Gordo Posted October 11, 2017 Report Share Posted October 11, 2017 Over in the Costa Rica thread, I touched on this but decided to make a new thread. I'm very interested now in plant compounds that stimulate neurogenesis and cognitive-enhancing effects. I've been reading about the connection between ayahuasca and brain health specifically. Anecdotally, after using ayshuasca one time, in the weeks that followed I experienced a significant "afterglow" and have felt like my brain has been performing at an enhanced capacity. This piqued my curiosity so I did additional research and found many others describing similar effects. A newly published paper explores this: The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro.Another published just this year: Effects of the Natural β-Carboline Alkaloid Harmine, a Main Constituent of Ayahuasca, in Memory and in the Hippocampus: A Systematic Literature Review of Preclinical Studies.Harmine is a natural β-carboline alkaloid found in several botanical species, such as the Banisteriopsis caapi vine used in the preparation of the hallucinogenic beverage ayahuasca and the seeds of Syrian rue (Peganum harmala). Preclinical studies suggest that harmine may have neuroprotective and cognitive-enhancing effects, and retrospective/observational investigations of the mental health of long-term ayahuasca users suggest that prolonged use of this harmine-rich hallucinogen is associated with better neuropsychological functioning. Thus, in order to better investigate these possibilities, we performed a systematic literature review of preclinical studies analyzing the effects of harmine on hippocampal neurons and in memory-related behavioral tasks in animal models. We found two studies involving hippocampal cell cultures and nine studies using animal models. Harmine administration was associated with neuroprotective effects such as reduced excitotoxicity, inflammation, and oxidative stress, and increased brain-derived neurotrophic factor (BDNF) levels. Harmine also improved memory/learning in several animal models. These effects seem be mediated by monoamine oxidase or acetylcholinesterase inhibition, upregulation of glutamate transporters, decreases in reactive oxygen species, increases in neurotrophic factors, and anti-inflammatory effects. The neuroprotective and cognitive-enhancing effects of harmine should be further investigated in both preclinical and human studies. A study published last year: Harmine stimulates proliferation of human neural progenitors. (harmine is the main alkaloid in b. caapi in ayahuasca) Along similar lines of brain health: Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies. Seems like an active area of research that may be of particular interest to biogerontologists and others seeking to maintain peak brain health. Perhaps harmine is most important here, I don't know. Harmine is very inexpensive in the form of syrian rue seed (which can be further extracted quite easily to isolate the desired alkaloids), and does not have the profound psychotropic affects like ayahuasca nor does it contain DMT, it is a reversible MAO inhibitor and certainly has numerous side effects and potential interactions so I'm not advocating its use or especially routine use, mostly just watching intently at this point and learning. Link to comment Share on other sites More sharing options...
mccoy Posted October 12, 2017 Report Share Posted October 12, 2017 Gordo, your experience is sure interesting, but the obvious issue is that it stemmed from very empirical conditions. With an unknown quantity of the active compound(s), you experienced a cognitive improvement. Have you consulted with Dean? Has he experienced the same? Also, what if you partecipated to a ritual in California or in your State with different dosages and provenance of plants? Are the preparations standardized to an extent or can the active principle vary significantly? It may even be that the range of variability is not significant and we may expect similar results in different rituals. But is that true? And is there a frequency threshold beyond which the cognitive improvement becomes a cognitive impairment? Link to comment Share on other sites More sharing options...
Gordo Posted October 16, 2017 Author Report Share Posted October 16, 2017 I'm more interested in the published research than any anecdotes (including my own). As for "is there a frequency threshold beyond which the cognitive improvement becomes a cognitive impairment?", the only thing I've seen so far along those lines is: Personality, Psychopathology, Life Attitudes and Neuropsychological Performance among Ritual Users of Ayahuasca: A Longitudinal Study"...In conclusion, we found no evidence of psychological maladjustment, mental health deterioration or cognitive impairment in the ayahuasca-using group." Link to comment Share on other sites More sharing options...
mccoy Posted October 17, 2017 Report Share Posted October 17, 2017 Their research did not pinpoint cognitive impairment or psychopathological problems in a relatively numerous group of long date users, although they don't rule out the possibility that those who experienced problems may have retired from the use of Ayahuasca and simply not be present in the sample. In other words, they say that their sample is obviously representative of the longtime users who did not experience negative effects but may not be representative of the whole population. The takeaway lesson is probably that Ayahusca can bestow definite mental improvements to those who tolerate it, not barring the possibiity of detrimental effects (which were not observed in long date users). Link to comment Share on other sites More sharing options...
mccoy Posted November 12, 2017 Report Share Posted November 12, 2017 On John Cohen's site 'selfhacked' there is a recent chapter on DMT. It's pretty extensive and makes many things clear, like the use of more plants to inhibit MAO-A which woudl disrupt DMT. https://selfhacked.com/blog/dmt/ Link to comment Share on other sites More sharing options...
Gordo Posted June 14, 2018 Author Report Share Posted June 14, 2018 Just found a lecture on YouTube along the lines of what I was researching in this thread: https://youtu.be/M5RFHgHeR18 Link to comment Share on other sites More sharing options...
