Besides illicit drugs such as heroin and cocaine, some PWID inject pharmaceutical drugs. The injection of such drugs is becoming more and more common in many countries, like France, the USA, Canada and Australia [1,2,3,4,5,6,7].
There may be different reasons for using or even preferring pharmaceutical drugs. They may be easier to obtain in some contexts, their nature and dosage are known, and their use may be more acceptable in some groups.
The injection of pharmaceuticals entails complications which, for some, are inherent to insoluble tablet fillers such as talc, starch and microcrystalline cellulose. Their injection can give rise to several complications such as abscesses, ulcers, granulomas and phlebitis, pulmonary embolism, fibrosis and talcosis [8,9,10,11]. Filtration can prevent or delay these complications by removing insoluble particles from the suspension prior to injection. Membrane filters, such as the Sterifilt and wheel filters, are more efficient in eliminating particles from a solution than cotton or cigarette filters that are commonly used by PWID [12,13,14].
In France, one of the pharmaceuticals commonly diverted by injection is Skenan, a slow release capsule formula of morphine sulphate. The injection of this drug increased from 7 to 17% among people attending needle exchange programmes and drop-in centres between 2003 and 2015 [15, 16].
The major preparation method for this drug involves heating after adding the active substance to the solution [17, 18]. Because of the presence of starch, when heated, the suspension becomes highly viscous. Therefore, the more efficient membrane filters tend to clog up and are not often used. Keijzer and Imbert  found that only 11% of the people who inject this drug used membrane filters, while these have been accepted and are now widely used for the filtration of drugs such as buprenorphine that are extracted from standard, non-slow release tablets.
New drug preparation guidelines have also been taken up by PWID in other contexts . But, despite the promotion, by harm reduction professionals of a cold preparation technique for Skenan, this advice has not been followed up . It is thus plausible that there is a good reason to heat this drug. Some mention a lack of tingling feelings when they use the cold technique and a membrane filter; others mention an enhanced high when heating .
This might be true. The solubility of morphine is 53.8 mg/mL at a temperature of 25 °C . Most PWID in France inject 100-mg or 200-mg capsules; they may heat in order to dissolve the available morphine in a small volume (1-mL and 2-mL syringes are used). McLean et al.  showed that heating does not increase the solubility of morphine sulphate. However, they used a volume of 3 mL to dissolve 60 mg of morphine sulphate, and they waited 5 min before filtering the suspension. Low solubility may not be a limiting factor under these conditions. According to other sources [23, 24], a higher temperature does seem to enhance morphine or morphine sulphate solubility.
Our hypothesis is that more morphine is extracted in a 2-mL solution after heating.
Preparation practices used in the field
The hot preparation method, commonly used for slow release capsules of morphine sulphate (81% of the users of this drug heat their solution -), is performed as follows: The microbeads contained in the capsule are placed in a cooker (either whole, or after being crushed), water is added and the solution is subsequently heated until the first bubbles appear. Thereafter, the suspension is stirred and filtered through either a small piece of cigarette filter or a cotton filter.
Though the majority use this method, other preparation methods are used.
Though very rare (personal observation in the field), some people use the cold preparation method. They crush the microbeads, put them in the cooker, add water, stir, wait for about 5 min, stir again and filter. Membrane filters can be easily used with this preparation method.
Another method has been developed by the attendees of a harm reduction centre in France that is managed by a drug users’ organisation (ASUD, Nîmes). This technique seems promising as it is used by a large number of users, and it is compatible with membrane filtration. We will call this “the lukewarm method”. First of all, the microbeads contained in the capsule are crushed and put aside. Water is poured into the cooker and heated until the first bubbles appear. Fairly quickly, the crushed powder is added to the lukewarm water and the solution is stirred. Subsequently, the solution is filtered either through a membrane filter only or through a membrane filter that is positioned on top of a cotton filter, called combined filtration. Prepared in this fashion, the solution is still a little viscous, but it goes through membrane filters; the presence of a cotton filter underneath prevents the filter from clogging and enhances the filtration speed.
Many professionals in the field of harm reduction (including the author) have been wondering for a long time what would be the best technique for the preparation of this drug. The manufacturer of Skenan® turned to the Research and Prevention Fund Apothicom receiving a question from a drug users’ organisation (Psychoactif) on the harms associated to the injection of Skenan. This pushed the fund to write a protocol and to subsequently request Ethypharm to perform the lab work on its product.
Ethypharm Laboratories has been marketing Skenan® and Actiskenan® specialties since July 2015. Skenan®, mainly in the 100-mg and 200-mg dosage strengths, as well as other Morphine specialties, have been used off-label as an opiate substitution drug since the early 1990s. This “ancient” use is well documented (OFDT—French monitoring centre for drugs and drug addiction; Oppidum—monitoring centre for psychotropic drug that are illicit or diverted from their pharmaceutical use; Opema—monitoring centre for drug dependencies in ambulatory medicine). This use is not framed by a legal regulation, except the “Letter Girard” of 1995 that states that, in the absence of a marketing authorisation as a substitution drug, Skenan can only be prescribed as such in rare cases and after concertation between the general practitioner and the medical advisor of the social security. The lack of a clear regulation places health professionals and their patients in condition of random treatment success. Morphine as an option of opiate substitution, even for a limited number of patients, deserves to be explored and better supervised for the benefit of all.
This off-label use of morphine, including Skenan®, as an opiate substitution therapy is clearly not promoted and encouraged by Ethypharm.