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Our vision is that psychedelics can be used worldwide to better the lives of as many as 450 million people who suffer from mental health problems. Our information hopes to make that vision come to life just a little faster.
Here will be a narrative, readable, summary of the research.
In our literature study we came across the following studies of note. Browse the meta, review, commentary articles for an overview. Check out the individual studies for specific experiments and observations.
From Psychiatry to Neurology: Psychedelics as Prospective Therapeutics for Neurodegenerative Disorders
2021 | Figiel, M., Kozłowska, U., Nichols, C. D., Wiatr, K.
This review (2021) finds that psychedelics may act as modulators of the immune system by reducing levels of pro-inflammatory biomarkers. The early evidence points towards psychedelics also being effective in treating or preventing brain injury and neurodegenerative diseases (e.g. Alzheimer's Disease).
Banisteriopsis caapi, a Forgotten Potential Therapy for Parkinson’s Disease?
2015 | Bernschneider‐Reif, S., Lees, A., Poewe, W.
This review (2015) examines Banisteriopsis caapi and its active alkaloid harmine as a potential therapy for Parkinson’s disease based on its unique pharmacological profile, which includes selective MAO type A inhibition, serotonin affinity, NMDA receptor antagonism, and possible antioxidative and neuroprotective properties, and may also cause direct striatal dopamine release.
Catalysts for change: the cellular neurobiology of psychedelics
2021 | Banks, M. I., Jones, N. T., Sultan, Z. W., Wenthur, C. J., Zahid, Z.
This review (2021) examines the psychoplastogenic effects (neural plasticity) of psychedelics and summarizes the current understanding of the cellular and subcellular mechanisms underlying their ability to produce long-term structural changes and reduce inflammation.
Registered clinical studies investigating psychedelic drugs for psychiatric disorders
2021 | Gill, H., Lipsitz, O., Lui, L. M. W., McIntyre, R. S., Rosenblat, J. D., Siegel, A. N., Teopiz, K. M.
This review (2021) summarizes the study characteristics of all ongoing registered clinical trials investigating psychedelic drugs for psychiatric disorders and identifies that their majority focuses on investigating MDMA and psilocybin for treating depression or PTSD, while only 30% of their results are published.
Psychedelics as anti-inflammatory agents
2018 | Flanagan, T. W., Nichols, C. D.
This review (2018) examines the cellular pathways through which psychedelics act as anti-inflammatory agents by means of selectively blocking the expression of pro-inflammatory mediators and thereby modulating histone modifications and epigenetic signaling. It is thus hypothesized that psychedelics may be of therapeutic value to a wide range of inflammatory disorders in humans.
Do entheogen-induced mystical experiences boost the immune system? Psychedelics, peak experiences, and wellness
1999 | Roberts, T. B.
This article (1999) advances the hypothesis that entheogen-induced mystical experiences influence the immune system.
Immunological Effects of Ayahuasca in Humans
2014 | Dos Santos, R. G.
This meta-analysis (2014) examined double-blind, placebo-controlled clinical trials of acute ayahuasca administration and studies of long-term ayahuasca consumption that investigated its effects on the immune system. They found evidence that it reduces bloodstream levels of CD3 and CD4-type lymphocytes and increases the level of natural killer cells, or large granular lymphocytes, in the acute phase but not in the long term.
Anti-inflammatory activity of ayahuasca and its implications for the treatment of neurological and psychiatric diseases
2021 | da Silva, M. G., Daros, G. C., de Bitencourt, R. M.
This review (2021) examines the antioxidant, anxiolytic (anxiety), and antidepressant effects of ayahuasca, with a particular emphasis on its anti-inflammatory action yielding therapeutic benefits for disorders related to neuroinflammatory factors.
Dimethyltryptamine (DMT): a biochemical Swiss Army knife in neuroinflammation and neuroprotection?
2016 | Frecska, E., Szabo, A.
This commentary reviews the role of DMT as an endogenous ligand of the Sigma-1 receptor, and although the exact physiological role of endogenous DMT is yet to be identified, there is evidence that suggests that it can modulate immune responses through the suppression of inflammatory cytokines. These neuroprotective and neuroregenerative effects may render DMT a potentially useful therapeutic tool in a broad range of chronic inflammatory and autoimmune diseases.
A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity
2013 | Frecska, E., Luna, L. E., McKenna, D., Szabo, A., Winkelman, M. J.
