About six months ago, the Dutch minister of Health, Ernst Kuipers, wrote an official response towards the Dutch parliament after receiving a report on psychedelic-assisted therapy (PAT). This report was commissioned by the Dutch funding organisation ZonMw. It provided a first overview of the current state of affairs of PAT in the Netherlands. According to Kuipers in an earlier blog post, the ZonMw report provided “a significant contribution to the conversation about PAT and decisions about future steps.”
Kuipers exhibited a healthy dose of enthusiasm towards PAT as a potential innovative treatment for treatment-resistant psychiatric disorders. But he also recognised various challenges when moving towards the ultimate legislation of psychedelics as medicine. Kuipers was not alone in this. Indeed, four political parties of the Dutch House of parliament, in particular VVD, D66, CDA, and PvdA/GroenLinks, responded to Kuipers’ letter and raised several questions.
Psychedelics as Medicine
PvdA/GroenLinks, for example, were happy to see that the minister was positive towards future research of PAT and its ultimate implementation. In addition, PvdA/GroenLinks understood from reading Kuipers’ response that he was “encouraging university medical centres and special health care institutions to work together within a national cooperation to conduct the necessary scientific research.” Such an endeavour would allow for the collection of information in a structured and coordinated manner that could in turn evaluate the quality, efficacy, and safety of PAT. However, the party members of PvdA/GroenLinks did wonder what this “encouraging” essentially means by asking “in what way the minister is going to support this?”
In response, Kuipers announced that he will provide 1.6 million euros for future research on PAT in the Netherlands. This will be a grant proposal within the Dutch grant organisation ZonMw. Kuipers: “The program is targeted at the development of new medications and, in the event of positive results, to the registration of one or more medications. Funding will be used to set up an overarching partnership, draw up a development plan by the partnership for registering and marketing one or more medications and/or indication areas. The program will primarily be focused on carrying out clinical research.”
Hopefully, the clinical research studies will also determine the potential long-term effects of PAT. Indeed, political party VVD already raised concerns about this unknown in their response to Kuipers’ letter and wanted to know “which studies are already being conducted on the long-term effects of PAT.” Kuipers responded to this question by referring to the websites of CCMO and ClinicalTrials.gov where all scientific research is listed. In addition to this, I highly recommend the Atlas of Psychedelic Research where you can find any current study on PAT filtered by phase, topic, and psychedelic substance.
On the Taboo Against Knowing What Psychedelics Are
Now all of this is great news of course. But some parties also recognise the multitude of barriers scientists have to confront when trying to conduct clinical research on PAT. According to D66, for example, there still rests “a taboo on psychedelics” that can have “a negative effect on the potential for developing new treatments.” Not surprisingly, D66 raised the question to Kuipers “what plans the minister has to diminish this taboo?” and whether he could “present an overview of which conversations or campaigns are taking place or in what other way information is provided to combat this taboo?”
The round table discussion about PAT, which took place within the Dutch parliament on October 13th, 2022, is one example given by D66 that provided a lot of new information and potentially led to more understanding of PAT. Kuipers agrees that “increasing the amount of knowledge can contribute to the acceptance of these new types of treatments” and adds that “it is important that in the future psychedelics are seen as medical applications, not as drugs, and that this view is shared amongst professionals, patients and the general public.” The research program within ZonMw can be a first step in diminishing the taboo on psychedelics, says Kuipers.
Kuipers continues that there are a lot of substances that are on the so-called Dutch ‘Opiumwet’ but are used as medicines. These include opioid medications for individuals struggling with pain or the use of Ritalin for ADHD. “Psychedelics are no exception in this”, says Kuipers. Yet, because psychedelic substances are illegal and on the list of the ‘Opiumwet’ remains a problem for researchers. Indeed, to do any clinical research at all, you have to receive an exemption from the Dutch government with a decision period of approximately three months. And if you manage to do this, you then must face the next hurdle at the CCMO and apply for ethical approval that can take up to one year (if you’re lucky!).
