substances

1. OVERVIEW
5-MeO-DMT is a psychedelic of the tryptamine class, four to six times more powerful than its better-known cousin, DMT (N,N-dimethyltryptamine). It can be found in a wide variety of trees and shrubs, often alongside DMT and bufotenine (5-HO-DMT).
In Central and South America, some of the best known plant sources are Anadenanthera peregrina (yopo or cohoba) and Virola theiodora—both of which are traditionally harvested to make psychoactive snuff. It’s also found in the milky white venom of the Bufo alvarius toad native to the southwestern United States and northwestern Mexico.
In keeping with its ceremonial use among indigenous Amazonians, 5-MeO-DMT shows great promise in the treatment of certain medical conditions. Many people also find its effects to be personally useful or even life changing.


2. HISTORY & STATS
Traditional use of 5-MeO-DMT in the Americas goes back hundreds – maybe even thousands – of years. Ancient snuffing paraphernalia and traces of the compound found in northern Chile date the practice to at least the 8th century.[1] The use of 5-MeO-DMT-containing snuff was first recorded in 1496 by Friar Ramón Pané. Reporting to Christopher Columbus on the Taíno people of Hispaniola, Pané observed inhalation of cohoba snuff through reeds. Typically, it was used as a purgative for the sick, as well as a medium through which to obtain medical diagnoses from spirits.[2]
In 1737, Joseph Gumilla observed a similar practice, with yupa (or yopo), among the Otomac of southern Venezuela.[3] Some time later, Alexander von Humboldt described how the snuff was made. First, the seeds of the Acacia niopo (Adenanthera peregrina) were left to blacken, then mashed into a paste with cassava flour and lime from snail shells. This mixture was dried over a fire and pulverized for use—typically inhaled through a Y-shaped bone tube, such as a plover leg, with the forked ends straddling the septum.[4] Another account from Richard Spruce in the mid-1800s described the use of tubes between two people—one to blow the snuff into the nostrils of the other.[5] Spruce also collected specimens of the Adenanthera peregrina for identification.
In 1936, 5-MeO-DMT was synthesized by the chemists Toshio Hoshino and Kenya Shimodaira.[6] But it wasn’t until 1959 that it was finally identified as the major psychoactive component of yopo/cohoba.[7] It was also found in the venom of the Bufo alvarius (Sonoran Desert or Colorado River toad), sometimes at levels of up to 15% by volume.[8]
From the early 1970s, 5-MeO-DMT could be legally ordered in the US and other countries via mail order from the Church of the Tree of Life[9] and the Church of the Toad of Light.[10] Since scales accurate to the milligram weren’t widely available, it was typically added to parsley or cannabis to help with dosing.[11]
Recreational use steadily increased over the ensuing decades while remaining underground. In the 1990s, ethnobotanist Jonathan Ott and others popularized 5-MeO-DMT and developed it for sale on the internet. In 2001, research chemical vendor Mark Niemoller was arrested under the Controlled Substances Analogue Act of 1986. He was released on house arrest after agreeing to stop selling 5-MeO-DMT and a number of other substances.[12] In July 2004, “Operation Web Tryp” saw the DEA shut down five more research chemical vendors, prompting numerous others to stop trading voluntarily. In January 2011, 5-MeO-DMT was declared a Schedule I drug in the United States.

Sources of 5-MeO-DMT
Both N, N-DMT and 5-MeO-DMT are made endogenously in the human body. Contrary to popular belief, we do not have much information on how either DMT is made in the body or how it is used as a neurotransmitter. Dr. Rick Strassman hypothesized that DMT it is made in the pineal gland and that it is released during birth and at death in the introduction to his book, DMT, The Spirit Molecule. There has been some evidence to suggest that it is made in the pineal gland of rats, but nothing else has been proven. Consumable 5-MeO-DMT can be acquired by synthesizing it in a lab in its pure form, extracting it from a number of plants, or from the bufotoxin of the Sonoran Desert Toad. We will be working with medicine extracting from Phalaris grass.

CURRENT USE
5-MeO-DMT is often conflated with other tryptamines or “novel psychoactive substances” in major drug surveys, so it’s difficult to gauge its exclusive prevalence.
However, it’s possible to get a general feel for its popularity over time by looking at Google search statistics. Between 2004 (the year of “Operation Web Tryp”) and 2007, searches for 5-MeO-DMT fell dramatically and have remained at a steady low ever since.

