• Psychedelic Medicine

DMT | +50 articles

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World’s First clinical trial for DMT-assisted therapy in Major Depressive Disorder confirms safety, tolerability*

by Louise Sommerfeld | The Dales Report | 22 Feb 2022

In the Phase I clinical trial, participants were administered SPL026 and underwent a 20-minute psychedelic experience.

Phase I full dataset demonstrates consistent dose related effects on the intensity and quality of the psychedelic experience.


Small Pharma, a neuropharmaceutical company focused on psychedelic-assisted N,N-dimethyltryptamine (“DMT”) therapies for mental health, is pleased to share the analysis of Phase I data from the combined Phase I/IIa clinical trial of SPL026 with psychotherapy for the treatment of Major Depressive Disorder (“MDD”).

In the dose-escalating, placebo-controlled Phase I study, 32 healthy psychedelic naïve volunteers across four dose cohorts received either SPL026 in combination with psychotherapy or placebo. This analysis provides additional insight into dose-related effects on the primary outcomes of safety and tolerability as well as on pharmacodynamic measures, including the treatment experience and subject well-being.​

The analysis of the unblinded data set supports our choice to explore the antidepressant potential of our selected dose of SPL026 in the Phase IIa trial. Given the subjectivity of the psychedelic experience, it was exciting to see a close correlation between levels of drug in the body and pharmacodynamic endpoints. As for the subjects’ experience, most reported that it was pleasurable, not too challenging, and most importantly, nobody expressed any regrets. Additionally, the strong safety profile and rapid clearance of SPL026 from the body provides the potential for a scalable treatment with limited monitoring needs post dosing.
Dr. Carol Routledge, Chief Medical and Scientific Officer of Small Pharma

Key Results

  • No drug-related serious adverse events and minimal short-lived adverse events reported on dosing day.
  • Of 20 drug-related adverse events, all were mild or moderate and resolved rapidly and independently.
  • No statistically significant negative effects on anxiety and well-being identified at any point during the three-month follow-up.
  • Data show a clear correlation between quality of psychedelic experience and dosing levels, starting at 9mg and up to 21.5mg, across all four cohorts.
    • Participant-reported scores, using a 0 to 100 scale, on the richness of the psychedelic experience demonstrated increasing values of 48 (9mg), 79, 79, 88 (21.5mg) across the four increasing doses. A dose correlation was seen across most patient-reported scores.
    • Therapist assessment of the predicted therapeutic benefit of SPL026 demonstrated a positive relationship with dose.
  • In the majority of participants, there was a strong correlation between levels of N,N-dimethyltryptamine (“DMT”) in the body and the quality and intensity of the psychedelic experience.
  • IV administration of SPL026 offers a short-lived, well-tolerated psychedelic experience of ~20 minutes, enabling a dosing session to last only ~30 minutes.
  • Pharmacokinetic sampling supported rapid clearance out of the body, showing near undetectable DMT levels in the blood by 60 minutes at all investigated doses.
The data confirms the selected dose of SPL026 taken forward into Phase IIa most consistently delivers the target treatment profile across subjects through a multi-dimensional assessment including safety, tolerability, pharmacokinetic and pharmacodynamic parameters. The full dataset is anticipated to be published in a peer reviewed journal.

David Erritzoe of Imperial College London, Chief Investigator of the Phase I/IIa study said: “Psychedelic-assisted therapies have the potential to completely change the treatment paradigm of mental health conditions. The additional insights from Small Pharma’s Phase I study show promising results at this stage of the development. The dosing time of 30 minutes, in comparison with up to 6 hours seen with alternative approaches, has the potential to offer a real benefit in terms of treatment regimen for both patients and providers.”

The blinded, randomized, placebo-controlled, proof-of-concept Phase IIa study of SPL026 in combination with psychotherapy in 42 patients with MDD remains on track to deliver topline results in the first half of 2022. This study will assess the efficacy of one dose of SPL026 versus a placebo, and one versus two doses of SPL026 in combination with psychotherapy in patients with MDD while bolstering existing safety and tolerability data.​

To view the original press release in its entirety click here.

*From the article here :
 
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Tackling Trauma with Pharmahuasca and DMT*

by Nathan White, PhD | Psychedelic Science Review | 24 Feb 2022

Post-traumatic stress disorder (PTSD) typically develops in response to an extremely threatening or distressing experience (or a series of experiences), with symptoms presenting as re-experiencing the trauma through dreams and vivid intrusive thoughts, avoidant behaviour, anxiety, and a persisting state of hypervigilance. People afflicted with PTSD have been shown to present with prolonged inflammation due to an increased level of pro-inflammatory molecules, such as interleukin-1 beta (IL-1β).

In addition, the levels of reactive oxygen species (ROS), which are typically generated through normal cellular processes, are also found in excess. In this scenario, the ROS are implicated in premature cell ageing and induce mutagenesis, i.e., they can modify DNA. Sustained inflammation and ROS delays healing, resulting in altered cell behaviour or even cell death, and eventually leading to disease. The mechanisms underlying inflammation and ROS are interconnected, which makes them an attractive potential target for future PTSD therapies.

Dimethyltryptamine (DMT) is a compound capable of inducing potent psychedelic experiences that are typically much shorter than other “classical” psychedelics such as psilocybin or LSD. Despite its discovery in western medicine in the late 50’s by Dr. Stephen Szara, indigenous tribes of the Amazon rainforest have been using DMT ritualistically for hundreds of years in the form of a brewed tea, commonly known as ayahuasca.

Ayahuasca is a complex mixture containing DMT, the monoamine oxidase inhibitors harmine and harmaline (which prevent the body from breaking down DMT when ingested orally), as well as various other compounds that may have clinical relevance. However, these mixtures vary in their composition from batch to batch. To ensure treatments are replicable, the complexity of the mixture can be standardized and reduced to a combination of DMT and a monoamine oxidase inhibitor such as harmine or harmaline, known as “pharmahuasca”.

Study Aims

Psychedelics have shown promising efficacy in treating mental health disorders, with potential mechanisms including the promotion of neural plasticity, reducing inflammation, or even stimulating positive emotional processes. Exposure to a single dose of a psychedelic is enough to sustainably ablate the fear response in animal models of anxiety, however the potential of DMT (or ayahuasca) to treat PTSD has not been extensively investigated. In a recently published paper, Dr. Kelley and colleagues sought to bring new light to this matter by exploring the mechanisms through which DMT and pharmahuasca could help treat PTSD.

Study Overview

Validation of the Rat PTSD Model

To study how DMT and pharmahuasca affect the expression of genes associated with PTSD, a previously developed PTSD model induced in rats (henceforth referred to as PTSD rats) was used. Although the behavioural and biochemical profiles of the PTSD rats were previously established, it is unclear which genes are differentially expressed (DEGs) when compared to a control (i.e., rat models without PTSD) and to what extent they overlap with DEGs in humans affected by PTSD.

The researchers identified around 200 genes expressed in PTSD rats to be differently regulated in contrast to controls. This compares to around 400 DEGs in the brains of humans affected with PTSD relative to healthy individuals. When comparing the DEGs identified in both human and rat datasets, they found an overlap of 20 DEGs (henceforth referred to as ‘PTSD genes’) that are involved in processes including inflammation, cell growth, and cell signalling between neurons (GABA signalling – a pathway found to be affected in PTSD patients).

Rescue of Differentially Expressed Genes

When PTSD rats were administered DMT, harmaline, or pharmahuasca, around 4000, 5000, and 3000 genes were found to be differently regulated, respectively, compared to controls. Out of the 20 overlapping ‘PTSD genes’ between PTSD rats and PTSD afflicted humans, the expression of 9, 12 and 14 genes was restored closer to that of the controls after DMT, harmaline, or pharmahuasca treatment, respectively. DMT treatment also downregulated genes involved in the production of ROS and upregulated those associated with neurotransmission and neural plasticity. Harmaline does not only inhibit the enzymes that prevent DMT from being degraded, but it also plays an active role in both reducing the levels of ROS products and promoting neuroplasticity.

Unlike harmaline or DMT alone, pharmahuasca did not rescue the expression of the gene encoding somatostatin, a molecule involved in neurotransmission and found to be downregulated in both this rat PTSD model and in PTSD sufferers. Nevertheless, pharmahuasca increased the expression of genes encoding the receptors to which somatostatin binds to. In addition, pharmahuasca was shown to downregulate the expression of a major factor (NFKB2) involved in regulating the inflammatory response and to upregulate the expression of genes implicated in pathways which allow neurons to form connections to other neurons (synaptogenesis). Interestingly, pharmahuasca reduced the expression of an enzyme involved in the production of endogenous DMT, which is expressed in the brains of both humans and rats.

ROS Production Reversed

It was previously shown that PTSD rats have an increased level of ROS products in their brain and other tissues. The study conducted by Dr. Kelley and colleagues not only corroborated these findings, but also demonstrated that both DMT and pharmahuasca treatment can reduce the levels of ROS closer to those found in a non-PTSD control group.

Study Limitations

Previous research has shown that a single treatment of a serotonin receptor binding psychedelic results in lasting synaptic structure changes. In this study, however, it is unclear whether the rescued expression of the ‘PTSD genes’ following the treatments is sustained in their absence and longer timepoints would be required to observe this. Although expression of ‘PTSD genes’ was restored to levels similar to the control groups after treatment, it is unclear whether the behaviour of the PTSD rats changed, an observation that could have strengthened their results.

In addition, the neuroanatomy of the brains of PTSD affected individuals is known to be structured differently compared to non-affected individuals, however, no histological examinations of the brains from PTSD rats that underwent the various treatments were performed. Consequently, it is unclear whether the neuroanatomy is altered in this PTSD model, although this is something that could be further explored in future research to strengthen the model. Lastly, this study was largely limited to gene expression analysis, which does not necessarily translate into the function of the cells. Nevertheless, they did show that actual ROS levels were reduced, complimenting some of their gene expression data.

Some of these limitations were discussed by the authors of this study, who emphasized that their aim was to expand the knowledge regarding transcriptional regulation following psychedelic treatment by building and analyzing a large gene expression dataset.

Conclusion

The results presented in the study carried out by Dr. Kelley and colleagues advanced our knowledge regarding the validation of an animal model of PTSD and the expression of genes after psychedelic exposure. They also showed a decrease in the actual levels of ROS following psychedelic treatment, emphasizing the validity of their gene expression data. This study expands our understanding of PTSD and opens an avenue of developing effective psychedelic based treatment regimens for this disorder.

*From the article (including references) here :
 
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Positive results for DMT-analogue in treating glaucoma*

Psilocybin Alpha | 23 Feb 2022​
  • PharmaDrug receives encouraging potency data for candidate DMT-analogue molecules designed to treat primary open angle glaucoma
  • Terasaki Institute advances PharmaDrug’s candidate DMT-analogue molecules into next phase of potency/kinetics study
  • Terasaki Institute initiates fabrication of novel medical device designed to deliver PharmaDrug’s lead candidate to glaucoma patients
PharmaDrug, a specialty pharmaceutical company focused on the research, development and commercialization of controlled-substances and natural medicines such as psychedelics, cannabis and naturally-derived approved drugs, is pleased to announce that it has successfully completed a head-to-head potency comparator study of its two undisclosed DMT-analogue candidates for the treatment of primary open angle glaucoma (POAG). Following this successful outcome, the Company, in collaboration with the Terasaki Institute for Biomedical Innovation (TIBI), has initiated fabrication activities necessary to produce a novel medical device capable of delivering sustained, low (sub-psychedelic) quantities of their undisclosed tryptamine-based pharmaceutical to the front of the eye. The Company intends to use the current results in combination with several planned upcoming in vitro studies to elect its final development candidate. Future in vivo efficacy testing in an accepted model of POAG is currently being planned with the goal of providing all necessary support to file an investigative new drug (IND) application with the FDA to conduct clinical studies.

Paul Van Slyke, CSO of PharmaDrug commented, “Despite the availability of several approved medications, irreversible vision loss related to elevated intraocular pressure (IOP) remains a significant risk for patients suffering from glaucoma. We are excited to announce that our recently generated data demonstrates that the concept of using select DMT-analogues to activate protective pathways within critical cellular compartments of the eye may provide significant utility in treating elevated IOP. The next few months will be vital in further characterizing relative drug potency, selecting a single lead candidate to take forward and fabricating a novel medical device capable of delivering constant and sustained levels of drug to the anterior portion of the eye. The following research phase will focus on IND enabling efficacy studies using a well accepted animal model of POAG.”