This review (2012) postulates that DMT may play a role in cell protection, regeneration, and immunity through activation of a cell-endogenous sigma-1 receptor pathway which regulates oxidative stress-induced changes at the endoplasmic reticulum–mitochondria interface. Supportive experimental data are still necessary for advancing the outlined concepts, such as the endogenous role of DMT or the immunoprotective benefits of exogenous DMT ingested in larger quantities.
Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities
2015 | Szabo, A.
This review (2015) describes the immunomodulatory potential of classical serotonergic psychedelics (DMT, LSD, MDMA, etc) from a perspective of molecular immunology and pharmacology. With a particular focus on functional interaction of serotonin and sigma-1 receptors and cross-talk with toll-like and RIG-I-like pattern-recognition receptor-mediated signalling.
Psychedelics as a Novel Approach to Treating Autoimmune Conditions
2020 | Szabo, A., Thompson, C.
This literature review (2020) argues that psychedelics may be used to treat autoimmune conditions. This may be done via inflammatory pathways, immune modulation or other methods.
Family of Structurally Related Bioconjugates Yields Antibodies with Differential Selectivity against Ketamine and 6-Hydroxynorketamine
2021| Kyzer, J. L., Wenthur, C. J., Worob, A., Zheng, Z.
As ketamine is being increasingly used in therapeutic settings, this in vivo study explored the possibility of developing an antidote for ketamine intoxication/overdose. To do so, three hapten molecules (small molecules that elicit an immune response only when attached to a large carrier such as a protein) similar in structure to ketamine were synthesized. All three haptens elicited immune responses in mice, leading to the production of antibodies with varying affinities for ketamine. These findings indicate a potential approach toward mitigating ketamine overdose and further study the antidepressant effects of ketamine and its metabolites.
Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome
2017| Charney, D. S., Costi, S., Horn, S. R., Iosifescu, D. V., Kiraly, D. D., Murrough, J. W., Schwartz, J., Van Dam, N. T.
This between-subjects study (n=59) examined the peripheral immune profiles in patients with depression (n=33) before and after ketamine treatment (35mg/70kg) compared to healthy participants (n=26). Pro-inflammatory cytokines were consistently elevated among patients with depression, and although ketamine infusion transiently lowers these markers of inflammation, these changes appear not to be directly linked to clinical antidepressant effects on the long-term.
Associations between lifetime classic psychedelic use and cardiometabolic diseases
2021| Carhart-Harris, R. L., Hendricks, P. S., Osika, W., Simonsson, O.
This observational survey study (n=752.374) investigated the relationship between lifetime classic psychedelic use and cardiometabolic diseases and found that lifetime classic psychedelic use was associated with a 23% lower odds of heart disease and a 12% lower odds of diabetes in the past year.
Hemorheological and metabolic consequences of renal ischemia-reperfusion and their modulation by N,N-dimethyl-tryptamine on a rat model
2018| Bidiga, L., Deak, A., Frecska, E., Ghanem, S., Magyar, Z., Mester, A., Nemeth, N., Nemes, B., Peto, K., Somogyi, V., Tanczos, B.
This rodent study investigates the effects of administering DMT in renal ischemia-reperfusion (I/R) injury (robust inflammatory and oxidative stress response to hypoxia and reperfusion which disturbs the organ function) and its hematological (blood-related) and metabolic consequences. It found that DMT could diminish but cannot completely prevent the impairment post the renal I/R.
Salvia divinorum: from recreational hallucinogenic use to analgesic and anti-inflammatory action
2019| Coffeen, U., Pellicer, F.
This review (2019) examines the analgesic, anti-inflammatory, and psychoactive properties of the hallucinogenic plant Salvia Divinorum and its bioactive (analog) constituents.
N,N-Dimethyltryptamine attenuates spreading depolarization and restrains neurodegeneration by sigma-1 receptor activation in the ischemic rat brain
2021| Bari, F., Berkecz, R., Cozzi, N. V., Dvorácskó, S., Farkas, A. E., Farkas, E., Frank. R., Frecska, E., Hantosi, D., Kecskés, S., Kömöczi, T., Krizbai, I. A., Menyhárt, À., Szabó, Ì., Tömmböly, C., Varga, V. È.
