Guides | Tripping While Sleep-Deprived: What You Need to Know
Tripping while sleep deprived – what are the potential risks and other things to consider?...
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Disclaimer: The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of Chemical Collective or any associated parties. Always practice good set and setting when exploring any psychedelic compounds. We have a fantastic article looking into this subject you can read here.
5-MeO-DMT (N,N-Dimethyl-5-methoxytryptamine) is a psychedelic tryptamine, 4 – 6 times stronger than the better-known DMT (N,N-dimethyltryptamine).
Tryptamines are psychoactive compounds including both psychedelics, such as psilocybin (O-phosophory-4HO-DMT), and neurotransmitters, such as serotonin (5-hydroxytryptamine or 5-HT) and melatonin (N-acetyl-5-methoxytryptamine). 5-MeO-DMT can be found endogenously in a wide variety of plants, in the glands of at least one species of toad, and it has even been detected in minor amounts in the human body, in cerebrospinal fluid, urine, and blood. It is usually found in combination with DMT and other tryptamine-class chemicals. It is also possible to produce 5-MeO-DMT synthetically in a lab setting.
Given its potency, 5-MeO-DMT is widely regarded as non-recreational and is frequently used in spiritual and ceremonial contexts. Over the last several years, the popularity of 5-MeO-DMT has risen dramatically as stories of spiritual enlightenment and healing have emerged. However, the powerful effects of 5-MeO-DMT are still not yet fully understood.
5-MeO-DMT was first produced in a lab in 1936 by German Canadian chemist Richard Manske. The Western world was unaware of naturally occurring 5-MeO-DMT until 1956 when it was ‘isolated from the bark of Dictyoloma incanescens’  a shrub native to Brazil. It was subsequently discovered as the main ingredient of Yopo, a psychoactive snuff used for thousands of years in South America. Yopo is produced by grinding the seeds of Anadenanthera Peregrina, a tree native to South America and the Caribbean, which contains 5-MeO-DMT, DMT and Bufotenin.
In 1965 5-MeO-DMT was discovered in ‘the skin of Bufo Alvarius, a desert toad of Arizona’  The now infamous Sonoran Desert Toad is now known to be native to both Northwestern Mexico and the Southwestern United States, but up until the 1980s, this was completely unknown to the psychedelic community at large.
In 1983, Ken Nelson, an activist, and psychedelic researcher, began to experiment with 5-MeO-DMT found in nature. He traveled to Arizona in the Southwestern United States to harvest and smoke the venom of Bufo Alvarius becoming the first known Westerner to consume the substance. Following this experience, he went on to release a pamphlet Bufo “Psychedelic Toad of the Sonoran Desert”  under the pen-name, Albert Most. The pamphlet was a guide on the identification of Bufo Alvarius and step-by-step instructions on how to collect some of the 5-MeO-DMT-containing venom. It also contained details on how to synthesise 5-MeO-DMT. While in 1994 Dr Andrew Weil speculated that ‘ancient peoples of Mesoamerica used a toad as a ritual intoxicant.’ This is purely speculation as there is no real evidence of shamanic use before the discovery of the substance by Westerners such as Ken Nelson, who were interested in consciousness-altering substances.
Throughout the 1970s and ‘80s, it was still possible to legally purchase 5-MeO-DMT worldwide. There was even a religious sect in the US called the “Church of the Tree of Life”, which held regular ceremonies in which 5-MeO-DMT was a key element. The church even sold 5-MeO-DMT themselves, mailing the substance to interested parties, sprinkled on parsley leaves.
It wasn’t until the early 2000s that the synthesis, usage, and trade of 5-MeO-DMT began to be regulated by countries worldwide.
Due to the increase in popularity of 5-MeO-DMT, Bufo Alvarius has become a valuable commodity. This has resulted in a corresponding increase in the exploitation of the unfortunate toad. A harsh desert environment is already a difficult place for any creature to survive, let alone an amphibious creature, which requires a source of freshwater. Human intervention has already furthered the difficulty of this environment, with industrial activities causing “habitat loss, pesticides, parasitic fungi and climate change.”  Now on top of this Bufo Alvarius, as the only known natural source of 5-MeO-DMT, is also an attractive target for poachers. Wildlife experts are asking the public to leave the toads in their natural habitat as they are “susceptible to exploitation”  and their continued usage is “threatening the survival of the species” 
In an attempt to curb this exploitation two friends, a naturalist, Robert Anthony Villa, Research Associate at the University of Arizona Desert Laboratory, and an artist, Patrick Foley, have come together to raise awareness of the dangers to both the toad itself and the users of the venom it secretes. Villa was worried about the decline and increasing abuse of Bufo Alvarius and was aware that his friend Foley had harvested and consumed 5-MeO-DMT extracted from Bufo Alvarius many years prior. Foley remembered that during the process the toads “seem scared. You are pulling it out of its habitat during its mating cycle.”  the toad is “trying to get away, struggling, and you really have to hold and squeeze it, itt seems like a pretty traumatic experience.” 