The aim of PharmaDrug’s DMT-analogue research program in ocular health is to develop suitable prototype medical devices capable of sustained ocular drug-delivery while also confirming efficacy, biocompatibility and stability of its candidate molecules in models of elevated IOP. The research program scope includes full establishment and demonstration of candidate molecule loading capacity as well as release rate evaluations of conjugated materials using appropriate models that will be used to support an IND application with the FDA in the future.

The Company has completed its initial potency evaluation of two test articles using an in vitro calcium mobilization assay on trabecular meshwork cells; a cell type known to be critically important in the maintenance of healthy IOP. Calcium mobilization is understood to provoke cellular contraction, and specifically in the case of trabecular meshwork cells, is thought to contribute to the maintenance of healthy IOP by channeling aqueous humor away from the front of the eye. Both test articles were found to activate calcium mobilization, to levels that were comparable or greater than the experimental positive control, ionomycin. The Company’s test articles were previously examined for in vitro toxicity and were found to be non-toxic to trabecular meshwork cells at concentrations expected to be used in treatment for various eye diseases. Fabrication of a drug-loaded prototype medical device has been initiated and studies, including biocompatibility are underway to evaluate drug release in cell and cell-free model systems. Collectively the results of these studies will be used to select a lead development candidate that will be taken forward into in vivo efficacy models for eye diseases, including glaucoma.

The need for improved medications to treat Primary Open Angle Glaucoma

Glaucoma is a disorder of the optic nerve that results in irreversible vision loss and is the second leading cause of blindness in the world, according to the World Health Organization. Glaucoma impacts more than 2.7 million people aged 40 or older in the United States and current treatments are known to have poor rates of compliance of up to 80% of patients. The global market for glaucoma was estimated by Market Scope at $4.8 billion in 2019 with the U.S. market representing $1.9 billion. Although the exact etiology of primary open angle glaucoma remains poorly understood, and may be variable across patient subsets, it is generally accepted that the observed increase in intraocular pressure (IOP) correlates with progressive vision loss. Current treatments for POAG primarily consist of eyedrops that can be grouped into three main categories: prostaglandin analogues, carbonic anhydrous inhibitors, and alpha-2 agonists. While these approaches usually provide partial improvement, they often result in side effects such as redness and stinging and require multiple daily applications; all of which diminish patient compliance. Tryptamines, including DMT-analogues are thought to work in a completely distinct way to lower IOP and as such potentially embody a new class of glaucoma medications that may be used alone, or in combination with already approved medications. The Company’s streamlined focus on two highly promising, undisclosed tryptamines as a potential therapeutic solution in treating glaucoma represents a potential paradigm shift.

Modulating the serotonin receptor pathway to improve glaucoma outcomes

Key regions of the eye that regulate fluid dynamics, including maintenance of healthy IOP, are known to be richly decorated with various serotonin receptor family members. Previous research has highlighted the role of serotonin receptor signaling in the regulation of IOP2-5. Tryptamines, often hallucinogenic above certain threshold concentrations, constitute a large collection of molecules that selectively act on multiple different serotonin receptors including 5-HT1A and 5-HT2A. Topical application of several different tryptamines have shown early promise in preclinical models of elevated IOP, however formulation, delivery, the potential for undesirable hallucinogenic side effects, and the controlled substances act of 1970 have all contributed to a lack of development of tryptamines to treat this serious threat to vision.

The Terasaki Institute for Biomedical Innovation is a biotechnology institute which develops medical devices and cutting-edge protocols for a variety of diagnostic, monitoring and treatment applications. Their research platforms include work in biomaterials, cellular and tissue engineering, wearable biosensors and organs-on-a-chip, with specific expertise in novel polymer development.

*From the article here :
 
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Interview with Leading DMT Researcher Dr. Jimo Borjigin Chavez
by John Chavez | Psychedelics Today

These are the people who toil away in obscurity for years doing the hard lab work with little to no recognition for their efforts. It is my opinion that “science” gets way too much credit while real scientists (not celebrities in lab coats) should be the ones getting the credit and publicity of groundbreaking research. I believe that the recent DMT study published in Scientific Reports is by far the most important study in 2019 and all the scientists involved in the study should deserve wide name recognition and credit for their efforts. Credit needs to go to the following: lead author and fast-rising DMT researcher Jon Dean, Dr. Jimo Borjigin, Dr. Steven Barker, Dr. Rick Strassman, Dr. Michael M. Wang, Dr. Tiecheng Liu, Dr. Sean Huff, and Dr. Ben Sheler.

It’s difficult to recall the last time that I had a great meal and made the generic claim of “I love food”. Generally speaking, it’s either the restaurant that receives compliments, the type of meal that receives praise, or homage is paid to the chef directly. This is why it’s so amusing and yet perplexing when people seem to generically pronounce their “love for science” when an interesting study is published. Similarly to the cooks of a great meal… it is humans, people, scientists that actually carry out the experiments.

I recently had a chance to have a conversation with a woman who is leading the scientific pathway to researching the mysterious compound DMT… Dr. Jimo Borjigin from the University of Michigan. Dr. Borjigin received her PhD from John’s Hopkins University and has published ground-breaking research regarding increased brain oscillatory speeds & coherence following cardiac arrest, the neurochemical fluctuations following asphyxia-based cardiac arrest, the discovery of DMT production in the pineal gland of live rats, and now the most recent study that has observed comparable levels of DMT to common neurotransmitters (dopamine, serotonin, and norepinephrine) in the brain. If Dr. Rick Strassman can be considered the “King” of DMT research based on his studies from the early 1990’s and wildly popular book “DMT: The Spirit Molecule”… Dr. Borjigin can be considered the “Queen” based on her extremely important work in the field since 2012.

JC: So… while many people have heard the backstory of how Dr. Rick Strassman got involved in DMT research due to his book “The Spirit Molecule”, not many know about how you got your start in this field. Would you mind giving us a little bit of background as to how all of this came about?

Jimo: I had been working on the pineal gland and studying how dynamic secretion of melatonin from the pineal gland teaches us about how circadian clock works in the mid-2000. I was also teaching our graduate students about the pineal gland. One day in 2011, when I googled the word “pineal gland” (hoping to find some cool pictures to include for my class teaching), I came across Rick Strassman’s book (DMT: The Spirit Molecule) and the documentary about the book. I was very surprised when I heard Rick saying that DMT was made and secreted in the pineal gland, since I knew nothing about it. I emailed Rick directly and asked him for the evidence that his statement was based on, and was told that it was just his speculation. I told Rick that I was interested in testing his theory, as we were routinely performing pineal microdialysis experiments and I believed that if DMT is ever secreted from the pineal gland, we should have them in the dialysates. Rick was nice and encouraging; he introduced me to Steve Barker who routinely analyzing controlled substances in his lab, and the rest was history.

JC: Good stuff… so let’s just dive right into it…you did a really big study recently. I’m obviously biased but this is probably the most important study of the year for sure. Your research team found the circulating levels of DMT at similar levels to very commonly studied neurotransmitters serotonin, dopamine, norepinephrine. Being that you stated that this was found in the extracellular fluid am I correct in assuming that this is the cerebrospinal fluid? If so, where do you hypothesize that the DMT is synthesized in terms of the measurements you took at the cerebral cortex?

Jimo: Oh wow (laughing). Thank you I’m very flattered. Well, it’s within tissue in the extracellular space… we didn’t really stick a probe only into the brain ventricles where the cerebrospinal fluid is in abundance. We stuck our probe into the brain tissue where neurons are packed. So it is definitely extracellular. So, these are not the quantities within individual cells… I’m assuming that DMT is a neurotransmitter and it might be actually packed and stored inside the vesicles within neurons. The release is only activity-dependent if DMT is truly a neurotransmitter. The basal levels of the 3 monoamine neurotransmitters (serotonin, dopamine, norepinephrine), which the DMT concentrations were compared with, were also assayed the same way. This means that they inserted a microdialysis probe into the brain to measure the basal level of those 3 neurotransmitters, which is why we think DMT is comparable.

JC: Where do you hypothesize that the DMT was synthesized when taking measurements at the cerebral cortex? Any specific cells?

Jimo: We believe that DMT is made in the neurons. The reason for that is the following… we showed that one of the DMT synthetic enzymes AADC which is also called DDC… the same protein with 2 different names. This is the first of the two DMT enzymes that converts tryptophan into tryptamine. It is essential for all other monoamine neurotransmitter synthesis, but it is also required for DMT synthesis. For a long time people knew that there are neurons in the cerebral cortex (really all over the brain) that contain AADC. However, none of the other 2 enzymes (tyrosine hydroxylase or tryptophan hydroxylase) that are essential for the synthesis of canonical monoamine neurotransmitters such as serotonin, dopamine, norepinephrine were found. It is tryptophan hydroxylase (-TPH2 in the brain) that is required for the synthesis of serotonin together with AADC; tyrosine hydroxylase (TH) together with AADC required for the synthesis of dopamine (and norepinephrine). So when people look for monoamine neurons that synthesize serotonin, dopamine, norepinephrine, … they always have to look for both enzymes (AADC + TH/TPH2). So in these scattered cortical neurons that contain AADC (called D-neurons), people couldn’t find either one of those enzymes (TH/TPH2). So clearly there is a lot of work to do for us to really have a thorough understanding of the details of the localization of potentially DMT produced in neurons in the brain. The reason we think these are neurons is because D-neurons were confirmed to be neurons in both human brains and animal brains in the cortex by others. But we still need to use a neuron-specific biomarker to measure the colocalization of a neuronal marker in the INMT- positive cells to thoroughly demonstrate that these neurons are the source of DMT or have the capacity to produce DMT.

JC: Prior to this study much of the discussion surrounding endogenous DMT from researchers in the field was based on stating that the lungs were the primary source of DMT.

Jimo: Right, right.

JC: From what I understand this was based on the levels of INMT found in the lungs… right?

Jimo: Correct! Yeah it’s amazing (laughing).

JC: But this recent study found not only INMT but AADC co-localized which we basically just covered. But in essence… the same people that were saying that DMT is not produced in the brain or not produced in the pineal gland…based on the INMT-DMT lung hypothesis it would seem that they would be forced to concede that DMT is produced in the brain now?

Jimo: Yeah (laughing)… I would think that any reasonable person would say that. It’s amazing to me that a lot of people were saying that DMT is made in the lungs. In the case of DMT production, it’s been known for a long time that it requires 2 enzymes and ideally, the 2 enzymes would be situated in the same cells in order for that cell to produce DMT. And yet… people are simply just looking at INMT expression and assuming that that alone is sufficient to produce DMT (without AADC).

JC: Some people think that this study puts the pineal gland theory to rest. I feel like that’s not entirely correct.

Jimo: I think you’re right.

JC: This is the first study that actually shows that the human pineal gland has INMT/AADC in order to make DMT.

Jimo: Yes.

JC: While the extracellular levels of DMT in the cerebral cortex were similar between normal and pinealactomized rats, is it possible that the pineal produced DMT has a greater effect in the third ventricle or thalamus region in comparison to the cerebral cortex levels?

Jimo: Well… all I can say is that the neocortex can produce DMT in the absence of a pineal gland. Our study did not really address the issue of pineal DMT production. The fact is that in our data in the absence of the pineal gland the DMT levels go up (not significantly, though). Our data is relatively crude based on the fact that we surgically removed the pineal gland. When you yank the pineal gland out you disturb the blood-brain barrier a bit since the pineal gland is part of the blood-brain barrier preventing things from going in and out. So we don’t know why it goes up in the absence of the pineal gland. I haven’t given it too much thought but all we’re showing is that the brain doesn’t really require the pineal gland to produce DMT. The pineal may produce a small level of DMT but it’s clearly not contributing a huge amount. If the pineal gland produced 3X as much then we should have seen a difference. I strongly believe that the cortex (where we utilized our microdialysis probe) makes and secretes DMT independent of the pineal gland. The pineal gland is not essential and is not required… it doesn’t mean the pineal gland itself cannot make DMT since all the machinery is there. But we had a long paragraph in the discussion part of the paper discussing why we think the pineal gland may not contribute much to DMT production. If you look at the affinity of the AADC enzyme, it actually prefers to convert 5-hydroxtryptophan (5-HTP) into 5-hydroxytryptamine (5-HT). For serotonin production tryptophan is first converted to 5-hydroxtryptophan by TPH and the second step for serotonin synthesis is converting 5-hydroxytrytophan (5-HTP) to 5-hydroxytryptamine (5-HT); so apparently, AADC has a higher affinity for 5-HTP than tryptophan. So if both 5-HTP and tryptophan are around (in this case in the pineal gland) AADC would prefer to catalyze the reaction of 5-HTP to 5-HT… so it kind of ignores tryptophan. However, in other cells if AADC is only looking at tryptophan and if 5-HTP is not around, it should readily convert tryptophan to tryptamine.

