In the case of opioids, there are many factors at play in determining the overall safety of the drugs. The only serious risk with opioids is the acute risk of toxicity. Aside from this, opioids cause no organic tissue damage to the organs or otherwise, even taken over years. The sole mechanism behind acute opioid toxicity is respiratory depression - via a reduction in brain responsiveness/sensitivity to increasing CO2 levels.
Respiratory depression is mediated via the mu-2 receptor subtype, whereas analgesia and euphoria is mediated via the mu-1 receptor type. Therefore, we can conclude that the rate at which tolerance develops (if even at all) may not be consistent between these two distinctly mediated effects.
Tuesday, May 7, 2013
After the War on Drugs, Opioids in a Free Marketplace
What would a legal market for opioids look like after the end of prohibition? An ideal situation would respect people's rights to use opioids for recreation or self-medication while also seeking to minimize harms. The major risks due to recreational use is mainly an acute overdose, chronic administration also includes a risk of acute overdose as well as dependence (tolerance and withdrawal).
Traditional opiates such as morphine act on both mu receptor subtypes. As the dosage increases to provide additional analgesic or euphorigenic effect there is a corresponding increase in respiratory depression. At a high enough dose breathing stops altogether and the individual may die without administration of an opioid antagonist (naloxone) or artificial respiration.
A synthetic opioid that has a higher affinity for the mu-1 receptor subtype than the mu-2 subtype would be significantly safer. The synthetic opioid sufentanil, a fentanyl analog, appears to do just that. It has a therapeutic index of approximately 25,000, the highest among the commercially available opioids. Sufentanil is highly lipophilic and easily absorbed through mucosal tissues. For recreational uses it could be formulated similar to "bresh freshener" strips that dissolve under the tongue. A variety of dosages (such light, medium, heavy) could be made available to age appropriate consumers depending on the experience desired. A drug delivery mechanism similar to electronic cigarettes could offer an alternative, fast acting delivery mechanism.
Further research could provide a number of synthetic opioids with different pharmacokinetics. Opioids with short half-lives would allow someone to get high during their lunch break and be sober by the time they return to work. The important point is that the large therapeutic index of sufentanil puts it squarely at the top of the safest recreational drugs, in the same ballpark as cannabis and LSD. Cannabis users love to point out that no one has ever died from smoking cannabis, if opioids were as safe a major objection to their recreational use would be removed.
Opium itself is also a relatively safe drug, certainly no more dangerous than alcohol (and arguably quite a bit less so.) Establishments for smoking opium (opium dens) would be available for those who prefer a "natural" experience. Proprietors would be both trained and equipped to handle an accidental overdose, though there is little evidence that overdoses would be any more common in an opium den than an alcohol bar.
Low doses of opioids would be available over the counter much like codeine is some countries. For highly concentrated formulations greater restrictions may be necessary. Ampules for IV use of concentrated and potent opioids such as diamorphine (heroin) or hydromorphone (dilaudid) do have some risk in the hands of ignorant and reckless users. For this reason I suggest two restrictions on distribution. The first is the current prescription system where a qualified medical practitioner could provide some quantity of the medication with detailed instructions on its use.
The second restriction would be a licensing system akin to driver's licenses. It is generally conceded that an automobile can be a dangerous machine in the wrong hands. Their use is limited to adults who must also demonstrate a certain level of competency. I propose a similar licensing system for the purchase and use of the more dangerous drugs. To receive a license to purchase and use such drugs, an individual would first have to demonstrate competency. A basic knowledge of pharmacokinetics, safe injection practices, overdosing symptoms and treatment and safe disposal of syringes would be required before a license is issued.
With the proper license, the individual may then purchase sterile ampules of the opioid of their choice and the knowledge to use it safely. Recreational users would have less choices, but far safer one's. Far fewer people would die from acute overdoses or diseases not specifically caused by opiate use, but a result of our misguided drug policies.