3. PHARMACOLOGY
Like the other tryptamines, 5-MeO-DMT has the same basic indole ring structure as DMT. It is so-called for having a methoxy group in the R5 position.
RECEPTOR BINDING
5-MeO-DMT works primarily through the serotonin (5-HT) system, with a particular binding affinity for the 5-HT1A receptor subtype.[13] It also binds to 5-HT2A and trace amine receptors, possibly mediating hallucinogenic effects via the latter.[14]

SAFETY AND TOXICITY
There is some evidence that indolealkylamines, including 5-MeO-DMT, cause serotonin syndrome when overdosed or combined.[15] Of particular concern are possible interactions with monoamine oxidase inhibitors (MAOIs) such as harmaline or harmine.[16][17] These are sometimes combined with the drug to enhance its effect, but can dangerously increase exposure to both 5-MeO-DMT and its active metabolite bufotenine.[18]
Some other safety concerns have been flagged up by animal studies. In rats, 5-MeO-DMT was found to induce hypothermia at low doses (0.5-1 mg/kg) and hyperthermia at high doses (3-10 mg/kg). In sheep, grazing on the 5-MeO-DMT-containing Phalaris tuberose/aquatica (or bulbous canary-grass) caused fatal tachycardia and respiratory failure.[13] Although more likely due to other toxins in the plant[19], this severe reaction underscores the need for caution when approaching 5-MeO-DMT’s many and varied natural sources.

4. EFFECTS
In its crystalline form, 5-MeO-DMT is often vaporized or insufflated (snorted). Effects from vaporizing are usually felt within the first 30 seconds, peaking from 1-15 minutes and lasting for up to half an hour. A threshold dose is around 1-2 mg, while a moderate-to-strong dose is 5-10 mg.
Insufflated, it may take up to five minutes to feel the effects, despite the higher dose ranges involved (threshold: 3-5 mg; moderate: 8-15 mg). Effects tend to peak after 10-30 minutes and subside from around 30-45.[20]
5-MeO-DMT may also be swallowed[21], taken sublingually (under the tongue), or injected.[22] Much higher doses are required for swallowing and results can be unreliable.
WHAT TO EXPECT
Effects come on strong, often with a loss of physical coordination and control. Users experience bright colors, moving environments, or recursive patterns, and perhaps even “environmental orbism” at higher doses. However, visual effects are limited. Unlike DMT, 5-MeO-DMT isn’t known for its visionary properties. The experience is more often described as a “perspective shift” characterized by physical, emotional, and conceptual effects.
One of the most common features of the 5-MeO-DMT experience is an enhancement of tactile awareness to the point of sensory overload. The body may also feel heavier. Intense emotions are typical, ranging from extreme fear to euphoria, and especially include anxiety or excitement during onset. It’s common to experience an overwhelming sense of oneness with the universe, or a sense of being outside of time and space while seeming to experience the totality of both. The concept of the ego as a separate entity is typically lost. Other effects include auditory hallucinations, time distortion, nausea, and memory loss.[22][23][24][25][26]
Click here to listen to Ashley Booth describe her life-changing 5-MeO-DMT experience

PRECAUTIONS
5-MeO-DMT should not be taken with MAOIs, including some antidepressants. Combining them may cause severe hypertensive symptoms (elevated blood pressure, heart rate, and temperature), seizures, long-term kidney damage, serotonin syndrome, and death.[27]
Because of the somewhat unpredictable nature of 5-MeO-DMT, a sitter is definitely recommended. Short-term unconsciousness, respiratory depression, and delusional interactions with the environment are some of the things to watch out for.[28] At the very least, it should be taken in a comfortable seated or lying position to avoid falling over.
Those new to 5-MeO-DMT should start out with a low dose, weighed on a scale accurate to 0.002 g (2 mg). Since people tend to react differently to the same doses (and it’s not entirely clear why) caution is advisable even if you have prior experience of tryptamines.
As with any psychedelic, follow the 6Ss of psychedelic use to minimize the risks of a bad experience.