JC: Are there any neurotransmitters or any endogenous biochemical(s) for that matter that have been identified to be rat specific in comparison to that of humans as far as we know? What I mean by this is whether there is any data to suggest that rats produce different biochemicals than humans in the brain or throughout the body?

Jimo: Usually when you go up the evolutionary tree, it is higher-order animals such as humans that have something that the rats don’t have and it doesn’t go the other way around. Especially being that both rats and humans are both mammals, so it’s highly unlikely. On the other hand, if you go down to invertebrates or lower vertebrates who have very unique habitats they may have stuff that humans don’t need. So my answer is NO, not as far as I know. There are genes and proteins only found in humans, but not in mice or rats. I am not aware of any genes or proteins present only in rats but not in humans.

JC: So that would mean that for someone to claim that DMT is not found in the human brain because the research only took place in live rats (although you took in vitro sampling of human brains that observed the same exact enzymes that rats produced in order to synthesize DMT) that they would be making claims that fall outside the scope of scientific data to date?

Jimo: Unless I’m mistaken Dr. Steven Barker has already measured DMT in the brains of deceased individuals and trace amounts in their blood. This could be a question for Steven regarding the solid evidence of showing DMT is found and collected from humans. All reasonable people would agree that if human brains are found to express both INMT and AADC, it is highly likely that DMT will be made in the human brain. The next step would be to stick a probe in a live human’s brain so we could monitor DMT at a level comparable to other neurotransmitters but usually, that level of proof is rarely demanded for research because it is so unusual to be able to get samples using such invasive techniques. No one would want to volunteer for that kind of experiment being that it comes with some kind of risk. So I don’t believe it is necessary. Having experimental proof from humans would certainly help, but it is not always feasible to do so.

JC: I think all the hard-nosed “skeptics” continuing to question whether humans brains produce DMT following this recent study should volunteer for the brain-probe study…

Jimo: (laughing) But remember we don’t want to really make any enemies. My take is that unless you have evidence against the human brain-DMT hypothesis there isn’t much to say. We are doing our best effort.

JC: Going back to the yanking out of the pineal gland… Being that DMT has been observed to have anti-inflammatory properties, is it possible that yanking out the pineal gland causes cerebral inflammation-inducing a periphery response to synthesize more DMT to alleviate this then causing the levels to go up?

Jimo: That is highly unlikely as in the periphery, there are very few cells that contain both AADC and INMT in contrast to the brain. Plus, if there were any inflammation, it should be within the brain near where the pineal gland was in touch with, which is not known to exert peripheral inflammatory responses. We performed numerous pineal removal surgeries over the years, have never observed any signs of notable inflammatory responses in rats.

(JC Note: I didn’t clarify when I stated “periphery.” I meant the periphery area of the brain in near proximity to the pineal gland wound not peripheral nervous system outside of the brain. It was my fault for not clarifying.)

JC: Ok. I find it super interesting that much of the same team that did this study also did the 2013 cardiac arrest study which observed the global and coherent surge in gamma waves in the brain. Based on the literature out there it seems as though exogenous DMT and Ayahuasca also induce increases in gamma waves. Do you believe that there is a possibility of a tight correlation between the upregulation of endogenous DMT and gamma activity?

Jimo: Well… in this recent paper we didn’t even have cardiac arrest in the title so it wasn’t our focus. The main message from this recent paper is that DMT can be produced and released from the neurons in the brain at the level that is comparable to other monoamine neurotransmitters. My students are super excited about our 2013 cardiac arrest paper and the link between the DMT and near- death experiences. The two areas of studies (near-death consciousness and DMT) emerged coincidentally at the same time in our lab as 2 independent branches of research which appear to have the potential to converge into a related research theme. Clearly Rick Strassman talked about this hypothesis and the idea has been floating around out there for many years and it sounds reasonable. In the recent paper, we wanted to know whether there was anything that could upregulate or downregulate DMT release. So when we induced experimental cardiac arrest in animals, their DMT levels went up in some but not all animals, which is interesting. The recent study was not done to demonstrate DMT levels in cardiac arrest but it was more based on showing that there are physiological events that can increase DMT. Some kind of physiological event can regulate DMT release. Regulated release of chemicals is required steps for something to be called a neurotransmitter. We are trying to push this work toward demonstrating DMT as a neurotransmitter. Some interpret our data as DMT being linked to NDE’s which is not my intention or the goal of the study; but clearly a lot of people are interested in the study because of that potential link. However, for DMT-NDE to be linked, we would have to do the same exact study we did in our 2015 PNAS paper where we monitored neurotransmitter release at 60 second intervals and measured the amounts of neurotransmitters released… and it was a huge amount. Within 2 minutes of asphyxic cardiac arrest, dopamine went up, norepinephrine went up, serotonin went up, GABA went up… not all neurotransmitters went up so high though. Glutamate only went up 2-fold… so it’s a massive release of various neurotransmitters, a tightly regulated process that happens super- fast. So we would have to monitor the release of DMT at a finer resolution in order to really say anything about whether DMT is potentially involved. That study still remains to be done.

JC: I guess what I’m asking you is to maybe hypothesize about… in the 2013 study you saw a huge surge in global gamma waves. Basically faster brain activity…

Jimo: Yes.

JC: In the 2015 study you basically saw a “brainstorm” in which a bunch of neurotransmitters were upregulated.

Jimo: Yes.

JC: Do you think it’s that far-fetched to think that DMT might be a part of that biochemical mix and that it could contribute to the gamma wave correlation or is that still too speculative?

Jimo: It’s possible. I guess until we do the experiment we’re not sure, we don’t know. There’s a possibility that those 2 are linked.

JC: In terms of a definitive way to know whether DMT is tightly correlated with gamma waves… is that something that you could figure out with an INMT-KO animal?

Jimo: Yeah… I think if a gamma surge disappeared then that might be a way to support the hypothesis.

JC: That makes sense… but it wouldn’t even really have to disappear necessarily right? It could just be affected.

Jimo: Correct… yes.

JC: Switching gears… One of the biggest issues I’ve seen is that people are so excited about psychedelic research and there seems to be a decent amount of funding for the field but I think that the endogenous research is even more interesting.

Jimo: I think so too (laughing). I agree with you there.

JC: Much of the psychedelic research these days focuses on fMRI studies so it seems like cerebral blood flow seems to be the predominant measure of perceived activity. However, in a yet to be published interview I did with Dr. Mauro Zappaterra he stated that based on his research, cerebrospinal fluid can act as a signaling medium being that it can carry the neurotransmitters and signaling throughout the brain on a global level. This would seem to add another layer of complexity in terms of analyzing brain activity when comparing fMRI to EEG. What are your thoughts regarding this?

Jimo: FMRI monitors changes associated with blood flow. Robin Carhart- Harris has done psychedelic work with fMRI and the subjects actually show the lowering of fMRI measures. It’s a different mode of regulation so we don’t really know… I wish when Rick Strassman did his study he had everybody monitored for EEG or fMRI to see what happened to them. My guess is that study is coming and somebody is working on that. We can easily do an EEG study on animals but we just cannot ask them what they experience. Sooner or later it will have to be done.

JC: It’s interesting that fMRI shows a decrease in whatever might be termed as brain activity but in EEG studies it shows that there’s an increase in faster oscillations and a decrease in slower ones.

Jimo: Right.

JC: A lot of stuff to uncover there…

Jimo: Correct.

JC: While the recent study focused on DMT and the enzymes INMT and AADC… what are your thoughts on researching endogenous monoamine oxidase inhibitors (MAOI) such as tribulin, tryptoline, neurocatin or pinoline and their relationship with endogenous DMT?

Jimo: Yeah, there is a lot to do and the future research is just wide- open for these questions to be addressed. Our study simply points out that there is a whole new world out there for people who are interested in the molecular basis of altered states of consciousness and a potential new direction for looking into psychiatric disorders. So I think there are lots of interesting things that can happen but right now we have to focus on something that the National Institutes of Health (NIH) could consider funding. We have to convince them that this is something that may be medically relevant and that we’re not just thinking about euphoric states and psychedelic states… something that can benefit patients.

JC: Yeah… would you consider private funding?

Jimo: Oh yeah totally.

JC: We’ll go off the record with that discussion…

Jimo: (laughing)

JC: Do you have any interest in replicating this recent study but also measuring levels of 5-MEO-DMT and Bufotenine?

Jimo: Oh yeah. Once again this is another area that is wide open that one can do. It all depends… once again… on funding. Right now people are lined up to want to work in my lab. Every year, lots of graduate students contact me for a position my lab; and the first thing I tell them is: I am sorry that I can’t take you in my lab because I don’t have NIH funding for DMT research.

JC: (Cutting in) Horrible

Jimo: (laughing) That’s the standard answer for several years now. I just recently accepted a very good student who insisted on joining my group regardless of the lack of NIH funding. In any case, we try to collaborate with people that have grants to make it happen; but the key is to have research funding to support the DMT endeavor.

JC: Absolutely. That’s one of the most frustrating things I see in terms of scientific research. There’s so much money that goes into genetic research and things of that nature but there’s so little funding that goes into endogenous DMT research by comparison.

Jimo: There are various ways that this line of research can now be supported because we’ve shown that DMT is really in the brain and may serve some kind of functions; we just need funding support to do more studies. That’s why I’m happy to discuss this research with the media, so we can raise more awareness and hopefully garner funding for our DMT research. Scientists tend to stay in their labs and do their own research and it takes years to get their data out there to be in the public and to gain support from the public. I think that the publicity this paper has created (which surprised me) may generate a lot of interest.

JC: Yeah… I think the public is starving for it. I know I am (laughing). You’re one of the only labs doing endogenous DMT research and everybody is speculating on it but people want definitive answers. I definitely see the money coming in but certain people need to get in motion to make this happen. I keep on asking you about speculative studies so I apologize but one of the co-authors of the recent paper was Steven Barker and in an interview he discussed an unpublished study in which rats administered LSD showed a 1000% increase in 5-MEO-DMT and a 400% increase in DMT. Do you have any interest in possibly attempting to replicate that study?

Jimo: (laughing) I think it would be faster to just wait for the paper to be published right? I don’t know who the author of the paper is though.

JC: It was a study in which the author of the paper passed away so that’s why Dr. Barker said it didn’t end up getting published.

Jimo: Oh. I see.

JC: I think it would be a really interesting replication study in the sense of Barker’s speculations that we have an endogenous hallucinatory system and that a lot of hallucinogens might just be activating that system rather than simply acting on their own.

Jimo: That’s interesting… hmmm. Yeah… well… I’m not sure. There are so many things to do. We have to choose wisely… I have to pick my fights wisely (laughing). I guess it depends on whether the funder is really interested in pushing that line of research and if it’s somehow in-line with my own interest. I am interested in things like demonstrating that DMT is a neurotransmitter which is something that requires some work, and establishing the whole system of DMT centric neurotransmission. Beyond that… as far as looking at the homologues and endogenous system… like you said monoamine oxidase inhibitors and the recent study you mentioned regarding Barker & LSD, there are a lot of interesting things to do (laughing). It would require more dedicated, highly motivated students and people working hard to making it happen.

JC: I know that this falls outside of the realm of your research but Dr. Michael Persinger developed a device called “the god helmet” in which people would experience mystical experiences due to ultra weak magnetic stimulation. From his EEG research he observed that these magnetic fields induced an increase in gamma waves in the brain. He even hypothesized that DMT could play a role in this… what are your thoughts on external magnetic field influence on secretion of different biochemicals such as DMT in the brain coinciding with the mystical experience?

Jimo: Gamma waves need to be mediated by neurotransmitter secretion that is acting on the post-synaptic neurons. So there has to be a neurochemical reaction that translates into electrical signaling. So I wouldn’t be surprised at all if DMT could be one of the many neurochemicals (not the only one), contributing to the experience although it could be a key chemical. The only real way to test how much DMT plays a role in the experience is to have a DMT deficient human (or group of them) undergo the “God Helmet” and have them report the types of experiences they have and compare them to people secreting DMT normally. So basically I would say that it is not impossible, unless data shows otherwise.