This animal study (n=69) examined whether DMT (1mg/kg/h) administration achieves neuroprotection via Sig-1R activation during an experimentally induced forebrain ischemia in rats and found that DMT attenuated the electrophysiological signature neurodegeneration even when 5-HTR binding was inhibited with a serotonergic antagonist, which confirmed the neuroprotective role of Sig-1R activation in their hypothesis.
Harmines inhibit cancer cell growth through coordinated activation of apoptosis and inhibition of autophagy
2018| Geng, X., Ren, Y., Tang, J., Tian, D., Wang, F., Yao, X., Zhang, Y.
This in vivo cell culture study investigated the effects of harmine (and its derivatives) on cancer cell growth and determined that it inhibits cancerous growth via the coordinated action of two cellular pathways that initiate cell death, without inflicting damage to DN
A Single Dose Of Ayahuasca Modulates Salivary Cortisol In Treatment-Resistant Depression
2018| Adams, T.
This randomized double-blinded placebo-controlled between-subjects study (n=71) investigated the effects of ayahuasca (23.52mg DMT, 130.2mg harmine, 16.8mg harmaline, 84mg tetrahydroharmine /70kg) on salivary and plasma cortisol levels in patients with depression compared to healthy controls. Ayahuasca restored the corticosteroid insufficiency of depressed patients and increased their cortisol response to that of healthy controls.
Psychedelic N,N-Dimethyltryptamine and 5-Methoxy-N,N-Dimethyltryptamine Modulate Innate and Adaptive Inflammatory Responses through the Sigma-1 Receptor of Human Monocyte-Derived Dendritic Cells
2014| Frecska, E., Kovacs, A., Rajnavolgyi, E., Szabo, A.
This in vitro (neuronal cell culture) study investigated the anti-inflammatory effects of NN-DMT and 5-MeO-DMT (100 μM), and demonstrate that its immunomodulatory effects on the functional activities of human dendritic cells operate through the sigma-1 receptor.
Psychopathological, neuroendocrine and autonomic effects of 3,4-methylenedioxyethylamphetamine (MDE), psilocybin and d-methamphetamine in healthy volunteers: results of an experimental double-blind placebo-controlled study
1999| Gouzoulis-Mayfrank, E., Habermeyer, E., Hermle, L., Kovar, K., Kunert, H. J., Lindenblatt, H., Sass, H., Spitzer, M., Thelen, B.
This randomized, double-blind, placebo-controlled, between-subjects study (n=32) investigated the effects of MDE (140mg/70kg), psilocybin (14mg/70kg), and methamphetamine (14mg/70kg) on the mental state and the neuroendocrine and autonomic nervous system of healthy participants. The entactogen MDE took an intermediate position between the stimulant methamphetamine and the hallucinogen psilocybin and elicited highly characteristic emotional effects, that were qualitatively different from the effects of the other two drugs, which supports the hypothesis that entactogens constitute a distinct psychoactive substance class.
The effect of Banisteriopsis caapi (B. caapi) on the motor deficits in the MPTP-treated common marmoset model of Parkinson’s disease
2018| Abbate, V., Fisher, R., Hider, R., Jackson, M. J., Jenner, P., Lees, J., Lincoln, L., Rose, S.
This animal study (n=8) investigated the efficacy of Banisteriopsis caapi (0.1 - 0.3 mg/kg harmine) alone and in combination with L‐DOPA (4 - 7 mg/kg) to treat parkinsonian dyskinesia in a marmoset disease model. B. caapi alone has a mild antiparkinsonian effect but does not enhance the L‐DOPA response or reduce dyskinesia.
First Time View on Human Metabolome Changes after a Single Intake of 3,4-Methylenedioxymethamphetamine in Healthy Placebo-Controlled Subjects
2017| Boxler, M. I., Kraemer, T., Liechti, M. E., Schmid, Y., Steuer, A. E.
This randomized, double-blind, placebo-controlled crossover study (n=15) investigated changes in endogenous plasma metabolites following a single intake of MDMA (125 mg) and found an overall increase in oxidative stress indicated by the metabolic ratio of methionine-sulfoxide over methionine.
Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports
2019| Cassol, H., Charland-Verville, V, Erowid, E., Erowid, F., Greyson, B., Laureys, S., Martial, C., Pallavicini, C., Sanz, C., Tagliazucchi, E., Vivo, R. M, Zamberlan, F.
