Tramadol Addiction Explained
What Is Tramadol?
Tramadol is a completely synthetic drug classified as an opioid analgesic. It does not occur in nature, and the drug was not derived from a natural substance. German scientists who specialized in pain-relieving medications created tramadol in 1962, calling it Tramal. (1, 2)
The drug, now known as tramadol, underwent 15 years of testing before it was approved for sale. It was approved for use in the United States and United Kingdom in the mid-1990s. Tramadol is not just an opioid. It is also a serotonin-norepinephrine reuptake inhibitor, or SNRI. SNRI properties are usually associated with antidepressants. (1)
Tramadol was once considered safer and less prone to abuse than other opioids, but now the risks of tramadol itself are concerning. Tramadol shares characteristics of both antidepressants and opioids. (3)
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Available forms of Tramadol
The most common forms of tramadol are tablets and capsules in instant-release, sustained-release or extended-release formulations. The dosage ranges from 50 to 300 milligrams. Tramadol suppositories of varying doses are available but rarely used. Tramadol is also available as a 50 milligram per 1 millilitre injection or intravenous solution. (4)
Instant-release tramadol is also formulated as drops, soluble effervescent tablets and sublingual tablets. Tramadol drops are mixed into a full glass of water to drink. Soluble tablets are dissolved in 50 millilitres of water.
Sublingual tablets are placed under the tongue to dissolve, although some people prefer to place the tablets against the inner cheek instead. Tramadol in sublingual formulations is absorbed through mucous membranes in the mouth. (4)
Medical Uses of Tramadol
Tramadol is used to treat moderate to severe pain after non-opioid pain relief medications have not been effective. It is usually taken by mouth every four to six hours or as needed to relieve pain. Tramadol can be taken with or without food, but taking it with food may avoid an upset stomach. (3, 4)
The initial dose of tramadol is small and gradually increased to find the minimum dosage necessary to relieve pain and avoid unnecessary side effects. Instant-release tramadol formulations are used to treat acute pain. They are also used in conjunction with a long-acting pain reliever to treat breakthrough pain. (3)
Extended- or sustained-release tramadol can be taken routinely to manage chronic or long-term pain around the clock. The maximum total amount of tramadol in a day should not exceed 400 milligrams of instant-release formulations or 300 milligrams of extended-release formulations. (4)
Tramadol is not advised for use during pregnancy or while breastfeeding. There is not enough research on tramadol during pregnancy to declare it safe. Tramadol should also be avoided in children unless it is given under specialist supervision. Numerous adverse effects of tramadol in children have been reported. (4)
Tramadol Legal Status (UK)
Tramadol become a schedule 3 controlled drug in the United Kingdom in 2014, although it is exempt from safe custody regulations. Tramadol falls under the Controlled Drug prescription rules. Tramadol prescriptions are only valid for 28 days, and the prescription must be signed by the prescriber. (5)
The maximum amount of tramadol prescribed for each patient cannot exceed a 30-day supply. The total quantity of tramadol has to be written in words and numerals on the prescription, along with a clearly defined dose. Tramadol is not part of the NHS repeat dispensing scheme because schedule 2 and 3 controlled drugs are not eligible for the arrangement. (5)
Routes of Tramadol Administration
Tramadol is taken by mouth far more often than any other route of administration. Instant-release tablets can be crushed or dissolved to administer through a G-tube or create a suppository, but sustained- or extended-relief tablets should not be crushed or altered in any way. (4)
Tramadol can be given in solution as an intramuscular injection or a slow intravenous infusion when analgesia is needed quickly. Intravenous tramadol infusion usually takes place in a hospital after surgery, although sometimes it is given to patients before outpatient surgical procedures. (8)
The Pharmacology of Tramadol
Tramadol increases the levels of serotonin in the brain. Serotonin is a neurotransmitter that helps cells in the brain and central nervous system communicate. The analgesic and mood-lifting effects of tramadol come from a combination of the interaction with opioid receptors and the serotonergic effects. (6, 7)
Tramadol has almost 100% bioavailability when taken orally. Bioavailability refers to the percentage of a drug that makes it to the site of action and how much time was necessary to do so. Almost 100% of oral doses of tramadol hydrochloride reach the brain.