JC: Do you know if there are any methods to induce respiratory fluctuations in animals without inducing anesthesia? The reason why I ask is because breathing techniques such as the Wim Hof Method (WHM), Stan Grof’s Holotropic Breathwork, Joe Dispenza’s meditation, and the more ancient yogic renditions (Pranayama) have all been cited to induce visionary states when carried out for prolonged periods of time. There’s much speculation regarding DMT’s involvement and based on our conversation (and recent study) it wouldn’t be the least bit surprising as to the upregulation of DMT (alongside everything else) from these breathing exercises. Is it feasible to do a comparable study of breathing exercises in live animals?

Jimo: It’s something that I haven’t looked into so I don’t have an answer right now. Changes in breathing patterns can lead to excitation in the central nervous system. In an animal model I think you can create alterations to their trachea… it would be kind of a reversible time-controlled experiment in which you stimulate the nervous system of the animal to breathe harder. Experimentally it seems doable, as long as there are animal models to induce hyperventilation similar to that as humans it’s possible. I’m almost thinking it would be much faster and easier to do this study in humans but the invasive nature of measurement is an issue.

JC: I hear you Jimo. If it was up to you… what would you say are the top 5 studies that need to take place within this field that you are specifically focused on right now?

Jimo: The first one is that DMT is actually a neurotransmitter. After that, we would like to know how the DMT synthesis is controlled; and how it’s release is regulated. My prediction is that some of the regulatory mechanisms in charge of DMT release might be dysfunctional in patients with psychiatric disorders that feature hallucinations. We know that DMT has hallucinatory properties, so it’s not too far-fetched to predict the link there. The potential role of DMT in regards to Near Death consciousness remains to be experimentally tested explored with the gamma waves as you discussed in your blog. That’s something we can easily do to demonstrate that endogenous DMT can stimulate gamma waves.

JC: Ok.

Jimo: And, of course, whether DMT contributes to neural correlates of dream states is also an interesting question.

JC: I remember a few years back having correspondence with Dr. J.C. Callaway… a scientist who postulated in 1988 that DMT and endogenous MAOI Pinoline played a role in the dream state. When I asked him whether he ever carried out the study he basically said the same thing that you’re telling me now… there was no funding for research so he moved on to another field.

Jimo: So we’re not the first one to bring up the lack of funding! (laughing)

JC: It’s amazingly horrible. In terms of the human studies… do you have any ideas on how you might go about doing endogenous human studies? Have you looked into any of the technology out there that might be able to do it less invasively?

Jimo: Well… I believe there are human patients who are helped and being diagnosed with a microdialysis setup in certain parts of their brain. I think if we can find patients like that, we could potentially collaborate with their physicians or scientists who are working with those patients and maybe get a sample from them.

JC: That makes sense… like somebody being treated for hydrocephalus or something?

Jimo: Yeah something like that or even from someone undergoing surgery for brain tumor removal. Their brains are already exposed so maybe we can share a little bit of CSF from them and monitor their levels while the patients are alive.

JC: Yeah that makes a lot of sense. Have you heard much about a technology called proton magnetic resonance spectroscopy? I was reading that it has the ability to measure brain fluctuations in glutamate and glutathione non-invasively. Would this be applicable to DMT?

Jimo: Hmm… I’m not sure. I haven’t really looked into any measurement of DMT in humans yet. But that’s something to look into once we’re going that route… I’ll think about that (laughing).

JC: Well Jimo… it seems like I have some work to do in terms of reaching out to some people to try and get your lab some funding to continue this very important research. Thank you very much for your time… do you have anything you’d like to say in closing?

Jimo: What I’d like to emphasize is how important collaboration is to make science happen, not just the funding. If Rick (Strassman) did not introduce me to Steve Barker, our first DMT paper would not have been materialized, and Jon Dean, the first author of our DMT paper and a very dedicated graduate student passionate about psychedelic research, would not have joined my team to produce the current publication. Collaboration with Mike Wang (a co-author on the Dean paper) on the role of a stroke on sleep and circadian rhythms in rats allowed us to discover the surge of neurochemicals in the brain of dying rats, which ultimately lead to the discovery of the surge of gamma activities in the dying rats. Collaboration with George Mashour’s group was essential for the computational analysis of the brain’s electrical signals. Collaboration with Bob Kennedy’s laboratory allowed the high resolution (every 60-sec) measurement of neurotransmitters in dying rats. All I can say in closing is that I have been extremely fortunate to be able to work with these fantastic scientists. Teamwork rocks!

 
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Powerful psychedelic improves depression in one hour*

Psychedelic found to treat mental health conditions more efficiently than psilocybin, study.

by Molly Hanson | BIG THINK
  • A survey study found that around 80 percent of people using the psychedelic 5-MeO-DMT in a ceremonial setting said that their depression or anxiety improved following its use.​
  • The "mystical" experience of drug trip might allow people to gain unique insight into themselves or their relationships and make positive life changes.​
  • While the substance is found in the poison of the Sonoran Desert Toad, researchers say there is no reason to disturb the toad because the synthetic version of 5-MeO-DMT is identical in its effect.​
A new, powerful — yet still relatively rare — hallucinogen called 5-MeO-DMT has made its way into United States psychedelic circles, and research is backing its use as an effective treatment for certain mental health conditions.

Said to be up to six-times more intense than its sensationalized cousin DMT, researchers have found strong evidence to suggest that 5-MeO-DMT could be used to treat anxiety, depression, and addiction more efficiently than psilocybin.​

What is 5-MeO-DMT?

5-MeO-DMT, is an extremely potent natural psychedelic found in certain plants and the poisonous secretions of the Sonoran Desert Toad, also known as the Colorado River Toad. It can also be made synthetically in a lab.

Typically, the experience a person has after ingesting 5-MeO-DMT, a schedule 1 classified substance, is described as feeling unified with the universe or some holy, transcendent “other.” The perception of bright colors and recursive patterns are often associated with the experience. It can also lead to extreme nausea and confusion days after ingesting it.

Assistant Professor at Ohio State University Alan Davis, who is also affiliated with the Department of Psychiatry and Behavioral Sciences at John Hopkins University, has conducted two large-scale survey studies examining the use of 5-MeO-DMT in the general population and in a specific ceremonial group in the United States.

Despite reports dubbing it the “hottest new psychedelic” among trend setters in the United States, Davis’s research has found that the drug is still rare, and most people are using it for psycho-spiritual endeavors rather than for recreation. Typically, he says, it is used in a ritualistic setting with a specific process similar to what might be done during an ayahuasca ritual.

And, he emphasizes, it definitely isn’t a party drug.

“This is a very potent and powerful psychedelic substance that usually has an onset within seconds and a person is completely incapacitated,” he says. “They are in a whole different realm of consciousness for 20 to 60 minutes.”



Research in treating anxiety and depression

In a survey study of 362 adults, Davis found that when administered in a ceremonial group setting with a knowledgeable facilitator, approximately 80 percent of people said that their depression or anxiety is improved following the use of 5-MeO-DMT.

According to Davis, this is likely because of the type of “mystical” experience one has on the drug trip, which allows the person to gain new, novel insight into themselves or their relationships through a shift in consciousness.

“This information, these experiences, seem to be really powerful and profound and they seem to help people to change, and to make different choices in their life,” says Davis.

Interestingly, this fits in with research on other psychedelic substances such as psilocybin, which has also been found to have significant anti-depression and anti-anxiety effects. One of the major downsides to the potential use of psilocybin in a clinical setting is that the psychedelic experience lasts four to six hours. Tacking on an extra hour before to get ready and after to ensure the patient is ready to be discharged, psilocybin would mean a whole day of treatment. That will add up to a very expensive session if it is eventually approved for public use, according to Davis.

Enter 5-Meo-DMT.

“One of the interesting things about 5-Meo-DMT is that the duration of effect is anywhere from 20 to 60 minutes,” says Davis. “You can start to imagine a world where if this was a medication, you could actually have someone there for more of a standard psychotherapy time frame and have an entire psychedelic healing experience.”

Because this treatment could more easily be scaled into our current mental health care, it would likely be more accessible to people who might benefit from the treatment. Currently, Davis is working with a larger team on creating a clinical trial with the aim to eventually look at the administration of the drug in a laboratory setting.

Although Davis’s team has heard of potential risks involved with use of the drug, in part because of instances of it being mis-administered, he says that the data indicates that in the right setting where facilitators pay proper attention to people’s well-being, users are having mostly positive experiences.

As far as researchers know, the only animal on Earth that produces the chemical compound is the Sonoran Desert Toad, although it is also found in some plant species.

But the mystical psychedelic association with the toad has facilitated an ecologically harmful market for the amphibian’s poisonous secretions. This has led researchers to strongly condemn the practice of harvesting the toads for the compound.

According to local Tucson naturalist Robert Villa, the toad produces is milky white poison as a defense mechanism, so there is no humane way to obtain it. People in the Sonoran Desert region, where the toad is native, have noticed a decline in the amphibians’ numbers likely due to the psychedelic community’s demand for 5-MeO-DMT.​

“Traumatizing an animal (or plant) for personal benefit is fraught with ethical dilemmas,” Villa wrote in an email.

Faced with other threats to its habitat, the psychedelic blackmarket is one more problem the Sonoran Desert Toad doesn’t need. Davis stresses that there is no need to disturb the toads or their environments at all.

“What we’ve been able to show is that the synthetic version is no different in terms of the intensity or the positive effects of taking it compared to the toad,” says Davis. In fact, he found that most of the people he surveyed in his study were using the synthetic version of the drug.​

*From the article here :
 
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DMT could revolutionize the treatment of depression*

by Scotty Hendricks | BIG THINK

As psychedelic research returns to the mainstream of medical science, several lesser known drugs are being seen as possible therapies for mental illness. One of these is DMT, which is the subject of a slew of new studies about its potential use in treating depression.

DMT is the common term for N,Ndimethyltryptamine, a powerful psychedelic drug. Its chemical structure is similar to that of serotonin and melatonin, and it is believed to bind to certain serotonin receptors in the brain.

Since the 1960s, scientists have thought that some mammals may produce DMT in their bodies. Its presence in the brains of rodents has been reported, and trace amounts have been found in the human body and cerebrospinal fluid. Exactly what naturally occurring DMT is doing remains a subject of investigation.

Because DMT is also found in a variety of plants, teas containing the drug have been consumed by many native peoples of South America for at least 1,000 years, often for religious purposes. It only received serious scientific attention as a therapeutic drug beginning in the 1950s.

Dr. Stephen Szára, a Hungarian psychologist working in the mid-20th century, was denied access to LSD by the Western companies that then produced it. At the time, LSD was considered a powerful tool with applications in spycraft, so neither communist countries nor their biomedical scientists were allowed access to it. Unable to work with that psychedelic, he turned to DMT as an alternative.

Eventually moving to the U.S., he continued to work with DMT and explored its possible applications as well as those of other psychedelics.

Effects

Unlike the more famous LSD or psilocybin, DMT trips are often quite short, sometimes lasting as little as five minutes. The short duration is more than made up in its intensity, however, with users reporting extremely vivid hallucinations. Typical doses lead to visions of complex, multicolored geometric patterns, ego death, and altered thought patterns.

DMT has another unique feature: high doses of it can lead to an occurrence called a “breakthrough,” at which point the user no longer perceives themself as being in the same plane of existence. The new location can be truly phantasmagoric, ranging from hyperspace to non-Euclidean realms. These strange places are often populated by even stranger creatures known as “machine elves.”

The machine elves, named by the ethnobotanist Terence McKenna who popularized DMT in certain circles, have been reported by users since Dr. Szára’s experiments. Reports of the elves can vary dramatically, especially in appearance, but users tend to agree that the hallucinated creatures are intelligent and benevolent. The frequency with which these beings are reported may explain the use of DMT as a religious tool for contacting the spirit world. Though some users have speculated if these beings are real, author and psychedelic authority James Kent stresses that they are hallucinations.

Legality

Generally speaking, DMT is not legal. The Convention on Psychotropic Substances, an international treaty signed in 1971, bans the drug but not the plants that contain it. Many countries have their own bans on the substance or the plants from which it can be extracted. However, many jurisdictions have exemptions for the use of DMT-containing products (like ayahuasca) by certain religious groups as part of their rituals. Some American cities have recently decriminalized the drug.

Ayahuasca

Typically, DMT cannot be consumed orally. It must be smoked or, as is common in medical studies, injected. If it is combined with a monoamine oxidase inhibitor, it can be consumed in tea. Variations of this tea, some including different hallucinogenic substances, are often known as ayahuasca from one of the names given it by indigenous South Americans.

