Abstract

5-MeO-DMT, or 5-methoxy-N,N-dimethyltryptamine, is an indole alkaloid belonging to the tryptamine class, characterized by its ring substitution. Tryptamines are defined by a core structure that features a bicyclic indole heterocycle, with a terminal amine group linked at the R3 position through an ethyl side chain. In the case of 5-MeO-DMT, a methoxy (MeO) group (CH3O−) is attached at the R5 position of the indole heterocycle, and there are two methyl groups (CH3-) connected to the terminal amine nitrogen (RN) of the tryptamine backbone, which is derived from DMT. This article presents a comprehensive overview of 5-MeO-DMT, including its general information, physico-chemical properties, pharmacology in recreational use, effects and symptoms, use street names, prices and approximate dosage, dangerous interactions, legal status, synthesis of 5-MeO-DMT, conclusion, and bibliography.

General Information About 5-MeO-DMT [1-3]

Other synonyms names of 5-MeO-DMT are: N,N-Dimethyl-5-methoxytryptamine; 5-Methoxy-N,N-dimethyltryptamine; O-Methylbufotenine; 5-Methoxydimethyltryptamine; Methylbufotenine; 3-(2-Dimethylaminoethyl)-5-methoxyindole; Mebufotenin; 2-(5-Methoxy-1H-indol-3-yl)-N,N-dimethylethanamine; 5-Methoxy-N,N-dimethyl-1H-indole-3-ethanamine; 5-Methoxy-N,N-dimethyl-1H-indole-3-ethylamine; 3-(2-(N,N-Dimethyl)aminoethyl)-5-methoxyindole; N,N-Dimethyl-5-methoxy tryptamine

IUPAC Name of 5-MeO-DMT: 2-(5-methoxy-1H-indol-3-yl)-N,N-dimethylethanamine

CAS numbers is 1019-45-0

Trade names are The God Molecule, Toad, Jaguar

Physico-Chemical Properties of 5-MeO-DMT [1-4]

• Molecular Formula C₁₃H₁₈N₂O
• Molar Weight 218.29 g/mol
• Melting Point 69.5°C (free base)
• Solubility: Water solubility is >32.7 μg/mL
• Color/Form: solid

Structural formula present on Figure 1.

General Information About 5-MeO-DMT, Recreational Use and Pharmacology [1, 4, 5]

5-MeO-DMT was first synthesized in 1936 and later isolated in 1959 as a psychoactive component of the seeds from Anadenanthera peregrina, which are used in making Yopo snuff. It was once thought to be a primary contributor to the psychoactive effects of the snuff; however, recent findings suggest otherwise, as the seeds contain minimal to negligible amounts of the substance. Instead, the psychoactivity is mainly attributed to bufotenin, a metabolite formed when 5-MeO-DMT is O-demethylated. In 1971, John Mann established the Church of the Tree of Life in California, which, although now inactive, recognized 5-MeO-DMT as a sacramental substance. From around 1971 until the late 1980s, it was subtly accessible to church members. Between 1970 and 1990, smoking 5-MeO-DMT with parsley was likely one of the two most prevalent methods of consumption in the United States.

Сrystalline solid possible of the 5-MeO-DMT can be seen in the picture provided in Figure 2.

5-MeO-DMT is a methoxylated variant of DMT. Unlike many typical psychedelics that primarily engage serotonin 5-HT2A receptors, 5-MeO-DMT has a striking 1000-fold higher affinity for 5-HT1A receptors compared to 5-HT2A. This strong affinity allows 5-MeO-DMT to effectively inhibit the activity of dorsal raphe 5-HT neurons. In experiments with rats, the effects of 5-MeO-DMT were diminished when the selective 5-HT1A antagonist WAY-100635 was administered, while the 5-HT2A antagonist volinanserin showed no significant impact. Additionally, other mechanisms, such as the inhibition of monoamine reuptake, might also play a role. A 2019 study in Europe involving 42 participants found that a single inhalation of 5-MeO-DMT led to lasting improvements in life satisfaction and reductions in anxiety, depression, and PTSD symptoms. Furthermore, a 2018 study indicated that a single dose of 5-MeO-DMT could promote neurogenesis in mice.

