TABLE OF CONTENTS
- What is the difference between an opiate and an opioid?
- What are the medicinal purposes of opioids?
- How are opioids taken?
- What are the short-term and long-term effects of opioids?
- What parts of the brain and nervous system to opiates affect?
- What are opiate receptors and how do they work?
- What drugs and foods should be avoided while on opioids?
- How and why are opioids abused?
- What is withdrawal and when does it occur?
- How does snorting (insufflating) opiates get a person high?
- How is an opiate overdose treated?
- I have this pill marked xxxxx. What is it?
There are generally three categories—natural, semi-synthetic, and synthetic. In many cases, the words opiate and opioid are used interchangeably, depending on the source; however, there are nuanced differences to consider when using either term. Specifically, the word opiate refers to the naturally-occurring alkaloids found in the poppy plant (e.g. morphine, thebaine, codeine, papaverine). On the other hand, the word opioid represents any compound resembling opium and its effects (e.g. oxycodone, hydromorphone). For the sake of terseness, an opiate is naturally occurring, and an opioid can be synthetic.
SO, TAKE AWAY THE POPPYCOCK AND YOU HAVE…
— Opioids include all semi- and fully synthetic narcotic analgesics (e.g. oxycodone, methadone), as well as the remainder of the opiate class.
— The word opiate describes narcotic analgesics from a natural source (e.g. morphine, codeine).
Clinical Uses: Analgesic, acute pulmonary edema (slows respiration and calms patient), in preanesthetic medicine for analgesic and sedative effects, anesthetic, antitussive, and antidiarrheal.
Off-Label Uses: Diabetic neuropathy, restless leg syndrome, treatment-resistant depression.
Opioids are administered in a variety of ways from ingestion to injection. Opioids are generally well-absorbed via intramuscular and subcutaneous routes, as well as at muscosal sites. Oral consumption is often accompanied by extensive first-pass metabolism making it less efficient than the aforementioned methods of delivery. For some opioids like buprenorphine, oral administration renders the drug useless; thus, requiring sublingual or intravenous administration. Because intravenous injection typically provides the highest bioavailability (typically close to 100 percent) and the fastest peak (the “rush”), drug users often prefer this method of administration.
- POSITIVE — pain relief (analgesia), euphoria, drowsiness, relaxation, cough suppression
- NEUTRAL — itching, pupillary constriction, stimulation, sweating
- NEGATIVE — difficulty concentrating, blurred vision, reduced respiratory rate, nausea, vomiting, reduced appetite, anxiety, lethargy, constipation, dysphoria, reduced libido, death, spontaneous abortion
Long-term use of opioids can lead to depression, reduced pain threshold, difficulty concentrating, malnutrition, insomnia, sexual problems, and addiction. As the body becomes accustomed to a specific dosage, the drug will no longer provide the same level of pain relief or euphoria; this is called tolerance. As tolerance builds, the person will find himself requiring increasingly larger doses, sometimes at a higher frequency. In addition, the body starts producing fewer endorphins and withdrawal becomes more severe.
Injecting opioids carries additional risks, especially when using dirty needles, sharing needles, or injecting incorrectly. The sharing of needles contributes to the spread of diseases such as AIDS/HIV and hepatitis. Intravenous drug use can also lead to collapsed veins, bacterial/viral infections, skin infections, and increased risk of stroke.
Limbic system (red) - The limbic system is a part of the brain that controls emotion, motivation, and emotional association with memory. Opiates affect the limbic system leading to feelings of pleasure, relaxation, and contentment.
Brainstem (blue) - The brainstem coordinates certain types of movements, as well as automatic functions, such as breathing and coughing. Opiates affect the brainstem causing slowed breathing, and suppression of coughs.
Spinal cord (yellow) - The spinal cord is responsible for the communication between the body and brain. One specific function of the spinal cord is the transmission of pain signals from the body. Opiates act on the spinal cord, blocking pain messages, which can sometimes lead to serious injury.
Within the three parts of the brain mentioned above, the limbic system, brainstem, and spinal cord, as well as the large intestines, there are sites on specific nerve cells that recognize opioids. When these sites on the nerve cells are stimulated by an opioid, the brain and body are affected.
There are four major subtypes of opioid receptors: mu, delta, kappa, and recently discovered nociceptin (ORL-1). Each of major receptor subtype is named after a letter of the Greek alphabet. According to Wikipedia, the opiate receptors were named “using the first letter of the first ligand that was found to bind to them.” Each receptor initiates a different response in the body, and there are three different methods of binding to a receptor.