5. MYTHS
5-MEO-DMT IS A FORM OF DMT
This myth is based on a common, and potentially very dangerous, misunderstanding of pharmacology. It’s no more a form of DMT than psilocybin is. Although chemically related, 5-MeO-DMT has a substantially different toxicity profile. It’s also active at much lower doses, so a case of mistaken identity could lead to overdose.[29]
LICKING TOADS IS AN EASY WAY TO GET HIGH
Alexander Shulgin attributed this myth (or rather, very bad idea) to sensationalism in the media.[30] Licking Bufo alvarius toads has never been a common method for obtaining 5-MeO-DMT, for the simple reason that it’s deadly. Other chemicals in raw toad secretions are known to be cardiotoxic, which means they’ll disrupt the functioning of the heart. Numerous humans have died after licking toads and one child who was hospitalized with seizures from Bufo alvarius venom took a week to recover.[31] Given that just this one, geographically isolated species is known to be psychoactive, there’s also the danger of licking the wrong toad entirely, which can cause death or permanent paralysis.

6. THERAPEUTIC USE
5-MeO-DMT is routinely used to alleviate depression, anxiety, PTSD, and addiction.[32][33] It’s sometimes used alongside ibogaine treatment to help patients integrate what they’ve learned.[34]
Limited clinical research appears to support such use of 5-MeO-DMT in treating addiction and depressive disorders. After administering the compound to mice, researchers found a major downregulation in mGluR5, a receptor involved in the reward mechanism of drug abuse. Not only are mice without the mGluR5 gene less likely to self-administer cocaine and ethanol, they also show less severe symptoms of nicotine withdrawal. Furthermore, cells treated with 5-MeO-DMT showed an upregulation of integrins, a response similar to that of depressed patients to antidepressant medications.[35]
5-MeO-DMT also appears to have a placebo analgesic effect comparable to hypnosis.[36][37][38] Like the other classical psychedelics, it may be useful in the treatment of acute and chronic inflammatory conditions[39][40], including some cancers.[41][42]
More indirectly, 5-MeO-DMT helps researchers to better understand the neurobiological basis of schizophrenic hallucinations—ultimately paving the way for more effective antipsychotic drugs.[43]

7. PERSONAL GROWTH
Ego loss on 5-MeO-DMT is often described in positive terms—even if the experience was terrifying at the time. Many see it as a process of death and rebirth followed by lasting self-improvements, including mental clarity, increased motivation, enhanced awareness, joy in living, and a sense of inner peace. Some have also had empowering “enlightenment” experiences characterized by a sense of inseparability from the universe or of being “all that exists.”[44][45][46]
Being forced to let go of the ego is precisely what draws many people to 5-MeO-DMT. The dissolution experience can impart an understanding and acceptance of mortality that helps to overcome the fear of death.[32] It can also break attachments with past trauma, negative behaviors, and habitual negative thought patterns.

8. LEGALITY
5-MeO-DMT is a Schedule I controlled substance in the United States, which means it’s illegal to manufacture, buy, possess, or distribute. It’s also illegal in the United Kingdom, Australia, New Zealand, and many European countries—although in Denmark, at least, it’s permitted for use in research.
In Canada, it remains unregulated and widely available for purchase online.[47]

9. FAQ
CAN IT BE DETECTED IN A DRUG TEST?
5-MeO-DMT isn’t detected in any standard or extended drug tests, nor are there specialized tests to look for it. Also, since it’s unlike other drugs tested for, it shouldn’t trigger a false positive.

WILL IT MAKE ME GO CRAZY?
Most people find the effects overwhelming. Consensus reality, the physical environment, body, and self tend to fall away and behavior can become irrational. While long-term psychosis seems improbable, it may take several days to a week to fully recover from the experience.

ARE THERE RISKS?
Taken in the presence of a sitter with no other drugs or contraindicated medications (like MAOI antidepressants), 5-MeO-DMT appears to be relatively safe. That said, persistent anxiety has been reported after just one use, along with sleep disruption and panic attacks. To help minimize the risks, it’s a good idea to start with low, precisely measured doses, and have an experienced sitter present.

IS IT LEGAL TO KEEP TOADS OR GROW PLANTS CONTAINING 5-MEO-DMT?
Cultivating natural sources of Schedule I drugs (except in specified cases like cannabis and peyote) is a bit of a legal grey area. While the law prohibits “any material containing any quantity” of illegal substances, the likelihood of prosecution is slim. On the other hand, extracting 5-MeO-DMT from any source is definitely illegal and will lead to prosecution if caught.
Regarding toads, the rules are clearer. In New Mexico, only state residents may collect them without a license. Both residents and non-residents of Arizona need a fishing license to collect a maximum of 10 Bufo alvarius toads. In California, meanwhile, it’s a misdemeanor to collect toads and possession is against the law. Regardless of the legality, though, Bufo alvarius is a threatened species. Keeping toads in captivity—not to mention regular “milking”—is found to damage their health.

