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Tramadol

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Also known as

Ultram, ultracet, ralivia, conzip, ryzolt, trammies, chill pills and ultras

Classification

Psychoactive substance, depressants

Overview

Tramadol, like other opiates, stimulates brain opioid receptors but it also increases brain serotonin levels. It is a medicine used to treat moderate to severe pain. It is only available with a prescription from your doctor. Other opiates include codeine, methadone and heroin.

Although tramadol is not as strong as heroin, it shares many of the same effects and both are addictive [1].

Tramadol can -

  • produce feelings of warmth and well-being, relaxation and sleepiness.
  • cause fatigue, drowsiness, loss of appetite, nausea and retching, diarrhoea, and dizziness or fainting.
  • worsen side-effects and risks when used with certain antidepressants that tend to increase serotonin levels [1].

What does it look like?

Tramadol is usually available as white pills, tablets or coloured capsules, although liquid forms are produced [1].

Source

This is a pharmaceutical drug which is sometimes diverted from manufacturers, pharmacies or GP's prescriptions [2].

Street price

'Street' tramadol costs between £1 - £2.50 per pill/tablet/capsule [1].

Sought after effects

  • relaxation,
  • sleepiness,
  • pain relief,
  • mild euphoria,
  • warmth,
  • well-being [2].

Undesired effects

  • dizziness,
  • nausea,
  • constipation,
  • dry mouth,
  • headaches,
  • sleepiness,
  • sweating,
  • tiredness,
  • vomiting [2].

What are the different forms?

Tramadol is normally swallowed, but some people crush up the tablets and snort them [1].

How long do its effects last?

Onset of effects

  • oral - 15 - 60 minutes [3], 1 - 2 hours [4].

Peak

  • oral - 2 - 6 hours [3], 3 - 4 hours [4].

Offset

  • oral - 2 - 4 hours [3].

Duration of effects

  • oral - 6 - 10 hours [3], 5 - 7 hours [4].

Pharmacology

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 [5], [6] serotonin releasing agent, [7], [8], [9], norepinephrine reuptake inhibitor, [10] NMDA receptor antagonist, [11] 5-HT2C receptor antagonist, [12] (α7)5 nicotinic acetylcholine receptor antagonist, TRPV1 receptor agonist, [13] and M1 and M3 muscarinic acetylcholine receptor antagonist [14], [15].

The euphoric effects of this compound stem from the way in which opioids bind to and activate 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 [3].

Bioavailability

  • Oral - 68% - 72%,
  • Rectal - 77% [3].

Toxicity

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 [3].

Mode of use

Tablets and capsules are swallowed orally [2].

Signs of usage

  • pinpoint pupils,
  • changes in appetite,
  • nausea or vomiting,
  • drowsiness,
  • seizures (without a history of epilepsy),
  • slurred speech,
  • headaches,
  • impaired coordination [16].

Another potentially dangerous symptom of tramadol abuse is serotonin syndrome, which can be life-threatening if left untreated. It occurs when too much serotonin, a chemical that relays signals in the brain, is produced or remains in the brain. Serotonin syndrome most commonly occurs in patients who take tramadol and antidepressants at the same time [16].

Effects

Tramadol is an opiate. Although it is weaker than heroin and methadone, it still causes all the typical opiate effects, alongside some effects due to increases in serotonin activity [1]. The effects include -

Feelings of warmth and well-being, relaxation and sleepiness [1].

Common effects

  • fatigue,
  • drowsiness,
  • nausea,
  • retching,
  • constipation,
  • confusion [1].

Less often effects

  • diarrhoea,
  • dizziness,
  • fainting,
  • excessive sweating,
  • itching,
  • raised blood pressure,
  • tightness in the airways,
  • muscle weakness,
  • sensory disturbances,
  • hallucinations,
  • fits,
  • blood disorders [1].

Physical effects

  • physical euphoria,
  • pupil constriction,
  • stimulation,
  • appetite suppression,
  • cough suppression
  • orgasm suppression,
  • pain relief,
  • sedation,
  • constipation,
  • difficulty urinating,
  • itchiness,
  • nausea [3].

Cognitive effects

  • cognitive euphoria,
  • compulsive redosing,
  • dream potentiation,
  • thought acceleration,
  • anxiety suppression,
  • decreased libido [3].

Positive

  • euphoria,
  • pain relief,
  • elevated mood,
  • overall feeling of contentedness [4].

Neutral

Negative

Some users may experience -

  • nausea,
  • constipation,
  • CNS depression,
  • drowsiness,
  • hot/cold flashes,
  • dizziness,
  • vomiting,
  • urinary retention [4].