By combining Foley’s interest in psychedelic art with Villa’s scientific knowledge, the pair organised a campaign designed to appeal to those likely to be set on consuming the substance. Foley drew inspiration from the Albert Most pamphlet, mentioned previously, with references to psychedelic culture, “such as an upside-down version of the iconic Grateful Dead skull.” The pamphlet includes artwork depicting Bufo Alvarius, the 5-MeO-DMT molecule and a plea for potential users to: “Please trip responsibly.” 
The pair are selling T-shirts, posters and other items to promote their message, with a portion of the profits donated to the Tucson Herpetological Society, directly in support of the toad population. They have so far managed to raise over $1,300 for the conservation group.
In 2017, Villa also appeared in an episode of Hamilton’s Pharmacopeia, on Vice, to discuss 5-MeO-DMT and the exploitation of Bufo Alvarius. The show presented an alternative to toad venom as Morris investigated the production of synthetic 5-MeO-DMT and the benefits of assured purity, and lack of impact on the natural world.
5-MeO-DMT is structurally analogous to the neurotransmitters serotonin and melatonin with effects similar to other psychedelic tryptamines such as N,N-DMT and 5-HO-DMT. The 5-MeO-DMT molecule’s structure is a methoxylated (modified by the addition of one or more methoxy groups ) derivative of DMT.
5-MeO-DMT creates its characteristic psychedelic effects by “binding to various serotonin, or 5-hydroxytryptamine, receptors, primarily the 5-HT2 and 5-HT1A receptors.” 
Other mechanisms of action have not been confirmed but may include monoamine reuptake inhibition. The CYP2D6 enzyme metabolises 5-MeO-DMT in the liver, which also metabolises a wide range of other psychoactive substances. 
5-MeO-DMT has been far less thoroughly studied in clinical trials than other classical psychedelics, such as psilocybin and LSD. “A recent industry report from BrainFutures’ psychedelics medicine report identified only 26 randomised clinical trials for 5-MeO-DMT as compared to more than 150 for LSD.” 
It is hypothesised that 5-MeO-DMT may be a particularly useful addition to the field of psychedelic medicine due to its short duration of action and the fact that the visual effects of the substance are less pronounced than the alternatives. 5-MeO-DMT is also known to cause higher rates of ego death and spiritual experiences – which may also increase its therapeutic potential.
5-MeO-DMT has been studied in a variety of animal models, but the possibilities for clinical studies with humans are only just beginning to be explored.
Epidemiological studies indicate that, like other psychedelics, 5-MeO-DMT induces profound alterations in consciousness (including mystical experiences), with potential beneficial long-term effects on mental health and well-being. 
5-MeO-DMT has already been shown to potentially “alleviate depression, anxiety, PTSD, and addiction.”  In one study, researchers administered 5-MeO-DMT to mice and discovered a significant “downregulation in mGluR5, a receptor involved in the reward mechanism of drug abuse.”  Mice without this gene are far less prone to self-administer cocaine and ethanol. Symptoms of nicotine withdrawal were also significantly reduced. “Cells treated with 5-MeO-DMT showed an upregulation of integrins.”  (“proteins involved in the adhesion of cells to each other and to their substrate.” ) Antidepressant medications have a similar effect, suggesting that 5-MeO-DMT potentially also has potential benefits for people suffering with depressive disorders.
The John Hopkins Centre for Psychedelic Research is currently studying the effects of 5-MeO-DMT. Researchers have discovered that the substance is associated with “unintended improvements in self-reported depression and anxiety when given in a ceremonial group setting.”  Lead researcher Alan Davis posits that the drug could be effective at treating mental illness because of the “neurological changes in users’ brains caused by the substance as well as insights gained through the psychedelic experience.” 
In two recent studies of more than 400 people, the majority self-reported “improvements in anxiety and depression after using 5-MeO-DMT, as well as an increase in well-being and life satisfaction.” 
Additionally, 5-MeO-DMT appears to have a placebo analgesic (painkiller) effect comparable to hypnosis. This could provide relief to those with (albeit relatively mild) conditions that cause them physical pain, as opposed to mental distress. It may also “be useful in the treatment of acute and chronic inflammatory conditions, including some cancers.” 
While not actively studied for the purpose, the exploration of the powerful hallucinatory effects of 5-MeO-DMT is also assisting researchers in better understanding the “neurobiological basis of schizophrenic hallucinations—ultimately paving the way for more effective antipsychotic drugs” 
This year, 2022, the first official human trial of 5-MeO-DMT usage was started.S Beckley Psytech, a private company based in Oxford, UK, which investigates neurological and psychiatric disorders with the usage of psychedelic medicines, announced that “the first healthy volunteers have been dosed in a Phase 1 clinical trial exploring the safety and pharmacokinetics of BPL-003”  BPL-003 is a particular formation of 5-MeO-DMT synthesised by Beckley Psytech. The substance is administered as a dry powder and dosed intranasally. It is believed this particular formation of the chemical as well as the method of ingestion “may provide potential benefits in tolerability and absorption…and could potentially change the manner in which patients experience the treatment.” 