While the production and consumption of ayahuasca go back millennia, it has only recently become popular with Western psychonauts. An entire industry of ayahuasca tourism has formed in South America, focused around northeastern Peru, with more than a few psychedelic tourists and celebrities shelling out for a chance to drink the tea in a ritual setting.

By all accounts, a trip on ayahuasca is similar to a DMT trip but with a much longer duration. It also prominently features the purging of the contents of the participants’ stomach and bowels. Some practitioners consider this part of the purification process. However, tourists looking for an “authentic” experience may be getting high on hype.

DMT as medicine

Current studies focus on how the drug works in the brain and how it might be used to treat mental illness. As Dr. Carol Routledge of Small Pharma explained to Freethink, the extreme effects of this drug might be exactly what some patients need, especially when more common drugs like SSRIs have failed:

“A lot of the mental health disorders like depression, like post-traumatic stress disorder, even OCD, have this real negative cycling thought process which leads to ingrained neuronal processes. And it’s almost impossible to get out of those, and I think that’s why SSRIs don’t really even attempt to do that. What psychedelics do is they break that pathway, they break those neuronal connections, and then they increase neuronal connectivity and synaptic connectivity.”

Early reports from Small Pharma suggest that DMT, in conjunction with therapy, can be used to help break away from undesired behavioral patterns. Other studies also suggest that it could prove useful in helping with depression and anxiety. Dr. Routledge suggests that the stimulated connectivity among neurons allows the brain to “reset.” As a result, these conditions can be more effectively treated. There is also discussion about how the mystical experiences triggered by the drug might help those with mental health problems to examine the root causes.

Whatever the outcome of this research, definitely don’t try this at home. At least a dozen tourist deaths have been associated with the consumption of improperly brewed ayahuasca. These poor souls have permanently relocated to a different plane of existence.

*From the article here :
 
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DMT and its Potential Psychiatric Promise

by Samoon Ahmad | Technology Networks | 31 Mar 2022

Psychedelics’ potential is rivaled only by their power. They are extremely potent substances that have been used in various cultures dating back thousands of years, largely for ritualistic and spiritual purposes. In addition, they have traditionally been called upon to offer those who wish to gain insight into realms believed to be inaccessible to the conscious mind.

This is more or less the same reason why interest in psychedelics has skyrocketed among clinicians, researchers, and the general public. For clinicians, these drugs are being touted as potential groundbreaking treatment options for a host of psychiatric and inflammatory conditions as they can potentially treat symptoms that are extremely difficult to manage with conventional medicines. For researchers, studying psychedelics can help them understand how these substances can eliminate the interference of ego structures and conscious experiences in their subjects to unveil the most fundamental dynamics of the mind, thereby offering new insights into our understanding of neuroscience, consciousness, and how the two intersect. For the general public, they offer relief from symptoms of hobbling psychiatric conditions, fuel for philosophical musings, and the opportunity to take part in deeply meaningful experiences. As has been frequently reported in research dating back to at least 2006, psychedelic sessions are frequently ranked among the top five most meaningful experiences in individuals’ lives even more than a year later.

Psychiatrists are very excited about the potential of psychedelics, particularly with respect to drugs like psilocybin, LSD, and MDMA. Despite the excitement about adding these substances to psychiatrists’ toolkits, one of the most potent psychedelic compounds available, DMT has received very little attention from clinicians until recently.

While there is no question that DMT holds enormous potential, as clinicians we must first understand how to harness it.

What is DMT?

DMT is a classic psychedelic that can induce profound changes in sensory perception (hallucinations), feelings of euphoria, and radical alterations in typical thought patterns. On the neurochemical level, DMT behaves similar to other psychedelics (e.g., LSD, psilocybin, mescalin) by not only binding to serotonin 2A (5-HT2A) receptors in the central nervous system, but also interacting with other serotonergic (5-HT1A, 5-HT2C, and 5-HT7) and glutaminergic receptors, sigma-1 receptors, and trace-amine associated receptors. DMT also interacts with acetylcholine and dopamine signaling.2 Interestingly, DMT exists naturally in the brains of mammals, including humans, though the reason is unclear. Some have speculated that it may play a role in altering consciousness to allow for dream states, spiritual or mystical experiences, or even passage from life onto death. Currently, there is no evidence to support these claims, and it is not even clear if DMT exists in concentrations high enough to produce measurable effect.

DMT is the main ingredient in medicines that have traditionally been prepared and consumed as teas by indigenous peoples from throughout South America well before any European contact. The most well-known example is ayahuasca. In conjunction with DMT (from Psychotria viridis), ingredients in these teas include naturally occurring monoamine oxidase inhibitors, which delay onset and extend the duration of DMT’s effects for several hours. If one takes synthetic DMT, which is often inhaled using a vape pen, the effects may take a few minutes to manifest and may peak within five to ten minutes before beginning to wear off. The entire experience may only last 30 minutes or so.

What are the effects of DMT?

One of the most promising areas of research for psychedelics in recent years has been its potential role in mitigating anxiety and depression among terminal cancer patients suffering with existential crisis. Unfortunately, there are few pharmacotherapies or interventions in the field of psychiatry that can be used to help patients as they struggle to come to terms with their own mortality. “The ego, faced with the prospect of its own extinction, turns inward and becomes hypervigilant, withdrawing its investment in the world and other people,” Michael Pollan wrote in his paean to psychedelics, How to Change Your Mind. Psychedelics offer the opportunity to suspend the ego temporarily, which can be experienced initially as terrifying, but it is followed by a gradual sense of surrender, acceptance, love, and a greater sense of unity with the universe as the ego dissolves and one experiences simulated death and rebirth. Psychedelics are not treating end-of-life anxiety and depression pharmacologically; rather, they are treating these conditions phenomenologically (i.e., through the subjective experience it induces).

Though DMT acts upon the same serotonin receptors as other classical psychedelics, the DMT experience is unique. With smoked DMT, the ego is not just dissolved in a transcendent experience; it is obliterated.

According to DMT users, the visible world is often replaced by extremely vivid kaleidoscopic patterns of color. Furthermore, users report being transported to what they describe as another plane of reality with the presence of godlike creatures, and many of those who have taken DMT have reportedly interacted with these creatures. An online survey conducted by researchers at Johns Hopkins School of Medicine involving 2,561 individuals (median age 32 years; 77% male) who reportedly had encounters with these ostensibly autonomous beings found that half of participants who considered themselves atheists before the experience no longer did afterwards, and more than half of total participants believed that these beings are conscious, intelligent, benevolent and continued to exist after the encounter in a real but different reality.

Characterized by Davis as an “ontological shock,” over half of the participants claimed that the DMT experience was one of the most spiritually significant and meaningful moments in their lives. Many respondents also reported profound changes in outlook and positive changes in life satisfaction and subjective well-being.
Potential Directions for DMT Research

Clinical trials of DMT are only now beginning, so it will likely be years before we even start to glean its full potential. However, years of research has shown us that the beneficial psychological effects of psychedelics appear to be tied to their long-term subjective effects and how they change patient perspective. The important question to ask is that if DMT imparts its effect through ego annihilation, wouldn’t it make sense that it could be even more effective than other psychedelics?

Theoretically, yes.

Like other psychedelics, it may prove capable of easing existential distress among terminally ill patients and promoting subjective well-being. It may even help individuals with substance use disorders overcome their dependence. A pharmaceutical company based in the United Kingdom, in conjunction with Imperial College London’s Centre for Psychedelic Research, initiated a phase I trial earlier this year to see if DMT could be used to treat major depressive disorder.

However, there are potential roadblocks to DMT’s use in a clinical setting, too—at least in its smoked or vaped form. As Stephen Ross, one of my colleagues at New York University who has studied psychedelics extensively, observed during a conversation we had about frontiers of psychedelic research, psychedelics are only part of the equation in a larger model of medication-assisted psychotherapy. Patients should not simply be given these extremely potent drugs, and then left on their own to process the experience. They need guidance from people who have the tools and training to place it into a larger narrative.

To properly provide care, staff members need to be trained to be effective guides to patients who are experiencing the acute effects of the drugs and to help them contextualize and absorb the experience. Furthermore, patients need to be psychologically prepared for the experience and will likely require several sessions before and after the experience to effectively process it. Given the enormous difference between the acute effects of DMT and LSD or psilocybin, it stands to reason that protocols and models that provide the best therapeutic experience are not even remotely interchangeable.

To fully harness the therapeutic power of DMT, as well as psychedelics in general, research will need to focus not only on the potential conditions it can help treat or the neurophysiological effects of the drug, but how the drug is administered and how patients are guided through the experience. We will need to embrace the role of navigator, rather than simply impartial facilitator of awareness, growth, and psychological development of our patients.

About the author:Samoon Ahmad, M.D., is Professor of Psychiatry at NYU Grossman School of Medicine.

*From the article here :
 
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Positive results in world’s first trial for DMT Therapy

by Microdose Psychedelic Insights | 22 Feb 2022

- First clinical trial for DMT-assisted therapy in MDD Shows Consistent Quality of Psychedelic Response in Phase I
- In the Phase I clinical trial, participants were administered SPL026 and underwent a 20-minute psychedelic experience
- Phase I full dataset demonstrates consistent dose related effects on the intensity and quality of the psychedelic experience

Small Pharma Inc., a neuropharmaceutical company focused on psychedelic-assisted N,N-dimethyltryptamine (“DMT”) therapies for mental health, is pleased to share the analysis of Phase I data from the combined Phase I/IIa clinical trial of SPL026 with psychotherapy for the treatment of Major Depressive Disorder (“MDD”).

In the dose-escalating, placebo-controlled Phase I study, 32 healthy psychedelic naïve volunteers across four dose cohorts received either SPL026 in combination with psychotherapy or placebo. This analysis provides additional insight into dose-related effects on the primary outcomes of safety and tolerability as well as on pharmacodynamic measures, including the treatment experience and subject well-being.

Dr. Carol Routledge, Chief Medical and Scientific Officer of Small Pharma said:

“The analysis of the unblinded data set supports our choice to explore the antidepressant potential of our selected dose of SPL026 in the Phase IIa trial. Given the subjectivity of the psychedelic experience, it was exciting to see a close correlation between levels of drug in the body and pharmacodynamic endpoints. As for the subjects’ experience, most reported that it was pleasurable, not too challenging, and most importantly, nobody expressed any regrets. Additionally, the strong safety profile and rapid clearance of SPL026 from the body provides the potential for a scalable treatment with limited monitoring needs post dosing.”

Key results
  • No drug-related serious adverse events and minimal short-lived adverse events reported on dosing day.​
  • Of 20 drug-related adverse events, all were mild (85percent) or moderate (15 percent) and resolved rapidly and independently.​
  • No statistically significant negative effects on anxiety and well-being identified at any point during the three-month follow-up.​
  • Data show a clear correlation between quality of psychedelic experience and dosing levels, starting at 9mg and up to 21.5mg, across all four cohorts.
    • Participant-reported scores, using a 0 to 100 scale, on the richness of the psychedelic experience demonstrated increasing values of 48 (9mg), 79, 79, 88 (21.5mg) across the four increasing doses. A dose correlation was seen across most patient-reported scores.​
    • Therapist assessment of the predicted therapeutic benefit of SPL026 demonstrated a positive relationship with dose.​
  • In the majority of participants, there was a strong correlation between levels of N,N-dimethyltryptamine (“DMT”) in the body and the quality and intensity of the psychedelic experience.​
  • IV administration of SPL026 offers a short-lived, well-tolerated psychedelic experience of ~20 minutes, enabling a dosing session to last only ~30 minutes.​
  • Pharmacokinetic sampling supported rapid clearance out of the body, showing near undetectable DMT levels in the blood by 60 minutes at all investigated doses.​
The data confirms the selected dose of SPL026 taken forward into Phase IIa most consistently delivers the target treatment profile across subjects through a multi-dimensional assessment including safety, tolerability, pharmacokinetic and pharmacodynamic parameters. The full dataset is anticipated to be published in a peer reviewed journal.

David Erritzoe of Imperial College London, Chief Investigator of the Phase I/IIa study said:

"Psychedelic-assisted therapies have the potential to completely change the treatment paradigm of mental health conditions. The additional insights from Small Pharma’s Phase I study show promising results at this stage of the development. The dosing time of 30 minutes, in comparison with up to 6 hours seen with alternative approaches, has the potential to offer a real benefit in terms of treatment regimen for both patients and providers.”