This large-scale data-analytic study compared the semantic similarity of psychoactive trip reports (n≈15,000) and narrative accounts Near-Death Experiences (n=625), and found that ketamine (followed by salvinorin A and DMT) bared the most resemblance to the experience of 'dying'. The authors speculate that a ketamine model of Near-Death Experiences may indicate a neuroprotective function of endogenous NMDA antagonists released in the proximity of death.
Serotonin 5-HT₂ receptor activation prevents allergic asthma in a mouse model
2015| Ahlert, T., Cormier, S. A., Happel, K. I., Miller, J., Nau Jr, F., Nichols, C. D., Saravia, J., Yu, B.
This animal study investigated the effects of the highly selective 5-HT₂ receptor agonist (R)-DOI (0.01-1mg/kg) in a mouse model of allergic asthma. They demonstrate that inhaled (R)-DOI has potent anti-inflammatory effects and blocks the development of allergic asthma through the activation of the serotonin 5-HT2A receptor subtype.
Structure–Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore
2020| Billac, G. B., Cormier, S. A., Flanagan, T. W., Landry, A. N., Sebastian, M. N.
This animal study (n=52) investigated structure−activity relationships between 5-HT2A receptor agonists within a novel rat model of allergic asthma and identified that phenylalkylamine structure 2,5-dimethoxyphenethylamine (2C-H) mediated anti-inflammatory activity. There was no apparent correlation between behavioral and anti-inflammatory effects, which indicates distinct structural features of 5-HT2A receptor activity that can be utilized for the development of asthma treatments independent of subjective psychedelic effects.
The therapeutic potentials of ayahuasca: possible effects against various diseases of civilization
2016| Bokor, P., Frecska, E., Winkelman, M. J.
This review (2016) examines the therapeutic potential of ayahuasca based on a summary of its neurobiological, neuroregenerative, and psychophysiological mechanisms and effects on vegetative states and the central nervous system. It emphasizes highlights the therapeutic utility of ayahuasca on a biological level as an anti-inflammatory agonist of the Sigma-1 receptor while incorporating its effects on higher-order psychotherapeutic effects within a bio-psycho-socio-spiritual model.
Acute effects of lysergic acid diethylamide on circulating steroid levels in healthy subjects
2016| Dolder, P. C., Kratschmar, D. V., Liechti, M. E., Odermatt, A., Rentsch, K. M., Schmid, Y., Strajhar, P.
This randomized, double‐blind, placebo‐controlled, cross‐over study (n=16) investigated the effects of LSD (200μg) on the plasma concentration-time profiles of steroid levels. LSD induced significant effects on plasma glucocorticoids, including cortisol and particularly corticosterone, which was also closely related to the subjective effects of LSD. The glucocorticoid response to LSD showed no acute pharmacological tolerance, in contrast to the glucocorticoid response to MDMA.
The DMT and Psilocin Treatment Changes CD11b+ Activated Microglia Immunological Phenotype
2021| Figiel, M., Klimczak, A., Kozłowska, U., Wiatr, K.
This study on neuronal-glial cells (CD11b+ microglia, from mice) found that the direct application of psilocin (a metabolite of psilocybin) and DMT, led to increased capacity for the cells to fulfill their immune responses. Specifically, it reduced levels of TLR4, p65, CD80 proteins (markers of the immune response), and upregulated TREM2 (neuroprotective receptor).
Low Doses of LSD Acutely Increase BDNF Blood Plasma Levels in Healthy Volunteers
2020| Dolder, P. C., Eckert, A., Feilding, A., Holze, F., Hutten, N. P. W., Kuypers, K. P. C., Liechti, M. E., Mason, N. L., Ramaekers, J. G., Theunissen, E. L., Varghese, N.
A low/micro (20µg) dose of LSD increased neuroplasticity as measured by brain-derived neurotrophic factor (BDNF) levels at 6 hours (n=24). The results are however ambiguous and not present at all values/times.
This section compares the research with psychedelics to other therapies, medicines, or treatments.
This section highlights the various measures used and their use in research.
Who are the top researches in this area, the ones who have done the groundbreaking research.
What do we not know at this time? Where are the gaps in our knowledge and are we closing it?
The companies that are actively engaged in researching this topic or (planning to) provide therapy focussed on this topic.
This section highlights everything done outside of academia, from popular press to books and non academic research.