, K. H., & Lenggenhager, B. (2019). Neuropharmacological modulation of the aberrant bodily self through psychedelics. Neuroscience & Biobehavioral Reviews., https://doi.org/10.1016/j.neubiorev.2019.12.006
Link to full text

Neuropharmacological modulation of the aberrant bodily self through psychedelics Read More »

Injury-Triggered Blueing Reactions of Psilocybe “Magic” Mushrooms

/ Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry / Leave a Comment / / , , , , , , ,

Abstract

Upon injury, psychotropic psilocybin-producing mushrooms instantly develop an intense blue color, the chemical basis and mode of formation of which has remained elusive. We report two enzymes from Psilocybe cubensis that carry out a two-step cascade to prepare psilocybin for oxidative oligomerization that leads to blue products. The phosphatase PsiP removes the 4-O-phosphate group to yield psilocin, while PsiL oxidizes its 4-hydroxy group. The PsiL reaction was monitored by in situ 13 C NMR spectroscopy, which indicated that oxidative coupling of psilocyl residues occurs primarily via C-5. MS and IR spectroscopy indicated the formation of a heterogeneous mixture of preferentially psilocyl 3- to 13-mers and suggest multiple oligomerization routes, depending on oxidative power and substrate concentration. The results also imply that phosphate ester of psilocybin serves a reversible protective function.

Lenz, C., Wick, J., Braga, D., García-Altares, M., Lackner, G., Hertweck, C., Gressler, M., & Hoffmeister, D. (2020). Injury-Triggered Blueing Reactions of Psilocybe “Magic” Mushrooms. Angewandte Chemie (International ed. in English), 59(4), 1450–1454. https://doi.org/10.1002/anie.201910175

Link to full text

Injury-Triggered Blueing Reactions of Psilocybe “Magic” Mushrooms Read More »

Modulation of Social Cognition via Hallucinogens and “Entactogens”.

/ Ayahuasca, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / / ,

Abstract

Social cognition is a fundamental ability in human everyday lives. Deficits in social functioning also represent a core aspect of many psychiatric disorders. Yet, despite its significance, deficits in social cognition skills are insufficiently targeted by current treatments. Hallucinogens and entactogens have been shown to have the potential to modulate social processing. This article reviews the literature on the influence of hallucinogens and entactogens on social processing in controlled experimental studies in humans and elucidates the underlying neurobiological and neuropharmacological mechanisms. Furthermore, it identifies current knowledge gaps and derives implications for hallucinogen-assisted treatment approaches as well as the development of novel medication for trans-diagnostic impairments in social cognition.

Preller, K. H., & Vollenweider, F. X. (2019). Modulation of Social Cognition via Hallucinogens and “Entactogens”. Frontiers in Psychiatry, 10., https://doi.org/10.3389/fpsyt.2019.00881
Link to full text

Modulation of Social Cognition via Hallucinogens and “Entactogens”. Read More »

Therapeutic use of serotoninergic hallucinogens: A review of the evidence and of the biological and psychological mechanisms.

/ Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, DMT, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / / ,

Abstract

Serotoninergic hallucinogens include drugs such as lysergic acid diethylamide (LSD), dimethyltryptamine (DMT) and psilocybin. Recent trials with single/few doses of these compounds show that they induce rapid and sustained antidepressive, anxiolytic, and antiaddictive effects. These effects are also observed in religious groups using the DMT-containing brew ayahuasca. The agonist action of these substances on 5-HT2A receptors expressed in frontal and limbic areas increase glutamatergic transmission and neuroplasticity. These neurochemical effects are associated with acute alterations on self-perception and increases in introspection and positive mood, and with subacute and long-term decreases in psychiatric symptoms, increases in some personality traits such as openness, improvements in emotional processing, and increases in empathy. These are preliminary but promising results that should be further explored in controlled trials with larger sample sizes, especially considering that these compounds could be beneficial in the treatment of treatment-resistant psychiatric disorders.
dos Santos, R. G., & Hallak, J. E. C. (2019). Therapeutic use of serotoninergic hallucinogens: a review of the evidence and of the biological and psychological mechanisms. Neuroscience & Biobehavioral Reviews., https://doi.org/10.1016/j.neubiorev.2019.12.001
Link to full text
 

Therapeutic use of serotoninergic hallucinogens: A review of the evidence and of the biological and psychological mechanisms. Read More »

Embedding existential psychology within psychedelic science: reduced death anxiety as a mediator of the therapeutic effects of psychedelics.

/ Anxiety Disorders / PTSD, Depressive Disorders, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / / , , ,

Abstract

Psychedelic therapies can engender enduring improvements in psychological well-being. However, relatively little is known about the psychological mechanisms through which the salutary effects of psychedelics emerge. Through integrating extant research on psychedelics with contemporary existential psychology, we present a novel hypothesis that reduced death anxiety may be a key mechanism underpinning the therapeutic effects of psychedelics. In developing this hypothesis, we also provide a complementary review of mechanisms through which psychedelics may reduce death anxiety. We conclude that an awareness of the role of death anxiety in psychopathology has the potential to guide future research into psychedelic therapies.

