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Does CBD Interact With Pethidine (Demerol)?

CBD and pethidine (Demerol) may interfere with the body’s ability to metabolize both substances. This could lead to an increased risk of side effects over time.

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Daily CBD , last updated on January 27, 2022

Pethidine and CBD share a minimal risk of interaction when used within the recommended dosage ranges. 

However, proceed with caution and speak to your doctor before using CBD if you’ve been prescribed painkillers of any kind. 

Illustration of pethidine tablets

Pethidine or meperidine (Demerol) is an analgesic belonging to the opioid class. It’s used to treat moderate to severe pain. 

Cannabidiol (CBD) and pethidine may compete with each other for metabolism — causing their effects to last longer but also increasing the risk of side effects.

Here’s everything you need to know about using cannabinoids like CBD with meperidine or pethidine. 

Does CBD Interact With Pethidine (Demerol)?

Yes. CBD may interact with pethidine; however, serious interactions are rare. 

Even if the interaction is mild, it may be different for every person, especially on taking these drugs together for a long time. CBD can cause similar effects on the body as pethidine, such as changes in mood, sedation or drowsiness, and dizziness. 

It’s important to speak with your doctor about using CBD if you’ve been prescribed Demerol or other opiate medications. 

CBD may interact with pethidine in two ways:

A) CBD Can Slow Down Pethidine’s Metabolism (Metabolic Inhibition)

The cytochrome enzymes of the P450 family metabolize most drugs in the body. Often, the same enzymes are needed to metabolize more than one kind of drug. 

This means if you take two or more drugs that need the same enzyme for metabolism, they may end up competing against each other for the power over those enzymes. This is called metabolic inhibition, which could result in slowing down the metabolism of one or both drugs. 

Pethidine gets metabolized by the liver in two ways; First, hydrolysis is used to produce an inactive metabolite called pethidine acid. Second, pethidine acid is demethylated by the CYP2B6, CYP3A4, and CYP2C19 enzymes [1].

CBD metabolism requires similar enzymes, including both CYP2C19 and CYP3A4.

Hence, consuming CBD and pethidine together can lead to a slowdown in the metabolism of one or both drugs, leading to raised plasma levels of pethidine. 

An excess amount of pethidine in the blood means more side effects, such as dizziness, fainting, low blood pressure, etc. 

B) CBD Can Increase Pethidine’s Effects on the Body (Agonistic Interaction)

Pethidine is used in treating severe pain. Some of its effects include drowsiness, confusion, clouded consciousness, etc. 

CBD has similar abilities as a painkiller as well, and some of the effects of both compounds may overlap. When this happens, the chances of side effects will increase. 

The most commonly reported side effect of this combination is excessive sleepiness. This can be dangerous while driving, caring for young children, or working. Caution is advised. 

Similar Medications: CBD & Opioids

Pethidine is classified as an opioid analgesic. CBD and opiate analgesics all share similar risks for interaction and side effects. It is used for treating severe pain. 

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

  • Buprenorphine (Cizdol, Brixadi)
  • Codeine (Codotab)
  • 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)
  • Tramadol (Ultram, Ryzolt, ConZip)

Is It Safe to Take CBD and Pethidine (Demerol) Together?

CBD and pethidine have a low risk of interacting together. So it may be relatively safe to take them together for a short time. 

However, the long-term consumption of both drugs may cause pethidine’s over-accumulation in the body, leading to some more serious side effects. 

So take these medications only after you have consulted with your prescribing physician.

Is CBD A Viable Alternative to Pethidine (Demerol)?

CBD cannot be considered a viable alternative to pethidine.

CBD has some analgesic properties. But in cases of severe pain where medicines with extremely high pain-relieving ability are used, CBD may fall short in treating those conditions.  

A study showed that cannabis can decrease pain in patients with chronic pain. It may even help to improve their quality of life [2]. 

CBD has anti-inflammatory and antioxidant properties as well [3]. So it may be possible to use it in treating the inflammatory conditions that induce pain. 

CBD has shown to have enough potential to become a good pain reliever and has no addiction or drug-seeking side effects like opioids do. So they may be used for treating low levels of pain or as an adjunct to other pain relievers. However, it may not be as effective as stronger medications like pethidine.  

What is Pethidine (Demerol)?

Pethidine is an analgesic and sedative drug belonging to the opioid class of medications. It’s used in the treatment of severe pain in conditions such as post-surgery and during labor. Demerol is one of its most commonly used brand names. 

It’s approved for use by the FDA as a prescription-only drug. 