The blinded, randomized, placebo-controlled, proof-of-concept Phase IIa study of SPL026 in combination with psychotherapy in 42 patients with MDD remains on track to deliver topline results in the first half of 2022. This study will assess the efficacy of one dose of SPL026 versus a placebo, and one versus two doses of SPL026 in combination with psychotherapy in patients with MDD while bolstering existing safety and tolerability data.

About Small Pharma

Small Pharma is a neuropharmaceutical company specialized in IP led development of novel treatments for mental health conditions, with a focus on depression. Small Pharma initiated a clinical program into DMT-assisted therapy in February 2021. This program includes a Phase I/IIa trial on its lead candidate, SPL026, alongside development of a robust pipeline of proprietary preclinical assets.

*From the article here :
 
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University Hospital Onofre Lopes in Rio Grande do Norte, Brazil
World 1st trial of inhaled DMT formulation*

STOCKHOUSE | 27 Apr 2022

This week, a biotech research and development company on the NEO Exchange commenced dose administration of the first subject in a Phase I/IIa clinical trial of its novel drug candidate BMND01, for Treatment Resistant Depression with inhaled administration.

Biomind Labs Inc. is developing the next generation of pharmaceuticals to treat patients suffering from neurological and psychiatric disorders by scientifically harnessing the medicinal power of psychedelic molecules.

The Phase I/IIa clinical trial on Biomind's first innovative formulation of N,N-Dimethyltryptamine (DMT) is evaluating the safety, pharmacokinetics, behavioral and brain effects of BMND01, for inhaled administration.

The trial is being administered by medical practices at Biomind's new clinical psychedelic research facility in the University Hospital Onofre Lopes. Led by Biomind’s Scientific and Clinical advisor, Dr. Dráulio Araújo, the team is a renowned group of scientists that conducted the first randomized placebo-controlled trial with ayahuasca for treatment-resistant depression. This study is the world’s first clinical trial to test an inhaled formulation of DMT, Biomind’s novel drug candidate BMND01.

Speaking on this news for investors, Biomind CEO Alejandro Antalich said that the company's new psychedelic therapeutic model, as a psychiatry intervention-based approach, may allow a rapid and feasible merge of DMT therapy into clinical practices.

“Our intervention model has the capacity to be more easily integrated into existing mental health clinics worldwide, which will democratize the access to significantly more patients than the traditional psychedelic assisted therapy model.”

Dr. Araújo added that an inhaled formulation could allow DMT to be rapidly delivered directly into the systemic circulation, bypassing the first-pass metabolism, recognized as a major problem for some routes of DMT administration.

“Due to the chosen inhaled route of administration, the DMT is likely to exert plenty of its potency in approximately 10 minutes, which will allow more affordable interventions to be designed and implemented.”

*From the article here :
 
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DMT found to improve depression and anxiety*

Alan K. Davis, Sara So and Roland R. Griffiths | Hopkins Medical

Johns Hopkins researchers have discovered that use of the synthetic psychedelic 5-methocy-N,-N-dimethyltryptamine (5-MeO-DMT) appears to be associated with unintended improvements in self-reported depression and anxiety when given in a ceremonial group setting. 5-MeO-DMT is a psychedelic that is found in the venom of Bufo Alvarius toads, in a variety of plants species, and can be produced synthetically.

In a survey of 362 adults, approximately 80 percent of respondents reported improvements in anxiety and depression after use. These improvements were related to more intense acute mystical effects during the 5-MeO-DMT experience, as well as increases in rating of the personal meaning and spiritual significance of the experience. Improvements were also related to stronger beliefs that the experience contributed to enduring well-being and life satisfaction. These results were published in The American Journal of Drug and Alcohol Abuse.

One of the unique properties of 5-MeO-DMT is the fast action and short duration of the psychedelic effects when compared to other psychedelics. “Research has shown that psychedelics given alongside psychotherapy help people with depression and anxiety. However, psychedelic sessions usually require 7 – 8 hours per session because psychedelics typically have a long duration of action,” says Alan K. Davis, Ph.D., a postdoctoral research fellow in the Behavioral Research Unit, at the Johns Hopkins University School of Medicine. “Because 5-MeO-DMT is short-acting and lasts approximately 30-90 minutes, it could be much easier to use as an adjunct to therapy because current therapies usually involve a 60 – 90 minute session.”

Last year, Davis published a study in Frontiers in Psychology that found that 5-MeO-DMT administered in a psychospiritual retreat setting produced comparable ratings of mystical experience as a high-dose psilocybin session in the laboratory setting. Another study by Davis that came out last year in The Journal of Psychopharmacology showed that 5-MeO-DMT had a safe profile of use and low risk for health and legal consequences.

“It is important to examine the short- and long-term effects of 5-MeO-DMT, which may enhance mood in general or may be particularly mood enhancing for those individuals experiencing clinically significant negative mood,” says Davis. “Regardless, this research is in its infancy and further investigation is warranted in healthy volunteers.”

*From the article here :
 
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The Power of DMT and my experience of the afterlife


by Simon | Hidden From Humanity | 28 May 2022

I'm not a drug taker, or drinker for that matter. I had heard of DMT but it wasn’t until I was ready did DMT find me. I only took it a handful of times and this experience I am sharing here with you was the final one, the one that gave me the answers. After this experience my life changed completely, my questions had answers and I no longer needed DMT…

My final experience was reality shattering, ego destroying and fear eliminating. What you may witness if you break through is a peak into the after-life. If you push all the way through, you might not only see the after-life, but you may also understand the how and whys (including where do we come from and why we are here).

That sounds hard to believe I know. Governments have known about DMT for decades and have banned it. Answer me this; how can a chemical that we ALL produce each and every night be illegal? The problem they face with DMT is that it is life changing.

Once you’ve broken through and come back, you see the World for what is truly is and your role within it. No longer are there any controls, fears, labels, separation.

A person, devoid of the DMT experience, will never understand the sheer scale of what has been witnessed by the person taking it. It is easy to postulate that what was witnessed was what the mind created. I know it is impossible for any mind, on any type of level, to create what is shown. It's a non-human reality where my own mind was just a bystander, an observer, to layers and layers of simultaneous impossibilities all interwoven to create the fabric of existence on many different levels and dimensions at the same time.

The problem for the person taking DMT is that there are no words in any language to accurately describe much of what was seen.

How do I know it isn’t just a psychedelic drug?

Even on a good experience you’ll be lucky to bring back 10% of what you saw. This is because our matter-based reality is too condensed (squashed) to be able to understand the complexity of creation. Up there it is incredibly easy to understand everything and you get all the answers. You’ll come back remembering the emotions of having these big questions answered, you may even see the answers still in your mind, but there is simply no way of conveying most of them.

With DMT you are in complete control of your faculties the whole way through. At no stage do you feel you are “tripping”. You are fully awake and aware that you’ve just been hurled through our spec of reality into the immense “place” behind this reality. You move into a World outside of time and outside of any boundaries your mind can deal with or create.

How do you describe the indescribable? How do you explain the impossible? The experience-teller is so limited by words that often what was seen cannot be said. With DMT it is the world that is replaced, instantly, it’s all gone! Reality is completely swapped out for something else vastly greater. It doesn’t even retain organic matter, 3-dimensional space or linear time as reference points.

I have seen what many would describe as an angel, but the moment I say that, people conjure up images of winged humans. That is infinitely understating what “it” is. This “angel” is not solid, the outline can barely be seen. Her brightness, yet super-sharp clarity, cannot ever be justly described. Her touch made every single last atom in my body below and my soul up there explode in the most intense joy and happiness.

The light-energy surrounding us changed when my soul realized who it was and she smiled. On this final DMT journey I was taken to where they/we come from, our life-between-life. There are no words to describe what this place is because it sits outside of words. It is the energy of everything that creates it, the higher level feelings that control it. Simply describing it isn’t enough because you need to also experience the energy, emotion and harmony to fully understand how it works.

No longer does fear play a part in your life. Controls? Gone. Ego? Gone. It is life-changing, indescribable, and the most intense experience you will ever have on this planet.

DMT is NOT a party drug, and it should not be used if you just fancy something different. If you think you are strong enough to handle an experience that will completely change your life, then and only then would I advise it. If you are not ready you may experience a bad trip. My advice is to let DMT find you because it will once you’re truly ready.

The clarity is something so incredible that I have not seen any image of a DMT experience being close to what you see once broken through. The reason is it cannot be drawn. I have however found one image that may give you a tiny idea of the scale of clarity.

This is an image of a sunflower as we see it and a sunflower as you may see it on DMT…

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What I’m trying to show is that what you see isn’t “man, that’s trippy” but more like “how can everything have a clarity so far beyond what we can see!” The picture isn’t an exact visual, but it’s heading in the right direction.

Is it dangerous?

Only if you fear death by astonishment (thank you Terence!) You don’t change but the World is instantly replaced, it dissolves this boundary and pushes you through to a place of few words. You don’t expect to be greeted by a being who tells you how vitally important it is that you are there and not to give in to astonishment. You don’t expect to have the most difficult asked questions answered. The questions are not only answered but completely understood.

The problem is our language cannot express what the afterlife is. You can see and feel the answers, but you can’t come back and DESCRIBE the answers well enough to do them justice.

My DMT Experience

On this occasion I took a big hit because I wanted to push through the veil we are trapped in to discover what is on the other side.

Initially I saw the usual geometric shapes but this time I felt a much greater pull as my soul pushed hard to leave my body suit. There was so much pressure against my body it felt like I could hardly breathe but as I lifted out everything changed!

All emotion had gone except for peace. Everything that seemed to matter in life now felt meaningless and laughable. I felt as if I had woken from a dream. I had moved from this tiny little sliver of reality back home to the full expanse of our true reality.

How difficult it is to describe that we are the universe observing itself, how difficult for many to believe that we are all connected, we are all one with all things. We are each an infinite flow of energy that can slow down its pulse or vibration enough to experience the universe through ourselves via these body-suits.

I felt my soul leave my body, lifting upwards towards the geometric shapes in front of me. As I was almost on top of them a sort of gateway opened up and these geometric shapes seeped through into the next dimension, our home. It was truly the most incredible thing I have ever seen!

The meeting of the entity

The first thing I noticed was that time had stopped. I immediately became aware that I was now in a place where time and distance no longer had any meaning.

Emotionally all I could feel was a kind of love and peace but more advanced, more powerful. There were no negative emotions here. It was like being inside a blanket of calm.

I was now in the same location but in the afterlife—pure energy and frequency, all things connected to each other in a way I cannot put into words. Visually I could see, and not see, the connections both at the same time which I know makes no sense at all.

I was still trapped in the geometric grid as it followed me through and I saw a transparent, blue glowing hand reach down in front of me. I looked up and saw the most beautiful, incredible entity. My soul and body below literally wept as this being smiled at me. This being was so bright and translucent that I could barely make out any features.

I could see through this being and yet her glow was magnificent! Her touch made every atom inside me come alive, both soul and my body suit below. It was as if my entire existence was dancing with joy and love that smothered everything.

My soul instantly knew that I had been connected to this being for aeons, she was the one who stayed there for each of my lives to assist me when needed. My Brain couldn’t understand how this could be so but my soul was dancing with immense joy to see her again.

She took my hand and guided me up. The geometric shapes restricting me fell behind but I still had some kind of barrier, like a coral, in front of me. I asked what it was for and she said that I was always welcome here, but for their and my true-self’s safety I was to be an observer and I wasn’t allowed too near, or to access the places I use between lives.

I could see other beings like her but further away moving about in this place. It was light but in a way that is hard to explain. The energy/emotion of everything created the light. There was no real distance, and it felt like I could be in all places at all times.

Still holding my hand she led me to near where they/we come from. Inside this energy building (the word ‘building’ does it no justice at all) I could feel ‘my’ presence. I am a fragment of this whole, experiencing a matter-based existence through myself. I no longer felt alone in this place—I was this place, a part of the whole.

Our material existence is an illusion, but one which we've created. It is not possible for our matter-based brains to comprehend this place when we are living in our bodies. In our real home, all the answers are found. All questions become clear because we already knew them, I just needed to remember that I knew them.

When I say answers it wasn’t one after another, it was thousands of answers all at the same time flowing through my soul. My brain could not keep up with even a tiny fraction but my soul was absorbing it all, glowing with joy as the energy of the answers flowed through it.

I knew where we come from, I understood how it works, why we don’t remember, what happens before we are born and what happens after we die. I was looking at the energy force I knew so well because this is where it all happens—where I’ve come from and gone many, many times.