The study of 5-MeO-DMT is still in its infancy, but judging by the limited data on the substance, its efficacy in combating particular issues and alleviating symptoms seems overwhelmingly positive.
The effects of 5-MeO-DMT are similar to N,N-DMT, though there are fewer visuals.
Bear in mind your experience may differ and not all effects will be present.
POTENTIAL PHYSICAL EFFECTS
Strong rush sensation
Spontaneous feeling in the body
Vocalising – laughter, singing, shouting, crying, speaking in tongues
POTENTIAL MENTAL EFFECTS
A sense of endlessness or infinity
The feeling of flying
Fully immersive visual and physical experiences
Huge shifts in perspectives
Life-changing spiritual experiences
Feelings of euphoria
Loss of perception of time
Fear, worry, and anxiety
DISCLAIMER: 5-MeO-DMT can produce wildly differing effects in different people, even if the dosage is identical. Effects will also be very different depending on the method of consumption.
Insufflation dosage: Threshold- 3-5 mg, Light- 5-10 mg, Common/Strong (it is a fine line)- 8-15 mg.
Insufflation (inhaling into the nose) produces a long-lasting, generally less intense psychedelic experience.
Smoked dosage: Threshold- 1-2 mg, Light- 2-5 mg, Common/Strong- 5-10 mg
Smoking 5-MeO-DMT will create a much shorter, much more intense psychedelic experience.
Oral dosage: N/A – DO NOT DO THIS.
5-MeO-DMT is orally active with an MAOI inhibitor (as with its cousin DMT) but due to its strength in comparison to DMT it is potentially a VERY DANGEROUS combination that can result in serotonin syndrome, hypertension, and seizures.
Tolerance develops immediately after dosing, and you will return to baseline within roughly two hours. There is however no cross-tolerance with other psychedelics or consciousness-altering substances.
It is difficult to provide an accurate micro-dosing range for 5-Meo-DMT due to the wide variance of its effects from person to person. Some people experience intense effects on a smaller amount than what we would consider a threshold dose, while others will experience only little or very mild effects from a moderate dose. If you are considering using 5-MeO-DMT for microdosing it is advisable to start lower than you initially may assume, then slowly titrate the dosage upwards as required.
5-MeO-DMT is not controlled under Czech law.
5-MeO-DMT is not controlled under Belgian law.
5-MeO-DMT is not controlled under French law.
5-MeO-DMT is not controlled under Dutch law.
5-MeO-DMT is not controlled under Canadian law.
5-MeO-DMT is a schedule 1 controlled substance in all United States as of January 2011
As a structural analog of N,N-dimethyltryptamine (DMT), 5-MeO-DMT is a Schedule 9 prohibited substance under the Poisons Standard.
5-MeO-DMT is controlled in China as a Category I psychotropic substance, illegal to sell, buy, import, export, and manufacture, as of October 2015
As of December 1, 2004, 5-MeO-DMT is legally restricted to ‘medical or scientific purposes’.
5-MeO-DMT was banned in Finland in December 2014.
Schedule I / Highest level of control, unable to be prescribed, manufactured or possessed as of Sep, 1999.
5-MeO-DMT became a controlled substance in Greece on Feb 18, 2003
5-MeO-DMT is controlled as a ‘designated Substance’ by the Pharmaceutical Affairs Law, making it illegal to possess or sell
5-MeO-DMT is not controlled under Mexican law.
5-MeO-DMT is Schedule I (Class A) in New Zealand
5-MeO-DMT became controlled in Russia starting October, 2011.
5-MeO-DMT is not controlled under South African law.
Controlled in Sweden as of Oct 1, 2004
5-MeO-DMT is Schedule I in Switzerland.
5-MeO-DMT has been controlled since December 2013
5-MeO-DMT is a Schedule I/Class A drug in the United Kingdom, making it illegal to buy or possess without a license
5-MeO-DMT is not detectable in any standard or extended drug tests. Also, as it is different to other drugs tested for, it is unlikely to trigger a false positive.
David Blackbourn | Community Blogger at Chemical Collective
David is one of our community bloggers here at Chemical Collective. If you’re interested in joining our blogging team and getting paid to write about subjects you’re passionate about, please reach out to Matt via email at firstname.lastname@example.org
Pachter, I. J. Z., D.E.Ribeiro, O. (1959) “Indole alkaloids of acer saccharinum (the Silver Maple), Dictyoloma incanescens, Piptadenia colubrina, and Mimosa hostilis.” J Org Chem
Weil, A. T. and W. Davis (1994) “Bufo alvarius: a potent hallucinogen of animal origin.” Journal of ethnopharmacology
V. Erspamer et al. (1965) “5-Methoxy- and 5-hydroxy-indolealkylamines in the skin of Bufo alvarius.” Experientia
James Oroc (2009) “Tryptamine Palace: 5-MeO-DMT and the Bufo alvarius Toad: A Journey from Burning Man to the Akashic Field: 5-MeO-DMT and the Bufo Alvarius Toad: 5-MeO-DMT and the Sonoran Desert Toad” Inner Traditions / Park Street Press
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