Psychedelic research has been associated with the Czech Republic since the early 19th century and, after a long period of involuntary dormancy, it has recently gained new opportunities to follow up on its roots and evolve. This article briefly describes the history of psychedelic research in the Czech Republic, summarizes the role of the UN Drug Conventions, and discusses the Czech and international legislation pertaining to psychedelics. The discussion focuses on the dependence/abuse potential of classical psychedelics, their medical use, and their safety in medical versus non-medical environment. Despite the assertions of the UN and occasional media disinformation about the dangers of psychedelics, recent investigations have shown that classical psychedelics are not addictive, show great promise in a broad spectrum of medical uses, and have been repeatedly proven to be safe in a clinical setting. Finally, the authors suggest a procedure for the preparation and implementation of controlled psychedelic therapy in the Czech medical and legal system.

Introduction The so-called classical psychedelics, or serotonergic hallucinogens, include mainly lysergic acid diethylamide (LSD), psilocybin, mescaline, dimethyltryptamine (DMT), and methoxy-N,N-dimethyltryptamine (5-MeO-DMT). Serotonergic hallucinogens are a subgroup of three classes of compounds: tryptamines, ergolines, and phenethylamines, of which the latter group also includes the so-called entactogens/empathogens (MDMA or 2C-B). In a broader context, the hallucinogen class could also include a selective kappa-opioid agonist salvinorin A found in Salvia divinorum, dissociative anesthetics (ketamine), cholinergic delirogens (tropane alkaloids and their plant sources such as datura or deadly nightshade), and sometimes also cannabis (marijuana and hashish). This article only discusses serotonergic hallucinogens, which will be referred to as psychedelics. Naturally occurring psychedelics have been associated with various human societies since time immemorial. The ritual use of psychedelics has been preserved to the present times mostly in native South American tribes, typically in various naturally occurring forms (DMT in the hallucinogenic brew ayahuasca, psilocybin in magic mushrooms, mescaline in cacti, 5-MeO-DMT in the venom of hallucinogenic toads). The discovery of psychedelics by Western society in the 20th century sparked a surge of extensive research, mainly due to their potential in the treatment of psychiatric disorders, which showed great promise (Tylš, Páleníček, & Horáček, 2014). During that time, the Czech Republic was one of the focal points of psychedelic research. First self-experiments with psychotropic substances were conducted and later reported by Purkyně in early 19th century, namely with the deadly nightshade, nutmeg, opium, and other substances. In 1947, psychiatrist Světozar Nevole published a book recounting his experiences with peyote and its ability to expand consciousness, significantly inspiring many other Czech physicians including Stanislav Grof [American psychiatrist born in Prague, founder of transpersonal psychology. With his wife Christina, he developed the Holotropic Breathwork method and wrote several books about spiritual emergency. His famous works include LSD Psychotherapy (1980) or The Cosmic Game: Explorations of the Frontiers of Human Consciousness (1998)] or Milan Hausner (Czech psychiatrist who administered LSD to patients as part of psychotherapy in a psychiatric hospital in Sadská in the 1970s. He wrote a book named LSD: The Highway to Mental Health with Erna Segal; Winkler & Csémy, 2014). In addition, psychiatrist Roubíček (1961) started to self-experiment with LSD shortly after its discovery by Albert Hofmann. Psychedelic therapy in the Czech Republic started in 1954 and ended in 1974, making the country one of the very last to introduce the spreading ban on psychedelics, which effectively halted the research for many years. The main research sites included the Psychiatric Hospital in Sadská near Poděbrady and the Psychiatric Research Institute in Prague. In these institutions, hundreds of research subject underwent psycholytic and psychedelic therapy and Dr. Hausner personally conducted over 3,000 psychedelic sessions in the Sadská Hospital. Self-experimentation with psychedelics was an official part of psychedelic-assisted psychotherapy training, requiring five controlled LSD (or occasionally psilocybin) intoxications (Hausner & Segal, 2016). In the 1960s, psychedelics started to gain significant popularity among the general public, mainly in the USA, and brought about a surge of panic in the rigid society of the time also due to their ability to affect the individual’s value system. Politically motivated prohibition, the so-called War on Drugs [The War on Drugs was another unsuccessful prohibition campaign (Austin & McVey, 1989; Blocker, 2006), directed against an inanimate object that has no agency of its