CBD Oil And Tramadol


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Can CBD interact with tramadol, an opioid analgesic? Learn more about the mechanism and type of interaction between CBD and tramadol below. A prospective cohort study stated that CBD could lessen opioid use and improve chronic pain & sleep quality among patients who use opioids to manage pain.

Does CBD Interact With Tramadol (Ultram)?

Information on risks & possible interactions between CBD & tramadol.

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One of the most common uses of CBD is for managing chronic pain. Currently, the most common prescription painkillers are opioid drugs such as tramadol (Ultram).

Is it safe to take CBD with tramadol? What are the potential risks of taking both together?

Table of Contents

Does CBD Interact With Tramadol (Ultram)?

CBD and tramadol (Ultram) may interact in three different ways — each one has the potential to cause side effects.

Be very cautious when taking CBD with tramadol, and always speak to your doctor before taking both at the same time.

Separating the dose of CBD and tramadol 2 hours apart may reduce the chances of side effects.

1. Agonistic Interaction

Tramadol and opioid analgesics cross the blood-brain barrier to produce their benefits. To cross the blood-brain barrier, drugs like tramadol require the help of P-glycoprotein, which is inhibited by CBD, hence reducing the clearance of the drug from the brain.

CBD also inhibits the enzymes required for metabolism and, consequentially, excretion of tramadol from the body resulting in prolonged presence of the drug in the system.

This increases the time the drug spends in the system, allowing it to have prolonged effects, resulting in an agonistic interaction between CBD and tramadol.

2. Antagonistic Interaction

CBD, in high doses, is known to inhibit the analgesic activities of tramadol or reduce them, making the drug inefficient. The exact mechanism for CBD’s action is not yet known, but it is referred to as an antagonistic interaction between CBD and tramadol.

3. Metabolic Inhibition

Tramadol (Ultram) and CBD require enzymes for their metabolism; they share some of these enzymes, creating competition between the agents. This is referred to as metabolic competition and is one type of interaction between CBD and tramadol.

Other Names for Tramadol

Tramadol is sold under many different names. All share the same risk and potential interactions.

Other names for tramadol include:

Similar Medications: CBD & Opiates

Tramadol (Ultram) is classified as an opiate medication. CBD and opiates all share similar risks for interaction and side effects.

Here’s a list of similar medications that share a similar level of risk when combined with CBD:

  • Buprenorphine (Cizdol & Brixadi)
  • Codeine
  • Pethidine (Meperidine & Demerol)
  • Fentanyl (Abstral & Actiq)
  • Hydrocodone (Hysingla ER, Zohydro ER & Hycodan)
  • Hydromorphone (Dilaudid)
  • Methadone (Methadose & Dolophine)
  • Morphine (Kadian & Roxanol)
  • Oxycodone (Percodan, Endodan, Roxiprin, Percocet, Endocet, Roxicet & OxyContin)

Is It Safe to Take CBD & Tramadol (Ultram) Together?

CBD interacts with tramadol (Ultram), producing significant clinical symptoms mainly in respiratory depression and coma, which can be fatal if not appropriately treated and managed. Moreover, CBD in high doses inhibits the analgesic effects of tramadol, hence reducing the positive effects of the drug while increasing the negative effects.

Given the risk of severe side-effects along with CBD’s ability to decrease the effects of tramadol, it is not recommended to take CBD and tramadol together.

Is CBD a Viable Alternative to Tramadol (Ultram)?

CBD initially gained traction for its analgesic and anti-inflammatory properties, which help alleviate different types of pain in patients [1]. Tramadol (Ultram) and CBD are potent pain-relieving agents; however, the former tends to cause dependence and addiction and requires a prescription. On the other hand, CBD can be used freely without any risk of addiction or habit formation.

Moreover, tramadol and other opioid analgesics have a higher risk of patient overdoses than CBD or even average pain killers. As CBD decreases the risk of fatal overdoses and provides similar benefits as opioid analgesics, it may be a viable alternative for these medications, including tramadol [2].

While anecdotal evidence points to the benefits of CBD over tramadol, further scientific research and evidence are required for CBD to become the standard medical analgesic, replacing opioid analgesics like tramadol.

What Is Tramadol (Ultram)?

