OPEN Foundation

Scienitific Discipline

Synesthesias in the context of hallucinogen-induced persistent perception disorder following the use of lsd

Abstract

The hallucinogen-induced persistent perception disorder (hppd) is a disturbing complication resulting from the use of hallucinogens. We report on a case-study in which an artist suffering from visual, auditory and olfactory hallucinations also experienced chromatic-phonemic synesthesias that had persisted for two years after he had stopped using lysergic acid diethylamide (lsd). The case described demonstrates that individuals suffering from hppd can also experience synesthesias that may in fact differ phenomenologically from ‘coloured hearing’, which is a symptom known to occur in the context of substance abuse.

Neven, A., & Blom, J. D. (2013). [Synesthesias in the context of hallucinogen-induced persistent perception disorder following the use of lsd]. Tijdschrift voor psychiatrie, 56(11), 748-752.
Link to full text

Harmine mediated neuroprotection via evaluation of glutamate transporter 1 in a rat model of global cerebral ischemia.

Abstract

Global cerebral ischemia (GCI) causes energy deficiency results in excessive release of glutamate from neurons. Astrocytic glutamate transporters play a predominant role in keeping extracellular glutamate concentrations below excitotoxic levels. Glutamate transporter 1 (GLT-1) may account for more than 90% of glutamate uptake in adult forebrain. Preclinical findings implicate that Harmine present neuroprotection effects in a rat model of amyotrophic lateral sclerosis disease, and the beneficial effects were specifically due to up-regulation of GLT-1. However, no experiments have explored the potential of Harmine to provide neuroprotection in the setting of GCI. The current study was designed to determine whether Harmine could attenuate cerebral infarction as well as improve neuronal survival after GCI. Furthermore, to test whether the mechanisms were associated with up-regulating of GLT-1, we used a GLT-1 specific inhibitor dihydrokainate (DHK) and analysis the expression of GLT-1 mRNA and protein in cortex of brain. We also examined whether Harmine treatment affected astrocytes activation via immunofluorescence. Our results showed that post-GCI administration of Harmine could attenuate cerebral infarct volume and decrease neurons death. It also caused significantly elevation of GLT-1 mRNA and protein and remarkably attenuation of astrocyte activation. We provide novel clues in understanding the mechanisms of which Harmine exerts its neuroprotective activity in neurological disorders.

Sun, P., Zhang, S., Li, Y., & Wang, L. (2014). Harmine mediated neuroprotection via evaluation of glutamate transporter 1 in a rat model of global cerebral ischemia. Neuroscience letters, 583, 32-36. http://dx.doi.org/10.1016/j.neulet.2014.09.023
Link to full text

Dictyonema huaorani (Agaricales: Hygrophoraceae), a new lichenized basidiomycete from Amazonian Ecuador with presumed hallucinogenic properties

Abstract

Dictyonema huaorani, a new species represented by a well-developed specimen found in the Ecuadorian Amazon region, is described in this paper. The material was collected during a Harvard ethnobotanical expedition in 1981 and originally determined by Mason E. Hale Jr. as belonging in the genus Dictyonema (D. sericeum s.lat.) and possibly representing an undescribed species. The species is morphologically distinctive in forming densely woven, semicircular thalli, closely resembling those of the paleotropical D. ligulatum but lacking clamps and with hyphal sheath around the photobiont filaments that resembles those of Cyphellostereum species. The species was reported to have hallucinogenic properties and chemical analyses suggest certain substances present that are shared with the hallucinogenic mushroom Psilocybe cubensis. Due to our inability to use pure reference compounds and scarce amount of sample for compound identification, however, our analyses were not able to determine conclusively the presence of hallucinogenic substances.

Schmull, M., Dal-Forno, M., Lücking, R., Cao, S., Clardy, J., & Lawrey, J. D. (2014). Dictyonema huaorani (Agaricales: Hygrophoraceae), a new lichenized basidiomycete from Amazonian Ecuador with presumed hallucinogenic properties. The Bryologist, 117(4), 386-394. http://dx.doi.org/10.1639/0007-2745-117.4.386