WHAT’S THE SAFEST WAY TO TAKE IT?
There is no entirely safe way to take 5-MeO-DMT. That said, vaporizing is by far the most popular way and it also seems to be the safest. The onset of effects is shorter than with insufflated or sublingual use, however some people experience chest pains from the smoke. Others experience no effects whatsoever and prefer intravenous or intramuscular injections. These induce rapid, intense effects even at low doses. Swallowing the drug isn’t recommended due to safety concerns and it’s often ineffective anyway.

CAN I MICRODOSE WITH 5-MEO-DMT?
As people’s reactions vary immensely, it’s hard to give a reliable microdose range. Some have felt profound effects on less than a threshold dose, while others experience only mild effects from a moderate dose.

CAN I DEVELOP A TOLERANCE?
Yes, tolerance develops almost immediately and takes two hours to return to baseline. But there is no cross-tolerance with other psychedelics.

CAN I MIX IT WITH OTHER DRUGS?
It shouldn’t be mixed with MAOIs or RIMAs, including some antidepressants, due to the risk of serotonin syndrome and death. Releasing agents and reuptake inhibitors, for serotonin and dopamine especially, can be dangerous in combination. For this reason, mixing 5-MeO-DMT with other psychoactive drugs or alcohol is generally discouraged.

10. FOOTNOTES
[1] Erowid. (2015). 5-MeO-DMT Timeline.
[2] Pané, R. (1999). An Account of the Antiquities of the Indians. Juan Arrom, J. (Ed.). Duke University Press.
[3] Torres, C. M., Repke, D. B. (2014). Anadenanthera: Visionary Plant of Ancient South America. Routledge.
[4] von Humboldt, A. (1907). Personal Narrative of Travels to the Equinoctal Regions of America, During the Years 1799-1804. London: George Bell & Sons.
[5] Tryptamine Palace. Traditional Use.
[6] Hoshino, T., Shimodaira, K. (1936). ÜBER DIE SYNTHESE DES BUFOTENIN-METHYL-ÄTHERS (5-METHOXY-N-DIMETHYL-TRYPTAMIN) UND BUFOTENINS (SYNTHESEN IN DER INDOL-GRUPPE. XV). Bulletin of the Chemical Society of Japan, 11(3), 221-224.
[7] Beckley Foundation. DMT.
[8] The Sonoran Desert Toad. Erowid.
[9] Stuart, R. Entheogenic Sects and Psychedelic Religions. MAPS.
[10] Most, A. (1983). Bufo alvarius: The Psychedelic Toad of the Sonoran Desert. Erowid.
[11] Turner, D. M. (1994). The Essential Psychedelic Guide. San Francisco, CA: Panther Press.
[12] Dunn, T. (2002). The Strange Case of Mark Niemoller. AlterNet.
[13] Shen, H., Jiang, X., Winter, J. C., Yu, A. (2010). Psychedelic 5-Methoxy-N,N-dimethyltryptamine: Metabolism, Pharmacokinetics, Drug Interactions, and Pharmacological Actions. Current Drug Metabolism, 11(8), 659-666.
[14] Wallach, J. V. (2009). Endogenous hallucinogens as ligands of the trace amine receptors: a possible role in sensory perception. Medical Hypotheses, 72(1), 91-4.
[15] Yu, A. (2008). Indolealkylamines: Biotransformations and Potential Drug–Drug Interactions. The AAPS Journal, 10(2), 242.
[16] Brush, D. E., Bird, S. B., Boyer, E. W. (2004). Monoamine oxidase inhibitor poisoning resulting from Internet misinformation on illicit substances. Journal of Toxicology: Clinical Toxicology, 42(2), 191-5.
[17] Sklerov, J., Levine, B., Moore, K. A., King, T., Fowler, D. (2005). A fatal intoxication following the ingestion of 5-methoxy-N,N-dimethyltryptamine in an ayahuasca preparation. Journal of Analytical Toxicology, 29(8), 838-41.