Tramadol is an opioid analgesic commonly sold under the brand name Ultram and used to manage moderate to severe pain, bringing relief within an hour of oral ingestion of the pill. Tramadol is commonly prescribed for pain, over other opioid analgesics, because of its reduced ability to produce side effects such as dependence and addiction. Tramadol is addictive, however, and special care should be taken when prescribing this medication to high-risk populations.

Tramadol is metabolized in the liver into desmetramadol, an opioid with a higher affinity for opioid receptors. It helps treat pain disorders such as fibromyalgia and trigeminal neuralgia. The FDA has not approved the use of this medication in treating these pain disorders but rather only for the treatment of acute and chronic pain. The FDA has approved the use of tramadol IV for the management of pain, while the National Health Service (NHS) has approved tramadol as a secondary drug for the treatment of pain disorders.

Tramadol is sold under different brand names such as Ultram, Zytram, Qdolo, Ryzolt, and ConZip, with Ultram being the most readily available and commonly used brand.

The drug becomes effective within an hour of ingesting, but it takes around 2 hours to 4 hours for the medication levels to peak in the body. It belongs to two different classes of medications, namely, opioid analgesics and Serotonin Norepinephrine Reuptake Inhibitors (SNRI), with the former being the more commonly known class.

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Compared to other opioid painkillers such as morphine and codeine, tramadol is not that effective, but it is still used because it’s less addictive.

Tramadol is metabolized in the liver using demethylation and glucuronidation via the enzymes CYP2D6 and CYP3A4. Its elimination half-life and duration of action is approximately 6 hours, with most of the drug excreted in the urine.

Tramadol interacts with CBD, another potent analgesic agent, to produce majorly significant clinical symptoms and side effects that have the potential to be fatal without appropriate medical attention. CBD has both an agonistic and antagonistic effect on tramadol, depending on its dosage.

Tramadol Specs:

Drug Name Tramadol
Trade Name Ultram, Zytram, Qdolo, Ryzolt, ConZip
Classification Opioid Analgesic
CYP Metabolism Liver (CYP2D6 and CYP3A4)
Interaction with CBD Antagonistic (Decreased effects) of high dose Tramadol Agonistic (Increased Effects)
Risk of Interaction Major

How Does Tramadol (Ultram) Work?

Tramadol (Ultram) is an opioid agonist that targets the noradrenergic system, serotonergic system, and opioid system.

Tramadol affects the following receptors and processes in the body to produce its analgesic effects:

  1. Mu Opioid Receptor or MOR, as an agonist, followed by other opioid receptors such as DOR and KOR. Tramadol has the highest affinity for MOR amongst the three opioid receptors in the body.
  2. Serotonin and norepinephrine reuptake from the synapses as tramadol is an active inhibitor of these reuptakes, hence belonging to the SNRI class of antidepressants.
  3. M1 and M3 muscarinic receptors in the body, as an antagonist.
  4. Serotonin 2C receptor, as an antagonist.
  5. Alpha 7 nicotinic acetylcholine receptor, also as an antagonist.

The main benefit of tramadol is pain management, and it does so by binding to the MOR using its active metabolite, desmetramadol. This metabolite is formed as a result of the metabolism of the drug in the liver.

Side Effects of Tramadol (Ultram)

Tramadol (Ultram) is an opioid analgesic with a few common side effects associated with its use, such as:

  • Abdominal Pain
  • Anxiety
  • Constipation
  • Dizziness
  • Drowsiness
  • Dry mouth
  • Flatulence
  • Headache
  • Irritation and Agitation
  • Itching
  • Menopausal symptoms
  • Nausea
  • Rash
  • Sleep Disorders
  • Urinary frequency
  • Urinary retention
  • Vertigo
  • Visual disturbance
  • Vomiting
  • Weight loss

Tramadol also has some rare side effects associated with its use that are also higher in severity:

  • Bradycardia
  • Dyspnoea
  • Epileptiform convulsions
  • Gastrointestinal bleeding
  • Hallucinations
  • Heart Attack
  • Hepatitis
  • Hypertension
  • Kidney damage presenting with Proteinuria
  • Liver failure
  • Migraine
  • Pulmonary edema
  • Pulmonary embolism
  • Respiratory depression
  • Stevens-Johnson syndrome
  • Tinnitus

Tramadol can also produce dependence and addiction, two of the most severe and common side effects of the medication. It is essential to take this medication only when prescribed by a medical professional and follow precautions carefully. The side effects mentioned above can increase in intensity and severity if tramadol is taken with CBD, a potent pain-relieving cannabinoid.