This is another characteristic that makes tramadol unique. Most medications have a higher bioavailability through intravenous injection than oral administration; tramadol is at peak bioavailability when taken orally. (6, 7)
Tramadol can have significantly different effects between individuals. This phenomenon is at least partly due to the cytochrome (CYP) P450 enzyme. The enzyme is controlled by the CYP2D6 gene. People with one type of CYP2D6 gene are CYP2D6 poor metabolisers, or PMs. People with a different type of CYP2D6 gene are ultra-rapid metabolisers, or UMs. (6)
Chemical formula – C16H25NO2
Tramadol’s chemical formula is C16H25NO2, and its PubChem CID number is 33741. Other chemical names for tramadol include tramadol hydrochloride, (+)-tramadol, ()-cis-(2-dimethylaminomethyl)-1-(3-methoxyphenyl)-cyclohexanol and 27203-92-5. Tramadol is a synthetic analogue of codeine, which means the two drugs have a similar chemical structure and some similar effects. (6)
Tramadol Brand and Street Names
Tramadol is sold under the brand names Ultram, Ultram ER, Ultracet, ConZip, Ryzolt and Rybix orally dissolving tablet, or ODT. (D) Other brand names include Invodol, Larapam, Mabron, Maneo, Marol, Maxitram, Oldaram, Tilodol, Tradorec, Tramquel, Tramulief, Zamadol, Zeridame and Zydol. (4)
Tramadol’s street names include trammies, chill pills, tramal lite and ultras. It does not have many street names because it is relatively new compared to many other commonly used recreational drugs. Tramadol is a popular street drug in Cameroon, where pills are called tomatoes because of their packaging. Street names in the Gabonese Republic in Africa include kobolo, pink baby and kemeka. (7)
Tramadol Addiction and How It Develops
Tramadol addiction is not the same thing as dependence on tramadol. Dependence on an opioid develops when the drug is taken for more than a short time. The time necessary to become dependent on the drug varies between individuals. Tramadol addiction develops when the user starts taking tramadol for reasons other than controlling pain.
It is not always easy for people to admit, even to themselves, that they are taking a drug for anything but the intended purpose. Addiction can happen to anyone. An injury or illness that requires pain medication may become the start of an addiction, but it usually is not. Despite the surging numbers of substance users addicted to tramadol and other opioids, most people with a one-time prescription for opioid pain relievers do not become addicted. (12)
Why is tramadol addictive?
Tramadol was considered a very low-risk medication in terms of addiction and abuse, but misuse of the drug is increasing. It is an atypical opioid analgesic with mild effects compared to other opiates and opioids. The opioid-like effects of tramadol are only evident when it is taken orally. IV infusion of tramadol does not produce any effects similar to opioids. This may explain why tramadol has never been a problem as an IV street drug. (7, 9)
As a serotonin reuptake inhibitor, tramadol has a similar mechanism of action to many antidepressants. The antidepressant effects may contribute to tramadol’s addictive properties, but physical dependence on antidepressants does not develop quickly. (7)
Who becomes addicted to tramadol?
Most cases of tramadol addiction have occurred in people who were already dependent opioid users. Tramadol can suppress opioid withdrawal symptoms to a limited extent. Although tramadol is similar to an opioid in many ways, it is not strong enough to completely suppress withdrawal symptoms in people who were using stronger opioids like oxycodone, morphine or heroin. (7, 10)
Cases of tramadol dependence are rising in people without prior substance abuse history, but most people using tramadol recreationally in the United Kingdom are poly-substance users. This means they do not limit themselves to any particular drug of choice and use several different substances. (7)
Causes & risk factors of tramadol addiction
The risk of addiction is always a concern for anyone taking an opioid. People can become addicted taking opioid medications exactly as prescribed, but certain behaviours raise the risk significantly. Choosing to take ‘just one extra’ is a warning sign. Taking more than the prescribed dose one time is not a full-fledged path to addiction, but it is something to be very cautious of.
Tramadol is only prescribed for 28 days at a time.