Moreton, S. G., Szalla, L., Menzies, R. E., & Arena, A. F. (2019). Embedding existential psychology within psychedelic science: reduced death anxiety as a mediator of the therapeutic effects of psychedelics. 29, 1-12., https://doi.org/10.1007/s00213-019-05391-0
Link to full text

Embedding existential psychology within psychedelic science: reduced death anxiety as a mediator of the therapeutic effects of psychedelics. Read More »

Twenty percent better with 20 micrograms? A qualitative study of psychedelic microdosing self-rapports and discussions on YouTube.

/ LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / / ,

Abstract

Background

Psychedelic microdosing is the trending practice of using tiny repeated doses of psychedelic substances to facilitate a range of supposed benefits. With only a few published studies to date, the subject is still under-researched, and more knowledge is warranted. Social media and internet discussion forums have played a vital role in the growing visibility of the microdosing phenomenon, and the present study utilized YouTube contents to improve comprehension of the microdosing practice as well as the social interactions and discussions around microdosing.

Methods

Microdosing self-disclosure in YouTube videos and their following comments were qualitatively analyzed by inductive thematic analysis. Various software was utilized to enable gathering and sorting relevant data.

Results

Microdosing of psychedelic substances, primarily LSD and psilocybin, was used for therapeutic and enhancement purposes, and predominantly beneficial effects were reported. Many different applications and outcomes were discussed, and therapeutic effects for depression appeared especially noteworthy. Intentions for use were recognized as an influencing factor for the progression and outcomes of microdosing. The function of social interactions was mainly to discuss views on the microdosing phenomenon, strategies for optimal results, minimize risks, and share emotional support.

Conclusions

Potentially, microdosing could provide some of the same benefits (for certain conditions) as full-dose interventions with less risk of adverse reactions related to the sometimes intense experiences of higher doses. Microdosing may well also mean additional benefits, as well as risks, through the repeated exposure over extended periods.
Andersson, M., & Kjellgren, A. (2019). Twenty percent better with 20 micrograms? A qualitative study of psychedelic microdosing self-rapports and discussions on YouTube. Harm reduction journal, 16(1), 1-12., https://doi.org/10.1186/s12954-019-0333-3
Link to full text

Twenty percent better with 20 micrograms? A qualitative study of psychedelic microdosing self-rapports and discussions on YouTube. Read More »

Microdosing psychedelics: Motivations, subjective effects and harm reduction

/ LSD, Microdosing, Mushrooms / Psilocybin, Papers, Psychology / Leave a Comment / / , , , ,

Abstract

Background: In recent years there has been growing media attention on microdosing psychedelics (e.g., LSD, psilocybin). This refers to people routinely taking small doses of psychedelic substances to improve mental health and wellbeing, or to enhance cognitive performance. Research evidence is currently limited. This paper examines microdosing motivations, dosing practices, perceived short-term benefits, unwanted effects, and harm reduction practices.

Methods: An international online survey was conducted in 2018 examining people’s experiences of using psychedelics. Eligible participants were aged 16 years or older, had used psychedelics and could comprehend written English. This paper focuses on 525 participants who were microdosing psychedelics at the time of the survey.

Results: Participants were primarily motivated to microdose to improve mental health (40%), for personal development (31%) and cognitive enhancement (18%). Most were microdosing with psilocybin (55%) or LSD/1P-LSD (48%). Principal components analysis generated three factors examining perceived short-term benefits of microdosing: improved mood and anxiety, enhanced connection to others and environment, and cognitive enhancement; and three factors examining negative and potentially unwanted effects: stronger-than-expected psychedelic effects, anxiety-related effects, and physical adverse effects. Most participants (78%) reported at least one harm reduction practice they routinely performed while microdosing.

Conclusion: Our findings suggest that people microdosing are commonly doing so as a self-managed therapy for mental health, either as an alternative or adjunct to conventional treatments. This is despite psychedelics remaining prohibited substances in most jurisdictions. Recent findings from clinical trials with standard psychedelic doses for depression and anxiety suggest that a neurobiological effect beyond placebo is not unreasonable. Randomised controlled trials are needed, complemented by mixed methods social science research and the development of novel resources on microdosing harm reduction.

Lea, T., Amada, N., Jungaberle, H., Schecke, H., & Klein, M. (2020). Microdosing psychedelics: Motivations, subjective effects and harm reduction. The International journal on drug policy, 75, 102600. https://doi.org/10.1016/j.drugpo.2019.11.008

Link to full text

Microdosing psychedelics: Motivations, subjective effects and harm reduction Read More »

Online Community Meet-Up with Janis Phelps - Online Event - June 26

REGISTER NOW