Many derivatives of natural morphine have been discovered throughout the last century and several are used in modern medicine for their profound analgesic properties and their positive effects on mood
The Forbidden Fruit (Forget what you've been taught)
Perhaps morphine's most well known derivative is heroin, known chemically as diacetylmorphine. It is a one of a series of morphine analogues known as the 3, 6 esters of morphine. Morphine and heroin are closely related, the only difference being that heroin is essentially an acetyled, lipophilic form of morphine, allowing it to more effectively penetrate brain tissue. Heroin is roughly twice the potency of morphine. It's rapid brain penetration facilitates a stronger 'rush' than morphine upon injection; essentially, the quicker the opioid diffuses tissue, the more pronounced the effect will be perceived. Heroin itself has modest affinity at the mu receptor; upon administration however, heroin is rapidly broken down (i.e. metabolized) in the bloodstream to form the potent compound 6-acetylmorphine, and further broken down into morphine, followed by morphine conjugates. These 3 metabolites in addition to the parent drug, are potent agonists at the mu receptor and are responsible for heroin's effect. Additionally, 6-acetylmorphine and morphine-6-glucuronide are believed to bind to a novel type of mu receptor. Following the initial rush, heroin's effect is more or less equivalent to morphine. Its dependence, tolerance, and addiction liability is nearly identical to morphine. Another perhaps less stigmatizing name for heroin is morphine diacetate.
Street heroin typically occurs an white to tan, or even brown, fine powder, and is almost never completely pure. The presence of obscure cutting agents, many of which are non soluble, poses a significant danger to users; illicit heroin is far more toxic and dangerous than pure heroin.
Hydromorphone: A Cleaned Up & Polished Morphine on Steroids
Hydromorphone: The "one" suffix at the end - morphONE rather than morphINE - derives from the term ketone; as hydromorphone is a hydrogenated ketone of morphine. Hydromorphone is licensed for medical use in the US as an alternative to morphine for all indications. Hydromorphone is 5 to 7 times stronger than morphine depending on the route of administration, with 1 to 2 milligrams intravenously being equianalgesic to 10 milligrams IV morphine. Its effects are similar to those of morphine, though side effects are generally less pronounced; specifically it is less likely to produce less itching, nausea, vomiting, or sedation. This is most apperant when the drug is taken orally, as it very effectively relieves pain but produces little rush or body buzz. Hydromorphone may cause less respiratory depression than morphine in equianalgesic doses, however an accidental overdose of this opioid is very serious and can easily cause coma or death. Due to its high potency, non tolerant users who are unaware of its relative strength may be at risk for severe overdose, especially those unfamiliar with its subtle nature of effects. Hydromorphone is rapidly absorbed by any route. Peak plasma levels are reached within 30 to 60 minutes when taken orally. Effects are felt within seconds when injected, and within minutes when swallowed or snorted. Likewise, these effects are generally short lived. The half life of intravenous hydromorphone is less than 2 hours, and the oral half life is not much longer. Effects generally last about 2 to 3 hours. When injected intravenously, hydromorphone produces an intense rush that is similar to heroin; some users prefer this rush to that of heroin, and for this reason hydromorphone is widely taken by recreational users or addicts; usually in the form of tablets which are swallowed, crushed & snorted, or dissolved & injected.
The Codeine Family
Among opioids are derivatives of the naturally occurring opiate codeine, which are used in a similar fashion to morphine-derived drugs and produce the same constellation of effects. Codeine itself is a relatively weak opioid; it relies heavily upon its metabolites, codeine-6-glucuronide and morphine. Codeine, which is sometimes known as 6-methylmorphine, is a methyl ether of morphine, which is more resistant to first pass when taken orally - Substitution with a methyl or an ethyl ether at the 6-hydroxy reduces the potency but increases the bioavailability, of morphine-class molecules, by making the compound resistant to enzymatic attack during its pass through the gut wall, liver, and kidneys; Essentially with codeine, a large portion of the potency is exchanged for a much better oral efficacy. Codeine is approximately 10 to 15 % as potent as morphine depending on the route administered, but its oral bioavailability is as high as 90 percent, compared to morphine's 30 to 40 %. Codeine is therefore much easier than morphine to titrate, allowing one to better gauge the response of a given dose.
