Tapentadol

Fatal overdose may occur when opiates are combined with other depressants such as benzodiazepines, barbiturates, gabapentinoids, thienodiazepines, alcohol or other GABAergic substances.

It is strongly discouraged to combine these substances, particularly in common to heavy doses.

Summary sheet: Tapentadol

Tapentadol
Chemical Nomenclature
Common names	Tapentadol, Nucynta, Palexia, Yantil, Yantil SR
Systematic name	3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol
Class Membership
Psychoactive class	Opioid
Chemical class	Phenylpropylamine
Routes of Administration
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. ⇣ Oral Dosage Threshold 12.5 mg Light 25 - 50 mg Common 50 - 75 mg Strong 75 - 150 mg Heavy 150 mg + Duration Total 4 - 6 hours Onset 15 - 30 minutes Come up 30 - 45 minutes Peak 1 - 2 hours Offset 2 - 3 hours DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Interactions
MAOIs
Nitrous
PCP
Stimulants
SNRIs
Alcohol
Benzodiazepines
DXM
GHB
GBL
Ketamine
MXE
Tramadol
Grapefruit
MAOIs
Serotonin releasers
SSRIs
5-HTP

Tapentadol often sold under the brand name Nucynta is a synthetic opioid analgesic similar in structure to tramadol. Tapentadol has a duel mechanism of action, working on both the μ-opioid receptor and also acting as a norepinephrine reuptake inhibitor. Tapentadol is used in the management of moderate to severe pain. The subjective effects of tapentadol are similar to those of tramadol. Many users report extreme pain when trying to insufflate tapentadol.

Chemistry

Tapentadol (3-((1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl) phenol hydrochloride) is a non-racemic molecule. The molecular formula of Tapentadol is C14H23NO.HCl. It was first synthesized in USA and marketed by Ortho-McNeil-Janssen Pharmaceuticals; its trade name was Nucynta.

Tapentadol is similar in structure to both tramadol and dextropropoxyphene. Tapentadol has one cyclic ring, unlike tramadol which has two. The empirical formula of tapentadol is C₁₄H₂₃NO and has a molar mass of 221.339 grams per mole. Tapentadol has thefull IUPAC name: 3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol.

Pharmacology

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. Tapentadol has an oral bioavailability of about 32%. Tapentadol is metabolized by the Cytochrome P450 system in the liver and is excreted by the kidneys in urine as well as in feces. Unlike most opioids, tapentadol is also a norepinephrine reuptake inhibitor and also has weak serotonergic effects as well.

Tapentadol is an orally available, synthetic benzenoid that acts as an agonist for the mu-opioid receptor (MOR) and inhibits the reuptake of noradrenaline, with potential anti-nociceptive activity. Upon oral administration, tapentadol binds to the MOR which enhances MOR-mediated signaling, interferes with the sensation of pain and results in an analgesic effect. Tapentadol also inhibits the reuptake of noradrenaline, which increases the levels of noradrenaline (NA), activates the inhibitory alpha-2 receptors and results in an analgesic effect.

Tapentadol and its metabolites are excreted almost exclusively (99%) via the kidneys. Approximately 70% (55% O-glucuronide and 15% sulfate of tapentadol) is excreted in conjugated form. A total of 3% of drug was excreted in urine as unchanged drug.

Subjective effects

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 ☠.

Physical effects

• The general sensation of tapentadol can be described as one of euphoria, relaxation, anxiety suppression and pain relief.
  • Pain relief
  • Physical euphoria - This particular substance can be considered as less intense in its physical euphoria when compared with that of morphine or diacetylmorphine (heroin). The sensation itself can be described as extreme feelings of intense physical comfort, warmth, love and bliss.
  • Itchiness
  • Respiratory depression - At low to moderate doses, this effect results in the sensation that the breath is slowed down mildly to moderately, but does not cause noticeable impairment. At high doses and overdoses, opioid-induced respiratory depression can result in a shortness of breath, abnormal breathing patterns, semi-consciousness, or unconsciousness. Severe overdoses can result in a coma or death without immediate medical attention.
  • Constipation
  • Cough suppression
  • Difficulty urinating
  • Nausea
  • Sedation
  • Double vision
  • Pupil constriction
  • Decreased libido
  • Appetite suppression
  • Dizziness - Tapentadol causes dizziness at a higher rate than other opioids
  • Orgasm suppression
  • Dry mouth

Cognitive effects

• The cognitive effects of Tapentadol can be broken down into several components which progressively intensify proportional to dosage. The most prominent of these cognitive effects generally include:
  • Anxiety suppression
  • Cognitive euphoria - In comparison to other opioids, Tapentadol can be considered as less intense in its cognitive euphoria when compared with that of morphine or heroin.
  • Dream potentiation
  • Increased music appreciation
  • Focus enhancement - Focus enhancement occurs at lower doses and disappears as the dose is increased and the sedative and euphoric effects take over.
  • Motivation enhancement
  • Sleepiness - In high dosages this can get to the point where the user may be drifting in and out of consciousness or even experience what is called "nodding".
  • Thought acceleration
  • Irritability

Visual effects

• The visual effects of Tapentadol are much more pronounced compared to other opioids of its class. They can be broken down into several components which progressively intensify proportional to dosage.

  Suppressions

  • Double vision
  • Visual acuity suppression

  Hallucinatory states

  • Internal hallucination - The internal hallucinations of Tapentadol can be described as much more solid than psychedelics and do not seem to be composed of visual geometry. They typically manifest themselves through hypnagogic scenarios. They are noticeable at most doses and can cause difficulty sleeping. They can be described variations as lucid in believability, fixed in style, autonomous in controllability, and equal in new experiences and memory replays in content.

Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

• Experience: 100 mg Tapentadol (Oral) - A Fun Time

Additional experience reports can be found here:

• Erowid Experience Vaults: Tapentadol

Toxicity and harm potential

Tapentadol 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. Tapentadol is known to lower the seizure threshold. It should not be taken during benzodiazepine withdrawals as this can potentially cause seizures.

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 tapentadol 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 tapentadol 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). Tapentadol presents cross-tolerance with all other opioids, meaning that after the consumption of tapentadol 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. 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. 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.
• 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

Legal status

This legality section is a stub. As such, it may contain incomplete or wrong information. You can help by expanding it.

• Australia: Tapentadol is a Schedule 8 substance, the highest schedule behind illegal substances. It can only be accessed through a request & prescription.

• Germany: Tapentadol is a controlled substance under Anlage III of the BtMG. It can only be prescribed on a narcotic prescription form.
• Switzerland: Tapentadol is a controlled substance specifically named under Verzeichnis A. Medicinal use is permitted.
• United Kingdom: Tapentadol is a Class A, Schedule 2 drug in the United Kingdom.
• United States: Tapentadol is a Schedule II Controlled Substance.

See also

• Responsible use
• Opioid
• Tramadol
• Fentanyl
• O-Desmethyltramadol

External links

• Tapentadol (Wikipedia)
• Tapentadol (Isomer Design)
• Tapentadol (DrugBank)
• Tapentadol (Drugs.com)
• Tapentadol (Drugs-Forum)