own.], supported by the media, gradually led to a worldwide ban on selected psychedelics. During the entire duration of the ban, psychedelics were widely used by the alternative culture with relatively minimal negative effects on mental health (Krebs & Johansen, 2013). In the scientific community, however, the discussion of the potential uses of psychedelics in the treatment of a broad spectrum of psychiatric disorder has been gaining more and more attention – from depression, post-traumatic stress disorder and obsessive–compulsive disorder (OCD) to addictions. Furthermore, psychedelics can be used as a tool for the study of severe psychiatric illnesses such as schizophrenia (Geyer & Vollenweider, 2008) or the unconscious processes that underlie various neurotic spectrum disorders (Viktorinová & Tylš, 2016). The Czech Republic remains in the forefront of psychedelic science even today – the Czech National Institute of Mental Health is currently conducting a clinical trial on psilocybin as a model of psychosis. To date, psilocybin has been administered to 20 healthy volunteers (Bravermanová et al., 2018). Moreover, a new multicenter research sponsored by Compass Pathways will study the use of psilocybin in a new sample of patients with treatment-resistant depression. This review focuses on the legal, social, and medical status of psychedelics in research and therapy in the Czech context, aiming to illustrate the dysfunctional nature of the contemporary system of substance control and to reevaluate the current legislative position of psychedelics in light of the most recent scientific findings. Its goals include opening the discussion on the possibility of facilitating new psychedelic research and helping it reach the depths it needs to present the therapeutic and self-developmental potential of these substances to the professional public.

Current Position of Psychedelics in the Czech Republic The Parties, Being concerned with the health and welfare of mankind, Noting with concern the public health and social problems resulting from the abuse of certain psychotropic substances, Determined to prevent and combat abuse of such substances and the illicit traffic to which it gives rise, Considering that rigorous measures are necessary to restrict the use of such substances to legitimate purposes, Recognizing that the use of psychotropic substances for medical and scientific purposes is indispensable and that their availability for such purposes should not be unduly restricted, (…) (Preamble to the Convention on Psychotropic Substances, 1971) The Code of Ethics of the Czech Medical Chamber instructs physicians that they should freely choose and perform preventative, diagnostic, and therapeutic procedures that comply with the present state of medical science and that they consider appropriate for the patient, in accordance with their professional qualification and competence (provisions of Section 2 of the professional directive of the Czech Medical Chamber – The Code of Ethics of the Czech Medical Chamber). The Charter of Fundamental Rights and Freedoms, one of the cornerstones of the Czech legal system, guarantees the freedom of scholarly research (Article 15 of the Constitutional Act No. 2/1993 Coll. as amended by Constitutional Act No. 162/1998 Coll.). The authors of this paper are of the opinion that it is necessary to update the current legal framework, which reflects a stigmatized approach toward psychedelics, because recent studies have shown that psychedelics have a positive effect on patients with certain psychiatric disorders, particularly in cases where other treatment modalities fail. The current legal framework hampers the introduction of psychedelics into medicine in various direct and indirect ways. As a member of the UN, the Czech Republic is bound as any other UN countries by three conventions – Single Convention on Narcotic Drugs, 1961; Convention on psychotropic substances, 1971; and Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances from 1988 (Figure 1). These conventions also govern all member states of the European Union and the list of substances includes four basic groups divided according to their safety and therapeutic utility. Classical psychedelics are listed in Schedule 1, which is, according to the UN Commission on Narcotics, defined as a group of substances that pose a great risk to society and have no therapeutic potential. Despite this claim, certain UN member countries have successfully used Schedule 1 substances in research and therapy [Czech Republic (LSD; e.g., Crockford, 2007), Switzerland (MDMA, LSD, psilocybin, 2C-B; e.g., Fischer, 2015), UK (psilocybin; e.g., Carhart-Harris et al., 2016), Peru, Columbia, Brazil [ayahuasca, used for thousands of years by shamans as medicine for various ailments, has been recognized as the cultural heritage of Peru and Columbia, and its use within the shamanic practice is therefore protected by the state. Later, Brazil permitted the use of ayahuasca