Once administered, codeine is extensively metabolized by cytochrome P-450 enzymes to form multiple active metabolites, including codeine-6-glucuronide and morphine; both of which are agonists at mu receptors and contribute to its angalgesic, antidiarrheal, and antitussive properties.
Hydrocodone: An Improvement of Codeine That Competes With Morphine
Hydrocodone is perhaps the most commonly used narcotic in the nation aside from codeine itself. It is best known as the primary component of the trade name analgesic Vicodin; a compound tablet form of hydrocodone and acetaminophen (tylenol). Used together, the combination of both analgesics should be theoretically more effective than either taken alone; however, the addition of acetaminophen is largely for the purpose of deterring misuse of the tablets and retaining a class III regulatory status. Hydrocodone is six times more potent than codeine; the name Vicodin originates with the first two letters 'V I', taken from the roman numeral for the number six (being 6X stronger than codeine), and "Codin" obviously due to its origin as a semi-synthetic codeine derivative.
Hydrocodone like most opioids of the codeine class, is well absorbed by the gut when taken orally. Its bioavailability is similar to codeine or oxycodone (i.e. 60 to 80%). Hydrocodone is useful in treating the moderate to severe pain of fractures, dental pain, pulled muscles and other bone or tissue injury as well as the pain following surgery. On a mg to mg basis, oral hydrocodone is dose-equivalent to oral morphine; but is strikingly more potent by weight in producing euphoria. Hydrocodone should not be injected unless in pure, USP form. Although it is known to be similar to oxycodone by this route, the presence of excess, insoluble filler along with acetaminophen makes this extremely dangerous. For this reason, hydrocodone is almost always used orally in tablet or liquid form, as intended.
Oxycodone - A Sibling to Hydrocodone & Oxymorphone
Oxycodone is a codeine derived opiate similar in structure to both codeine and hydrocodone, and is used medically in tablet and oral liquid forms. Unlike other drugs of the codeine family, oxycodone is often injected by users, and is unlike codeine in that it is not prone to cause dangerous histaminic reactions; In the United States however, injection is not an approved ROA, though it is elsewhere. Oral oxycodone is 1.5 to 2x stronger than oral morphine and slightly stronger than oral hydrocodone. It is effectively absorbed by the gut with a bioavailability ranging 60 to 90 percent.
Oxycodone produces effects similar to hydrocodone and other opioids, but less sedation than morphine. Along with hydrocodone, oxycodone retains its efficacy as a euphoriant when swallowed; producing marked elation and excitement. This along with its inhibition of soreness & fatigue often leads to a transient improvement in activity or productivity, leading many to consider the drug "stimulating" or "speedy" (however, no available opioid acts as a stimulant in the proper pharmacological sense). Oxycodone when injected produces a rush similar to morphine but less pronounced & with less histamine release. It is one of the multiple drugs of choice for IV users, but not to the extent that the potent morphine type drugs typically are. Its effects by any route generally last 2 to 4 hours, similar to morphine. Intravenous doses generally fall toward the short-lived end of the spectrum. Early studies of the drug found that it might produce a slightly greater degree of respiratory depression than morphine in equianalgesic doses.
Synthetic Morphine-Like Analgesics
Over the last century, a number of agents with opioid activity have been produced synthetically and used medically. Most available synthetic opioids target the same receptors in the brain and central nervous system as natural opiates such as morphine, and therefore produce similar effects. Synthetic opioids are produced entirely within the laboratory (or kitchen... or bathtub), from various precursors, and are not products of natural opium or opiates. Their molecular structures are unique from the typical 3 ring morphine (morphinan) based structure, with few exceptions.
