Morphine vs Fentanyl Comparison

Fentanyl exhibits signaling bias with greater arrestin relative to G-protein signaling, as measured by GTPγS binding in cells expressing mouse or human MORs (Schmid et al., 2017). In cell culture experiments, fentanyl promotes robust receptor phosphorylation, beta-arrestin-2 recruitment and receptor internalization but morphine has much weaker effects on these parameters. Perhaps surprising given the agonist bias of fentanyl for beta-arrestin signaling is that analgesic tolerance to fentanyl is not perturbed in beta-arrestin-2 knockout mice (Raehal and Bohn, 2011), whereas morphine tolerance is attenuated (Bohn et al., 2000). The above discussion specifically relates to differences between fentanyl and morphine, but comprehensive reviews of mechanisms underlying the development and maintenance of opioid tolerance have been published previously (Morgan and Christie, 2011; Williams et al., 2013). Fentanyl is poorly absorbed from the gastrointestinal tract but is exclusively metabolized where renal excretion accounts for less than 10% of the dose. Metabolism by piperidine N-dealkylation to norfentanyl, an inactive metabolite, is the predominant degradative pathway in humans, accounting for 99% of fentanyl metabolism (Labroo et al., 1997).

U.S. Overdose Deaths, ​ Select Drugs or Drug Categories, 1999-2023

You can access naloxone from most pharmacists in the U.S. without a prescription. If you, a family member, or a friend take illegal drugs, it is important to have immediate access to naloxone to help possibly save a life. One 2 milligram (mg) dose of fentanyl is enough to kill an adult, but may be more or less depending upon your body size, opioid tolerance, and former usage. Fentanyl can kill you within a matter of 2 minutes, usually due to respiratory failure (breathing that has stopped).

Check with your doctor if you have confusion or drowsiness that is severe enough to interfere with your daily activities. If you feel that the medicine is not working as well, do not use more than your prescribed dose. Prolonged use during pregnancy may result in neonatal opioid withdrawal syndrome. Outpatients, healthcare professionals who prescribe to outpatients, pharmacies, and distributors are required to enroll in the program.

At intravenous (i.v.) doses up to approximately 250 μg/70 kg, fentanyl increased positive subjective effects in 4 studies (e.g., it increased ratings of euphoria, feelings of well-being, or pleasantness of drug effects in Hoehe, 1988; Hoehe et al., 1988; Manner et al., 1987; and Matussek and Hoehe, 1989). Fentanyl doses ranging between 50 μg/70 kg and approximately 200 μg/70 kg, fentanyl did not increase positive subjective responses (Ghoneim et al., 1975; Scamman et al., 1984; Zacny et al., 1996a), and in 2 additional studies, the positive subjective effects produced by fentanyl were equivocal (Zacny et al., 1992a, b). The negative findings reported by Ghoneim et al. (1975) and Scamman et al. (1984) were possibly due to the fact that the peak effects of fentanyl were missed because measurements of subjective responses did not begin until 30 min after drug administration.

The MOR produces its effects via interactions with inhibitory heterotrimeric G-proteins (Gi/o), which are responsible for producing most opioid-related pharmacological effects, including analgesia and euphoria. However, MOR also produce G-protein-independent signaling through beta-arrestin complexes. A biased agonist is defined by the ability of agonist binding to the same receptor to differentially activate signaling cascades that results in the fentanyl laced weed : an overview formation of different protein complexes that trigger different downstream cellular events. The beta-arrestin-2 knockout mouse is protected from morphine-induced respiratory depression and acute constipation (Raehal et al., 2005), although analgesic effects are enhanced by the absence of beta-arrestin 2 (Bohn et al., 1999). A spectrum of signaling bias for different opioid drugs was recently reviewed (Williams et al., 2013).

How does fentanyl compare to heroin or other opiates?