High doses

In high doses, overdoses, or in patients not tolerant to opiates, tramadol can cause -

  • shallow breathing,
  • bradycardia,
  • cold-clammy skin,
  • apnoea,
  • hypotension,
  • miosis,
  • circulatory collapse,
  • respiratory arrest,
  • death [4].

Side-effects

  • nausea,
  • vomiting,
  • constipation,
  • lightheadedness or dizziness,
  • drowsiness,
  • headache,
  • loss of appetite,
  • dry mouth [17].

Overdose

  • sleepiness,
  • unconsciousness,
  • coma,
  • seizures,
  • respiratory depression,
  • abnormally low blood pressure,
  • slow heart rate,
  • sweating or clammy skin,
  • weak muscles,
  • pinpoint pupils [16],
  • irregular heart rhythm,
  • vomiting,
  • hyperthermia,
  • muscle rigidity,
  • muscle pain,
  • limp or weakened body,
  • cyanosis [18].

Side-effects of snorting tramadol

  • insomnia,
  • muscle tension,
  • headache,
  • shakiness,
  • feeling nervous or worried,
  • shifting moods/irritability,
  • sexual dysfunction,
  • problems with breathing,
  • difficulty swallowing,
  • hoarseness,
  • hallucinations,
  • dry mouth,
  • heartburn,
  • poor appetite,
  • nausea and vomiting,
  • constipation,
  • drowsiness,
  • loss of consciousness,
  • an inability to smell,
  • nosebleeds,
  • runny nose,
  • difficulty swallowing [18].

Risks

Although tramadol is not as potent as the strongest opiates like heroin, it still acts as an opiate, and also has additional risks due to its actions on serotonin levels -

  • if you have epilepsy or are taking certain antidepressants you should definitely only take tramadol with clear medical advice because of the known risks,
  • tramadol can depress breathing and may be risky in asthma and chronic obstructive pulmonary disease,
  • tramadol use has been linked with 'serotonin syndrome'. This is a potentially life threatening condition where the serotonin receptors are over stimulated, which can lead to high fever, rapid pulse, shivering, sweating, trembling, muscle twitches and agitation and confusion,
  • pregnant women should not use tramadol as it can be toxic to the developing foetus [1].

Long-term

  • tolerance,
  • physical dependence,
  • psychological dependence,
  • withdrawal symptoms,
  • increased risk of adverse effects [2].

Purity

Only tramadol tablets that were dispensed from a pharmacy directly to you are reliably pure and have the strength indicated. It is important to think quite hard about any 'medications' you take from an uncertain source [1].

Addiction

Can you get addicted

Tramadol is addictive.

Over time, using tramadol produces 'cravings' and a psychological desire to keep on using.

Tolerance can also build, so that users have to take more just to get the same effects or to avoid an unpleasant withdrawal [3].

Tolerance

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 [3].

Dangerous interactions

  • depressants (1,4-Butanediol, 2m2b, alcohol, barbiturates, benzodiazepines, GHB/GBL, methaqualone) - This combination can result in dangerous or even fatal levels of respiratory depression. These substances potentiate the muscle relaxation, sedation and amnesia caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
  • dissociatives - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
  • stimulants - It is dangerous to combine tramadol, a depressant, with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of tramadol, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of tramadol will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only taking a certain amount of tramadol.
  • psychedelics - Tramadol is well known to lower seizure threshold and psychedelics also cause occasional seizures [3].

Dangerous

  • αMT
  • Ketamine
  • MXE
  • DXM
  • PCP
  • Amphetamines - Tramadol and stimulants both increase the risk of seizures.
  • MDMA - Tramadol and stimulants both increase the risk of seizures.
  • Cocaine - Tramadol and stimulants both increase the risk of seizures.
  • Alcohol - 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.
  • GHB/GBL - The sedative effects of this combination can lead to dangerous respiratory depression.
  • Opioids - Concomitant use of tramadol increases the seizure risk in patients taking other opioids. These agents are often individually epileptogenic and may have additive effects on seizure threshold during coadministration. Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present
  • Benzodiazepines - 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.
  • MAOIs
  • SSRIs [3].

Unsafe

  • Mushrooms - Tramadol is well known to lower seizure threshold and psychedelics also cause occasional seizures.
  • LSD - Tramadol is well known to lower seizure threshold and psychedelics also cause occasional seizures.
  • DMT - Tramadol is well known to lower seizure threshold and psychedelics also cause occasional seizures.
  • Mescaline - This combination can cause seizures due to the lowering of the threshold by tramadol and the potential of mescaline to cause seziures.
  • DOx - Tramadol is well known to lower seizure threshold and psychedelics also cause occasional seizures.
  • NBOMes - Tramadol is well known to lower seizure threshold and NBOMes have also shown a tendency to cause severe seizures
  • 2C-x - Tramadol is well known to lower seizure threshold and psychedelics raise the risk of seizures.
  • 2C-T-x
  • 5-MeO-xxT [3].