to the practitioners of two religions: Santo Daime and União de Vegetal (Kavenská & Simonová, 2014)], USA [psilocybin; e.g., – (a) Bogenschutz et al., 2015; (b) Grob et al., 2011; (c) Johnson, Garcia-Romeu, Cosimano, & Griffiths, 2014; MDMA, e.g., Mithoefer, Wagner, Mithoefer, Jerome, & Doblin, 2011; complete history of the use of psychedelics in psychotherapy from 1931 to 1995 in Passie, 1997], introduced decriminalization and controlled sales [Netherlands (https://www.government.nl/topics/drugs/contents/toleration-policy-regarding-soft-drugs-and-coffee-shops), Spain, Sri Lanka, and Uruguay] and some have even legalized these substances for medical [Marijuana legalized for medicinal use – Argentina, certain Australian states, Canada, Chile, Colombia, Croatia, Cyprus, Czech Republic, Denmark, Finland, Germany, Greece, Israel, Italy, Jamaica, Luxembourg, Malta, Macedonia, Netherlands, Norway, Peru, Poland, Portugal, Puerto Rico, San Marino, South Africa, Spain, Sri Lanka, Switzerland, Turkey, UK, Uruguay, certain states in the USA, Vanuatu, Zimbabwe (as of November 27, 2018)] as well as recreational use [The recreational use and the possession of marijuana for personal use is legal or decriminalized – either completely or below specific quantities – in Antigua and Barbuda, Argentina, certain states or territories of Australia, Austria, Belgium, Belize, Bolivia, Brazil, Canada, Chile, Costa Rica, Croatia, Czech Republic, Ecuador, Estonia, Georgia, certain states of India, Italy, Jamaica, Luxembourg, Malta, Mexico, Moldova, Netherlands, Paraguay, Peru, Portugal, Russia, Uruguay, Slovenia, South Africa, Spain, Sri Lanka, Switzerland, Columbia, and certain states and cities in the USA (as of November 27, 2018).], since the time these conventions came into effect. Figure 1. Download Figure

Download figure as PowerPoint slide International UN conventions on narcotic and psychotropic substances and their relation to the drug laws in the Czech Republic and elsewhere. Green color boxes represent conventions, laws, and regulations that are directly related to psychedelics, and yellow box the laws that are directly related to psychedelics, stem from the UN conventions on narcotic and psychotropic substances, but do not affect Czech drug legislation. The yellow list, accompanying the Single Convention on Narcotic Drugs, contains the current list of controlled narcotic substances, and the green list, which is based on the Convention on Psychotropic Substances, contains the up-to-date list of controlled psychotropic substances Citation: Journal of Psychedelic Studies 3, 1; 10.1556/2054.2019.003 Even though Schedule 1 substances from the Convention on psychotropic substances are considered the most strictly controlled, they still should be available for medical and research purposes as the convention itself in Article 7, stipulates a unified regulatory framework, which among other things includes a recommendation for member states to prohibit all use except for scientific and very limited medical purposes by duly authorized persons, in medical or scientific establishments which are directly under the control of their Governments or specifically approved by them (https://www.unodc.org/pdf/convention_1971_en.pdf, p. 6). In the Czech Republic, this issue is further covered by the Government Regulation 463/2013 Coll. on the lists of addictive substances (the “Government Regulation on Addictive Substances”), which classifies DMT, LSD, MDMA, psilocybin, and others into List no. 4, which is equivalent to the aforementioned Schedule 1 of the UN Convention on Psychotropic Substances and the US Controlled Substances Act (Figure 2; http://www.fda.gov/regulatoryinformation/legislation/ucm148726.htm). It stipulates that these substances should only be “used for limited purposes of research and science and very limited therapeutic purposes specified in the handling permit” (https://www.zakonyprolidi.cz/cs/2013-463#f5150334). However, this benevolence has its limits, as determined by the Ministry of Health, which issues the authorization for the production, import, export, and handling of narcotic and psychotropic substances, and by the State Institute for Drug Control, which is authorized to issue certificates confirming compliance with good manufacture practice (GMP) standards [GMP is a quality management system in pharmaceutical manufacturing. It works to protect the consumer market from medicinal products, which are of unsatisfactory quality or are not suitable for the intended application. Legislative framework: Act no. 79/1997 Coll. as amended by Act no. 269/2003 Coll. as subsequently amended; Directives 2003/94/EC, 2004/27/EC and 2004/28/EC; ICH Q7 guidelines (for EU, USA, and Japan). GMP guidelines are detailed in the Ordinance of the Ministry of Health no. 411/2004 Coll. and the EU document “Good Manufacturing Practice” in Volume 4 of the rules governing medicinal products in the European Union (Czech translation in SÚKL Directive VYR-32 published in Věstník SÚKL č. 2/2006)], good distribution practice, good clinical practice, good pharmaceutical practice, and good practice of restricted medicine sales. Figure 2. Download Figure