As questions came into my head they were answered before I finished the question. Everything was SO clear and easy to understand. I was laughing at myself because my brain was trying to rationalize the impossible so in the end it gave up and just went from astonishment to amazement as the answers flew through my soul.

I started moving away from this place and my very old friend released me and smiled the warmest of smiles because we both knew it was time to go back. The way back was slow and in my mind I was desperate to retain the knowledge I had discovered. She knew what I was thinking before I finished thinking it and told me it was not possible to take with me what I found there because everything has to be condensed (squashed?) down so much that it is not possible to retain it on matter-based dimensions. My soul can, my brain can’t. She also pointed out that I already knew and I would know again. “Your mind will remember the feelings and emotions you had as the answers came to you.” she said warmly.

---

I didn’t find DMT. It found me... when I was ready. The few people I have spoken to about it said exactly the same thing. It is absolutely not a play-thing for your mind. It rips apart the very foundations of beliefs and can… no, probably will, change every aspect of your life.

Final thought..

Life on earth has changed for me completely. I care much more about living things. None of the troubles in this life amount to anything. When we are reborn we bring with us some of the emotion and experiences of other lives but they are locked in the soul and hidden from the consciousness mind. This “data” isn’t in the mind, it’s in atoms spread across time and space. Everything is connected and so is the data.

Some more for you to ponder…

We join these bodies during pregnancy at around the 3 month mark but during the pregnancy, and for a few months after birth we tend to leave the body quite often. We are here and there at the same time. My soul in this body is simply a piece of the whole. The remainder on the other side cannot participate in much else because it is focused on what’s happening here.

Seventy years may seem like a long time here, but there it ends almost as quickly as it starts.

We do choose our parents (we each have a goal we need to reach when we come into this life) and we base our choice on which parents would help us towards that “goal.” There could be a couple of options for parents or several. We tend to choose the ones that would help us with the “goal” rather than the ones who may be the best parents to raise us.

Whatever this goal is your life will keep steering you towards it until you have either accomplished it or you pass away before you could achieve it. If your life is forever taken down the same path then there is a high likelihood that something on this repeating path is the one you need to learn.

There is no hell or damnation. If you commit suicide you will come back and repeat the same experience again and again, life after life until you reach your goal, through choice and not force. You cannot progress if you don’t reach your goal, so you will want to keep going at it until you succeed.

Humanity tends to think that being rich or successful are the things to strive for but it is those who reach their goals that find real success, because whatever hardship was faced in this life won’t need to be faced again.

We think of suffering as a bad thing, but 70 years is just a heartbeat in the grand scheme of things. The body may suffer but the soul is simply experiencing it and cannot be harmed.

There could be one to five people in your life who have been connected to you many times before. It appears to me that there may be a small core group who can come in together to help each other, planned before we enter this World again. Personally I have discovered two in my life that are in this category.

At the moment of death there will be no fear and no doubt. You will start to wake up from this dream hidden from humanity…

http://hiddenfromhumanity.com/though...the-afterlife/
 
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‘I’m not a shaman – I just want to help people’

Shoe designer Patrick Cox on his psychedelic toad awakening.

by Hadley Freeman | The Guardian | 10 Sep 2022

The celebrity shoemaker was a fixture of the 90s London scene, then after the collapse of his business – and his mental health – he found salvation from a very unlikely source ...

This morning in my garden I picked literally kilos of tomatoes. What am I supposed to do with kilos of tomatoes?!” asks Patrick Cox, once one of the most famous shoemakers in the world, as he drives me to his home in Ibiza, which he shares with his beloved pit bull, Titus. “It’s got solar panels and a well. So I’m pretty much completely off grid, which is the dream.”

Once, this would have been Cox’s nightmare. “Getting up at 5am to do the gardening? When I was 30, I’d have been like: ‘What the fuck is wrong with you?!’” he says, and makes one of his bend-forward-at-the-belly big laughs. Back in the 90s and early 2000s, Cox, now 59, was shoemaker to the moneyed – through his high-end Patrick Cox line – and the masses, with his cheaper, mega-selling brand Wannabe, whose chunky loafers became the defining footwear of the era. Spindly stilettos by Manolo Blahnik might have made more appearances on Sex and the City, but at their peak Wannabe loafers sold 1m pairs a year. Cox’s handsome, impish face was frequently photographed at all the A-list parties. He was Elizabeth Hurley’s plus-one on the red carpet, best friends with Elton John and David Furnish. “I was the last one every night to hang up my disco shoes,” he says. He wasn’t nicknamed Party Pat by Janet Jackson for nothing.

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Patrick Cox in his Toronto store in 1992. At their peak, his Wannabe loafers sold 1m pairs a year.

Then suddenly, he seemed to disappear. Out of the blue, he emailed me this summer and wrote that he’s working on a documentary about his new life as a toad facilitator. “A toad what?!” Cox himself would have once replied. A toad facilitator is someone who helps people while they smoke toad poison, also known as 5-MeO‑DMT, the strongest hallucinogen known to man.

“I know, it’s such a cliche: ‘Patrick moves to Ibiza and becomes a shaman.’ But I am not a shaman and never will be. I just want to be part of something that is helping people,” he says.

Helping them to smoke toad poison?

“I am aware of how ridiculous it can seem, but I don’t care.”
I always had this voice in my head that I wasn’t good enough. But this isn’t some sob story. I had an amazing time. Until it stopped.

It’s my first day in Ibiza and Cox has kindly picked me up from the airport to spare me the taxi queue. When I last saw him, 15 years ago, he was wearing a smart suit. Despite being Canadian, Cox always dressed like the nattiest of Englishmen. Today, he’s wearing a button-down shirt with a magic mushroom print and loose, tie-dyed trousers. “Welcome to the Toad-mobile!” he says as we climb into his bright green Jeep. Instead of his once-signature brogues, he is wearing a pair of multicoloured slip-ons made out of, he says, “old carpets”. Did he change his wardrobe when he changed his career? “Ha! My friends ask that, but I’ve had a lot of these clothes for 20 years. I’m just putting them together in a different way now,” he says with the cackle that punctuates most of his sentences.

Cox lost his eponymous shoe line in 2007 due to various business shenanigans. “We went into kind of, like, this bankruptcy state. It gets very technical,” he explains. Suffice to say, there was overexpansion, a new CEO and an investor who ended up taking over the company. “Then I got hit by a car and spent six weeks in hospital. It was bad, bad, bad,” he says. He’d already lost Wannabe a few years earlier when the Italian factory where the shoes were made “ended up being taken over by the mafia. I didn’t go back to that part of Italy for a few years, let’s just say, ha ha ha!” In his small but very pretty home in Ibiza, there are occasional mementoes from the glory days: photos of old friends such as Kylie Minogue and Natalie Imbruglia; pictures in the bathroom of him with Elton John, Elizabeth Hurley and … the Queen. “That was from some event called something like Canadians of Note, when Canadians who had made a contribution to the country were invited to the Palace. David Furnish and I were like: ‘Who besides us will be there?!’” he says. (A lot of Canadians who work in the foreign service turned out to be the answer.)

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Cox at home in Ibiza, where he moved in 2017.

But in the main, his home feels blissfully far from the frenetic London world he once lived in and loved. Cox moved to Ibiza in 2017, and he has resisted the usual decor cliches of the island: instead of wind chimes, he has 18th-century plaster casts of ancient Greek friezes on the walls. “I bought them in the south of France with Elton,” he says. “For the first time, I managed to get something before Elton got them, because shopping with him is insane. You see something you like and he’s already bought six of them.”

Outside, Titus sleeps in the sun. Despite Cox’s previous aversion to gardening, he has a garden that verges on Eden-like behind his house, with orange and lemon trees, and rows of artichokes, courgettes, onions, carrots. It looks like absolute paradise, I tell him. “Well, if you’d come in 2018 you’d have found me lying on the floor where you’re standing now. I was crying, beyond depressed, I couldn’t even stand up. I was completely desperate,” he says, then takes a pause. “Let’s sit down, because this will take a while.” And for the next several days, we sit on his terrace and we talk.

Cox was born in Edmonton, Alberta, and his childhood was complicated. His father worked as a teacher overseas, and by the time Cox was eight he had lived in Nigeria, Chad and Cameroon, with moves back to Canada in between each posting. In 1971, Cox’s mother left his father, and when she landed back in Alberta with her two young sons, she discovered her husband had cut off all their financial support. Cox went from living in relative luxury in the southern hemisphere to being a latchkey kid in a two-room basement in western Canada, and he wouldn’t see his father for another decade. His mother struggled to cope. (He is now on good terms with her and has made efforts to re‑establish a relationship with his father.) He left home as soon as he could at 17 – a gay, disco-loving, fashion-obsessed teenager already looking for the party. He moved to Toronto, and from there to London to study shoe design in 1983.

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With Boy George in 1987.

His progress through the British fashion world is like a snapshot of the 1980s London style scene in all its ramshackle glory. He first worked for Vivienne Westwood, after meeting some of her employees in the bathroom of a club. He made moccasins by hand for the influential label BodyMap, and then worked for John Galliano after they bonded at the now-legendary 80s nightclub Taboo over a shared love of Madonna. (“We did the whole Like a Virgin routine, and John was always Madonna and I was always one of the backing boys.”) He launched his own label when he was in his mid-20s, and it did pretty well, selling around 3,000 pairs a season. But when he started Wannabe in the mid-90s, he went stratospheric. Before he had to work in his own stores to keep them going, but now he had to hire doormen to keep the crowds at bay. “I knew Elton because he came to my store and bought more shoes than anyone I’ve ever met in my life. Elizabeth came to my store. And these people are still my best, best friends,” he says.

If you were even vaguely interested in style in the late 90s and early 00s, Cox seemed ubiquitous: he helped to fund the magazine Wallpaper*, which was created by his then boyfriend Tyler Brûlé; he had stores around the world, adverts in every magazine. He was friends with everyone because he was fun to be around, and he still is: in all our time together, we drink nothing stronger than water, but he never runs out of energy, always full of “OK, now this is really off the record” anecdotes. I can’t even imagine what he was like when he was still, as he puts it, “partying”.

Does he mean “partying” in the euphemistic sense?

“Yeah, yeah, cocaine, drinking – let’s blow that euphemism apart,” he says. But despite his success he was riddled with self-doubt: “I always had this voice in my head that I wasn’t good enough, that I didn’t know what I was doing. Even when I won accessories designer of the year twice [at the British Fashion Awards], I thought: ‘Well, they made a mistake.’”

Did that voice come from his parents?

“Yeah. Telling me that I wasn’t good enough. But look, this isn’t some sob story. I had an amazing time. Until it stopped.”
I felt I had to please everyone, to prove I wasn’t as worthless as I knew I was. Then it all collapsed. Who even was I now?

When Cox lost his labels, he had a breakdown. He became so agoraphobic he couldn’t leave his house in west London, and when his PA eventually dragged him to therapy, he clung desperately to the lamp-post in the road. “Ever since I was four, I felt like I had to please everyone, trying to prove to myself that I wasn’t as worthless as I knew I was. And then it all collapsed. Who even was I now?” he says. He had been single since breaking up with Brûlé in 1997, “because how can you love someone when you can’t love yourself?” He went through the Hoffman Process, an intensive seven days of therapy that participants are not allowed to discuss afterwards, but Cox sums it up as “you prosecute your parents”. They patched him up enough that afterwards he was able to dabble in some ventures: he opened a saucy bakery in London called Cox, Cookies & Cake (“As in cock, balls and fanny,” he explains helpfully), and designed shoes occasionally for other brands. But he had made enough money in fashion to not have to work very much at all, and in 2017 decided he needed another change, so he and his two bulldogs, Brutus and Caesar, moved to Ibiza – where he later got Titus. “It was great at first. But then this cunt called Patrick Cox followed me out here,” he says.

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In 2019 with Elizabeth Hurley, who staged an intervention with Elton John and
David Furnish when Cox hit his lowest point.

He went into a severe depression, triggered when Brutus suddenly died in Ibiza while Cox was back in London for Kylie Minogue’s 50th birthday. “So I had that extra self-flagellation of feeling like: so not only has my dog died, but it happened while I was in London at a pop star’s birthday, doing things I didn’t want to be doing any more. I mean, Kylie is a friend, not just some pop star, but yeah. I completely flipped out,” he says. He talked to friends about wanting to kill himself. “Elizabeth is so no-nonsense, so she was like: ‘Well, you are NOT doing that.’ Then unbeknownst to me, she called David and Elton and said: ‘I think we need to do an intervention.’”