Finally, the political party CDA wondered “if research using psychedelics as medicine were promising, wouldn’t there be full commercial interest in financing?” Indeed, authors from the aforementioned ZonMw report already indicated that there are problems with the funding of psychedelic research because of the lack of commercial interest. I have asked this question myself many times and was happy to see a Dutch political party came to the same conundrum. Kuipers clear in his response and stated that “pharmaceutical companies have little incentive to focus on this market, partly because most drugs can no longer be patented. Only through chemical modifications or new methods of administration is it possible to obtain a patent, such as with Janssen’s esketamine nasal spray.”
Don’t Believe the Media Hype
Across the political spectrum, Dutch political parties raised their concerns regarding the potential self-experimentation with psychedelics due to increased media exposure. VVD, for example, highlighted that “increased media attention can lead to an increase in non-medical use. The hype that raises too high expectations regarding PAT and that people with a mental illness do not want to wait for PAT to be approved and start experimenting themselves is something that worries the members of the VVD faction.” Similarly, D66 recognises “the danger of self-experimentation with psychedelics and acknowledges this as a political signal to get psychedelics within regular healthcare as fast as possible, while simultaneously maintaining caution.” Both parties CDA and PvdA/GroenLinks shared similar concerns and acknowledge the risk of new groups of users with severe psychological issues that essentially require education, prevention, and the improvement of harm reduction measures. After all, psychedelic substances, let alone their therapeutic use, remain out of reach for a lot of patients who are in dire need of treatment.
Kuipers general response is that the ZonMw of 1.6 million euros should help mitigate these concerns, in particular regarding the urgent need to register psychedelics as a medication. In addition, Kuipers has commissioned both ‘Stichting Mainline’ and the ‘Trimbos Instituut’ to conduct an investigation that is aimed at obtaining more insight into the various (new) user groups of psychedelics and reasons for (non-medical) use. What is more, this investigation includes an evaluation of whether the current education is not already appropriate for these groups, but also to develop new (online and offline) information material about psychedelics together with prevention of risks and limitation of harm when these compounds are used. Kuipers concludes that “this investigation will be completed before the summer of 2024 and a report will be send towards the Dutch parliament.” It would be interesting to see whether the results from this investigation also shed light on the ‘imprinting’ phenomenon, where environmental influences from the past are able to shape the psychedelic experience.
In any case, the fact that there is already a lot of information available on the internet is hopeful. For example, Kuipers refers to the website of the Trimbos Instituut that has “released a factsheet [of 26 pages] about PAT that details the various mechanisms of psychedelics and the potential risks.” In addition, Kuipers mentions the website www.drugsinfo.nl which has added four pages all dedicated to the inner workings of PAT. And, last but certainly not least, the National Drugs Monitor of the Trimbos Instituut will monitor the non-medical use of psychedelics in the Netherlands. Here, Kuipers mentions in brief that “the recreational use of psychedelics is below 1% and for MDMA/ecstasy this was 3.9% in 2022.”
Building the Infrastructure of Psychedelic-Assisted Therapy on Rock ‘n Roll
Another concern was raised by both the VDD and PvdA/GroenLinks regarding the infrastructure of PAT. For example, VVD said mentions that “the minister stated [in the ZonMw report] that there is no infrastructure for PAT training yet and that he is in consultation with the Dutch Psychiatry Association (NVvP) about this.” This is a good sign, but VVD was left with some questions: “How does the minister include the NVvP in the entire process to provide training regarding PAT? When will there be more implementation? Are others involved in the training?”
The political party PvdA/GroenLinks first announced that they “are happy with the ‘Platform Psychedelica’,” which was founded to accommodate the discussion about the possible applications of PAT within the NVvP. Similar to VVD, the political party wondered “what additional steps the minister is going to take in creating an infrastructure for training for PAT as was already recommended by the authors of the ZonMw report?”
To both questions, Kuipers reiterates that “it is up to the NVvP to develop and implement training requirements for additional training in PAT in collaboration with other parties. The Dutch ministry of Health, Welfare, and Sport has an advisory role and, where necessary, facilitates with other parties. This includes the Dutch Institute of Psychologists (NIP) and patient associations.”