Unfortunately, addiction can leave people with a nearly empty medication bottle or package six or seven days before the prescription is filled again. The first time that happens should set off alarm bells. It is a sign that an extra pill was taken several times instead of just once. (9, 10)
Looking forward to tramadol to make the workday more pleasant or to calm down after an upsetting event is a warning sign that addiction is a concern. People very rarely take any drug with the thought of becoming addicted. A personal tragedy or catastrophic life event does drive a few people to become addicted to something on purpose, but that is very rare. Addiction is usually an accident, and people often know they are addicted long before admitting it. Genetics is a significant risk factor too. (10, 14)
Co-Occurring Disorders with Tramadol Addiction
Having a mental health disorder along with a substance use disorder is called dual diagnosis. Common mental health disorders co-occurring with tramadol addiction include schizophrenia, delusional disorders, bipolar disorder and depression. The Public Health and Social Care Centre estimates that 20-37% of people using mental health services and 6-15% of people in substance abuse treatment have a dual diagnosis. The numbers could be higher because secondary disorders often go unnoticed. (15)
People with dual diagnosis need treatment for both the mental health disorder and the substance abuse disorder. The National Collaborating Centre for Mental Health (NCCMH) is evaluating care models and service availability for mental health and substance abuse treatment. Individuals with dual diagnosis are at risk of poor health and social outcomes and can be a very vulnerable population overall. (15)
Substance abuse treatment providers can recognize mental health disorders, and mental health providers outside of substance abuse services can also recognize addiction. Unfortunately, co-occurring disorders may not be diagnosed immediately because symptoms overlap.
The NCCMH recommends combining mental health services when it is possible to do so. People struggling with addiction or other mental health disorders are more likely to comply with treatment if services are all in one place. Providing treatment for one person from multiple locations or facilities adds unnecessary complications. (15)
The Effects of Tramadol Abuse
Short-term effects of tramadol on the body
Tramadol causes a wide range of short-term physical effects. An allergic reaction is possible, but more common adverse effects include a slow heart rate, hypoactivity and low blood pressure. The effects can also be a rapid heartbeat, hyperactivity and high blood pressure. People can have very different reactions depending on how their bodies metabolize tramadol and interactions with other medications. (1, 8)
Nervousness, anxiety and tremors are also short-term effects, and some people with asthma feel symptoms worsen shortly after using tramadol. Tramadol may trigger hypoglycaemia, or low blood sugar. Serious but very rare short-term effects of tramadol use include hepatitis, liver failure, pulmonary oedema, seizures, Stevens-Johnson syndrome and suicidal tendencies. (1, 8)
Long-term effects of prolonged tramadol use
The probability of developing physical or psychological dependence on tramadol rises the longer the drug is used. Movement disorders such as dyskinesia and dystonia have been linked to tramadol, but there is no proven connection showing that tramadol caused the movement disorders. (11)
Tramadol is metabolized mostly through the liver, but it can be hard on kidneys too. Older people who have been taking tramadol on a long-term basis should have regular lab work to check kidney and liver function. (1, 12)
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Common Drug Combinations with Tramadol and the Inherent Dangers
Tramadol is often used with benzodiazepines or Ambien. These combinations used recreationally are dangerous because they are all CNS depressants and alter a person’s mental state. Using them together can cause respiratory depression or loss of consciousness. People can aspirate if they vomit while unconscious. Tramadol paired with alcohol is dangerous for the same reasons. (3, 12)
Recreational users also take tramadol with other opioids. A person using tramadol and another opioid together may not realize tramadol is increasing the opioid-like effects. This could lead to overdose.
