Stigma in drug research holding back new therapies

Therapy is turning to drugs previously known for being illicit party substances. But there’s no reason to abandon proper trials.

A range of new therapies for mental illness were previously considered unthinkable — party drugs including ketamine, medicinal cannabis and psychedelics like MDMA, psilocybin and DMT. With mental health disorders a growing cause of disability in our communities, the need is acute. But the question is whether the desire for new approaches will see shortcuts from the usual process of trialling and regulating drugs. All medicines require careful examination of efficacy and safety prior to being used publicly. A healthy balance between caution and need can avoid missing important opportunities for new treatments. A process that enables scientists to investigate medicines safely needs a structured approach supported by research bodies and national regulators to allow for the development of new therapies whilst safeguarding patients.

Typically this process involves multiple phases of clinical trials before wide release. These trials will initially demonstrate safety, establish efficacy, dosing and place in therapy. All trials will need ethical approval, informed consent and independent analysis before regulators would consider broad approval. Early consultation between researchers and regulators may be useful in establishing what trials are needed to establish the appropriate place in therapy and safety.

Party drugs have been around for decades, and some psychedelics have been around for centuries – they are not new. But their use in clinical practice is. As therapy, they still require evaluation with clear ethical frameworks and standard research practice.

Each of these new therapies has a proposed rationale for its utility. Ketamine and its molecular sister esketamine increase the effect of glutamate, the most widespread natural chemical stimulant in the brain. Cannabis binds to a series of receptors for its active ingredients, tetrahydrocannabinol and cannabidiol existent in the brain. Psychedelics are known to act on multiple brain chemistry systems which can create altered states of the mind. In psychotherapy, this has been harnessed to achieve mental breakthroughs. The availability of medicinal cannabis is an example of the need for careful evaluation before releasing to the open market. Medicinal cannabis has become more widely available based on evidence supporting its use in chronic pain and some forms of severe epilepsy. But it has also been touted as a treatment for a range of mental health conditions despite little quality evidence.

Careful research is beginning to show that cannabidiol, one of the components of cannabis, may have benefits for anxiety. But the production of medicinal cannabis in Australia, and its regulation, are inconsistent. It appears not to be subject to the same regulations of promotion as traditional medicines produced by large pharmaceutical companies and must abide by strict national regulations, particularly on claims of its medicinal benefits. It’s not clear why these compounds should be treated differently and their high promotion has created a risk that ineffective treatments will be trialled, and more effective ones delayed. That is, a compound with inadequate evidence that may not be efficacious will be used by an individual first in preference to established treatments with known efficacy. Delayed treatment of mental illness is generally seen as associated with worse outcomes.

The use and regulation of ketamine and psychedelics for medical purposes are also complex. The misuse of LSD in some pockets of mental health care in the 1960s has established a stigma about the potential for substance abuse. This perception has been difficult to correct even with evidence from trials showing the risks of abuse are very low, especially in carefully monitored environments. As a researcher these challenges create tension around involvement in this area; do I want my name or reputation associated with an area that may bring criticism and potentially be difficult to fund? This area can also easily be confused with the purported benefits of psychedelics in enhancing normal thinking and creativity. It’s the contemporary equivalent of 1960s psychologist Timothy Leary’s famous phrase “turn on, tune in, drop out”. The main purpose of research should focus on its treatment abilities, looking at its applications and whether it’s safe and effective. The history of medicine, including mental health, is replete with examples where treatments have been hastily greeted and trumpeted before careful evaluation has occurred with significant human cost, such as the historical use of insulin coma, malarial therapy in mental health or thalidomide in more recent medical care.

And while some harbour hopes that such long-established drugs will be free of the conflicts of interest often alleged of large traditional pharmaceutical companies, this is not automatically valid. All pharmacological health treatments are invented, produced and marketed by someone who is likely to have personal and financial interest in its widespread use.

Stigma in all its forms has long surrounded mental illness and its treatments. A great deal of evidence tells us that stigma leads to a risk of poor practice and further suffering. In this area, the stigma of both mental illness and research into illicit drugs threatens to impede research into whether or not these drugs have uses in the treatment of mental health. The emphasis is to place value on mental health research long given to other areas of health research, such as oncology. Research into new therapies for mental health needs to be funded in proportion to the disability that mental illness causes — whether or not they once party drugs. And only a good process will enable us to find the therapies we sorely need.