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Summary sheet: Tramadol
Tramadol (Racemate).svg
Chemical Nomenclature
Common names Tramadol, Tramal, Tadol, Tramacur, Tramundin
Substitutive name Tramadol
Systematic name 2-[(Dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol
Class Membership
Psychoactive class Opioid
Chemical class Cyclohexanol
Routes of Administration


Bioavailability 70 - 90%[2]
Threshold 25 mg
Light 50 - 100 mg
Common 100 - 250 mg
Strong 250 - 300 mg
Heavy 300 mg +
Total 6 - 10 hours
Onset 15 - 60 minutes
Peak 2 - 6 hours
Offset 2 - 4 hours


Psilocybin mushrooms

Tramadol (also known as Ultram, Ralivia or Tramal) is a synthetic opioid substance of the cyclohexanol class that is structurally related to codeine and morphine. It acts as a weak μ-opioid receptor agonist and a reuptake inhibitor of norepinephrine and serotonin.[3][4]

Tramadol was developed in 1962 and launched under the name "Tramal" by the German pharmaceutical company Grünenthal GmbH in 1977. In the mid-1990s, it was approved for use in the United Kingdom and the United States.[5] It is used to treat moderate to moderately severe pain.

Subjective effects are largely consistent with that of traditional opioids and include sedation, pain relief, anxiety suppression, muscle relaxation, and euphoria. Tramadol is also known to produce mild to moderate entactogenic effects like increased music appreciation and empathy, affection, and sociability enhancement, which is thought to be due to its serotonergic effects.

Unlike other opioids, tramadol has been established to lower the seizure threshold in humans[6] as well as increase the risk of serotonin syndrome. This makes its effects and interactions relatively unpredictable. As a result, high doses or combinations with other psychoactive substances are strongly advised against. It is highly advised to use harm reduction practices if using this substance.

History and culture

History icon.svg

This History and culture section is a stub.


Tramadol was synthesized in 1962 by the German pharmaceutical company Grünenthal. However, it was not approved in Germany until 1977, entering the market as Tramal. It became the leading analgesic drug in Germany and during the past 38 years it has been approved in over 100 countries, including the UK, USA, Republic of China and Canada.[7]

For a period of time it was believed tramadol was not a purely synthetic drug after its apparent discovery in the roots of the pin cushion tree.[8] These reports later proved to be erroneous; the tramadol had been excreted by cows treated with the drug, resulting in the tramadol having seeped into the roots through their urine.[9]


(+/-)Tramadol, or 2-[(Dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol, is an atypical synthetic opioid. The chemical structure of tramadol consists of two rings that include a cyclohexane ring bonded to a phenyl ring at R1. This phenyl ring is substituted at R3 with a methoxy group (CH3O-). At the same location (R1) the cyclohexane ring is bonded to the phenyl ring, an additional hydroxy group is found. Tramadol features a second substitution on its cyclohexane ring at R2. Here, the ring is bonded to a dimethylamine group connected through a methyl bridge.

Tramadol is unique as it is found in a racemate (combination) of its stereoisomers. These 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. The picture seen above is the R- enantiomer of tramadol, switching the dashed and solid wedges seen on the molecule skeleton results in the S- enantiomer. It is produced as a hydrochloride salt.[10]

Tramadol is a 4-phenylpiperidine analog of codeine. Notably, it is not a morphinan opiate.


The R- and S- enantiomers of tramadol act on different receptors in a complimentary manner. The R- enantiomer is a selective agonist of the mu receptors and inhibits serotonin reuptake while the S- enantiomer inhibits noradrenaline reuptake. Tramadol acts as an opioid receptor agonist,[11][12] serotonin releasing agent,[13][14][15][16] norepinephrine reuptake inhibitor,[17] NMDA receptor antagonist,[18] 5-HT2C receptor antagonist,[19] (α7)5 nicotinic acetylcholine receptor antagonist,[20] TRPV1 receptor agonist,[21] and M1 and M3 muscarinic acetylcholine receptor antagonist.[22][23]

Tramadol is metabolised to O-Desmethyltramadol (O-DSMT), a significantly more potent opioid.


Subjective effects


Physical effects

Cognitive effects

Experience reports


Toxicity and harm potential


This toxicity and harm potential section is a stub.


Tramadol has a low toxicity relative to dose. 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 and generally has a wider range of substances which it is dangerous to combine with in comparison to other opioids. It should not be taken during benzodiazepine withdrawals as this can potentially cause seizures.