Tramadol’s unique chemical structure is similar to an opioid, but it has enough differences to lower the effectiveness of the medication used to treat opioid overdoses, Narcan. Narcan, or naltrexone, usually removes 80-90% of opioid molecules from opiate receptors in the brain, but it only removes approximately 30% of tramadol and so cannot be fully relied on to reverse an overdose that involves tramadol. (6, 12)
Serotonin syndrome, or SS, occurs when two drugs that elevate serotonin levels are taken together. There is no fixed formula to determine how much a drug can elevate serotonin levels. People metabolize and react to antidepressants and other serotonergic medications in different ways. Antidepressants, including SSRIs, SNRIs, MAOIs and tricyclics, to a lesser extent, can contribute to serotonin syndrome. Hundreds of prescription, over-the-counter and herbal drugs have serotonergic effects. A medical professional should be consulted before taking any serotonergic medication with tramadol. (9, 11)
Signs and Symptoms of Tramadol Addiction
People exhibit many behavioural symptoms related to tramadol addiction, including rapid mood swings between agitation, uncontrollable excitement, irritation, happiness and depression. Other common signs of tramadol addiction are a loss of interest in activities, hobbies or socialization if tramadol is not involved. (1)
- Trying to illegally obtain a prescription for tramadol or attempting to acquire this drug via another illicit means
- Trying to borrow or steal money or goods to get tramadol
- Stealing tramadol that has been prescribed to someone else
- Declining performance at work or school
- Attempting but failing to end one’s use of tramadol
- Abusing tramadol when it is obviously risky or reckless to do so
Physical symptoms of tramadol addiction are a combination of effects caused by opioids and antidepressants. Many symptoms are related to function of the central nervous system. Symptoms are hormonal as well. Men might experience erectile dysfunction, and women might have irregular or absent menstruation. (1,9)
- Pinpoint (very small) pupils
- Changes in appetite
- Nausea or vomiting
- Seizures (without a history of epilepsy)
- Slurred speech
- Impaired coordination
- Jerky, rigid muscles
- Lack of coordination
- Slow breathing and heart rates
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Tramadol impairs cognitive function because it blocks neurotransmitters that brain and nerve cells use to send signals. Cognitive function may seem to improve when a person starts taking tramadol, but changes in the brain over time and consistent unnatural levels of neurotransmitters impair reasoning, decision-making and other cognitive functions. (1,9)
- Poor spatial ability
- Poor focus
- Poor concentration
- Impaired memory
- Impaired judgment
The psychosocial symptoms of tramadol addiction can turn hanging out with friends into a chore if there is no tramadol available. Anger and depression rooted in the addiction may cause people to lash out and push family and friends away. Loneliness, regret, guilt and maybe even anger can make it harder to repair relationships. (1, 10)
- Mood swings
- Loss of interest in significant activities
- Angry outbursts
Impact of Long-Term Tramadol Abuse on the Brain
Tramadol is one of several synthetic opioids that damage cells through oxidation. Brain cells are more vulnerable than the rest of the body because the brain always has very high oxygen levels. Long-term tramadol abuse eventually damages brain cells faster than cells can recover. (6, 13)
Long-term tramadol abuse creates pathways between brain and nerve cells that were not present or needed before drug use began. The brain and nerve cells gradually adapt to the drug. An abrupt absence of tramadol and its metabolites can impair cognitive function until the brain begins relearning pathways without the drug. (10, 13)
Tramadol elevates norepinephrine, serotonin and dopamine levels. All three neurotransmitters have powerful effects on the brain and nerve cells. The elevated levels are ‘normal’ during long-term tramadol use, but levels drop fast without tramadol to prop them up. Depression, anger and anxiety are
very common when people stop taking tramadol. The brain reacts to neurotransmitters that seem very low after years of artificial elevation. Adapting to the drug’s absence can take a few months or up to two years. (10, 13)
Tramadol Overdose Explained
A tramadol overdose is not straightforward or predictable. Overdose can occur long before the 400 milligram per day threshold is reached. A tramadol overdose may cause typical symptoms of an opioid overdose, including central nervous system depression, respiratory depression and cardiovascular collapse. (3, 9)
Tramadol overdose can cause serotonin syndrome. Symptoms of serotonin syndrome include neuromuscular hyperactivity, rapid heart rate, agitation, confusion, involuntary muscle movements, high fever and seizures. Serotonin syndrome ranges in severity from very mild to fatal. Sometimes medical treatment is not effective in the worst cases. Death or permanent damage to the brain and nervous system are possible. (9)
Tramadol Withdrawal and Detox
Withdrawal from tramadol can may include withdrawal symptoms from two drug classes.