Opioids that activate opioid receptors in the brain are termed opioid agonists. Opioid agonists bind to opioid receptors and turn them on, or activate them, resulting in some sort of effect in that organism. Full mu-opioid agonists activate the mu-opioid receptors. As the dose of a full agonist is increased, the effects will be increased until a maximum effect is reached or the receptor becomes fully activated. This class of opioids, the opioid agonists, have the highest abuse potential (e.g., heroin, methadone, morphine, oxycodone, hydromorphone).
Antagonists also work by attaching to the opioid receptors, but instead of activating the receptors, they block them. Antagonists also have the property of preventing the receptors from activation from agonists. An antagonist is much like a key that fits in a lock but does not open it and prevents another key from being inserted to open the lock. Examples of opioid antagonists include naloxone and naltrexone.
Partial agonists, such as buprenorphine, have qualitative effects similar to both full agonists and antagonists. Like agonists, partial agonists will bind to receptors and activate them, but with lower intrinsic activity. For individuals not opioid-tolerant or dependent upon opioids, full agonists and partial agonists produce indistinguishable effects. Like its counterpart, the agonist, increased doses produce increasing effects; however, at a certain point, the effects of partial agonists reach a maximum and will not increase further, even if the dose is increased. This quality is known as the ceiling effect. At higher doses, partial agonists exert effects much like an antagonist—maintaining binding affinity to the receptor and partial activation (or no activation), while simultaneously displacing or blocking full opioid agonists from the receptors.
Mu-receptors (found in periaqueductal gray region, spinal cord, olfactory bulb, nucleus accumbens) - Activation of the mu-receptor causes analgesia, sedation, reduced blood pressure, itching, nausea, euphoria, decreased respiration, miosis (constricted pupils) and decreased bowel motility. Some of these effects, such as sedation, decreased respiration, and euphoria, tend to disappear as tolerance develops; however, very little tolerance develops to analgesia, miosis, and decreased bowel motility. Tolerance varies from effect-to-effect because of the activation of different mu-receptor subtypes (µ1 and µ2). To be specific, µ1-receptors block pain, while µ1-receptors cause reduced bowel motility and respiratory depression. The mu-receptors possess high affinity for enkephalins and beta-endorphin, and a low affinity for dynorphins.
Delta-receptors - Delta-receptor activation produces analgesia, and some research points to the possibility of a lowered seizure threshold. Enkephalins are the endogenous opioids that bind to the delta-receptor. Only recently have scientists been able to study this receptor, and as a result, available information is very limited. On the other hand, there are studies indicating that stimulation of the delta-receptor may result in some sort of cardioprotection, given certain circumstances.
Kappa-receptors (found in periphery by pain neurons, spinal cord, brain) – Like the other opiate receptors, the kappa-receptor also induces analgesia, but also causes nausea and dysphoria. Stimulation of the kappa-receptor is neuroprotective against hypoxia, which may lead to kappa-agonism being used therapeutically in the future. The kappa-receptor has high affinity for dynorphins. Kappa-agonism, whether induced by a full-agonist or partial-agonist, causes psychotomimetic effects, which includes hallucinations, delusions, and other forms of psychotic behavior. Psychotomimetic effects are largely undesirable, which naturally serves to limit abuse potential. Drugs with this sort of effect include buprenorphine (found in Suboxone/Subutex), butorphanol, and nalbuphine. Salvinorin A, the primary active psychotropic chemical in Salvia divinorem, is also a kappa-receptor agonist. Salvia divinorem’s effects are actually sought after, but differ from typical hallucinogens, whose primary method of action is 5-HT2A serotonin receptor agonism.
Nociceptin receptor (also known as ORL-1) - The natural ligands for the ORL-1 receptors are nociceptin, and orphanin FQ. Orphanin FQ was found to inhibit the GABA transporter type I, which indirectly alters dopamine transmission. ORL-1 receptor agonists are currently being researched as possible treatments for heart failure, and migranes. Nociceptin antagonists may be effective for treating depression. Though the implications seem promising, research into the ORL-1 receptors is still in an adolescent stage, so it is hard to tell what the conclusion will be. Buprenorphine, used in the treatment of opioid addiction and also as a painkiller, is a partial agonist at the ORL-1 receptors, while its active metabolite norbuprenorphine is a full agonist at these receptors.