On the Varieties of Ketamine Formulations
There were also some questions about the atypical psychedelic ketamine. VDD, for instance, asked whether Kuipers is able to provide “an overview of the different types of ketamine and for which treatments they are and are not registered?” to which Kuipers simply referred to the website Medicines Evaluation Board (CBG/MEB) that contains all registered medications in the Netherlands.
The party of VVD agrees that “compassionate use is subject to strict rules, but also notice that oral ketamine is currently applied as off-label while a registered variant is already available.” This variant that the VVD is referring to is Spravato, which is a nasal formulation of ketamine approved for treatment-resistant depression. The off-label use of oral ketamine, however, is not yet registered, but can be used in this way “as long it meets the criteria for off-label use” says Kuipers. These criteria that ‘compassionate use’ has to meet are set up by the CBG/MEB. At this moment, Kuipers mentions that “the funding program ‘veelbelovende zorg’ subsidizes research into the (off-label) oral formulation of esketamine for the treatment of patients with severe, non-psychotic, treatment-resistant depression.”
In addition to oral esketamine, PvdA/GroenLinks were also curious about “the current status and availability of the nasal formulation of esketamine (Spravato) for patients with a severe treatment-resistant depression.” In particular, the party wanted to know “how many actual treatments there currently are with Spravato?” and whether “the contracts between healthcare providers and health insurances are well set up?” Kuipers responded by presenting the current state of affairs in the Netherlands. “Currently, there are 17 active locations centres in which nasal esketamine is provided. Kuipers expectation is that there will be 4 extra centres in the upcoming months. As of 2023, there were more than 30 healthcare providers with a contract, but within the budget only 12 of them have made an invoice. Organizing the healthcare of providing esketamine nasal spray for treatment-resistant depression takes time, because the criteria must be met in terms of facilities, staff, and participation in national research. This means that some centres have been contracted but are not yet active. A careful approach to implementation and good coordination with centres that are already operational and have thus gained experience are considered valuable.”
A First Step towards the Legislation of Psychedelic-Assisted Therapy
As stated almost two years ago by Kuipers, the Netherlands should be at the forefront of psychedelic research. Indeed, D66 recognises that the Netherlands “is in an excellent position to play a leading role internationally in research and implementation of PAT” but is also somewhat concerned. At the same time, D66 “sees that developments are happening very quickly in other countries” and wonders whether “the Netherlands risks to walk behind other countries? What is needed to actually capitalize on that leading role?”
Kuipers confirms that on a global scale “there have indeed been many developments in the field of research, but so far PAT has not yet been accepted as a registered treatment by pharmaceutical authorities.” However, there are countries, such as Australia and Switzerland, that provide PAT on a limited scale through a form of compassionate use. Moreover, in three states of the US the use of psychedelics is regulated within a therapeutic setting. Other developments from the past year come from Canada, where the government has invested nearly 3 million dollars in clinical research of PAT involving psilocybin for the potential treatment of alcohol use disorder, treatment-resistant depression, and end-of-life distress in cancer patients.
Essentially, Kuipers agrees with D66 that “the Netherlands has an excellent starting position to play a pioneering role alongside these other countries. The Dutch mental health care system has the infrastructure for this with highly trained professionals and the high-quality amount of research that is being conducted. More investments have to be made in a coordinated approach to research and implementation.”
One week following this back and forth between Dutch politicians, minister Kuipers wrote an official letter to the chair of Dutch parliament on December 19th. Specifically, the minister reiterated his concerns regarding the unmet medical need in a large group of patients that are currently unable to receive treatment. This is simply due to a lack of availability in effective medications for this particular group. Accordingly, Kuipers states that he “wants more control on medicine development.” This claim to responsibility and research policy is partly in response to an earlier research rapport concluding “that a drug’s expected financial return ultimately determines whether it is developed up to launch.” According to Kuipers and another study, “psychedelics are the most promising” for meeting the unmet medical needs of patients with depression, but that “pharmaceutical companies lack interest for this market because most substances cannot be patented.”
Ultimately, the ZonMw grant of 1.6 million dollars will aid Netherlands’ pioneering role and to establish a national cooperation for conducting coordinated clinical research. This will bring us one step closer to the registration of psychedelics as medicine and the implementation of PAT within general healthcare.
Image credit: D66.nl
