Author: James Anderson

Carfentanil: Uses, Interactions, Mechanism of Action DrugBank Online

Carfentanil and its stereoisomers and salts are controlled by the Betäubungsmittelgesetz as a Anlage I substance and can only be used with the special permission of the authorities. American Addiction Centers (AAC) is committed to delivering original, truthful, accurate, unbiased, and medically current information. The onset of these symptoms usually occurs within seconds to minutes of opioid exposure. Street carfentanil first appeared in the early 2000s, and there has been an escalation in cases. Carfentanil is an analogue of fentanyl and is also known as (4‑methoxycarbonyl)fentanyl. Related analogues of fentanyl include 4‑phenylfentanyl, lofentanil (3‑methylcarfentanyl), N-Methylnorcarfentanil, R (4‑methoxymethylfentanyl), sufentanil, and thiafentanil.

Carfentanil Mixed With Other Drugs

Although the term overdose might imply taking too much, with carfentanil, breathing any of the aerosolized powder can lead to serious side effects and death. Due to inexpensive manufacturing and high potency, carfentanil has been added as a filler to other illegal drugs, such as heroin and cocaine. The illicitly manufactured analogs may not be routinely detected in emergency settings because specialized toxicology testing is usually required. Other powerful fentanyl analogs such as acetyl fentanyl, acryl fentanyl, furanyl fentanyl and ocfentanil are also fully synthesized opioids and considered illegal.

Can You Use Naloxone For Carfentanil Overdose?

Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited.

Which drugs cause opioid-induced constipation?

A 25-year-old male with a history of tobacco, alcohol, marijuana, spice, and prescription pain medication use was found face down on a mattress in a tent where he had been living with his mother. Before his death, he complained of “itching all over” and his sister described him as sounding “very intoxicated.” Initial peripheral blood screening was positive for benzoylecgonine (460 ng/mL). His urine screening was highly suggestive of carfentanil, but these results were inconclusive due to the relatively low dose. Given his symptoms of “itching all over” and inconclusive urine results, cardiac blood was tested specifically for the presence of carfentanil, which was ultimately positive at very low quantities (0.12 ng/mL). Additional testing of vitreous humor showed cocaine (40 ng/mL) and benzoylecgonine (510 ng/mL), but no evidence of carfentanil. Ultimately, given the significant history and positive cardiac blood toxicology, cause of death was determined as carfentanil intoxication 36.

Potential as a chemical weapon

Currently, carfentanil still sees medical and scientific use as a radiotracer for positron emission tomography imaging, related to its high affinity for MORs in brain tissue 14. Outside of its legitimate clinical uses, carfentanil is commonly known by street-names such as “drop dead” and “elephant tranquilizer”. It has been commonly found as an additive in other illicit drugs such as heroin and cocaine, meaning many unwitting users may be completely unaware of its presence 15. As carfentanil is not regularly tested for in most routine drug screening panels, investigators are still unsure of the extent to which it contributes to yearly opioid overdose deaths.

The lethal dose for carfentanil in humans is not known; however, it is 100 times more potent than fentanyl. Fentanyl is known to be lethal at the 2 milligram range, 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). Additional control under Schedule IV imposes the strongest possible regulations on substances by prohibiting production and supply of substances except under licence for specific purposes, such as medical treatment and research. Carfentanil is a powerful derivative of fentanyl, a synthetic narcotic analgesic produced from morphine.

Fentanyl users are at a greater risk of precipitated withdrawal by buprenorphine when treatment is initiated 30, 31. The withdrawal mechanism may be due to fentanyl’s lipophilicity, which causes prolonged and varied renal clearance, or due to MOR desensitization/availability 30. Current methadone treatment protocols are conservative, and the dosing regimen does not reach a therapeutic dose quickly enough, causing a lack of perceived efficacy in patients 29. Through ongoing research, it is pertinent that optimal treatment strategies and dosing for fentanyl-related OUD are created regarding buprenorphine, methadone, and naloxone 28.

Can You Overdose On Carfentanil?

He explained that his previous withdrawal symptoms often included sweating, nausea, jaw tension, and intense psychic stress. While detoxing in the hospital, he exhibited psychomotor agitation, insomnia, and episodes of cold sweats consistent with opioid withdrawal. The patient was discharged after only 7 days at his request following the cessation of withdrawal symptoms. Providers in the hospital conducted a psychoeducational interview and determined that his judgment was intact with the absence of cravings; therefore, he was allowed to leave 35. Naloxone can reverse the effects of a carfentanil overdose, though multiple doses may be required.

Current evidence also shows that cannabidiol is not likely to be abused or create dependence as for other cannabinoids (such as Tetra Hydro Cannabinol (THC), for instance). Like protonitazene, isotonitazene also belongs to the novel benzimidazole class of opioids. This drug never saw any medical use and remained in relative obscurity until being identified by authorities in Midwestern USA in 2019 24. However, in mid-2020, the USA classified isotonitazene as a Schedule I substance 25.

A 38-year-old male with a known history of alcoholism was found deceased on the floor of his friend’s bathroom. His family denies any history of illicit drug use, but drug paraphernalia including a syringe, spoon, and powdery substance was found at the scene. Analysis of the powdery substance identified a mixture of heroin, fentanyl, and carfentanil. No formal autopsy was conducted but given the presence of opioids and track marks on the decedent’s arms, further toxicology analysis was performed. Initial urine screening was positive for morphine, hydromorphone, fentanyl, and norfentanyl, but there was no evidence of carfentanil. Carfentanil (30.1 ng/L) was only identified after analysis of the subclavian blood 33.

As a fentanyl derivative, carfentanil produces effects similar to other opioids, including analgesia, euphoria, bradycardia, respiratory depression, hypotension, loss of consciousness, and death. For instance, it is over 1000 times more potent than morphine at the MOR, and its affinity for the MOR is 50 times greater than fentanyl 17. Given the implication of MOR in respiratory depression, the high potency of carfentanil means that even very small doses can produce extremely rapid detrimental effects.

1. Given the increased potency of synthetic opioids, it has been hypothesized that increased dosages of naloxone are necessary to reverse their effects 11, 13.
2. Hospital protocols, clinician training in addiction, and legal restrictions have perpetuated ongoing challenges to successfully and effectively manage pain and limit addiction and overdose 26.
3. His urine toxicology screening was positive for benzodiazepines and marijuana, but no evidence of opioids.
4. The top five carfentanil states witnessed the largest increase in overdose deaths +13.7% in 2017 followed by the largest decline −14.3% in 2018.

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. No funding or sponsorship was received for this study or publication of this article.