Tramadol is an opioid agonist, so opiate withdrawal symptoms are expected, but some people experience antidepressant withdrawal symptoms too. Only a small percentage of people using tramadol long term experience antidepressant withdrawal. The reason it only affects a tiny proportion of users may be related to genetic differences that influence how the body metabolizes tramadol. (2, 13)
Detox services are extremely helpful in the first stages of recovery to help people get through the acute withdrawal stage comfortably and safely. The risk of relapse during the first stages of withdrawal is much lower with medically supervised detox treatment instead of trying it ‘cold turkey‘ at home. (7, 13)
Seeking help for tramadol withdrawal and detox is especially important because the people who do experience antidepressant withdrawals may experience severe side effects such as hallucinations or suicidal ideation. Detox offers support and help to get through potentially dangerous side effects safely. (10, 13)
Signs and symptoms of withdrawal
Stomach pain and cramping, vomiting, diarrhoea, chills and goose bumps occur two to three days after the last dose of tramadol. Other symptoms are loss of appetite, pupil dilation, problems with concentrating and thinking clearly, irritability, depression and cravings for tramadol. (3)
Withdrawal symptoms related to tramadol’s antidepressant effects are extreme anxiety, panic attacks, hallucinations, confusion, numbness, paranoia and numbness or tingling in the upper and lower limbs. Vertigo, headaches and insomnia could be symptoms of either type of withdrawal. Some people experience antidepressant withdrawal, while others are never bothered by those symptoms. (3, 12)
Tramadol detox process
Withdrawal symptoms can start as soon as a few hours or as long as a day or two after the last dose. Tramadol withdrawal lasts approximately two weeks, although some symptoms last beyond the medical detox stage. (10, 13)
Tramadol withdrawal is different for everyone, but people generally start sweating, feeling nauseous and having strong cravings in the first three days. Stronger cravings, confusion, disorientation and insomnia occur on days four through seven. Anxiety and depression usually drop to manageable levels during the eighth through fourteenth days of withdrawal. Most physical symptoms are finished within the first two weeks after the last dose of tramadol. (10, 13)
Medications given during detox include substitution medications or medication to manage symptoms. NSAIDs like ibuprofen or naproxen help headaches and body aches. Anti-nausea medication can be immensely helpful because individuals in treatment are able to move around, participate in discussions or activities and eat meals instead of lying down due to nausea or vomiting. (10, 13)
Restlessness and insomnia during withdrawal result in exhaustion and may exacerbate other withdrawal symptoms. Medications to relieve restlessness and sleep aids help people get sufficient rest instead of tossing and turning at night. The probability of staying in treatment and avoiding relapse during acute withdrawal increases with every symptom that is prevented or relieved. People seeking treatment in detox are able to work towards recovery and feel hopeful instead of dealing with withdrawal symptoms alone. (10, 13)
How to treat tramadol withdrawal
Some people experience protracted withdrawal, also known as post-acute withdrawal syndrome, or PAWS, and extended withdrawal. Protracted withdrawal occurs when withdrawal symptoms last longer than the anticipated period of time. The most common long-lasting symptoms include anxiety, depression, poor sleep, irritability, fatigue, poor concentration and emotional detachment. (1, 10)
Detoxification refers to treatments and methods for managing withdrawal. The evaluation stage of detox is when medical, psychological and social factors are evaluated to start planning the best way forward. Stabilization is the period when a person in detox is under medical supervision with psychological support. Encouraging further treatment is the third stage because detox alone is not enough to recover from addiction. Additional support, mental health services and long-term plans and goals are necessary for successful recovery. (7, 13)
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Tramadol Addiction Treatment
The first step in treating tramadol addiction is reaching out to seek help. A general practitioner can point patients in the right direction for appropriate services. People can also reach out to drug and alcohol treatment facilities or organizations themselves. The NHS has a helpline available for guidance, too. (10, 13)
Counsellors, therapists, doctors or other medical staff help patients choose a method to stop using tramadol and plan the next step after detox. Some people stop using tramadol immediately, while others benefit from tapering or substitution of methadone or suboxone. Any method is fine as long as it is comfortable for the person seeking help. (12)
Detox programs are available in many settings from inpatient hospitalization to scheduled visits at a treatment centre. The appropriate setting depends on an individual’s level of dependence, current living conditions, possible risk of violence or suicide and reliable transportation to attend detox appointments and other necessary services. (12)
Inpatient vs outpatient treatment for tramadol addiction treatment
Outpatient detox programs do not interfere with life to the extent that inpatient treatment does. Detox on an outpatient basis is much less disruptive for work, school or family life. Finances may be a concern if the program is not paid for through the NHS. Outpatient detox is less expensive than inpatient programs. (12)
Outpatient detox also lets participants start developing relationships in the community, finding support groups and working on a long-term plan to continue counselling or other types of psychological care. Outpatient care works well for people with short-term or mild levels of dependency, people without health complications or people who were using low doses of tramadol. (12)
Inpatient treatment may be a better choice for people who have misused tramadol for over a year, use multiple drugs or used tramadol at high doses. Inpatient care is also the best option for people with other mental or physical health issues that may need medical supervision during detox. Inpatient care provides constant medical assistance along with support and encouragement.
