O-Desmethyltramadol

(+/-)O-Desmethyltramadol, or 3-(2-((dimethylamino)methyl)-1-hydroxycyclohexyl)phenol, is an atypical synthetic opioid. O-Desmethyltramadol is loosely analogous to codeine, but is not a morphinan opiate. Instead, it contains two rings including a cyclohexane ring that is bonded to a phenyl ring at R₁. This phenyl ring is substituted at R₃ with a hydroxy group (OH-). An additional hydroxy group is found at the same location the cyclohexane ring is bonded to at the phenyl ring, R₁. O-DMST features a third substitution on its cyclohexane ring at R₂. Here the ring is bonded to a dimethylamine group connected through a methylene bridge.

O-Desmethyltramadol is atypical as it is found in a racemate (combination) of its stereoisomers. Stereoisomers are two molecules that share the same chemical structure, but are three-dimensional mirror images of each other. Tramadol is produced as a racemate of its two isomers because the combination is proven to be more effective. Flipping the direction of the R₂ and R₁ bonds results in the R- and S- enantiomers of O-Desmethyltramadol. O-DMST is nearly identical to tramadol, and is named for the lack of the methyl group of tramadol's R₃ methoxy substituion.

O-DSMT is considerably more potent as a μ-opioid agonist compared to tramadol.^[3] Additionally, unlike tramadol, it is a high-affinity ligand of the δ- and κ-opioid receptors.^[4]

The two enantiomers of O-DSMT show quite distinct pharmacological profiles;^[5] both (+) and (−)-O-DSMT are inactive as serotonin reuptake inhibitors,^[6] but (−)-O-DSMT retains activity as a norepinephrine reuptake inhibitor,^[6] and so the mix of both the parent compound and metabolites contributes significantly to the complex pharmacological profile of tramadol. While the multiple receptor targets can be beneficial in the treatment of pain (especially complex pain syndromes such as neuropathic pain), it increases the potential for drug interactions compared to other opioids, and may also contribute to side effects.

Opioids exert their effects by binding to and activating the μ-opioid receptor. This occurs because opioids structurally mimic endogenous endorphins which are naturally found within the body and also work upon the μ-opioid receptor set. The way in which opioids structurally mimic these natural endorphins results in their euphoria, pain relief and anxiolytic effects. This is because endorphins are responsible for reducing pain, causing sleepiness, and feelings of pleasure. They can be released in response to pain, strenuous exercise, orgasm, or general excitement.

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.

Experience reports

There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:

• Erowid Experience Vaults: O-Desmethyltramadol

O-DSMT has a moderate potential toxicity relative to its dose due to its potency. As with all opioids, long-term effects can vary but can include diminished libido, apathy and memory loss. It is also potentially lethal when mixed with depressants like alcohol or benzodiazepines.

O-DSMT has recently been marketed as a currently legal substitute for illegal opioid drugs, either in powder form or mixed into various other preparations. One such blend was sold under the brand Krypton and contains powdered kratom leaf (Mitragyna speciosa) laced with O-DSMT and was reportedly linked to at least 9 accidental deaths from overdose during 2010–2011.^[7][8][9]

It is strongly recommended that one use harm reduction practices when using this drug.

Tolerance and addiction potential

As with other opioids, the chronic use of O-DSMT can be considered moderately addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal symptoms may occur if a person suddenly stops their usage.

Tolerance to many of the effects of O-DSMT develops with prolonged and repeated use. The rate at which this occurs develops at different rates for different effects, with tolerance to the constipation-inducing effects developing particularly slowly for instance. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). O-DSMT presents cross-tolerance with all other opioids, meaning that after the consumption of O-DSMT all opioids will have a reduced effect.

Dangerous interactions

Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).

Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.

• Alcohol - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place affected patients in the recovery position to prevent vomit aspiration from excess. Memory blackouts are likely
• Stimulants - Stimulants increase respiration rate which allows for a higher dose of opiates than would otherwise be used. If the stimulant wears off first then the opiate may overcome the user and cause respiratory arrest.
• Benzodiazepines - Central nervous system and/or respiratory-depressant effects may be additively or synergistically present. The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position blackouts/memory loss likely.
• DXM - Generally considered to be toxic. CNS depression, difficulty breathing, heart issues, and liver toxicity have been observed. Additionally if one takes DXM, their tolerance of opiates goes down slightly, thus causing additional synergistic effects.
• GHB/GBL - The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position
• Ketamine - Both substances bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.
• MAOIs - Coadministration of monoamine oxidase inhibitors (MAOIs) with certain opioids has been associated with rare reports of severe adverse reactions. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresis, hyperpyrexia, flushing, shivering, myoclonus, rigidity, tremor, diarrhea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases.
• MXE - MXE can potentiate the effects of opioids but also increases the risk of respiratory depression and organ toxicity.
• Nitrous - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are common.
• PCP - PCP may reduce opioid tolerance, increasing the risk of overdose.
• Tramadol - Increased risk of seizures. Tramadol itself is known to induce seizures and it may have additive effects on seizure threshold with other opioids. Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present.
• Grapefruit - While grapefruit is not psychoactive, it may affect the metabolism of certain opioids. Tramadol, oxycodone, and fentanyl are all primarily metabolized by the enzyme CYP3A4, which is potently inhibited by grapefruit juice^[10]. This may cause the drug to take longer to clear from the body. it may increase toxicity with repeated doses. Methadone may also be affected^[10]. Codeine and hydrocodone are metabolized by CYP2D6. People who are on medicines that inhibit CYP2D6, or that lack the enzyme due to a genetic mutation will not respond to codeine as it can not be metabolized into its active product: morphine.

Serotonin syndrome risk

Combinations with the following substances can cause dangerously high serotonin levels. Serotonin syndrome requires immediate medical attention and can be fatal if left untreated.

• MAOIs - Such as banisteriopsis caapi, syrian rue, phenelzine, selegiline, and moclobemide.^[11]
• Serotonin releasers - Such as MDMA, 4-FA, methamphetamine, methylone and αMT.
• SSRIs - Such as citalopram and sertraline
• SNRIs - Such as tramadol and venlafaxine
• 5-HTP

There is little information online regarding the international legalities of O-Desmethyltramadol possession but it is confirmed as a controlled substance within the United Kingdom.^[12]

• Germany: O-DSMT is not a controlled substance under the BtMG.^[13] It is legal, as long as it is not sold for human consumption, according to §2 AMG.^[14]
• Sweden: O-DSMT is a controlled substance and considered a narcotic by law.
• Switzerland: O-DSMT is not controlled under Buchstabe A, B, C and D. It could be considered legal.^[15]
• United Kingdom: It is illegal to produce, supply, or import this drug under the Psychoactive Substance Act, which came into effect on May 26th, 2016.^[16]

• Responsible use
• Tramadol
• Opioid

• O-Desmethyltramadol (Wikipedia)
• O-Desmethyltramadol (Isomer Design)