Supporting the hypothesis that pain negatively influences the abuse potential of opioid analgesics are reports that non-contingent delivery of analgesics such as indomethacin (Lyness et al., 1989) or dexamethasone (Colpaert et al., 2001) decreased intravenous morphine or oral fentanyl self-administration, respectively. However, others have reported an increase in oral fentanyl consumption in a model of polyarthritis compared to pain-free or chronic neuropathic pain in rats (Kupers and Gybels, 1995). Fentanyl is highly lipophilic, lending itself to rapid absorption by highly-perfused tissues (including the brain) before redistributing from these tissues to muscle and fat. Fentanyl is eliminated primarily by metabolism and urinary excretion of metabolites (norfentanyl and other minor metabolites). Fentanyl has a long terminal elimination, with a documented secondary peaking phenomenon that can manifest as “fentanyl rebound”. Clinical implications in overdose (respiratory depression, muscle rigidity and “wooden chest syndrome”) and opioid use disorder treatment (subjective effects, withdrawal and buprenorphine-precipitated withdrawal) are discussed.

Serious side effects of fentanyl

Fentanyl moving through the street market comes in a powder form and can be injected, smoked, or snorted. It has also been found in other drugs, like heroin, meth, cocaine, and pressed pills. Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use fentanyl only for the indication prescribed.

Why Do People Lace Weed With Fentanyl?

According to the DEA, 42% of pills they tested for fentanyl contained at least 2 mg of fentanyl, a potentially lethal dose. One kilogram of fentanyl has the potential to kill 500,000 people. One report has suggested that epidural fentanyl may mask the pain of myocardial ischemia in patients treated with fentanyl for other reasons. Another report has suggested that QTc interval prolongation may occur in some patients receiving the related narcotic sufentanil.

It is 50 to 100 times more potent than morphine, and therefore lethal. Even two milligrams of illicit fentanyl, equivalent to two grains of sand, can cause an overdose and death. Fentanyl is currently a leading cause of overdose deaths in the US. Some of the early studies of the abuse liability of fentanyl were conducted in normal, healthy volunteers who did not use drugs recreationally, although most of the participants used alcohol occasionally. In this population, fentanyl did not reliably increase positive subjective responses.

• Interestingly, morphine failed to facilitate ICSS in the presence of chronic neuropathic pain (Ewan and Martin, 2011b) or in an acute model of acute visceral pain (Altarifi et al., 2015).
• The addition of the anaesthetic can “intensify the drug’s side effects” — and because it isn’t an opioid, it also means an overdose on purple fentanyl can’t be reversed with Narcan, the Omaha Police Department warned.
• It is not currently possible to predict the occurrence of secondary plasma peaks, and it is not known if secondary peaking in the plasma affects IMF-related withdrawal presentation or contributes to late-onset overdose risk via respiratory depression.
• Fentanyl can slow or stop your breathing and may be habit-forming.

Naloxone (Narcan) for fentanyl overdose

• The risk of death can be higher with the use of fentanyl compared to heroin due to its high potency.
• Another reason fentanyl is so dangerous is that many people are simply unaware of this ongoing threat.
• This practice often causes dangerous overdoses, when people unknowingly ingest powerful substances in potentially deadly combinations.
• Many studies have demonstrated that fentanyl and morphine differ with regard to mechanisms of opioid tolerance and reinforcing effects.
• Cicero et al., 2017 asked 10,900 individuals who were entering treatment for opioid use disorder about fentanyl.
• See the impact of fentanyl and other synthetic opioids on drug overdose deaths.

Surprisingly little is known about the exact signaling mechanisms underlying fentanyl-related respiratory depression or the effectiveness of naloxone in reversing this effect. Similarly, little is known about the ability of treatment medications such as buprenorphine, methadone, or naltrexone to reduce illicit fentanyl use. The present article reviews the receptor, preclinical and clinical pharmacology of fentanyl, and how its pharmacology may predict the effectiveness of currently approved medications for treating illicit fentanyl use. Fentanyl is a potent synthetic (man-made) opioid used to relieve post-surgery pain, and to manage pain caused by chronic illnesses such as cancer.

Zepbound (tirzepatide) is an FDA-approved weekly injection for weight loss and obstructive sleep … This is not all the information you need to know about fentanyl and does not take the place of your healthcare provider’s advice. Discuss this information and any questions you have with your doctor or other health care provider. Prescription fentanyl is dosed in micrograms, designated by the abbreviation “mcg”. Most other drugs are dosed in milligrams (“mg”) — for example, 500 mg of acetaminophen (Tylenol) or 25 mg of diphenhydramine (Benadryl). Along with its needed effects, fentanyl may cause some unwanted effects.