Types of Drug Interactions With CBD

CBD has gained traction recently and has been made widely available for its several benefits. However, it can interact with other medications and drugs, resulting in severe side effects and complications.

The interactions between the drugs and CBD can be of low clinical significance, moderate clinical significance, or major clinical significance. In case of low interactions, CBD can be used alongside the drug, whereas for moderate interactions, the use of CBD with the drug should be avoided unless medically necessary. If CBD has significant interaction with a drug, then the two agents should not be taken together.

Based on the effect of CBD on the medication and its properties, drug interactions with CBD are classified as:

1. Agonistic Interaction

CBD increases the effects or the time the medications spend in the system by inhibiting the clearance of the drug or working synergistically with the drug. Although the net effect is increased effects of the medication, it does not produce positive results but rather unfavorable results.

2. Antagonistic Interaction

CBD inhibits the activity of the drug or hastens the clearance of the drug, decreasing the overall positive effect of the medication, hence, producing an antagonistic interaction.

3. Metabolic Inhibition

CBD competes for the drug for the enzymes that both agents need for their own metabolism.

Key Takeaways: Is CBD Safe to Take With Tramadol (Ultram)?

Tramadol (Ultram) is an opioid analgesic with a weak inhibitory effect on serotonin reuptake and norepinephrine reuptake. It has one-tenth of morphine’s analgesic properties and is often used as a secondary treatment for pain disorders or as a primary treatment of acute and chronic pain.

It is widely used because it’s less likely to produce dependence and addiction. CBD also has potent analgesic properties. However, it’s not recommended for them to be used together as CBD, in high doses, inhibits the action of tramadol and the enzymes necessary for metabolism and clearance of the drug, resulting in prolonged effects of tramadol on the system.

Prolonged effects increase the risk and severity of the several side effects of tramadol, most important of which are respiratory depression and coma.

CBD and Tramadol – August 2022

Does CBD Oil interact with Tramadol & other analgesics?

  • CBD oil lessens Tramadol’s high dosage analgesic effects (1 ) .
  • A National Institutes of Health research showed that using CBD in high doses with Tramadol may considerably lessen Tramadol’s analgesic effectiveness. It does not state CBD’s effect with low doses of Tramadol (2 ) .
  • A prospective cohort study stated that CBD could significantly lessen opioid use and improve chronic pain and sleep quality among patients who use opioids to manage pain (3 ) .
  • However, a study made by The American Society for Pharmacology and Experimental Therapeutics concludes that using CBD may inhibit the liver enzyme CYP2DC responsible for metabolizing Tramadol in the body (4 ) .
  • With not enough studies regarding specific drug dosage interaction between CBD oil and Tramadol, it is still best to consult a physician before use.
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Can CBD Oil Be Taken with Tramadol?

Tramadol has been used as a pain reliever for years. However, because of its potential for abuse, it may not be for everyone. Veterinarians also use Tramadol for dogs in pain.

CBD and tramadol may be useful pain relievers. However, using them in combination brings about adverse effects and is, therefore, not recommended.

Many drug interaction reports between CBD oil and Tramadol do not state specific dosage interaction, except for the National Institutes of Health research which stated that CBD oil could lessen the analgesic efficacy of high dosage Tramadol (5 ) .

Tramadol is an analgesic that modulates moderate to severe pain by traveling within the central nervous system through metabolite binding to specific opioid receptors (6 ) .

The primary mu-opioid receptors (muORs) mediate the analgesic effects of opioids (7 ) .

A prospective cohort study stated that the use of full-spectrum cannabidiol, which has psychoactive effects, could significantly lessen opioid use and improve chronic pain and sleep quality among patients who use opioids to manage pain (8 ) .

However, a study made by The American Society for Pharmacology and Experimental Therapeutics concluded that the use of CBD might inhibit the liver enzyme CYP2DC responsible for metabolizing Tramadol and other opioids, such as codeine which is commonly used as an alternative to Tramadol when pain is mild to moderate, in the body (9 ) . By inhibiting the drugs’ metabolisms, there would be higher levels of both tramadol and codeine in the system and so the analgesic effect of CBD could be from that mechanism alone, rather than from the direct effects of CBD.