One of Many German Inventions
Methadone was produced by german chemists during the period of the second world war. Natural opium supplies during the war era were scarce, which had prompted researchers to develop synthetic alternatives to morphine. Many claim that methadone was invented by the nazis as a painkiller for use during the war, this was not the case. Methadone was never supplied to the german military during the war, as pethidine (and to some extent, morphine) was already available for military use at the time. Methadone had not seen significant clinical use, or even adopted its name, until the end of WWII.
Methadone is a highly potent and fully synthetic opioid and produces similar effects to morphine, acting as an agonist primarily at mu opioid receptors. In addition, it binds as an antagonist at the NMDA receptor, which may lend to its efficacy in the treatment of neuropathic pain. It's used in medicine much like morphine for the treatment of severe pain of all types, and in recent decades (since the 1970's) has become a centerpiece in the treatment of addiction to herion, morphine and other narcotics. Methadone is well absorbed when taken orally, and produces a slow onset of effect over 1 to 2 hours. While its analgesic effect lasts 6 to 8 hours, other effects such as respiratory depression, miosis, and attenuation of opioid withdrawal may last 12 to 24 hours. Its high lipophilicity allows it to remain in fat tissue for long periods and distribute itself gradually into the bloodstream. Effects of methadone are very potent, particularly to non tolerant users; toxicity manifests as respiratory depression which is potentially life threatening. Users maintained on daily doses for extended periods become tolerant to the effects, and experience negligible sedation or repiratory depression when dosed properly.
Methadone In Addiction Treatment
In a clinical setting, daily doses of methadone (as well as buprenorphine) are given to suppress opioid withdrawal and satisfy narcotic "craving", allowing a degree of freedom from the illicit underworld of "unnapproved" narcotic use. . Methadone essentially helps to promote stability in addicts; promoting a level of normalcy in lifestyle, career, etc. Maintenance treatment is what some consider to be a harm reduction approach to narcotic addiction. Opioid replacement therapy has the potential to save lives of those with heavy ties to the many hazards of illicit use such as bad injecting practices or questionably pure street heroin.
Because of its additional activity as NMDA antagonist, methadone has demonstrated tolerance sparing properties, allowing for less dose escalation over time; making it a suitable canidate for maintenance therapy.
Tramadol: Synthetic Analogue of Codeine
Tramadol is worth mentioning, considering its common use. Not by any means a typical opioid, but does produce opioid agonist activity. Tramadol is fully synthetic, and is used in the treatment of mild to moderate pain. Tramadol is a very basic, analogue of codeine. There are 2 modes of action; weak agonism at mu opioid receptors, as well as serotonin & norepinephrine reuptake inhibition. Drugs which block reuptake of serotonin and norepinephrine (ssri, snri) are commonly used in the treatment of depression, but may also be effective as analgesics due to their action on descending pain modulatory pathways of the spine. They are therefore used to enhance the actions of opioid analgesics. Though the opioid agonist effects of tramadol are weak, it jives with the monoaminergic activity quite well. A user with little opioid experience may find tramadol pleasant, similar to codeine, but those with significant tolerance to potent opioids report little high from the drug. Tramadol is often useful in attenuating the symptoms of acute opioid withdrawal. Tramadol is one of the very few opioid agonists not listed as a Controlled Substance by US law. In the summer of 2009, the original producers of Ultram (tramadol) released a similar agent into US market; Tapentadol (trade name Nucynta) is somewhat related to Tramadol; but is much more similar to tramadol's primary active metabolite 'o-desmethyltramadol' or 'M1'. Tapentadol produces opioid agonist activity stronger than tramadol, relieving pain on the scale of mid-range opioids such as oxycodone and hydrocodone. In the dosage units available by prescription, tapentadol is suggested to produce narcotic effects (marked in studies as "drug liking") as pronounced as the available forms of oral hydromorphone.