Link to full text

Immunological Effects of Ayahuasca in Humans

Abstract

Ayahuasca is a botanical hallucinogen traditionally used by indigenous groups of the northwest Amazon. In the last decade, the use of ayahuasca has spread from Brazil, Colombia, Ecuador, and Peru to the U.S., Europe, Asia, and Africa. Despite acute and long-term evidence of good tolerability and safety for ayahuasca administered in the laboratory or ritually consumed in religious contexts, little is known about the immunological impact of ayahuasca on humans. Since ayahuasca is used by an increasing number of consumers, and considering its therapeutic potential, more information is needed regarding ayahuasca potential risks. This article presents a brief overview of the available data regarding the immunological impact of ayahuasca in humans.

dos Santos, R. G. (2014). Immunological Effects of Ayahuasca in Humans. Journal of psychoactive drugs, 46(5), 383-388. https://dx.doi.org/10.1080/02791072.2014.960113

Link to full text

On the transmethylation hypothesis: stress, N,N-dimethyltryptamine, and positive symptoms of psychosis

Abstract

Past research suggests a relationship between stress and positive symptoms of psychosis. However, the biological substrate of this relationship remains unknown. According to the transmethylation hypothesis, schizophrenia could result from a biochemical disruption in the stress mechanism. This biochemical disruption would lead to the production of a substance that would account for the symptoms of psychosis. Moreover, some studies have tested endogenous N,N-dimethyltryptamine (DMT) in the context of the transmethylation hypothesis. Stress has been found to elevate DMT levels in rodents. Also, elevated DMT levels have been associated with positive features of psychosis in psychiatric patients. Additionally, healthy participants treated with exogenous DMT experience predominantly positive symptoms of psychosis. The present paper examines endogenous DMT as a possible biological mediator of the relationship between stress and positive symptoms of psychosis.

Grammenos, D., & Barker, S. A. (2014). On the transmethylation hypothesis: stress, N, N-dimethyltryptamine, and positive symptoms of psychosis. Journal of Neural Transmission, 1-7. https://dx.doi.org/10.1007/s00702-014-1329-5
Link to full text

Single Ketamine Infusion and Neurocognitive Performance in Bipolar Depression

Abstract

We estimated neurocognitive performance using the trail making test (TMT) and the Stroop color-word interference test before, and on the 3rd day after a single infusion of ketamine, in 18 bipolar depressed patients receiving mood-stabilizing drugs. The performance on all tests significantly improved on the 3rd day after ketamine infusion which correlated positively with baseline intensity of neuropsychological impairment and was not associated either with baseline intensity of depression or reduction of depressive symptoms after 3 or 7 days. The results suggest that in such population of patients, single ketamine infusion may improve neuropsychological performance independently of antidepressant effect.

Permoda-Osip, A., Kisielewski, J., Bartkowska-Sniatkowska, A., & Rybakowski, J. K. (2014). Single Ketamine Infusion and Neurocognitive Performance in Bipolar Depression. Pharmacopsychiatry. https://dx.doi.org/10.1055/s-0034-1394399

Link to full text

Effect of psilocin on extracellular dopamine and serotonin levels in the mesoaccumbens and mesocortical pathway in awake rats

Abstract

Psilocin (3-[fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][2-(dimethylamino)ethyl]-1H-indol-4-ol) is a hallucinogenic component of the Mexican mushroom Psilocybe mexicana and a skeletal serotonin (5-HT) analogue. Psilocin is the active metabolite of psilocybin (3-[2-(dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate). In the present study, we examined the effects of systemically administered psilocin on extracellular dopamine and 5-HT concentrations in the ventral tegmental area (VTA), nucleus accumbens, and medial prefrontal cortex of the dopaminergic pathway in awake rats using in vivo microdialysis. Intraperitoneal administration of psilocin (5 and 10 mg/kg) significantly increased extracellular dopamine levels in the nucleus accumbens. Psilocin did not affect the extracellular 5-HT level in the nucleus accumbens. Conversely, systemic administration of psilocin (10 mg/kg) significantly increased extracellular 5-HT levels in the medial prefrontal cortex of rats, but dopamine was decreased in this region. However, neither extracellular dopamine nor 5-HT levels in the VTA were altered by administration of psilocin. Behaviorally, psilocin significantly increased the number of head twitches. Thus, psilocin affects the dopaminergic system in the nucleus accumbens. In the serotonergic system, psilocin contribute to a crucial effect in the medial prefrontal cortex. The present data suggest that psilocin increased both the extracellular dopamine and 5-HT concentrations in the mesoaccumbens and/or mesocortical pathway.