Download figure as PowerPoint slide Conventions, laws and regulations that contain lists of narcotic and psychotropic substances. Green color boxes represent regulations that are directly related to psychedelics, yellow boxes the laws and their segments that are directly related to psychedelics but do not affect Czech drug legislation. The Government Regulation no. 463/2013 Coll. contains the lists of narcotic and psychotropic substances and comprises the yellow list and the green list, which reflect international drugs conventions. The US Controlled Substances Act is also based on international conventions and it contains substance lists and applicable laws that govern the handling of controlled substances. It also provides the rationale for substance scheduling. However, this system is not applicable or enforceable in the Czech Republic Citation: Journal of Psychedelic Studies 3, 1; 10.1556/2054.2019.003 Due to numerous legislative and administrative setbacks that impede the research of psychedelics and the tendency to demonize these substances in Europe and elsewhere in the world, the scientific community often lacks the pharmaceutical dosage forms necessary for research and therapy. Apart from the psychotropic substances handling permit (conditions for applicants are listed in Sections 4, 8, and 9 of Act no. 167/1998 Coll. on addictive substances as amended; hereinafter the “Act on Addictive Substances”), which is fully dependent on the decision of the Ministry of Health and is not legally enforceable (Section 8, paragraph 1 of the aforementioned act), the sponsor also needs to procure a supplier with the same permit, willing to manufacture the given substance for the purposes of the research. Moreover, the manufacturer is also required to have a certificate on GMPs for narcotic and psychotropic drugs issued by the Czech Institute for Drug Control. At this point, there is no such manufacturer for classical psychedelics in the Czech Republic (negotiations with potential manufacturers located in the Czech Republic are currently underway.). At present, the only way to obtain a psychedelic substance for a research project is to import it from another country that manufactures. Each individual import of Group 4 substances also requires an authorization by the Ministry of Health based on the provisions of Section 22 of the Act on Addictive Substances. Import of course substantially increases the price of the preparation and research costs in general.

Proposed Solution for the Current Situation in the Czech Republic and the World The question remains: How is it possible that psychedelics – substances that have been used by humans for millennia, be it as medicines or tools for spiritual enlightenment – are not available in the Western society? Tomáš Páleníček, head of psychedelic research in the Czech National Institute of Mental Health, claims that one of the main obstacles is the current classification of psychedelics among substances without therapeutic utility (personal correspondence). It would therefore be advisable to take the steps necessary in order to reclassify these substances into another schedule (with medicinal use). This process should start at the level of scientific research, but it also needs to incorporate the education of the general public, while both levels should use correct and consistent terminology and adhere to a common procedure in order to facilitate such changes in the future as effectively as possible. If we choose a particular psychedelic substance as a prospective medicinal product, we can align research interests with the application for marketing authorization of a new medicinal product. One option is to conduct a clinical trial of a non-authorized medicinal product pursuant to Section 51–59 of Act no. 378/2007 Coll. on pharmaceuticals and on amendments to some related acts (“Act on Pharmaceuticals”). Such clinical trials are subject to approval by the Czech State Institute for Drug Control (“SÚKL”) and an ethics committee appointed by the healthcare provider or the Ministry of Health. Clinical trials of non-authorized medicinal products, preclinical trials, and pharmaceutical safety trials (Section 26 of Act no. 378/2007 Coll.) are a prerequisite for obtaining a marketing authorization for any new medicinal product in the Czech Republic. In order to perform these trials, a certified supplier of the investigational product is needed as well; moreover, for Schedule 4 substances, both the research team and the supplier need a handling permit. Upon successful completion of the clinical trial, it is possible to file an application for marketing authorization of the medicinal product in a specific pharmaceutical formulation pursuant to Act no. 228/2008 Coll. on the marketing authorization