Therapy for Tramadol Addiction
Detox is only the first step in recovery from tramadol addiction.
Family therapy is useful when there is a tendency towards drug and alcohol addiction in the family or if family members do not have any experience with addiction. Trained counsellors and therapists can help with either situation. Therapy is a safe place to talk through feelings and find a supportive environment.
Continuing therapy or attending support groups helps individuals stay on track and stick to their recovery plans. Some counsellors or peer support specialists have experienced addiction themselves and decided they wanted to help others recover too. It can be very easy to talk oneself into using again ‘just once’, but a counsellor or support group can quickly point out rationalizations and the possible harm that could result from using one more time. Support groups are also quick to offer encouraging advice if a relapse does occur. It’s easier to stick to recovery and manage cravings with supportive people than trying to manage alone.
- Cognitive behavioural therapy (CBT)
- Biofeedback therapy
- Group therapy
- One-on-one counselling
- Holistic therapy
- Motivational enhancement therapy (MET)
- Dialectical behaviour therapy (DBT)
- 12-step programmes
- Family and social therapy
- Peer support group participation
- Experiential therapy to manage mental conditions that contribute to addiction
Tramadol addiction medications
The symptoms of tramadol withdrawal are not life-threatening in most cases, but self-destructive thoughts or behaviour can occur as a result of those symptoms. Relapse is also a significant concern during acute withdrawal. Medications help people get through the acute stage and may be beneficial after detox as well.
Methadone is a full opioid agonist that is often used to help people recovering from an opioid addiction. Methadone helps clients resist cravings and prevents withdrawal, but the feeling of euphoria caused by most opioids is very mild with methadone. Some people never notice a high from methadone at all, and others notice a euphoric feeling only in the first few weeks of treatment. There is some evidence that methadone eases antidepressant withdrawals as well as opioid withdrawal symptoms, but further research is needed to confirm this. (14)
Buprenorphine is a partial opioid agonist. It is an ingredient in Suboxone and Subutex. Buprenorphine interacts with the same opioid receptors in the brain that opioid medications interact with, but buprenorphine binds to the receptors so strongly it blocks other opioid molecules. Buprenorphine does not cause the euphoria or high that comes from full opioid agonists, and it helps clients resist cravings. (15)
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- (2) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268194/
- (3) https://journals.lww.com/anesthesia-analgesia/Fulltext/2017/01000/Trends_in_Tramadol___Pharmacology,_Metabolism,_and.10.aspx
- (4) https://www.nhs.uk/medicines/tramadol/
- (6) https://pubchem.ncbi.nlm.nih.gov/compound/Tramadol
- (7) https://www.who.int/medicines/access/controlled-substances/Tramadol.pdf?ua=1
- (8) https://www.medicines.org.uk/emc/product/3420/smpc
- (9) https://www.ebmconsult.com/articles/tramadol-interaction-ssri-serotonin-syndrome-mechanism
- (10) https://www.medsafe.govt.nz/profs/PUArticles/TramSerious.htm
- (11) https://www.livescience.com/41174-tramadol.html
- (12) https://www.nice.org.uk/guidance/cg52/evidence/drug-misuse-opioid-detoxification-full-guideline-196515037
- (13) https://www.webmd.com/drugs/2/drug-64748/buprenorphine-sublingual/details
- (14) https://www.drugs.com/methadone.html
- (15) https://www.nice.org.uk/guidance/ng58/documents/evidence-review
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