Caution

  • Nitrous oxide - 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 likely [3].

Serotonin syndrome risk

Combinations in the list below may increase the amount of neurotransmitters such as serotonin and dopamine to dangerous or even fatal levels [3].

  • MAOIs such as syrian rue, banisteriopsis caapi, 2C-T-2, 2C-T-7, αMT, and some antidepressants,
  • Serotonin releasers such as MDMA, 4-FA, MDAI and αMT
  • Selective serotonin re-uptake inhibitors (SSRIs)
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)
  • 5-HTP [3].

See Serotonin syndrome for more information.

Withdrawal

Symptoms include -

  • nervous tremors,
  • anxiety,
  • yawning,
  • sweating,
  • runny nose,
  • sleep disturbance,
  • nausea,
  • diarrhoea,
  • goose-bumps,
  • restlessness,
  • abdominal cramps,
  • muscle spasms [1],
  • agitation,
  • depression,
  • cravings,
  • nausea and vomiting,
  • headaches,
  • confusion,
  • loss of appetite,
  • blurred vision,
  • insomnia,
  • mood swings,
  • irritability,
  • tingling sensations,
  • nightmares,
  • dizziness [16].

Timeline

  • days 1 - 3 - onset of general withdrawal symptoms, including feelings of pins and needles, sweating, nervousness, nausea, anxiety, palpitations, insomnia and drug cravings.
  • days 4 - 7 - drug cravings persist, along with insomnia, disorientation and confusion, and blurred vision.
  • days 8 - 14 - symptoms should be fairly mild by this point. Depression, anxiety, and irrational thoughts may persist [16].

Legality

Tramadol is a class C drug and is only available with a prescription from a doctor or other healthcare professional that is qualified to prescribe. As a class C drug, it is illegal for anyone else to supply tramadol, to have it or to give it away, even to friends [1].

What if you're caught?

If the Police arrest you in possession of tramadol unlawfully, they'll always take some action. This could be a formal caution or arrest and possible conviction.

Having tramadol that is not prescribed for you for your own use (called illegal possession) could result in up to two years in prison and/or an unlimited fine. While selling or giving tramadol away for free, even to friends (called supplying) could result in up to fourteen years in prison and/or an nlimited fine.

A conviction for a drug-related offence could have a serious impact. It could make it harder, even impossible, to visit certain Countries- for example the United States - and limit the types of jobs you can apply for [1].

Did you know?

Allowing other people to supply drugs in your house or any other premises is illegal. If the police catch people supplying illegal drugs in a club they can potentially prosecute the landlord, club owner or any person concerned in the management of the premises.

Like drinking and driving, driving when high is illegal - and you can still be unfit to drive the day after using tramadol. You can get a heavy fine, be disqualified from driving or even go to prison [1].

Mixing with other drugs

Mixing tramadol with alcohol can have serious consequences – an overdose is more likely and this can lead to a coma or respiratory failure and death [1].

Harm reduction

  • do not drive or operate machinery while under the influence of tramadol,
  • alcohol and many other drugs are extremely dangerous to combine with tramadol,
  • mainly, do not combine with benzos, other opiates, or other serotogenic drugs,
  • tramadol effects serotonin levels in the brain. For this reason it is recommended to taper on and taper off use over an extended time period [4].

Seizure Risk

We cannot stress this enough - if you have a history of seizures, we strongly urge you to stay away from tramadol as a recreational substance. By itself, it can decrease the seizure threshold. When combined with SSRIs, tricyclic antidepressants, or in patients with epilepsy, the seizure threshold is further decreased. Seizures have been reported in humans receiving excessive single oral doses (700 mg) or large intravenous doses (300 mg). However, there have been several rare cases of people having grand-mal seizures at doses as low as 100 - 400 mg orally [4].