Can another analgesic be a substitute for Tramadol so that CBD Oil can be taken?

There is no established alternative to Tramadol so that CBD oil can be taken.

Tramadol relieves acute and chronic pain with moderate to severe intensity. It is used in the pain management of osteoarthritis, acute myocardial infarction, acute myocardial infarction, and Brugada syndrome (10 ) .

It is also used for dental, post-operative, chronic cancer, back pain, and acute renal pain relief (11 ) .

However, Tramadol can cause common side effects like headaches, constipation, and dry mouth (12 ) .

The more severe side effects are breathing difficulty or short, shallow breathing, hallucinations, urinary difficulty, seizures, confusion, and the low blood pressure symptoms of dizziness, exhaustion, and lack of energy (13 ) .

Severe allergic reaction (anaphylaxis) also happens, but rarely (14 ) .

Other analgesics can be used as a replacement for Tramadol that have fewer side effects when compared to Tramadol.

A 2005 experimental study in rats concluded that metoclopramide is a viable low-cost alternative to Tramadol in treating post-operative pain because it offers fewer side effects commonly linked to Tramadol, such as nausea, tremor, and vomiting (15 ) .

Since there are no studies currently available about drug interactions between metoclopramide and CBD oil, consulting a doctor before use is highly recommended.

According to a February 2020 JAMA medical journal research, Tramadol had a higher mortality risk compared to the anti-inflammatory medications naproxen, diclofenac, and etoricoxib (16 ) .

More clinical trials are needed to confirm the research because it did not attribute the result to specific causes. Several external factors may have led to the conclusion (17 ) .

An NIH study stated that naproxen is not recommended to use with CBD products from the cannabis plant because naproxen’s CYP2C8/9 enzyme substrate interacts with CBD oil (18 ) .

The study has advised avoiding administering CBD oil with naproxen, decreasing the naproxen dose, or monitoring for adverse effects and toxicity to minimize side effects (19 ) .

It is also not recommended to take CBD oil while taking diclofenac because there are indications that CBD decreases its metabolization because CBD may inhibit the hepatic enzyme CYP2C9 (20 ) .

Take caution in using CBD products like cannabis oil with etoricoxib and corticosteroids because of possible drug interaction even if there is no published report (21 ) .

Drug interactions between ibuprofen, over-the-counter medications, and other NSAIDS with cannabinoids have not yet been demonstrated.

Can CBD replace Tramadol?

CBD can help relieve pain similarly addressed by prescribing Tramadol.

Pain associated with cancer, neuropathy, and central pain such as multiple sclerosis can be suitably managed with CBD (22 ) .

A study proves that CBD subdues inflammatory and neuropathic pain (23 ) .

CBD’s anti-inflammatory properties are expounded in the Journal of Pharmacology and Experimental Allergic Contact Dermatitis (24 ) .

CBD may also relieve muscle weakness, which is a significant symptom of neuropathy (25 ) .

CBD can also be used to manage pain that does not respond well to other treatments like optimized opioid therapy in conditions such as intractable cancer pain and chronic musculoskeletal pain (26 ) .

The University of Michigan Health Lab published an article declaring that the benefits of opioids like Tramadol and cannabinoids are similar, but that opioids are not as useful for chronic pain even though physicians prefer to use opioids over the use of cannabis, primarily due to its Schedule 1 status. (27 )

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Opioids are more useful for pain associated with peripheral damage or inflammation resulting in nerve pain. Symptoms of this condition include (28 ) :

  • numbness, prickling, and tingling in hands and feet
  • sharp, burning, or throbbing pain
  • touch sensitivity
  • muscle weakness
  • paralysis (rare)

The endocannabinoid system plays an important role in the central nervous system.

Cannabinoids are preferred for neuropathic and centralized pain conditions like fibromyalgia (29 ) .

Other conditions with neuropathic and centralized pain conditions are allodynia, where the pain is experienced with ordinary touch, chronic pain syndrome, and neurological injuries such as stroke and spinal cord injury (30 ) .

Although their benefits are comparable, the article expressed that both opioids and cannabinoids should not be used as primary therapies for chronic pain because the benefits are minimal (31 ) .