Dependence and abuse potential

As with other opioids, the chronic use of tramadol 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 tramadol 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). Tramadol presents cross-tolerance with all other opioids, meaning that after the consumption of tramadol all opioids will have a reduced effect.

Dangerous interactions

Although many psychoactive substances are reasonably safe to use on their own, they can quickly become harmful and even life-threatening when taken with other substances. The following section lists some known dangerous combinations, but it may not include all of them. Furthermore, a combination that seems to be harmless in low doses can still greatly increase the risk of injury or death when the doses are slightly increased. Independent research should always be conducted to ensure that a combination of two or more substances is safe to consume. Some interactions listed have been sourced from Tripsit.

  • Psychedelics (Psilocybin mushrooms, LSD, DMT, mescaline, DOx, 2C-x, 2C-T-x, 5-MeO-xxT) - Tramadol is well known to lower seizure threshold and psychedelics also cause occasional seizures.
    • 25x-NBOMe - Tramadol is well known to lower seizure threshold and NBOMes have also shown a tendency to cause severe seizures.
  • Dissociatives (Ketamine, MXE, PCP)
  • Stimulants (Amphetamines, Cocaine)
  • Depressants (Alcohol, GHB/GBL, opioids, benzodiazepines) - Heavy CNS depressants, risk of seizures. 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. Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present. Vomit aspiration a risk when passed out, lay down in recovery position if ingested.

Serotonin syndrome risk

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

Legal status

  • Germany: Tramadol is a prescription medicine, according to Anlage 1 AMVV.[25]
  • Sweden: As of May 2008, Sweden has chosen to classify tramadol as a controlled substance in the same way as codeine and dextropropoxyphene. This means that the substance is a scheduled drug. But unlike codeine and dextropropoxyphene, a normal prescription can be used at this time.[26]
  • United Kingdom: On June 10th, 2014, tramadol was made a Class C drug under the Misuse of Drugs Act.[27]
  • United States: Tramadol is a Schedule IV controlled substance in the United States.[28]

See also

External links


  1. Risks of Combining Depressants (Tripsit) |
  2. Klotz, U. (2003). Tramadol—the impact of its pharmacokinetic and pharmacodynamic properties on the clinical management of pain. Arzneimittelforschung, 53(10), 681-687.
  3. Induction of 5-hydroxytryptamine release by tramadol, fenfluramine and reserpine (ScienceDirect) |
  5. Tramadol as an analgesic for mild to moderate cancer pain |
  7. Lassen, D., Damkier, P., & Brøsen, K. (2015). The pharmacogenetics of tramadol. Clinical pharmacokinetics, 54(8), 825-836.
  8. Occurrence of the Synthetic Analgesic Tramadol in an African Medicinal Plant |
  10. 1: Dayer P, Desmeules J, Collart L. [Pharmacology of tramadol]. Drugs. 1997;53 Suppl 2:18-24. Review. French. PubMed PMID: 9190321.
  11. Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids ( / NCBI) |
  12. Influence of tramadol on neurotransmitter systems of the rat brain ( / NCBI) |
  13. Induction of 5-hydroxytryptamine release by tramadol, fenfluramine and reserpine ( / NCBI) |
  15. Interaction of the central analgesic, tramadol, with the uptake and release of 5-hydroxytryptamine in the rat brain in vitro ( / NCBI) |
  17. Influence of tramadol on neurotransmitter systems of the rat brain ( / NCBI) |
  18. The Effects of Tramadol and Its Metabolite on Glycine, γ-Aminobutyric AcidA, and N-Methyl-d-Aspartate Receptors Expressed in Xenopus Oocytes |
  19. The Inhibitory Effects of Tramadol on 5-Hydroxytryptamine Type 2C Receptors Expressed in Xenopus Oocytes |
  21. The analgesic drug, tramadol, acts as an agonist of the transient receptor potential vanilloid-1 ( / NCBI) |
  22. Inhibition by tramadol of muscarinic receptor-induced responses in cultured adrenal medullary cells and in Xenopus laevis oocytes expressing cloned M1 receptors ( / NCBI) |
  23. The Inhibitory Effects of Tramadol on Muscarinic Receptor-Induced Responses in Xenopus Oocytes Expressing Cloned M3 Receptors |
  28. DEA Controlled Drugs |