From prohibited to prescribed

The legislation and prescribing laws surrounding controlled drugs (Schedules 1-5) are widely taught in both a pharmacy setting and during my pharmacy university course. Controlled drugs are named as such due to their risk for misuse and harm and thus, their use should be monitored and regulated by a healthcare provider.

Schedule 5 includes drugs such as codeine whereas Schedule 4 includes anabolic steroids and benzodiazepines. As a general statement, Schedule 3 drugs, such as buprenorphine, are to be kept under safe custody (under lock and key). Schedule 2 drugs, including opiates and cannabis-based products, are all kept under safe custody, need to be recorded in a CD register and require the holder to always hold proof of their prescription. However, when learning about Schedule 1 drugs at university, the blanket statement given was "Schedule 1 CDs have no recognised medicinal use". Furthermore, when asking my pharmacist about Schedule 1 CDs on placement, I was told that she was unsure of any benefits and essentially, they didn't really have any use outside recreational drug use.

However, cannabis-based products can now be legally prescribed to patients in the UK on a case-by-case basis. This legislation came into place as recently as November 2018, which led me to the question: what possible therapeutic benefits are being explored for other Schedule 1 drugs? Surely if cannabis-based products had been lowered from a Schedule 1 drug to a Schedule 2 drug, there may be future advancements for other Schedule 1 drugs?

According to Gov.uk, all handling of Schedule 1 drugs requires a home office license, both in academia and industry. Realistically, therapeutic benefits can only be appropriately explored during clinical trials (after required research). However, on top of a Home Office license, clinical trials would require HRA and MHRA approval. These requirements are appropriate in terms of the high risks associated with Schedule 1 drugs but can also introduce some roadblocks in terms of exploring their therapeutic benefits; the costs and time constraints can be detrimental to the study before it even starts.

It is important to note that some Schedule 1 drugs, notably cocaine, are likely to have a negative therapeutic benefit. Cocaine, as discussed by Joseph Pergolizzi et al. (https://doi.org/10.7759/cureus.14594), has cardiotoxic effects (especially due to increased blood pressure) which can lead to heart failure or myocardial infarction in certain situations. Over time, it has been noted that cocaine can cause permanent structural damage to the heart such as increasing the size of the left ventricular wall. This growth ultimately leads to the death of heart tissue due to increased oxygen demand and essentially will be a recipe for disaster.

In opioid-dependant patients, it is well-known that methadone and buprenorphine can be prescribed as a treatment. Opioid dependance has always been an issue of great importance, potentially being the cause death in many patients around the world, not only in the UK. In every pharmacy that I have worked in, there have been "blue-script patients" who either have a frequent prescription of methadone (Schedule 2) or buprenorphine (Schedule 3). However, in some rare cases where other treatment options have failed for 3-6 months, heroin (Schedule 1) has been used as a treatment for opioid dependant patients. This is discussed in a journal article written by Nicholas Lintzeris (https://doi.org/10.2165/00023210-200923060-00002), and was very surprising to me. Heroin has been available as a prescription drug (under specific conditions) in the UK for around 50 years, with Switzerland opening specialist heroin clinics in the 1990s. However, when compared to methadone treatment in clinical trials, there are mixed reviews with some saying methadone yields better results, some saying heroin yields better results, and some saying there is no difference between either treatment. Nevertheless, it is something to consider in terms of opioid-dependence treatment and further exploration could be beneficial.

One particular use of Schedule 1 drugs, and the last one that I will be discussing, is the use of certain substances for mental health conditions as discussed by Collin Reiff et al. (https://doi.org/10.1176/appi.ajp.2019.19010035). In 1943, Albert Hofman, a Swiss chemist, initially synthesised LSD, and it was briefly used as a psychotherapy medication. In 1960, Timothy Leary experimented with psilocybin in the US as an adjunct for psychotherapy. Ultimately, public use of both substances were prohibited and experimental clinical trials were banned, especially due to the upcoming 'War on Drugs'. Recently however, clinical trials surrounding LSD and psilocybin have faced a resurgence, with many self-medicating themselves with these hallucinogenic drugs, similarly to with cannabis. Psilocybin has been experimentally used in clinical trials for treating end-of-life depression, anxiety and mood disorders, and as mentioned in the aforementioned journal (which is definitely worth a read), there are current attempts in the US to investigate psilocybin as a legitimate treatment. LSD, which has the ability to produce even more powerful psychedelic experiences, alongside being explored as an end-of life depression treatment, is also being explored as a treatment for PTSD.

The most recent Schedule 1 substance which has been progressively talked about online and in the real world is ayahuasca. Although it has been used by people in the Amazon region, it has only recently been talked about in the Western world. Often, celebrities and influencers discuss their experiences with ayahuasca. Most recently, Catherine Paiz has released a book and a series of videos discussing her frequent ayahuasca use and how it has helped her overcome her depression and self-hatred. Pharmacologically, ayahuasca contains DMT which can cause auditory and/or visual hallucinations, mystical experiences and euphoria, similarly to LSD and psilocybin. An important thing to note with ayahuasca is the fact that it's ingredients are not specifically confirmed; additional compounds have been added as the use of the substance has broadened and therefore, there is not enough sufficient data to standardise ayahuasca for clinical trials.

In all the aforementioned drugs, it is crucial to recognise that although some therapeutics benefits are being explored to an extent, there is still uncertainty about their benefits or toxicity. Clinical trials take many years and many trials until a conclusion can be made: therapeutic potential does not guarantee therapeutic approval. Clinical trials require time, funding, and rigorous evidence to validate safety and efficacy.

Personally, I’ve gained a deeper appreciation for the ethical and legal considerations involved in researching Schedule 1 drugs. This evolving knowledge base will guide me in future pharmacy practice as new therapies continue to emerge.