[18] Tittarelli, R., Mannocchi, G., Pantano, F., Romolo, F. S. (2015). Recreational Use, Analysis and Toxicity of Tryptamines. Current Neuropharmacology, 13(1), 26-46.
[19] Oram, R. N., Edlington, J. P. (1996). Breeding Non-Toxic Phalaris (Phalaris Aquatica L.). The Regional Institute.
[20] Erowid. (2015). 5-MeO-DMT Dosage.
[21] Earth Erowid. (2015). Ayahuasca Conference.
[22] Shulgin, A., Shulgin, A. (1997). TiHKAL: The Continuation. U.S.: Transform Press.
[23] Netrunner. (2014). The Power and The Glory: An Experience with Harmaline, 5-MeO-DMT & DMT (ID 34866). Erowid.
[24] PsychonautWiki. 5-MeO-DMT.
[25] Vegan. (2006). Otherworldly Bliss: An Experience with 5-MeO-DMT (ID 523111). Erowid.
[26] Bowers, J. (2015). Personal Story: My 5-MeO-DMT Experience. Reset.me.
[27] Erowid. (2015). 5-MeO-DMT (5-Methoxydimethyltryptamine) Health.
[28] Bateman, D. N., Jefferson, R. D., Thomas, S., Thompson, J. P., Vale, A. (2014). Oxford Desk Reference: Toxicology. Oxford University Press.
[29] Erowid Crew. (2009). 5-MeO-DMT is Not “DMT”: Differentiation is Wise. Erowid Extracts, 17, 16.
[30] Oroc, J. (2009). Tryptamine Palace: 5-MeO-DMT and the Sonoran Desert Toad. Inner Traditions / Bear & Co.
[31] Weil, A. T., Davis, W. (1994). Bufo alvarius: a potent hallucinogen of animal origin. Journal of Ethnopharmacology, 41, 1-8.
[32] Psychedelic Times Staff. (2016). Exploring the Sacred Power of 5-MeO-DMT and the Psychedelic Toad: Podcast with Dr. Gerardo Sandoval. Psychedelic Times.
[33] Roger R. (2016). What is the Difference between 5-MeO-DMT and DMT? Choosing a DMT Therapy. Psychedelic Times.
[34] Wes T. (2015). At the Crossroads of Ibogaine and 5-MeO-DMT: An Interview with Dr. Martin Polanco. Psychedelic Times.
[35] Dakic, V. et al. (2017). Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N,N-dimethyltryptamine. bioRxiv preprint.
[36] Archer, T., Minor, B. G., Post, C. (1985). Blockade and Reversal of 5-Methoxy-N,N-Dimethyltryptamine-Induced Analgesia Following Noradrenaline Depletion. Brain Research, 333, 55-61.
[37] Archer, T. et al. (1987). (+)-8-OH-DPAT and 5-MeODMT Induced Analgesia is Antagonised by Noradrenaline Depletion. Physiology & Behavior, 39, 95-102.
[38] Q4LT. (2016). Placebo Effect.
[39] Szabo, A., Kovacs, A. Frecska, E., Rajnavolgyi, E. (2014). Psychedelic N,N-Dimethyltryptamine and 5-Methoxy-N,N-Dimethyltryptamine Modulate Innate and Adaptive Inflammatory Responses through the Sigma-1 Receptor of Human Monocyte-Derived Dendritic Cells. PLOS ONE.
[40] dos Santos, R. G., Osório, F. L., Crippa, J. A. S., Riba, J, Zuardi, A. W., Hallak, J. E. C. (2016). Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years. Therapeutic Advances in Psychopharmacology, 6(3), 193-213.
[41] Szabo, A. (2015). Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities. Frontiers in Immunology, 6, 358.
[42] Frontiers in. Research Topic: Psychotropic Substances and the Immune System: Implications in Allergy, Autoimmunity, Cancer, and Neuropsychiatric Disorders.
[43] Riga, M. S., Soria, G., Tudela, R., Artigas, F., Celada, P. (2014). The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs. International Journal of Neuropsychopharmacology, 17(8), 1269-1282.
[44] Tryptamine Palace. Smoking 5-MeO-DMT; Ceremony, Method and Dosage.
[45] Wes T. (2016). Psychedelic Research with Ibogaine and 5-MeO-DMT: An Interview with Dr. Joseph Barsuglia. Psychedelic Times.
[46] Lola B. Prime, Probe, Process: An Experience with 5-MeO-DMT (ID 56384). Erowid.
[47] Erowid. (2015). 5-MeO-DMT Legal Status.