Effects and symptoms of 5-MeO-DMT Use [1, 4-8]

When smoked, the effects can last as briefly as ten minutes, while insufflation can extend the duration to nearly two hours. The experiences can vary widely, encompassing profound shifts in perspective, feelings of euphoria, immersive states, dissociation, and enhanced sensuality. Conversely, some may experience dysphoria, fear, terror, panic, and even ego dissolution.

Tripping on the World’s Oldest Psychedelic | HAMILTON’S PHARMACOPEIA

All effects in different categories [4-8]

Physical effects

Spontaneous bodily sensations are perhaps the most striking aspect of the 5-MeO-DMT experience. This substance can amplify physical and tactile sensations to such an extraordinary level that it may evoke a prolonged and repeatable full-body orgasm, affecting every nerve ending throughout the body—an intensity not seen with other psychedelics. This sensation can lead to a feeling of difficulty in maintaining breath; however, it’s important to note that this is not a true respiratory depression and is generally regarded as safe, although research on this specific phenomenon is limited.

• Physical euphoria
• Tactile enhancement
• Perception of bodily heaviness
• Bodily control enhancement
• Bodily pressures
• Changes in felt bodily form
• Changes in felt gravity
• Physical autonomy
• Muscle contractions
• Muscle spasms
• Muscle tremors
• Motor control loss
• Respiratory depression
• Nausea – Nausea is perhaps more pronounced and consistently produced on 5-MeO-DMT than any other psychedelic. It is not uncommon for users to vomit while in an unconscious or semi-conscious state, which is one of the reasons supervised usage is always advised. However, some people report experiences with minimal or brief nausea. When nausea does occur, it typically disappears after the come up phase.
• Pupil dilation
• Skin flushing
• Spatial disorientation
• Temperature regulation suppression

Visual effects

• Visual acuity enhancement or Visual acuity suppression – 5-MeO-DMT is equally capable of both decreasing and increasing visual acuity. The outcome of which effect will manifest seems to be chosen almost entirely at random and is largely setting dependent.
• Drifting (Morphing, Breathing, Melting, Flowing) – In comparison to other psychedelics, this effect can be described as identical to DMT in its style, highly detailed, slow and smooth in motion and static in appearance.
• Colour shifting
• Environmental orbism
• Recursion

Cognitive effects

• Amnesia
• Analysis enhancement
• Anxiety
• Conceptual thinking
• Catharsis
• Confusion
• Delusion
• Emotion enhancement
• Memory suppression
• Ego death – This effect is more consistent and reproducible on 5-MeO-DMT than on any other known substance.
• Mindfulness
• Rejuvenation
• Autonomous voice communication
• Thought connectivity
• Time distortion
• Wakefulness

Auditory effects

• Enhancements
• Distortions
• Hallucinations

Transpersonal effects

• Perception of eternalism
• Perception of self-design
• Perception of predeterminism
• Perceived exposure to inner mechanics of consciousness
• Unity and interconnectedness

Street Names, Prices and Approximate Dosage [1-8]

5-MeO-DMT molecule and Bufo alvarius on Figure Figure 3.

Street Names

5-MeO-DMT is commonly referred to by several intriguing street names, including The God Molecule, Toad and Jaguar. These names often reflect the substance’s powerful effects and its association with spiritual or transformative experiences.

Dosage

When it comes to dosage, 5-MeO-DMT can be categorized as follows:

-Threshold: 10 – 20 mg – This is the minimum dose that may produce noticeable effects.