TomBAvoider Posted June 14, 2018 Report Share Posted June 14, 2018 There is no doubt that psychedelics have an impact on human psychology, and so might be useful in such things as depression and ptsd, but it's also the case that apparently some compounds have the ability to physically alter the very structure of neural cells: https://www.ucdavis.edu/news/psychedelic-drugs-change-structure-neurons/ Link to comment Share on other sites More sharing options...
Gordo Posted June 14, 2018 Author Report Share Posted June 14, 2018 Its the β-carbolines (harmalas in particular) that interest me, they seem to have anti-cancer, anti-parasite properties and pro-brain health properties. The guy in the video echoed my own thoughts, there is a lot of commercial potential there for big pharma. I hope we see more research on these compounds, harmalas aren't really psychedelic (at least not in the typical sense, I'd say the effects of a harmala mix taken by itself in a typical dose is similar to drinking a glass or 2 of wine). J Psychoactive Drugs. 2017 Jan-Mar;49(1):1-10. doi: 10.1080/02791072.2016.1260189. Epub 2016 Dec 5. Effects of the Natural β-Carboline Alkaloid Harmine, a Main Constituent of Ayahuasca, in Memory and in the Hippocampus: A Systematic Literature Review of Preclinical Studies. Dos Santos RG1,2,3, Hallak JE4,5. Author information AbstractHarmine is a natural β-carboline alkaloid found in several botanical species, such as the Banisteriopsis caapi vine used in the preparation of the hallucinogenic beverage ayahuasca and the seeds of Syrian rue (Peganum harmala). Preclinical studies suggest that harmine may have neuroprotective and cognitive-enhancing effects, and retrospective/observational investigations of the mental health of long-term ayahuasca users suggest that prolonged use of this harmine-rich hallucinogen is associated with better neuropsychological functioning. Thus, in order to better investigate these possibilities, we performed a systematic literature review of preclinical studies analyzing the effects of harmine on hippocampal neurons and in memory-related behavioral tasks in animal models. We found two studies involving hippocampal cell cultures and nine studies using animal models. Harmine administration was associated with neuroprotective effects such as reduced excitotoxicity, inflammation, and oxidative stress, and increased brain-derived neurotrophic factor (BDNF) levels. Harmine also improved memory/learning in several animal models. These effects seem be mediated by monoamine oxidase or acetylcholinesterase inhibition, upregulation of glutamate transporters, decreases in reactive oxygen species, increases in neurotrophic factors, and anti-inflammatory effects. The neuroprotective and cognitive-enhancing effects of harmine should be further investigated in both preclinical and human studies. KEYWORDS:Harmine; hippocampus; learning; memory; neuroprotection PMID: 27918874 ________________________________________________________________________ https://www.ncbi.nlm.nih.gov/pubmed/26496827 Mol Med Rep. 2015 Dec;12(6):7985-91. doi: 10.3892/mmr.2015.4437. Epub 2015 Oct 13. Treatment with harmine ameliorates functional impairment and neuronal death following traumatic brain injury. Zhong Z1, Tao Y2, Yang H1. Author information AbstractTraumatic brain injury (TBI) is a leading cause of mortality in young individuals, and results in motor and cognitive deficiency. Excitotoxicity is an important process during neuronal cell death, which is caused by excessive release of glutamate following TBI. Astrocytic glutamatetransporters have a predominant role in maintaining extracellular glutamate concentrations below excitotoxic levels, and glutamate transporter 1 (GLT‑1) may account for >90% of glutamate uptake in the brain. The β‑carboline alkaloid harmine has been demonstrated to exert neuroprotective actions in vivo, and the beneficial effects were specifically due to elevation of GLT‑1. However, whether harmine provides neuroprotection following TBI remains to be elucidated. The present study performed intraperitoneal harmine injections in rats (30 mg/kg per day for up to 5 days), in order to investigate whether harmine treatment attenuates brain edema and improves functional recovery in a rat model of TBI. The neuronal survival ratio and the protein expression of apoptosis‑associated caspase 3 were also assessed in the hippocampus of the rat brain. Furthermore, the expression levels of GLT‑1 and inflammatory cytokines were detected, in order to determine the underlying mechanisms. The results of the present study demonstrated that administration of harmine significantly attenuated cerebral edema, and improved learning and memory ability. In addition, harmine significantly increased the protein expression of GLT‑1, and markedly attenuated the expression levels of interleukin‑1β and tumor necrosis factor‑α, thereby attenuating apoptotic neuronal death in the hippocampus. These results provided in vivo evidence that harmine may exert neuroprotective effects by synergistically reducing excitotoxicity and inflammation following TBI. PMID: 26496827 Link to comment Share on other sites More sharing options...