References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 Tramadol, 2017, http://www.talktofrank.com/drug/tramadol
  2. 2.0 2.1 2.2 2.3 2.4 Tramadol, 2014, http://www.dan247.org.uk/Drug_Tramadol.asp
  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 Tramadol, 2017, https://psychonautwiki.org/wiki/Tramadol
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 Tramadol, 2017, https://wiki.tripsit.me/wiki/Tramadol
  5. Hennies, H. H. and Friderichs, E. and Schneider, J., Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids, Arzneimittel-Forschung, 1988, 38, 7, 877-880, https://www.ncbi.nlm.nih.gov/pubmed/2849950
  6. Frink, M. C. and Hennies, H. H. and Englberger, W. and Haurand, M. and Wilffert, B., Influence of tramadol on neurotransmitter systems of the rat brain, Arzneimittel-Forschung, 1996, 46, 11, 1029-1036, http://www.ncbi.nlm.nih.gov/pubmed/8955860
  7. Gobbi, M. and Moia, M. and Pirona, L. and Ceglia, I. and Reyes-Parada, M. and Scorza, C. and Mennini, T., p-Methylthioamphetamine and 1-(m-chlorophenyl)piperazine, two non-neurotoxic 5-HT releasers in vivo, differ from neurotoxic amphetamine derivatives in their mode of action at 5-HT nerve endings in vitro, Journal of Neurochemistry, 2002, 82, 6, 1435-1443, http://dx.doi.org/10.1046/j.1471-4159.2002.01073.x, http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2002.01073.x/abstract
  8. Driessen, B. and Reimann, W., Interaction of the central analgesic, tramadol, with the uptake and release of 5-hydroxytryptamine in the rat brain in vitro, British Journal of Pharmacology, 1992, 105, 1, 147-151, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1908625/
  9. Bamigbade, A. T. and Davidson, C. and Langford, R. M. and Stamford, J. A., Actions of tramadol, its enantiomers and principal metabolite, O-desmethyltramadol, on serotonin (5-HT) efflux and uptake in the rat dorsal raphe nucleus, British Journal of Anaesthesia, 1997, 79, 3, 352-356, https://doi.org/10.1093/bja/79.3.352, https://academic.oup.com/bja/article/79/3/352/386035/Actions-of-tramadol-its-enantiomers-and-principal
  10. Frink, M. C. and Hennies, H. H. and Englberger, W. and Haurand, M. and Wilffert, B., Influence of tramadol on neurotransmitter systems of the rat brain, Arzneimittel-Forschung, 1996, 46, 11, 1029-1036, https://www.ncbi.nlm.nih.gov/pubmed/8955860
  11. Hara, K. and Minami, K. and Sata, T., The Effects of Tramadol and Its Metabolite on Glycine, -Aminobutyric AcidA, and N-Methyl-d-Aspartate Receptors Expressed in Xenopus Oocytes, Anesthesia & Analgesia, 2005, 100, 5, 1400-1405, https://doi.org/10.1213/01.ANE.0000150961.24747.98, http://journals.lww.com/anesthesia-analgesia/pages/articleviewer.aspx?year=2005&issue=05000&article=00037&type=abstract
  12. Ogata, J. and Minami, K. and Uezono, Y. and Okamoto, T. and Shiraishi, M. and Shigematsu, A. and Ueta, Y., The Inhibitory Effects of Tramadol on 5-Hydroxytryptamine Type 2C Receptors Expressed in Xenopus Oocytes, Anesthesia & Analgesia, 2004, 98, 5, 1401-1406, https://doi.org/10.1213/01.ANE.0000108963.77623.A4, http://journals.lww.com/anesthesia-analgesia/pages/articleviewer.aspx?year=2004&issue=05000&article=00038&type=abstract
  13. Marincsák, R. and Tóth, B. I. and Czifra, G. and Szabó, T. and Kovács, L. and Bíró, T., The analgesic drug, tramadol, acts as an agonist of the transient receptor potential vanilloid-1, Anesthesia & Analgesia, 2008, 106, 6, 1890-1896, https://doi.org/10.1213/ane.0b013e318172fefc, https://www.ncbi.nlm.nih.gov/pubmed/18499628
  14. Shiraishi, M. and Minami, K. and Uezono, Y. and Yanagihara, N. and Shigematsu, A., Inhibition by tramadol of muscarinic receptor-induced responses in cultured adrenal medullary cells and in Xenopus laevis oocytes expressing cloned M1 receptors, Journal of Pharmacology and Experimental Therapeutics, 2001, 299, 1, 255-260, https://www.ncbi.nlm.nih.gov/pubmed/11561087
  15. Shiga, Y. and Minami, K. and Shiraishi, M. and Uezono, Y. and Murasaki, O. and Kaibara, M. and Shigematsu, A., The Inhibitory Effects of Tramadol on Muscarinic Receptor-Induced Responses in Xenopus Oocytes Expressing Cloned M3 Receptors, Anesthesia & Analgesia, 2002, 96, 5, 1269-1273, https://doi.org/10.1097/00000539-200211000-00031, http://journals.lww.com/anesthesia-analgesia/pages/articleviewer.aspx?year=2002&issue=11000&article=00031&type=abstract
  16. 16.0 16.1 16.2 16.3 16.4 Tramadol Symptoms and Warning Signs, 2017, https://www.addictioncenter.com/painkillers/tramadol/symptoms-signs/
  17. Tramadol Abuse, 2017, http://drugabuse.com/library/tramadol-abuse/
  18. 18.0 18.1 Tramadol, 2017, http://drugabuse.com/?s=tramadol