Pethidine (Demerol) Specs:

Drug Name Pethidine
Trade Name  Demerol, Verpat, Opigesic
Classification  Opiate analgesic
CYP Metabolism  CYP2B6, CYP3A4, & CYP2C19
Interaction With CBD  Metabolic inhibitor, Agonistic
Risk of Interaction  Mild Risk

Other Names For Pethidine (Demerol)

Pethidine is sold by a few different names. All share the same risk and potential interactions.

Other names for Pethidine include:

  • Meperidine
  • Opigesic
  • Verpat

What Does Pethidine (Demerol) Do?

Pethidine is a type of opioid agonist analgesic. It acts on the central nervous system. It’s kept into a second-line agent for the treatment of acute pain.

Opioids work by binding to specific opioid receptors of the nervous system. There are three main classes of opioid receptors called μ, κ, δ (mu, kappa, and delta). An opioid’s actions depend on the receptor that it binds to. 

Each group of opioid receptors evokes a particular set of neurological responses. These receptors can mediate both the psychoactive and the somatic effects of opioids. 

Pethidine works as an agonist on the mu receptor and kappa-opiate receptor. It has more affinity to the kappa receptor compared to morphine. 

Opioid receptors are G-protein coupled receptors that positively and negatively regulate synaptic transmission through downstream signaling. The binding of the opiate to their receptors causes the exchange of GTP guanosine triphosphate (GTP) to guanosine diphosphate (GDP) on the G-protein complex. 

The effector system is adenylate cyclase and cAMP, which is located at the inner surface of the plasma membrane. Opioids decrease intracellular cAMP by inhibiting adenylate cyclase. This causes the various actions shown by pethidine. It can also inhibit nociceptive neurotransmitters like GABA, dopamine, acetylcholine, and noradrenaline. 

Pethidine can also inhibit the release of vasopressin, somatostatin, insulin, and glucagon. Pethidine also closes N-type voltage-operated calcium channels and opens the potassium channels, which are dependent on calcium, causing hyperpolarization and reduced neuronal excitability. 

Pethidine’s metabolite norpethidine is considered more toxic than other opioids, especially if used for the long term. It can also have serotonergic effects and can cause serotonin syndrome.

How Long Does Pethidine Last?

Pethidine has a faster onset but a shorter duration of action compared to morphine, another potent opioid analgesic. It has a half-life of 3.2 hours, and the effects last for two to four hours. 

Is Pethidine Addictive? 

Prolonged use of pethidine can cause dependence. It can cause withdrawal symptoms which occur faster than with morphine use. Since it has an addictive nature, pethidine use must be supervised and done with much caution. 

Using it in pregnancy is generally not recommended as prolonged use of pethidine can cause neonatal opioid withdrawal syndrome.

Side Effects of Pethidine (Demerol)

  • Abdominal pain
  • Adrenal insufficiency
  • Agitation
  • Angina
  • Bradycardia
  • Cardiac arrest
  • Coma
  • Constipation
  • Dizziness
  • Dry mouth
  • Dysphoria
  • Euphoria
  • Fainting
  • Flushing
  • Hypersensitivity
  • Hypotension
  • Mental confusion
  • Myocardial infarction
  • Nausea
  • Neonatal opioid withdrawal syndrome
  • Nervousness
  • Palpitation
  • Physical dependence
  • Pruritus
  • Psychological dependence
  • Respiratory depression
  • Restlessness
  • Sedation
  • Seizures
  • Serotonin syndrome
  • Severe cardiac arrhythmias
  • Severe hypotension
  • Shock
  • Sweating
  • Syncope
  • Tachycardia
  • Urinary retention
  • Urticaria
  • Visual disturbances
  • Vomiting
  • Weakness
Two CBD oil containers and a couple of hemp leaves over white background.

Key Takeaways: Is it Safe to Take Pethidine (Demerol) With CBD?

CBD and pethidine share a mild risk of interacting with each other. However, this can worsen with long-term medication and with high doses due to over-accumulation of pethidine in the body.

It’s wise to avoid combining these compounds if you can, and always talk to your prescribing physician before taking CBD alongside any prescription pain medications. 

CBD may have the potential to become an effective painkiller but may not be as effective as pethidine in severe cases. 


  1. Ramírez, J., Innocenti, F., Schuetz, E. G., Flockhart, D. A., Relling, M. V., Santucci, R., & Ratain, M. J. (2004). CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes. Drug metabolism and disposition, 32(9), 930-936. 
  2. Capano, A., Weaver, R., & Burkman, E. (2020). Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study. Postgraduate medicine, 132(1), 56-61. 
  3. Atalay, S., Jarocka-Karpowicz, I., & Skrzydlewska, E. (2020). Antioxidative and anti-inflammatory properties of cannabidiol. Antioxidants, 9(1), 21. 

Learn More About CBD-Drug Interactions

Learn More About CBD-Drug Interactions

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