Combining opiates with any drug that suppresses breathing can be fatal. This includes, but is not limited to:
- Sedative-hypnotics/benzodiazepines – alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium), etc.
Opioids are abused for their euphoric and sedative qualities; however, with repeated dosing tolerance develops. Tolerance develops to many of the effects of opiates, but at different rates for each effect. Tolerance develops very quickly to the ability of opiates to reduce the perception of pain, as well as the suppression of breathing. Two effects that don’t really change as tolerance develops are pinpoint pupils and constipation.
Heroin: Many heroin users begin with insufflation or subcutaneous injection (“skin-popping”) and eventually end up injecting the drug. Smoking heroin, the second fasted method of administration is also popular; however, the fastest way to get heroin to the brain is via intravenous injection.
OxyContin: Abusers generally pulverize the pills and insufflate or “parachute” the resultant fine powder. This is extremely dangerous, especially to opiate-naive individuals, who have little to no tolerance to opioids. An 80 mg OxyContin pill, which is meant to be released over a period of 12 hours, is equivalent to taking sixteen 5 mg Percocets. The instant release of 80 milligrams of oxycodone can be fatal.
Fentanyl: Because fentanyl is very fat-soluble and very fast-acting, it makes it a prime candidate for abuse. One popular form is the transdermal patch, some of which can be worn for three days delivering a steady dose of the drug. Many people cut open the patch and suck the contents out. This is even more dangerous than insufflation of OxyContin; instead of a 12-hour dose, it is a 72-hour dose. It is very hard to determine how much of the drug is actually being taken. Also, by weight, fentanyl is about 80 times stronger than morphine, and is subsequently measured in micrograms. Fentanyl is also frequently found in an injectable preparation.
Withdrawal occurs when an opioid-addicted individual ceases taking opioids. In some cases, withdrawal can begin in as little as a few hours after the last dose, but typically starts within 12-24 hours. For many people, it begins with sweating, yawning, a runny nose and “teary”-eyes. As withdrawal peaks, the individual will be extremely uncomfortable and exhibit symptoms such as diarrhea, shivering, sweating, insomnia, muscle aches, abdominal cramps, restlessness, irritability, loss of appetite, and anxiety. It is often compared to the flu, but for many, the flu is a play day in comparison. Withdrawal generally lasts about a week with the acute symptoms peaking on day three and subsiding by day seven. With long-acting opioids, such as methadone and buprenorphine, the withdrawal can last twice as long.
Recent studies have indicated there is often a “post-acute withdrawal syndrome” which can mean months of muscle aches, insomnia, and depression; however, this doesn’t mean the afflicted individual will be suffering for months on end. PAWS often shows its ugly head in the form of regular “flare-ups.” Sometimes the post-withdrawal feelings may even be the result of a preexisting condition, a condition that the user may or may not have been using drugs to control (self-medicating). This should be discussed with a licensed healthcare professional.
In the nose, there is a mucosal lining which can absorb chemicals depending on the fat-solubility of the molecule. The more fat-soluble the opioid, the better it will be absorbed. Perhaps the best example of this is fentanyl, which is the most fat-soluble of the opioid family; not too far behind is its opiate cousin diacetylmorphine, also known as heroin. It is important to remember that insufflation is not without consequence. In general, snorting wears away the tissues in the nose, which can lead to a gaping hole, or unpleasant whistling through the nostril.
In the movie Pulp Fiction, one of the female characters overdosed on heroin. While trying to save her life, John Travolta was screaming at a man to bring over an adrenaline shot. The man frantically brought over the adrenaline shot, which was subsequently injected directly into her heart, jump-starting her body back to life. Hold up! Back to reality. Adrenaline is cannot be used to counter an opioid overdose. In order to counter an opioid overdose, an opioid antagonist with a high binding affinity is needed to strip the opioid off the receptors; thus, preventing respiratory depression. In the movie Transpotting, one of the characters is left at the entrance of a hospital emergency room, discovered, and given an opioid antagonist. Within moments he is jumping out of his skin. This is a much better representation of the effects of an opioid antagonist; the drug almost always used is naloxone, also known as Narcan. Naloxone works in a matter of seconds by stripping any opioids off the opioid receptors. Instant withdrawal, but one life saved.
Due to the overwhelming number of requests to identify pills, TPC! has put together an extensive list of pill identification guides for numerous medications with a focus on opioids.