By now, Elton John has a long record of swooping in and packing substance-addicted celebrities off to rehab, sometimes successfully (Eminem, Rufus Wainwright, Donatella Versace), sometimes less so (George Michael replied to Elton’s offer of assistance in an open letter: “Elton John needs to shut up and get on with his life”). Cox didn’t think drugs were his problem, but he was grateful for any help, so Elton sent in the cavalry, which in this case meant his private plane. “He knew I wouldn’t leave Ibiza without Caesar, especially after what had happened to Brutus, so he very kindly sent the plane for us,” he says, and he shows me photos on his phone of a nonplussed bulldog sitting in a private plane. When they landed in England, Elton’s bodyguard drove off with Caesar in a Bentley to stay with the pop star and his family, and Cox was packed off to rehab.

He pauses at this point and walks me around the side of his house. There, under a tree, is Caesar’s gravestone, the bulldog who went on more private planes than I ever will. Next to that is the one for Brutus. Cox is still single, and while he may struggle with accepting love from a partner, he has no such difficulties when it comes to his dogs, and he becomes a little tearful when talking about the ones that are gone. It is possibly no coincidence that it was when Caesar’s health started to fail in the summer of 2019 that Cox discovered what he always calls “toad”.

Rehab stopped Cox from killing himself, but he was too much of a cynic to buy into the 12-step programme. “I kept saying: ‘What is this, a Moonie cult? I understand you’ve saved millions of people’s lives, but you do have a huge failure rate. There must be something more,’” he says.

In the past decade, there has been an enormous amount of research into whether psychedelics can alleviate mental health conditions, especially depression, anxiety and PTSD. Of course for every medical study proving the psychological benefits of LSD, you can find an anecdote about someone losing their mind after a bad acid trip. But the theory that psychedelics can be beneficial has definitely gone mainstream. Cox had always been sceptical about the grand claims people make for psychedelics: “I thought it was people just wanting to be high,” he says. But he tried microdosing LSD and was amazed at the instant impact on his mental state. But, he complained to a friend, it aggravated his stomach. “Maybe you should try some toad,” his friend replied.

Toad – or 5-MeO-DMT – is found in the poison of Bufo alvarius, a toad native to the Sonoran desert in Mexico. To extract it, the toads are “milked”, and the poison is then dried, and when it is smoked in a pipe the heat burns off the poison (so don’t go around licking toads, unless you want to be poisoned). The milking doesn’t hurt the toads, although it does potentially leave them defenceless against predators. "But 5-MeO-DMT can also be made synthetically, and while some toad purists balk at that," Cox says "the synthetic version is just as good as the natural version, but much stronger." Like all psychedelics, it is non-addictive, but it still comes with massive risks: a handful of people are known to have died from smoking toad, and anyone with heart or kidney conditions, or a predisposition to psychosis or schizophrenia, should stay well away. It is extremely fast acting and very strong – up to six times stronger than the better-known and similarly named hallucinogen DMT, which is why it has become known as the “Mount Everest of psychedelics”, as one bestselling book about psychedelics put it. Fans of toad insist that, despite its reputation, it’s a lot easier to handle than other hallucinogens. Unlike mushrooms and LSD, its effects only last for about 15 minutes, and unlike ayahuasca, there is no vomiting and purging. They claim there is no hangover or comedown afterwards, but rather they feel clear-headed and calm. I heard about one 5-MeO-DMT fan who smokes it an hour before doing the afternoon school run, as if she were grabbing an extra latte.
Some of his friends are sceptical: ‘They’re like: You call it doing the work and holding space, Patrick. But it’s called taking drugs’

There is no evidence that smoking toad poison was part of any ancient indigenous tradition. Instead, it is a late 20th-century discovery, and one that is now rocketing in popularity: Mike Tyson, of all people, said smoking toad has helped him to be “more creative”. It is illegal to possess and distribute 5-MeO‑DMT in the US and UK, and it is illegal to supply it in Spain, and in recent years several people have been arrested there for hosting toad ceremonies; in 2020, several people, including the porn actor Nacho Vidal, were arrested after a photographer died at a toad ceremony in Valencia. Vidal was later charged for reckless homicide – he maintains his innocence. But there are a growing number of “toad retreats”, on which the wealthy pay thousands of pounds to go to Central or South America – where toad is legal – to smoke it. It is likely that toad will go the same way ayahuasca has over the past decade – not mainstream exactly, but commodified and something a certain type of person likes to tick off their bucket list, along with bungee jumping in Australia and off-piste skiing in Japan. It is, allegedly, already popular among Silicon Valley titans.

In his 2018 book How To Change Your Mind: the New Science of Psychedelics, the award-winning writer Michael Pollan says his experience of smoking toad was “just horrible”, but it also gave him “a sense of relief so vast and deep as to be cosmic”. Unlike with DMT, acid and mushrooms, you don’t have visions. “It’s an experiential drug. You don’t see things when you take it. You experience them,” says Cox. And he experienced them so deeply that when he came round after taking it he found that, for the first time in his life, “I didn’t hate myself any more. There was nothing wrong with me. I’d never known that before. And now I did.” Studies have shown that 5-MeO-DMT has a psychotherapeutic effect, with some people feeling “greater life satisfaction” after trying it.

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Cox with his friends Elton John and David Furnish in 2015.

Cox smokes toad on average once a month “the way some people might go to church or mosque or synagogue”, he says. Because toad is not about getting high, but healing and “doing the work” – exploring what toad shows him. I assumed that being a “toad facilitator” was someone who sells toad poison – a drug dealer, in other words – but it turns out to be more like a drug doula: he “holds the space”for people who smoke it, a psychedelic term for sitting with someone who is smoking and making sure they feel safe. “Watching someone go through these huge transformations – there’s nothing better than that,” says Cox with feeling. He himself has gone through a huge transformation. His devotion to toad was so quick and full-hearted that he was chosen by Cesar Reyes, a very experienced toad facilitator, to be his apprentice (Reyes, 49, died last December from cancer; memories of him spark even more tears from Cox than references to Brutus and Caesar). He no longer drinks alcohol or does any drugs (other than toad) because, he says, they sever the feeling of connection he gets from toad. When he visited Elton John and Furnish in 2019, they told him they hadn’t seen him so happy in years, and he told them he had started smoking toad.
No one was a bigger cynic than me about psychedelics. Sometimes I hear what comes out of my mouth now and I’m like: Oh my God, shut up!

“Well, I’m really glad we paid for you to go to rehab, Patrick, because it sounds like you’re doing a shitload of drugs,” the singer said drily.

“But then he said: ‘If you’re happy, who am I to judge’, which I thought was just beautiful,” Cox says.

Some of his other friends are a little more sceptical: “They’re like: ‘You call it “doing the work” and “holding space”, Patrick. But it’s called taking drugs,’” he laughs, conceding the point a little.

Before I flew to Ibiza, my editor expressly warned me not to go gonzo and smoke 5-MeO-DMT. But, I tell Cox, even after hours of talking to him, I still have so many questions about toad. Like, doesn’t he think he’s simply substituted a more powerful drug for less satisfying ones? When he says that the world would be better off if everyone smoked toad, is it possible that he has given himself brain damage from all these psychedelics? Cox is spending this autumn filming his documentary, even going to Mexico to see the toads. His commitment to spreading the word is impressive, but is he ready to give up his reputation as a talented shoe designer to be known as the crazy toad guy? “No one was a bigger cynic than me about psychedelics, and sometimes I hear the stuff that comes out of my mouth now and I’m like: ‘Oh my God, shut up!’ But trying to explain toad to someone who has never taken it is like trying to explain sex to someone who has only ever watched it,” he says. Pretty convenient fob-off, the sceptical side of my brain says. The curious part says: “Well, let’s smoke some toad, then.”

Patrick Cox relaxing on a sofa with his dog Titus outside his home in Ibiza

Wearing his toad T-shirt with Titus.

Firmly ignoring my editor’s instruction, I find someone, who I’ll call C, who has toad, and I ask Cox to come with me to see him and keep me safe – to hold the space. He replies firmly that I’ll first have to answer some questions. After ascertaining whether I have any history of cardiac problems, depression or psychosis (none all round), he asks if I’ve had any alcohol or narcotics in the past three days, whether I’m on selective serotonin reuptake inhibitors (SSRIs, a common kind of antidepressant, which combined with toad can lead to the potentially fatal serotonin syndrome), and if I’m just doing this to get high. I answer in the negative to all, so he agrees. I hand over €200 of my own money to C and he tells me to sit on a mat on the ground and to breathe through my mouth. He weighs a small amount of toad poison on a scale and puts it in the bulb of a glass pipe. Cox sits beside me and murmurs a blessing, touching each of my shoulders and my back, while C heats the bulb. As the poison smokes in the bulb, C tells me to take a deep inhale on the glass pipe. I think: “Am I really putting my life and my mind in the hands of Patrick Cox?” And then I don’t think anything at all.

I expected to see fractals, wavy lines, kaleidoscopic colours – the things you might see on an LSD or mushroom trip. Instead, I fall into a darkness that goes beyond blackness, and my mind dissolves. This is what toad fans describe as “ego death”. Somewhere, a bell rings, and I fall deeper and fly higher, and then I experience something that I – normally hyper verbal to a fault – cannot describe.

After an unknowable amount of time (14 minutes, it turns out) the blue sky appears in the darkness, fragment by fragment. Cox is holding my hand, telling me that I am safe. I feel terrified and ecstatic. I look at Cox, and as tears stream down my face, I hear myself say to him, in a voice that doesn’t sound like mine: “Now I understand.”

It’s my last day with Cox and we are back on his terrace. He’s as chipper as ever and I feel, well, great: clear-headed, calm and full of energy. Is this the toad or just the effect of a trip to Ibiza? Cox says all psychedelic experiences are affected by “the set and the setting”, ie your mindset and where you’re doing it. Certainly something has had a strong impact on me, because it no longer seems entirely ridiculous that I smoked toad poison with the man who used to make my loafers.

Cox knows he has the zeal of a convert, and he tries to dial it down a little. When he first got into toad, he grew his hair long, diving into the psychedelic look. Then a friend stood him in front of a mirror and said: “Would you fuck you?” “Point taken!” he hoots at the memory. (Whatever toad has done to him, it has not – thankfully – taken away his sense of humour.) His focus now is to teach people how to do toad safely, and to try to keep it accessible to anyone who wants it, not just the 1% crowd. I ask if he’ll ever go back to fashion and he recoils; instead, he’s thinking of opening an animal sanctuary. A part of him would like to be part of “the psychedelic community”, he says, but the same cynical mindset that resisted rehab pulls him away from joining this group, too: “There’s a lot in that world that I don’t agree with. I’m not a new ageist and I’m not a conspiracy theorist,” he says. "Easier just to explore things on his own without putting a label on it," he says.
People think change is only possible when you’re younger, and who you are when you’re 30 is who you are for ever, which is crazy

When I told a friend in the fashion world about my interview with Cox, they asked if I thought he had lost his mind. I don’t. I think he’s happy to have found a purpose – to feel needed – after being adrift for so long, and I think he’s relieved to feel as if there’s something greater out there when he’d grown so jaded with the little world he knew. I also think there is something beyond explanation about toad. For the week after I smoked it, I felt calmer and slept better than I had in years. The thought of smoking it every month, as Cox does, blows my mind almost as much as the toad did. But doing it once a year, a kind of psychedelic MOT? That doesn’t sound totally crazy to me any more. It’s entirely possible that Cox is at the forefront of a new understanding of psychology and neurology. It’s also possible that he’s another guy who went to Ibiza and dropped out, and those two things aren’t mutually exclusive.

Cox doesn’t plan to smoke toad for ever, because the goal is to be able to access the feelings without the drug. “People think change is only possible when you’re younger, and who you are when you’re 30, that’s who you are for ever, which is crazy,” he says. When he was 30, he was a famous shoe designer. Now he’s almost 60 and he’s a toad facilitator. "I don’t know if we would all benefit from smoking toad poison," as he says, "but I do think people would be happier if they had the freedom – and the courage – to keep evolving, as he has done. To not cling on to one identity, but to keep exploring, and to not care if we look, maybe, a bit ridiculous."

It’s my last day and Cox is wearing trousers with an image of Jesus on them and a T-shirt with a giant picture of a toad on it. It matches the charm on his necklace. I hug him goodbye and ask one last question: doesn’t he worry, just a little, about losing his mind on toad?

“Of course not, because I’ll be happy,” he grins, and the golden toad around his neck glints in the sun.
Patrick Cox’s documentary, The Road to Toad, is due to be released in spring 2023.

 
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