Sakashita, Y., Abe, K., Katagiri, N., Kambe, T., Saitoh, T., Utsunomiya, I., … & Taguchi, K. (2014). Effect of psilocin on extracellular dopamine and serotonin levels in the mesoaccumbens and mesocortical pathway in awake rats. Biological and Pharmaceutical Bulletin, 38(1), 134-138. http://dx.doi.org/10.1248/bpb.b14-00315
Link to full text[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

Ketamine: Promising Path or False Prophecy in the Development of Novel Therapeutics for Mood Disorders?

Abstract

Large ‘real world’ studies demonstrating the limited effectiveness and slow onset of clinical response associated with our existing antidepressant medications has highlighted the need for the development of new therapeutic strategies for major depression and other mood disorders. Yet, despite intense research efforts, the field has had little success in developing antidepressant treatments with fundamentally novel mechanisms of action over the past six decades, leaving the field wary and skeptical about any new developments. However, a series of relatively small proof-of-concept studies conducted over the last 15 years has gradually gained great interest by providing strong evidence that a unique, rapid onset of sustained, but still temporally limited, antidepressant effects can be achieved with a single administration of ketamine. We are now left with several questions regarding the true clinical meaningfulness of the findings and the mechanisms underlying the antidepressant action. In this Circumspectives piece, Dr Sanacora and Dr Schatzberg share their opinions on these issues and discuss paths to move the field forward.

Sanacora, G., & Schatzberg, A. F. (2015). Ketamine: Promising Path or False Prophecy in the Development of Novel Therapeutics for Mood Disorders&quest. Neuropsychopharmacology, 40(2), 259-267. https://dx.doi.org/10.1038/npp.2014.261

Link to full text

Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics

Abstract

Ketamine is the prototype for a new generation of glutamate-based antidepressants that rapidly alleviate depression within hours of treatment. Over the past decade, there has been replicated evidence demonstrating the rapid and potent antidepressant effects of ketamine in treatment-resistant depression. Moreover, preclinical and biomarker studies have begun to elucidate the mechanism underlying the rapid antidepressant effects of ketamine, offering a new window into the biology of depression and identifying a plethora of potential treatment targets. This article discusses the efficacy, safety, and tolerability of ketamine, summarizes the neurobiology of depression, reviews the mechanisms underlying the rapid antidepressant effects of ketamine, and discusses the prospects for next-generation rapid-acting antidepressants.

Abdallah, C. G., Sanacora, G., Duman, R. S., & Krystal, J. H. (2015). Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics. Medicine, 66. https://dx.doi.org/10.1146/annurev-med-053013-062946

Link to full text

Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression

Abstract

Anhedonia—which is defined as diminished pleasure from, or interest in, previously rewarding activities—is one of two cardinal symptoms of a major depressive episode. However, evidence suggests that standard treatments for depression do little to alleviate the symptoms of anhedonia and may cause reward blunting. Indeed, no therapeutics are currently approved for the treatment of anhedonia. Notably, over half of patients diagnosed with bipolar disorder experience significant levels of anhedonia during a depressive episode. Recent research into novel and rapid-acting therapeutics for depression, particularly the noncompetitive N-Methyl-D-aspartate receptor antagonist ketamine, has highlighted the role of the glutamatergic system in the treatment of depression; however, it is unknown whether ketamine specifically improves anhedonic symptoms. The present study used a randomized, placebo-controlled, double-blind crossover design to examine whether a single ketamine infusion could reduce anhedonia levels in 36 patients with treatment-resistant bipolar depression. The study also used positron emission tomography imaging in a subset of patients to explore the neurobiological mechanisms underpinning ketamine’s anti-anhedonic effects. We found that ketamine rapidly reduced the levels of anhedonia. Furthermore, this reduction occurred independently from reductions in general depressive symptoms. Anti-anhedonic effects were specifically related to increased glucose metabolism in the dorsal anterior cingulate cortex and putamen. Our study emphasizes the importance of the glutamatergic system in treatment-refractory bipolar depression, particularly in the treatment of symptoms such as anhedonia.

Lally, N., Nugent, A. C., Luckenbaugh, D. A., Ameli, R., Roiser, J. P., & Zarate, C. A. (2014). Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression. Translational psychiatry, 4(10). https://dx.doi.org/10.1038/tp.2014.105

Link to full text

interested in becoming a trained psychedelic-assisted therapist?

Online Event - Psychedelic Care in Recreational Settings - 3 October 2024