What are Nitazenes?

Nitazenes are a class of high-potency synthetic opioids originally developed in the 1950s but never approved for medical use. They are structurally unrelated to fentanyl yet can be far stronger—some analogs estimated to be 20–40x more potent than fentanyl. Nitazenes such as isotonitazene, protonitazene, metonitazene, and etonitazene have re-emerged in illicit drug markets in recent years, often found in counterfeit pills, powders, or mixed with heroin or fentanyl without the user’s knowledge. They typically appear as off-white, beige, or brown powders but can be pressed into tablets or blended into other substances.

Because they were never developed for clinical use, nitazenes have no legal medical applications and are considered illicit in all forms. Their extreme potency greatly increases the risk of overdose, respiratory depression, and death—even in very small quantities. Many users unknowingly consume nitazenes when contaminants are present in counterfeit opioid pills or “heroin” mixtures. Due to their rising prevalence and high mortality risk, nitazenes have become a growing concern for public health agencies, law enforcement, and toxicology programs.

For point-of-care testing environments, nitazenes present a challenge because standard opioid or fentanyl panels may not detect them, prompting the development of specialized assays. Their legal classification and rising presence in overdose cases have made nitazene screening increasingly relevant for workplaces handling safety-sensitive roles, medical environments, corrections, and treatment programs.

Effects:

• Extreme respiratory depression

• Sedation and impaired consciousness

• Pinpoint pupils

• Euphoria (in some cases, but much less predictable than other opioids)

• Profound drowsiness or “nodding off”

• Reduced blood pressure and slowed heart rate

• High risk of overdose even at very small doses

• Loss of coordination and slowed motor skills

• Severe physical dependence potential

• Withdrawal symptoms similar to—but often more intense than—other opioids

What is Tramadol?

Tramadol is a synthetic opioid analgesic used medically to treat moderate to moderately severe pain. It acts on the central nervous system by binding to opioid receptors while also inhibiting the reuptake of serotonin and norepinephrine—giving it both opioid and atypical antidepressant-like properties. Because of its dual mechanism, tramadol carries risks of dependence, withdrawal, seizures, and serotonin syndrome.

Prescription tramadol is supplied as tablets, capsules, or extended-release formulations. Colors, shapes, and markings vary by manufacturer, but most tablets appear white or off-white. Illicit or misused tramadol may appear as loose tablets, counterfeit pills, or crushed powder.

Medical use:

• Prescribed for pain management

• Often used after surgery, injury, or for chronic conditions

• Available in immediate-release and extended-release forms

Recreational misuse:

Some individuals misuse tramadol for its sedative, mood-altering, and opioid-like effects. High doses increase the risk of overdose, seizures, respiratory depression, and dangerous interactions with other CNS depressants or SSRIs/SNRIs.

Effects:

• Pain relief and reduced discomfort

• Mild euphoria or mood elevation

• Drowsiness or sedation

• Dizziness or impaired coordination

• Constipation or gastrointestinal slowing

• Nausea or vomiting

• Headache

• Risk of seizures at high doses

• Respiratory depression (especially with other depressants)

• Dependence, tolerance, and withdrawal over time

What is [text]?

Tricyclic antidepressants (TCAs) are a class of medications originally developed in the 1950s to treat major depressive disorder, anxiety disorders, and certain chronic pain conditions. They work by increasing levels of serotonin and norepinephrine in the brain while also affecting several other neurotransmitter systems, which gives them both therapeutic benefits and a higher side-effect profile compared to newer antidepressants. Common TCAs include amitriptyline, nortriptyline, imipramine, desipramine, and clomipramine. These medications are usually dispensed as tablets or capsules, varying in color and dosage depending on formulation.

In healthcare settings, TCAs remain valuable for conditions such as neuropathic pain, migraine prevention, fibromyalgia, obsessive-compulsive disorder (clomipramine), and treatment-resistant depression. Because they affect multiple receptor systems—including cholinergic, adrenergic, and histaminergic pathways—TCAs can produce sedation, anticholinergic effects, and cardiovascular changes. Recreational misuse is rare but possible; when misused, individuals may attempt to achieve sedative or euphoric effects, though doing so poses significant toxicity risk. Overdose is particularly dangerous due to the drug’s effect on cardiac conduction and the central nervous system.

For toxicology screening programs, TCAs are often included in point-of-care testing panels because of their narrow therapeutic window and risk of accidental or intentional overdose. Detection helps medical providers monitor adherence, assess toxicity, and identify potential misuse or dangerous drug interactions.

Effects:

• Reduced symptoms of depression and anxiety

• Pain modulation and relief in neuropathic pain conditions

• Sedation, which can aid sleep in some patients

• Migraine and tension-headache prevention

• Dry mouth, blurred vision, constipation (anticholinergic effects)

• Drowsiness, dizziness, or cognitive slowing

• Increased heart rate and blood-pressure fluctuations

• Risk of cardiac arrhythmias, especially in overdose

• Seizures, confusion, or delirium at toxic levels

• High overdose lethality due to cardiac and CNS toxicity

What is PPX?

Propoxyphene (PPX) is a synthetic opioid analgesic that was once commonly prescribed for mild to moderate pain. Structurally similar to methadone but significantly weaker, it was marketed under brand names like Darvon and Darvocet. In medical form, PPX appeared as tablets or capsules, often pink, orange, or white, depending on formulation. It was taken orally and typically combined with acetaminophen.

Recreationally, propoxyphene was misused for its mild opioid effects, though it was never as powerful or euphoric as stronger opioids. Misuse involved taking higher-than-prescribed doses or crushing and ingesting tablets to intensify sedation. However, PPX also carried significant cardiac risks, including arrhythmias and fatal heart conduction abnormalities, even at therapeutic levels. Because of these dangers, the FDA removed propoxyphene from the U.S. market in 2010, though it may still appear in illicit circulation or older patient supplies.

Despite its discontinuation, PPX remains relevant in toxicology testing because legacy prescriptions, leftover medication, or diversion can still occur. Its presence in a screen may indicate misuse, accidental ingestion, or exposure to outdated pharmaceuticals.

Effects:

• Mild euphoria

• Pain relief and reduced physical discomfort

• Drowsiness and sedation

• Dizziness or lightheadedness

• Nausea or vomiting

• Impaired motor coordination

• Constipation

• Respiratory depression at high doses

• Risk of cardiac conduction abnormalities

• Potential progression to opioid dependence