• Light: 20 – 50 mg – At this level, users may experience mild psychedelic effects.
• Common: 50 – 100 mg – This is a typical range for most users seeking a moderate experience.
• Strong: 100 – 200 mg – Doses in this range can lead to intense and profound experiences, often characterized by significant alterations in perception and consciousness.

Duration

• The effects of 5-MeO-DMT are relatively short-lived compared to some other psychedelics, with the following timeline:
• Total Duration: 20 – 40 minutes – The entire experience tends to be brief, making it distinct among psychedelics.
• Onset: 5 – 60 seconds – Effects can begin almost immediately after administration, particularly when smoked or vaporized.
• Come Up: 30 – 60 seconds – Users typically begin to feel the effects build up rapidly.
• Peak: 5 – 15 minutes – The peak experience is often intense and can involve profound shifts in consciousness.
• Offset: 10 – 20 minutes – The decline from peak effects occurs fairly quickly.

• After Effects: 15 – 60 minutes – After the main effects wear off, users may still feel lingering effects or a sense of introspection.

Price

In terms of pricing, 5-MeO-DMT can be acquired at varying amounts:

– 5 grams: Approximately $170 – This smaller quantity is often enough for personal use or experimentation.

– 50 grams: Around $1400 – This larger amount is typically sought by those looking to stock up or provide for a group setting.

Dangerous interactions [6-8]

• 2C-T-X: Both classes of compounds can produce unpredictable effects when taken alone.
• 2C-X: The 5-MeO psychedelics may unpredictably enhance the effects of other psychedelics.
• Cannabis: Can increase the likelihood of negative psychological effects, including anxiety, paranoia, and psychosis.
• DOx: The 5-MeO class of tryptamines can lead to unpredictable interactions, heightening the risk of unpleasant physical side effects.
• MDMA: Some 5-MeO tryptamines may produce unpredictable effects, so caution is advised when combining them with MDMA.
• Mescaline: Similar to other 5-MeO tryptamines, interactions can be unpredictable.
• NBOMe: This combination is best avoided, as both the 5-MeO tryptamines and NBOMes can exhibit unpredictable effects when used alone.
• Amphetamines: The stimulating and anxiogenic effects of amphetamines can lead to unpleasant thought loops. Generally, combining them with psychedelics is unnecessary due to the stimulating properties of both.
• Cocaine: Similar to amphetamines, the anxiogenic effects may increase the risk of negative thought patterns, and combining them with psychedelics is typically unnecessary.
• DXM: Limited information is available on the effects of this combination.
• Tramadol: There is an increased risk of serotonin syndrome when combined with 5-MeO substances.
• aMT: Also associated with a heightened risk of serotonin syndrome.
• MAOIs: Carry an increased risk of serotonin syndrome when combined with 5-MeO tryptamines.
• PCP: Little information is available about this combination, but it may increase the risk of psychosis and excessive stimulation.
• While fatalities from 5-MeO-DMT are rare, caution is essential. As a potent monoamine reuptake inhibitor (MRI), taking excessive doses or combining it with substances such as MAOIs, RIMAs, stimulants, or any compounds that act as releasing agents or reuptake inhibitors of neurotransmitters like serotonin and dopamine can lead to serious injuries. There have been documented cases of fatal poisonings that could have been avoided with proper caution.

Legal Status [1, 6]

This is overview of the legal status of 5-MeO-DMT in various countries:

• – Australia: Classified as a Schedule 9 prohibited substance under the Poisons Standard.
• – Austria: Illegal to possess, produce, or sell under the Suchtmittelgesetz (SMG).
• – Brazil: Possession, production, and sale are illegal, listed under Portaria SVS/MS n 344.
• – China: Controlled substance as of October 2015.
• – Czech Republic: Legal, as it is not included in Government Regulation n. 463/2013.
• – Denmark: Restricted to medical or scientific purposes since December 2004.
• – Germany: Controlled under Anlage I BtMG since October 10, 2000; illegal without a license.
• – Greece: Became a controlled substance on February 18, 2003.
• – Latvia: Classified as a Schedule I drug.
• – Netherlands: Considered a controlled substance but available through online research chemical sellers.
• – New Zealand: Classified as Schedule I (Class A).
• – Romania: Illegal to produce and sell since February 2010 under the controlled substance analogue act.
• – Sweden: Classified as a health hazard and illegal to sell or possess since October 1, 2004.
• – Switzerland: Specifically named as a controlled substance under Verzeichnis E.
• – Turkey: Illegal to possess, produce, supply, or import.
• – United Kingdom: Classified as a Class A drug due to its relation to 5-HO-DMT.
• – United States: Added to Schedule I on January 19, 2011; illegal without a DEA license.

Synthesis of 5-MeO-DMT [9]

To a clean and dry reactor was charged 4-methoxyphenylhydrazine hydrochloride followed by water under a nitrogen atmosphere at 20-25 °C. The contents of the reactor were then stirred at 30-35 °C and a dark red colored suspension was observed. To the suspension, concentrated H2SO4 was cautiously added dropwise under a nitrogen atmosphere over 10 min while maintaining the temperature below 40 °C. (Note: This addition is slightly exothermic.) The brown/red solution was heated to 35-40 °C (with a target temperature of 37 °C) and stirred for an additional 10 min. A solution of 4,4-diethoxy-N,N-dimethylbutan-1-amine was prepared in acetonitrile and added dropwise to the reactor under a nitrogen atmosphere over approximatively 60 min while maintaining the temperature between 35 and 40 °C. The addition funnel was rinsed with acetonitrile and added dropwise to the reactor. The temperature was maintained at 40 °C and the contents were agitated for an additional 4 h. The mixture was cooled to 20-25 °C. The acidic aqueous solution was washed with 2-MeTHF. After each wash, the layers were allowed to settle for 15 min. The lower acidic aqueous layer was collected and the upper 2-MeTHF wash was discarded. The acidic aqueous layer was recharged to the reactor and sodium hydroxide solution was added dropwise while maintaining the temperature at 20- 25 °C to bring the pH to 11-12 providing a milky suspension. The suspension was extracted with 2-MeTHF; following each extraction, the layers were allowed to settle for 15 min, the lower alkaline water layer was separated into a drum, and the upper organic layer was collected. The lower aqueous layer was discarded. The solution was concentrated in vacuo to an oily amber residue. Residual water was removed azeotropically by redissolving the residue with fresh 2-MeTHF and repeating the concentration step. This oily residue was dried on the rotatory evaporator under vacuum (10-20 mbar) for 1 h at 40-45 °C to provide 64.9% yield of crude 5-MeODMT freebase.

Synthesis of 5-MeO-DMT according to the scheme Figure 5.

Hamilton Morris synthesizes 5-MeO-DMT

Conclusion

5-MeO-DMT, often referred to as The God Molecule, Toad or Jaguar, is a potent psychedelic with a short duration of effects. Dosages range from a threshold of 10 mg to strong experiences of 200 mg, with effects peaking within minutes. The substance’s rapid onset and brief experience make it unique among psychedelics. Caution is advised regarding its use, given the potential for intense experiences and the legal considerations surrounding its acquisition.

Bibliography

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2. https://pubchem.ncbi.nlm.nih.gov/compound/1832
3. https://www.chemspider.com/Chemical-Structure.1766.html
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7. https://www.erowid.org/experiences/subs/exp_5MeODMT.shtml
8. https://combo.tripsit.me/
9. Alexander M. Sherwood, Romain Claveau, Rafael Lancelotta, Kristi W. Kaylo and Kelsey Lenoch. ACS Omega, 2020, V. 5, pp. 32067−32075. https://doi.org/10.1021/acsomega.0c05099 https://pubs.acs.org/doi/10.1021/acsomega.0c05099