Gordo Posted June 14, 2018 Author Report Share Posted June 14, 2018 I didn't realize beta-carbolines were in coffee: https://www.ncbi.nlm.nih.gov/pubmed/16139309 Life Sci. 2006 Jan 18;78(8):795-802. Epub 2005 Aug 31. Human monoamine oxidase enzyme inhibition by coffee and beta-carbolines norharman and harman isolated from coffee. Herraiz T1, Chaparro C. Author information AbstractMonoamine oxidase (MAO) is a mitochondrial outer-membrane flavoenzyme involved in brain and peripheral oxidative catabolism of neurotransmitters and xenobiotic amines, including neurotoxic amines, and a well-known target for antidepressant and neuroprotective drugs. Recent epidemiological studies have consistently shown that coffee drinkers have an apparently lower incidence of Parkinson's disease (PD), suggesting that coffee might somehow act as a purported neuroprotectant. In this paper, "ready to drink" coffee brews exhibited inhibitory properties on recombinant human MAO A and B isozymes catalyzing the oxidative deamination of kynuramine, suggesting that coffee contains compounds acting as MAO inhibitors. MAO inhibition was reversible and competitive for MAO A and MAO B. Subsequently, the pyrido-indole (beta-carboline) alkaloids, norharman and harman, were identified and isolated from MAO-inhibiting coffee, and were good inhibitors on MAO A (harman and norharman) and MAO B (norharman) isozymes. beta-carbolines isolated from ready-to-drink coffee were competitive and reversible inhibitors and appeared up to 210 microg/L, confirming that coffee is the most important exogenous source of these alkaloids in addition to cigarette smoking. Inhibition of MAO enzymes by coffee and the presence of MAO inhibitors that are also neuroactive, such as beta-carbolines and eventually others, might play a role in the neuroactive actions including a purported neuroprotection associated with coffee consumption. PMID: 16139309 Link to comment Share on other sites More sharing options...
Sibiriak Posted June 15, 2018 Report Share Posted June 15, 2018 Some raisins with your coffee? Identification and occurrence of beta-carboline alkaloids in raisins and inhibition of monoamine oxidase (MAO).Herraiz T1 J Agric Food Chem. 2007 Oct 17;55(21):8534-40. https://www.ncbi.nlm.nih.gov/pubmed/17883257 The potential anxiety-causing effects of beta-carbolines might be a concern for some. An overview of cognitive aspects of β-carbolines http://journals.sbmu.ac.ir/jps/article/download/5209/4522 Link to comment Share on other sites More sharing options...
TomBAvoider Posted June 15, 2018 Report Share Posted June 15, 2018 Good catch, Gordo! I wonder if there are differing amounts of beta-carbolines depending on coffee varietal, roast amount, preparation method etc. This is not a trivial question, as f.ex. I noted that most studies referencing the purported benefits of green tea focused on EGCG rather than other tea catechins. Meanwhile, it is totally dependant on brewing conditions temperature and duration as EGCG changes into other catechins very rapidly and you have a very narrow window in which to capture the most EGCG. If you drink green tea hoping for the same effects that were indentified in studies highlighting EGCG, then you better focus your tea preparation on maximising EGCG. This is the context in which I wonder how beta-carbolines are affected by the above mentioned variables. Link to comment Share on other sites More sharing options...
TomBAvoider Posted June 15, 2018 Report Share Posted June 15, 2018 The raisin study identified the effects in vitro, does that matter? Gordo's study seems to cite epidemiological evidence rather than in vivo or vitro studies showing coffee directly affecting MAO. I wonder if beta-carboline alkaloids in raisins are equally bio-available as in coffee. Link to comment Share on other sites More sharing options...
Sibiriak Posted June 15, 2018 Report Share Posted June 15, 2018 There are quite a few natural substances touted as MAO inhibitors and numerous articles on the subject, scientific and non-scientific. A small selection: Herbal natural products as a source of monoamine oxidase inhibitors: a review. Viña D1, Serra S, Lamela M, Delogu G. Curr Top Med Chem. 2012;12(20):2131-44. AbstractDrugs of natural origin still play a major role in the treatment of many diseases and as lead structures for the development of new synthetic drug substances. This review article deals the pharmacological effects on the Central Nervous System (CNS) of some plant extracts and their isolated chemical components due to their monoamine oxidase (MAO) activity. Herbs and herbal preparations containing MAO-A inhibitors have been widely used as an effective alternative in the treatment of neuropsychiatric diseases such as depression. Inhibitors of MAO-B not only enhance dopaminergic neurotransmission but also prevent activation of toxin and free radical formation, alleviating the process of neuron denaturalization, on account of which they are used in Parkinson disease (PD). Several methods have been developed for monitoring MAO activity and its inhibitor screening of bioactive natural products. Natural Monoamine oxidase inhibitors : A Review https://www.researchgate.net/publication/41805982_Natural_Monoamine_oxidase_inhibitors_A_Review Monoamine Oxidase-A Inhibition and Associated Antioxidant Activity in Plant Extracts with Potential Antidepressant Actions https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820675/ Monoamine oxidase inhibitors [long list of natural substances] https://www.botanical-online.com/english/vegetalmaois.htm Common Herbs With MAO Inhibitor Activity https://www.livestrong.com/article/82970-common-herbs-mao-inhibitor-activity/ Why We Should Be Interested in Natural MAO Inhibitors https://thesunlightexperiment.com/blog/2017/2/14/natural-mao-inhibitors Link to comment Share on other sites More sharing options...
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