of medicinal products, which defines the steps and documents required for such an application. Successfully completed authorizations can also be processed by way of the mutual recognition procedure from other member countries of the EU in accordance with Section 44 of the Act on Pharmaceuticals. If the psychedelic substance succeeds in obtaining marketing authorization pursuant to Section 39 of the Act on Pharmaceuticals, which introduces the classification of human medicinal products for the dispensing and sale of designated pharmaceuticals, the Ministry of Health determines whether the medicinal product will be available by prescription only, by restricted prescription only, or without prescription (“over the counter”). This would require reclassification of the given substance into a schedule of substances available by prescription, as currently no Schedule 4 drug can be made available by prescription or sold over the counter in pharmacies. Relevant indications – such as treatment-resistant depression (in this particular case it is, moreover, necessary to further specify the diagnostic criteria for this condition), OCD, anxiety associated with terminal illness, addiction, and others – should be specified in the application for marketing authorization as well. Another necessary step is to create a list of medical professions authorized to handle such medicinal products. The authors are of the opinion that the requirements should include expertise in clinical psychiatry as well as in psychotherapy due to the specifics of psychedelic treatment. These areas of expertise could be provided by multiple persons within one team. The presence of a clinical psychiatrist appears to be beneficial mainly due to the necessity of evaluating potential risks during the screening phase, but also in order to allow for pharmacological intervention in the event of serious adverse effects (e.g., administering an antihypertensive or an anxiolytic). Psychedelics should be available by restricted prescription only and prescription should be limited to certified psychiatrists. The presence of an experienced psychotherapist is essential and the requirements should include a completed certified psychotherapy training of a non-directive, dynamic modality, and a specialized follow-up certification in psychedelic-assisted psychotherapy, accredited by the Ministry of Health. There is no such certification in the Czech Republic to date, but any future efforts could draw inspiration from the program of Psychedelic-assisted Therapy and Research at the California Institute of Integral Studies, which has been started in 2016 and is currently the only one of its kind in the world. The Swiss Medical Society for Psycholytic Therapy is currently preparing a similar training. Another important issue is to secure the supply of these substances, logistically as well as economically, that is, to find or establish a laboratory with the capacity to produce psilocybin for human use in accordance with applicable law, to arrange for appropriate distribution and availability in pharmacies, decide on an adequate price for the medicinal product, and possibly negotiate potential coverage with health insurance companies. At this point, more preclinical and pharmaceutical trials of psilocybin are still needed. Furthermore, certain documents required for the application for marketing authorization of psilocybin as a medicinal product need to be drafted and submitted to SÚKL (the requirements are listed in Section 26 of the Act on Pharmaceuticals or on SÚKL’s website). One clinical trial with psilocybin is already underway at the Czech National Institute of Mental Health, led by Dr Páleníček and his team. In the context of the Czech drug legislation, there is one more option apart from the rescheduling of psilocybin: to create a subunit of medicinal psilocybin, similar to the current legal status of medicinal cannabis. In this case, marijuana remained in List no. 3, but a new subunit named “cannabis for therapeutic use” was created and scheduled as List no. 1, making it available for medical use. The example of cannabis and its reclassification (or, in some countries, even complete legalization for recreational purposes) shows that the fact that a substance is classified as Schedule 1 – equivalent to the Czech List no. 4 and also List no. 3 in the case of cannabis – does not preclude it from being used in therapy as long as the particular country takes the necessary steps to amend its legal framework. Fear of violating international conventions is unfounded and results from social pressure, political disinformation, and lack of knowledge about the applicable Czech as well as international law. Unfortunately, the newly established Workgroup for the Medicinal Use of Psychoactive Substances and Plants, part of the Government Council for Drug Policy Coordination, has not yet started to engage itself with the issue of rescheduling psilocybin and other classical psychedelics.