The article suggested that physicians are reluctant to prescribe cannabis because the appropriate formulation and dose has not been determined (32 ) .

It also advised pharmaceutical companies to stop marketing opioids for a broad range of conditions until studies confirm opioids’ extensive scope of efficacy (33 ) .

Tramadol vs. CBD

Tramadol was not yet classified as an opiate in 1995. However, the FDA identified Tramadol as a controlled substance in 2014 due to widespread abuse and addiction to it. It is Schedule IV, lower risk of abuse than OxyContin, a Schedule II drug (34 ) .

Contrary to Tramadol and some similar prescription medications, CBD is non-addictive according to a 2015 research conducted by Nora Volkow (35 ) .

However, Wayne Hall of the Society for the Study of Addiction stated in 2018 that it was premature to expand access to medical cannabis to solve the U.S. opioid crisis of addiction (e.g., to Xanax) and overdose (36 ) .

What To Look for in a CBD Oil When You Are Taking Tramadol

Obtain medical advice before taking CBD products in the form of oils or tinctures.

It is best to follow these steps before purchasing:

  1. Although CBD products with hemp oil are legal in the U.S. federal system, verify the laws regarding the sale, possession, and use of CBD products in the state of purchase.
  2. Read online reviews before buying in the website store. Confirm whether the clinics and brick-and-mortar and stores you buy from are authorized to sell CBD products. Buy only from reliable and legitimate brands.
  3. Select pure CBD oils falling under the crystalline isolate category over full-spectrum oils that retain tetrahydrocannabinol (THC) and other cannabinoids that cause a high sensation.
  4. Check for additional ingredients. MCT oils and melatonin are safe and beneficial. Beware of high-risk ingredients like vegetable glycerin and propylene.
  5. Determine appropriate dosing by corresponding the dose for the condition it is used for.

Trust the advice of an experienced medical professional specializing in CBD from hemp plants instead of searching online in Google to avoid risks and side effects like withdrawal symptoms. Proper medical guidance is needed in corresponding use, dosage, and administration concerning a patient’s health condition and maintenance medications.

CBD can interact with other compounds that are metabolized in the body by cytochrome P450 or CYP3A4 enzymes (37 ) .

These CYP450 and CYP3A4 enzymes break down substances such as drug medications and toxins that are formed within the cells.

Since CBD competes for these enzymes, CBD products limit the metabolism of drugs, heightening the concentration levels of drugs in the bloodstream.

CBD can increase the blood levels when taken with the blood thinner Coumadin, and it can raise levels of certain other medications in your blood by the same mechanism that grapefruit juice does.

Important Facts About Tramadol

The pain medication Tramadol was discovered and synthesized in 1962 by the German company Grunenthal GmbH. It was introduced in the market under the name Tramadol in 1977. It became available in the U.S. after 1995 (38 ) .

Tramadol has severe drug interactions with alvimopan, procarbazine, rasagiline, and selegiline. It has severe interactions with approximately 49 drugs and moderate interactions with around 269 drugs (39 ) .

Mild drug interactions with Tramadol include the following (40 ) :

  • marijuana
  • sage
  • asenapine
  • brimonidine
  • darifenacin
  • eucalyptus
  • naloxone
  • nilotinib
  • dextroamphetamine
  • maraviroc
  • ziconotide
  • paroxetine
  • lidocaine

As a prescription drug, oral doses of Tramadol come in tablets, reconstituted suspension, and extended-release capsules (41 ) .

Veterinarians are in consensus that Tramadol is the most common painkiller for dogs because of the minimal risk of side effects and addiction (42 ) .


CBD could significantly lessen opioid use and improve chronic pain and sleep quality among patients who use opioids such as oxycodone to manage pain.

Using CBD with high doses of Tramadol can lessen its analgesic effects. The effect when Taking Tramadol in lower doses is unknown.

Using CBD with Tramadol may slow the drug’s metabolism in the body and increase the high levels of Tramadol in the bloodstream, which appears to contradict the statement above. If the metabolism of tramadol is slower, then higher levels of tramadol (in the face of CBD) would mean a higher analgesic effect. Thus, the end result is that we do not have all the answers, yet.

It is, therefore, best to seek medical advice before using CBD oil when taking Tramadol.

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